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Sample records for interferon-alpha maintenance treatment

  1. Anti-interferon alpha treatment in SLE.

    PubMed

    Kirou, Kyriakos A; Gkrouzman, Elena

    2013-09-01

    Several studies in the last decade have highlighted the role of the type I interferon (IFN-I) pathway, and particularly interferon alpha (IFNα) in SLE pathogenesis. As a result, a multitude of potential treatments targeting IFNα have emerged in the last few years, a few of which have already completed phase II clinical trials. Some of the treatment strategies have focused on blocking IFNα or its receptor and others the plasmacytoid dendritic cell (pDC), which is the principal IFNα producing cell. In this review, we will discuss the evidence supporting a pathogenic role of IFNα and pDC in SLE, provide an update on the current status of these therapeutic strategies, and discuss the potential advantages and disadvantages of each therapeutic approach.

  2. Interferon alpha 2b as maintenance therapy improves outcome in follicular lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Huerta-Guzmán, Judith; Pérez, Felipe; Sotelo, León

    2004-11-01

    The role of interferon alpha as maintenance therapy in follicular lymphoma (FL) remains unsolved. We started a controlled clinical trial to assess if interferon alpha 2b could improve outcome, measured with event free survival (EFS) and overall survival (OS) in patients with FL in complete remission after chemotherapy based anthracyclines and adjuvant radiotherapy to sites of initial bulky disease. Three hundred and eighty four patients in complete response after 6 cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone and bleomycin, at standard doses), and adjuvant radiotherapy when necessary, were randomized to received Interferon alpha 2b, three times a week for 1 year or no treatment (control group). Median follow up was 9.8 years (range 7.0-15 years); actuarial curves showed that EFS was 64% (95% confidence interval (CI) 56-71%) in patients treated with interferon that was statistically significant to patients in the control group: 35% (95% CI: 28-43%) (p<.01). OS was also statistically significant: 81% in patients treated with interferon (95% CI: 74-93%) and 57% (95% CI: 50-63%) in the control group (p<.001). Toxicity was mild, all patients received the planned dose of interferon on time. The use of aggressive chemotherapy and maintenance therapy with interferon alpha 2b in follicular lymphoma improved outcome; more than 60% of patients remain alive free of disease at longer follow-up. PMID:15512813

  3. Successful Treatment of Provisional Cutaneous Mastocytosis with Interferon Alpha

    PubMed Central

    Rosario, Andrea; Bhat, Ramesh M

    2016-01-01

    Mastocytosis is a disorder characterized by the clonal proliferation of mast cells and their accumulation in skin, bone marrow, liver, and spleen. Cutaneous mastocytosis presents in children in over 90% of the cases and any cutaneous manifestation in an adult is the earliest sign of the systemic disease. A 45-year-old patient presented with itchy dark lesions over the body since childhood and Darier's sign was positive. Skin biopsy showed features of mastocytosis and immunohistochemistry was positive for CD34. Since the patient was refractory to treatment with antihistamines and psoralen-ultraviolet A therapy, injections of interferon alpha were given – 3 million IU twice weekly subcutaneously as they have been proven to improve constitutional symptoms. Very few reports of successful treatment of cutaneous mastocytosis using interferon alpha have been published. PMID:27293273

  4. Successful Treatment of Provisional Cutaneous Mastocytosis with Interferon Alpha.

    PubMed

    Rosario, Andrea; Bhat, Ramesh M

    2016-01-01

    Mastocytosis is a disorder characterized by the clonal proliferation of mast cells and their accumulation in skin, bone marrow, liver, and spleen. Cutaneous mastocytosis presents in children in over 90% of the cases and any cutaneous manifestation in an adult is the earliest sign of the systemic disease. A 45-year-old patient presented with itchy dark lesions over the body since childhood and Darier's sign was positive. Skin biopsy showed features of mastocytosis and immunohistochemistry was positive for CD34. Since the patient was refractory to treatment with antihistamines and psoralen-ultraviolet A therapy, injections of interferon alpha were given - 3 million IU twice weekly subcutaneously as they have been proven to improve constitutional symptoms. Very few reports of successful treatment of cutaneous mastocytosis using interferon alpha have been published. PMID:27293273

  5. Maintenance therapy with interferon-alpha 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Castañeda, Claudia; Talavera, Alejandra; Huerta-Guzmán, Judith; Murillo, Edgar

    2004-04-01

    Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy. PMID:15186737

  6. Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b.

    PubMed Central

    Bell, J. B.; Barfoot, R.; Iveson, T.; Powles, R. L.; Millar, B. C.

    1994-01-01

    In a study of 29 patients who were receiving or had received interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, antibodies were detected in 58% (17/29) of patients measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). Only 7/17 patients who were positive for antibody in the ELISA had neutralising antibody to IFN-alpha 2b, measured by virus growth inhibition. These patients comprised six who were receiving IFN-alpha 2b at the time of assessment and one who had finished treatment. Among patients who were receiving the cytokine, four had progressive disease, one was in complete remission and one in partial remission. Neutralising activity was also detected to natural human leucocyte IFN-alpha in the same patients. Two patients who were positive for neutralising antibody remain in remission and are continuing to receive IFN-alpha 2b. These two patients have since lost their neutralising titre. No neutralising antibody to IFN-alpha 2b or natural human leucocyte IFN-alpha was detected in serum from six normal donors. The data suggest that neutralising antibody formation in patients with multiple myeloma is not responsible for relapse in patients receiving IFN-alpha 2b. The transient nature of neutralising antibody production in patients who remain in remission suggests that this response to IFN-alpha 2b is not associated with memory B cells. PMID:7917911

  7. Interferon alpha 2b as maintenance therapy in low grade malignant lymphoma improves duration of remission and survival.

    PubMed

    Aviles, A; Duque, G; Talavera, A; Guzman, R

    1996-02-01

    We assessed the efficacy and toxicity of interferon alpha 2b (IFN) as maintenance therapy in patients with low grade malignant lymphoma. Between March 1986 and December 1989, 98 patients with low-grade malignant lymphoma in complete remission after conventional chemotherapy were randomly assigned to received IFN, 5.0 MU three times a week for one year, as maintenance therapy (n = 48), or to receive no treatment (control group, n = 50). In March 1994, the median duration of response had not yet been reached in the patients treated with IFN compared to 46 months in the control group. At 9-years 62% of the patients in the IFN arm remain in first complete remission compared to only 25% in the control group (p <.001). In addition, the median duration of survival has not yet been reached in either the IFN arm compared to 74 months in the control group (p <.001). Quality of life was excellent in both groups and severe side effects secondary to IFN treatment were not observed. All patients completed the planned dose of IFN. We conclude that IFN as maintenance therapy in low-grade malignant lymphoma is an excellent therapeutic option because it improves the duration of remission and survival without producing severe side effects or reducing the quality of life. PMID:8833409

  8. Thyroiditis after treatment with interleukin-2 and interferon alpha-2a.

    PubMed Central

    Pichert, G.; Jost, L. M.; Zöbeli, L.; Odermatt, B.; Pedia, G.; Stahel, R. A.

    1990-01-01

    Serial thyroid functions studies were carried out in patients with melanoma and renal cell carcinoma treated with interleukin-2 (3 MU m-2 by continuous infusion days 1-4) and interferon alpha-2a (6 MU m-2 subcutaneously on days 1 and 4), both given on alternate weeks. The results on eight patients who completed at least three cycles of treatment are described. Four patients developed thyroid dysfunction with a hyperthyroid phase of 2 weeks followed by a hypothyroid phase ranging from 12 to 24 weeks. Two patients became clinically symptomatic and required treatment. Fine-needle aspirates of the thyroid were obtained in three patients with thyroid dysfunction. The cytology revealed a mixed cellular infiltrate with lymphocytes and histiocytes, and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes, both suggestive of an autoimmune thyroiditis. One patient with thyroiditis developed anti-thyroglobulin antibodies, the serology of all other patients was normal. Patients with thyroid dysfunction tended to have higher in vivo stimulated lytic activity of peripheral mononuclear blood cells and had significantly higher levels of CD16 positive blood cells as compared to euthyroid patients. The possibility of autoimmune thyroiditis should be anticipated in future trails combining interleukin-2 and interferon alpha-2a. Images Figure 2 Figure 3 PMID:2390468

  9. Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha.

    PubMed

    Jones, T H; Wadler, S; Hupart, K H

    1998-02-01

    Fatigue occurs in more than 70% of patients treated with interferon-alpha (IFN-alpha) and is the most problematic toxicity associated with IFN-based immunotherapy. Abundant evidence suggests that immune-mediated endocrine disease occurs during IFN-alpha therapy, which may contribute to the etiology of fatigue. Autoimmune thyroid disease is a well-recognized consequence of IFN-alpha therapy and may be mediated by the induction of IFN-gamma production by lymphocytes. Administration of exogenous IFN-gamma has been associated with upregulation of class II major histocompatibility antigens in the thyroid and the development of thyroiditis. Interferon-alpha also stimulates the production of interleukin-6; both interleukin-6 and IFN-gamma have specific effects on thyrocyte function. There also is evidence suggesting that IFN-alpha initiates a cytokine cascade that effects the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, thus affecting regulation of glucocorticoid and sex steroid hormone secretion, but the clinical significance of these observations has not been established. Although endocrine disease will not explain the occurrence of fatigue symptoms in all patients, there is clear evidence that hormonal deficiency syndromes occur in a relatively large portion of patients receiving systemic IFN-alpha therapy. Most importantly, the possibility of hypothyroidism must be considered; however, diagnosis of hypothyroidism in cancer patients is complicated by the occurrence of the "sick euthyroid syndrome." Clinical recommendations for assessment and treatment of IFN-alpha-induced fatigue are offered. Most importantly, measurements of thyroid-stimulating hormone and antithyroid autoantibodies should be used to evaluate thyroid status. Acknowledging the limitations of current clinical data, adrenal- and gonadal-axis dysfunction also must be considered in patients with IFN-alpha-induced fatigue.

  10. Hypothalamic-pituitary axis remains intact after interferon-alpha treatment in hematologic diseases.

    PubMed

    Kauppila, M; Koskinen, P; Remes, K; Viikari, J; Irjala, K

    1997-09-01

    Many endocrinologic disturbances have been reported during and after interferon-alpha (IFN-alpha) treatment. These disturbances have often been caused by autoantibodies. The aim of this prospective study was to evaluate whether IFN-alpha causes hormonal changes and if it is necessary to search for such disturbances routinely. Ten patients with hematologic malignancies were examined before and after 4 months of IFN-alpha treatment. Pituitary function was tested by hypothalamic releasing hormones (thyrotropin-releasing hormone, TRH, growth hormone-releasing hormone, GHRH, gonadotropin-releasing hormone, GnRH). The adrenal glands were tested with the adrenocorticotropin (ACTH) test. The human chorionic gonadotropin (hCG) test was performed on the men (n = 4). The IFN treatment was well tolerated, and no long-term hormonal side effects were found. The testosterone/sex hormone binding globulin (SHBG) index tended to improve. There were no significant differences between the hormone responses before and after IFN-alpha treatment. We conclude that the hypothalamic-pituitary axis remains intact after IFN-alpha treatment. There is no need to follow patients endocrinologically if the patients are not predisposed by autoantibodies.

  11. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

    PubMed Central

    Rowan, Paul J; Bhulani, Nizar

    2015-01-01

    Chronic hepatitis C virus (HCV) is a global concern. With the 2014 Food and Drug Administration approvals of two direct-acting antiviral (DAA) regimens, ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpha-related depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. All-pill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed. PMID:26380046

  12. Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts.

    PubMed Central

    Armstrong, D K; Maw, R D; Dinsmore, W W; Blaakaer, J; Correa, M A; Falk, L; Ferenczy, A S; Fortier, M; Frazer, I; Law, C; Moller, B M; Oyakawa, N

    1996-01-01

    OBJECTIVE: To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and/or perianal warts produces a 30% or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy. DESIGN: Randomised, triple-blind, placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery. SETTING: International, multicentre study in 10 genitourinary medicine clinics. PATIENTS: Two hundred and fifty patients with anogenital warts. MAIN OUTCOME MEASURES: Lasting response at week 38. RESULTS: Standard efficacy analysis at week 38 showed a lasting response in 51% (35/68) of 3 MIU interferon-treated patients, 48% (30/63) of 1 MIU interferon-treated patients and 43% (29/67) of placebo-treated patients. CONCLUSIONS: With the doses and regime described, treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy. PMID:8698355

  13. Three open-label studies of oral interferon alpha in the treatment of HIV disease.

    PubMed

    Jordan, W C

    1994-04-01

    Three open-label studies were conducted in which natural human interferon-alpha (nHuIFN-alpha) was given orally to human immunodeficiency virus (HIV)-infected patients at a daily dosage of 150 IU for 12 months in an attempt to assess the effects of this treatment on their CD4+ cell counts. In the first study, 110 patients received nHuIFN-alpha, and 142 patients received nHuIFN-alpha and azidothymidine (AZT). At 12 months, patients given nHuIFN-alpha alone had a mean increase of 14% in their CD4+ counts, although the mean increase in absolute CD4+ count was similar between the groups. Blacks in this study were more likely to experience an increase in CD4+ count than other ethnic groups (P < 0.001). In the second study, 40 black, male homosexuals with CD4+ count between 350 and 500/mm3 were enrolled in groups of 10 to receive either nHuIFN-alpha or AZT, or both nHuIFN-alpha and AZT, or nothing (untreated controls). At 12 months, the mean CD4+ counts of the patients in the group given nHuIFN-alpha alone were significantly higher than the mean CD4+ counts in both the group given AZT alone and the untreated controls (P < 0.01). In the third study, 38 patients with CD4+ cell counts > 700/mm3 were enrolled in groups of 19, matched by gender and ethnic group, to receive nHuIFN-alpha or nothing (untreated controls). Patients given nHuIFN-alpha experienced a mean increase of 12% in their CD4+ counts by the end of the 12-month study.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Lack of effect of recombinant bovine interferon alpha I1 in the treatment of experimentally-induced bovine warts.

    PubMed Central

    Lassauzet, M L; Salamin, P A

    1993-01-01

    Fifteen four-month old calves were inoculated, on five scarified sites on each side of the neck, with a suspension of ground wart tissue from a steer naturally infected with bovine papilloma virus 1. Warts started to appear about one month postinfection and were measurable in ten calves two months postinfection, when the trial started. After stratification on the size of the warts, all fifteen calves were allocated randomly to one of the following treatment groups: twice weekly intramuscular injections of 5 mg recombinant bovine interferon alpha I1 (rBoIFN alpha I1), weekly injection of 5 mg of rBoIFN alpha I1 or placebo, for three weeks. The biggest wart on each calf at the beginning of the trial was measured and photographs of all warts were taken weekly for five weeks. An analysis of covariance on the log of the volumes of warts during the five weeks of the trial showed a significant difference between groups (p = 0.026). Warts in treated groups tended to grow faster than in the placebo group. PMID:8358676

  15. Original Research: Analysis of hepatic microRNA alterations in response to hepatitis B virus infection and pegylated interferon alpha-2a treatment.

    PubMed

    Jinato, Thananya; Chuaypen, Natthaya; Poomipak, Witthaya; Praianantathavorn, Kesmanee; Makkoch, Jarika; Kiatbumrung, Rattanaporn; Jampoka, Kanisa; Tangkijvanich, Pisit; Payungporn, Sunchai

    2016-10-01

    Interferons play important roles in defense mechanisms against viral infection, and thus interferon therapy has been a standard treatment in chronic hepatitis B patients. Interferons signaling pathways promote interferon-inducible genes including microRNAs. In this research, we aimed to determine microRNAs expression profiles in vitro and in vivo For in vitro model, Huh7 cells were transfected with or without hepatitis B virus plasmid for 6 h, and then treated with 100 ng of pegylated-interferon alpha-2a for 24 h. In vivo, we defined microRNAs expression profiles in pair-liver tissues of chronic hepatitis B patients in comparison between before and after treatment of pegylated-interferon alpha-2a for 48 weeks. Cellular small RNAs were extracted followed by library preparation. To determine microRNAs expression profiles, the next-generation sequencing was carried out on MiSeq platform (Illumina®). In vitro analysis demonstrated that microRNAs can be classified into up-regulated and down-regulated microRNAs in response to hepatitis B virus, interferon, and combination of hepatitis B virus and interferon. Moreover, in vivo analysis revealed microRNAs profiles in non-responders, responders without hepatitis B surface antigen clearance, and responders with hepatitis B surface antigen clearance. The target genes of the candidate microRNAs were determined in terms of roles in cellular pathways and immune response, which might be related to treatment in chronic hepatitis B patients. Results revealed that two down-regulated microRNAs including miR-185-5p and miR-186-5p were correlated in both in vitro and in vivo studies. These two microRNAs might be represented as specific hepatic microRNAs responding to hepatitis B virus and pegylated-interferon alpha-2a treatment, which may remarkable and attractive for further study involving in the association of their target genes and prediction of pegylated-interferon alpha-2a response. Interestingly, micro

  16. Chemotherapy plus interferon-alpha2b versus chemotherapy in the treatment of follicular lymphoma.

    PubMed

    Neri, N; Avilés, A; Cleto, S; Díaz, N; Talavera, A; García, E L; Díaz-Maqueo, J C

    2001-10-01

    The best treatment of follicular lymphoma remains to be determined because the long natural history of follicular lymphoma requires mature data for accurate analysis. Although the goal of primary treatment remains durable remission, the sequential application of effective treatments may also result in a prolongation of median survival time. The use of interferon (IFN) with doxorubicin-based chemotherapy has demonstrated an increase of event-free survival but not in overall survival; however, its acute and late cardiac toxicity limits its use. For this reason, we began a controlled clinical trial to assess the efficacy and toxicity of chemotherapy: COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) + IFN alternating every month for six cycles compared to six cycles of chemotherapy. In an intent-to treat analysis, 55 patients were enrolled (median age 61 years). Most cases (91%) with advanced disease were randomly assigned to chemotherapy + IFN (28 cases) or chemotherapy (27 cases). Complete remission was observed in 16 patients: 59% (95% CI, 53-70%) in the chemotherapy arm compared to 20 patients 71% (95% CI, 58-79%) in the chemotherapy + IFN arm; total responses were 74% and 86%, respectively. At a median follow-up of 60 months, event-free survival was 100% for patients treated with chemotherapy + IFN, which was statistically different from patients treated with chemotherapy 70%. At 7 years, median survival has not yet been reached; 72% of patients chemotherapy + IFN remain alive without disease (95% CI, 59-81%), which is not statistically different from 72% (95%CI, 50-73%) in the chemotherapy arm. Non-hematological toxicity was most frequent and severe in the chemotherapy arm; hematological toxicity was similar in both groups. Thus, it appears that chemotherapy + IFN, as described herein, improves event-free survival but the overall survival rates remain unchanged. The use of COPP appears to be better that anthracycline-based chemotherapy because

  17. Opening the flood gates: interferon-alpha treatment for Sjögren's syndrome.

    PubMed

    Shiozawa, S; Cummins, J M; Fox, P C

    2000-05-01

    Interferon (IFN)-alpha is the main IFN produced in response to viral infection. Low levels of IFNalpha can be detected in nasal secretions after exposure to viruses in vivo. Radioimmunoassay has shown that endogenous IFNalpha is low in children, reaches a peak in young adults, and gradually declines with aging. Importantly, this endogenous IFNalpha is significantly decreased in patients with Sjögren's syndrome (SS). IFNalpha has been tested as a therapeutic agent in patients with SS. Intramuscular human leucocyte IFNalpha increases saliva production significantly in patients with SS. Improvements have been noted in lacrimal function and in dryness symptoms. Since IFNalpha infrequently induces autoimmune phenomena and high dose IFNalpha treatment sometimes has a serious adverse event profile, treatment focus has shifted to use of low dose orally-administered IFNalpha. In a single-masked controlled trial, 60 patients with SS randomly received natural human IFNalpha 150IU 3 times a day in an oral lozenge formulation or sucralfate as control for 6 months. At study end, 15 (50%) of the 30 IFNalpha-treated patients had saliva production increases at least 100% above baseline. IFNalpha treatment was well tolerated and no patients withdrew. Labial minor salivary gland biopsies indicated significant decreases in lymphocytic infiltration accompanied by a significant increase in intact salivary gland tissue after 6 months of treatment. In another 12-week double-masked, randomised, placebo-controlled trial, stimulated saliva production in patients with SS receiving IFNalpha lozenges 150IU 3 times daily was significantly increased. This dosage was also suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. The tolerability profile of these low dose oral IFNalpha lozenges is excellent; no serious adverse events have been recorded. Adverse effects were generally mild and there were no clinically significant changes in laboratory or clinical safety

  18. A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients.

    PubMed

    El Sabaawy, Dalia; El-Haggar, Sahar; El-Bahrawy, Hoda; Waked, Imam; El-Said, Hala

    2015-06-01

    HCV infection presents a vast burden in the regions of high prevalence such as Egypt, where most HCV isolates are genotype 4b. Combined treatment of three variants of pegylated interferon and ribavirin is still the standard of care in Egypt. However, no conclusive data confirming their efficacy are available. Here, 60 chronic HCV patients were randomized for ribavirin plus Peg Intron (PEG-IFNα-2b), Pegasys (PEG-IFNα-2a) or Reiveron Retard (PEG-IFNα-2a). Serum interferon and antibody (Ab) levels were measured, and responses and costs were compared. Serum interferon levels were higher in Pegasys group (1625.1 ng/mL) followed by Reiveron Retard (1076.5 ng/mL), and Peg Intron group (857.72 ng/mL). Moreover, Ab levels were the lowest in Reiveron Retard group (318.4 ng/mL), followed by Peg Intron (439.93 ng/mL), and Pegasys cases (610.83 ng/mL). The best 24-week response rates were detected in the Pegasys group (73.3%), followed by Peg Intron (66.67%), and Reiveron Retard (40%). Treatment with both Pegasys and Peg Intron were most cost-effective. Furthermore, Pegasys was superior in both 6-month response and serum interferon, despite having higher Ab levels (more antigenicity). Our data have notable clinical implications and suggest that Pegasys may be a superior choice of interferon therapy for chronic HCV under low socioeconomic conditions. PMID:25904442

  19. The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-alpha 2a and etretinate.

    PubMed

    Dréno, B; Claudy, A; Meynadier, J; Verret, J L; Souteyrand, P; Ortonne, J P; Kalis, B; Godefroy, W Y; Beerblock, K; Thill, L

    1991-11-01

    Forty-five patients with cutaneous T-cell lymphomas (CTCL), 32 with mycosis fungoides (MF) and 13 with Sézary syndrome (SS), were treated with interferon-alpha 2a (IFN-alpha 2a) (6-9 x 10(6) IU daily) for 3 months. Those responding to treatment were then treated with interferon-alpha alone (6-9 x 10(6) IU three times weekly), and non-responders received a combination of etretinate (0.5 mg/kg/day) and IFN-alpha 2a in similar concentrations. After 12 months of treatment, 28/45 patients (62.2%) were in complete or partial (greater than 50%) remission. Of these, 17 (60.7%) were receiving IFN-alpha alone and 11 the combined interferon-retinoid therapy. Of the patients with MF stage I and II, 20/25 were responders (12 receiving IFN-alpha alone and eight on combined therapy), whereas only 8/20 with stage IV or SS responded to treatment (five receiving IFN-alpha 2a alone and three combined therapy). These results suggest that the association of etretinate with low-dose recombinant IFN-alpha 2a is an effective means of treating epidermotropic CTCL, particularly in the early stages.

  20. Nanomedicines in the treatment of patients with hepatitis C co-infected with HIV--focus on pegylated interferon-alpha.

    PubMed

    Zoller, Heinz; Vogel, Wolfgang

    2006-01-01

    In immuno-competent individuals, the natural course of chronic hepatitis C virus (HCV) infection is highly variable and 5%-30% of patients develop cirrhosis over 20 years. Co-infection with HCV and human immunodeficiency virus (HIV) is an important prognostic factor and associated with more frequent and accelerated progression to cirrhosis. Until recently HIV/AIDS-related complications were life limiting in patients co-infected with HCV; the introduction of highly active antiretroviral treatment (HAART) and the better prognosis of HIV infection has made HCV-related complications an emerging health problem in HCV/HIV coinfected individuals. Treatment of chronic HCV infection has also evolved since the introduction of interferon-alpha. Recently, introduction of pegylated interferon-alpha (peginterferon-alpha) has resulted in an increase in sustained virus clearance rates of up to 80% in selected genotypes and patient populations. The safety and efficacy of modern anti HCV treatment regimens - based on peginterferon-alpha in combination with ribavirin - was evaluated in 4 controlled trials. Sustained clearance of hepatitis C virus can be achieved in up to 35% of patients with HIV/HCV co-infection, and novel HCV treatment regimens based on peginterferon-alpha have no negative effect on the control of HIV disease. In conclusion, if HIV infection is well controlled and CD4+ cell counts >100/mm3, treatment of chronic hepatitis C with peginterferon in combination with ribavirin is safe and should be given for 48 weeks regardless of the HCV genotype. Introduction of peginterferon-alpha has significantly improved adherence to treatment and treatment efficacy; in particular sustained virologic response in patients with HCV genotype 1 or 4 infection improved, but sustained viral clearance in only 7%-38% of patients infected with genotype I and 4 cannot be the final step in development of effective treatments in patients with HCV/HIV co-infection.

  1. CD3(bright)CD56(+) T cells associate with pegylated interferon-alpha treatment nonresponse in chronic hepatitis B patients.

    PubMed

    Guo, Chuang; Shen, Xiaokun; Fu, Binqing; Liu, Yanyan; Chen, Yongyan; Ni, Fang; Ye, Ying; Sun, Rui; Li, Jiabin; Tian, Zhigang; Wei, Haiming

    2016-01-01

    Chronic hepatitis B (CHB) infection is a serious and prevalent health concern worldwide, and the development of effective drugs and strategies to combat this disease is urgently needed. Currently, pegylated interferon-alpha (peg-IFNα) and nucleoside/nucleotide analogues (NA) are the most commonly prescribed treatments. However, sustained response rates in patients remain low, and the reasons are not well understood. Here, we observed that CHB patients preferentially harbored CD3(bright)CD56(+) T cells, a newly identified CD56(+) T cell population. Patients with this unique T cell population exhibited relatively poor responses to peg-IFNα treatment. CD3(bright)CD56(+) T cells expressed remarkably high levels of the inhibitory molecule NKG2A as well as low levels of CD8. Even if patients were systematically treated with peg-IFNα, CD3(bright)CD56(+) T cells remained in an inhibitory state throughout treatment and exhibited suppressed antiviral function. Furthermore, peg-IFNα treatment rapidly increased inhibitory TIM-3 expression on CD3(bright)CD56(+) T cells, which negatively correlated with IFNγ production and might have led to their dysfunction. This study identified a novel CD3(bright)CD56(+) T cell population preferentially shown in CHB patients, and indicated that the presence of CD3(bright)CD56(+) T cells in CHB patients may be useful as a new indicator associated with poor therapeutic responses to peg-IFNα treatment. PMID:27174425

  2. CD3brightCD56+ T cells associate with pegylated interferon-alpha treatment nonresponse in chronic hepatitis B patients

    PubMed Central

    Guo, Chuang; Shen, Xiaokun; Fu, Binqing; Liu, Yanyan; Chen, Yongyan; Ni, Fang; Ye, Ying; Sun, Rui; Li, Jiabin; Tian, Zhigang; Wei, Haiming

    2016-01-01

    Chronic hepatitis B (CHB) infection is a serious and prevalent health concern worldwide, and the development of effective drugs and strategies to combat this disease is urgently needed. Currently, pegylated interferon-alpha (peg-IFNα) and nucleoside/nucleotide analogues (NA) are the most commonly prescribed treatments. However, sustained response rates in patients remain low, and the reasons are not well understood. Here, we observed that CHB patients preferentially harbored CD3brightCD56+ T cells, a newly identified CD56+ T cell population. Patients with this unique T cell population exhibited relatively poor responses to peg-IFNα treatment. CD3brightCD56+ T cells expressed remarkably high levels of the inhibitory molecule NKG2A as well as low levels of CD8. Even if patients were systematically treated with peg-IFNα, CD3brightCD56+ T cells remained in an inhibitory state throughout treatment and exhibited suppressed antiviral function. Furthermore, peg-IFNα treatment rapidly increased inhibitory TIM-3 expression on CD3brightCD56+ T cells, which negatively correlated with IFNγ production and might have led to their dysfunction. This study identified a novel CD3brightCD56+ T cell population preferentially shown in CHB patients, and indicated that the presence of CD3brightCD56+ T cells in CHB patients may be useful as a new indicator associated with poor therapeutic responses to peg-IFNα treatment. PMID:27174425

  3. Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial.

    PubMed Central

    Bernhard, H.; Jäger-Arand, E.; Bernhard, G.; Heike, M.; Klein, O.; Riemann, J. F.; Meyer zum Büschenfelde, K. H.; Dippold, W.; Knuth, A.

    1995-01-01

    Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients (23%) had progressive disease (PD). The median survival time was 10 months for all patients, 22 months for patients with partial remission and 5 months for patients with progressive disease. Many patients with tumour-related pain whose tumours were affected in terms of PR, MR, NC were free of pain during treatment with this regimen (22/36 patients). The common toxicities observed were fever (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical modulation of 5-FU with FA and IFN-alpha has some positive effects in the treatment of pancreatic cancer of moderate toxicity. PMID:7819023

  4. Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. AUSTIMS Research Group.

    PubMed Central

    1989-01-01

    The role of interferon-alpha (IFN-alpha) and transfer factor (TF) in the treatment of multiple sclerosis was investigated in a prospective, multi-centric, three year, double-blind, placebo-controlled trial. One hundred and eighty two patients with clinically definite multiple sclerosis were randomised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status. Subcutaneous injections of IFN-alpha (3 x 10(6) units), TF (0.5 units) manufactured from leucocytes of cohabiting donors, or placebo were given twice weekly for two months, once weekly for 10 months then fortnightly for 24 months. One hundred and fifty three patients completed the injection regimen. There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group. Similarly, change in visual evoked responses (VER), and in number of oligoclonal bands (OCB) and the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) over the trial period did not differ significantly between the three groups. However, the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups. PMID:2659737

  5. The effects of interferon-alpha/beta in a model of rat heart transplantation

    NASA Technical Reports Server (NTRS)

    Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

    1992-01-01

    Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

  6. Targeted Therapies: Bevacizumab and interferon-alpha in metastatic renal-cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2009-05-01

    Rini and colleagues provide additional data on bevacizumab and interferon-alpha in clear-cell carcinoma of the kidney; a comparison of these results with the findings from contemporary trials suggests that bevacizumab and interferon-alpha is another clinically useful treatment option for patients with metastatic renal-cell carcinoma.

  7. A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

    PubMed Central

    Armstrong, D K; Maw, R D; Dinsmore, W W; Morrison, G D; Pattman, R S; Watson, P G; Nathan, P M; Moss, T; Nayagam, A; Wade, A

    1994-01-01

    OBJECTIVES--The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN--Randomised, double-blind parallel group study. SETTING--Multicentre study in six genitourinary clinics within the U.K. PATIENTS--One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES--Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS--At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS--At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events. PMID:7705855

  8. Improved scar in postburn patients following interferon-alpha2b treatment is associated with decreased angiogenesis mediated by vascular endothelial cell growth factor.

    PubMed

    Wang, Jianfei; Chen, Hong; Shankowsky, Heather A; Scott, Paul G; Tredget, Edward E

    2008-07-01

    Hypertrophic scar (HTS) after thermal injury is a dermal fibroproliferative disorder, which leads to considerable morbidity. Previous clinical studies from our laboratory have suggested that interferon-alpha2b (IFN-alpha2b) improves scar quality as a result of the suppression of fibroblast function. More recently, our work has demonstrated that the improvement of scar in patients with HTS after IFN-alpha2b treatment may be associated with a decreased number of fibrocytes and/or altered fibrocyte function. In this study, we report that the improvement of HTS after IFNalpha-2b treatment may be associated with a decrease in angiogenesis. Using immunohistochemistry, we demonstrate an increase in angiogenesis in HTS compared to normal skin, and also show an increase in the expression of vascular endothelial cell growth factor (VEGF) in HTS. Subsequently, we demonstrate a significant reduction in angiogenesis in HTS tissue from patients after treatment with systemic IFN-alpha2b. By using a [3H] thymidine incorporation assay, we demonstrate that IFN-alpha2b suppresses the proliferation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. In addition, IFN-alpha2b inhibits VEGF-induced proliferation and tube formation by using HUVECs. All these effects may be a result of the blocking of VEGF receptor expression on endothelial cells by IFN-alpha2b. Taken together with previous results, the present study suggests that the improvement of scar quality in HTS patients after IFN-alpha2b treatment may also be associated with decreased angiogenesis in HTS. The current in vitro results may provide some insights into the scar improvement that is seen with systemic IFN-alpha2b treatment.

  9. Intrinsic Viral Factors Are the Dominant Determinants of the Hepatitis C Virus Response to Interferon Alpha Treatment in Chimeric Mice

    PubMed Central

    Chen, Ran; Kobewka, Michelle; Addison, William; Lachance, Gerald; Tyrrell, D. Lorne

    2016-01-01

    Background Hepatitis C virus infection is a global health problem. New direct-acting antiviral agents have been recently approved. However, due to their high cost and some genotypes remaining difficult to treat, interferon-based therapy with pegylated interferon and ribavirin likely may remain a component of hepatitis C virus treatment for some patients. Unfortunately, pegylated interferon / ribavirin treatment achieved favorable outcomes in less than 50% of patients. Factors determining the outcome to pegylated interferon / ribavirin include both host and viral factors. It has been a major challenge to separate the host and viral factors in most in vivo systems. Aims & Methods We used two hepatitis C virus strains from patients with different interferon-sensitivities and three hepatocyte donors, each with distinct interleukin 28B and interferon lambda 4 single nucleotide polymorphisms to investigate the contributions of viral and host factors to the response of hepatitis C virus to interferon treatment in chimeric mice. Results and Conclusions We found that viral factors were the dominant factors in determining the interferon treatment outcomes in chimeric mice. Host factors, such as pre-treatment liver interferon-stimulated gene expression and single nucleotide polymorphisms near interleukin 28B and interferon lambda 4 coding regions, were less important determinants of the response to interferon in the chimeric mice than they were in patients. Our results also suggest that a complete immune system as seen in patients may be required for host factors such as single nucleotide polymorphisms near interleukin 28B / interferon lambda 4 and pre-treatment liver interferon-stimulated gene upregulation to have an effect on the interferon response. PMID:26765841

  10. Chemokine gene expression in the murine renal cell carcinoma, RENCA, following treatment in vivo with interferon-alpha and interleukin-2.

    PubMed Central

    Sonouchi, K.; Hamilton, T. A.; Tannenbaum, C. S.; Tubbs, R. R.; Bukowski, R.; Finke, J. H.

    1994-01-01

    The expression of three chemoattractant cytokine (chemokine) messenger (m)RNAs in the murine renal cell carcinoma (RENCA) from mice treated with a combination of interferon-alpha (IFN-alpha) and interleukin-2 was examined and related to tumor infiltration by inflammatory leukocytes. Using a semi-quantitative reverse transcriptase polymerase chain reaction assay, mRNAs encoding the KC, JE, and IP-10 genes were all elevated in tumor tissue from mice treated systemically with IFN-alpha/interleukin-2 for 4 days. Similarly, the mRNA for tumor necrosis factor-alpha (TNF-alpha) was also increased in tumors from treated as compared to control animals. The same tumors showed a significant increase in Mac-1+ leukocytes, which correlated well with the increase in chemokine and TNF-alpha gene expression. The renal cell carcinoma tumor itself may be responsible for the expression of chemokine genes in the tumor bed following cytokine therapy. Cultures of freshly explanted RENCA cells expressed significant levels of chemokine mRNAs when stimulated in vitro with IFN alpha, IFN gamma, and/or interleukin-2, demonstrating that this tumor cell has potential for expression of these genes in vivo. In contrast, TNF-alpha expression was not detected in cultured tumor cells. Thus TNF-alpha may be expressed by infiltrating monocytes following exposure to recombinant cytokine therapy. Images Figure 1 Figure 2 Figure 4 PMID:8160774

  11. Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

    PubMed

    Ship, J A; Fox, P C; Michalek, J E; Cummins, M J; Richards, A B

    1999-08-01

    The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events. PMID:10476942

  12. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

    PubMed Central

    Atzpodien, J; Schmitt, E; Gertenbach, U; Fornara, P; Heynemann, H; Maskow, A; Ecke, M; Wöltjen, H H; Jentsch, H; Wieland, W; Wandert, T; Reitz, M

    2005-01-01

    We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy. PMID:15756254

  13. Interferon-. alpha. selectively activates the. beta. isoform of protein kinase C through phosphatidylcholine hydrolysis

    SciTech Connect

    Pfeffer, L.M.; Saltiel, A.R. ); Strulovici, B. )

    1990-09-01

    The early events that occur after interferon binds to discrete cell surface receptors remain largely unknown. Human leukocyte interferon (interferon-{alpha}) rapidly increases the binding of ({sup 3}H)phorbol dibutyrate to intact HeLa cells a measure of protein kinase C activation, and induces the selective translocation of the {beta} isoform of protein kinase C from the cytosol to the particulate fraction of HeLa cells. The subcellular distribution of the {alpha} and {epsilon} isoforms is unaffected by interferon-{alpha} treatment. Activation of protein kinase C by phorbol esters mimics the inhibitory action of interferon-{alpha} on HeLa cell proliferation and down-regulation of protein kinase C blocks the induction of antiviral activity by interferon-{alpha} in HeLa cells. Increased phosphatidylcholine hydrolysis and phosphorylcholine production is accompanied by diacylglycerol production in response to interferon. However, inositol phospholipid turnover and free intracellular calcium concentration are unaffected. These results suggest that the transient increase in diacylglycerol, resulting from phosphatidylcholine hydrolysis, may selectively activate the {beta} isoform of protein kinase C. Moreover, the activation of protein kinase C is a necessary element in interferon action on cells.

  14. Efficacy and safety of pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

    PubMed

    Santin, Miguel; Shaw, Evelyn; Garcia, M Jose; Delejido, Antonio; de Castro, Eduardo Rodriguez; Rota, Rosa; Altés, Jordi; Baguena, Francisco; Valero, Silvia; Sala, Montserrat; Casanova, Aurora

    2006-04-01

    Low response rates and concerns about safety have limited the implementation of treatment for chronic hepatitis C (CHC) in patients with HIV infection. The efficacy and safety of pegylated interferon (peg-IFN) plus ribavirin in HIV-infected patients with CHC were evaluated in a prospective, open-label, multicenter study. Sixty patients with persistently high transaminases, positive HCV-RNA, CD4 count > or = 300 cells/microl, and HIVRNA <10,000 copies/ml were included. Patients were given peg-IFN 80-150 microg/week plus ribavirin 800-1200 mg/day. Treatment was scheduled for 24 weeks for genotypes 2/3 and 48 weeks for genotypes 1/4. In an intent- to-treat analysis, 16 (26.7%) patients achieved a sustained virological response (SVR). Twenty patients (33.3%) discontinued treatment prematurely, but only in 10 (16.6%) was discontinuation due to adverse events. Negative predictive values for SVR on the basis of HCV-RNA decline between baseline and week 4 were 100% for 1- and 2-log10 fall, and positive predictive values were 40% and 58.3% for 1- and 2-log10 fall, respectively. CD4 fell by a median of 216 cells during treatment, but no HIV-associated complications occurred. In conclusion, treatment with peg-IFN alpha-2b plus ribavirin is safe and clears RNA-HCV in about one-quarter of HIV-infected patients with CHC. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment. Assessment of HCV-RNA at week 4 may help guide early therapeutic decision making. PMID:16623633

  15. MONOCYTE CHEMOTACTIC PROTEIN AND RESPONSE TO PEGYLATED INTERFERON-ALPHA-2A TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) GENOTYPE 4.

    PubMed

    Mohamed, Amal A; Sayed, Ola; Ali, Omnia E; Sayed, Ghadir A; Moustfa, Zainab; Elagawy, Waleed Ahmed

    2016-04-01

    The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology & Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naive patients were treated with PEG-IFN-a2b, at a dose of 1801 g/kg subcutaneously every week plus ribavirin at a dose of 1000- 1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a sta- tistically significant difference between patients and control group as regards the quantity of MCP-1 (P < 0.05) (Mann-Whitney test) (P = 0.004). There was a significant difference between responders and nonresponses regarding MCP-1 (P < 0.05), responders showed a higher percentage of cases with initial MCP-1 < 306 (P < 0.05). We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin. PMID:27363047

  16. Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

    PubMed Central

    Heidrich, Benjamin; Cordes, Hans-Jörg; Klinker, Hartwig; Möller, Bernd; Naumann, Uwe; Rössle, Martin; Kraus, Michael R.; Böker, Klaus H.; Roggel, Christoph; Schuchmann, Marcus; Stoehr, Albrecht; Trein, Andreas; Hardtke, Svenja; Gonnermann, Andrea; Koch, Armin; Wedemeyer, Heiner; Manns, Michael P.; Cornberg, Markus

    2015-01-01

    Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group. Trial Registration ClinicalTrials.gov NCT00803309 PMID:26057627

  17. [Hyper-IgE syndrome treated with interferon alpha 2 beta. Report of a case].

    PubMed

    Segura Mendez, N H; del Rivero Hernández, L; Mejía Ortega, J; Ubaldo Ortiz Vázquez, J; Varela Delgado, A L; Espínola Reyna, G; Rico, G

    2000-01-01

    The hyper IgE syndrome is characterized by recurrent abscess on the skin, and airways and itching dermatitis. The data acquired in the lab is hypergammaglobulinemy, eosinophil in blood, tissue, sputum, with fagocitos, and quimiotaxis defect. Since 1972 it has been reported 150 cases in the world without no geographic difference and 2:1 relation with the masculine gender. The therapeutic ways are even controversial. The therapy with interferon alpha 2 beta is the alternative treatment so diminish the dermis inflammation as the seric IgE reduction. This case shows a patient with the classic clinic data and seric IgE levels who didn't present response to the habitual therapy, because of this. He was the switch to the interferon alpha 2 beta. Later on the therapy it wasesented clinical changes over the symptomatology with reduction in the over seric IgE. PMID:11558395

  18. [Interferon alpha antibodies show no cross reactions with typical autoantibodies].

    PubMed

    Görg, S; Klouche, M; Wilhelm, D; Kirchner, H

    1993-04-01

    Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.

  19. Effect of interferon-alpha 2a on malignant mesothelioma.

    PubMed

    Christmas, T I; Manning, L S; Garlepp, M J; Musk, A W; Robinson, B W

    1993-02-01

    Malignant mesothelioma (MM) is a tumor that is resistant to conventional therapy. Interferon-alpha (IFN-alpha) has been used in the treatment of some human tumors, and we have previously demonstrated an in vitro anti-proliferative effect of IFN against MM cell lines. Therefore, the effect of recombinant human IFN-alpha (IFN-alpha 2a) (Roferon-A, Hoffmann-La Roche) on previously untreated patients with MM has been studied. Twenty-five patients (24 male and 1 female), with a mean age of 59 +/- 9.9 years, were treated for 3 months with IFN-alpha 2a. The starting dose was 3 x 10(6) IU daily increasing to a maximum of 18 x 10(6) IU daily or as tolerated. All patients had measurable tumor on thoracic CT prior to commencement. CT scans were performed at 6 and 12 weeks to determine tumor response. Twenty patients completed 3 months of treatment. Five patients were withdrawn because of disease progression. Side effects were predictable and dose related. Dose reductions were necessary in 12 patients for grade 2 toxicity. One patient had a complete response (CR), 2 patients had partial responses (PR) (response rate = 12%), 13 (52%) patients remained stable, 1 of whom exhibited a delayed PR, and 9 (36%) had progressive disease. These data suggest that IFN-alpha 2a is well tolerated in patients with MM and is active against MM in a proportion of patients.

  20. Rapid response to 2'-deoxycoformycin in advanced hairy cell leukemia after failure of interferons alpha and gamma.

    PubMed

    Lembersky, B C; Ratain, M J; Westbrook, C; Golomb, H M

    1988-01-01

    A patient with advanced hairy cell leukemia initially had a short-lived minor response to interferon alpha therapy and failed to respond to interferon gamma. Subsequent treatment with 2'-deoxycoformycin (dCF) administered biweekly for 12 wk resulted in a complete hematological remission which has continued for 16 months without additional therapy. PMID:3128105

  1. Probable involvement of p11 with interferon alpha induced depression

    PubMed Central

    Guo, Jiqiang; Zhang, Wen; Zhang, Lili; Ding, Huaxia; Zhang, Jingjing; Song, Chen; Zhang, Yanfei; Xia, Namei; Li, Mingfang; Liang, Yinming; Hu, Xianzhang; Luan, Haojiang; Wang, Hui

    2016-01-01

    Depression is one of the major side effects of interferon alpha (IFN-α) treatment, but the molecular mechanism underlying IFN-α-induced depression remains unclear. Several studies have shown that the serotonin receptors 5-HTR1b and 5-HTR4 play key roles in the anti-depression effects associated with p11 (S100A10). We investigated the effects of IFN-α on the regulation of p11, 5-HTR1b and 5-HTR4 in mice and human neuroblastoma cells (SH-sy5y). We found that intraperitoneal injection with IFN-α in Balb/c mice resulted in an increased immobility in FST and TST, and potently lowered the protein levels of p11, 5-HTR1b and 5-HTR4 in the hippocampus or cingulate gyrus. IFN-α significantly down-regulated the protein levels of p11, 5-HTR1b and 5-HTR4 in SH-sy5y cells, in a time- and dose-dependent manner. Our study revealed that over-expression of p11 could prevent the IFN-α-induced down-regulation of 5-HTR1b and 5-HTR4. The results indicated that IFN-α treatment resulted in p11 down-regulation, which subsequently decreased 5-HTR1b and 5-HTR4 in vitro or in vivo. Our findings suggested that p11 might be a potential regulator on 5-HTR1b and 5-HTR4 as well as a predictor of or a therapeutic target for IFN-α-induced depression. PMID:26821757

  2. Combination therapy of cutaneous T cell lymphoma with interferon alpha-2a and photochemotherapy.

    PubMed

    Stadler, R; Otte, H G

    1995-01-01

    The efficacy of a combination treatment with interferon alpha-2a and photochemotherapy was investigated in 16 patients with cutaneous T cell lymphoma. During the initial treatment, interferon alpha-2a was given subcutaneously at maximum dose of 9 million IU. Simultaneously, photo-chemotherapy with a maximum single dose of 3.0 J/cm2 was applied. After a complete or partial remission had been achieved, the dose of interferon was continued as permanent treatment at 3-9 million IU a week. Photochemotherapy was maintained twice a week for a minimum of 2 months and then stopped depending on the course of the disease. The combination treatment was well tolerated and all patients responded to the initial therapy. Three patients were withdrawn at an early stage of therapy, as they developed erythrodermia after photochemotherapy. The permanent treatment led to a complete remission in ten out of 13 patients and to a partial remission in three patients. During the follow-up period (now 10-40 months), therapy was stopped in four patients because of progression and in one patient because of newly diagnosed Hodgkin's disease. In another three patients, who developed local recurrences, a repetition of the initial treatment schedule was necessary to keep them in remission.

  3. Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

    PubMed Central

    Facendola, G.; Locatelli, M. C.; Pizzocaro, G.; Piva, L.; Pegoraro, C.; Pallavicini, E. B.; Signaroldi, A.; Meregalli, M.; Lombardi, F.; Beretta, G. D.

    1995-01-01

    Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur. PMID:8519672

  4. Cytokine therapeutics: lessons from interferon alpha.

    PubMed Central

    Gutterman, J U

    1994-01-01

    Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease. PMID:8108387

  5. Interferon alpha-2a in cutaneous T-cell lymphoma.

    PubMed

    Vegna, M L; Papa, G; Defazio, D; Pisani, F; Coppola, G; De Pità, O; Puddu, P; Ferranti, G; Simoni, R; Mandelli, F

    1990-01-01

    23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.

  6. Organization, structure and expression of murine interferon alpha genes.

    PubMed

    Zwarthoff, E C; Mooren, A T; Trapman, J

    1985-02-11

    Using a human interferon-alpha probe we have isolated recombinant phages containing murine interferon-alpha (Mu IFN-alpha) genes from a genomic library. One of these phages contained two complete Mu IFN-alpha genes and part of a third gene. The insert of a second phage held two IFN genes. This indicates that the Mu IFN-alpha genes are clustered in the genome as is the case for the analogous human genes. The nucleotide sequences of these 5 genes were determined. They show that the genes are all different, albeit highly homologous. The deduced amino acid sequences show that four of the five genes contain a putative glycosylation site. Three genes were transiently expressed in COS cells and they gave rise to protein products showing antiviral properties. The expression of the five Mu IFN-alpha genes and the Mu IFN-beta gene was studied in virus-induced mouse L cells. The individual mRNAs were visualized in a nuclease S1 experiment, using a specific probe for each gene. In RNA preparations from induced cells mRNAs for each of the five alpha genes and the beta gene were present. However, substantial differences in the amounts of the individual mRNAs were observed.

  7. Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model.

    PubMed

    Souza, M M; Paraná, R; Trepo, C; Barbosa, A A; Oliveira, I; Andrade, Z A

    2001-04-01

    Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

  8. Secretion of human interferon alpha 2b by Streptomyces lividans.

    PubMed

    Pimienta, E; Fando, R; Sánchez, J C; Vallin, C

    2002-02-01

    Biologically active human interferon alpha 2b (HuIFNalpha-2b) was secreted into the culture medium by Streptomyces lividans transformed with recombinant plasmids coding for HuIFNalpha-2b fused to the Streptomyces exfoliatus M11 lipase A signal sequence. Levels were low, 15 or 100 ng/ml, depending on the plasmid used. Neither processed nor unprocessed HuIFNalpha-2b was detected in cell lysates of the transformants secreting the recombinant product. However, the secreted recombinant product was found to partially degrade when cultures reached the stationary phase by the action of an, as yet, unidentified mycelium-associated factor. Experimental evidence suggests that the degrading factor is related to mycelium-associated proteolytic activity.

  9. Polymorphism in the interferon-{alpha} gene family

    SciTech Connect

    Golovleva, I.; Lundgren, E.; Beckman, L.; Kandefer-Szerszen, M.

    1996-09-01

    A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases {open_quotes}nested{close_quotes} PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-{alpha} 1 and interferon-{alpha} 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines. 44 refs., 4 figs., 4 tabs.

  10. Interferon Alpha as a Primary Pathogenic Factor in Human Lupus

    PubMed Central

    2011-01-01

    Interferon alpha (IFN-α) is a critical mediator of human systemic lupus erythematosus (SLE). This review will summarize evidence supporting the role for IFN-α in the initiation of human SLE. IFN-α functions in viral immunity at the interface of innate and adaptive immunity, a position well suited to setting thresholds for autoimmunity. Some individuals treated with IFN-α for chronic viral infections develop de novo SLE, which frequently resolves when IFN-α is withdrawn, supporting the idea that IFN-α was causal. Abnormally high IFN-α levels are clustered within SLE families, suggesting that high serum IFN-α is a heritable risk factor for SLE. Additionally, SLE-risk genetic variants in the IFN-α pathway are gain of function in nature, resulting in either higher circulating IFN-α levels or greater sensitivity to IFN-α signaling in SLE patients. A recent genome-wide association study has identified additional novel genetic loci associated with high serum IFN-α in SLE patients. These data support the idea that genetically determined endogenous elevations in IFN-α predispose to human SLE. It is possible that some of these gain-of-function polymorphisms in the IFN-α pathway are useful in viral defense, and that risk of SLE is a burden we have taken on in the fight to defend ourselves against viral infection. PMID:21923413

  11. Remission of liver fibrosis by interferon-alpha 2b.

    PubMed

    Moreno, M G; Muriel, P

    1995-08-01

    Fibrosis is a dynamic process associated with the continuous deposition and resorption of connective tissue, mainly collagen. Therapeutic strategies are emerging by which this dynamic process can be modulated. Since interferons are known to inhibit collagen production, the aim of this study was to investigate if the administration of interferon-alpha 2b (IFN-alpha) can restore the normal hepatic content of collagen in rats with established fibrosis. Fibrosis was induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was administered to fibrotic rats for 15 days. Bile duct ligation increased liver collagen content 6-fold. In addition, serum and liver markers of hepatic injury increased significantly; liver histology showed an increase in collagen deposition, and the normal architecture was lost, with large zones of necrosis being observed frequently. IFN-alpha administration reversed to normal the values of all the biochemical markers measured and restored the normal architecture of the liver. Our results demonstrated that IFN-alpha is useful in reversing fibrosis and liver damage induced by biliary obstruction in the rat. However, further investigations are required to evaluate the therapeutic relevance of interferons on non-viral fibrosis and cholestasis. PMID:7646558

  12. Treatment of naïve patients with chronic hepatitis C genotypes 2 and 3 with pegylated interferon alpha and ribavirin in a real world setting: relevance for the new era of DAA.

    PubMed

    Heidrich, Benjamin; Wiegand, Steffen B; Buggisch, Peter; Hinrichsen, Holger; Link, Ralph; Möller, Bernd; Böker, Klaus H W; Teuber, Gerlinde; Klinker, Hartwig; Zehnter, Elmar; Naumann, Uwe; Busch, Heiner W; Maasoumy, Benjamin; Baum, Undine; Hardtke, Svenja; Manns, Michael P; Wedemeyer, Heiner; Petersen, Jörg; Cornberg, Markus

    2014-01-01

    Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10-20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN± sofosbuvir/RBV in well-selected naïve G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources. PMID:25302676

  13. Treatment of Naïve Patients with Chronic Hepatitis C Genotypes 2 and 3 with Pegylated Interferon Alpha and Ribavirin in a Real World Setting: Relevance for the New Era of DAA

    PubMed Central

    Buggisch, Peter; Hinrichsen, Holger; Link, Ralph; Möller, Bernd; Böker, Klaus H. W.; Teuber, Gerlinde; Klinker, Hartwig; Zehnter, Elmar; Naumann, Uwe; Busch, Heiner W.; Maasoumy, Benjamin; Baum, Undine; Hardtke, Svenja; Manns, Michael P.; Wedemeyer, Heiner; Petersen, Jörg; Cornberg, Markus

    2014-01-01

    Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10–20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN± sofosbuvir/RBV in well-selected naïve G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources. PMID:25302676

  14. Interferon-alpha therapy for refractory kaposiform hemangioendothelioma: a single-center experience

    PubMed Central

    Wu, Hai Wei; Wang, Xuan; Zhang, Ling; Zhao, Hai Guang; Wang, Yan An; Su, Li Xin; Fan, Xin Dong; Zheng, Jia Wei

    2016-01-01

    Kaposiform hemangioendothelioma (KHE) is a relatively rare vascular tumor with an aggressive and infiltrating nature. Previous studies have revealed an exclusive relationship between KHE and Kasabach-Merritt Phenomenon (KMP), which is associated with high morbidity and mortality. No universally accepted treatment modality exists for refractory KHE with or without KMP. The aim of this study was to evaluate the safety and efficacy of interferon-alpha (IFN-α) therapy for treatment of refractory KHE. Twelve consecutive patients with KHE were treated with subcutaneous injections of IFN-α after other treatments had failed. Eleven patients exhibited a reduction in tumor size of more than 50%, and the platelet count for all five patients with KMP returned to normal level after IFN-α therapy. The duration of IFN-α treatment ranged from 3 months to 9 months (mean: 6.3 months). The response time for IFN-α treatment ranged from 10 days to 5 weeks (mean: 3.6 weeks). Additionally, no severe complications, such as neurological damage or spastic diplegia, were observed in these patients. In conclusion, our study suggested that IFN-α therapy is effective and safe for refractory KHE, and IFN-α may be used as an alternative after other treatments have failed. PMID:27796340

  15. Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

    PubMed

    Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

    1999-02-01

    Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

  16. Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

    PubMed

    Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

    1999-02-01

    Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment. PMID:10850283

  17. The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.

    PubMed Central

    de Waard, J. W.; Wobbes, T.; de Man, B. M.; van der Linden, C. J.; Hendriks, T.

    1996-01-01

    The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine. PMID:8795572

  18. Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling.

    PubMed

    Nguyen, Vinh-Phúc; Saleh, Abu Z M; Arch, Allison E; Yan, Hai; Piazza, Flavia; Kim, John; Krolewski, John J

    2002-03-22

    The interferon-alpha (IFNalpha) receptor consists of two subunits, the IFNalpha receptor 1 (IFNaR1) and 2 (IFNaR2) chains. Following ligand binding, IFNaR1 is phosphorylated on tyrosine 466, and this site recruits Stat2 via its SH2 domain. In contrast, IFNaR2 binds Stat2 constitutively. In this study we have characterized the Stat2-IFNaR2 interaction and examined its role in IFNalpha signaling. Stat2 binds the major IFNaR2 protein but not a variant containing a shorter cytoplasmic domain. The interaction does not require a STAT SH2 domain. Both tyrosine-phosphorylated and non-phosphorylated Stat2 bind IFNaR2 in vitro; however, relatively little phosphorylated Stat2 associates with IFNaR2 in vivo. In vitro binding assays defined IFNaR2 residues 418-444 as the minimal interaction domain and site-specific mutation of conserved acidic residues within this domain disrupted in vitro and in vivo binding. An IFNaR2 construct carrying these mutations was either (i) overexpressed in 293T cells or (ii) used to complement IFNaR2-deficient U5A cells. Unexpectedly, the activity of an IFNalpha-dependent reporter gene was not reduced but, instead, was enhanced up to 2-fold. This suggests that this particular IFNaR2-Stat2 interaction is not required for IFNalpha signaling, but might act to negatively inhibit signaling. Finally, a doubly truncated recombinant fragment of Stat2, spanning residues 136-702, associated with IFNaR2 in vitro, indicating that the interaction with IFNaR2 is direct and occurs in a central region of Stat2 marked by a hydrophobic core.

  19. Hepatitis C Virus Clearance after Discontinuation of Pegylated Interferon Alpha-2a Monotherapy in a Child

    PubMed Central

    Endo, Takeshi; Ito, Koichi; Sugiura, Tokio; Goto, Kenji

    2012-01-01

    The present patient was a 4-year-old boy. His hepatitis C virus genotype was 2a, and his viral load was high (1400,000 U/mL). The pretreatment liver biopsy revealed no fibrosis or malignancy and mild chronic hepatitis; his Knodell's histological activity (HAI) score was 4. Single nucleotide polymorphism of IL28B (rs8099917) was major type. The patient began antiviral treatment with pegylated interferon alpha 2a (90 μg/week). At week 9, serum HCV RNA became undetectable, with a sensitivity of 50 copies/mL. Antiviral treatment was discontinued at week 11 because the ALT level increased to 610 U/L. After discontinuation of therapy, the patient's serum HCV RNA status became positive again. The serum viral load increased to 100,000 U/mL. During this period, he had been observed without medication. Sixteen months after stopping treatment, serum HCV became undetectable. Over a 4-year period, HCV RNA became negative and his anti-HCV antibody titer gradually decreased. In conclusion, though antiviral therapy resulted in failure or incomplete therapy, a reduced viral load resulted in viral clearance in the present patient. Interleukin 28B genotype might have association with the clearance of hepatitis C virus after discontinuation of antiviral therapy. PMID:23118765

  20. [Long-term complete response of multiple lung metastases from renal cell carcinoma induced by combination therapy with interferon alpha and UFT: a case report].

    PubMed

    Terachi, T; Okada, Y; Takeuchi, H; Yoshida, O

    1993-04-01

    We report a case of long-term complete response of multiple lung metastases of renal cell carcinoma (RCC) by the combination therapy with interferon alpha (IFN alpha) and UFT. A 38 year-old man having left RCC with lung metastases underwent radical left nephrectomy and extended lymph node dissection, the pathological stage being pT2N2. Although metastatic lung tumors increased in size and number against intravenously admitted interferon gamma (IFN gamma) therapy after the surgery, they completely disappeared following the subsequent combination therapy with intramuscularly admitted interferon alpha (IFN alpha) and oral intake of UFT in about 2 years. The patient has been disease-free for 5 years after cessation of the treatment. Combination therapy with IFN alpha and UFT might be more effective on metastases of RCC than single use of IFN alpha or IFN gamma.

  1. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    PubMed

    Coulstock, Edward; Sosabowski, Jane; Ovečka, Milan; Prince, Rob; Goodall, Laura; Mudd, Clare; Sepp, Armin; Davies, Marie; Foster, Julie; Burnet, Jerome; Dunlevy, Gráinne; Walker, Adam

    2013-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb) specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR). Our results show that the murine IFNα2 homolog (mIFNα2) fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR) was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  2. Total chemical synthesis of human interferon alpha-2b via native chemical ligation.

    PubMed

    Li, Jing; Lehmann, Clara; Chen, Xishan; Romerio, Fabio; Lu, Wuyuan

    2015-07-01

    Interferon-alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFNα composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications. PMID:25810135

  3. Emerging therapies for systemic lupus erythematosus--focus on targeting interferon-alpha.

    PubMed

    Lichtman, Eben I; Helfgott, Simon M; Kriegel, Martin A

    2012-06-01

    Current therapies for systemic lupus erythematosus (SLE), a debilitating, potentially lethal, multifactorial systemic autoimmune disease, are limited to suppressing disease activity and are associated with multiple adverse effects. Recent advances in basic and translational sciences have elucidated a crucial role for the interferon-alpha (IFNα) pathway in the pathogenesis of this enigmatic disease. The so-called "type I interferon signature" has emerged as a major risk factor for disease activity of SLE. Multiple genes encoding for molecules within the type I interferon pathway have been associated with SLE in genome wide association studies. In addition, innate immune receptors are thought to be triggered by either endogenous and/or exogenous stimuli that lead to hypersecretion of IFNα. We review the multiple emerging treatment strategies targeting IFNα-related pathways. These include monoclonal antibodies against IFNα, anti-IFNα antibody-inducing vaccines, and inhibitors of Toll-like receptors. We also summarize the current status of these pharmaceutical agents in early clinical trials.

  4. Total chemical synthesis of human interferon alpha-2b via native chemical ligation

    PubMed Central

    Li, Jing; Lehmann, Clara; Chen, Xishan; Romerio, Fabio; Lu, Wuyuan

    2015-01-01

    Interferon-alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses, and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, over-expression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor, and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFNα composed entirely of D-amino acids. Here we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications. PMID:25810135

  5. IgE plasma cell leukemia successfully treated with combination VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon-alpha.

    PubMed

    Yamagata, N; Shimazaki, C; Goto, H; Hirata, T; Ashihara, E; Oku, N; Inaba, T; Fujita, N; Nakagawa, M

    1994-03-01

    A 69-year-old woman with IgE/kappa plasma cell leukemia (PCL) was treated with a sequential combination of VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon-alpha (IFN alpha). A complete remission was achieved for 14 months. Maintenance therapy with IFN alpha has continued for an additional 10 months. IgE PCL is extremely rare. The biological characteristics of the myeloma cells, including surface marker, adhesion molecule, karyotype, DNA analysis, and the response to various cytokines, are presented.

  6. Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue

    PubMed Central

    Dowell, Nicholas G.; Cooper, Ella A.; Tibble, Jeremy; Voon, Valerie; Critchley, Hugo D.; Cercignani, Mara; Harrison, Neil A.

    2016-01-01

    Background Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used clinically for hepatitis C treatment. Though effective, IFN-α induces marked behavioral changes that, when severe, can appear indistinguishable from major depression. Curiously, fatigue and motivational impairment evolve rapidly, suggesting acute engagement of immune-brain communicatory pathways, yet mood impairments typically emerge later, after weeks of treatment. Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanisms is currently unclear. Methods Here, we used quantitative magnetization transfer (qMT) imaging, an advanced microstructural neuroimaging technique sensitive to effects of inflammation, in a prospective study design to measure acute brain changes to IFN-α and relate these to later development of discrete behavioral changes. Twenty-three patients initiating IFN-α treatment for hepatitis C underwent qMT imaging and blood sampling at baseline and 4 hours after their first IFN-α injection. Comprehensive behavioral and psychological assessments were completed at both scanning sessions and at treatment weeks 4, 8, 12, and 24. Results IFN-α injection stimulated an acute inflammatory cytokine response and evoked fatigue that peaked between 4 and 12 weeks, preceding mood change by 4 weeks. In the brain, IFN-α induced an acute change in striatal microstructure that additionally predicted development of fatigue but not mood symptoms. Conclusions Our findings highlight qMT as an in vivo biomarker of central effects of peripheral inflammation. We demonstrate exquisite sensitivity of the striatum to IFN-α, implicate striatal perturbation in IFN-α-induced fatigue, and dissociate this from mechanisms underlying IFN-α-induced mood symptoms, providing empirical support for distinct neural substrates mediating actions on motivation and mood. PMID:26169252

  7. Expression of biologically active human interferon alpha 2 in aloe vera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  8. Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).

    PubMed

    Kchour, Ghada; Tarhini, Mahdi; Kooshyar, Mohamad-Mehdi; El Hajj, Hiba; Wattel, Eric; Mahmoudi, Mahmoud; Hatoum, Hassan; Rahimi, Hossein; Maleki, Masoud; Rafatpanah, Houshang; Rezaee, S A Rahim; Yazdi, Mojtaba Tabatabaei; Shirdel, Abbas; de Thé, Hugues; Hermine, Olivier; Farid, Reza; Bazarbachi, Ali

    2009-06-25

    Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappaB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.

  9. Pharmacokinetic characteristics, pharmacodynamic effect and in vivo antiviral efficacy of liver-targeted interferon alpha.

    PubMed

    Rycroft, Daniel; Sosabowski, Jane; Coulstock, Edward; Davies, Marie; Morrey, John; Friel, Sarah; Kelly, Fiona; Hamatake, Robert; Ovečka, Milan; Prince, Rob; Goodall, Laura; Sepp, Armin; Walker, Adam

    2015-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis B virus infection, and whilst efficacious, it is associated with multiple adverse events caused by systemic exposure to interferon. We therefore hypothesise that targeting IFN directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. Furthermore we investigated whether directing IFN to the reservoir of infection in the liver may improve antiviral efficacy by increasing local concentration in target organs and tissues. Our previous results show that the mIFNα2 fused to an ASGPR specific liver targeting antibody, DOM26h-196-61, results in a fusion protein which retains the activity of both fusion partners when measured in vitro. In vivo targeting of the liver by mIFNα2-DOM26h-196-61, hereafter referred to as targeted mIFNα2, was observed in microSPECT imaging studies in mice. In this study we show by pharmacokinetic analysis that antibody mediated liver-targeting results in increased uptake and exposure of targeted mIFNα2 in target tissues, and correspondingly reduced uptake and exposure in systemic circulation, clearance organs and non-target tissues. We also show that cytokine activity and antiviral activity of liver-targeted IFN is observed in vivo, but that, contrary to expectations, liver-targeting of mIFNα2 using ASGPR specific dAbs actually leads to a reduced pharmacodynamic effect in target organs and lower antiviral activity in vivo when compared to non-targeted mIFNα2-dAb fusions.

  10. Interferon-alpha induces transient upregulation of c-FLIP through NF-kappaB activation.

    PubMed

    Kanetaka, Yuki; Hayashida, Miho; Hoshika, Akinori; Yanase, Noriko; Mizuguchi, Junichiro

    2008-01-15

    Interferon-alpha (IFN-alpha) induces apoptosis in some cell types and promotes cell survival in other cell types, but the molecular mechanisms underlying distinct IFN-alpha-induced cell behaviours remain poorly understood. In the present study, we show that IFN-alpha induced the cellular FLICE (FADD-like interleukin-1 beta-converting enzyme) inhibitory protein (c-FLIP), which serves as a promoter of cell survival in human B lymphoma cells. IFN-alpha induction of transient upregulation of c-FLIP was partially abrogated by the NF-kappaB inhibitor BAY11-7082 (BAY). Pretreatment with BAY sensitized both Daudi and U266 cells to the IFN-alpha-induced loss of mitochondrial membrane potential (DeltaPsi(m)). IFN-alpha phosphorylated the PKC isoform PKCalpha at a threonine residue, and the PKCalpha/betaI inhibitor Go6976 abrogated upregulation of IFN-alpha-induced NF-kappaB activity, leading to sensitization of cells to IFN-alpha-induced apoptosis. To analyze the role of PKCalpha in the IFN-alpha-induced signaling, Daudi cells overexpressing a constitutively active mutant of PKCalpha (caPKCalpha) were used. The caPKCalpha-expressing Daudi cells were partially resistant to the IFN-alpha-induced loss of DeltaPsi(m), concomitant with elevated levels of c-FLIP protein. Together, these results demonstrate that IFN-alpha causes a transient upregulation of c-FLIP expression, at least through PKCalpha-mediated activation of NF-kappaB. The balance between IFN-alpha-induced pro-apoptotic and survival signals determines the cell fate. Thus, therapeutic intervention in this balance may be effective for treatment of patients with IFN-alpha-refractory tumours.

  11. Pharmacokinetic Characteristics, Pharmacodynamic Effect and In Vivo Antiviral Efficacy of Liver-Targeted Interferon Alpha

    PubMed Central

    Rycroft, Daniel; Sosabowski, Jane; Coulstock, Edward; Davies, Marie; Morrey, John; Friel, Sarah; Kelly, Fiona; Hamatake, Robert; Ovečka, Milan; Prince, Rob; Goodall, Laura; Sepp, Armin; Walker, Adam

    2015-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis B virus infection, and whilst efficacious, it is associated with multiple adverse events caused by systemic exposure to interferon. We therefore hypothesise that targeting IFN directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. Furthermore we investigated whether directing IFN to the reservoir of infection in the liver may improve antiviral efficacy by increasing local concentration in target organs and tissues. Our previous results show that the mIFNα2 fused to an ASGPR specific liver targeting antibody, DOM26h-196-61, results in a fusion protein which retains the activity of both fusion partners when measured in vitro. In vivo targeting of the liver by mIFNα2-DOM26h-196-61, hereafter referred to as targeted mIFNα2, was observed in microSPECT imaging studies in mice. In this study we show by pharmacokinetic analysis that antibody mediated liver-targeting results in increased uptake and exposure of targeted mIFNα2 in target tissues, and correspondingly reduced uptake and exposure in systemic circulation, clearance organs and non-target tissues. We also show that cytokine activity and antiviral activity of liver-targeted IFN is observed in vivo, but that, contrary to expectations, liver-targeting of mIFNα2 using ASGPR specific dAbs actually leads to a reduced pharmacodynamic effect in target organs and lower antiviral activity in vivo when compared to non-targeted mIFNα2-dAb fusions. PMID:25689509

  12. Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

    PubMed

    Gisslinger, H; Svoboda, T; Clodi, M; Gilly, B; Ludwig, H; Havelec, L; Luger, A

    1993-03-01

    The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Incidence and severity of infections according to the development of neutropenia during combined therapy with pegylated interferon-alpha2a plus ribavirin in chronic hepatitis C infection.

    PubMed

    Juarez-Navarro, A; Vera-de-León, L; Navarro, J M; Chirino-Sprung, R; Díaz-Hernandez, M; Casillas-Davila, L; Dehesa-Violante, M

    2005-06-01

    The evolution of treatment of chronic hepatitis C virus infection has led to improved therapeutic efficacy. However, a major problem is the presence of side effects that require modification or withdrawal of drug therapy in 15-20% of cases. This could potentially influence the lack of sustained viral response in 50% of the cases. Side effects are common, even with pegylated interferon. This study aimed to assess the incidence and severity of infections based on the development of neutropenia associated with combined therapy with pegylated interferon-alpha2a plus ribavirin in 209 patients with chronic hepatitis C infection. All patients were administered pegylated interferon-alpha2a (180 microg/week) plus ribavirin (800 mg/day for 24 weeks in cases of nongenotype 1, or 1000-1200 mg/day for 48 weeks for genotype 1, according to whether patients weighed more or less than 75 kg). Patients with preexisting neutropenia of any cause or cirrhosis were excluded. Neutropenia was defined as a neutrophil count (NC) of <1500 cells/microl. Neutropenia was classified into three levels during treatment: 750treatment of chronic hepatitis C virus infection with a combined therapy based on pegylated interferon-alpha2a plus ribavirin did not show a higher infection rate or increased severity of the disease. PMID:16082419

  14. In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer.

    PubMed

    Scheithauer, W; Temsch, E M; Schieder, K; Funovics, H; Schiessel, R; Grabner, G

    1985-07-01

    The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02).

  15. Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha.

    PubMed

    Voltchek, I; Sologub, T; Nowicky, J W; Grigoryeva, T; Belozyorova, L; Belopolskaya, M; Semenyako, N; Lamanova, E

    2000-01-01

    The effects of Ukrain and recombinant human interferon-alpha 2b (IFN) on the state of the thiol-disulfide ratio (SH/SS) of the blood (Russian Federation patent no. 2150700) were studied in vitro using the amperometric titration method. The blood of 73 chronic hepatitis C (CHC) hepatitis C virus (HCV)-RNA-positive patients was examined. Ukrain was tested in doses of 0.05-2.0 micrograms/ml and IFN in 20-1000 U/ml of blood. After in vitro examination, 59 patients were treated: 28 with Ukrain and 31 with IFN. The first group of 16 patients (including eight with HCV genotype 1b) was treated with individually selected optimal doses of Ukrain (0.5-2.5 mg every second day). The second group of 12 patients was treated with doses of 2.5 mg Ukrain independent of in vitro test results. The third group of 31 patients was treated with individually selected optimal doses of IFN (0.5-2 MU 3 times a week). It was found that 79.4% of CHC patients were sensitive to Ukrain in vitro and 65.1% were sensitive to IFN. CHC patients with genotype 1b were sensitive to IFN only in 16.7% of cases while the figure for Ukrain was 92.3%. CHC patients with other HCV genotypes (3, 1a, 2) were sensitive to Ukrain in 86.7% of cases and to IFN in 70.6%. After 1 month of individual therapy with Ukrain, 87.5% of CHC patients, including six of eight cases with HCV genotype 1b, became PCR-HCV negative. In the group receiving the standard dose of Ukrain, virological response was only 33.3%. After 1 month, 74.2% of CHC patients treated with individual doses of IFN became PCR-HCV negative and after 3 months 90.3% were PCR-HCV negative. The prognostic significance of the method for screening preparations for the treatment of CHC patients was 89.8%. Treatment with Ukrain was without serious negative effects and the number of side effects of IFN in individual therapy was significantly reduced. Ukrain can be used in the treatment of CHC patients, alone or in combination with IFN preparations; in the cases with

  16. Lack of effect of interferon alpha 2a upon fluorouracil pharmacokinetics.

    PubMed Central

    Seymour, M. T.; Patel, N.; Johnston, A.; Joel, S. P.; Slevin, M. L.

    1994-01-01

    The disposition of 5-fluorouracil (FUra) was studied in 19 colorectal cancer patients during treatment with FUra and high-dose leucovorin (LV) with or without interferon alpha 2a (IFN-alpha). All received LV 200 mg m-2 over 2 h, then FUra 400 mg m-2 over 5 min then FUra 400 mg m-2 over 22 h, repeated on day 2, on a 14 day cycle. Nine patients also received IFN-alpha 6 MU every 48 h, starting at least 2 weeks before the study. Series of 14 blood samples were assayed for FUra by reversed-phase high-performance liquid chromatography (HPLC). Minimum Akaike information criterion estimation was used to determine the simplest effective pharmacokinetic model. This consisted of a single compartment with first-order (linear) and Michaelis-Menten (non-linear) components to drug elimination. This model gave r2 > 0.98 in 19/20 data sets. With the Michaelis constant (KM) set at 15 microM, values were derived for the volume of distribution (Vd), the maximum rate of non-linear elimination (Vmax) and the first-order elimination rate constant (K1.e). Mean (+/- s.d.) values in control (no IFN-alpha) patients were: Vd 10.4 (+/- 1.9) l m-2, Vmax 182 (+/- 59) mumol l-1 h-1 and k1.e 4.35 (+/- 0.58) h-1. No significant differences were detected in patients receiving IFN-alpha, in whom the equivalent mean values were Vd 10.0 (+/- 0.9) l m-2, Vmax 141 (+/- 27) mumol l-1 h-1 and k1.e 3.96 (+/- 0.5) h-1. Mean trapezoidal AUC0-22 h was similar in the two groups (control patients 116 microM h, IFN-alpha patients 125 microM h). No significant correlations with renal or hepatic function were detected. These results, while not inconsistent with previous reports of a reduced rate of FUra elimination at higher IFN-alpha doses, suggest that any clinical effect of this moderate dose of IFN-alpha on FUra toxicity or activity is due to modulation at target cells, not to pharmacokinetic interaction. PMID:7917928

  17. Macroscale production and analysis of crystalline interferon alpha-2B in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Reichert, Paul; Nagabhushan, Tattanahalli L.; Long, Marianna M.; Bugg, Charles E.; DeLucas, Lawrence J.

    1996-03-01

    The development and production of a zinc-interferon alpha-2b crystalline suspension on STS-52 has accelerated our ability to prepare novel high quality pharmaceutical preparations. Crystalline suspensions of protein therapeutics have applications in drug delivery, formulation, and manufacturing. These applications require crystalline suspensions of relatively small particles (<100 microns) of uniform size and shape. Previously, a crystalline form of interferon alpha-2b was identified from microscale crystallization methods with utility in pharmaceutical applications from microscale crystallization methods. Conditions for macroscale crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alpha-2b in high yield and under ``cleanroom'' conditions. These conditions were maintained in microgravity. Greater than 95% of the available protein crystallized in both the ground and flight experiments. The samples were analyzed using a battery of physical, biochemical, and biological characterization methods. The results demonstrated that sample processing, polysulfone bottle confinement, and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Subcutaneous injections of space grown crystalline preparation was compared to a non-crystalline interferon preparation in a primate pharmacokinetic study. The crystalline interferon preparation had a measured serum half-life of 12 hours as compared

  18. Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha.

    PubMed

    El Eit, Rabab M; Iskandarani, Ahmad N; Saliba, Jessica L; Jabbour, Mark N; Mahfouz, Rami A; Bitar, Nizar M A; Ayoubi, Hanadi R El; Zaatari, Ghazi S; Mahon, Francois-Xavier; De Thé, Hugues B; Bazarbachi, Ali A; Nasr, Rihab R

    2014-02-15

    Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction/transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic/IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control. PMID:23934954

  19. Activity and tolerance of a continuous subcutaneous infusion of interferon-alpha2b in patients with chronic hepatitis C.

    PubMed

    Schenker, S; Cutler, D; Finch, J; Tamburro, C H; Affrime, M; Sabo, R; Bay, M

    1997-11-01

    We administered interferon-alpha2b (IFN-alpha2b) by continuous subcutaneous infusion (60,000 IU/h, or 10 million IU/week) over 3 months to 7 patients with chronic hepatitis C. All had previously responded, as assessed by normalization of transaminases to the same dose of IFN administered by intermittent injection over 6 months, but had relapsed after cessation of therapy. The continuous infusion was tolerated well at the site of infusion, and the systemic side effects were similar in type but were lesser in intensity than with intermittent dosage. Four of 7 subjects had normalization of transaminase at the end of week 12 of therapy. Serum HCV RNA and HCV by PCR decreased with treatment, and there was a prompt and sustained increase in serum beta2-microglobulin and of 2', 5' OAS activity. The level of the latter appeared to correlate with response of the transaminase. Serum IFN concentrations were low but detectable throughout therapy. After stopping IFN administration, the transaminases in responders increased again to pretreatment levels.

  20. Development of a drug-coated microneedle array and its application for transdermal delivery of interferon alpha.

    PubMed

    Kusamori, Kosuke; Katsumi, Hidemasa; Sakai, Ryota; Hayashi, Rie; Hirai, Yuka; Tanaka, Yutaro; Hitomi, Kaori; Quan, Ying-Shu; Kamiyama, Fumio; Yamada, Keigo; Sumida, Shun-ichiro; Kishi, Kazumasa; Hashiba, Katsunori; Sakane, Toshiyasu; Yamamoto, Akira

    2016-03-01

    Interferon alpha (IFNα) is one of the most famous drugs for the treatment of chronic hepatitis C and various types of human malignancy. Protein drugs, including IFNα, are generally administered by subcutaneous or intramuscular injection due to their poor permeability and low stability in the bloodstream or gastrointestinal tract. Therefore, in the present study, novel IFNα-coated polyvinyl alcohol-based microneedle arrays (IFNα-MNs) were fabricated for the transdermal delivery of IFNα without the painful injection. IFNα was rapidly released from MNs in phosphate buffered solution and these MNs presented piercing ability in the rat skin. Slight erythema and irritation were observed when MNs were applied to the rat skin, but these skin damages completely disappeared within 24 h after removing the IFNα-MNs. Furthermore, the pharmacokinetic parameters of IFNα-MNs were similar to those of IFNα subcutaneous administration. Finally, IFNα-MNs showed a significant antitumor effect in tumor bearing mice similar to that of IFNα subcutaneous administration. These results indicate that IFNα-MNs are a useful biomaterial tool for protein drug therapy and can improve the quality of life in patients by avoidance of painful injections. PMID:26756832

  1. Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha.

    PubMed

    El Eit, Rabab M; Iskandarani, Ahmad N; Saliba, Jessica L; Jabbour, Mark N; Mahfouz, Rami A; Bitar, Nizar M A; Ayoubi, Hanadi R El; Zaatari, Ghazi S; Mahon, Francois-Xavier; De Thé, Hugues B; Bazarbachi, Ali A; Nasr, Rihab R

    2014-02-15

    Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction/transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic/IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control.

  2. Presence of lichen planus during a course of interferon alpha-2a therapy for a viral chronic C hepatitis.

    PubMed

    Guijarro Guijarro, B; López Sánchez, A F; Hernández Vallejo, G

    2001-01-01

    We present the case of a 66-year-old woman with a diagnosis of chronic active viral C hepatitis, for whom a course of interferon alpha-2A was prescribed at a dose of 4.5 MU per day for a 2 month period, followed by the same dose on alternate days for 4 months. After completion of a month of therapy, the patient presented with painful oral lesions that made normal oral food intake impossible. These lesions persisted, in spite of withdrawal of interferon therapy. Intraoral examination revealed erosive intraoral lesions in both yugal mucosae, the upper vestibular gum, the floor of the mouth, the ventral region of the tongue, and the lower lip. A diagnosis of erosive lichen planus induced by interferon therapy was established. The prescribed treatment was 0.1% triamcinolone acetonide in orabase applied 3 times a day for 4 weeks. Following the therapeutical course, the erosive lesions disappeared, and the symptoms stopped, although the reticular lesions remained visible.

  3. Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse (41939)

    NASA Technical Reports Server (NTRS)

    Rose, Andrea; Steffen, Joseph M.; Musacchia, X. J.; Sonnenfeld, Gerald; Mandel, Adrian D.

    1984-01-01

    Mice were suspended in a model that simulates the weightlessness that occurs during prolonged space flight. After one and two weeks of suspension in an antiorthostatic (head-down tilt) position, the mice were challenged with polyriboinosinic-polyribocytidylic acid to induce interferon-alpha/beta. Interferon production was severely reduced in mice that had been suspended. When mice were allowed to recover in cages for a week following removal from suspension, they recovered their full interferon-production capacity. Mice suspended in an orthostatic (horizontal) position did not have their interferon production capabilities affected, which indicates that stress per se was not a major component in the effects of antiorthostatic suspension on interferon induction.

  4. Expressions of VEGF and its receptors in rat corpus luteum during interferon alpha administration in early and pseudopregnancy.

    PubMed

    Celik-Ozenci, Ciler; Akkoyunlu, Gokhan; Korgun, Emin Turkay; Savas, Burhan; Demir, Ramazan

    2004-04-01

    It is accepted that angiogenesis plays an important role in the development of the corpus luteum (CL) and is probably necessary for normal lutein cell function. A number of drugs currently being tested in clinical trials as possible angiogenesis inhibitors were not originally developed with the intention of suppressing tumor angiogenesis. Interferon alpha (IFN-alpha) is one of the notable examples of such 'accidental angiogenesis inhibitors' and daily administration of IFN-alpha is known to suppress tumor growth, tumor vascularization, and down-regulation of various growth factors. We investigated the effects of IFN-alpha treatment on the expression of vascular endothelial growth factor (VEGF), and its receptors KDR and Flt-1, and CD34 in CL during the first week of pseudopregnancy and pregnancy in hormonally induced rat ovaries by immunohistochemistry and Western blot techniques. Basal body temperatures of the drug-treated rats, as an indicator of treatment effect, were determined daily and were increased significantly when compared to controls (38.03 +/- 0.18 vs. 36.6 +/- 0.1 degrees C), respectively. The effect of IFN-alpha treatment was minimal when the entire week was evaluated, however, the expression of VEGF decreased at 3rd, 5th, and 7th days of both pregnancy and pseudopregnancy, when compared to the 1st day, whereas there was not a such alteration in the untreated rats regarding these days. The daily subcutaneous administrations of 672.500 U IFN-alpha2b had minimal effects on the expressions of VEGF, and its two receptors KDR and Flt-1 in either pregnant or pseudopregnant corpora lutea utilizing HSCORE.

  5. Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids

    PubMed Central

    Lotrich, Francis E.; Sears, Barry; McNamara, Robert K.

    2013-01-01

    Objective Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure. Methods Plasma arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were determined prior to IFN-α therapy by mass spectroscopy. Repeated-measure analyses examined the relationship between AA/EPA+DHA and the subsequent development of labile anger and irritability in 82 subjects who prospectively completed the Anger, Irritability, and Assault Questionnaire (AIAQ) during the first eight weeks of IFN-α therapy. Results Prior to IFN-α therapy, AA/EPA+DHA did not correlate with either labile anger or irritability. Pre-treatment AA/EPA+DHA did correlate with the subsequent maximal increase in labile anger during IFN-α therapy (r=0.33; p=0.005). Over time, labile anger increased more in subjects with above median AA/EPA+DHA ratios (p<0.05). Of the 17 subjects ultimately requiring psychiatric intervention for anger, 14/17 had above-median AA/EPA+DHA ratios (p=0.009). There was also an interaction with the tumor necrosis factor-alpha (TNF-α) promoter polymorphism (A-308G), such that only those with both elevated AA/EPA+DHA and the A allele had increased labile anger (p=0.001). In an additional 18 subjects, we conversely observed that selective serotonin reuptake inhibitor treatment was associated with increased irritability during IFN-α therapy. Conclusion LCn-3 fatty acid status may influence anger development during exposure to elevated inflammatory cytokines, and may interact with genetic risk for increased brain TNF-α. LCn-3 supplements may be one strategy for minimizing this adverse side effect of IFN-α. PMID:24182638

  6. The effect of interferon-{alpha} on the expression of cytochrome P450 3A4 in human hepatoma cells

    SciTech Connect

    Flaman, Anathea S.; Gravel, Caroline; Hashem, Anwar M.; Tocchi, Monika; Li Xuguang

    2011-06-01

    Interferon {alpha} (IFN{alpha}) is used to treat malignancies and chronic viral infections. It has been found to decrease the rate of drug metabolism by acting on cytochrome P450 enzymes, but no studies have investigated the consequences of IFN{alpha} treatment on the CYP3A4 isoform, responsible for the metabolism of a majority of drugs. In this study, we have examined the effect of IFN{alpha} on CYP3A4 catalytic activity and expression in human hepatoma cells. We found that IFN{alpha} inhibits CYP3A4 activity and rapidly down-regulates the expression of CYP3A4, independent of de novo protein synthesis. Pharmacologic inhibitors and a dominant-negative mutant expression plasmid were used to dissect the molecular pathway required for CYP3A4 suppression, revealing roles for Jak1 and Stat1 and eliminating the involvement of the p38 mitogen-activated and extracellular regulated kinases. Treatment of hepatoma cells with IFN{alpha} did not affect the nuclear localization or relative abundance of Sp1 and Sp3 transcription factors, suggesting that the suppression of CYP3A4 by IFN{alpha} does not result from inhibitory Sp3 out-competing Sp1. To our knowledge, this is the first report that IFN{alpha} down-regulates CYP3A4 expression largely through the JAK-STAT pathway. Since IFN{alpha} suppresses CYP3A4 expression, caution is warranted when IFN{alpha} is administered in combination with CYP3A4 substrates to avoid the occurrence of adverse drug interactions.

  7. Quasispecies heterogeneity and constraints on the evolution of the 5' noncoding region of hepatitis C virus (HCV): relationship with HCV resistance to interferon-alpha therapy.

    PubMed

    Soler, Muriel; Pellerin, Muriel; Malnou, Cécile E; Dhumeaux, Daniel; Kean, Katherine M; Pawlotsky, Jean-Michel

    2002-06-20

    Hepatitis C virus (HCV) polyprotein translation depends on direct internal entry of the 40S ribosomal subunit mediated by an internal ribosome entry segment (IRES) located in the 5' noncoding (5'NC) region of the viral genome. HCV is genetically heterogeneous and is characterized by the existence of a quasispecies distribution of the virus population within a single infected individual. Cloning and sequencing strategies were used to characterize 5'NC quasispecies genetically. Similar to coding regions, the HCV 5'NC region was distributed as a quasispecies, but it appeared to be subjected to stronger conservatory constraints than other regions of the HCV genome, probably due to the need for structural (and functional) conservation of the IRES. Indeed, most of the quasispecies substitutions were in unpaired regions of the IRES or clustered such that base-pairing was maintained, whereas only 21% were expected to result in a loss of base-pairing. Quasispecies-related structural changes could be predicted in the core cruciform of IRES domain III composed of the RNA helices which extend from the four-way junction JIIIabc, mostly in minor variants, but sometimes in major ones. The results presented here suggest the simultaneous presence in infected patients of a mixture of genetically distinct but closely related IRES sequences that may have different structures. No significant genetic changes of 5'NC quasispecies were observed after interferon-alpha treatment, except in patients with mixed genotype infection who cleared one of the infecting strains during therapy, suggesting that the quasispecies distribution of IRES sequences does not play a role in HCV resistance to interferon-alpha therapy. In contrast, the overall quasispecies distribution of HCV genomes (including IRES sequences) might participate in regulation of hepatic and extrahepatic HCV replication.

  8. Rotational dynamics of bases in the gene coding interferon alpha 17 (IFNA17).

    PubMed

    Krasnobaeva, L A; Yakushevich, L V

    2015-02-01

    In the present work, rotational oscillations of nitrogenous bases in the DNA with the sequence of the gene coding interferon alpha 17 (IFNA17), are investigated. As a mathematical model simulating oscillations of the bases, we use a system of two coupled nonlinear partial differential equations that takes into account effects of dissipation, action of external fields and dependence of the equation coefficients on the sequence of bases. We apply the methods of the theory of oscillations to solve the equations in the linear approach and to construct the dispersive curves determining the dependence of the frequency of the plane waves (ω) on the wave vector (q). In the nonlinear case, the solutions in the form of kink are considered, and the main characteristics of the kink: the rest energy (E0), the rest mass (m0), the size (d) and sound velocity (C0), are calculated. With the help of the energetic method, the kink velocity (υ), the path (S), and the lifetime (τ) are also obtained.

  9. Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis and growth

    PubMed Central

    Gupta, Romi; Forloni, Matteo; Bisserier, Malik; Dogra, Shaillay Kumar; Yang, Qiaohong; Wajapeyee, Narendra

    2016-01-01

    Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth. IFI6 was transcriptionally upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress due to dysregulated DNA replication via E2F2. This stress consequentially inhibited cellular transformation and melanoma growth via senescence or apoptosis induction depending on the RB and p53 pathway status of the cells. NRAS-mutant melanoma were significantly more resistant to the cytotoxic effects of DNA replication stress-inducing drugs, and knockdown of IFI6 increased sensitivity to these drugs. Pharmacological inhibition of IFI6 expression by the MEK inhibitor trametinib, when combined with DNA replication stress-inducing drugs, blocked NRAS-mutant melanoma growth. Collectively, we demonstrate that IFI6, via E2F2 regulates DNA replication and melanoma development and growth, and this pathway can be pharmacologically targeted to inhibit NRAS-mutant melanoma. DOI: http://dx.doi.org/10.7554/eLife.16432.001 PMID:27608486

  10. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha.

    PubMed

    Browne, Edward P; Letham, Benjamin; Rudin, Cynthia

    2016-01-01

    Type 1 interferons such as interferon-alpha (IFNα) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses. PMID:27010978

  11. Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone.

    PubMed

    Kiladjian, J-J; Giraudier, S; Cassinat, B

    2016-04-01

    Interferon alpha (IFN-α) has been used for over 30 years to treat myeloproliferative neoplasms (MPNs). IFN-α was shown to induce clinical, hematological, molecular and histopathological responses in small clinical studies. Such combined efficacy has never been achieved with any other drug to date in such a significant proportion of patients. However, toxicity remains a limitation to its broader use despite the development of pegylated forms with better tolerance. Several on going phase 3 studies of peg- IFN-α versus hydroxyurea will help to define its exact place in MPN management. IFN-α efficacy is likely the consequence of a broad range of biological properties, including enhancement of immune response, direct effects on malignant cells and ability to cycle dormant malignant stem cells. However, comprehensive elucidation of its mechanism of action is still lacking. Sustained clinical, molecular and morphological responses after IFN-α discontinuation raised the hope that this drug could eradicate MPN. There is now consistent evidence showing that IFN-α is able to eliminate malignant clones harboring JAK2V617F or Calreticulin mutations. However, the molecular complexity of these diseases could hamper IFN-α efficacy, as the presence of additional non-driver mutations, like in the TET2 gene, could be associated with resistance to IFN-α. Therefore, combined therapy with another targeted agent could be required to eradicate MPN, and the best IFN-α companion for achieving this challenge remains to be determined.

  12. Photodegradation mechanism and reaction kinetics of recombinant human interferon-alpha2a.

    PubMed

    Kim, Hyong-Ha; Lee, Yun Mi; Suh, Jung-Keun; Song, Nam Woong

    2007-02-01

    The photodegradation mechanism of recombinant human interferon-alpha2a (IFNalpha2a) has been investigated using absorption, fluorescence, and circular dichroism (CD) spectroscopies, and fluorescence photobleaching kinetics measurements under various conditions. After photobleaching, the absorption profile of aromatic amino acid residues in IFNalpha2a was almost absent, and an absorption profile showing a monotonic increase toward short wavelengths was observed. According to the CD spectrum analysis, partial unfolding of IFNalpha2a was accompanied by a complete loss of fluorescence. This unfolding was attributed to tryptophan-mediated photoinduced disulfide bond cleavage. Photooxygenation and photoionization of tryptophan (Trp) residues followed by subsequent radical reactions were the main photodegradation pathways of IFNalpha2a. Photobleaching kinetics was faster in acidic solution (pH 2.5) than in neutral solution (pH 7.4). The variation of photobleaching kinetics seemed to be caused by the structural differences in IFNalpha2a according to the solution pH. The relationship between the protein conformation and photobleaching rate could be explained based on the competition between excited state energy transfer and the photoionization process in Trp residues. PMID:17277841

  13. [Effect of small doses of interferon-alpha on food conditioning in young and ageing rats].

    PubMed

    Loseva, E V; Loginova, N A; Biriukovan, L M; Mats, V N; Pasikova, N V

    2007-04-01

    Low doses (10 or 350 ME) of human interferon-alpha (HIA) were intranasally applied to young (3-4 months) and ageing (12-15 months) Wistar rats during food conditioning. In control groups, development of the conditioned reflex to acoustic stimulus (tone) did not differ significantly in young and ageing rats in the course of chronic applications of the HIA. However, the control ageing rats were better than young rats in time-interval conditioning. Small doses of HIA do not cause anorexia in rats whereas large doses do so. Tone-conditioning did not change in rats of both ages when they were treated with 10 ME of the HIA; moreover, 350 ME increased food motivation, especially in young rats. Time-interval conditioning in aging rats was descended by both doses to the level of young rats, whereas in young rats it did not change at all. We suggest that these differences between ages may by accounted for be different affinity and concentration of micro-opiod receptors (which are the targets for the HIA) in the brain structures responsible for food behaviour, and for counting time intervals.

  14. Repression of the murine interferon alpha 11 gene: identification of negatively acting sequences.

    PubMed Central

    Civas, A; Dion, M; Vodjdani, G; Doly, J

    1991-01-01

    The uninducible murine interferon alpha 11 gene (Mu IFN-alpha 11) shows strong homology with the highly inducible Mu IFN-alpha 4 gene in the promoter region. Negative regulatory sequences located between positions -470 and -145 were characterized in the Mu IFN-alpha 11 promoter. The removal of these sequences leads to virus-inducibility of Mu IFN-alpha 11 while their insertion in Mu IFN-alpha 4 corresponding region significantly reduced the inducibility of Mu IFN-alpha 4 promoter. On the other hand, the virus-responsive element (VRE) of the Mu IFN-alpha 11 differs by a single nucleotide substitution at position -78 from the VRE alpha 4. Constructions carrying either VRE alpha 11 or VRE alpha 4 upstream a heterologous promoter displayed different virus inducibilities. The -78 A/G substitution affects the inducibility by decreasing the affinity of VRE-binding trans-regulators. Our results suggest that the combined effect of the negative regulatory sequences and of the mutation in the VRE alpha 11, completely silences the Mu IFN-alpha 11 gene. PMID:1886773

  15. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha

    PubMed Central

    Browne, Edward P.; Letham, Benjamin; Rudin, Cynthia

    2016-01-01

    Type 1 interferons such as interferon-alpha (IFNα) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses. PMID:27010978

  16. Mutations of the human interferon alpha-2b (hIFN-α2b) gene in occupationally protracted low dose radiation exposed personnel.

    PubMed

    Shahid, Saman; Mahmood, Nasir; Chaudhry, Muhammad Nawaz; Sheikh, Shaharyar; Ahmad, Nauman

    2015-05-01

    Ionizing radiations impact human tissues by affecting the DNA bases which constitute genes. Human interferon alpha 2b gene synthesizes a protein which is an important anticancerous, immunomodulatory, anti-proliferative and antiviral protein. This study was aimed to identify interferon alpha-2b mutations as a consequence of the use of occupational chronic low dose radiation by hospital radiation exposed workers. A molecular analysis was done in which DNAs were extracted from blood samples from radiology, radiotherapy and nuclear medicine workers. The gene was amplified through polymerase chain reaction and further genetic data from sequencing results analyzed by bioinformatics tools in order to determine as to how mutations in interferon alpha 2b sequences will lead to changes in human interferon alpha-2b protein. A total of 41% gene mutations was detected among all radiation exposed workers in which higher percentage (5.4%) of base insertion mutations and 14% frameshift mutations were found in radiology workers. The chronic use of low dose of radiations by occupational workers has a significant correlation with mutational effects on interferon alpha 2b gene, further evident by depressed interferon alpha levels in serum. This can lead to depressed immunity in radiation exposed workers. Hematological profiling of this group also showed hyperimmune response in the form of lymphocytosis.

  17. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

    PubMed

    Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

    2013-06-01

    The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

  18. Interferon-alpha and bortezomib overcome Bcl-2 and Mcl-1 over-expression in melanoma cells by stimulating the extrinsic pathway of apoptosis

    PubMed Central

    Lesinski, Gregory B.; Raig, Ene T.; Guenterberg, Kristan; Brown, Lloyd; Go, Michael R.; Shah, Nisha N.; Lewis, Adrian; Quimper, Megan; Hade, Erinn; Young, Gregory; Chaudhury, Abhik Ray; Ladner, Katherine J.; Guttridge, Denis C.; Bouchard, Page

    2008-01-01

    We hypothesized that interferon-alpha (IFN-α) would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-α induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspases-3, -7, -8, -9, and with cleavage of Bid and PARP. Bortezomib plus IFN-α was effective at inducing apoptosis in melanoma cells that over-expressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The pro-apoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD prior to the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or siRNA targeting Fas. These data suggest that bortezomib and IFN-α act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-α displayed statistically significant anti-tumor activity as compared to either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-α for malignant melanoma. PMID:18922907

  19. A phase II trial of concomitant human interleukin-2 and interferon-alpha-2a in patients with disseminated malignant melanoma.

    PubMed

    Whitehead, R P; Figlin, R; Citron, M L; Pfile, J; Moldawer, N; Patel, D; Jones, G; Levitt, D; Zeffren, J

    1993-02-01

    Interleukin-2 (IL-2) and alpha-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 10(6) U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-alpha-2a at a dose of 6 x 10(6) U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and alpha-interferon does not appear to be better than the single agents used alone in optimal dosage. PMID:8318496

  20. Research in simple blind with natural interferon alpha at low dosage on subjects affected by labialis and genitalis herpes simplex.

    PubMed

    Scalvenzi, M; Ceddia, C

    2000-01-01

    According to the studies (1,2) on the stimulating activity of the immune defense of animals (mice, cats) treated with low doses by oral route of natural Interferon alpha, the activity of the product in human for labialis and genitalis herpetic infection in a simple blind study has been evaluated. The study has been performed on 40 patients (21 F and 19 M) aged between 18 and 62 years old, with dosage of 150 I.U. twice/thrice a day for 10 days. In the subjects treated we had a fast resolution, with statistical significativity of herpetic manifestations and associated symptoms.

  1. Homology model of human interferon-alpha 8 and its receptor complex.

    PubMed Central

    Seto, M. H.; Harkins, R. N.; Adler, M.; Whitlow, M.; Church, W. B.; Croze, E.

    1995-01-01

    Human interferon-alpha 8 (HuIFN alpha 8), a type I interferon (IFN), is a cytokine belonging to the hematopoietic super-family that includes human growth hormone (HGH). Recent data identified two human type I IFN receptor components. One component (p40) was purified from human urine by its ability to bind to immobilized type I IFN. A second receptor component (IFNAR), consisting of two cytokine receptor-like domains (D200 and D200'), was identified by expression cloning. Murine cells transfected with a gene encoding this protein were able to produce an antiviral response to human IFN alpha 8. Both of these receptor proteins have been identified as members of the immunoglobulin superfamily of which HGH receptor is a member. The cytokine receptor-like structural motifs present in p40 and IFNAR were modeled based on the HGH receptor X-ray structure. Models of the complexes of HuIFN alpha 8 with the receptor subunits were built by superpositioning the conserved C alpha backbone of the HuIFN alpha 8 and receptor subunit models with HGH and its receptor complex. The HuIFN alpha 8 model was constructed from the C alpha coordinates of murine interferon-beta crystal structure. Electrostatic potentials and hydrophobic interactions appear to favor the model of HuIFN alpha 8 interacting with p40 at site 1 and the D200' domain of IFNAR at site 2 because there are regions of complementary electrostatic potential and hydrophobic interactions at both of the proposed binding interfaces. Some of the predicted receptor binding residues within HuIFN alpha 8 correspond to functionally important residues determined previously for human IFN alpha 1, IFN alpha 2, and IFN alpha 4 subtypes by site-directed mutagenesis studies. The models predict regions of interaction between HuIFN alpha 8 and each of the receptor proteins, and provide insights into interactions between other type I IFNs (IFN-alpha subtypes and IFN-beta) and their respective receptor components. PMID:7613464

  2. Maintenance and Operations study for K basins sludge treatment

    SciTech Connect

    WESTRA, A.G.

    1998-11-30

    This study evaluates maintenance and operating concepts for the chemical treatment of sludge from the 100 K Basins at Hanford. The sludge treatment equipment that will require remote operation or maintenance was identified. Then various maintenance and operating concepts used in the nuclear industry were evaluated for applicability to sludge treatment. A hot cell or cells is recommended as the best maintenance and operating concept for a sludge treatment facility.

  3. Pharmacological maintenance treatments of opiate addiction.

    PubMed

    Bell, James

    2014-02-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

  4. Pharmacological maintenance treatments of opiate addiction

    PubMed Central

    Bell, James

    2014-01-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been ‘programmatic’, with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some ‘nonresponders’ and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy. PMID:23210630

  5. [Maintenance and monitoring of water treatment system].

    PubMed

    Pontoriero, G; Pozzoni, P; Tentori, F; Scaravilli, P; Locatelli, F

    2005-01-01

    Water treatment systems must be submitted to maintenance, disinfections and monitoring periodically. The aim of this review is to analyze how these processes must complement each other in order to preserve the efficiency of the system and optimize the dialysis fluid quality. The correct working of the preparatory process (pre-treatment) and the final phase of depuration (reverse osmosis) of the system need a periodic preventive maintenance and the regular substitution of worn or exhausted components (i.e. the salt of softeners' brine tank, cartridge filters, activated carbon of carbon tanks) by a competent and trained staff. The membranes of reverse osmosis and the water distribution system, including dialysis machine connections, should be submitted to dis-infections at least monthly. For this purpose it is possible to use chemical and physical agents according to manufacturer' recommendations. Each dialysis unit should predispose a monitoring program designed to check the effectiveness of technical working, maintenance and disinfections and the achievement of chemical and microbiological standards taken as a reference. Generally, the correct composition of purified water is monitored by continuous measuring of conductivity, controlling bacteriological cultures and endotoxin levels (monthly) and checking water contaminants (every 6-12 months). During pre-treatment, water hardness (after softeners) and total chlorine (after chlorine tank) should be checked periodically. Recently the Italian Society of Nephrology has developed clinical guidelines for water and dialysis solutions aimed at suggesting rational procedures for production and monitoring of dialysis fluids. It is hopeful that the application of these guidelines will lead to a positive cultural change and to an improvement in dialysis fluid quality. PMID:16342048

  6. The interferon-alpha gene family of Marmota himalayana, a Chinese marmot species with susceptibility to woodchuck hepatitis virus infection.

    PubMed

    Lu, Yinping; Wang, Baoju; Huang, Hongping; Tian, Yongjun; Bao, Junjie; Dong, Jihua; Roggendorf, Michael; Lu, Mengji; Yang, Dongliang

    2008-01-01

    The interferon-alpha (IFN-alpha) gene family is an important part of the immune system. Recombinant interferon-alpha is widely used to treat viral hepatitis and malignant diseases. Marmota himalayana has been found to be susceptible to woodchuck hepatitis virus, a virus genetically related to hepatitis B virus (HBV), and is suitable as an animal model for studies on HBV infection. Here, the IFN-alpha gene family of M. himalayana (cwIFN-alpha) was characterized. Sequence data indicate that the cwIFN-alpha family consists of at least 8 functional sequences and 6 pseudogenes with high homology within the family and to IFN-alpha of Marmota monax, a related species and well-established animal model. The recombinant cwIFN-alpha subtypes were expressed and tested to be active in viral protection assay and to induce expression of MxA in a species-specific manner. This work provides essential information for future work on testing new therapeutic approaches of HBV infection based on IFN-alpha in M. himalayana.

  7. Vaccination of patients with metastatic renal cancer with modified vaccinia Ankara encoding the tumor antigen 5T4 (TroVax) given alongside interferon-alpha.

    PubMed

    Hawkins, Robert E; Macdermott, Catriona; Shablak, Alaaeldin; Hamer, Caroline; Thistlethwaite, Fiona; Drury, Noel L; Chikoti, Priscilla; Shingler, William; Naylor, Stuart; Harrop, Richard

    2009-05-01

    Approximately 90% of renal cell tumors overexpress the tumor antigen 5T4. The attenuated strain of vaccinia virus, modified vaccinia Ankara, has been engineered to express 5T4 (TroVax). We conducted an open-label phase 1/2 trial in which TroVax was administered alongside interferon-alpha (IFNalpha) to 11 patients with metastatic renal cell carcinoma. Antigen-specific cellular and humoral responses were monitored throughout the study, and clinical responses were assessed by measuring the changes in tumor burden by computed tomography scan (Response Evaluation Criteria In Solid Tumors). The primary objective was to assess the safety, immunogenicity, and efficacy of TroVax when given alongside IFNalpha. Treatment with TroVax plus IFNalpha was well tolerated with no serious adverse events attributed to TroVax. All 11 patients mounted 5T4-specific antibody responses and 5 (45%) mounted cellular responses. No objective tumor responses were seen, but the overall median time to progression (TTP) of 9 months (range: 2.1 to 26+ mo) was longer than expected for IFNalpha alone. For the 10 clear cell patients the TTP ranged from 3.9 to 26+ months, with a median TTP of 10.4 months. The high frequency of 5T4-specific immune responses and prolonged median TTP for clear cell patients compared with that expected for IFNalpha alone is encouraging and warrants further investigation.

  8. The Recombinant Vaccinia Virus Gene Product, B18R, Neutralizes Interferon Alpha and Alleviates Histopathological Complications in an HIV Encephalitis Mouse Model

    PubMed Central

    Fritz-French, Cari; Shawahna, Ramzi; Ward, Jennifer E.; Maroun, Leonard E.

    2014-01-01

    Interferon-alpha (IFN-α) has been identified as a neurotoxin that plays a prominent role in human immunodeficiency virus (HIV)-associated neurocognitive disorders and HIV encephalitis (HIVE) pathology. IFN-α is associated with cognitive dysfunction in other inflammatory diseases where IFN-α is upregulated. Trials of monoclonal anti-IFN-α antibodies have been generally disappointing possibly due to high specificity to limited IFN-α subtypes and low affinity. We investigated a novel IFN-α inhibitor, B18R, in an HIVE/severe combined immunodeficiency (SCID) mouse model. Immunostaining for B18R in systemically treated HIVE/SCID mice suggested the ability of B18R to cross the blood–brain barrier (BBB). Real-time PCR indicated that B18R treatment resulted in a decrease in gene expression associated with IFN-α signaling in the brain. Mice treated with B18R were found to have decreased mouse mononuclear phagocytes and significant retention of neuronal arborization compared to untreated HIVE/SCID mice. Increased mononuclear phagocytes and decreased neuronal arborization are key features of HIVE. These results suggest that B18R crosses the BBB, blocks IFN-α signaling, and it prevents key features of HIVE pathology. These data suggest that the high affinity and broad IFN-α subtype specificity of B18R make it a viable alternative to monoclonal antibodies for the inhibition of IFN-α in the immune-suppressed environment. PMID:24564363

  9. Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is an economically significant, highly contagious swine disease. The etiological agent, CSF virus (CSFV), is an enveloped virus with a positive-sense, single-stranded RNA genome, classified as a member of the genus Pestivirus within the family Flaviviridae (Becher et al.,...

  10. Interferon-alpha gene therapy prevents aflatoxin and carbon tetrachloride promoted hepatic carcinogenesis in rats.

    PubMed

    Aziz, Talaat Abdel; Aziz, Mohammed Abdel; Fouad, Hanan Hassan; Rashed, Laila Ahmed; Salama, Hosny; Abd-Alla, Samira; Wehab, Mosaad Attia Abdel; Ahmed, Tauseef

    2005-01-01

    Retrovirus-mediated interferon alpha (IFN-alpha) gene transfer was evaluated with regard to its possible protective effects against aflatoxin B1 (AFB1)-initiated and carbon tetrachloride (CCl4)-promoted hepatic carcinogenesis in rats. To our knowledge, this is the first time an experimental in vivo gene therapy trial was conducted in Egypt. Two genes were examined in liver tissue by RT-PCR: the first was glutathione-S-transferase placental (GST-P) isoenzyme, as an early marker to detect hepatic malignancy; the second was IFN-alpha gene expression to detect the efficiency of gene uptake and its persistence after transduction. Forty male rats, divided equally into 4 groups, were included in the study: the first group was the control; the second group received CCl4 0.2 ml subcutaneously twice weekly for 12 weeks and AFB1 0.25 mg/kg body wt intraperitoneally twice weekly for 6 weeks; the third group received IFN-alpha (10(8) pfu) intravenously in the tail vein prior to the start of CCl4 and AFB1 injections; and the fourth group received IFN-alpha (10(8) pfu) by intrahepatic injection under ultrasonography guide after termination of the CCl4 and AFB1 injection schedule. The results showed that IFN-alpha has a marked and significant protective effect against hepatic fibrogenesis as well as hepatic carcinogenesis. Pathological examination of liver tissue proved that IFN-alpha minimized both fibrotic and cirrhotic processes. The amount of fibrosis was less in both groups receiving IFN-alpha, with more protection in the group that received IFN-alpha intravenously prior to CCl4 and AFB1. The results of RT-PCR showed that the IFN-alpha gene was significantly expressed in both groups receiving IFN-alpha, with a more intense expression in the group that received IFN-alpha by intrahepatic injection after termination of CCl4 and AFB1 injections. The IFN-alpha gene was detected after three months of gene transduction in rats receiving IFN-alpha intravenously prior to CCl4 and AFB1

  11. Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study

    PubMed Central

    Terrier, Benjamin; Lapidus, Nathanael; Pol, Stanislas; Serfaty, Lawrence; Ratziu, Vlad; Asselah, Tarik; Thibault, Vincent; Souberbielle, Jean-Claude; Carrat, Fabrice; Cacoub, Patrice

    2015-01-01

    AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin (PegIFN/RBV) therapy could improve the efficacy of PegIFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus (HCV) infection. METHODS: Genotype 1 or 4 HCV-infected patients with null response to previous PegIFN/RBV treatment and with hypovitaminosis D (< 30 ng/mL) prospectively received cholecalciferol 100000 IU per week for 4 wk [from week -4 (W-4) to W0], followed by 100000 IU per month in combination with PegIFN/RBV for 12 mo (from W0 to W48). The primary outcome was the rate of early virological response defined by an HCV RNA < 12 IU/mL after 12 wk PegIFN/RBV treatment. RESULTS: A total of 32 patients were included, 19 (59%) and 13 (41%) patients were HCV genotype 1 and 4, respectively. The median baseline vitamin D level was 15 ng/mL (range: 7-28). In modified intention-to-treat analysis, 29 patients who received at least one dose of PegIFN/RBV were included in the analysis. All patients except one normalized their vitamin D serum levels. The rate of early virologic response was 0/29 (0%). The rate of HCV RNA < 12 IU/mL after 24 wk of PegIFN/RBV was 1/27 (4%). The safety profile was favorable. CONCLUSION: Addition of vitamin D to PegIFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1 or 4 HCV infection. PMID:25987791

  12. Behavioral and physiological effects of a single injection of rat interferon-alpha on male Sprague-Dawley rats: a long-term evaluation.

    PubMed

    Kentner, A C; Miguelez, M; James, J S; Bielajew, C

    2006-06-20

    Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.

  13. Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon alpha

    PubMed Central

    Braybrooke, J P; Propper, D J; O’Byrne, K J; Koukourakis, M I; Patterson, A V; Houlbrook, S; Love, S D; Varcoe, S; Taylor, M; Ganesan, T S; Talbot, D C; Harris, A L

    2000-01-01

    Thymidine phosphorylase (TP) is an essential enzyme for the biochemical activation of 5-fluorouracil (5-FU). Interferon upregulates TP in vivo, although the dose and schedule of interferon for optimal biomodulation of 5-FU is not known. In this study, TP activity was measured in peripheral blood lymphocytes (PBLs) from patients with advanced carcinoma receiving treatment with 5-FU and folinic acid. Cohorts of patients were treated with interferon alpha (IFNα), immediately prior to 5-FU/folinic acid, at doses of 3 MIU m–2, 9 MIU m–2and 18 MIUm–2. IFNα was administered on day 0 cycle two, day –1 and day 0 cycle three and day –2, day –1 and day 0 cycle four. A fourth cohort was treated with IFNα 9 MIU m–2three times per week from cycle 2 onwards. Twenty-one patients were entered into the study with 19 evaluable for response. Six patients (32%) had stable disease and 13 (68%) progressive disease. There were no grade-IV toxicities. TP activity was detected in PBLs from all patients with wide interpatient variability in constitutive TP activity prior to chemotherapy, and in response to IFNα. 5-FU/folinic acid alone did not induce TP activity but a single dose of IFNα led to upregulation of TP within 2 h of administration with a further increase by 24 h (signed rank test, P = 0.006). TP activity remained elevated for at least 13 days (signed rank test, P = 0.02). There were no significant differences in TP activity between schedules or with additional doses of IFNα. A single dose of IFNα as low as 3 MIU m–2can cause sustained elevation of PBL TP activity in vivo indicating that biochemical markers are important pharmacodynamic endpoints for developing optimal schedules of IFNα for biomodulation of 5-FU. © 2000 Cancer Research Campaign PMID:10901374

  14. Behavioral Treatments During Outpatient Methadone Maintenance: A Controlled Evaluation.

    ERIC Educational Resources Information Center

    Bigelow, George; And Others

    The Treatment Evaluation Project was established to evaluate the feasibility of using behavioral treatment in conjunction with methadone maintenance to improve the effectiveness of methadone treatment. Over 100 outpatients were accepted into treatment and randomly assigned to one of four behavioral treatment modalities in addition to the usual…

  15. An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys)

    PubMed Central

    Chon, Young Eun; Kim, Dong Joon; Kim, Sang Gyune; Kim, In Hee; Bae, Si Hyun; Hwang, Seong Gyu; Heo, Jeong; Jang, Jeong Won; Lee, Byung Seok; Kim, Hyung Joon; Jun, Dae Won; Kim, Kang Mo; Chung, Woo Jin; Choi, Moon Seok; Jang, Jae Young; Yim, Hyung Joon; Tak, Won Young; Yoon, Ki Tae; Park, Jun Yong; Han, Kwang-Hyub; Suk, Ki Tae; Lee, Hyun Woong; Jang, Byoung Kuk; Ahn, Sang Hoon

    2016-01-01

    Abstract Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type. We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated. In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a. In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs. PMID:27057828

  16. An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys): TRACES Study.

    PubMed

    Chon, Young Eun; Kim, Dong Joon; Kim, Sang Gyune; Kim, In Hee; Bae, Si Hyun; Hwang, Seong Gyu; Heo, Jeong; Jang, Jeong Won; Lee, Byung Seok; Kim, Hyung Joon; Jun, Dae Won; Kim, Kang Mo; Chung, Woo Jin; Choi, Moon Seok; Jang, Jae Young; Yim, Hyung Joon; Tak, Won Young; Yoon, Ki Tae; Park, Jun Yong; Han, Kwang-Hyub; Suk, Ki Tae; Lee, Hyun Woong; Jang, Byoung Kuk; Ahn, Sang Hoon

    2016-04-01

    Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated.In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a.In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs.

  17. An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys): TRACES Study.

    PubMed

    Chon, Young Eun; Kim, Dong Joon; Kim, Sang Gyune; Kim, In Hee; Bae, Si Hyun; Hwang, Seong Gyu; Heo, Jeong; Jang, Jeong Won; Lee, Byung Seok; Kim, Hyung Joon; Jun, Dae Won; Kim, Kang Mo; Chung, Woo Jin; Choi, Moon Seok; Jang, Jae Young; Yim, Hyung Joon; Tak, Won Young; Yoon, Ki Tae; Park, Jun Yong; Han, Kwang-Hyub; Suk, Ki Tae; Lee, Hyun Woong; Jang, Byoung Kuk; Ahn, Sang Hoon

    2016-04-01

    Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated.In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a.In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs. PMID:27057828

  18. Dose-response studies of interferon-alpha 2b on liver fibrosis and cholestasis induced by biliary obstruction in rats.

    PubMed

    Muriel, P; Castro, V

    1997-04-01

    Interferons have been utilized widely in chronic liver diseases for their antiviral properties. In addition, there is evidence for their antifibrogenic actions. In this work we studied effects of various doses of interferon-alpha 2b on experimental liver fibrosis and cholestasis induced in the rat by biliary obstruction. Collagen was measured as hepatic hydroxyproline content. Cholestasis was determined by serum alkaline phosphatase and gamma-glutamyltranspeptidase activities and by bilirubin content. Glycogen was measured in the liver. Interestingly, the best effects (antifibrotic and anticholestatic) were observed in the group receiving the lowest dose of interferon. These results suggest that interferon-alpha 2b may be used at low doses, thereby decreasing side effects and costs. PMID:9211563

  19. Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

    PubMed

    Gupta, Samir K; Pittenger, Amy L; Swan, Suzanne K; Marbury, Thomas C; Tobillo, Emlyn; Batra, Vijay; Sack, Marshall; Glue, Paul; Jacobs, Sheila; Affrime, Melton

    2002-10-01

    This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.

  20. Interferon-alpha 2b quantification in inclusion bodies using reversed phase-ultra performance liquid chromatography (RP-UPLC).

    PubMed

    Cueto-Rojas, H F; Pérez, N O; Pérez-Sánchez, G; Ocampo-Juárez, I; Medina-Rivero, E

    2010-04-15

    Interferon-alpha 2b (IFN-alpha 2b) is a recombinant therapeutic cytokine produced as inclusion bodies using a strain of Escherichia coli as expression system. After fermentation and recovery, it is necessary to know the amount of recombinant IFN-alpha 2b, in order to determine the yield and the load for solubilization, and chromatographic protein purification steps. The present work details the validation of a new short run-time and fast sample-preparation method to quantify IFN-alpha 2b in inclusion bodies using Reversed Phase-Ultra Performance Liquid Chromatography (RP-UPLC). The developed method demonstrated an accuracy of 100.28%; the relative standard deviations for method precision, repeatability and inter-day precision tests were found to be 0.57%, 1.54% and 1.83%, respectively. Linearity of the method was assessed in the range of concentrations from 0.05 mg/mL to 0.5 mg/mL, the curve obtained had a determination coefficient (r(2)) of 0.9989. Detection and quantification limits were found to be 0.008 mg/mL and 0.025 mg/mL, respectively. The method also demonstrated robustness for changes in column temperature, and specificity against host proteins and other recombinant protein expressed in the same E. coli strain. PMID:20299292

  1. Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells

    PubMed Central

    Yin, Hongmei; Chen, Naifei; Guo, Rui; Wang, Hong; Li, Wei; Wang, Guanjun; Cui, Jiuwei; Jin, Haofan; Hu, Ji-Fan

    2015-01-01

    Pancreatic cancer is the most aggressive malignant disease, ranking as the fourth leading cause of cancer-related death among men and women in the United States. Interferon alpha (IFNα) has been used to treat pancreatic cancer, but its clinical application has been significantly hindered due to the low antitumor activity. We used a “cDNA in-frame fragment library” screening approach to identify short peptides that potentiate the antitumor activity of interferons. A short positively charged peptide derived from the C-terminus of placental growth factor-2 (PLGF-2) was selected to enhance the activity of IFNα. For this, we constructed a synthetic interferon hybrid molecule (SIFα) by fusing the positively charged PLGF-2 peptide to the C-terminus of the human IFNα. Using human pancreatic cell lines (ASPC and CFPAC1) as a model system, we found that SIFα exhibited a significantly higher activity than did the wild-type IFNα in inhibiting the tumor cell growth. The enhanced activity of the synthetic SIFα was associated with the activation of interferon pathway target genes and the increased binding of cell membrane receptor. This study demonstrates the potential of a synthetic SIFα as a novel antitumor agent. PMID:26584517

  2. Interactions of interferon-alpha 2a with 5'-deoxy-5-fluorouridine in colorectal cancer cells in vitro.

    PubMed

    Tevaearai, H T; Laurent, P L; Suardet, L; Eliason, J F; Givel, J C; Odartchenko, N

    1992-01-01

    The biological activity of 5'-deoxy-5-fluorouridine (5'-dFUrd) depends upon intracellular enzymatic cleavage by pyrimidine phosphorylase to form 5-fluorouracil (5-FU). Interferon-alpha 2a (IFN-alpha) effect was analysed alone and combined with 5-FU or 5'-dFUrd, on proliferation inhibition of eight human colorectal cancer cell lines. The toxicity of 5-FU was enhanced by IFN-alpha in only one line (SW-480). In contrast, interactive enhancement of IFN-alpha was observed with 5'-dFUrd in five lines (WiDr, HT-29, 513, SW-480 and Co-115). In each of the lines showing potentiation by IFN/5'dFUrd but not by IFN/5-FU, cytoplasmic pyrimidine phosphorylase activity was increased after 5 days' incubation with IFN-alpha in a dose-dependent manner. Two lines (LISP-1 and SW-620) showed no potentiation of either 5-FU or 5'-dFUrd toxicity by IFN-alpha, and no change in pyrimidine phosphorylase activity. Potentiation of 5'-dFUrd effect by IFN-alpha may thus be explained by an enhancement of its conversion to 5-FU through stimulation of pyrimidine phosphorylase activity. PMID:1534247

  3. Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP) in Patients with Malignant Melanoma

    PubMed Central

    Ensslen, Silke; Marquardt, Yvonne; Czaja, Katharina; Joussen, Sylvia; Beer, Daniel; Abele, Rupert; Plewnia, Gabriele; Tampé, Robert; Merk, Hans F.; Hermanns, Heike M.; Baron, Jens M.

    2016-01-01

    Introduction Interferon alpha (IFNα) is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1) is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling. Results We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs) of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment. Conclusion We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in ‘silent’ metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and

  4. Reversible myopathy during successful treatment with pegylated interferon and ribavirin for acute hepatitis C.

    PubMed

    Golstein, P E; Delforge, M L; Deviere, J; Marcellin, P

    2004-03-01

    There is no standard approved treatment for acute hepatitis C and the combination of pegylated interferon-alpha and ribavirin, currently recognized as the standard of care for chronic hepatitis C, has not been evaluated for acute hepatitis C. Adverse events induced by interferon therapy are numerous but myopathy is rare and has not been described with the use of pegylated interferon-alpha. We report the case of a 33-year-old Caucasian man who was successfully treated for acute hepatitis C with the combination of pegylated interferon-alpha2b and ribavirin, and who during treatment developed myopathy which proved reversible.

  5. Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China

    PubMed Central

    Wu, Qin; Zhan, Feng Yu; Chen, En Qiang; Wang, Cong; Li, Zhen Zhen; Lei, Xue Zhong

    2015-01-01

    Background: Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China. Objectives: We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR). Patients and Methods: We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0. Results: Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ2 = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ2 = 16.552, P < 0.001), RVR (χ2 = 37.339, P < 0.001), and EVR (χ2 = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ2 = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse. Conclusions: Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral

  6. Operation and Maintenance of Wastewater Treatment Facilities.

    ERIC Educational Resources Information Center

    Drury, Douglas D.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment: (1) operators, training, and certification; (2) solutions to operating problems; (3) collection systems; (4) operations manuals; (5) wastewater treatment facility case histories; (5) land application; and (6) treatment of industrial wastes. A list of 36 references is also presented. (HM)

  7. [Enhanced porcine interferon-alpha production by Pichia pastoris by methanol/sorbitol co-feeding and energy metabolism shift].

    PubMed

    Wang, Huihui; Jin, Hu; Gao, Minjie; Dai, Keke; Dong, Shijuan; Yu, Ruisong; Li, Zhen; Shi, Zhongping

    2012-02-01

    Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.

  8. Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent.

    PubMed

    Hillyer, Philippa; Mane, Viraj P; Schramm, Lynnsie M; Puig, Montserrat; Verthelyi, Daniela; Chen, Aaron; Zhao, Zeng; Navarro, Maria B; Kirschman, Kevin D; Bykadi, Srikant; Jubin, Ronald G; Rabin, Ronald L

    2012-09-01

    Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-α) and 3 IFN-λ subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) probes, and in some instances, LNA oligonucleotide inhibitors. We then measured IFN subtype expression by human peripheral blood mononuclear cells and by purified monocytes, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and monocyte-derived macrophages (MDM), and -dendritic cells (MDDC) in response to poly I:C, lipopolysaccharide (LPS), imiquimod and CpG oligonucleotides. We found that in response to poly I:C and LPS, monocytes, MDM and MDDC express a subtype pattern restricted primarily to IFN-β and IFN-λ1. In addition, while CpG elicited expression of all type I IFN subtypes by pDC, imiquimod did not. Furthermore, MDM and mDC highly express IFN-λ, and the subtypes of IFN-λ are expressed hierarchically in the order IFN-λ1 followed by IFN-λ2, and then IFN-λ3. These data support a model of coordinated cell- and ligand-specific expression of types I and III IFN. Defining IFN subtype expression profiles in a variety of contexts may elucidate specific roles for IFN subtypes as protective, therapeutic or pathogenic mediators.

  9. Topical Delivery of Interferon Alpha by Biphasic Vesicles: Evidence for a Novel Nanopathway across the Stratum Corneum

    SciTech Connect

    Foldvari, M.; Badea, B; Wettig, S; Baboolal, D; Kumar, P; Creagh, A; Haynes, C

    2010-01-01

    Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN {alpha}), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN {alpha} intercellularly, to a depth of 70 {micro}m, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN {alpha} by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN {alpha} below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN {alpha}. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.

  10. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    PubMed

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  11. Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C: case report.

    PubMed

    Carrillo-Esper, Raúl; González-Avila, Daniela; Uribe-Ríos, Marittza; Méndez-Sánchez, Nahum

    2008-01-01

    Since 2004, pegylated interferon (P-IFN) in combination with ribavirin has become the optimal choice of therapy for chronic hepatitis C virus (HCV) infection. IFN a-2b suppresses HCV replication and restores elevated serum aminotransferase levels, leading to improvements in the histological changes in the livers of patients with chronic hepatitis C. Unfortunately, P-IFN has several adverse effects, including pneumonitis. This complication has been reported in the treatment of malignant diseases and CHC. We report a patient with interstitial pneumonitis thought to be caused by an IFN-based treatment in an unusual scenario of a patient with HCV-related Child-Pugh stage A cirrhosis, who experienced dyspnea, fever, and cough after 12 months of treatment with P-IFN a-2b. Her lung injury and pulmonary symptoms did not disappear despite discontinuation of IFN and the administration of corticosteroid. We concluded that the patient developed a fatal interstitial pneumonitis associated with P-INF a-2b therapy. PMID:18376374

  12. 17β-Estradiol Protects Primary Macrophages Against HIV Infection Through Induction of Interferon-Alpha

    PubMed Central

    Tasker, Carley; Ding, Jian; Schmolke, Mirco; Rivera-Medina, Amariliz; García-Sastre, Adolfo

    2014-01-01

    Abstract Estrogen has been shown to increase resistance to HIV/SIV transmission by increasing the thickness of the genital epithelium. The immunological role of estrogen in HIV infection of primary target cells is less well characterized. We have found that primary macrophages are a target for anti-HIV activity of 17β-estradiol (E2). E2 did not affect surface expression of CD4 and HIV co-receptors nor HIV attachment to monocyte-derived macrophages (MDMs). In addition, E2 treatment blocked infection by a co-receptor-independent HIV-1VSV-G pseudotyped virus. Quantitative polymerase chain reaction analysis of HIV reverse transcribed DNA products indicated that E2 blocked HIV reverse transcription. E2 upregulated gene expression of interferons (IFNs) in MDMs from multiple donors. However, induction of host restriction factors APOBEC3G, APOBEC3F, or SAMHD1 was not consistent, with exception of APOBEC3A. Anti-HIV activity of E2 was abolished in the presence of IFN-α neutralizing antibody, and was absent in bone marrow–derived macrophages from IFN-α receptor deficient mice. Interestingly, HIV overcame E2-mediated HIV inhibition by suppressing induction of IFNs when MDMs were exposed to HIV before E2 treatment. These results offer a new mechanism of E2 on HIV inhibition. Future studies on the interplay between HIV and E2-mediated innate immune responses will likely provide insights relevant for development of effective strategies for HIV prevention. PMID:24801776

  13. [Interferon alpha 2b in pain caused by herpes zoster. Preliminary report].

    PubMed

    Montero Mora, P; Colín, D; González Espinosa, A; Almeida Arvizu, V

    1996-01-01

    We studied forty patients with Zoster Herpes, twenty two of them, with this acute disease, eighteen with postherpetic neuralgia, to those that were considered chronic. The evaluation of the effect of INF alpha 2b, in the secondary pain of Zoster Herpes acute disease, in the patients with chronic severe secondary neuralgia they shared; the evolution with the treatment for half for visual pain analog scale in both groups the patients with acute pain, entered for visual pain analog scale between 10 and two points, with medium of 8.2 SD 2.1. They did not find any significance difference with this values p < 0.6. Most of the patients with acute pain was of 6 a 0 points with the medium a 0.27 y SD: 1,2 in the chronics went from. 6 to 0 points with a medium of 1.27 (SD:2.4), with a significative difference for t Student for comparation the initial scale in final in both groups of (p < 0.0001). The comparation of the best days, the disease bettered in acute quicker than the chronics with significance difference: (p < 0.001). PMID:9053126

  14. [Interferon alpha 2b in pain caused by herpes zoster. Preliminary report].

    PubMed

    Montero Mora, P; Colín, D; González Espinosa, A; Almeida Arvizu, V

    1996-01-01

    We studied forty patients with Zoster Herpes, twenty two of them, with this acute disease, eighteen with postherpetic neuralgia, to those that were considered chronic. The evaluation of the effect of INF alpha 2b, in the secondary pain of Zoster Herpes acute disease, in the patients with chronic severe secondary neuralgia they shared; the evolution with the treatment for half for visual pain analog scale in both groups the patients with acute pain, entered for visual pain analog scale between 10 and two points, with medium of 8.2 SD 2.1. They did not find any significance difference with this values p < 0.6. Most of the patients with acute pain was of 6 a 0 points with the medium a 0.27 y SD: 1,2 in the chronics went from. 6 to 0 points with a medium of 1.27 (SD:2.4), with a significative difference for t Student for comparation the initial scale in final in both groups of (p < 0.0001). The comparation of the best days, the disease bettered in acute quicker than the chronics with significance difference: (p < 0.001).

  15. New Keys to Maintenance Treatment in Ulcerative Colitis

    PubMed Central

    Higgins, Peter D.R.

    2010-01-01

    Maintenance treatment in ulcerative colitis often fails to prevent flares and long term complications. The first key to maintenance is to use effective therapy, even when patients become asymptomatic. The second key is to communicate the importance of adherence to patients, and to help them achieve long term adherence. Simplified dosing schedules are of some benefit, but the bond between patient and doctor, and the patient's belief in the efficacy of the therapy are essential. Decreased co-pays (a fixed amount paid by patients seeking care that is not reimbursed my medical insurance) have been associated with increased adherence, and incentives for patients may be a cost-effective approach to improving adherence. While the most substantial data on the association between adherence and clinical outcomes is in 5-ASAs, non-adherence can also limit the efficacy of thiopurines and biologics. The third key to maintenance treatment is monitoring and maintaining control of inflammation. Decreased histologic and endoscopic damage to the colon has been associated with decreased risk of colon cancer. The most cost-effective way to monitor smoldering inflammation is not known, but endoscopy, structured symptom indices, and biomarkers may be valuable approaches. The fourth key to maintenance treatment is optimizing immunomodulator therapy with thiopurines, and possibly methotrexate in the future. The fifth key to maintenance treatment in ulcerative colitis is maintaining biologic efficacy by avoiding low trough levels and being vigilant for subclinical inflammation and symptom recurrence at the end of dose intervals. Combination therapy with immunomodulators improves trough levels in Crohn's, and may prove to have benefits for the maintenance of biologic efficacy in ulcerative colitis. PMID:20926876

  16. Physician Peer Assessments for Compliance with Methadone Maintenance Treatment Guidelines

    ERIC Educational Resources Information Center

    Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret

    2007-01-01

    Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…

  17. A Double-Blind Randomized Controlled Study to Evaluate the Efficacy of Low-Dose Oral Interferon-Alpha in Preventing Hepatitis C Relapse

    PubMed Central

    Lee, Chuan-Mo; Chen, Chi-Yi; Chien, Rong-Nan; Tseng, Kuo-Chih; Peng, Cheng-Yuan; Tung, Shui-Yi; Fang, Yi-Jen; Huang, Yi-Hsiang; Lu, Sheng-Nan; Hung, Chao-Hung; Tsai, Tsung-Jang; Fang, Chien-Chung; Hsu, Chao-Wei

    2014-01-01

    Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4–1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy. PMID:24237300

  18. Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better

    PubMed Central

    Rachmawati, Heni; Jessica, Adhitya; Sumirtaputra, Yeyet Cahyati; Retnoningrum, Debbie Sofie; Adlia, Amirah; Ningrum, Ratih Asmana

    2016-01-01

    Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhIFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT1, and DNA expression of caspase 3. PMID:27110503

  19. A double-blind randomized controlled study to evaluate the efficacy of low-dose oral interferon-alpha in preventing hepatitis C relapse.

    PubMed

    Lee, Chuan-Mo; Chen, Chi-Yi; Chien, Rong-Nan; Tseng, Kuo-Chih; Peng, Cheng-Yuan; Tung, Shui-Yi; Fang, Yi-Jen; Huang, Yi-Hsiang; Lu, Sheng-Nan; Hung, Chao-Hung; Tsai, Tsung-Jang; Fang, Chien-Chung; Hsu, Chao-Wei; Yeh, Chau-Ting

    2014-03-01

    Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4-1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy. PMID:24237300

  20. Lymphadenopathy in a novel mouse model of Bartonella-induced cat scratch disease results from lymphocyte immigration and proliferation and is regulated by interferon-alpha/beta.

    PubMed

    Kunz, Stefanie; Oberle, Karin; Sander, Anna; Bogdan, Christian; Schleicher, Ulrike

    2008-04-01

    In immunocompetent humans, cat scratch disease (CSD) is elicited by the Gram-negative bacterium Bartonella henselae and is characterized by a benign regional lymphadenopathy, the pathogenesis of which is poorly understood. Here, we describe a novel mouse model of Bartonella-induced CSD-like disease that allowed us to investigate the mechanisms leading to lymphadenopathy in vivo. In wild-type mice, a subcutaneous inoculation of either viable or inactivated B. henselae led to a strong swelling of the draining lymph node, which was long-lasting despite the rapid elimination of the bacteria. Carboxyfluorescein- and bromodesoxyuridine-labeling experiments showed that lymph node enlargement resulted from modified immigration and enhanced proliferation of lymphocytes, preferentially of B cells. A comparative analysis of B. henselae and the rodent pathogen B. grahamii in wild-type versus interferon-alpha/beta-receptor I chain-deficient mice revealed that interferon-alpha/beta is not only differentially induced by these two Bartonella species but also exerts an inhibitory effect on the development of lymphadenopathy both in vitro and in vivo. These data demonstrate that the lymphadenopathy of human CSD can be reproduced and studied in a mouse model and provide the first insights into the underlying immunological mechanisms.

  1. Selecting appropriate treatments for maintenance therapy for bipolar disorder.

    PubMed

    Thase, Michael E

    2008-01-01

    Long-term management of bipolar disorder is a crucial component of treatment because the recurrence of the illness negatively affects patients' daily lives and increases their risks for poor health and suicide. An ideal maintenance treatment for bipolar disorder is relatively simple to take, prevents recurrence of both manic and depressive episodes, and is well-tolerated over the long term. Although many different types of medications are used for maintenance therapy of bipolar disorder, none can be considered ideal for a majority of people with bipolar disorder, and each specific form of therapy has different strengths and limitations. Clinicians need to be aware of unique efficacy and side effect factors when choosing long-term therapy and consider treatment components, goals, and individual patient characteristics, which are essential to the successful long-term management of bipolar disorder. Additionally, several forms of psychotherapy specifically tailored to the needs of people with bipolar disorder should be considered as an adjunct to medication.

  2. Differential effects of human interferon alpha and interferon gamma on xenografted human thyroid tissue in severe combined immunodeficient mice and nude mice.

    PubMed

    Kawai, K; Enomoto, T; Fornasier, V; Resetkova, E; Volpé, R

    1997-03-01

    We have studied the in vivo effects of human interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) administration on human thyroid tissue xenografted into two mouse strains: severe combined immunodeficient (SCID) mice and nude mice. Human lymphocytes survive in SCID mice but are lysed in nude mice. Thyroid tissues from Graves' disease or Hashimoto's thyroiditis, or paranodular [normal, (N)] tissue was xenografted into SCID mice (0.8 g/mouse) pretreated with anti-asialo GM-1 antiserum and radiation and also into nude mice. One week after xenografting, SCID and nude mice were divided into three groups. Group A was treated with IFN-alpha intraperitoneally (2,000 units/mouse) three times weekly; group B was treated with IFN-gamma similarly; group C was treated with phosphate buffered saline (PBS) only (control). Autologous human peripheral blood mononuclear cells (PBMCs) were added to mice receiving N xenografts. Blood was taken every 2 weeks for levels of IgG and thyroid antibodies (TAb). After 6 weeks of treatment, mice were sacrificed, and xenograft thyrocyte histocompatibility leukocyte antigen (HLA-DR) and intercellular adhesion molecule (ICAM-1) expression were measured. In addition, thyrocyte cultures were stimulated in vitro with 200 units/ml of either IFN-alpha or IFN-gamma or PBS (control). SCID mice xenografted with autoimmune thyroid disease (AITD) in group A showed a significantly higher TAb production than group C, whereas in group B, TAb production was not statistically increased compared to control (group C). SCID mice xenografted with N did not produce TAb in any group, nor did nude mice xenografted with AITD. Thyrocyte HLA-DR expression was markedly increased in group A and B in SCID mice xenografted with Graves' disease, Hashimoto's thyroiditis, and N tissue compared to group C. In contrast, only group B (IFN-gamma) showed an increase in thyrocyte HLA-DR in nude mice. In the in vitro studies, only IFN-gamma (not IFN-alpha) stimulated

  3. Treatment of human papillomavirus infection with interferon alpha and ribavirin in a patient with acquired aplastic anemia.

    PubMed

    Mosa, Clara; Trizzino, Antonino; Trizzino, Angela; Di Marco, Floriana; D'Angelo, Paolo; Farruggia, Piero

    2014-06-01

    Genital warts caused by human papillomavirus (HPV) are the most frequent sexually transmitted infection. We describe a case of severe perianal and genital HPV infection in a patient with acquired aplastic anemia, unresponsive to traditional therapies and treated effectively with a combination of interferon and ribavirin. PMID:24661930

  4. Differential transcriptional expresión of the polymorphic myxovirus resistance protein A in response to interferon-alpha treatment.

    PubMed

    Fernández-Arcás, Nieves; Blanco, Asunción; Gaitán, M Jesús; Nyqvist, Maria; Alonso, Antonio; Reyes-Engel, Armando

    2004-03-01

    Levels of myxovirus resistance protein A (MxA) mRNA were studied for a single nucleotide polymorphism in the promoter region at nucleotide position -88 of the gene to identify individual-specific responses to interferon (IFN)-alpha2 that might predict responsiveness to IFN-alpha therapy. We quantified MxA expression by reverse transcription and real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) in vitro, induced by IFN-alpha2, from 22 healthy donors, in relation with G/T polymorphism located in the promoter of the MxA. MxA mRNA was significantly upregulated in all subjects (mean of 53-fold) in response to IFN-alpha2 in vitro (P < 0.01). Comparison of the inducibility of MxA mRNA expression in relation with G/T polymorphism showed a 4.26-fold higher induction of MxA mRNA levels in PBMC from carriers of the mutant allele (GT or TT) than homozygotes with the wild-type allele (GG) (P < 0.001). We propose that expression of the IFN-inducible MxA is affected by a single nucleotide polymorphism in the MxA promoter which can identify an individual response to IFN-alpha2.

  5. Urine naloxone concentration at different phases of buprenorphine maintenance treatment.

    PubMed

    Heikman, Pertti; Häkkinen, Margareeta; Gergov, Merja; Ojanperä, Ilkka

    2014-03-01

    In spite of the benefits of buprenorphine-naloxone co-formulation (BNX) in opioid maintenance treatment, the naloxone component has not prevented parenteral use of BNX. Current laboratory methods are not sufficient to differentiate between therapeutic and illicit use of buprenorphine, and little is known about urine naloxone concentrations. Measurement of urine naloxone, together with buprenorphine and norbuprenorphine, might help to determine the naloxone source and administration route. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for this purpose. Naloxone, buprenorphine, and norbuprenorphine total concentrations were measured in urine samples from opioid-dependent patients before and during stable and unstable phases of maintenance treatment with BNX. The limit of quantification in urine was 1.0 µg/L for naloxone, buprenorphine and norbuprenorphine. Before treatment, all samples contained buprenorphine but the median naloxone concentration was 0 µg/L. During the maintenance treatment with BNX all urine samples were positive for naloxone, buprenorphine and norbuprenorphine. The naloxone concentration at a stable phase of treatment (median 60 µg/L, range 5-200 µg/L) was not different from the naloxone concentration at an unstable phase (70 µg/L, 10-1700 µg/L). Applying an upper limit of 200 µg/L to the sample, the median naloxone/buprenorphine ratio was higher in the high than in the low naloxone concentration group (0.9 vs 0.3, respectively). This study suggests that naloxone in urine can act as an indicator of compliance with BNX. Parenteral use of BNX was associated with a high naloxone/buprenorphine ratio. Negative naloxone with positive buprenorphine suggests the use/abuse of buprenorphine alone. PMID:23512803

  6. [Obtaining of hairy-root, callus and suspension carrot culture (Daucus carota L.) able to accumulate human interferon alpha-2b].

    PubMed

    Luchakivskaia, Iu S; Olevinskaia, Z M; Kishchenko, E M; Spivak, N Ia; Kuchuk, N V

    2012-01-01

    Here we report the obtaining of suspension, callus and hairy root culture initiated from carrot plants of Nantskaya and Perfektzya variety with the highest level of recombinant human interferon alpha-2b accumulation exhibited the highest level of plant protein extract antiviral activity (up to 12.8 x 10(3) IU/mg TSP). The antiviral activity of callus extracts was significantly lower comparing to the activity of plant extracts from parent organisms. However, the antiviral activity level of suspension culture extracts (up to 4.42 x 10(3) IU/mg TSP) and Ri-root ones (up to 4.42 x 10(3) IU/mg TSP) appeared to be comparable to analogical data of antiviral activity of transgenic carrot leaf extracts, this way the described cultures could be possibly used for comparatively speedy obtaining of recombinant therapeutic protein for curing and preventing of virus diseases.

  7. OBTAINING OF THE TRANSGENIC HELIANTHUS TUBEROSUS L. PLANTS, CALLUS AND "HAIRY" ROOT CULTURES ABLE TO EXPRESS THE RECOMBINANT HUMAN INTERFERON ALPHA-2b GENE.

    PubMed

    Maistrenko, O M; Luchakivska, Yu S; Zholobak, N M; Spivak, M Ya; Kuchuk, M V

    2015-01-01

    This work is the first to our knowledge to describe the successful attempt of Agrobacterium rhizogenes-mediated transformation of topinambour in order to obtain the transgenic H. tuberosus plants, callus and "hairy" root cultures. The plasmid vectors contained the sequence of interferon gene fused with Nicotiana plumbagenifolia L. calreticulin apoplast targeting signal driven by 35S CaMV promoter or root-specific Mll promoter. Nearly 75% isolated Ri-root lines and callus cultures were proved (by PCR analysis) to contain HuINFa-2b transgene. We also managed to obtain H. tuberosus transgenic plants through somatic embryogenesis on the transgenic "hairy" root culture. The obtained transgenic H. tuberosus cultures exhibited high-level antiviral activity that ranged from 2000 to 54500 IU/g FW that makes this crop considered a promising source of recombinant interferon alpha 2b protein. PMID:26638495

  8. OBTAINING OF THE TRANSGENIC HELIANTHUS TUBEROSUS L. PLANTS, CALLUS AND "HAIRY" ROOT CULTURES ABLE TO EXPRESS THE RECOMBINANT HUMAN INTERFERON ALPHA-2b GENE.

    PubMed

    Maistrenko, O M; Luchakivska, Yu S; Zholobak, N M; Spivak, M Ya; Kuchuk, M V

    2015-01-01

    This work is the first to our knowledge to describe the successful attempt of Agrobacterium rhizogenes-mediated transformation of topinambour in order to obtain the transgenic H. tuberosus plants, callus and "hairy" root cultures. The plasmid vectors contained the sequence of interferon gene fused with Nicotiana plumbagenifolia L. calreticulin apoplast targeting signal driven by 35S CaMV promoter or root-specific Mll promoter. Nearly 75% isolated Ri-root lines and callus cultures were proved (by PCR analysis) to contain HuINFa-2b transgene. We also managed to obtain H. tuberosus transgenic plants through somatic embryogenesis on the transgenic "hairy" root culture. The obtained transgenic H. tuberosus cultures exhibited high-level antiviral activity that ranged from 2000 to 54500 IU/g FW that makes this crop considered a promising source of recombinant interferon alpha 2b protein.

  9. Interferon-alpha 2b increases fibrolysis in fibrotic livers from bile duct ligated rats: possible participation of the plasminogen activator.

    PubMed

    Rodríguez-Fragoso, L; González, M P; Muriel, P

    1995-12-01

    Interferons are known to prevent liver collagen by an antifibrogenic mechanism that involves mRNA procollagen regulation. The aim of the present work was to determine whether interferon could also decrease collagen by increasing its degradation. Fibrosis was induced in male Wistar rats by double ligation and section of the common bile duct. Interferon-alpha 2b (100,000 IU/rat s.c.) was administered to bile duct ligated rats daily after surgery for 4 weeks. Interferon increased the capacity of the liver to degrade type I and III collagens and matrigel. In addition, the plasminogen activator activity also increased. Since plasminogens are thought to be key participants in the balance of proteolytic activities that regulate extracellular matrix degradation, their elevation may also provide another antifibrotic (proteolytic) mechanism of action of interferon. PMID:8966190

  10. Effects of S-adenosyl-L-methionine and interferon-alpha2b on liver damage induced by bile duct ligation in rats.

    PubMed

    Muriel, P; Castro, V

    1998-01-01

    Interferon-alpha2b (IFN) is known to prevent and to reverse experimental liver fibrosis and damage. S-Adenosyl-L-methionine (SAM) is a well-known hepatoprotective substance. The aim of the present work was to determine the effect of the administration of both drugs simultaneously to bile duct-ligated rats. Administration of IFN (50000 IU s.c.) and/or SAM (10 mg kg[-1] i.m.) began 15 days after biliary obstruction and continued for a further 15 days. The liver was used for glycogen and collagen quantification. Bilirubins and enzyme activities were measured in serum. Either SAM or IFN ameliorated all markers of liver damage studied. However, when administered together their beneficial effects were markedly reduced. It is not possible to explain the antagonistic effect of these compounds on liver damage with the present data. More studies are needed to determine SAM-IFN interactions. PMID:9570697

  11. Pharmacologic treatments for opioid dependence: detoxification and maintenance options

    PubMed Central

    Kleber, Herbert D.

    2007-01-01

    While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses. The most effective withdrawal method is substituting and tapering methadone or buprenorphine, α-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment. Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction. PMID:18286804

  12. Intimate partner violence among individuals in methadone maintenance treatment

    PubMed Central

    de Dios, Marcel A.; Anderson, Bradley J.; Caviness, Celeste M.; Stein, Michael

    2013-01-01

    Background Intimate partner violence (IPV) is a highly prevalent and concerning problem among methadone maintenance populations, and previous studies have shown a relationship between a history of IPV and increased substance use and affective disturbances. Methods The current study examined 1) the association between recent IPV victimization and alcohol and cocaine use and 2) the relationship between recent IPV victimization and depression in a sample of smokers (n=203) in methadone maintenance treatment (MMT). Participants in this study completed a battery of assessments that included standard questionnaires of trauma, alcohol and substance use, and depression. Parallel logistic and linear regression models were used to estimate the adjusted association of IPV victimization and depressive symptoms and evaluate the adjusted association of victimization with recent substance use. Results Participants recently victimized by partners were shown to have significantly higher mean CES-D scores (b = 0.54, 95%CI 0.07; 1.02, p < .05) and were found to have a 6 times greater likelihood of cocaine use (OR = 6.65, 95%CI 1.61; 27.46, p < .01) after controlling for age, gender, education, opiate use and ethnicity. Conclusions These findings support the notion that IPV victimization can potentially increase depression and other substance use among MMT patients, which can have a deleterious impact on treatment. PMID:24821357

  13. Maintenance Check-Ups Following Treatment for Cannabis Dependence

    PubMed Central

    Walker, Denise D.; Stephens, Robert S.; Towe, Sheri; Banes, Kelsey; Roffman, Roger

    2015-01-01

    Substance use disorders, including cannabis use disorders and associated negative consequences, are best considered chronic and in need of continuing care. In contrast, most treatment efficacy studies evaluate a fixed number of intervention sessions at a single point in time. The present study evaluated the efficacy of posttreatment Maintenance Check-Ups (MCUs) in maintaining and improving outcomes following nine sessions of motivational enhancement treatment/cognitive behavioral treatment (MET/CBT). Adults dependent on cannabis (n = 74) were randomly assigned to the MCU or a No Check-Up (NCU) condition and followed up at 3-and 9-months. MCU sessions occurred 1 and 4 months following the completion of the base treatment. Additional MET/CBT sessions were available to participants throughout the follow-up period. The MCUs specifically encouraged treatment re-entry for those showing ongoing signs of disorder. Participants in the MCU condition reported significantly greater abstinent rates at both follow-ups and were using on fewer days at the 3-month but not the 9-month follow-up. Contrary to hypotheses, MCU participants did not attend more additional treatment and differences in rates of cannabis use emerged prior to the first MCU session. Future research with longer follow-up periods and longer monitoring of outcomes is needed to fully evaluate the utility of MCUs or other forms of continuing care. PMID:25922136

  14. Treatment effectiveness for legally coerced versus voluntary methadone maintenance clients.

    PubMed

    Brecht, M L; Anglin, M D; Wang, J C

    1993-01-01

    Analyses examined whether addicts reporting themselves coerced into drug abuse treatment by actions of the criminal justice system differed from voluntary admissions in their response to treatment, and whether such responsiveness varied across gender or ethnicity. Six hundred eighteen methadone maintenance clients admitted to programs in six southern California counties were categorized into high, moderate, and low legal coercion levels. Multivariate analysis of variance procedures for repeated measures (before, during, and after initial treatment episode) were used to test relevant hypotheses. Dependent variables included criminal justice system contact, criminal activities, drug and alcohol involvement, and measures of social functioning. Few differences within any measured domain were found among the three groups. All groups were similar in showing substantial improvement in levels of narcotics use, criminal activities, and most other behaviors during treatment with some regression in these behaviors posttreatment. Results support legal coercion as a valid motivation for treatment entry; those coerced into treatment respond in ways similar to voluntary admissions regardless of gender or ethnicity. PMID:8438834

  15. Maintenance Check-ups Following Treatment for Cannabis Dependence.

    PubMed

    Walker, Denise D; Stephens, Robert S; Towe, Sheri; Banes, Kelsey; Roffman, Roger

    2015-09-01

    Substance use disorders, including cannabis use disorders and associated negative consequences, are best considered chronic and in need of continuing care. In contrast, most treatment efficacy studies evaluate a fixed number of intervention sessions at a single point in time. The present study evaluated the efficacy of posttreatment maintenance check-ups (MCUs) in maintaining and improving outcomes following nine sessions of motivational enhancement treatment/cognitive behavioral treatment (MET/CBT). Adults dependent on cannabis (n=74) were randomly assigned to the MCU or a no check-up (NCU) condition and followed up at 3- and 9-months. MCU sessions occurred 1 and 4months following the completion of the base treatment. Additional MET/CBT sessions were available to participants throughout the follow-up period. The MCUs specifically encouraged treatment re-entry for those showing ongoing signs of disorder. Participants in the MCU condition reported significantly greater abstinent rates at both follow-ups and were using on fewer days at the 3-month but not the 9-month follow-up. Contrary to hypotheses, MCU participants did not attend more additional treatment and differences in rates of cannabis use emerged prior to the first MCU session. Future research with longer follow-up periods and longer monitoring of outcomes is needed to fully evaluate the utility of MCUs or other forms of continuing care. PMID:25922136

  16. Maintenance Check-ups Following Treatment for Cannabis Dependence.

    PubMed

    Walker, Denise D; Stephens, Robert S; Towe, Sheri; Banes, Kelsey; Roffman, Roger

    2015-09-01

    Substance use disorders, including cannabis use disorders and associated negative consequences, are best considered chronic and in need of continuing care. In contrast, most treatment efficacy studies evaluate a fixed number of intervention sessions at a single point in time. The present study evaluated the efficacy of posttreatment maintenance check-ups (MCUs) in maintaining and improving outcomes following nine sessions of motivational enhancement treatment/cognitive behavioral treatment (MET/CBT). Adults dependent on cannabis (n=74) were randomly assigned to the MCU or a no check-up (NCU) condition and followed up at 3- and 9-months. MCU sessions occurred 1 and 4months following the completion of the base treatment. Additional MET/CBT sessions were available to participants throughout the follow-up period. The MCUs specifically encouraged treatment re-entry for those showing ongoing signs of disorder. Participants in the MCU condition reported significantly greater abstinent rates at both follow-ups and were using on fewer days at the 3-month but not the 9-month follow-up. Contrary to hypotheses, MCU participants did not attend more additional treatment and differences in rates of cannabis use emerged prior to the first MCU session. Future research with longer follow-up periods and longer monitoring of outcomes is needed to fully evaluate the utility of MCUs or other forms of continuing care.

  17. Respiratory Variability during Sleep in Methadone Maintenance Treatment Patients

    PubMed Central

    Nguyen, Chinh D.; Kim, Jong Won; Grunstein, Ronald R.; Thamrin, Cindy; Wang, David

    2016-01-01

    Study Objectives: Methadone maintenance treatment (MMT) patients have a high prevalence of central sleep apnea and ataxic breathing related to damage to central respiratory rhythm control. However, the quantification of sleep apnea indices requires laborious manual scoring, and ataxic breathing pattern is subjectively judged by visual pattern recognition. This study proposes a semi-automated technique to characterize respiratory variability in MMT patients. Methods: Polysomnography, blood, and functional outcomes of sleep questionnaire (FOSQ) from 50 MMT patients and 20 healthy subjects with matched age, sex, and body mass index, were analyzed. Inter-breath intervals (IBI) were extracted from the nasal cannula pressure signal. Variability of IBI over 100 breaths was quantified by standard deviation (SD), coefficient of variation (CV), and scaling exponent (α) from detrended fluctuation analysis. The relationships between these variability measures and blood methadone concentration, central sleep apnea index (CAI), apnea-hypopnea index (AHI), and clinical outcome (FOSQ), were then examined. Results: MMT patients had significantly higher SD and CV during all sleep stages. During NREM sleep, SD and CV were correlated with blood methadone concentration (Spearman R = 0.52 and 0.56, respectively; p < 0.01). SD and CV were also correlated with CAI (R = 0.63 and 0.71, p < 0.001, respectively), and AHI (R = 0.45 and 0.58, p < 0.01, respectively). Only α showed significant correlation with FOSQ (R = −0.33, p < 0.05). Conclusions: MMT patients have a higher respiratory variability during sleep than healthy controls. Semi-automated variability measures are related to apnea indices obtained by manual scoring and may provide a new approach to quantify opioid-related sleep-disordered breathing. Citation: Nguyen CD, Kim JW, Grunstein RR, Thamrin C, Wang D. Respiratory variability during sleep in methadone maintenance treatment patients. J Clin Sleep Med 2016;12(4):607–616

  18. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    PubMed

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may

  19. Enhanced immunogenicity of multiple-epitopes of foot-and-mouth disease virus fused with porcine interferon alpha in mice and protective efficacy in guinea pigs and swine.

    PubMed

    Du, Yijun; Li, Yufeng; He, Hairong; Qi, Jing; Jiang, Wenming; Wang, Xinglong; Tang, Bo; Cao, Jun; Wang, Xianwei; Jiang, Ping

    2008-04-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In this study, three amino acid residues 21-60, 141-160 and 200-213 from VP1 protein of FMDV were selected as multiple-epitopes (VPe), and a recombinant adenovirus expressing the multiple-epitopes fused with porcine interferon alpha (rAd-pIFN alpha-VPe) was constructed. Six groups of female BALB/c mice (18 mice per group) were inoculated subcutaneously (s.c.) twice at 2-week intervals with the recombinant adenoviruses and the immune responses were examined. Following this the protective efficacy of rAd-pIFN alpha-VPe was examined in guinea pigs and swine. The results showed that both FMDV-specific humoral and cell-mediated immune responses could be induced by rAd-VPe and increased when rAd-pIFN alpha is included in this regime in mice model. Moreover, the levels of the immune responses in the group inoculated with rAd-pIFN alpha-VPe were significantly higher than the group inoculated with rAd-VPe plus rAd-pIFN alpha. All guinea pigs and swine vaccinated with rAd-pIFN alpha-VPe were completely protected from viral challenge. It demonstrated that recombinant adenovirus rAd-pIFN alpha-VPe might be an attractive candidate vaccine for preventing FMDV infection. PMID:18294705

  20. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in low-dose natural terrestrial ionizing radiation exposed dwellers.

    PubMed

    Shahid, Saman; Mahmood, Nasir; Chaudhry, Muhammad Nawaz; Ahmad, Nauman

    2015-12-01

    Natural terrestrial ionizing radiations emerge from uranium deposits and can impact human tissues by affecting DNA bases which constitute genes. Human interferon alpha-2b (hIFNα-2b) gene synthesizes a protein which exhibits anticancerous, immunomodulatory, anti-proliferative and antiviral properties. This research aimed to find out hIFNα-2b gene mutations for those residents who were chronically exposed to low-dose natural terrestrial ionizing radiations. The gene amplifications was done through PCR technique and gene mutations were identified by bioinformatics in order to conclude as to how mutations identified in hIFNα-2b gene sequences will lead to alterations in the hIFNα-2b protein in radiation exposed residents. The range of radiation dose exposure was 0.4383-4.55832 (mSv/y) for the selected radiation exposed locations which were having uranium mineralization. Mutations (24%) in hIFNα-2b gene shows that some of the radiation exposed inhabitants were having a modulated immune response. The CBC (Complete Blood Count) parameters: WBC (White Blood Cells), MCH (Mean Corpuscular Hemoglobin), MCHC (MCH Concentration) and PLT (Platelets) on average were below the normal range in 24% radiation exposed subjects who were having hIFNα-2b gene mutations. Immunomodulation is observed by the mixed trend of either lymphocytosis or lymphopenia and neutropenia or neutrophilia in the exposed population. Thus, a radioactive exposure from uranium can affect the immune system and can induce mutations.

  1. STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-{alpha}2b peptide

    SciTech Connect

    Blank, Viviana C.; Pena, Clara; Roguin, Leonor P.

    2010-02-15

    In the search of mimetic peptides of the interferon-{alpha}2b molecule (IFN-{alpha}2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-{alpha}2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-{alpha}2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

  2. Evaluation of recombinant human interferon alpha-2b structure and stability by in-gel tryptic digestion, H/D exchange and mass spectrometry.

    PubMed

    Cindrić, Mario; Galić, Nives; Vuletić, Marko; Klarić, Mia; Drevenkar, Vlasta

    2006-02-24

    Stability and structure of recombinant interferon alpha-2b (rHuINF alpha-2b) was studied by mass spectrometry (MALDI-TOF and Q-TOF MS), chromatography (LC-UV-FLD-DAD, LC-MS) and CD spectroscopy. Besides analysis of the substance according to Ph. Eur. methods, two additional mass spectrometric methods were developed. The aim of both methods was to estimate structure-stability relationship connected to methionine oxidation or protein degradation. Preservation or degradation of protein structure was confirmed by H/D exchange in four separate experiments. Kinetics of deuterium incorporation into macromolecule was monitored over 2670 min. Isoforms of rHuINF alpha-2b were separated by 2D gel electrophoresis. In-gel digestion with trypsin and mass spectrometric analysis, performed on four separated isoforms at the mass corresponding to the mass of rHuINF alpha-2b with oxidized methionines, confirmed oxidation of all methionines to a different extent. Another four isoforms observed in 2D gel are most likely dimers of the same macromolecules with scrambled disulphide bridges. Oxidation and dimerisation are consequences of protein interaction with oxidizing reagents in polyacrilamide gel.

  3. Quantitation of methadone and metabolite in patients under maintenance treatment.

    PubMed

    Diong, Shiau Hui; Mohd Yusoff, Nor Shuhadah; Sim, Maw Shin; Raja Aziddin, Raja Elina; Chik, Zamri; Rajan, Poppy; Abdul Rashid, Rusdi; Chemi, Norliza; Mohamed, Zahurin

    2014-01-01

    Gas chromatography-mass spectrometry quantitative method was developed to monitor concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma and urine of patients. The developed method was simple, accurate and reproducible to quantify methadone and EDDP in plasma and urine samples in the concentration range of 15-1,000 and 50-2,000 ng/mL, respectively. The proposed analytical method was applied to plasma and urine samples obtained from 96 patients undergoing methadone maintenance treatment (MMT) with daily methadone doses of 2-120 mg/day. Urinary methadone excretion was observed to be significantly affected by pH, in which the ratio of methadone to EDDP was two times higher in acidic urine (P = 0.029). The findings of this study further enhance the guidelines for monitoring of methadone treatment among outpatients. Methadone-to-EDDP ratio in urine was found to be consistent at 24 and 4 h, hence suggesting the possibility that outpatients may be monitored with single urine sample in order to check for compliance. This study which provides data on peak concentrations of methadone and EDDP as well as the ratio of both compounds has added to the body of knowledge regarding pharmacokinetic properties of methadone among heroin-dependent patients under MMT.

  4. The trajectory of methadone maintenance treatment in Nepal.

    PubMed

    Ambekar, Atul; Rao, Ravindra; Pun, Anan; Kumar, Suresh; Kishore, Kunal

    2013-11-01

    There are about 28,500 people who inject drugs (PWID) in Nepal and HIV prevalence among this group is high. Nepal introduced harm reduction services for PWID much earlier than other countries in South Asia. Methadone maintenance treatment (MMT) was first introduced in Nepal in 1994. This initial small scale MMT programme was closed in 2002 but reopened in 2007 as an emergency HIV prevention response. It has since been scaled up to include three MMT clinics and continuation of MMT is supported by the Ministry of Home Affairs (MOHA; the nodal ministry for drug supply reduction activities) and has been endorsed in the recent National Narcotics policy. Pressure from drug user groups has also helped its reintroduction. Interestingly, these developments have taken place during a period of political instability in Nepal, with the help of strong advocacy from multiple stakeholders. The MMT programme has also had to face resistance from those who were running drug treatment centres. Despite overcoming such troubles, the MMT programme faces a number of challenges. Coverage of MMT is low and high-risk injecting and sexual behaviour among PWID continues. The finance for MMT is largely from external donors and these donations have become scarce with the current global economic problems. With a multitude of developmental challenges for Nepal, the position of MMT in the national priority list is uncertain. Ownership of the programme by government, a cost-effective national MMT scale up plan and rigorous monitoring of its implementation is needed.

  5. Breastfeeding among Mothers on Opioid Maintenance Treatment: A Literature Review.

    PubMed

    Tsai, Lillian C; Doan, Therese Jung

    2016-08-01

    Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT. PMID:27053175

  6. Anterior ischemic optic neuropathy complicating interferon alpha and ribavirin therapy in patients with chronic hepatitisC.

    PubMed

    Kabbaj, N; Sentissi, S; Mohammadi, M; Benaïssa, A; Amrani, N

    2009-02-01

    Ophthalmological complications with interferon therapy are rare, usually mild and reversible, and do not require the withdrawal of antiviral treatment. Anterior ischemic optic neuropathy is an uncommon complication of interferon treatment. From January 1998 to December 2007, three patients developed anterior ischemic optic neuropathy during antiviral treatment, with a favourable course after interferon was discontinued. Periodic Ophthalmological examinations, including visual acuity and fundus examinations should be performed before starting and during treatment, particularly in patients with vascular risk factors. Antiviral therapy should be stopped immediately if severe ophthalmologic complications occur. PMID:19201118

  7. Expert consensus on maintenance treatment for metastatic colorectal cancer in China.

    PubMed

    Xu, Rui-Hua; Shen, Lin; Li, Jin; Xu, Jian-Ming; Bi, Feng; Ba, Yi; Bai, Li; Shu, Yong-Qian; Liu, Tian-Shu; Li, Yu-Hong; Bai, Chun-Mei; Yuan, Xiang-Lin; Zhang, Jun; Chen, Gong; Zhou, Ai-Ping; Yuan, Ying; Wang, Xi-Jing; Qian, Xiao-Ping; Deng, Yan-Hong

    2016-01-14

    The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile. Based on this evidence and common treatment practice in China, we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy, suitable candidates for such treatment, and appropriate regimens.

  8. Operation and Maintenance Manual for the Central Facilities Area Sewage Treatment Plant

    SciTech Connect

    Norm Stanley

    2011-02-01

    This Operation and Maintenance Manual lists operator and management responsibilities, permit standards, general operating procedures, maintenance requirements and monitoring methods for the Sewage Treatment Plant at the Central Facilities Area at the Idaho National Laboratory. The manual is required by the Municipal Wastewater Reuse Permit (LA-000141-03) the sewage treatment plant.

  9. Addict Descriptions of Therapeutic Community, Multimodality, and Methadone Maintenance Treatment Clients and Staff.

    ERIC Educational Resources Information Center

    Stuker, Patricia B.; And Others

    1978-01-01

    Compared the Adjective Check List descriptions of addicts in treatment toward methadone maintenance, multimodality, and therapeutic community clients and program staff. Results indicate client pessimism regarding methadone maintenance. Results suggest addict opinions represent a valuable source for evaluating treatment approaches and identifying…

  10. Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

    SciTech Connect

    Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen; Wyrobek, Andrew J.

    2009-03-03

    We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications. Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.

  11. Treatment outcome unaffected by initiation of full weekend closure of methadone maintenance treatment clinic.

    PubMed

    Peles, Einat; Schreiber, Shaul; Adelson, Miriam

    2014-01-01

    After changing the weekend closure of our methadone maintenance clinic from 1 to 2 days, we compared patients' retention in treatment, discount payment privileges, take-home doses, and rate of drugs in urine tests during the 6 months before and after the change. No differences were found in the 6-month retention rate (94.6% and 95.4%, respectively), take-home dose privileges (60.9% and 58%, respectively), or the rate of urines positive to all substance abuse. Expanding closure of the clinic for a 2-day weekend had no adverse effect on treatment parameters, suggesting that a methadone maintenance clinic may keep the same hours as other hospital's outpatient clinics. PMID:24717114

  12. Immune responses of recombinant adenovirus co-expressing VP1 of foot-and-mouth disease virus and porcine interferon alpha in mice and guinea pigs.

    PubMed

    Du, Yijun; Dai, Jianjun; Li, Yufeng; Li, Congzhi; Qi, Jing; Duan, Shuyi; Jiang, Ping

    2008-08-15

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In this study, we constructed and characterized the immune responses and vaccine efficacy conferred by the recombinant adenovirus co-expressing VP1 of FMDV and porcine interferon alpha as fusion protein (rAd-pIFNalpha-VP1). Six groups of female BALB/c mice each with 18 were inoculated subcutaneously twice 2-week intervals with the recombinant adenoviruses. The results showed that the levels of humoral and cell-mediated immune responses in the group inoculated with rAd-pIFNalpha-VP1 were significantly higher than those in the group inoculated with rAd-VP1+rAd-pIFNalpha (P<0.05). Then four groups of guinea pigs each with six were inoculated two times at 2-week intervals intramuscularly with rAd-pIFNalpha-VP1, commercial inactivated FMD vaccine, wild-type adenovirus (wtAd) or PBS, and the protective efficacy of rAd-pIFNalpha-VP1 was determined. The results indicated that all the guinea pigs vaccinated with rAd-pIFNalpha-VP1 as well as inactivated FMD vaccine were protected from FMDV challenge, even though the levels of neutralizing antibodies (1:32-1:40) of the animals vaccinated with rAd-pIFNalpha-VP1 was lower than that in the group inoculated with inactivated FMD vaccine (1:64-1:128). It demonstrated that the newly recombinant adenovirus rAd-pIFNalpha-VP1 might further be an attractive candidate vaccine for preventing FMDV infection in swine. PMID:18511133

  13. Lysis of HIV-1 Infected Autologous CD4+ Primary T cells by Interferon-alpha Activated NK cells Requires NKp46 and NKG2D

    PubMed Central

    Tomescu, Costin; Mavilio, Domenico; Montaner, Luis J.

    2015-01-01

    Objective Autologous HIV-1 infected CD4+ primary T cells (aHIV+CD4) have been shown to be largely resistant to Natural Killer (NK) cell mediated lysis due to viral strategies of immune evasion. We have previously shown that a pre-activation of NK cells with Plasmacytoid Dendritic Cells can significantly augment lysis of aHIV+CD4 through a mechanism dependent on Interferon-alpha (IFN-α). Design The goal of the present study is to identify the specific NK activating receptors involved in NK lysis of aHIV+CD4 following IFN-α activation. Methods PBMC were incubated with aHIV+CD4 to induce the secretion of endogenous levels of IFN-α and drive NK activation. We then utilized a standard chromium lysis assay to assess the degree of IFN-α activated lysis of aHIV+CD4 in the presence or absence of masking antibodies to a panel of NK activating receptors and co-receptors. Results Direct recognition of HIV-1 infected, but not uninfected, autologous CD4+ primary T cells by PBMC induced the secretion IFN-α (Median 2280 pg/ml, p<0.001, n=9) that, in turn, activated NK cells (p<0.001, n=12) and significantly increased their cytolytic potential against aHIV+CD4 (p<0.01, n=12). The masking of NKp46 (p<0.01, n=8) and NKG2D (p<0.05, n=8), but not 2B4, NTBA, NKp30 or NKp44, significantly reduced IFN-α activated lysis of aHIV+CD4. Conclusions Taken together, these results demonstrate that endogenous levels of IFN-α secreted by pDCs induce NK cells to lyse aHIV+CD4 via the engagement of NKp46 and NKG2D. PMID:26372382

  14. Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with more favorable long-term response in patients with chronic hepatitis C.

    PubMed

    Orito, E; Mizokami, M; Suzuki, K; Ohba, K; Ohno, T; Mori, M; Hayashi, K; Kato, K; Iino, S; Lau, J Y

    1995-06-01

    To determine the virological factors associated with a favorable long-term response to interferon-alpha (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks (780 million units in total) and followed for 8 to 16 months after cessation of therapy. Ten patients dropped out because of severe side effects. Of the 51 patients who completed IFN therapy, 23 showed complete and sustained response (CR --> SR), 13 complete response with early relapse (CR --> Rel), and 15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who had CR --> SR had < 10(6) eq/ml compared to 3/13 CR --> Rel and 1/15 NR (P < 0.01). Serologically defined HCV type 2 infection was also associated with a better opportunity to develop CR --> SR compared to CR --> Rel of NR (P < 0.01). Loss of serum HCV RNA at week 4 of IFN therapy was also associated with a more favorable long-term response [17/19 CR --> SR were HCV RNA negative compared to 3/11 CR --> Rel (P < 0.01) and 2/13 NR (P < 0.01)]. In contrast, normalization of serum alanine aminotransferase (ALT) levels at week 4 was found in 9/19 CR --> SR compared to 8/11 CR --> Rel (P = NS), and 0/13 in NR (P < 0.01). Six months after cessation of IFN therapy, 3/25 CR --> SR patients were HCV RNA positive despite normalization of serum ALT levels. These data indicated that in addition to pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN (at week 4) were also predictive of subsequent long-term response to IFN in patients with chronic HCV infection.

  15. Effects of all-trans retinoic acid and interferon alpha in peripheral neuroectodermal tumor cell cultures and xenografts.

    PubMed

    Rosolen, A; Favaretto, G; Masarotto, G; Cavazzana, A; Zanesco, L; Frascella, E

    1998-11-01

    Peripheral neuroectodermal tumors (PNET) have an unsatisfactory outcome when treated with standard approaches. Among novel treatments, the use of biological response modifiers has rarely been reported in this group of malignancies. We have previously demonstrated that both all-trans retinoic acid (ATRA) and interferon á (IFNá) can inhibit proliferation of human PNET cells and that ATRA can up-regulate IFNá receptor expression in vitro. In this study we evaluated the anti-tumor effects of ATRA and IFNá in PNET cells in vitro and in a human PNET xenograft model, using CHP100 cells. A synergistic inhibitory effect of ATRA and IFNá was observed on CHP100 cells in vitro. On the contrary, a significant inhibition of tumor growth was observed in mice treated with ATRA alone, whereas neither IFNá nor the combination of ATRA and IFNá, reached a statistically significant anti-tumor effect. Histologic examination of tumors revealed the presence of necrosis upon treatment with IFNá, whereas almost no necrosis, but a more differentiated morphology, confirmed by electron microscopy analysis, was associated with the ATRA containing treatments. Taken together these data show an in vitro and in vivo anti-tumor activity of ATRA in human PNET cells, although no synergism of ATRA and IFNá was observed in our xenograft model.

  16. Interferon-alpha therapy in patients with hepatitis C virus infection increases plasma phenylalanine and the phenylalanine to tyrosine ratio.

    PubMed

    Zoller, Heinz; Schloegl, Anna; Schroecksnadel, Sebastian; Vogel, Wolfgang; Fuchs, Dietmar

    2012-05-01

    Higher blood levels of the essential amino acid phenylalanine (Phe) together with impaired conversion of Phe to tyrosine (Tyr) have been observed in patients suffering from inflammatory conditions. Data suggest that inflammatory responses may interfere with Phe metabolism. This study aimed to investigate whether treatment with cytokine interferon-α (IFN-α) influences Phe concentrations and the Phe to Tyr ratios (Phe/Tyr) measured by HPLC. Twenty-five patients (9 females, 16 males, aged mean ± SD: 44.5 ± 11.0 years) with hepatitis C virus (HCV) infection were examined before and after 1 month of effective antiviral therapy with pegylated IFN-α and weight-based ribavirin. Results were compared to HCV-RNA titers and concentrations of neopterin. IFN-α treatment was associated with a drop of HCV load (from median 6.3 to 3.2 log10 copies/μL; P<0.001) and an increase of neopterin concentrations (from median 4.83 to 12.1 nM; P=0.001) which confirms effectiveness of therapy. Before therapy, median Phe concentration were 123.9 μM, Tyr was 98.8 μM, and Phe/Tyr was 1.23 μmol/μmol, and under therapy median Phe concentrations increased to 132.6 μM and Phe/Tyr to 1.33 (both P<0.05; paired rank test), Tyr levels remained unchanged. The increase of Phe concentrations and of Phe/Tyr in HCV infected individuals is caused by IFN-α therapy. Data indicate that activity of enzyme phenylalanine 4-hydroxylase becomes impaired. Future studies should show whether side effects of IFN-α treatment such as mood changes and depression will be associated with the alterations of Phe metabolism.

  17. Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue

    PubMed Central

    Felger, Jennifer C.; Alagbe, Oyetunde; Pace, Thaddeus W. W.; Woolwine, Bobbi J.; Hu, Fang; Raison, Charles L.; Miller, Andrew H.

    2011-01-01

    Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 hours for 12 hours following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFN-alpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS) score ≥15] during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38-positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r=0.85, p=0.001) and 12 (r=0.70, p=0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r=0.82, p=0.002) and cortisol responses to the initial injection of IFN-alpha (r=0.91, p=0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment. PMID

  18. Association between genetic mutations and the development of autoimmune thyroiditis in patients with chronic hepatitis C treated with interferon alpha

    PubMed Central

    2012-01-01

    Background Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFN-alpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA-4C (−318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene. Methods The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFN-alpha therapy, group 2 contained 9 patients with AT with the onset prior to IFN-alpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFN-alpha therapy. Results The frequency of C1858Tand C(−318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism. Conclusions No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFN-alpha therapy and the presence of polymorphisms within CTLA-4 C(−318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene. PMID:23072316

  19. Programming generalization and maintenance of treatment effects across time and across settings.

    PubMed

    Walker, H M; Buckley, N K

    1972-01-01

    Effects of three experimental and one control strategy were investigated in facilitating generalization and maintenance of treatment effects after two months in a token-economy classroom. At the conclusion of treatment, subjects were randomly assigned to one of three maintenance strategies or a control group and returned to their regular classrooms. The maintenance strategies were peer reprogramming, equating stimulus conditions between the experimental and regular classrooms, and teacher training in behavior management techniques. The maintenance strategies were implemented in the regular classroom for a two-month period and then terminated. Results indicated a powerful treatment effect produced by the token economy. Behavior maintenance effects following treatment were also obtained. The mean per cent appropriate behavior for the peer reprogramming and equating stimulus conditions strategies was significantly greater than the mean for the control subjects. The teacher training and control group means were not significantly different. PMID:16795344

  20. Programming generalization and maintenance of treatment effects across time and across settings.

    PubMed

    Walker, H M; Buckley, N K

    1972-01-01

    Effects of three experimental and one control strategy were investigated in facilitating generalization and maintenance of treatment effects after two months in a token-economy classroom. At the conclusion of treatment, subjects were randomly assigned to one of three maintenance strategies or a control group and returned to their regular classrooms. The maintenance strategies were peer reprogramming, equating stimulus conditions between the experimental and regular classrooms, and teacher training in behavior management techniques. The maintenance strategies were implemented in the regular classroom for a two-month period and then terminated. Results indicated a powerful treatment effect produced by the token economy. Behavior maintenance effects following treatment were also obtained. The mean per cent appropriate behavior for the peer reprogramming and equating stimulus conditions strategies was significantly greater than the mean for the control subjects. The teacher training and control group means were not significantly different.

  1. Programming generalization and maintenance of treatment effects across time and across settings1

    PubMed Central

    Walker, Hill M.; Buckley, Nancy K.

    1972-01-01

    Effects of three experimental and one control strategy were investigated in facilitating generalization and maintenance of treatment effects after two months in a token-economy classroom. At the conclusion of treatment, subjects were randomly assigned to one of three maintenance strategies or a control group and returned to their regular classrooms. The maintenance strategies were peer reprogramming, equating stimulus conditions between the experimental and regular classrooms, and teacher training in behavior management techniques. The maintenance strategies were implemented in the regular classroom for a two-month period and then terminated. Results indicated a powerful treatment effect produced by the token economy. Behavior maintenance effects following treatment were also obtained. The mean per cent appropriate behavior for the peer reprogramming and equating stimulus conditions strategies was significantly greater than the mean for the control subjects. The teacher training and control group means were not significantly different. PMID:16795344

  2. Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks.

    PubMed

    Manns, M P; Wedemeyer, H; Singer, A; Khomutjanskaja, N; Dienes, H P; Roskams, T; Goldin, R; Hehnke, U; Inoue, H

    2012-08-01

    Chronic hepatitis C patients often fail to respond to interferon-based therapies. This phase III study aimed at confirming the efficacy and safety of glycyrrhizin in interferon + ribavirin-based therapy non-responders. A randomised, double-blind, placebo-controlled, comparison of glycyrrhizin, administered intravenously 5×/or 3×/week, and 5×/week placebo for 12 weeks to 379 patients, was followed by a randomised, open comparison of glycyrrhizin i.v. 5×/versus 3×/week for 40 weeks. Primary endpoints were: (1) the proportion of patients with ≥50% ALT (alanine aminotransferase) reduction after 12 weeks double-blind phase, and (2) the proportion of patients with improvement of necro-inflammation after 52 weeks as compared with baseline. The proportion of patients with ALT reduction ≥50% after 12 weeks was significantly higher with 5×/week glycyrrhizin (28.7%, P < 0.0001) and 3×/week glycyrrhizin (29.0%, P < 0.0001) compared with placebo (7.0%). The proportion of patients with improvement in necro-inflammation after 52 weeks was 44.9% with 5×/week and 46.0% with 3×/week, respectively. Glycyrrhizin exhibited a significantly higher ALT reduction compared to placebo after 12 weeks of therapy and an improvement of necro-inflammation and fibrosis after 52-weeks treatment. Generally, glycyrrhizin treatment was well tolerated.

  3. A phase II randomised trial of 5-fluorouracil with or without interferon alpha-2a in advanced colorectal cancer.

    PubMed Central

    Piga, A.; Cascinu, S.; Latini, L.; Marcellini, M.; Bavosi, M.; Acito, L.; Bascioni, R.; Giustini, L.; Francini, G.; Pancotti, A.; Rossi, G.; Del Papa, M.; Carle, F.; Cellerino, R.

    1996-01-01

    With the association of 5-fluorouracil (5-FU) and alpha-interferon (IFN), objective responses as high as 26 63% have been reported in untreated patients with advanced colorectal cancer. However, grade 3-4 toxicity has also been reported. We have conducted a prospective phase II randomised study comparing 5-FU to 5-FU + IFN, to investigate whether the addition of IFN to a weekly 5-FU regimen devoid of significant toxicity used at our institutions could improve the effectiveness of 5-FU while maintaining acceptable toxicity. Patients with histologically proven advanced colorectal carcinoma were randomised to receive 5-FU 500 mg m-2 intravenous (i.v.) bolus on days 1-5 followed by 5-FU 500 mg m-2 i.v. bolus weekly from day 15, with or without IFN alpha-2a intramuscularly (i.m.) 1.5 mU daily on days 6-12 and 3 mU i.m. daily thereafter. The treatment was administered on an outpatient basis. Response was evaluated every 3 months, and treatment continued until progression or after two consecutive judgements of stable disease. Response rate was the main end point of the study. Of 141 patients eligible, 72 were randomised to 5-FU alone (arm A) and 69 to 5-FU + IFN (arm B). Responses were 9/72 (12.5%) in arm A and 6/69 (8.7%) in arm B; complete responses were three in arm A and two in arm B. Progression-free survival (median 4 months) and survival (median 12 months) were identical in the two arms. Toxicity was almost absent in arm A and moderate in arm B, represented mainly by haematological toxicity (usually leucopenia). In conclusion, overall survival was good in both arms of treatment and toxicity was moderate. While the response rate with 5-FU alone was in accord with the literature data, response to 5-FU + IFN was lower than expected. At least at this dosage and schedule, the association of 5-FU and IFN is no better than 5-FU alone and is of no clinical interest. PMID:8826868

  4. Bupropion for interferon-alpha-induced depression in patients with hepatitis C viral infection: an open-label study.

    PubMed

    Chen, Wei-Chun; Lai, Hsueh-Chou; Su, Wen-Pang; Palani, Mahalakshmi; Su, Kuan-Pin

    2015-01-01

    Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

  5. Interferon alpha-armed nanoparticles trigger rapid and sustained STAT1-dependent anti-viral cellular responses.

    PubMed

    Pollok, Sibyll; Ginter, Torsten; Günzel, Katharina; Pieper, Jana; Henke, Andreas; Stauber, Roland H; Reichardt, Werner; Krämer, Oliver H

    2013-04-01

    Interferon-α (IFNα) has enormous potential for anti-proliferative and anti-viral treatments. However, clinical success is still hampered due to its limited bioavailability and thus, lack of sustained modulation of disease-relevant protective programs. Consequently, we here examined whether IFNα immobilized on nanoscale ferromagnetic R-Chitosan carriers is capable of inducing rapid and sustained activation of STAT1 signaling. We report the spontaneous formation of a stable nanoparticle-IFNα protein corona, which was exploited to generate IFNα-loaded spheres, obviating the need to specifically couple the cytokine to the nanoparticles (NPs). Notably, comprehensive experimental approaches ensure that formation of the IFNα NP-corona does not affect the biological activity of the cytokine, as STAT1 signaling was efficiently activated. Employing human prostate cancer and melanoma cell models, we found that the intensity and duration of STAT1 phosphorylation as well as the downstream activation of pathobiologically relevant genes were dose and particle dependent. In comparison with free IFNα, IFNα-loaded spheres resulted in a more sustained biologically relevant STAT1 activation, demonstrated also by conferring innate cellular immunity against vesicular stomatitis virus (VSV) infection. For one, our study demonstrates the advantages of biodegradable IFNα-coated R-Chitosan NPs for controlled cytokine release, and thereby improved therapy. Second, we reveal that the permanent presence of IFNα and not just the initial STAT1 phosphorylation ensures sustained IFNα-dependent signaling. PMID:23333460

  6. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

    PubMed Central

    Gill, Upkar S.; Peppa, Dimitra; Micco, Lorenzo; Singh, Harsimran D.; Carey, Ivana; Foster, Graham R.; Maini, Mala K.; Kennedy, Patrick T. F.

    2016-01-01

    NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB. PMID:27487232

  7. Cost Effectiveness of Injectable Extended Release Naltrexone Compared to Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid Dependence

    PubMed Central

    Jackson, Heide; Mandell, Kara; Johnson, Kimberly; Chatterjee, Debanjana; Vanness, David J.

    2015-01-01

    Background The aim of this study was to estimate the cost-effectiveness of injectable extended release naltrexone (XR-NTX) compared to methadone maintenance and buprenorphine maintenance treatment (MMT and BMT respectively) for adult males enrolled in treatment for opioid dependence in the United States from the perspective of state-level addiction treatment payers. Methods We used a Markov model with daily time cycles to estimate the incremental cost per opioid-free day in a simulated cohort of adult males ages 18–65 over a six-month period from the state health program perspective. Results XR-NTX is predicted to be more effective and more costly than methadone or buprenorphine in our target population, with an incremental cost per opioid-free day gained relative to the next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX relative to MMT was driven by its effectiveness in deterring opioid use while receiving treatment. Conclusions XR-NTX is a cost-effective medication for treating opioid dependence if state addiction treatment payers are willing to pay at least $72 per opioid-free day. PMID:25775099

  8. The effect of interferon-alpha on the ecto 5'-nucleotidase of human lymphoblastoid B-cell lines depends on the class of immunoglobulin secreted.

    PubMed Central

    Johnson, S M

    1991-01-01

    Thirteen immunoglobulin-secreting mycoplasma-free human cell lines were treated with increasing concentrations of lymphoblastoid interferon-alpha (IFN-alpha) in order to study the activity of their CD73 ecto-5'-nucleotidase (5'N), their rate of growth and their immunoglobulin (Ig) production. Although IFN-alpha did not immediately affect the activity of the 5'N on the cell plasma membranes, the class of Ig secreted by the cell lines determined whether culturing the cells in the presence of IFN-alpha gave a small increase in the 5'N enzyme activity (IgM), or had no effect (IgE), or showed a marked decrease in activity (IgG). The 5'N activity of two IgG4-secreting clones was more suppressed by IFN-alpha than that of the four IgG1-secreting clones. The clone with the highest 5'N was killed by IFN-alpha. A high 5'N activity inhibited the growth rate of the cells, since the rate of growth of the three IgG-producing lines with high 5'N was increased when their 5'N was inhibited by increasing concentrations of IFN-alpha. The growth rate of three other Ig-producing lines was uninhibited by up to 10(5) U/ml IFN-alpha, whereas the rest were partially or strongly inhibited. Excluding the clone which died, 10/11 lines or cultures increased their Ig/cell by a mean of 25% at 100 U/ml IFN-alpha; their total Ig production also increased despite any growth inhibition. One IgG-secreting clone decreased its Ig production at 100 U/ml IFN-alpha by 11%. The Ig/cell of 4/5 of the cell lines increased with IFN-alpha concentrations up to at least 10(4) U/ml. The increase in Ig/cell was not related to the class of Ig, the growth rate of the cells or the amount of 5'N. PMID:1937572

  9. Baclofen in the short-term maintenance treatment of benzodiazepine dependence

    PubMed Central

    Shukla, Lekhansh; Kandasamy, Arun; Kesavan, Muralidharan; Benegal, Vivek

    2014-01-01

    Benzodiazepine (BZD) dependence is a significant public health problem. Apart from the long-term tapering doses of BZD, no others drugs are available for the maintenance treatment of BZD dependence. Baclofen has been used in alcohol and other drug dependence as long-term anti-craving agent. Since alcohol and BZD act through the GABA receptor, we attempted to study the effect of Baclofen as maintenance treatment in a series of five cases with BZD dependence. PMID:25540541

  10. Enhancing Treatment Integrity Maintenance through Fading with Indiscriminable Contingencies

    ERIC Educational Resources Information Center

    Gross, Thomas J.; Duhon, Gary J.; Doerksen-Klopp, Bethany

    2014-01-01

    School psychologists are often asked to develop treatment to remediate students' academic skills or social behavior problems. When teachers implement treatment recommendations with high levels of treatment integrity, students benefit. Treatment integrity has been enhanced by use of direct training, performance feedback, and negative…

  11. Operation, Maintenance and Management of Wastewater Treatment Facilities: A Bibliography of Technical Documents.

    ERIC Educational Resources Information Center

    Himes, Dottie

    This is an annotated bibliography of wastewater treatment manuals. Fourteen manuals are abstracted including: (1) A Planned Maintenance Management System for Municipal Wastewater Treatment Plants; (2) Anaerobic Sludge Digestion, Operations Manual; (3) Emergency Planning for Municipal Wastewater Treatment Facilities; (4) Estimating Laboratory Needs…

  12. Pharmacological Approaches in the Treatment and Maintenance of Weight Loss.

    PubMed

    Van Gaal, Luc; Dirinck, Eveline

    2016-08-01

    Obesity is a growing global health concern, associated with a number of important comorbid conditions. It increases the risk of diabetes and contributes to development of cardiovascular disease. While the benefits of weight loss are well established, weight reduction remains a difficult-to-reach goal in overweight and obese individuals due to several metabolic and psychological factors. For many patients, lifestyle intervention is insufficient to achieve long-term weight loss, and additional options, such as pharmacotherapy, need to be considered. Besides the challenging enterprise of weight reduction, weight maintenance remains an even more crucial and outcome-determining aspect of weight management. This article focuses on the potential of currently available pharmacological strategies to support weight loss and maintenance goals in individuals at risk. Two pharmacotherapy types are considered: those developed primarily to induce weight loss and those developed primarily for blood glucose control that have a favorable effect on body weight. Finally, the potential of very low- and low-calorie diets combined with pharmacotherapy and pharmacological combination therapies are discussed, as well as emerging approaches in development. PMID:27440841

  13. Suboxone misuse along the opiate maintenance treatment pathway.

    PubMed

    Furst, R Terry

    2013-01-01

    This study explores strategies that Suboxone misusers utilize while in drug treatment. Ethnographic interviews were conducted with 14 patients who had cycled in and out of Suboxone treatment. The objective of the study is to identify strategies implemented by patients who intermittently use opiates/opioids while in Suboxone treatment. Findings indicate that some patients serially stop and start treatment in a Harm Reduction setting in New York City. Many patients suggest that they manage their opiate/opioid dependency through a sequential use of Suboxone and heroin to avoid withdrawal and to continue their misuse of opiates/opioids. Results are discussed in conjunction with the difficulties inherent to substance abuse treatment and suggestions for improvement are offered. PMID:23480248

  14. Psychological Symptoms in Methadone Maintenance Patients: Prevalence and Change over Treatment.

    ERIC Educational Resources Information Center

    Corty, Eric; And Others

    1988-01-01

    Twice interviewed methadone maintenance patients in three cities using Addiction Severity Index. Of subjects followed, 35.4 percent reported having experienced recent psychological symptoms. Found no relation between length of time in treatment at first interview and psychiatric severity. Over one-year period, treatment that subjects received from…

  15. 42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of...

  16. 42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of...

  17. 42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of...

  18. Evaluation of Drug Abuse Treatment: A Repeated Measures Design Assessing Methadone Maintenance.

    ERIC Educational Resources Information Center

    Hser, Yih-Ing; And Others

    1988-01-01

    A repeated measures design was used to evaluate methadone maintenance (MM) treatment effects for 720 heroin addicts who entered MM in Southern California in 1971-1978. Compared to pretreatment measures, results show significant improvement for methadone users. Level of improvement was affected by sex, ethnicity, and treatment duration. (TJH)

  19. Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program

    PubMed Central

    Litwin, Alain H.; Harris, Kenneth A.; Nahvi, Shadi; Zamor, Philippe J.; Soloway, Irene J.; Tenore, Peter L.; Kaswan, Daniel; Gourevitch, Marc. N.; Arnsten, Julia H.

    2009-01-01

    Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in a methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C. PMID:19038524

  20. Reconsidering the benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer.

    PubMed

    Sunakawa, Y; Bekaii-Saab, T; Stintzing, S

    2016-04-01

    Colorectal cancer is one of the most frequent solid tumors in the western world, with low survival rates in patients with metastatic disease. Doublet chemotherapy regimens such as FOLFOX or FOLFIRI are the mainstay of standard first-line chemotherapy in the metastatic setting. The conventional treatment as a first-line approach is continuous application until progression or intolerable toxicities. However, only one third of patients are treated until progression mainly due to the side effects of chemotherapy. Notably, oxaliplatin-containing regimens such as FOLFOX/CapOx or FOLFOXIRI are associated with oxaliplatin-induced neuropathy, which is the main reason for treatment discontinuation or treatment de-escalation. On this basis, recent studies have investigated the clinical benefits of bevacizumab-based intermittent and continuous treatment regimens in the metastatic colorectal setting, together with various strategies to optimize maintenance therapy including regimens with targeted therapies, such as cetuximab, ziv-aflibercept and regorafenib. Recent studies have also investigated when maintenance therapy should be initiated as well individualizing treatment based on patient, tumor and treatment characteristics, as well as molecular biomarkers. This article reviews the current evidence for the clinical benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer, and also evaluates the effect of RAS and BRAF mutational status on maintenance strategies. PMID:27002945

  1. An Analysis of the Waste Water Treatment Maintenance Mechanic Occupation.

    ERIC Educational Resources Information Center

    Clark, Anthony B.; And Others

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the waste water treatment mechanics occupation. The document opens with a brief introduction followed by a job description. The bulk of the document is presented in table form. Twelve duties are broken…

  2. A 12-month controlled trial of methadone medical maintenance integrated into an adaptive treatment model.

    PubMed

    King, Van L; Kidorf, Michael S; Stoller, Kenneth B; Schwartz, Robert; Kolodner, Kenneth; Brooner, Robert K

    2006-12-01

    Methadone medical maintenance (MMM) reduces the reporting schedule for stable and well-functioning methadone maintenance patients to once a month, with counseling provided by medical staff. We report on the 12-month outcomes of 92 highly stable methadone maintenance patients randomly assigned to one of three study conditions: routine care, MMM at the methadone maintenance program, and MMM at a physician's office. Methadone medical maintenance patients received a 28-day supply of methadone, whereas routine care patients received five or six take-home methadone doses each week. All patients performed a medication recall once a month and submitted two urine samples each month. An adaptive stepped-care system of treatment intensification was used for patients who failed recall or who had drug-positive urine specimens. Seventy-seven patients completed the 12-month study period. Dropout was caused primarily by problems with handling methadone and disliking the recall frequency. There were low rates of drug use or failed medication recall. Treatment satisfaction was high in all groups, but the MMM patients initiated more new employment or family/social activities than did routine care patients over the study period. The stepped-care approach was well tolerated and matched patients to an appropriate step of service within a continuum of treatment intensity. PMID:17084792

  3. [The treatment of hypogonadism and maintenance of fertility in men].

    PubMed

    Rabijewski, Michał

    2016-03-01

    In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis.

  4. Maintenance of whitening with a power toothbrush after bleaching treatment.

    PubMed

    Kugel, Gerard; Aboushala, Ayman; Sharma, Shradha; Ferreira, Susana; Anderson, Chad

    2004-02-01

    A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of 2 toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15% carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer's instructions and then were randomly assigned to use either the Sonicare Advance power toothbrush or a manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial surfaces of the subjects' maxillary anterior dentition was assessed before bleaching and immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by comparison with Vita Classical shade tabs and by digital image analysis in the CIE L*a*b* color space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, a significant difference in the amount of rebound in each group was observed. Specifically, the rebound of the Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group. The 6-month difference was confirmed through digital image analysis, with the Sonicare brush group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better maintains whitening after bleaching treatment than a manual toothbrush.

  5. [The treatment of hypogonadism and maintenance of fertility in men].

    PubMed

    Rabijewski, Michał

    2016-03-01

    In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis. PMID:27088205

  6. 42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs. 2.34 Section 2.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE...

  7. Double-Blind 18-Month Trial of Lithium Versus Divalproex Maintenance Treatment in Pediatric Bipolar Disorder.

    ERIC Educational Resources Information Center

    Findling, Robert L.; McNamara, Nora K.; Youngstrom, Eric A.; Stansbrey, Robert; Gracious, Barbara L.; Reed, Michael D.; Calabrese, Joseph R.

    2005-01-01

    Objective: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate ([Li.sup.+]) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination [Li.sup.+] and DVPX ([Li.sup.+]/DVPX) pharmacotherapy. Method: Youths ages 5-17 years with bipolar I or II…

  8. The Correlation between Methadone Dosage and Comorbid Psychiatric Disorders in Patients on Methadone Maintenance Treatment

    PubMed Central

    Parvaresh, Nooshin; Masoudi, Arman; Majidi-Tabrizi, Shiva; Mazhari, Shahrzad

    2012-01-01

    Background Methadone Maintenance Treatment is a useful method for opioid dependents, which results in harm reduction and increased quality of life in opioid dependents. The prevalence of psychiatric disorders in addicts is higher than in the general population which can interfere with the course and treatment of substance dependents and decrease the efficacy of treatment. Methods This descriptive, cross-sectional study was aimed to determine the correlation between psychiatric disorders and methadone dosage. It was performed on 154 patients of Kerman Shahid Beheshti Hospital’s Methadone Clinic during a six month period from Dec 2010 to Jul 2011. The study population was chosen by convenience sampling. The searching tools were Socio-Demographic Questionnaire, psychiatric structured interview based on DSM-IV-TR, Beck Depression Inventory, Young Mania Rating Scales, and Anxiety and Depression Rating Scales. Findings Significant correlations were observed between increased methadone dosage and antisocial personality disorder. In addition, significant positive correlations were observed between increased methadone dosage and Hamilton anxiety scores, Hamilton depression scores and Young Mania scores. Conclusion High methadone dosage may be a marker of coexisting psychiatric disorders in patients on methadone maintenance treatment which indicates the necessity of devoting further attention to this group. Psychiatric services should be open and accessible to the patients, especially those who seek treatment voluntarily. Early diagnosis and treatment of patients with coexisting psychiatric disorders may increase the efficacy of methadone maintenance treatment. PMID:24494130

  9. Ways to manage hepatitis C without cirrhosis: Treatment by comparison of coded eastern medicine hepcinal with interferon alpha 2b and ribavirin.

    PubMed

    Nawaz, Allah; Nazar, Halima; Usmanghani, Khan; Sheikh, Zeeshan Ahmed; Chishti, Muhammad Amjad; Ahmad, Irshad

    2016-05-01

    Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment.

  10. Ways to manage hepatitis C without cirrhosis: Treatment by comparison of coded eastern medicine hepcinal with interferon alpha 2b and ribavirin.

    PubMed

    Nawaz, Allah; Nazar, Halima; Usmanghani, Khan; Sheikh, Zeeshan Ahmed; Chishti, Muhammad Amjad; Ahmad, Irshad

    2016-05-01

    Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment. PMID:27166535

  11. Opioid agonist maintenance for probationers: patient-level predictors of treatment retention, drug use, and crime.

    PubMed

    Gryczynski, Jan; Kinlock, Timothy W; Kelly, Sharon M; O'Grady, Kevin E; Gordon, Michael S; Schwartz, Robert P

    2012-01-01

    This study examined outcomes and their predictors among 181 probationers enrolling in opioid agonist maintenance with methadone or levo-alpha-acetylmethadol (LAAM). Participants were interviewed at treatment entry and 2-, 6-, and 12-month follow-ups. Treatment retention and frequency of heroin use, cocaine use, and income-generating criminal activity were examined using survival and longitudinal analyses. Participants reported marked reductions in drug use and crime relative to treatment entry. A number of patient characteristics associated with various outcomes were identified. The findings support engaging probationers in treatment and highlight patient factors that might influence outcomes.

  12. Slow-release oral morphine for opioid maintenance treatment: a systematic review

    PubMed Central

    Jegu, Jeremie; Gallini, Adeline; Soler, Pauline; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

    2011-01-01

    This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT. PMID:21265874

  13. Current and potential pharmacological treatment options for maintenance therapy in opioid-dependent individuals.

    PubMed

    Tetrault, Jeanette M; Fiellin, David A

    2012-01-22

    Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies.

  14. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations

    PubMed Central

    FitzGerald, J; Becker, A; Sears, M; Mink, S; Chung, K; Lee, J

    2004-01-01

    Background: Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma. Methods: Over a 6 month period a cohort of patients were evaluated prospectively and randomised in a double blind controlled trial to treatment with either a continued maintenance dose (MD) of inhaled corticosteroid or doubling the dose (DD) at the time of an exacerbation. Results: A total of 290 patients were randomised (33% male) and 98 (DD, n = 46) experienced evaluable asthma exacerbations during the study period. Mean (SD) baseline characteristics at randomisation (age 33.5 (14.0) years; forced expiratory volume in 1 second (FEV1) 2.8 (0.7) l; peak expiratory flow (PEF) 422.9 (110.5) l/min) were similar in both groups. In the DD group 41% of patients were considered treatment failures because they either required systemic steroids (n = 12), had an unscheduled visit to a physician (n = 1), or their asthma did not return to baseline (n = 6). This did not differ from the MD group in which 40% were treatment failures (n = 9, 0, and 12, respectively; p = 0.94). Conclusions: In patients who regularly take an inhaled corticosteroid, doubling the maintenance dose may not affect the pattern of the exacerbation. PMID:15223858

  15. Contracting for Treatment Termination to Reduce Illicit Drug Use among Methadone Maintenance Treatment Failures.

    ERIC Educational Resources Information Center

    Dolan, Michael P.; And Others

    1985-01-01

    Evaluated the effectiveness of a contingency contracting intervention on reducing illicit drug use by methadone maintenance outpatients. Illicit drug use was significantly reduced during the 30-day intervention and remained below baseline levels during 60-day follow-up. (Author/MCF)

  16. Lead particle size and its association with firing conditions and range maintenance: implications for treatment.

    PubMed

    Dermatas, Dimitris; Chrysochoou, Maria

    2007-08-01

    Six firing range soils were analyzed, representing different environments, firing conditions, and maintenance practices. The particle size distribution and lead (Pb) concentration in each soil fraction were determined for samples obtained from the backstop berms. The main factors that were found to influence Pb fragment size were the type of soil used to construct the berms and the type of weapon fired. The firing of high velocity weapons, i.e., rifles, onto highly angular soils induced significant fragmentation of the bullets and/or pulverization of the soil itself. This resulted in the accumulation of Pb in the finer soil fractions and the spread of Pb contamination beyond the vicinity of the backstop berm. Conversely, the use of clay as backstop and the use of low velocity pistols proved to be favorable for soil clean-up and range maintenance, since Pb was mainly present as large metallic fragments that can be recovered by a simple screening process. Other factors that played important roles in Pb particle size distribution were soil chemistry, firing distance, and maintenance practices, such as the use of water spray for dust suppression and deflectors prior to impact. Overall, coarse Pb particles provide much easier and more cost-effective maintenance, soil clean-up, and remediation via physical separation. Fine Pb particles release Pb more easily, pose an airborne Pb hazard, and require the application of stabilization/solidification treatment methods. Thus, to ensure sustainable firing range operations by means of cost-effective design, maintenance, and clean-up, especially when high velocity weapons are used, the above mentioned factors should be carefully considered.

  17. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

    PubMed Central

    Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  18. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  19. An empirical description of phases of maintenance following treatment for alcohol dependence.

    PubMed

    Murphy, S A; Hoffman, A L

    1993-01-01

    This article reports two longitudinal prospective studies conducted sequentially to describe participants' maintenance of abstinence experiences up to 36 months posttreatment. Study 1 reports responses of 102 subjects who maintained alcohol abstinence following treatment and who were assessed for duration and intensity of symptoms associated with postacute withdrawal at baseline, 3, 6, and 12 months. A decreasing linear trend of symptoms was found as time of alcohol abstinence increased. Study 2 obtained interview and survey data from 23 successful abstainers from Study 1 at 12, 18, and 36 months posttreatment to describe coping strategies, perceptions of relapse risk, extent and duration of "aftercare," and substitute addictions as these phenomena developed and changed over time. Multiple occasions of data collection supported the description of three phases of maintenance: symptom stabilization/management accompanied by a cognitive paradigm shift, distancing self from alcohol-dependent behavior, and normalization of life processes.

  20. Methadone maintenance in the treatment of opioid dependence. A current perspective.

    PubMed

    Zweben, J E; Payte, J T

    1990-05-01

    We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the understanding of the origins of opioid addiction, such as how receptor system dysfunction may affect the ability to remain abstinent once out of treatment. Specialized topics include the pregnant addict, the role of methadone maintenance in limiting the spread of the acquired immunodeficiency syndrome, and patients with a dual diagnosis. We also describe issues that arise when methadone is used in conjunction with prescribed or abused drugs, noting pharmacologic alternatives and adjuncts to methadone treatment. Finally, we comment on treatment issues such as methadone patients in 12-step programs and the growing legitimacy of this treatment method.

  1. Inhibition of hepatitis B virus by D-fraction from Grifola frondosa: synergistic effect of combination with interferon-alpha in HepG2 2.2.15.

    PubMed

    Gu, Chang-Qing; Li, JunWen; Li, Jun-Wen; Chao, Fu-Huan

    2006-11-01

    In this study, D-fraction extracted from Grifola frondosa (GF-D) and its combination with human interferon alpha-2b (IFN) were investigated for the inhibitory effect on hepatitis B virus (HBV) in HepG2 2.2.15 cells (2.2.15 cells). HBV DNA and viral antigens were analyzed by a quantitative real-time polymerase chain reaction and end-point titration in radioimmunoassays, respectively. The results showed that GF-D or IFN alone could inhibit HBV DNA in 2.2.15 cells with the 50% inhibitory concentration (IC50) of 0.59 mg/ml and 1399 IU/ml, respectively. We further investigated the combination of GF-D and IFN for anti-HBV activity and found that they synergistically inhibited HBV replication in 2.2.15 cells. In combination with 0.45 mg/ml GF-D, the apparent IC50 value for IFN was 154 IU/ml. This 9-fold increase in antiviral activity of IFN suggested that GF-D could synergize with IFN. These results indicate that GF-D, in combination with IFN, might provide a potentially effective therapy against chronic HBV infections.

  2. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment

    PubMed Central

    Yee, Anne; Danaee, Mahmoud; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

    2016-01-01

    Introduction Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients. Methods Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders. Results The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables. Conclusions Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus

  3. Methadone Maintenance for HIV Positive and HIV Negative Patients in Kyiv: Acceptability and Treatment Response

    PubMed Central

    Dvoriak, Sergii; Karachevsky, Andrey; Chhatre, Sumedha; Booth, Robert; Metzger, David; Schumacher, Joseph; Chychula, Nina; Pecoraro, Anna; Woody, George

    2014-01-01

    Background With up to 40% of opioid injectors infected with HIV, Ukraine has one of the most concentrated HIV epidemics in the world, mainly due to unsterile injection practices and a historical absence of effective prevention services. Harm reduction programs, including syringe exchange and a small buprenorphine treatment program, were introduced in 2004 and methadone maintenance was allowed in 2007. Despite an initial expansion, by 2009, only 3221 injectors were receiving methadone treatment. A growing body of research on methadone maintenance has found high retention rates with reduction in opioid use and HIV risk behaviors. We report on the acceptability and initial outcome of methadone treatment as a function of HIV status, an issue that has not yet been reported for injectors in Ukraine. Methods Longitudinal observational study of a 12-week course of methadone treatment in 25 HIV+ and 25 HIV− opioid addicted individuals recruited from a harm reduction program and the city AIDS Center. Drug use and HIV risk were assessed at baseline and weeks 4, 8, 12 and 20; all patients were offered continued methadone maintenance in the Kyiv city program at the end of 12 weeks. Results Fifty-four individuals were asked if they were interested in the study and 50, demographically similar to other samples of opioid addicted Ukrainians, agreed to participate. Two died of non-study related causes; the other 48 completed assessments at weeks 4, 8 and 12, and 47 completed followups at week 20. Significant reductions were seen in use of heroin (p<. 0001), other opiates/analgesics (p< 0.0001), and HIV risk behaviors (drug, sex, total; all p <0.0001). All 48 patients chose to continue methadone after the 12-weeks of study medication ended. Unlike most opioid treatment studies, sexual risk was somewhat higher than injecting risk at study intake. Conclusions Methadone maintenance was well accepted by HIV+ and HIV− opioid dependent individuals and has the potential for significant

  4. Compulsory Maintenance Treatment Program Amongst Iranian Injection Drug Users and Its Side Effects

    PubMed Central

    Eskandarieh, Sharareh; Jafari, Firoozeh; Yazdani, Somayeh; Hazrati, Nazanin; Saberi-Zafarghandi, Mohammad Bagher

    2014-01-01

    Background: Psychoactive substance use can cause a broad variety of mental health disorders and social health problems for the drug users, their family and society. Objectives: The Ministry of Health, Treatment, and Medical Education of Iran has recently proclaimed an estimated number of 2 million drug abusers and 200,000 injecting drug users (IDUs). Patients and Methods: For data collection, the directory of mental, social health, and Addiction designed a questionnaire in cooperation with Drug Control Headquarters of Iran. Results: Among 402 IDUs patients, a large amount of them were male, single, and younger than 39 years. Regarding psychotic and somatic symptoms caused by methadone therapy, most of the participants had no problem with methadone maintenance treatment (MMT). Conclusions: There is a need to train health staff, and the community, concerning preventive measures, treatment, and reducing harm for substance drug users. PMID:25741482

  5. Is Internet Addiction Prevalent Among Methadone Maintenance Treatment Patients? Data from Las Vegas and Tel Aviv.

    PubMed

    Peles, Einat; Linzy, Shirley; Sason, Anat; Tene, Oren; Adelson, Miriam

    2015-01-01

    Internet addiction is known to be associated with depression. The Internet Addiction Test (IAT) and the Center for Epidemiologic Studies Depression scale (CES-D) for depression were studied among non-selective methadone maintenance treatment patients from the United States (n = 164) and Israel (n = 113). Thirty percent were not exposed to the internet, and 2.9% (n = 8) had an "occasional/frequent problem." The IAT and CES-D scores correlated significantly (p = .03). The non-exposed group was older, less educated, and had more benzodiazepine abusers. Unlike other behavioral addictions that characterized these patients, the internet addiction problem is rare, but should not be ignored.

  6. Differences in maintenance of response upon discontinuation across medication treatments in attention-deficit/hyperactivity disorder.

    PubMed

    Buitelaar, Jan; Asherson, Philip; Soutullo, Cesar; Colla, Michael; Adams, David H; Tanaka, Yoko; Haynes, Virginia S; Escobar, Rodrigo; Upadhyaya, Himanshu

    2015-10-01

    The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse of ADHD symptoms upon discontinuation of medication treatment in children, adolescents, and adults with ADHD who have responded to medication treatment and to explore differences among different medications in maintaining treatment response. Randomized withdrawal studies of dexmethylphenidate hydrochloride (d-MPH), methylphenidate modified-release (MPH-LA), lisdexamphetamine dimesylate (LDX), guanfacine extended-release (GXR), and atomoxetine (ATX) in both children/adolescents and adults with ADHD were reviewed. The percentage of relapse was significantly higher and the time-to-relapse significantly shorter with placebo compared to active treatment in patients who were previously stable on 5 weeks to 1 year of active treatment, suggesting clinically significant benefit with continued long-term pharmacotherapy. However, percentage of relapse at each time point studied after discontinuing stimulants and GXR appears substantially higher than observed when discontinuing ATX, suggesting longer maintenance of response after discontinuing ATX than after stimulants and GXR. Additionally, slope of relapse percentages over time appears to be more rapid with stimulants or GXR than with ATX. These differences in maintenance of response among ATX, GXR, and stimulants may reflect differences in mechanisms of action and persistence of the medication effect. Alternatively, they may be due to methodological differences, including study design and response/relapse definitions. Continued investigation is needed regarding factors that affect risk of symptom relapse upon discontinuation of pharmacotherapy. PMID:26169574

  7. Sexual dysfunction during methadone maintenance treatment and its influence on patient's life and treatment: a qualitative study in South China.

    PubMed

    Xia, Yinghua; Zhang, Di; Li, Xiaoming; Chen, Wen; He, Qun; Jahn, Heiko J; Li, Xin; Chen, Jun; Hu, Pei; Ling, Li

    2013-01-01

    Methadone maintenance treatment (MMT) has become an important modality of substitution treatment for opioid addicts in China since 2006. However, data are limited regarding the change in sexual function from heroin use to MMT and the influence of sexual dysfunction (SD) during MMT on patient's life and treatment. Face-to-face in-depth interviews were conducted with 13 male and 14 female MMT patients, five of their partners, and three clinicians. The interviews took place in four MMT clinics in Guangdong Province between August 2010 and February 2011. The patients and their partners were asked separately for their perceptions of patient's sexual function during MMT, and the influence of SD on personal/family life and treatment. The main SD problems patients perceived were libido inhibition and decreased sexual pleasure. Methadone was thought to have a stronger inhibition effect on sexual desire than heroin. SD decreased quality of patient's sexual life and damaged intimate relationships. There was a gender difference in coping with SD. Men generally tended to refuse, escape, or alienate their partners. Women tended to hide sexual listlessness, endure sexual activity and tried to satisfy their partners. SD might increase risk of voluntary dropout from treatment and illicit drug use during treatment. Patients with SD did not get any effective therapy from clinicians and they also lacked skills on coping with SD-related problems. Sexual dysfunction prevented patients from reconstructing a normal intimate relationship, and affected stability of maintenance treatment. Response to patient's SD and SD-related problems from clinicians was inadequate. There is a need to develop a clinical guide to deal with both SD itself and SD-related problems. PMID:23092392

  8. Concurrent Group Treatment for Hepatitis C: Implementation and Outcomes in a Methadone Maintenance Treatment Program

    PubMed Central

    Stein, Melissa R.; Soloway, Irene J.; Jefferson, Karen S.; Roose, Robert J.; Arnsten, Julia H.; Litwin, Alain H.

    2012-01-01

    Chronic hepatitis C virus (HCV) infection is highly prevalent among current and former drug users. However, the minority of patients enrolled in drug treatment programs have initiated HCV treatment. New models are needed to overcome barriers to care. In this retrospective study, we describe the implementation and outcomes of 42 patients treated in a Concurrent Group Treatment (CGT) program. Patients participated in weekly provider-led group treatment sessions which included review of side effects; discussion of adherence and side effect management; administration of interferon injections; brief physical exam; and ended with brief meditation. Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response. Additionally, 87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24 weeks. The CGT model may be effective in overcoming barriers to treatment and improving adherence and outcomes among patients enrolled in drug treatment programs. PMID:23036920

  9. Concurrent group treatment for hepatitis C: implementation and outcomes in a methadone maintenance treatment program.

    PubMed

    Stein, Melissa R; Soloway, Irene J; Jefferson, Karen S; Roose, Robert J; Arnsten, Julia H; Litwin, Alain H

    2012-12-01

    Chronic hepatitis C virus (HCV) infection is highly prevalent among current and former drug users. However, the minority of patients enrolled in drug treatment programs have initiated HCV treatment. New models are needed to overcome barriers to care. In this retrospective study, we describe the implementation and outcomes of 42 patients treated in a concurrent group treatment (CGT) program. Patients participated in weekly provider-led group treatment sessions which included review of side effects; discussion of adherence and side effect management; administration of interferon injections; brief physical examination; and ended with brief meditation. Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response. In addition, 87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24 weeks. The CGT model may be effective in overcoming barriers to treatment and improving adherence and outcomes among patients enrolled in drug treatment programs.

  10. Physical Effects of Methadone Maintenance Treatment from the Standpoint of Clients

    PubMed Central

    Kheradmand, Ali; Banazadeh, Nabi; Abedi, Heidarali

    2010-01-01

    Background Studies have shown that methadone maintenance treatment (MMT) iseffective in improving the client’s quality of life and physical health.This study aimed to describe the nature and structure of drugdependents' experiences and the physical effects of MMT. Methods The present study is a qualitative and a phenomenology study on 32clients referred to methadone clinics in the city of Kerman in 2008.Colaizzi’s method was used for data analysis and to evaluate the data,validity and reliability criteria were used. Findings Encoded concepts were categorized in general groups of effectiveness ongeneral health, sleep, appetite and weight, sexual desire, appearance andother effects. These six categories showed the main structure of experienceand physical effects of MMT. Conclusion The clients' viewpoints towards this treatment had a role in theirexperience expression and feelings, but MMT had an overall positivephysical effect on the clients. PMID:24494103

  11. Social facilitation maintenance treatment for adults with obesity: study protocol for a randomised-controlled feasibility study (SFM study)

    PubMed Central

    Hilbert, Anja

    2016-01-01

    Introduction The long-term success of non-surgical weight loss treatment in adults with obesity is limited by substantial relapse, and only a few evidence-based weight loss maintenance treatments exist. This clinical trial investigates the feasibility and efficacy of a social facilitation maintenance programme for weight loss maintenance, tailored to meet the needs of obese adults who have undergone a lifestyle weight loss intervention. Methods and analysis In a single-centre, open feasibility trial, 72 adults currently or previously obese or overweight who have undergone a lifestyle weight loss intervention are centrally randomised to 4 months of social facilitation maintenance treatment or treatment as a usual control condition. In 16 outpatient group sessions, the social facilitation maintenance treatment, based on a socioecological model and on evidence supporting social facilitation as a key process in maintaining weight loss, focuses on promoting interpersonal relationships to build up a healthy lifestyle for long-term weight loss maintenance. Primary outcome is the amount of weight regain at 6-month follow-up, compared with pre-treatment weight, derived from measured body weight. Secondary outcomes address feasibility, including recruitment, attrition, assessment non-completion, compliance and patients' programme evaluation; and in comparison with pre-weight loss maintenance, social and interpersonal functioning, eating behaviour and physical activity, psychological and physical symptoms, body composition and risk of comorbidity, and quality of life at post-treatment and follow-up assessments. Ethics and dissemination The study was approved by the Ethical Committee at the University of Leipzig (165-13-15072013). The study results will be disseminated through peer-reviewed publications. Trial registration number DRKS00005182. PMID:27580827

  12. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

    PubMed

    Ardissino, Gianluigi; Testa, Sara; Possenti, Ilaria; Tel, Francesca; Paglialonga, Fabio; Salardi, Stefania; Tedeschi, Silvana; Belingheri, Mirco; Cugno, Massimo

    2014-10-01

    Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission. PMID:24656451

  13. Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) alone or administered in combination with interferon-alpha (IFN-alpha): a phase 2 trial.

    PubMed

    Amato, Robert J; Shingler, William; Goonewardena, Madusha; de Belin, Jackie; Naylor, Stuart; Jac, Jaroslaw; Willis, James; Saxena, Somyata; Hernandez-McClain, Joan; Harrop, Richard

    2009-09-01

    Attenuated vaccinia virus, modified vaccinia Ankara (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). MVA-5T4 has been evaluated in an open-label phase 2 trial in metastatic renal cell cancer patients in which the vaccine was administered alone or in combination with interferon-alpha-2b (IFN-alpha). The safety, immunologic, and clinical efficacy of MVA-5T4 with or without IFN-alpha was determined. Twenty-eight patients with metastatic renal cell cancer were treated with MVA-5T4 alone (13) or plus IFN-alpha (15). The 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan. MVA-5T4 was well tolerated with no serious adverse event attributed to vaccination. Of 23 intent-to-treat patients tested for immune responses postvaccination, 22 (96%) mounted 5T4-specific antibody and/or cellular responses. One patient treated with MVA-5T4 plus IFN-alpha showed a partial response for >7 months, whereas an additional 14 patients (7 receiving MVA-5T4 plus IFN and 7 receiving MVA-5T4 alone) showed periods of disease stabilization ranging from 1.73 to 9.60 months. Median progression free survival and overall survival for all intent-to-treat patients was 3.8 months (range: 1 to 11.47 mo) and 12.1 months (range: 1 to 27 mo), respectively. MVA-5T4 administered alone or in combination with IFN-alpha was well tolerated in all patients. Despite the high frequency of 5T4-specific immune responses, it is not possible to conclude that patients are receiving clinical benefit. The results are encouraging and warrant further investigation.

  14. Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells.

    PubMed

    Bazarbachi, A; El-Sabban, M E; Nasr, R; Quignon, F; Awaraji, C; Kersual, J; Dianoux, L; Zermati, Y; Haidar, J H; Hermine, O; de Thé, H

    1999-01-01

    Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL). ATL is an aggressive proliferation of mature activated T cells associated with a poor prognosis. The combination of the antiviral agents, zidovudine (AZT) and interferon (IFN), is a potent treatment of ATL. Recently, arsenic trioxide (As) was shown to be an effective treatment of acute promyelocytic leukemia (APL). We have tested the effects of the combination of As and IFN on cell proliferation, cell cycle phases distribution, and apoptosis in ATL-derived or control T-cell lines. A high synergistic effect between IFN and As was observed in ATL-derived cell lines in comparison to the control cell lines, with a dramatic inhibition of cell proliferation, G1 arrest, and induction of apoptosis. Similar results were obtained with fresh leukemia cells derived from an ATL patient. Although the mechanisms involved are unclear, these results could provide a rational basis for combined As and IFN treatments in ATL. PMID:9864171

  15. Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus.

    PubMed

    Hashimoto, Yuki; Kanto, Hiromi; Itoh, Masatoshi

    2007-08-01

    Pegylated interferon (IFN)-alpha-2b with ribavirin has recently replaced "standard" IFN-alpha for the treatment of chronic hepatitis C. The most common side-effect of pegylated IFN-alpha-2b plus ribavirin combination therapy is localized inflammatory skin lesions at the site of injection. A 66-year-old female treated with once-weekly pegylated IFN-alpha-2b plus ribavirin for active chronic hepatitis C developed inflammatory skin lesions 2 months after starting antiviral treatment. The type of skin reactions observed were vesicle erythematous eruptions at the injection sites, and pruritic papular erythematous eruptions located on the face, neck, distal limbs, dorsa of the hands, trunk and buttocks away from the injection sites. Histological examination was performed on the pruritic papular erythematous eruption located on the left forearm, away from the injection sites. It showed epidermal spongiosis, a spongiotic microvesicle, and perivascular infiltration of the upper dermis with lymphocytes. The treatment was interrupted subsequently and the patient was rechallenged with pegylated IFN-alpha-2b plus ribavirin combination therapy, oral prednisolone with olopatadine hydrochloride and topical 0.1% diflucortolone valerate, which led to a significant improvement of skin lesions. Erythema with infiltration can occur at the injection sites of pegylated IFN-alpha-2b. However, the occurrence of vesicle erythematous eruptions away from the injection sites and autosensitization dermatitis apart from injection sites have not yet been frequently reported. PMID:17683392

  16. From methadone to buprenorphine: changes during a 10 year period within a national opioid maintenance treatment programme.

    PubMed

    Riksheim, Marianne; Gossop, Michael; Clausen, Thomas

    2014-03-01

    Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. Maintenance programmes differ in various aspects and may also change over time. This paper investigates the changes in treatment practices within a national OMT programme during a 10 year period (2002-2011), especially with regard to the prescribing of methadone and buprenorphine. Data (n=34,001) were collected by annual assessments questionnaires. In 2002, only 16% of the OMT patients received buprenorphine as their maintenance medication. By 2011 this percentage had increased significantly (p<.001) to 50.3%. In the same period the number of patients more than tripled (from 1,984 to 6,640, p<.001), and programme attrition rates decreased (p=.020). This relatively rapid shift is a part of the increasing reliance of addiction medicine upon a range of medications administered by different routes which has not been previously charted within a national treatment programme.

  17. Interferon-alpha reduces insulin resistance and beta-cell secretion in responders among patients with chronic hepatitis B and C.

    PubMed

    Tai, T-Y; Lu, J-Y; Chen, C-L; Lai, M-Y; Chen, P-J; Kao, J-H; Lee, C-Z; Lee, H-S; Chuang, L-M; Jeng, Y-M

    2003-09-01

    This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

  18. Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease

    PubMed Central

    Shendi, Ali M.; Salama, Alan D.; Khosravi, Maryam; Connolly, John O.; Trompeter, Richard

    2016-01-01

    Abstract Aim Treatment of frequently relapsing or steroid‐dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long‐term efficacy and safety are still limited. Methods We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid‐dependent, biopsy‐proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re‐treatment. Biochemical and clinical parameters were monitored over an extended follow‐up period of up to 43 months. Results Median steroid‐free survival after RTX was 25 months (range 4–34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow‐up period. Conclusions Rituximab therapy is effective at maintaining prolonged steroid‐free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid‐dependent MCD. PMID:26860320

  19. Successful Integration of Hepatitis C Evaluation and Treatment Services With Methadone Maintenance

    PubMed Central

    Harris, Kenneth A.; Arnsten, Julia H.; Litwin, Alain H.

    2010-01-01

    Objectives Despite high rates of hepatitis C virus (HCV) infection, relatively few current or former injection drug users receive evaluation and treatment for HCV. Here, we demonstrate the feasibility and effectiveness of integrating HCV care and methadone maintenance treatment (MMT). We hypothesized that colocation of these services would result in improved access to and utilization of HCV care. Methods In this retrospective observational study, all patient charts from a single MMT clinic were reviewed 2 years after HCV care and MMT were integrated. Information obtained included screening for and counseling about HCV infection status, on-site HCV treatment and outcomes, and demographic and substance abuse data. Results Two hundred ninety-one patient charts were reviewed. Two hundred eighty-one (99%) patients were screened for HCV antibody (HCV-Ab), and 188 (65%) were positive. Forty-nine (17%) patients were HIV/HCV coinfected. Ninety-eight percent of the HCV-Ab-positive patients received HCV counseling. Hundred fifty-nine (85%) of the HCV-Ab-positive patients were eligible to receive further evaluation and treatment for HCV on site, and 125 (78%) accepted. Hundred eighteen (94%) patients were tested for chronic HCV, and 83 were determined to have chronic HCV. Twenty-five patients received liver biopsy; low-stage disease was found in 7 patients. Twenty-one patients initiated HCV treatment. Sustained viral response was achieved in 8 patients. Seventeen patients had contraindications to HCV treatment. Further workup was prevented or delayed in 45 patients for various reasons, most commonly due to personal choice (29 patients). Conclusions This study demonstrates that current and former injection drug users can be engaged successfully in evaluation and treatment of HCV infection when these services are collocated with MMT. PMID:20485532

  20. Curcumin inhibits interferon-{alpha} induced NF-{kappa}B and COX-2 in human A549 non-small cell lung cancer cells

    SciTech Connect

    Lee, Jeeyun |; Im, Young-Hyuck | E-mail: imyh@smc.samsung.co.kr; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh |; Kim, Kihyun |; Kim, Won Seog |; Ahn, Jin Seok

    2005-08-26

    The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-{alpha} treatment. The IFN-{alpha}-treated A549 cells showed increase in protein expression levels of NF-{kappa}B and COX-2. IFN-{alpha} induced NF-{kappa}B binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-{alpha}-induced COX-2 expression in A549 cells. Within 10 min, IFN-{alpha} rapidly induced the binding activity of a {gamma}-{sup 32}P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-{alpha}-induced activations of NF-{kappa}B and COX-2 were inhibited by the addition of curcumin in A549 cells.

  1. Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam.

    PubMed

    Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Do, Nhan Thi; Nguyen, Long Thanh; Mills, Steve; Houston, Stan; Jacobs, Philip

    2012-01-01

    Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six and nine months. Costs of MMT services were analyzed and converted to the year 2009. Quality-adjusted life years (QALYs) were modeled from changes in health-related quality of life of patients using the modified World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Inverse probability-of-treatment weights, constructed using propensity score of non-responses, were applied to adjust for potential confounding. Over nine months, MMT substantially improved QALYs of HIV/AIDS patients (0.076 QALY [0.066-0.084]). The increments in QALY were large and stabilized in those patients taking antiretroviral treatment and abstinent to drug use. For one QALY gained, the MMT program would cost US$3745.3, approximately 3.2 times Vietnam GDP per capita in 2009. The cost-effectiveness of MMT intervention was robust against HIV advanced status or co-morbidity, e.g., TB treatment, but it might not be cost-effective for those patients who continued to use drug. Findings of this study indicate that providing MMT for HIV-positive drug users is a cost-effective intervention in Vietnam. Integrating MMT to HIV/AIDS care and treatment services would be beneficial in injection-driven HIV epidemics.

  2. [Personality changes in opioid-dependent subjects in a methadone maintenance treatment program].

    PubMed

    Trémeau, F; Darreye, A; Leroy, B; Renckly, V; Ertlé, S; Weibel, H; Khidichian, F; Macher, J-P

    2003-01-01

    Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups.

  3. Differences in HCV Viral Decline between Low and Standard-Dose Pegylated-Interferon-Alpha-2a with Ribavirin in HIV/HCV Genotype 3 Patients

    PubMed Central

    Rivero-Juárez, Antonio; Lopez-Cortes, Luis F.; Camacho, Angela; Torres-Cornejo, Almudena; Pineda, Juan A.; Marquez-Solero, Manuel; Caruz, Antonio; Ruiz-Valderas, Rosa; Torre-Cisneros, Julian; Gutierrez-Valencia, Alicia; Rivero, Antonio

    2012-01-01

    Background The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. Methods Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG) included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. Results One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1∶1.72±0.74 log10 IU/mL versus 1.78±0.67 log10 IU/mL, p = 0.827; week 2∶2.3±0.89 log10 IU/mL versus 3.01±1.02 log10 IU/mL, p = 0.013; week 4∶3.52±1.2 log10 IU/mL versus 4.09±1.1 log10 IU/mL, p = 0.005). The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. Conclusions Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients. PMID:23145040

  4. A case of chronic hepatitis C patient of myocardial ischemia accompanied with interstitial pneumonia induced by pegylated interferon alpha-2a

    PubMed Central

    Qu, Caihong; Zheng, Zhenda; Liu, Weimin; Jiao, Ju; Zhu, Jieming

    2014-01-01

    After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a. PMID:25197402

  5. Antimicrobial preservatives induce aggregation of interferon alpha-2a: the order in which preservatives induce protein aggregation is independent of the protein.

    PubMed

    Bis, Regina L; Mallela, Krishna M G

    2014-09-10

    Antimicrobial preservatives (APs) are included in liquid multi-dose protein formulations to combat the growth of microbes and bacteria. These compounds have been shown to cause protein aggregation, which leads to serious immunogenic and toxic side-effects in patients. Our earlier work on a model protein cytochrome c (Cyt c) demonstrated that APs cause protein aggregation in a specific manner. The aim of this study is to validate the conclusions obtained from our model protein studies on a pharmaceutical protein. Interferon α-2a (IFNA2) is available as a therapeutic treatment for numerous immune-compromised disorders including leukemia and hepatitis C, and APs have been used in its multi-dose formulation. Similar to Cyt c, APs induced IFNA2 aggregation, demonstrated by the loss of soluble monomer and increase in solution turbidity. The extent of IFNA2 aggregation increased with the increase in AP concentration. IFNA2 aggregation also depended on the nature of AP, and followed the order m-cresol>phenol>benzyl alcohol>phenoxyethanol. This specific order exactly matched with that observed for the model protein Cyt c. These and previously published results on antibodies and other recombinant proteins suggest that the general mechanism by which APs induce protein aggregation may be independent of the protein.

  6. Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling

    PubMed Central

    Li, Lin; Lei, Qing-song; Zhang, Shu-Jun; Kong, Ling-na; Qin, Bo

    2016-01-01

    Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-α and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-α. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-α via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells. PMID:27227879

  7. Aripiprazole (ABILIFY MAINTENA®): a review of its use as maintenance treatment for adult patients with schizophrenia.

    PubMed

    Shirley, Matt; Perry, Caroline M

    2014-07-01

    Aripiprazole (ABILIFY(®)) is an atypical antipsychotic drug that is proposed to act via partial agonism of dopamine D2 receptors. Trials with oral aripiprazole have shown that, compared with some other atypical antipsychotics, aripiprazole is associated with fewer metabolic disturbances and has a favourable cardiovascular tolerability profile. Recently, an intramuscular long-acting injectable (LAI) depot formulation of aripiprazole (ABILIFY MAINTENA(®)) (aripiprazole LAI) has been approved for use as a treatment for schizophrenia in adults. The efficacy of aripiprazole LAI as a maintenance treatment for schizophrenia has been demonstrated in randomized clinical trials. In the trials, aripiprazole LAI was more effective than placebo, and noninferior to oral aripiprazole, in delaying relapse and in reducing relapse rates in schizophrenia. Aripiprazole LAI was generally well tolerated, with a tolerability profile consistent with that of oral aripiprazole. Thus, aripiprazole LAI is a valuable new treatment option for adult patients with schizophrenia. It may be of particular use for patients stable on oral aripiprazole who would prefer, or are likely to benefit from, a long-acting formulation.

  8. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

    PubMed Central

    2010-01-01

    Background Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2-ΔΔCT) with respect to hprt housekeeping gene was calculated. Results Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Conclusion Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and

  9. Variables associated with perceived sleep disorders in methadone maintenance treatment (MMT) patients.

    PubMed

    Peles, Einat; Schreiber, Shaul; Adelson, Miriam

    2006-04-28

    To characterize sleep disorders in methadone maintenance treatment (MMT) patients, we evaluated sleep quality of 101 non-selective patients from our MMT clinic in Israel between July, 2003 and July, 2004 by using the self-report questionnaire Pittsburgh Sleep Quality Index (PSQI). Patients' urine tests were analyzed for methadone metabolite, opiates, benzodiazepine, cocaine, cannabis and amphetamines. Their urine results for drug abuse throughout the months prior to filling in the questionnaire and their maintenance methadone doses were recorded. Drug abuse was defined by at least one positive urine test. Methadone serum levels were available in 55 patients, assessed by Gas Chromatography Mass Spectroscopy. The patients' self-reported chronic pain questionnaires and their diagnosed psychiatric disorders were analyzed. Out of the 101 study patients, 78.2% were male, 52.5% had psychiatric disorders, 46.5% reported having chronic pain and 46.5% had positive urine for benzodiazepine. The mean daily methadone dose was 157+/-52.9 mg. The mean PSQI score was 9+/-4.8 (75.2% had scores >5 indicating "poor sleepers"). PSQI scores were higher in patients with positive urine for benzodiazepine, chronic pain and psychiatric disorders and they correlated with years of opiate abuse before admission to MMT, and with the methadone dose (r=0.48, p<0.0005). The latter two also correlated with each other. The PSQI was not correlated with duration in MMT, gender, age, abuse of opiates, cannabis or cocaine. We concluded that sleep disorders should be evaluated and treated among MMT patients, particularly in those with psychiatric disorders, benzodiazepine abuse, chronic pain and high methadone dose. PMID:16154297

  10. Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates.

    PubMed

    Gerra, Gilberto; Manfredini, Matteo; Somaini, Lorenzo; Maremmani, Icro; Leonardi, Claudio; Donnini, Claudia

    2016-01-01

    A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that

  11. Predictors of One-Year Retention in Methadone Maintenance Treatment (MMT) in Iran, Rafsanjan

    PubMed Central

    Sheikh Fathollahi, Mahmood; Torkashvand, Fateme; Najmeddin, Hamid; Rezaeian, Mohsen

    2016-01-01

    Background Retention in treatment is a key factor to the success of methadone maintenance treatment (MMT) and considered an important measure in evaluation of treatment effectiveness. Objectives This study aimed to investigate the retention rate and predictors of retention in MMT in Rafsanjan. Patients and Methods This was a historical cohort study. A total of 1396 patients admitted between March 2011 and March 2012 in 16 MMT clinics (13 private and 3 state clinics) in Rafsanjan, entered the study and their retention rate was examined for one year. The patients’ data abstracted from their medical records using checklists and collected by clinics’ staff. Data analyses were performed using SPSS 15.0 and SAS 9.1. Kaplan-Meier method and Cox proportional hazards model were used to determine the retention rate and identify predictors of retention, respectively. Results The mean age of 1396 patients was 37.65 ± 10.77 years and most patients were men (93.8%). The mean and median of retention duration were 193.22 ± 3.83 and 153 ± 9.54 days, respectively. Three-month and one-year retention rates were 66.0% and 34.4%, respectively. Predictor variables of one-year retention in Cox proportional hazards model were high methadone dosage, polysubstance abuse and treatment under state clinics. Conclusions In this study, retention rate was lower compared to previous studies from other countries. The results suggested that program related factors are better predictors of retention than individual related ones. PMID:27803890

  12. Comorbid Psychopathology and Alcohol Use Patterns among Methadone Maintenance Treatment Patients

    PubMed Central

    Moussas, Georgios; Fanouraki, Irene; Pachi, Argiro; Asomatou, Arezina; Drylli, Olga; Paschalakis, Georgios; Giotakis, Konstantinos; Dermatis, Georgios; Malliori, Meni

    2015-01-01

    130 patients from a methadone maintenance treatment program agreed to complete Symptoms Checklist 90-Revised (SCL-90R) and Alcohol Use Disorders Identification Test (AUDIT) self-report scales. Scores higher than the proposed cut-score on SCL-90R scale were observed on depression, obsessions-compulsions, paranoid ideation, anxiety, anger-hostility, somatization, interpersonal sensitivity, and psychoticism subscales. In sum, 42.9% of our sample exhibited depressive symptomatology, 34.9% obsessive-compulsive symptoms, 29.1% somatization, 27.2% anxiety symptoms, 22.2% paranoid ideation, 19% phobic anxiety, 15.1% psychoticism, and 15.1% hostility and 11.9% presented with symptoms of interpersonal sensitivity. Mean score on AUDIT scale was 6.9 ± 7.9. 63.0% of our participants scored below cut-off and were classified as having a low level of alcohol-related problems; 24.4% scored in the range of 8–15 which is an indication of alcohol abuse whereas 12.6% scored 16 and above indicative of serious abuse/addiction. Scores on AUDIT scale were positively correlated with length of time on methadone treatment, but not with length of time on drug use or age of our participants. Positive correlations were observed among AUDIT and SCL-90R scores, namely, with global severity index score, positive symptom distress index, positive symptom total, and all primary symptom dimensions subscales except phobic anxiety. PMID:25878919

  13. Scaling up the national methadone maintenance treatment program in China: achievements and challenges

    PubMed Central

    Yin, Wenyuan; Hao, Yang; Sun, Xinhua; Gong, Xiuli; Li, Fang; Li, Jianhua; Rou, Keming; Sullivan, Sheena G; Wang, Changhe; Cao, Xiaobin; Luo, Wei; Wu, Zunyou

    2010-01-01

    China’s methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program’s expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs. PMID:21113034

  14. Integrating services for injection drug users infected with hepatitis C virus with methadone maintenance treatment: challenges and opportunities.

    PubMed

    Litwin, Alain H; Soloway, Irene; Gourevitch, Marc N

    2005-04-15

    Despite the high prevalence of hepatitis C virus (HCV) infection among drug users enrolled in methadone maintenance treatment programs, few drug users are being treated with combination therapy. The most significant barrier to treatment is lack of access to comprehensive HCV-related care. We describe a pilot program to integrate care for HCV infection with substance abuse treatment in a setting of maintenance treatment with methadone. This on-site, multidisciplinary model of care includes comprehensive screening and treatment for HCV infection, assessment of eligibility, counseling with regard to substance abuse, psychiatric services, HCV support groups, directly observed therapy, and enhanced linkages to a tertiary care system for diagnostic procedures. Our approach has led to high levels of adherence, with liver biopsy and substantial rates of initiation of antiviral therapy. Two cases illustrate the successful application of this model to patients with HCV infection complicated by active substance abuse and psychiatric comorbidity. PMID:15768345

  15. Maintenance Treatment With Varenicline for Smoking Cessation in Patients With Schizophrenia and Bipolar Disorder

    PubMed Central

    Evins, A. Eden; Cather, Corinne; Pratt, Sarah A.; Pachas, Gladys N.; Hoeppner, Susanne S.; Goff, Donald C.; Achtyes, Eric D.; Ayer, David; Schoenfeld, David A.

    2014-01-01

    Importance It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy. Objective To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment. Design, Setting, and Participants Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention. Interventions Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76. Main Outcomes and Measures Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior. Results Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P < .001). From

  16. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    PubMed Central

    GORDON, MICHAEL S.; KINLOCK, TIMOTHY W.; COUVILLION, KATHRYN A.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN

    2014-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference. PMID:25392605

  17. Technology-Enhanced Maintenance of Treatment Gains in Eating Disorders: Efficacy of an Intervention Delivered via Text Messaging

    ERIC Educational Resources Information Center

    Bauer, Stephanie; Okon, Eberhard; Meermann, Rolf; Kordy, Hans

    2012-01-01

    Objective: Given the lack of maintenance interventions for eating disorders, a program delivered via the short message service (SMS) and text messaging was developed to support patients after their discharge from inpatient treatment. Method: The efficacy of the intervention was studied in a randomized controlled trial. Additionally, its impact on…

  18. Treatment of childhood cutaneous T-cell lymphoma with alpha-interferon plus PUVA.

    PubMed

    Tay, Y K; Weston, W L; Aeling, J L

    1996-01-01

    All forms of cutaneous T-cell lymphoma are rare in childhood. We describe an 8-year-old boy with plaque-stage mycosis fungoides stage IIA whose cutaneous eruption had been present for 5 years. Histologic examination revealed the presence of a granulomatous infiltrate together with atypical lymphocytes within the dermis. The child had an excellent response to combination psoralen-UVA (PUVA) with interferon-alpha 2a treatment and is currently in remission.

  19. The role of maintenance treatment in advanced non-small-cell lung cancer: reality or early second line?

    PubMed

    Gridelli, Cesare; Rossi, Antonio; Maione, Paolo; Ambrosio, Rita; Barbato, Valentina; Bareschino, Maria Anna; Schettino, Clorinda; Palazzolo, Giovanni; Sacco, Paola Claudia

    2010-11-01

    First-line platinum-based chemotherapy has reached a plateau of effectiveness for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). In patients who reported a stable disease, no more than 4 cycles of chemotherapy are recommended while a maximum of 6 cycles is recommended in patients who are responding to therapy. A potential strategy with the aim of improving outcomes for NSCLC patients is to administer more therapy. This term includes different approaches: duration of therapy, sequential therapy, consolidation therapy, and maintenance therapy. Here, we attempt to define the different approaches that fall under the rubric of maintenance strategy, and discuss the results available to date.

  20. Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

    PubMed

    Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

    2015-07-01

    Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p < 0.0005), with no difference in age, gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study. PMID:25605438

  1. Reactivity of patients with maintenance hemodialysis to erythropoietin in the treatment of renal anemia.

    PubMed

    Hu, J P; Cheng, X; Xu, X F; Yu, G J; Luo, F; Zhang, G S; Yang, N; Shen, P; Yan, X Y

    2016-01-01

    To explore the reactivity of patients with renal anemia (MHD) to erythropoietin (EPO) in maintenance hemodialysis (HD), 31 patients were enrolled in this study. According to the level of serum ferritin (SF), they were divided into two groups; one group received treatment using recombinant human erythropoietin (rHuEPO) and the other group was given iron sucrose. Taking terminal EPO dosage, terminal erythropoietin resistance index (ERI) and rate of change of ERI (ΔERII) as target indexes, the influence of SF level on dosage of EPO was evaluated after usage conditions of relevant substances in a 3-month period. The results revealed that differences of dialysis age, albumin (ALB), blood calcium, initial and terminal SF, variable quantity of hemoglobin (Hb), terminal EPO and ERI between two groups had statistical significance. Furthermore, SF level and terminal EPO (r = -0.37, P < 0. 05) as well as SF level and terminal ERI (r = - 0.39, P <0.05) were negatively correlated. Difference of terminal ERI between the two groups had statistical significance. It can therefore be summarized that supplementing an iron agent intravenously to maintain SF level between 500 ng/ml and 1200 ng/ml may improve reactivity of patients with MHD to EPO. In addition, rHuEPO therapy in treating anemia of patients with MHD has the same effect with intravenous drug delivery, less side effects and is easy to administer. PMID:27358145

  2. Abnormal interhemispheric resting state functional connectivity of the insula in heroin users under methadone maintenance treatment.

    PubMed

    Wang, Peng-Wei; Lin, Huang-Chi; Liu, Gin-Chung; Yang, Yi-Hsin Connie; Ko, Chih-Hung; Yen, Cheng-Fang

    2016-09-30

    Abnormal interhemispheric functional connectivity is attracting more and more attention in the field of substance use. This study aimed to examine 1) the differences in interhemispheric functional connections of the insula with the contralateral insula and other brain regions between heroin users under methadone maintenance treatment (MMT) and healthy controls, and 2) the association between heroin users' interhemispheric insular functional connectivity using resting functional magnetic resonance imaging (fMRI) and the results of urine heroin analysis. Sixty male right-handed persons, including 30 with heroin dependence under MMT and 30 healthy controls, were recruited to this study. Resting fMRI experiments and urine heroin analysis were performed. Compared with the controls, the heroin users had a significantly lower interhemispheric insular functional connectivity. They also exhibited lower functional connectivity between insula and contralateral inferior orbital frontal lobe. After controlling for age, educational level and methadone dosage, less deviation of the interhemispheric insula functional connectivity was significantly associated with a lower risk of a positive urine heroin analysis result. Our findings demonstrated that the heroin users under MMT had abnormal long-range and interhemispheric resting functional connections. Those with a less dysfunctional interhemispheric insula functional connectivity had a lower risk of a positive urine heroin test. PMID:27497215

  3. Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

    PubMed

    Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

    2015-07-01

    Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p < 0.0005), with no difference in age, gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study.

  4. Forced withdrawal from methadone maintenance therapy in criminal justice settings: a critical treatment barrier in the United States.

    PubMed

    Fu, Jeannia J; Zaller, Nickolas D; Yokell, Michael A; Bazazi, Alexander R; Rich, Josiah D

    2013-01-01

    The World Health Organization classifies methadone as an essential medicine, yet methadone maintenance therapy remains widely unavailable in criminal justice settings throughout the United States. Methadone maintenance therapy is often terminated at the time of incarceration, with inmates forced to withdraw from this evidence-based therapy. We assessed whether these forced withdrawal policies deter opioid-dependent individuals in the community from engaging methadone maintenance therapy in two states that routinely force inmates to withdraw from methadone (N = 205). Nearly half of all participants reported that concern regarding forced methadone withdrawal during incarceration deterred them engaging methadone maintenance therapy in the community. Participants in the state where more severe methadone withdrawal procedures are used during incarceration were more likely to report concern regarding forced withdrawal as a treatment deterrent. Methadone withdrawal policies in the criminal justice system may be a broader treatment deterrent for opioid-dependent individuals than previously realized. Redressing this treatment barrier is both a health and human rights imperative. PMID:23433809

  5. Nutritional status of the opiate dependent persons after 4 years of methadone maintenance treatment.

    PubMed

    Kolarzyk, Emilia; Pach, Dorota; Wojtowicz, Barbara; Szpanowska-Wohn, Agnieszka; Szurkowska, Magdalena

    2005-01-01

    The aim of the study was to evaluate the nutritional status of opiate dependent patients before and after 4 years of participation in the methadone maintenance treatment. The examinations were performed in 30 opiates addicted persons (7 women and 23 men). The initial examination (exam 1) was done during the patients qualification for the methadone program, preceding methadone administration and final examination (exam 2) after 4 years of the treatment. In order to estimate the nutritional status body mass, the height, the arm circumference and the thickness of the triceps and subscapular fat-skin folds were measured. On the basis of them the BMI and mid arm muscle circumference (MAMC) were counted. The measurements of the body composition (using the bioimpedance method) were performed. The changes between the results of subsequent examination were tested using the t-Student test. In the examination that took place after 4 years of follow-up, body weight loss in the group of women was observed (mean--1.7 kg). It was followed by the decrease of BMI value (from 20.3 to 19.8 kg/m2). In both examinations the percentage of fatty tissue in general body mass was significantly below recommended values (10.7% in both examinations--the recommended values are 20%-22%). In the group of men an increase in body weight (mean--8.8 kg) and BMI value (from 23.3 to 25.9 kg/m2) was noticed. Arm circumference, muscle arm circumference and fat-skin folds values were increased. The analysis of particular body components showed increased fatty body mass (11.9% in the first and 18.5% in the second examination--the recommended values 16-19%) together with the decrease of lean body mass and body water.

  6. Long-term effects of methadone maintenance treatment with different psychosocial intervention models.

    PubMed

    Wang, Lirong; Wei, Xiaoli; Wang, Xueliang; Li, Jinsong; Li, Hengxin; Jia, Wei

    2014-01-01

    This study evaluated the long-term effects of different psychosocial intervention models in methadone maintenance treatment (MMT) in Xi'an China. Patients from five MMT clinics were divided into three groups receiving MMT only, MMT with counseling psychology (CP) or MMT with contingency management (CM). A five-year follow-up was carried out with daily records of medication, monthly random urine morphine tests, and tests for anti-HIV and anti-HCV every six months. Drug use behavior was recorded six months after initial recruitment using a survey. Adjusted RRs and their 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model or a Cox proportional hazard model. A total of 2662 patients were recruited with 797 in MMT, 985 in MMT with CP, and 880 in MMT with CM. Following six months of treatment, the injection rates of MMT with CP and MMT with CM groups were significantly lower than that of MMT (5.1% and 6.9% vs. 16.3%, x²  =  47.093 and 29.908, respectively; P<0.05). HIV incidences for MMT, MMT with CP and MMT with CM at the five year follow-up were 20.09, 0.00 and 10.02 per ten thousand person-years, respectively. HCV incidences were 18.35, 4.42 and 6.61 per hundred person-years, respectively, demonstrating that CP and CM were protective factors for HCV incidence (RR  =  0.209 and 0.414, with range of 0.146-0.300 and 0.298-0.574, respectively). MMT supplemented with CP or CM can reduce heroin use and related risk behaviors, thereby reducing the incidence of HIV and HCV. PMID:24498406

  7. Retention and HIV seroconversion among drug users on methadone maintenance treatment in Yunnan, China

    PubMed Central

    Duo, L.; Kumar, A. M. V.; Achanta, S.; Xue, H-M.; Satyanarayana, S.; Ananthakrishnan, R.; Srivastava, S.; Qi, W.; Hu, S-Y.

    2014-01-01

    Setting: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan, the province with the highest human immunodeficiency virus (HIV) burden in China. Objectives: To determine, among HIV-negative participants on MMT, the proportion lost to follow-up (defined as those who missed the 6-monthly follow-up examination), factors associated with loss to follow-up (LFU), HIV seroconversion rate and factors associated with seroconversion. Design: Prospective cohort study from October 2008 to April 2011. All participants were administered a pre-tested structured questionnaire to capture associated factors and offered HIV testing every 6 months. χ2 test and log-binomial regression were used for data analysis. Results: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5 years. Factors associated with higher LFU proportion include <6 months of previous MMT, inconvenient location of the MMT clinic and average methadone dose ⩽60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2–1.5), 1.2 (95%CI 1.0–1.4) and 1.1 (95%CI 1.0–1.3). The overall HIV seroconversion rate was 6.6 (95%CI 3.7–11.0) per 1000 person-years. Not living with a partner contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0–12.8). Conclusion: The retention rate of MMT participants in Yunnan was not satisfactory. Decentralising service delivery in the community and making directly observed treatment more convenient has the potential to improve retention. PMID:26423758

  8. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial

    PubMed Central

    Sandborn, W J; Hanauer, S B; Rutgeerts, P; Fedorak, R N; Lukas, M; MacIntosh, D G; Panaccione, R; Wolf, D; Kent, J D; Bittle, B; Li, J; Pollack, P F

    2007-01-01

    Background Adalimumab induced clinical remission after four weeks in patients with active Crohn's disease in the CLASSIC I trial. Objective To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn's disease in a follow‐on randomised controlled trial (CLASSIC II). Methods In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn's disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open‐label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re‐randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open‐label arm and received adalimumab 40 mg every other week. With non‐response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non‐response or disease flare could switch to open‐label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56. Results Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open‐label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well‐tolerated in all patients. Conclusions Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn's disease naive to anti‐TNF treatment. PMID:17299059

  9. Zolpidem extended-release: a single insomnia treatment option for sleep induction and sleep maintenance symptoms.

    PubMed

    Barkin, Robert L

    2007-01-01

    It is imperative that primary care clinicians have a thorough understanding of insomnia, because they are often the first point of contact for patients who seek assistance when they have difficulty sleeping. Insomnia may appear with different presentations: sleep onset, sleep maintenances, sleep offset, nonrestorative sleep, or a combination of these symptoms. Untreated symptoms result in clinically significant distress or impairment in social, occupational, or other important areas of following-day functionality. Physicians, pharmacists, and other clinicians should be aware of the conditions that contribute to, are antecedent to, and associated with insomnia. These pathophysiological conditions include advanced age; female gender; respiratory, gastrointestinal, vascular, and rheumatologic pain syndromes; and other conditions such as depression and/or anxiety. Additional health factors contributing to insomnia include chronic pain, stressors, grief reaction, pharmacotherapeutic side effects, lifestyle contributors such as social/recreational drugs, phytopharmaceuticals, and ethanol use. The pharmacotherapy focus in this article is a modified-release formulation of the BZ1 (omega1) receptor agonist zolpidem, zolpidem extended-release. Pharmacokinetic, pharmacodynamic, and safety studies that compare 12.5 mg zolpidem extended-release (Ambien CRtrade markCIV) and 10 mg original zolpidem were initially conducted in healthy volunteers to assess the potential for an improved clinical profile. Zolpidem extended-release (12.5 mg and 6.25 mg extended-release dosage forms) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Zolpidem extended-release is devoid of any short-term use limitation and can be prescribed for the duration of medical necessity. The modified-release zolpidem is a two-layer tablet with a biphasic release profile, releasing the first layer immediately, whereas the second layer is released at

  10. Percutaneous CT-guided microwave ablation as maintenance after first-line treatment for patients with advanced NSCLC

    PubMed Central

    Ni, Xiang; Han, Jun-Qing; Ye, Xin; Wei, Zhi-Gang

    2015-01-01

    Background Systemic therapy is recommended for advanced non-small-cell lung cancer (NSCLC). However, conventional first-line treatment has generated a plateau in response rate of 25% to 35%. Few studies have shown patients benefit from microwave ablation (MWA) in combination with radiotherapy and chemotherapy. This study aims to evaluate safety and efficacy of percutaneous computed tomography-guided MWA as maintenance after first-line treatment for patients with advanced NSCLC. Methods Patients with histologically verified NSCLC stage IIIB or IV between January 2010 and March 2014 were involved. After completion of first-line treatment with partial response or stable disease, 35 patients with 39 tumors underwent 39 MWA procedures. Complications, progression-free survival (PFS), overall survival (OS), and correlated predictors were analyzed. Results During a median follow-up of 17.7 months and 10.8 months after initial MWA, local efficacy was 87.2%, median MWA-related local control time was 10.6 months, and tumor size was the only predictor (P=0.002). Median MWA-related PFS, MWA-related OS, PFS, and OS were 5.4, 10.6, 11.8 and 17.7 months, respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003), MWA-related OS (P=0.000), and OS (P=0.001). There were no procedure-specific deaths. Total incidence of major complications was 12.8%, including pneumothorax resolved by closed pleural drainage and pneumonia controlled by antibiotics in a short time. Conclusion This study concluded two points, including: 1) patients benefited from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC. PMID:26604789

  11. Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia

    PubMed Central

    Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.

    2016-01-01

    Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics

  12. Psychiatric comorbidity of patients on methadone maintenance treatment with a history of sexual abuse.

    PubMed

    Peles, Einat; Potik, David; Schreiber, Shaul; Bloch, Miki; Adelson, Miriam

    2012-12-01

    The aim of this study was to assess the prevalence of a history of sexual abuse and its relation to psychiatric comorbidity among former opiate addicts currently on methadone maintenance treatment (MMT). We evaluated the history of sexual abuse and current clinical obsessive compulsive disorder (OCD), dissociative identity disorder (DID), and complex posttraumatic distress disorder (cPTSD), and administered the Life Events Inventory Questionnaire among 125 MMT patients (76 females and 49 males). Eighty (64%) patients had experienced sexual abuse, 69 (55.2%) met the criteria for clinical OCD, 20 (16.0%) for cPTSD and 13 (10.4%) for DID. More females had clinical OCD than males (63.2% vs. 42.9%, respectively, p=0.03). Sexually abused patients had higher rates of clinical OCD than their non-abused counterparts (67.5% vs. 33.3%, respectively, p<0.0005) and a higher mean number of negative life events (8.0±2.0 vs. 7.1±1.8, p=0.01). Sexually abused patients showed a trend towards a higher Dissociative Experiences Scale score (17.6±10.1 vs. 14.6±8.1, p=0.08) and rate of DID (13.8% vs. 4.4%, p=0.1), but no significant difference in the rate of cPTSD (17.5% vs. 13.3%, p=0.6) compared to non-abused subjects. The 80 sexually abused patients were mostly female (85%), and 57.5% of them were abused by a family member. In summary, more sexually abused MMT patients were diagnosed with clinical OCD and fewer with cPTSD and DID. Those with cPTSD were characterized by more negative life events, higher dissociation scores, and assaults by a family member. We conclude that sexually abused MMT patients should be screened for clinical OCD.

  13. Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers

    PubMed Central

    Woodcock, Eric A.; Lundahl, Leslie H.; Greenwald, Mark K.

    2014-01-01

    Background Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals’ heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes. Methods Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly). Results Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper. Conclusions Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes. PMID:25479914

  14. Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients.

    PubMed

    Wintenberger, C; Boccon-Gibod, I; Launay, D; Fain, O; Kanny, G; Jeandel, P Y; Martin, L; Gompel, A; Bouillet, L

    2014-10-01

    Angioedema (AE) is a clinical syndrome characterized by localised swelling lasting several hours. The swelling is often recurring and can be lethal if it is located in the laryngeal region. Much progress has been made recently in the treatment of acute episodes, but no consensus has been reached on maintenance treatment. We have performed a national retrospective observational study to assess the use of tranexamic acid (TA) as maintenance treatment for non-histaminergic AE [hereditary AE (HAE) or idiopathic non-histaminergic AE]. Records for 64 cases were collected from 1 October 2012 to 31 August 2013; 37 of these were included (12 HAE with C1-inhibitor deficiency, six with HAE with normal C1-inhibitor and 19 idiopathic non-histaminergic AE). When treated with TA over six months, the number of attacks was reduced by 75% in 17 patients, 10 patients showed a lower level of reduction and 10 had the same number of attacks. In no instances were symptoms increased. No thromboembolic events were observed, and the main side effects were digestive in nature. Thus, TA, which is well tolerated and inexpensive, appears to be an effective maintenance treatment for some patients with HAE or idiopathic non-histaminergic AE.

  15. Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients

    PubMed Central

    Wintenberger, C; Boccon-Gibod, I; Launay, D; Fain, O; Kanny, G; Jeandel, P Y; Martin, L; Gompel, A; Bouillet, L

    2014-01-01

    Angioedema (AE) is a clinical syndrome characterized by localised swelling lasting several hours. The swelling is often recurring and can be lethal if it is located in the laryngeal region. Much progress has been made recently in the treatment of acute episodes, but no consensus has been reached on maintenance treatment. We have performed a national retrospective observational study to assess the use of tranexamic acid (TA) as maintenance treatment for non-histaminergic AE [hereditary AE (HAE) or idiopathic non-histaminergic AE]. Records for 64 cases were collected from 1 October 2012 to 31 August 2013; 37 of these were included (12 HAE with C1-inhibitor deficiency, six with HAE with normal C1-inhibitor and 19 idiopathic non-histaminergic AE). When treated with TA over six months, the number of attacks was reduced by 75% in 17 patients, 10 patients showed a lower level of reduction and 10 had the same number of attacks. In no instances were symptoms increased. No thromboembolic events were observed, and the main side effects were digestive in nature. Thus, TA, which is well tolerated and inexpensive, appears to be an effective maintenance treatment for some patients with HAE or idiopathic non-histaminergic AE. PMID:24827773

  16. Ethnic identity, spirituality, and self-efficacy influences on treatment outcomes among Hispanic American methadone maintenance clients.

    PubMed

    Wong, Eunice C; Longshore, Douglas

    2008-01-01

    There is increasing concern over whether standard health care services, such as substance abuse treatment, adequately account for important cultural influences, yet studies focusing on the impact of cultural influences on substance abuse treatment continue to be limited. The current study prospectively examined the effects of two cultural factors (ethnic identity and spirituality) on substance abuse treatment outcomes among Hispanic American clients (N=114) enrolled in methadone maintenance treatment. In addition, this study examined whether a commonly studied treatment factor (i.e., self-efficacy) significantly influenced treatment outcomes. Higher levels of self-efficacy at intake were related to increased odds of reported heroin abstinence and a lower number of drugs used at 1-year follow-up. Greater levels of ethnic identity were related to a greater number of drugs used at follow-up. No significant effects were found for spirituality.

  17. Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment

    PubMed Central

    Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

    2014-01-01

    Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

  18. Prompt initiation of maintenance treatment following a COPD exacerbation: outcomes in a large insured population

    PubMed Central

    Coutinho, Anna D; Lokhandwala, Tasneem; Boggs, Robert L; Dalal, Anand A; Landsman-Blumberg, Pamela B; Priest, Julie; Stempel, David A

    2016-01-01

    Background The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT) following COPD exacerbations requiring hospitalization or an emergency department (ED) visit. Patients and methods Administrative claims data (collected between January 1, 2009 and June 30, 2012) from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit. Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt) were compared with those initiating MT within 31–180 days (delayed). COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year. The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively. Results A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT. Adjusted COPD-related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010), as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010) during the 1-year follow-up period. Patients receiving delayed MT were 68% more likely to have a subsequent exacerbation requiring hospitalization and 80% more likely to have an exacerbation requiring an ED visit. Conclusion Prompt initiation of MT following a COPD-related hospitalization or an ED visit was associated with a significant reduction in COPD-related costs and odds of exacerbation in the following year compared with

  19. Maintenance Model of Integrated Psychosocial Treatment in Pediatric Bipolar Disorder: A Pilot Feasibility Study

    ERIC Educational Resources Information Center

    West, Amy E.; Henry, David B.; Pavuluri, Mani N.

    2007-01-01

    Objective: The chronic and refractory course of pediatric bipolar disorder merits the study of adjunctive psychosocial interventions designed to facilitate long-term improvements. The objective of this study is to conduct a pilot study of a maintenance model of the child- and family-focused cognitive-behavioral therapy program (CFF-CBT), which…

  20. GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder

    PubMed Central

    Chen, Chih-Ken; Lee, Chau-Shoun; Chen, Hsuan-Yu; Wu, Lawrence Shih-Hsin; Chang, Jung-Chen; Liu, Chia-Yih

    2016-01-01

    Background Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders. Aims To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder. Method Frequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n=215). Results GADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence. Conclusions GADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27703793

  1. An Intervention Targeting Service Providers and Clients for Methadone Maintenance Treatment in China: A Cluster-randomized Trial

    PubMed Central

    Li, Li; Wu, Zunyou; Liang, Li-Jung; Lin, Chunqing; Zhang, Linglin; Guo, Sam; Rou, Keming; Li, Jianhua

    2012-01-01

    Aims This study examines the preliminary outcomes of an intervention targeting service providers in methadone maintenance therapy clinics in China. The intervention effects on both service providers and clients are reported. Design The MMT CARE intervention pilot was developed and implemented collaboratively with local health educators. After three group intervention sessions, trained providers in intervention clinics delivered two individual motivational interviewing sessions with their clients. Settings Six clinics in Sichuan, China, were randomized to either the MMT CARE intervention condition or a standard care condition. Participants A total of 41 providers and 179 clients were sampled from the six clinics. Measurements At baseline and 3-, 6-, and 9-month assessments, providers completed self-administrated paper/pencil questionnaires regarding provider-client interaction, methadone maintenance therapy knowledge, perceived job-related stigma, and clinic support. Clients completed a face-to-face survey about their concurrent drug use and drug avoidance self-efficacy. Mixed-effects regression models with clinic-level random effect were used to assess the intervention effects. Findings Significant intervention effects for providers were found in improved methadone maintenance therapy knowledge, provider-client interaction, and perceived clinic support. For clients, better improvements in drug avoidance self-efficacy and reduced concurrent drug use were observed for the intervention compared to the standard care group. Conclusions The methadone maintenance therapy CARE intervention targeting providers in methadone maintenance clinics can improve providers’ treatment knowledge and their interaction with clients. The intervention can also reduce clients’ drug using behavior through motivational interviewing sessions conducted by trained providers. PMID:22788780

  2. Cost-effectiveness analysis of electrochemotherapy with the Cliniporator™ vs other methods for the control and treatment of cutaneous and subcutaneous tumors

    PubMed Central

    Colombo, Giorgio L; Matteo, Sergio Di; Mir, Lluis M

    2008-01-01

    Introduction Tumors of any histological origin can give rise to cutaneous and subcutaneous metastases during follow-up. This study aims to evaluate the costs and benefits of electrochemotherapy (ECT) with the Cliniporator™ vs other currently used methods in the control and treatment of cutaneous and subcutaneous advanced neoplasms. Materials and methods A cost-effectiveness analysis was carried out on ECT using the Cliniporator vs other techniques (radiotherapy, hyperthermia associated with radiotherapy and chemotherapy, interferon-alpha, and isolated limb perfusion) for the control and treatment of cutaneous and subcutaneous neoplasms. The direct health costs were attributed a value according to the Italian National Healthcare System. Resource consumption and clinical outcomes were derived from cost survey data collection and literature review. Results ECT is cost-effective with an incremental cost effectiveness ratio (ICER) of €1,571.53 to achieve a further additional response. Radiotherapy and interferon-alpha are the least effective strategies. A combination of hyperthermia, chemotherapy, radiotherapy, and interferon-alpha treatment are dominated by ECT (more costly and less effective). Isolated limb perfusion is the most effective treatment, but is very costly (€18,530.47) because of the use of antiblastic drugs (TNFα), with an ICER of €92,717.29. Conclusions After sensitivity analysis, the study results confirm the favorable cost-effectiveness ratio of ECT with the Cliniporator and justify its wider use. PMID:18728828

  3. Through Thick and Thin: Identifying Barriers to Bariatric Surgery, Weight Loss Maintenance, and Tailoring Obesity Treatment for the Future

    PubMed Central

    Westerveld, Donevan; Yang, Dennis

    2016-01-01

    More than one-third of the adults in the United States are obese. This complex metabolic disorder is associated with multiple comorbidities and increased all-cause mortality. Bariatric surgery has been shown to be more effective than medical therapy and has been associated with weight loss maintenance and decreased mortality. In spite of these well-established benefits, less than 1% of candidates undergo surgery due to multiple factors, such as patient and physician perceptions and attitudes, patient-physician interaction, lack of resources, and cost burden. Furthermore, even in patients who do undergo bariatric surgery and/or alternate weight loss interventions, long-term weight control is associated with high-risk failure and weight regain. In this review, we highlight some of the current barriers to bariatric surgery and long-term weight loss maintenance and underscore the importance of an individualized multidisciplinary longitudinal strategy for the treatment of obesity. PMID:27314062

  4. Safety and efficacy of oral slow release morphine for maintenance treatment in heroin addicts: a 6-month open noncomparative study.

    PubMed

    Vasilev, Georgi N; Alexieva, Daniela Z; Pavlova, Rositsa Z

    2006-01-01

    This open-label, noncomparative, single-center trial evaluated the safety and efficacy of once-daily treatment with slow release oral morphine (SROM) capsules for the maintenance treatment of 20 outpatients with heroin dependency over 6 months at the National Institute for Addictions in Sofia, Bulgaria. Doses were individually titrated up to a mean daily maintenance dose of 760 mg (range 440-1,200 mg). SROM was effective in significantly reducing the signs and symptoms of opioid withdrawal and craving for heroin, with stabilization generally evident within two weeks. Nineteen patients completed 6 months of treatment and illicit opioid use was virtually eliminated. One patient withdrew voluntarily at 22 weeks. Validated questionnaires and tests indicated improvements in patients' well-being from baseline assessments. These included significant improvements with regard to suicidal depression (85%), anxiety and dysphoria (66%), general illness (58%), social dysfunction (54%), sense of hopelessness (34%), attention (25%), and self-reported typical depressive (27%) and disease-related (11%) symptoms. No deaths, serious adverse events, or withdrawals due to adverse events occurred. Five episodes of constipation and one episode of sweating (all nonserious and of mild or moderate severity) were reported. Vital signs were unaffected by SROM and no weight change was evident over the study period. The observations made in this study indicate a promising role for once-daily treatment with SROM in the clinical management of heroin dependency.

  5. Benefit–risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia

    PubMed Central

    Markowitz, Michael; Turkoz, Ibrahim; Fu, Dong-Jing; Gopal, Srihari; Alphs, Larry

    2016-01-01

    The purpose of this study was to conduct a post-hoc benefit–risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit–Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression–Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom–related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high–density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression–Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit–risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment. PMID:27434314

  6. Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

    PubMed

    Levitan, Bennett; Markowitz, Michael; Turkoz, Ibrahim; Fu, Dong-Jing; Gopal, Srihari; Alphs, Larry

    2016-11-01

    The purpose of this study was to conduct a post-hoc benefit-risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit-Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom-related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high-density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression-Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit-risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment. PMID:27434314

  7. Patient Satisfaction with Methadone Maintenance Treatment in Vietnam: A Comparison of Different Integrative-Service Delivery Models

    PubMed Central

    Tran, Bach Xuan; Nguyen, Long Hoang; Phan, Huong Thu Thi; Latkin, Carl A.

    2015-01-01

    Background Patient satisfaction is an important component of quality in healthcare delivery. To inform the expansion of Methadone Maintenance Treatment (MMT) services in Vietnam, we examined the satisfaction of patients with regards to different services delivery models and identified its associated factors. Methods We interviewed 1,016 MMT patients at 5 clinics in Hanoi and Nam Dinh province. The modified SATIS instrument, a 10-item scale, was used to measure three dimensions: “Services quality and convenience”, “Health workers’ capacity and responsiveness” and “Inter-professional care”. Results The average score was high across three SATIS dimensions. However, only one third of patients completely satisfied with general health services and treatment outcomes. Older age, higher education, having any problem in self-care and anxiety/depression were negatively associated with patient’s satisfaction. Meanwhile, patients receiving MMT at clinics, where more comprehensive HIV and general health care services were available, were more likely to report a complete satisfaction. Conclusion Patients were highly satisfied with MMT services in Vietnam. However, treatment for drug users should go beyond methadone maintenance to address complicated health demands of drug users. Integrating MMT with comprehensive HIV and general health services together with improving the capacity of health workers and efficiency of services organisation to provide interconnected health care for drug users are critical for improving the outcomes of the MMT program. PMID:26556036

  8. Effect of insertion of xanthan-based chlorhexidine gel in the maintenance phase following the treatment of chronic periodontitis

    PubMed Central

    Verma, Ashish; Sanghi, Swati; Grover, Dimple; Aggarwal, Shweta; Gupta, Rajan; Pandit, Nymphea

    2012-01-01

    Objectives: The aim of this study was to evaluate the efficacy of subgingivally administered xanthan-based chlorhexidine gel when used in the maintenance phase following scaling and root planing (SRP) in the treatment of chronic periodontitis. Materials and Methods: A randomized, controlled, single-center study was conducted involving 92 sites in 46 systemically healthy patients suffering from moderate to advanced chronic periodontitis with isolated pockets. The selected sites were randomized to two treatment arms: Group A (SRP alone) and Group B (SRP + insertion of chlorhexidine gel after 1 month). The gingival index, plaque index, probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline and subsequently after 1 month and 3 months. Results: Both the groups showed significant reductions in PPD and CAL at both follow-up visits when compared with the baseline values (P<0.001). Conclusions: The results suggest that the application of xanthan based chlorhexidine gel following SRP in the maintenance phase might be beneficial in treatment of the chronic periodontitis in comparison to SRP alone. Greater improvements may be achieved when antimicrobial agents are used following SRP. PMID:23162333

  9. Comparing Treatment Effect Measurements in Narcolepsy: The Sustained Attention to Response Task, Epworth Sleepiness Scale and Maintenance of Wakefulness Test

    PubMed Central

    van der Heide, Astrid; van Schie, Mojca K.M.; Lammers, Gert Jan; Dauvilliers, Yves; Arnulf, Isabelle; Mayer, Geert; Bassetti, Claudio L.; Ding, Claire-Li; Lehert, Philippe; van Dijk, J. Gert

    2015-01-01

    Study Objectives: To validate the Sustained Attention to Response Task (SART) as a treatment effect measure in narcolepsy, and to compare the SART with the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). Design: Validation of treatment effect measurements within a randomized controlled trial (RCT). Patients: Ninety-five patients with narcolepsy with or without cataplexy. Interventions: The RCT comprised a double-blind, parallel-group, multicenter trial comparing the effects of 8-w treatments with pitolisant (BF2.649), modafinil, or placebo (NCT01067222). MWT, ESS, and SART were administered at baseline and after an 8-w treatment period. The severity of excessive daytime sleepiness and cataplexy was also assessed using the Clinical Global Impression scale (CGI-C). Measurements and Results: The SART, MWT, and ESS all had good reliability, obtained for the SART and MWT using two to three sessions in 1 day. The ability to distinguish responders from nonresponders, classified using the CGI-C score, was high for all measures, with a high performance for the SART (r = 0.61) and the ESS (r = 0.54). Conclusions: The Sustained Attention to Response Task is a valid and easy-to-administer measure to assess treatment effects in narcolepsy, enhanced by combining it with the Epworth Sleepiness Scale. Citation: van der Heide A, van Schie MK, Lammers GJ, Dauvilliers Y, Arnulf I, Mayer G, Bassetti CL, Ding CL, Lehert P, van Dijk JG. Comparing treatment effect measurements in narcolepsy: the Sustained Attention to Response Task, Epworth Sleepiness Scale and Maintenance of Wakefulness Test. SLEEP 2015;38(7):1051–1058. PMID:25902810

  10. Maintenance and Generalization Effects of Semantic and Phonological Treatments of Anomia: A Case Study

    ERIC Educational Resources Information Center

    Macoir, Joel; Routhier, Sonia; Simard, Anne; Picard, Josee

    2012-01-01

    Anomia is one of the most frequent manifestations in aphasia. Model-based treatments for anomia usually focus on semantic and/or phonological levels of processing. This study reports treatment of anomia in an individual with chronic aphasia. After baseline testing, she received a training program in which semantic and phonological treatments were…

  11. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    PubMed Central

    Reguart, Noemí; Cardona, Andrés Felipe; Rosell, Rafael

    2010-01-01

    Erlotinib hydrochloride (Tarceva®) is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents. PMID:21188105

  12. Text message content preferences to improve buprenorphine maintenance treatment in primary care.

    PubMed

    Tofighi, Babak; Grossman, Ellie; Bereket, Sewit; D Lee, Joshua

    2016-01-01

    Few studies have evaluated text message content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple-choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a "few months" into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed.

  13. A Study of the Sexual Function, Sleep, and Weight Status of Patients after 6 Months of Methadone Maintenance Treatment

    PubMed Central

    Parvaresh, Noushin; Sabahi, Abdol Reza; Mazhari, Shahrzad; Gilani, Hoda

    2015-01-01

    Background Methadone is a synthetic opioid and receptor agonist morphine; thus, its consumption has the effects and side effects of opioid. Methadone maintenance treatment (MMT) is used as an alternative treatment for people who are suffering from substance abuse and do not have the ability to withdraw. Despite its benefits, this drug also has side effects. The purpose of this study was to investigate the effects of methadone treatment on sexual function, sleep, and weight after 6 months. Methods The study subjects consisted of 200 patients who had referred to the Methadone Clinic of Shahid Beheshti Training Hospital, Kerman, Iran, during a 6-month period and were treated using MMT. Data collection tools consisted of the demographic questionnaire, Pittsburgh sleep quality index (PSQI), and Arizona sexual experience scale (ASEX). The questionnaires were completed by the participants before and 6 months after the treatment. Findings The results of this study showed that methadone consumption has significant effects on sexual dysfunction, sleep disorders, and weight gain. Conclusion The consideration of the side effects of MMT can result in consumers’ commitment to the treatment. PMID:26322207

  14. Meta-analysis comparing maintenance strategies with continuous therapy and complete chemotherapy-free interval strategies in the treatment of metastatic colorectal cancer.

    PubMed

    Zhao, Lei; Wang, Jing; Li, Huihui; Che, Juanjuan; Cao, Bangwei

    2016-05-31

    There is as yet no consensus as to the best choice among the three treatment options (maintenance, complete chemotherapy-free intervals [CFIs], and continuous) for metastatic colorectal cancer (CRC). We performed a meta-analysis of six trials (N = 2, 454 patients) to compare the safety and efficacy of those three treatment strategies. Maintenance appeared to offer an advantage over CFI with respect to progression-free survival (PFS) (hazard ratio [HR]: 0.53, 95% confidence interval [CI], 0.40-0.69). PFS and overall survival (OS) were comparable between the maintenance and continuous strategies (HR: 1.18, 95% CI, 0.96-1.46; HR: 1.05, 95% CI, 0.98-1.27, respectively), as was OS between the maintenance and CFI strategies (HR: 0.84; 95% CI, 0.70-1.00). The incidence of grade 3/4 toxicity, including neutropenia, neuropathy, hand-foot syndrome and fatigue, was lower with maintenance than with continuous therapy. A maintenance regimen utilizing bevacizumab-based doublets appeared to confer a slight advantage over bevacizumab monotherapy with respect to PFS (P = 0.011). Maintenance appeared to reduce cumulative grade 3/4 toxicity as compared to the continuous strategy, while showing comparable efficacy. Bevacizumab-based doublets appeared to be of particular value in patients with metastatic CRC.

  15. Combined Behavioral and Pharmacologic Treatment for Obesity: Predictors of Successful Weight Maintenance.

    ERIC Educational Resources Information Center

    Rodin, Judith; And Others

    1988-01-01

    Tested an anorectic agent, diethylpropion hydrochloride (Tenuate), with a 20-week cognitive-behavioral (CB) weight loss program. Demonstrated significant weight loss under all treatment conditions, with the Tenuate/CB group superior to placebo plus therapy and therapy alone, during the latter half of the drug treatment period. (Author/KS)

  16. Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment.

    PubMed

    Binder, Philippe; Messaadi, Nassir; Perault-Pochat, Marie-Christine; Gagey, Stéphanie; Brabant, Yann; Ingrand, Pierre

    2016-01-01

    As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76-24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.

  17. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... relating to sickle cell anemia or infection with the human immunodeficiency virus. 1.478 Section 1.478... treatment programs; not applicable to records relating to sickle cell anemia or infection with the...

  18. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... relating to sickle cell anemia or infection with the human immunodeficiency virus. 1.478 Section 1.478... treatment programs; not applicable to records relating to sickle cell anemia or infection with the...

  19. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... relating to sickle cell anemia or infection with the human immunodeficiency virus. 1.478 Section 1.478... treatment programs; not applicable to records relating to sickle cell anemia or infection with the...

  20. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... relating to sickle cell anemia or infection with the human immunodeficiency virus. 1.478 Section 1.478... treatment programs; not applicable to records relating to sickle cell anemia or infection with the...

  1. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... relating to sickle cell anemia or infection with the human immunodeficiency virus. 1.478 Section 1.478... treatment programs; not applicable to records relating to sickle cell anemia or infection with the...

  2. 40 CFR Appendix B to Subpart E of... - Federal Guidelines-User Charges for Operation and Maintenance of Publicly Owned Treatment Works

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... are set forth in subpart E (40 CFR part 35). (b) Authority. The authority for establishment of the... Operation and Maintenance of Publicly Owned Treatment Works B Appendix B to Subpart E of Part 35 Protection... ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act Pt. 35, Subpt. E, App. B Appendix B...

  3. 40 CFR Appendix B to Subpart E of... - Federal Guidelines-User Charges for Operation and Maintenance of Publicly Owned Treatment Works

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... are set forth in subpart E (40 CFR part 35). (b) Authority. The authority for establishment of the... Operation and Maintenance of Publicly Owned Treatment Works B Appendix B to Subpart E of Part 35 Protection... ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act Pt. 35, Subpt. E, App. B Appendix B...

  4. Patterns of abstinence or continued drug use among methadone maintenance patients and their relation to treatment retention.

    PubMed

    White, William L; Campbell, Michael D; Spencer, Robert D; Hoffman, Howard A; Crissman, Brian; DuPont, Robert L

    2014-01-01

    The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes. PMID:25052787

  5. Effects of maintenance lithium treatment on serum parathyroid hormone and calcium levels: a retrospective longitudinal naturalistic study

    PubMed Central

    Albert, Umberto; De Cori, David; Aguglia, Andrea; Barbaro, Francesca; Lanfranco, Fabio; Bogetto, Filippo; Maina, Giuseppe

    2015-01-01

    Objective The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. Methods A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010–2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. Results A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. Conclusion Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added. PMID:26229473

  6. Efficacy of contingency management in improving retention and compliance to methadone maintenance treatment: a random controlled study

    PubMed Central

    Jiang, Haifeng; Du, Jiang; Wu, Fei; Wang, Zhaowei; Fan, Shujun; Li, Zhibin; Hser, Yih-Ing; Zhao, Min

    2012-01-01

    Background Compliance with methadone maintenance treatment (MMT) in China is poor. Objective To evaluate the effects of adjunctive contingency management (CM) on the efficacy of methadone maintenance treatment (MMT) in patients with opioid dependence. Hypothesis A 12-week prize-based contingency management (CM) intervention can increase the retention and compliance of heroin abusers to standardized MMT programs in Shanghai. Methods 160 heroin-dependent patients from three voluntary MMT clinics in Shanghai were randomly assigned to a treatment as usual group (MMT, n=80) and an intervention group (MMT+CM, n=80). Daily use of methadone was recorded and urine drug tests were conducted weekly during the first 12 weeks and then at week 16, week 20 and week 24. Results The 12-week retention rates for the intervention (MMT+CM) and treatment-as-usual (MMT) groups were both quite high: 87.5% and 86.2%, respectively. The average durations of using methadone in the two groups were equal (70 days versus 71 days, respectively). There was a non-significant increase in the mean longest drug-free period (7.4 weeks versus 6.5 weeks) and in the mean number of negative urine tests (7.9 versus 7.6). Secondary analysis of the 24-week outcomes (12 weeks after termination of the adjunctive CM treatment) also found no significant differences between the groups. Among those who remained in the program the severity of addiction as assessed by the Addiction Severity Index decreased dramatically over the 24 weeks but, again, there were no significant differences in the addiction measures between those in the intervention group and those in the treatment-as-usual group. Conclusion Prize-based CM is not effective in improving the retention and compliance of heroin abusers to MMT in Shanghai. The main reasons for failure to replicate western studies were the unexpectedly high baseline rates of compliance in this sample (86%) and the relatively weak financial incentives provided by the CM program

  7. A psychoeducational approach to methadone maintenance treatment: a survey of client reactions.

    PubMed

    Stark, M J; Campbell, B K

    1991-01-01

    STAR, a methadone clinic in Portland, Oregon employs a psychoeducational approach in an attempt to provide coherent, comprehensive treatment in meeting diverse client needs. Two hundred and thirty-eight STAR clients completed a 133 item survey as part of an evaluative review of the efficacy of the psychoeducational model. Clients were asked about their perceived treatment needs and expectations, drug use, criminality, mental and physical health, social and economic stability, and their sense of self-worth and life satisfaction. Respondents reported that receiving methadone was the most useful and best liked aspect of treatment, followed by individual counseling, and education and skill classes. Clients indicated low rates of criminal behavior and drug use, but acknowledged high rates of psychological symptoms including depression, anxiety, and irritability, and rated as very important the need to reduce drug use and to improve health, to achieve a sense of life satisfaction, to enhance feelings about self and relationships, especially those with their children. A majority of the respondents had less than adequate income, and a substantial minority had less than a high school education. Longer time in treatment at STAR was associated with reduced heroin and cocaine use and improvements in social, economic and legal realms. The discussion focuses on implications for methadone treatment in general and possible modifications of the STAR program.

  8. Peginesatide for Maintenance Treatment of Anemia in Hemodialysis and Nondialysis Patients Previously Treated with Darbepoetin Alfa

    PubMed Central

    Roger, Simon D.; Martin, Edouard; Runyan, Grant; O’Neil, Janet; Qiu, Ping; Locatelli, Francesco

    2013-01-01

    Summary Background and objectives Peginesatide (Omontys) is a novel, synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent (ESA) that is designed to specifically stimulate the erythropoietin receptor. This study evaluated maintenance of hemoglobin levels in patients after conversion from darbepoetin alfa to once-monthly peginesatide. Design, setting, participants, & measurements This open-label, multicenter study included 101 CKD patients, 52 of whom were receiving dialysis. The duration of the study was 24 weeks. The primary endpoint was the mean change in hemoglobin from baseline to the evaluation period (weeks 19–24). The study was conducted during the period from September 22, 2008 to December 24, 2009. Results The mean change among hemodialysis patients was –0.42 g/dl (95% confidence interval, –0.65 to –0.19) and the mean change among CKD nondialysis patients was 0.49 g/dl (95% confidence interval, 0.26–0.71). The percentages of patients who maintained hemoglobin levels within ±1.0 g/dl of baseline values were as follows: 80.0% for hemodialysis and 68.1% for nondialysis, and73.3% for hemodialysis and 68.1% for nondialysis within the target range of 10.0–12.0 g/dl. Few patients received red blood cell transfusions (hemodialysis, 5.8%; nondialysis, 2.0%). Seventy-nine patients experienced adverse events, the majority of which were mild or moderate in severity. There were 40 serious adverse events and 2 deaths reported. Conclusions In this study, once-monthly peginesatide resulted in a slight decrease in mean hemoglobin levels in individuals on hemodialysis and a small increase in individuals with CKD who were not on dialysis. PMID:23243269

  9. A case with reversible neurotoxicity after 2 years of dementia secondary to maintenance lithium treatment.

    PubMed

    Soriano-Barceló, Juan; Alonso, María Tajes; Traba, María Begoña Portela; Vilar, Alberte Araúxo; Kahn, David A

    2015-03-01

    Chronic neurotoxicity caused by lithium salts can be reversible or irreversible and may appear after years of treatment, even at serum levels considered within the usual therapeutic range. The authors present the case of a patient with bipolar disorder who developed dementia at the age of 54 after being treated with lithium carbonate at therapeutic levels for 4 years. Nevertheless, lithium treatment was continued. At age 56, the patient presented with an acute encephalopathy caused by toxic lithium levels, which resolved only after lithium carbonate was discontinued. Full recovery from the dementia, which had started 2 years earlier, occurred only after cessation of lithium. The authors conclude that when patients treated with lithium develop subacute cognitive impairment, the possibility of lithium toxicity should be considered, even if the serum levels are considered within the therapeutic range. A long duration of neurotoxicity associated with lithium treatment does not necessarily indicate an irreversible prognosis. PMID:25782766

  10. The diverse and complex roles of radiation on cancer treatment: therapeutic target and genome maintenance

    PubMed Central

    Baskar, Rajamanickam; Yap, Swee Peng; Chua, Kevin Lee Min; Itahana, Koji

    2012-01-01

    Cancer is a genetic disease, grows exponentially with the development of intrinsic and acquired treatment resistance. Past decade has witnessed a considerable progress towards the treatment and understanding of proposed hallmarks of cancer and together with advances in early detection and various treatment modalities. Radiation therapy is an integral part of cancer treatment armamentarium. In developed countries more than half of all cancer patients receive radiation therapy during their course of illness. Although radiation damages both cancer and normal cells, the goal of radiation therapy is to maximize the radiation dose to abnormal cancer cells while minimizing exposure to normal cells, which is adjacent to cancer cells or in the path of radiation. In recent years, life expectancy increases among cancer patients and this increase is due to the results of early diagnosis, screening efforts, improved treatments and with less late effects mostly secondary cancer development. Therefore, cancer survivorship issues have been gaining prominence in the area of radiation oncology research. Understanding the tradeoff between the expected decreases in normal tissue toxicity resulting from an improved radiation dose distribution to the targeted site is an increasingly pertinent, yet needed attention and research in the area of radiation oncology. In recent years, a number of potential molecular targets that involve either with radiation increased tumor cell killing or protecting normal cells have been identified. For clinical benefits, translating these findings to maximize the toxicity of radiation on tumor cells while safeguarding early or late normal cell toxicities using molecular targeted radioprotectors will be useful in radiation treatment. PMID:22860229

  11. Field performance of maintenance treatments constructed with reclaimed asphalt pavement (RAP). Final research report, September 1992-August 1994

    SciTech Connect

    Estakhri, C.K.

    1994-11-01

    In the study, RAP was blended with recycling emulsions and conventional maintenance mixtures in attempts to improve its field performance as a maintenance mixture. RAP was also mixed with stabilizers and used as a base material in maintenance projects. Several field experiments were constructed throughout the state, and the report documents their performance.

  12. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

    PubMed

    Foà, Robin; Del Giudice, Ilaria; Cuneo, Antonio; Del Poeta, Giovanni; Ciolli, Stefania; Di Raimondo, Francesco; Lauria, Francesco; Cencini, Emanuele; Rigolin, Gian Matteo; Cortelezzi, Agostino; Nobile, Francesco; Callea, Vincenzo; Brugiatelli, Maura; Massaia, Massimo; Molica, Stefano; Trentin, Livio; Rizzi, Rita; Specchia, Giorgina; Di Serio, Francesca; Orsucci, Lorella; Ambrosetti, Achille; Montillo, Marco; Zinzani, Pier Luigi; Ferrara, Felicetto; Morabito, Fortunato; Mura, Maria Angela; Soriani, Silvia; Peragine, Nadia; Tavolaro, Simona; Bonina, Silvia; Marinelli, Marilisa; De Propris, Maria Stefania; Starza, Irene Della; Piciocchi, Alfonso; Alietti, Alessandra; Runggaldier, Eva Josephine; Gamba, Enrica; Mauro, Francesca Romana; Chiaretti, Sabina; Guarini, Anna

    2014-05-01

    In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

  13. Descriptive Aspects of Injection Drug Users in Iran’s National Harm Reduction Program by Methadone Maintenance Treatment

    PubMed Central

    ESKANDARIEH, Sharareh; NIKFARJAM, Ali; TARJOMAN, Termeh; NASEHI, Abassali; JAFARI, Firoozeh; SABERI-ZAFARGHANDI, Mohammad-Bagher

    2013-01-01

    Background The Ministry of Health, Treatment and Medical Education of Iran has recently announced an estimated figure of 200,000 injecting drug users (IDUs). The aim of this study was to pilot a national program using demographics, types of drug abuse and prevalence of blood-borne infections among IDUs. Methods: In order to elicit data on demographics, types of drug abuse and prevalence of blood-borne infections among IDUs, a questionnaire was designed in the Bureau of Mental-Social Health and Addiction in collaboration with Iran’s Drug Control Headquarters of the Police Department. Therapeutical alliance of addiction in Shafagh Center was based on Methadone Maintenance Therapy (MMT). Results: Among 402 reported IDUs most of them were male, single and in age range of 20 to 39 years old with 72.7% history of imprisonment. Most of them had elementary and high school education and a history of addiction treatment. The majority were current users of opioid, heroin and crack. The prevalence of blood-borne infections was 65.9% and 18.8% for HCV and HIV/AIDS infections, respectively. Conclusion: Prevention programs about harm reduction, treatment and counseling should include young IDUs as a core focus of their intervention structure. PMID:23967426

  14. Treatment of hypereosinophilic syndromes with prednisone, hydroxyurea, and interferon.

    PubMed

    Butterfield, Joseph H

    2007-08-01

    The hypereosinophilic syndromes continue to challenge our clinical acumen and skills. Prednisone, hydroxyurea, and interferon alpha 2b are three of the oldest agents that allow control of eosinophilia and its devastating clinical consequences. They still work. As our experience with them has grown, it has become evident that use of these agents in combination will control eosinophilia in most patients. Moreover, with time, the doses can frequently be reduced. Even with the advent of newer agents for treatment of hypereosinophilic syndromes, these three medications still afford an excellent, cost-effective avenue for disease management.

  15. [No best treatment for severe outbreaks: Maintenance, the key in colitis].

    PubMed

    Sicilia, Beatriz

    2011-12-01

    Several drugs are currently available to maintain remission in patients who have responded after one or other type of induction therapy, depending on the initial severity of the outbreak. Salicylates are the drugs of choice to maintain remission after a mild-to-moderate outbreak controlled by salicylates or oral corticosteroids. To maintain remission after a severe outbreak or in patients with corticosteroid dependence or resistance, thiopurines are the drugs of choice. In patients who have failed to respond to thiopurines and in those with thiopurine intolerance, biological agents, mainly infliximab, can be used to maintain remission in patients after induction therapy with infliximab for a severe outbreak. However, these scenarios may not reflect reality of gastroenterologists' daily clinical practice. Treatment will therefore be based on the patient's individual characteristics (age, clinical course, previous treatment, adverse effects and personal preferences) as well as the physician's medical art. PMID:25443222

  16. Effect of lithium maintenance treatment on hypothalamic pituitary gonadal axis in bipolar men.

    PubMed

    Kusalic, M; Engelsmann, F

    1996-05-01

    This was a cross-sectional study assessing short- and long-term effects of lithium (Li) treatment on hormone levels. Levels of testosterone (T), prolactin (PRL), luteinizing hormone (LH), and follicule-stimulating hormone (FSH) were compared. Sixty-one lithium-treated, euthymic, stable, bipolar men were compared with 67 hospital controls and 22 healthy volunteers. Prolactin (P < or = 0.01) and luteinizing hormone (P < or = 0.001) were higher in all patients compared with healthy volunteers. Li-treated patients were evaluated at 22 to 24 mo, 2 to 5 y, and after more than 5 y of Li therapy. At 22 to 24 mo of Li treatment, levels of PRL and LH did not differ from the values of healthy volunteers or of patients treated for longer periods. In addition, the value of T was higher (P < or = 0.003) than in the group treated longer. Levels of T after more than 5 y of treatment, however, did not differ from those of the healthy volunteers.

  17. Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor: A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection

    SciTech Connect

    Venkatraman, Srikanth; Bogen, Stephane L.; Arasappan, Ashok; Bennett, Frank; Chen, Kevin; Jao, Edwin; Liu, Yi-Tsung; Lovey, Raymond; Hendrata, Siska; Huang, Yuhua; Pan, Weidong; Parekh, Tejal; Pinto, Patrick; Popov, Veljko; Pike, Russel; Ruan, Sumei; Santhanam, Bama; Vibulbhan, Bancha; Wu, Wanli; Yang, Weiying; Kong, Jianshe; Liang, Xiang; Wong, Jesse; Liu, Rong; Butkiewicz, Nancy; Chase, Robert; Hart, Andrea; Agrawal, Sony; Ingravallo, Paul; Pichardo, John; Kong, Rong; Baroudy, Bahige; Malcolm, Bruce; Guo, Zhuyan; Prongay, Andrew; Madison, Vincent; Broske, Lisa; Cui, Xiaoming; Cheng, Kuo-Chi; Hsieh, Yunsheng; Brisson, Jean-Marc; Prelusky, Danial; Korfmacher, Walter; White, Ronald; Bogdanowich-Knipp, Susan; Pavlovsky, Anastasia; Bradley, Prudence; Saksena, Anil K.; Ganguly, Ashit; Piwinski, John; Girijavallabhan, Viyyoor; Njoroge, F. George

    2008-06-30

    Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-{alpha} or polyethylene glycol (PEG)-interferon-{alpha} alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

  18. Effect of 1-methylcyclopropene and calcium chloride treatments on quality maintenance of 'Lingwu Long' Jujube fruit.

    PubMed

    Li, Li; Ban, Zhaojun; Li, Xihong; Xue, Ting

    2014-04-01

    'Lingwu Long' jujube (Zizyphus jujuba cv. Mill) fruits were harvested at mature-green stages and then treated with 1.0 μL L(-1) 1-methylcyclopropene (1-MCP), 1.0% CaCl2 or their combination. All treatments were stored at room temperature (22 ± 1 °C) and 80-90% relative humidity (RH) up for 15 days. Results indicated that 1.0 μL L(-1) 1-MCP, 1.0% CaCl2 or their combination were effective in terms of senescence inhibition, and the storage life was extended by 6, 4 and 9 days, respectively. 1-MCP and CaCl2 treatment had a synergic effect on the inhibition of ethylene production and microbial population of 'Lingwu Long' jujube fruit. The combination of 1-MCP and CaCl2 significantly reduced polygalacturonase (PG) and polyphenoloxidase (PPO) activities. It also maintained higher concentrations of titratable acid and ascorbic acid. PMID:24741163

  19. Effect of 1-methylcyclopropene and calcium chloride treatments on quality maintenance of 'Lingwu Long' Jujube fruit.

    PubMed

    Li, Li; Ban, Zhaojun; Li, Xihong; Xue, Ting

    2014-04-01

    'Lingwu Long' jujube (Zizyphus jujuba cv. Mill) fruits were harvested at mature-green stages and then treated with 1.0 μL L(-1) 1-methylcyclopropene (1-MCP), 1.0% CaCl2 or their combination. All treatments were stored at room temperature (22 ± 1 °C) and 80-90% relative humidity (RH) up for 15 days. Results indicated that 1.0 μL L(-1) 1-MCP, 1.0% CaCl2 or their combination were effective in terms of senescence inhibition, and the storage life was extended by 6, 4 and 9 days, respectively. 1-MCP and CaCl2 treatment had a synergic effect on the inhibition of ethylene production and microbial population of 'Lingwu Long' jujube fruit. The combination of 1-MCP and CaCl2 significantly reduced polygalacturonase (PG) and polyphenoloxidase (PPO) activities. It also maintained higher concentrations of titratable acid and ascorbic acid.

  20. First year survival of patients on maintenance dialysis treatment in Poland.

    PubMed

    Brodowska-Kania, Dorota; Rymarz, Aleksandra; Gibin Ski, Krzysztof; Kiełczewska, Julia; Smoszna, Jerzy; Saracyn, Marek; Szamotulska, Katarzyna; Niemczyk, Stanisław

    2015-11-01

    Retrospective analysis of demographic and clinical data of all patients starting dialysis over two years in our Department (n = 105) has been conducted. Factors such as type of dialysis treatment, reason of end-stage renal disease, Body Mass Index (BMI), laboratory tests results, number and cause of death during first year of dialysis were taken under consideration. Five patients have been excluded from the analysis of mortality (four received renal transplantation, one changed dialysis center). Twenty tree deaths have been noted during first year of dialysis treatment. Nine of them occurred during the first three months of therapy. The leading cause of death was cardio-vascular events (n = 14, 60.9%), the second was malignancy (8, 34,8%), one patient died due to catheter associated infection. Malignancy as a cause of end-stage renal disease, lack of outpatient nephrology care, acute mode of beginning renal replacement therapy and lack of erythropoiesis stimulating agents therapy were associated with higher risk of all-cause mortality during first year of dialysis. Being under the outpatient nephrology care, etiology of ESRD other than malignancy and erythropoiesis stimulating agents therapy were independently associated with better survival during this period of time. Other independent variables did not reach statistical significance. To conclude, in order to improve one year survival of dialysis patients, outpatient nephrology care with adequate amount of visits and associated dialysis therapy should be employed. PMID:26663941

  1. Factors associated with one year retention to methadone maintenance treatment program among patients with heroin dependence in China

    PubMed Central

    2014-01-01

    Objective The aim of this study was to evaluate the risk factors associated with dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow-up cohort study in China. Methods A data analysis is to explore the adherence of MMT during one year from three hundred and twenty patients with heroin dependence at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were from the part of China-United States cooperation project entitled “Research about improving the compliance and efficacy of methadone maintenance treatment in China”. Our data analysis includes the patients’ attendance in the 6 months clinical study and the data in another 6 months afterward. The data of patients at baseline were collected with the Addiction Severity Index (ASI) which is a semi-structured questionnaire covering socio-demographic characteristics and drug use history. The one year attendance after recruitment at the clinics and daily dose were abstracted from the MMT clinic register system. The Cox proportional hazards model were used to explore the risk factor of dropout, defined as seven consecutive days without methadone. Results By the end of 1 year of treatment 86 patients still remained in MMT without dropout (87% in Shanghai and 13% patients in Kunming). Over the entire 1-year period the median days of remaining in the program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The factors associated with retention included age (HR = 0.98, 95%C.I.:0.96-0.99, P = 0.0062) and ASI alcohol scores (HR = 5.72, 95%C.I.:1.49-21.92, P = 0.0109) at baseline. Conclusion One year retention of newly recruited patients with heroin dependence was related to age and ASI alcohol scores at baseline. The adherence is poorer for the patients who are young and having more serious alcohol problems. PMID:24565169

  2. Psychosocial outcomes in patients with recurrent major depressive disorder during 2 years of maintenance treatment with venlafaxine extended release

    PubMed Central

    Trivedi, Madhukar H.; Dunner, David L.; Kornstein, Susan G.; Thase, Michael E.; Zajecka, John M.; Rothschild, Anthony J.; Friedman, Edward S.; Shelton, Richard C.; Keller, Martin B.; Kocsis, James H.; Gelenberg, Alan

    2013-01-01

    Background Psychosocial outcomes from the Prevention of Recurrent Episodes of Depression with Venlafaxine ER for Two Years (PREVENT) study were evaluated. Methods Adult outpatients with recurrent major depressive disorder (MDD) and response or remission following 6-month continuation treatment with venlafaxine extended release (ER) were randomized to receive venlafaxine ER or placebo for 1 year. Patients without recurrence on venlafaxine ER during year 1 were randomized to venlafaxine ER or placebo for year 2. Psychosocial functioning was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire—Short Form (Q-LES-Q), Life EnjoymentScale—Short Version (LES-S), Social Adjustment Scale—Self-Report (SAS-SR) total and individual factors, Short Form Health Survey (SF-36) (vitality, social functioning, and role function-emotional items), and Longitudinal Interval Follow-up Evaluation (LIFE). Results At year 1 end, better overall psychosocial functioning was seen among patients randomly assigned to venlafaxine ER (n=129) vs placebo (n=129), with significant differences at end point on SF-36 role function-emotional, Q-LES-Q, and SAS-SR total, and work, house work, social/leisure, and extended-family factor scores (p≤0.05). At year 2 end, significant differences favored venlafaxine ER (n=43) vs placebo (n=40)on SF-36 vitality and rolefunction-emotional, Q-LES-Q, LES-S, LIFE, and SAS-SR total, social/leisure, and extended-family factor scores (p≤0.05). Limitations Patients with chronic MDD or treatment resistance were excluded and long-term specialist care was a financial incentive for treatment compliance. Discontinuation-related adverse events may have compromised the integrity of the treatment blind. Conclusions For patients with recurrent MDD, 2 years’ maintenance therapy with venlafaxine ER may improve psychosocial functioning vs placebo. PMID:20510459

  3. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

    PubMed Central

    Manchia, Mirko; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Aubry, Jean-Michel; Backlund, Lena; Banzato, Claudio EM.; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Biernacka, Joanna M.; Brichant-Petitjean, Clara; Bui, Elise; Calkin, Cynthia V.; Cheng, Andrew Tai Ann; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Czerski, Piotr M.; Dantas, Clarissa; Zompo, Maria Del; DePaulo, J. Raymond; Detera-Wadleigh, Sevilla D.; Etain, Bruno; Falkai, Peter; Frisén, Louise; Frye, Mark A.; Fullerton, Jan; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs; Hoban, Rebecca; Hou, Liping; Jamain, Stéphane; Kahn, Jean-Pierre; Kassem, Layla; Kato, Tadafumi; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kuo, Po-Hsiu; Kusumi, Ichiro; Laje, Gonzalo; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; López Jaramillo, Carlos A.; Maj, Mario; Malafosse, Alain; Martinsson, Lina; Masui, Takuya; Mitchell, Philip B.; Mondimore, Frank; Monteleone, Palmiero; Nallet, Audrey; Neuner, Maria; Novák, Tomás; O’Donovan, Claire; Ösby, Urban; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Potash, James B.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Richardson, Sara; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Schofield, Peter R.; Schubert, Oliver K.; Schweizer, Barbara; Seemüller, Florian; Grigoroiu-Serbanescu, Maria; Severino, Giovanni; Seymour, Lisa R.; Slaney, Claire; Smoller, Jordan W.; Squassina, Alessio; Stamm, Thomas; Steele, Jo; Stopkova, Pavla; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Wray, Naomi R.; Wright, Adam; Zandi, Peter P.; Zilles, David; Bauer, Michael; Rietschel, Marcella; McMahon, Francis J.

    2013-01-01

    Objective The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. PMID:23840348

  4. A critical analysis of user satisfaction surveys in addiction services: opioid maintenance treatment as a representative case study

    PubMed Central

    Trujols, Joan; Iraurgi, Ioseba; Oviedo-Joekes, Eugenia; Guàrdia-Olmos, Joan

    2014-01-01

    Background Satisfaction with services represents a key component of the user’s perspective, and user satisfaction surveys are the most commonly used approach to evaluate the aforementioned perspective. The aim of this discursive paper is to provide a critical overview of user satisfaction surveys in addiction treatment and harm reduction services, with a particular focus on opioid maintenance treatment as a representative case. Methods We carried out a selective critical review and analysis of the literature on user satisfaction surveys in addiction treatment and harm reduction services. Results Most studies that have reported results of satisfaction surveys have found that the great majority of users (virtually all, in many cases) are highly satisfied with the services received. However, when these results are compared to the findings of studies that use different methodologies to explore the patient’s perspective, the results are not as consistent as might be expected. It is not uncommon to find that “highly satisfied” patients report significant problems when mixed-methods studies are conducted. To understand this apparent contradiction, we explored two distinct (though not mutually exclusive) lines of reasoning, one of which concerns conceptual aspects and the other, methodological questions. Conclusion User satisfaction surveys, as currently designed and carried out in addiction treatment and harm reduction services, do not significantly help to improve service quality. Therefore, most of the enthusiasm and naiveté with which satisfaction surveys are currently performed and interpreted – and rarely acted on in the case of nonoptimal results – should be avoided. A truly participatory approach to program evaluation is urgently needed to reshape and transform patient satisfaction surveys. PMID:24482571

  5. QT Interval Screening in Methadone Maintenance Treatment: Report of a SAMHSA Expert Panel

    PubMed Central

    Martin, Judith A.; Campbell, Anthony; Killip, Thomas; Kotz, Margaret; Krantz, Mori J.; Kreek, Mary Jeanne; McCarroll, Brian A.; Mehta, Davendra; Payte, J. Thomas; Stimmel, Barry; Taylor, Trusandra; Wilford, Bonnie B.

    2014-01-01

    In an effort to enhance patient safety in Opioid Treatment Programs (OTPs), the Substance Abuse and Mental Health Services Administration (SAMHSA) convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members reviewed the literature, regulatory actions, professional guidances, and OTPs’ experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every OTP should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, ECG assessment, risk stratification, and prevention of drug interactions) for all patients, and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining ECGs as indicated by a particular patient’s risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events. The Panel also suggested specific modifications to informed consent documents, patient education, staff education, and methadone protocols. PMID:22026519

  6. Postharvest sour cherry quality and safety maintenance by exposure to Hot- water or treatment with fresh Aloe vera gel.

    PubMed

    Ravanfar, Rahele; Niakousari, Mehrdad; Maftoonazad, Neda

    2014-10-01

    Iranian sour cherries (Prunus cerasus) were coated with fresh Aloe vera gel or treated with hot water (40 ± 2 °C) for 2 min and stored for 17 days at 4 ± 1 °C. The physicochemical characteristics of gel coated and hot water treated samples were compared with untreated fruit during the cold storage period. Untreated fruit showed increased respiration rate, rapid weight loss and colour change, accelerated aging and ripening. On the contrary, sour cherries, particularly those coated with gel significantly delayed the above mentioned parameters allowing a fruit storability extension. The sensory analysis in both treatments revealed beneficial effects in terms of delaying dehydration, maintenance of fruit visual aspect without any detrimental effect on taste, aroma or flavours. Consequently, Aloe vera gel coating and immersion in hot water maintained the properties during postharvest storage of sour cherries and could be introduced as two valuable, simple and non-contaminating treatments. PMID:25328241

  7. Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment Patients in Dehong Prefecture of Yunnan Province, China

    PubMed Central

    Duan, Song; Ye, Runhua; Yang, Yuecheng; Wang, Jibao; Tang, Renhai; Gao, Meiyang; He, Na

    2015-01-01

    Objective Methadone maintenance treatment (MMT) was introduced to China in 2004 to reduce the harm of injecting drug users (IDUs). However, little is known about continued drug use, especially methamphetamine (MAMP), among MMT patients. Methods A survey was conducted among patients attending five major MMT clinics in Dehong Prefecture in 2014 to investigate the heroin and MAMP use and their associated risk factors. Participants were administered with face-to-face interviews, and urine tests for morphine and MAMP. Results A total of 2,121 were eligible and participated in the study. Among them, 220 (10.4%) were only positive for morphine, 12.9% were only positive for MAMP, and 196 (9.2%) were positive for both morphine and MAMP. Compared with neither use of heroin nor MAMP during MMT, heroin use (not using MAMP) was associated with ethnicity, shorter duration of MMT, lower dose of methadone, and having had no more than two sex partners in the past year; MAMP use (not using heroin) was associated with ethnicity, longer duration of MMT, higher dose of methadone and being aged <30 years (vs. ≥50 years); use of both heroin and MAMP was associated with being Dai minority (vs. Han), a marital status of divorced or widowed, having used drugs for ≥10 years and shorter duration of MMT. Conclusion These findings indicate the complexity in the treatment of heroin users and underscore the importance in prescribing appropriate methadone dosages in order to reduce both heroin and MAMP use. PMID:26196394

  8. Aripiprazole once-monthly 400 mg for long-term maintenance treatment of schizophrenia: a 52-week open-label study

    PubMed Central

    Peters-Strickland, Timothy; Baker, Ross A; McQuade, Robert D; Jin, Na; Eramo, Anna; Perry, Pamela; Johnson, Brian R; Duca, Anna; Sanchez, Raymond

    2015-01-01

    Background: Long-term maintenance treatment with an antipsychotic is often required to prevent relapse and mitigate functional deterioration in patients with schizophrenia. Aims: This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia. Methods: This 52-week, open-label study included patients previously enrolled in 1 of 2 AOM 400 randomized controlled trials (RCTs) and de novo patients. Safety endpoints included adverse events (AEs), suicidality, extrapyramidal symptoms, injection-site pain, and clinically relevant changes in clinical and laboratory values. The primary efficacy endpoint was the percentage of stable patients at baseline who remained stable at the last visit of the AOM 400 maintenance phase. All endpoints were assessed with descriptive statistics; there were no formal planned statistical analyses. Results: Of 1,247 patients screened, 1,178 enrolled in the study (194 de novo and 984 patients from the RCTs) and 1,081 received maintenance treatment with AOM 400. The maintenance phase completion rate was 79.4% at 52 weeks. Treatment-emergent AEs in ⩾5% of patients during open-label AOM 400 treatment were headache (7.6%), nasopharyngitis (7.0%), anxiety (6.8%), and insomnia (6.6%). There were no clinically relevant changes in safety parameters of interest. Ninety-five percent of stable patients at baseline remained stable at their last visit during the AOM 400 maintenance phase. Conclusions: The long-term safety and tolerability profile of AOM 400 was comparable to the RCTs, and the long-term therapeutic effect was maintained. PMID:27336044

  9. Impact of methadone maintenance treatment on women offenders' post-release recidivism.

    PubMed

    Farrell-MacDonald, Shanna; MacSwain, Mary-Ann; Cheverie, Madelon; Tiesmaki, Maija; Fischer, Benedikt

    2014-01-01

    Drug--including opioid--dependence is common in correctional populations, however little research exists on interventions for women offenders. Based on retrospective administrative data, we examined rates of return to custody (RTC) among three samples of Canadian federal women offenders with problematic opioid use (total n=137): (1) a group initiated on MMT during incarceration who continued MMT post-release (MMT-C; n=25); (2) a group initiated on MMT but who terminated treatment post-release (MMT-T; n=67), and (3) a non-MMT control group (MMT-N; n=45). Study groups were similar regarding socio-demographic, drug use and criminogenic indicators. Based on an unadjusted Cox proportional hazards model, the MMT-C group had a 65% lower risk of RTC than the MMT-N (reference) group (HR 0.35, CI 0.13-0.90); RTC risk was not different between the MMT-T and the reference group. Most RTCs were for technical revocations (e.g. violation of a legal condition of their release). Continuous MMT following release from corrections appears to be effective in reducing recidivism in women offenders with opioid problems; barriers to MMT in the study population should be better understood and ameliorated. PMID:24513717

  10. Visual mental imagery in psychopathology--implications for the maintenance and treatment of depression.

    PubMed

    Weßlau, Charlotte; Steil, Regina

    2014-06-01

    Negative mental images are a common feature in a range of mental disorders as well as in healthy subjects. Intrusive negative mental images have only recently become a focus of attention in clinical research on depression. Research so far indicates that they can be an important factor regarding the onset and chronicity of affective disorders. This article is the first to provide an extensive overview of the current state of research in the field of visual mental images in depression. It aims to investigate disorder-specific characteristics, as well as the role of imagery as a maintaining factor. A detailed definition and description of empirical results about mental images in depressive disorders is followed by a presentation and analysis of treatment studies using imagery techniques in depressed samples. Additionally, methodological issues like small sample sizes and the lack of control groups are pointed out and implications for future research are discussed. Case vignettes are included in the appendix to exemplify the importance of negative mental images in patients suffering from depression. PMID:24727643

  11. Orthopedic and orthodontic treatment in central giant cell granuloma treated with calcitonin.

    PubMed

    Romero, Martín; Romance, Ana; Garcia-Recuero, José Ismael; Fernández, Álvaro

    2011-09-01

    Central giant cell granuloma of the jaw is a benign lesion of unknown etiology that occurs with very low frequency. It mainly occurs in children and young adults and is more common in the mandible. The most common treatment is surgical removal; however, alternative therapies (intralesional injections of corticosteroids, interferon alpha, and calcitonin) have been used in order to avoid undesirable damage to the jaws and teeth. The lesion may cause root resorption, tooth germ displacement, and other dental problems, as well as malocclusion that must be treated orthodontically. The orthodontic, orthopedic, and calcitonin-based treatments of one of these cases is presented.

  12. Orthopedic and orthodontic treatment in central giant cell granuloma treated with calcitonin.

    PubMed

    Romero, Martín; Romance, Ana; Garcia-Recuero, José Ismael; Fernández, Álvaro

    2011-09-01

    Central giant cell granuloma of the jaw is a benign lesion of unknown etiology that occurs with very low frequency. It mainly occurs in children and young adults and is more common in the mandible. The most common treatment is surgical removal; however, alternative therapies (intralesional injections of corticosteroids, interferon alpha, and calcitonin) have been used in order to avoid undesirable damage to the jaws and teeth. The lesion may cause root resorption, tooth germ displacement, and other dental problems, as well as malocclusion that must be treated orthodontically. The orthodontic, orthopedic, and calcitonin-based treatments of one of these cases is presented. PMID:20815718

  13. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients.

    PubMed

    de Waal, Esther G M; de Munck, Linda; Hoogendoorn, Mels; Woolthuis, Gerhard; van der Velden, Annette; Tromp, Yvonne; Vellenga, Edo; Hovenga, Sjoerd

    2015-12-01

    Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow-up was 27·1 (0·46-54·4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18·4 months (range 0·13-43·5) and the median OS was 28·1 months (range 0·13-54·4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate.

  14. Clinical correlates and treatment of bone/joint pain and difficulty with sexual arousal in patients on maintenance hemodialysis.

    PubMed

    Carreon, Myra; Fried, Linda F; Palevsky, Paul M; Kimmel, Paul L; Arnold, Robert M; Weisbord, Steven D

    2008-04-01

    Bone/joint pain and difficulty with sexual arousal are prevalent, frequently severe, and potentially treatable in patients on maintenance hemodialysis. However, the mediators and adequacy of treatment for these symptoms have been less well studied. We sought to assess the clinical correlates and treatment of these symptoms in patients receiving chronic hemodialysis. Using the Dialysis Symptom Index, we assessed the presence and severity of bone/joint pain and difficulty with sexual arousal in 75 patients on chronic hemodialysis. Associations of demographic and clinical variables with these 2 symptoms were assessed. We also recorded the use of analgesics for bone/joint pain and, among men, phosphodiesterase-5 inhibitors for difficulty with sexual arousal. Twenty-eight patients (37%) reported bone/joint pain, of whom 20 (71%) described it as moderate to severe. Nineteen of 50 male patients (38%) reported difficulty with sexual arousal, which was described as moderate to severe by 15 (79%). Patients' demographic and clinical characteristics were not correlated with bone/joint pain. Among men, there were no correlations between patients' demographic and clinical characteristics and difficulty with sexual arousal. Only 48% of patients with bone/joint pain were receiving analgesics, while 21% of men who described difficulty with sexual arousal were receiving phosphodiesterase-5 inhibitors. Demographic, clinical, and dialysis-related variables are poorly correlated with bone/joint pain and difficulty with sexual arousal. However, these symptoms are prevalent and under-treated, which should spur efforts to assess the impact of improving provider assessment and treatment of these symptoms on patient outcomes, including health-related quality of life.

  15. Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment.

    PubMed

    Perez de Los Cobos, Jose; Trujols, Joan; Siñol, Núria; Duran-Sindreu, Santiago; Batlle, Francesca

    2016-04-01

    Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone. PMID:26825608

  16. How Much Do We Know about Maintaining Treatment Response after Successful Acne Therapy? Systematic Review on the Efficacy and Safety of Acne Maintenance Therapy.

    PubMed

    Dressler, Corinna; Rosumeck, Stefanie; Nast, Alexander

    2016-01-01

    After cessation of successful initial acne therapy, patients often experience flares. Consecutive maintenance treatment after successful induction therapy is promoted by guidelines; however, little is known about the efficacy/safety of different maintenance regimens. A systematic review on acne maintenance treatments was conducted. We identified 5 randomized controlled trials [RCTs; adapalene vs. vehicle or vs. no treatment (3 RCTs), adapalene/benzoyl peroxide (BPO) vs. vehicle, combination/monotherapy of minocycline (systemic)/tazarotene/placebo] and 3 non-RCTs on systemic isotretinoin, adapalene/BPO and azelaic acid. The results of adapalene versus vehicle/no treatment varied depending on the reported outcome. The 'number of patients maintaining at least 50% improvement' counting inflammatory lesions/non-inflammatory lesions with adapalene was superior to vehicle (risk ratio, RR 1.24, 95% confidence interval, CI 1.08-1.43/RR 1.34, 95% CI 1.18-1.59). However, no significant differences were found in 2 of 3 RCTs for maintaining 'clear/almost clear' or 'mild acne' or on the global grading score. For the combination regimens of minocycline/tazarotene/placebo, no significant differences were found. Adapalene/BPO was superior to vehicle counting inflammatory lesions/non-inflammatory lesions (RR 1.61, 95% CI 1.31-1.99; RR 1.80, 95% CI 1.44-2.26). Due to the scarcity of studies, few conclusions can be drawn. More homogeneous outcome measures and specific maintenance study designs may lead to more robust findings.

  17. The reductions in monetary cost and gains in productivity with methadone maintenance treatment: one year follow-up.

    PubMed

    Hsiao, Chih Yin; Chen, Kao Chin; Lee, Lan-Ting; Tsai, Hsin Chun; Chang, Wei Hung; Lee, I Hui; Chen, Po See; Lu, Ru-Band; Yang, Yen Kuang

    2015-02-28

    While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US$26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US$10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants׳ mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants׳ improved, but limited gains were seen with regard to their QOL. PMID:25500321

  18. Risks and realities: dyadic interaction between 6-month-old infants and their mothers in opioid maintenance treatment.

    PubMed

    Sarfi, Monica; Smith, Lars; Waal, Helge; Sundet, Jon Martin

    2011-12-01

    A number of studies point to methadone exposure in utero as a possible risk factor in the developing mother-infant relationship in the first year of life. This study is part of a larger, national follow-up of 38 infants prenatally exposed to methadone or buprenorphine and 36 comparison, low-risk infants. The aim of the present paper is to assess the quality of mother-infant relationship when the infants are 6 months old. Videotaped mother-infant interactions were rated in a global scale (NICHD). Maternal and infant contributions collapsed into the variables "infant style" and "maternal style" showed that the only factor making significant contribution to the outcome measure "dyadic mutuality" was maternal style. The importance of group membership (exposed versus non-exposed), was reduced when controlling for maternal drug use prior to opioid maintenance treatment (OMT), maternal depression and parenting stress as well as infants' developmental status and sensory-integrative functions. This suggests that prediction of dyadic mutuality should be based on individual characteristics rather than group characteristics. These results support previous research findings that methadone and buprenorphine use per se does not have direct influence on the quality of early mother-infant relationship, but tailored follow-up procedures targeting drug-free pregnancies and parenting support are beneficial for women in OMT and their children.

  19. Epidemiology of syphilis infection among drug users at methadone maintenance treatment clinics in China: systematic review and meta-analysis.

    PubMed

    Wang, Bing-xiang; Zhang, Li; Wang, Yu-jie; Yan, Jun-wei; Wan, Ya-nan; Peng, Wen-jia; Wang, Jing

    2014-07-01

    Illicit drug trade has re-emerged in China since 1979 and the number of drug addicts had increased. Syphilis is mainly spread through sexual contact and blood. The incidence of syphilis is high among drug users. Methadone maintenance treatment (MMT) clinics have been implemented in China since 2004. The aim of this study was to estimate the prevalence and risk factors of syphilis among drug users at MMT clinics in China between 2004 and 2013. Chinese and English databases (CBM, CNKI, Weipu, Pubmed) of literature were searched for studies reporting syphilis among drug users in MMT clinics from 2004 to 2013. The prevalence estimates and risk factors were summarized through a systematic review and meta-analysis of published literatures. In all, 29 eligible articles with a total of 8899 drug users, were selected in this review. The pooled prevalence of syphilis infection was 7.78% (95%CI: 5.83%-9.99%). The meta-analyses demonstrated significant differences in syphilis infection rates between men and women (OR = 0.34 [95%CI: 0.26-0.45]) but not between drug users and non-intravenous drug users (OR = 0.82 [95%CI: 0.51-1.32]). Enhanced detection of syphilis and health promotion is warranted in MMT clinics in China.

  20. The role of substance use and morality in violent crime - a qualitative study among imprisoned individuals in opioid maintenance treatment

    PubMed Central

    2014-01-01

    Background Opioid maintenance treatment (OMT) is regarded as a crime control measure. Yet, some individuals are charged with violent criminal offenses while enrolled in OMT. This article aims to generate nuanced knowledge about violent crime among a group of imprisoned, OMT-enrolled individuals by exploring their understandings of the role of substances in violent crime prior to and during OMT, moral values related to violent crime, and post-crime processing of their moral transgressions. Methods Twenty-eight semi-structured interviews were undertaken among 12 OMT-enrolled prisoners. The interviews were audio recorded and transcribed verbatim. An exploratory, thematic analysis was carried out with a reflexive and interactive approach. Findings Prior to OMT, substances and, in particular, high-dose benzodiazepines were deliberately used to induce ‘antisocial selves’ capable of transgressing individual moral codes and performing non-violent and violent criminal acts, mainly to support costly heroin use. During OMT, impulsive and uncontrolled substance use just prior to the violent acts that the participants were imprisoned for was reported. Yet, to conduct a (violent) criminal act does not necessarily imply that one is without moral principles. The study participants maintain moral standards, engage in complex moral negotiations, and struggle to reconcile their moral transgressions. Benzodiazepines were also used to reduce memories of and alleviate the guilt associated with having committed violent crimes. Conclusions Substances are used to transgress moral codes prior to committing and to neutralize the shame and guilt experienced after having committed violent crimes. Being simultaneously enrolled in OMT and imprisoned for a (violent) crime might evoke feelings of ‘double’ shame and guilt for both the criminal behavior prior to treatment and the actual case(s) one is imprisoned for while in OMT. Treatment providers should identify individuals with histories

  1. Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra

    PubMed Central

    Podestà, Manuel Alfredo; Graziani, Giorgio; Reggiani, Francesco; Buemi, Michele; Badalamenti, Salvatore; Ponticelli, Claudio

    2014-01-01

    Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by infiltrates of lipid-laden CD68+/CD1a− histiocytes, affecting heart, lungs, central nervous system, and bones. Kidney and adjacent structures can also be affected, leading to renal failure in about 30% of cases. The diagnosis is challenging, and treatment is generally based on administration of interferon-alpha (IFNα), but preliminary results also showed the therapeutic efficacy of anakinra, an antagonist of the receptor of interleukin-1 (IL-1). We report the case of an elderly patient with ECD and severe involvement of the heart and kidneys who was successfully treated with anakinra. PMID:26877969

  2. Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra.

    PubMed

    Podestà, Manuel Alfredo; Graziani, Giorgio; Reggiani, Francesco; Buemi, Michele; Badalamenti, Salvatore; Ponticelli, Claudio

    2014-09-01

    Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by infiltrates of lipid-laden CD68(+)/CD1a(-) histiocytes, affecting heart, lungs, central nervous system, and bones. Kidney and adjacent structures can also be affected, leading to renal failure in about 30% of cases. The diagnosis is challenging, and treatment is generally based on administration of interferon-alpha (IFNα), but preliminary results also showed the therapeutic efficacy of anakinra, an antagonist of the receptor of interleukin-1 (IL-1). We report the case of an elderly patient with ECD and severe involvement of the heart and kidneys who was successfully treated with anakinra.

  3. Methadone Maintenance Treatment Promotes Referral and Uptake of HIV Testing and Counselling Services amongst Drug Users and Their Partners

    PubMed Central

    Nguyen, Lan Phuong; Nguyen, Cuong Tat; Phan, Huong Thi Thu; Latkin, Carl A.

    2016-01-01

    Background Methadone maintenance treatment (MMT) reduces HIV risk behaviors and improves access to HIV-related services among drug users. In this study, we assessed the uptake and willingness of MMT patients to refer HIV testing and counseling (HTC) service to their sexual partners and relatives. Methods Health status, HIV-related risk behaviors, and HTC uptake and referrals of 1,016 MMT patients in Hanoi and Nam Dinh were investigated. Willingness to pay (WTP) for HTC was elicited using a contingent valuation technique. Interval and logistic regression models were employed to determine associated factors. Results Most of the patients (94.2%) had received HTC, 6.6 times on average. The proportion of respondents willing to refer their partners, their relatives and to be voluntary peer educators was 45.7%, 35.3%, and 33.3%, respectively. Attending MMT integrated with HTC was a facilitative factor for HTC uptake, greater WTP, and volunteering as peer educators. Older age, higher education and income, and HIV positive status were positively related to willingness to refer partners or relatives, while having health problems (mobility, usual care, pain/discomfort) was associated with lower likelihood of referring others or being a volunteer. Over 90% patients were willing to pay an average of US $17.9 for HTC service. Conclusion The results highlighted the potential role of MMT patients as referrers to HTC and voluntary peer educators. Integrating HIV testing with MMT services and applying users’ fee are potential strategies to mobilize resources and encourage HIV testing among MMT patients and their partners. PMID:27046029

  4. Reduced responses to heroin-cue-induced craving in the dorsal striatum: effects of long-term methadone maintenance treatment.

    PubMed

    Wang, Yarong; Wang, Hanyue; Li, Wei; Zhu, Jia; Gold, Mark S; Zhang, Dongsheng; Wang, Lina; Li, Yongbin; Yan, Xuejiao; Cheng, Jiajie; Li, Qiang; Wang, Wei

    2014-10-01

    Methadone maintenance treatment (MMT) is safe and effective for heroin addiction, but the neural basis of the length effects of long-term MMT on brain activity during craving in former heroin addicts is unclear. This study explored it by comparing the brain activations of heroin addicts with different length of MMT during pictorial presentation of heroin-related cue. Fifteen male former heroin addicts successfully treated by MMT less than 1 year (Group A), 15 matched patients with 2-3 year MMT (Group B) and 17 healthy controls underwent functional magnetic resonance imaging while heroin-related and neutral stimuli were present to them. Subjective cue-elicited craving was measured with visual analog scale before and after imaging. Then, partial correlation analysis to reveal the relationship between drug-related blood oxygen level dependent (BOLD) signal intensity and heroin or methadone use history. Finally, self-reported craving was not different between Group A and B before and after scanning. Compared with Group A, Group B had a significant reduced brain activity to heroin-related minus neural cues in the bilateral caudate. After controlling for the variable heroin use history, the drug-related BOLD signal intensity in the bilateral caudate was negatively correlated with MMT duration and total methadone consumption. When MMT history was controlled, the drug-related activity intensity in right caudate had a positive correlation with heroin daily dosage. Long-term MMT may improve heroin-craving response by modulating the impaired function in the bilateral dorsal striatum caused by former heroin use.

  5. The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment

    SciTech Connect

    Era, Saho; Abe, Takuya; Arakawa, Hiroshi; Kobayashi, Shunsuke; Szakal, Barnabas; Yoshikawa, Yusuke; Motegi, Akira; Takeda, Shunichi; Branzei, Dana

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer SENP1 knockout chicken DT40 cells are hypersensitive to spindle poisons. Black-Right-Pointing-Pointer Spindle poison treatment of SENP1{sup -/-} cells leads to increased mitotic slippage. Black-Right-Pointing-Pointer Mitotic slippage in SENP1{sup -/-} cells associates with apoptosis and endoreplication. Black-Right-Pointing-Pointer SENP1 counteracts sister chromatid separation during mitotic arrest. Black-Right-Pointing-Pointer Plk1-mediated cohesion down-regulation is involved in colcemid cytotoxicity. -- Abstract: SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockout chicken DT40 cells. SENP1{sup -/-} cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2{alpha}{sup +/-} mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2{alpha} is SUMOylated during mitosis, the TOP2{alpha}{sup +/-} mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1{sup -/-} cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.

  6. METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation.

    PubMed

    D'Egidio, Pietro Fausto; Bignamini, Emanuele; De Vivo, Enrico; Leonardi, Claudio; Pieri, Maria Chiara; González-Saiz, Francisco; Lucchini, Alfio

    2013-12-01

    METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years. The Opiate Dosage Adequacy Scale has been used for the evaluation of the "adequacy" of the methadone dosage and to stratify patients in adequate and not adequate groups. The treatment efficacy has been evaluated in correlation to the dosage adequacy during the visits. Moreover, patients have been evaluated according to the retention rate and duration of retention in treatment and a series of questionnaires.

  7. The relationship between self-reported substance use and psychiatric symptoms in low-threshold methadone maintenance treatment clients

    PubMed Central

    2011-01-01

    Background Ongoing psychiatric symptoms and substance use are common difficulties experienced by clients enrolled in methadone maintenance treatment (MMT). However, little research to date has evaluated if specific types of current substance use are related to specific types of current psychiatric symptoms. The present study investigated these relationships with a sample of clients enrolled in a low-threshold MMT program (i.e., clients are not expelled if they continue to use substances). Some clients enrolled in low-threshold programs may never achieve complete abstinence from all substances. Thus, understanding the possibly perpetuating relationships between concurrent substance use and psychiatric symptoms is important. Understanding such relationships may aid in developing possible target areas of treatment to reduce substance use and/or related harms in this population. Methods Seventy-seven individuals were interviewed regarding methadone usage and current and past substance use. Current psychiatric symptoms were assessed using a modified version of the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Relationships between types of substances used in the past 30 days and the types and number of psychiatric symptoms experienced in the same timeframe were examined. Results The majority of participants (87.0%) reported using alcohol, illicit substances, non-prescribed prescription opioids, or non-prescribed benzodiazepines in the past 30 days and 77.9% of participants reported currently experiencing psychiatric symptoms at levels that would likely warrant diagnosis. Current non-prescribed benzodiazepine use was a predictor for increased severity (i.e., symptom count) of almost all anxiety and mood disorders assessed. Conversely, number and presence of generalized anxiety symptoms and presence of social phobia symptoms predicted current non-prescribed benzodiazepine and alcohol use, respectively. Conclusions Individuals enrolled in the present low

  8. Maintenance Downtime

    Atmospheric Science Data Center

    2013-07-10

    ... will be unavailable March 5, 2013 8:00 am to 5:00 pm due to database maintenance. Date(s):  Tuesday, March 5, 2013 ... will be unavailable March 5, 2013 8:00 am to 5:00 pm due to database maintenance. ...

  9. Preventative Maintenance.

    ERIC Educational Resources Information Center

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  10. Software Maintenance.

    ERIC Educational Resources Information Center

    Cannon, Glenn; Jobe, Holly

    Proper cleaning and storage of audiovisual aids is outlined in this brief guide. Materials and equipment needed for first line maintenance are listed, as well as maintenance procedures for records, audio and video tape, film, filmstrips, slides, realia, models, prints, graphics, maps, and overhead transparencies. A 15-item quiz on software…

  11. Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models.

    PubMed

    Rosthøj, S; Keiding, N; Schmiegelow, K

    2012-02-28

    Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynamic. In 1992-1996, the Nordic Society of Paediatric Haematology and Oncology (NOPHO) conducted a randomised study (NOPHO-ALL-92) to investigate the effect of a new and more sophisticated dynamic treatment strategy. Unexpectedly, the new strategy worsened the outcome for the girls, whereas there were no treatment differences for the boys. There are as yet no general guidelines for optimising the treatment. On basis of the data from this study, our goal is to formulate an alternative dosing strategy. We use recently developed methods proposed by van der Laan et al. to obtain statistical models that may be used in the guidance of how the physicians should assign the doses to the patients to obtain the target of the treatment. We present a possible strategy and discuss the reliability of this strategy. The implementation is complicated, and we touch upon the limitations of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy.

  12. Buprenorphine maintenance treatment retention improves nationally recommended preventive primary care screenings when integrated into urban federally qualified health centers.

    PubMed

    Haddad, Marwan S; Zelenev, Alexei; Altice, Frederick L

    2015-02-01

    Buprenorphine maintenance therapy (BMT) expands treatment access for opioid dependence and can be integrated into primary health-care settings. Treating opioid dependence, however, should ideally improve other aspects of overall health, including preventive services. Therefore, we examined how BMT affects preventive health-care outcomes, specifically nine nationally recommended primary care quality health-care indicators (QHIs), within federally qualified health centers (FQHCs) from an observational cohort study of 266 opioid-dependent patients initiating BMT between 07/01/07 and 11/30/08 within Connecticut's largest FQHC network. Nine nationally recommended preventive QHIs were collected longitudinally from electronic health records, including screening for chronic infections, metabolic conditions, and cancer. A composite QHI score (QHI-S), based on the percentage of eligible QHIs achieved, was categorized as QHI-S ≥80% (recommended) and ≥90% (optimal). The proportion of subjects achieving a composite QHI-S ≥80 and ≥90 % was 57.1 and 28.6%, respectively. Screening was highest for hypertension (91.0%), hepatitis C (80.1%), hepatitis B (76.3%), human immunodeficiency virus (71.4%), and hyperlipidemia (72.9%) and lower for syphilis (49.3%) and cervical (58.5%), breast (44.4%), and colorectal (48.7%) cancer. Achieving QHI-S ≥80% was positively and independently associated with ≥3-month BMT retention (adjusted odds ratio (AOR) = 2.19; 95% confidence interval (CI) = 1.18-4.04) and BMT prescription by primary care providers (PCPs) rather than addiction psychiatric specialists (AOR = 3.38; 95% CI = 1.78-6.37), and negatively with being female (AOR = 0.30; 95% CI = 0.16-0.55). Within primary health-care settings, achieving greater nationally recommended health-care screenings or QHIs was associated with being able to successfully retain patients on buprenorphine longer (3 months or more) and when buprenorphine was prescribed

  13. The partial characterization of tumor necrosis factor-[alpha] resistance, and differential interferon-[alpha] and -[gamma] regulation of the indoleamine 2,3-dioxygenase gene in a human cell line

    SciTech Connect

    Kimbro, K.S.

    1993-01-01

    In order to understand the mechanisms of action of Tumor Necrosis Factor(TNF) on human tumor cells, the author has analyzed a TNF-resistant (TNFr) cell variant of ME180. Studies of the resistant clone showed an increase in in vitro generated free radical resistance, superoxide dismutase, and catalase mRNAs. The analysis of a TNFr clone and its karyotype compared to the parental line, suggest that TNFr could be due to an increase in free radical scavenger proteins and/or chromosomal aberrations. The second component of the thesis involves the analysis of another cytotoxic cytokine, interferon-[gamma], and its ability to induce indoleamine 2,3-dioxygenase (IDO). IDO is the rate limiting enzyme in the catabolism of tryptophan in most cell types. It is predominantly induced following treatment with IFN-[gamma], at a low level or not at all by IFN-[alpha] or-[beta]. The author has determined that the differential regulation of the IDO gene by IFNs may be the result of different interactions of proteins with the regulatory sequences of the IDO gene. The IDO gene has been mapped to chromosome 8.

  14. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

    PubMed Central

    Lu-Qun, Wang; Hao, Li; Xiao-Peng, He; Fang-Lin, Li; Ling-Ling, Wang; Xue-Liang, Chen; Ming, Hou

    2014-01-01

    Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL). Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlow regimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity. PMID:24963332

  15. Guidelines for maintenance treatment of childhood asthma: development of a score card system by multivariate cluster analysis.

    PubMed

    Donnelly, W J; Donnelly, J E; Thong, Y H

    1987-01-01

    Multivariate cluster analysis of data on 128 asthmatic children resulted in the identification of 8 major discriminating variables. Stepwise divisions by this computer programme resulted in the formation of 6 grades of severity. There was significant correlation between higher grades of severity and early onset of the disease (P less than 0.02). There was also significant correlation between higher grades of severity and greater use of interval medications (P less than 0.002). However, 27.3% were receiving inadequate interval medications in respect of their grade of severity. Assignation of a 5-point scale to each of the 8 major discriminating variables resulted in the generation of computer-designated scores commensurate with each grade of severity. This was coupled to current recommendations for stepwise maintenance medications appropriate for each grade. This Score Card system for maintenance management of childhood asthma may prove useful in busy clinical settings.

  16. Maintenance of potential spermatogonial stem cells in vitro by GDNF treatment in a chondrichthyan model (Scyliorhinus canicula L.).

    PubMed

    Gautier, Aude; Bosseboeuf, Adrien; Auvray, Pierrick; Sourdaine, Pascal

    2014-10-01

    Previous work in dogfish, Scyliorhinus canicula, has identified the testicular germinative area as the spermatogonial stem cell niche. In the present study, an in vitro co-culture system of spermatogonia and somatic cells from the germinative area was developed. Long-term maintenance of spermatogonia has been successful, and addition of GDNF has promoted the development of clones of spermatogonia expressing stem cell characteristics such as alkaline phosphatase activity and has allowed maintenance of self-renewal in spermatogonia for at least 5 mo under culture conditions, notably by decreasing cell apoptosis. Furthermore, clones of spermatogonia expressed the receptor of GDNF, GFRalpha1, which is consistent with the effect of GDNF on cells despite the lack of identification of a GDNF sequence in the dogfish's transcriptome. However, a sequence homologous to artemin has been identified, and in silico analysis supports the hypothesis that artemin could replace GDNF in the germinative area in dogfish. This study, as the first report on long-term in vitro maintenance of spermatogonia in a chondrichthyan species, suggests that the GFRalpha1 signaling function in self-renewal of spermatogonial stem cells is probably conserved in gnathostomes. PMID:25143357

  17. Fibrinolytic response to interferon-alpha in healthy human subjects.

    PubMed

    Corssmit, E P; Levi, M; Hack, C E; ten Cate, J W; Sauerwein, H P; Romijn, J A

    1996-01-01

    Interferons (IFNs) are used for a variety of disorders. It has been postulated that part of the effects of IFN may be mediated by IFN-induced modulation of endothelial cells. Since the principal activating and inhibiting factors of the fibrinolytic system are synthesized and stored in endothelial cells, we have studied the effects on fibrinolysis and coagulation of the administration of recombinant IFN-alpha (5 x 10(6) U/m2) to healthy human subjects (n = 8) in a randomized controlled cross-over study. IFN-alpha significantly increased plasma levels of tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Simultaneously, plasma levels of the inhibitor of plasminogen activation, PAI-1, sharply increased. The net effect on plasma plasminogen activator activity (PA-activity) was a modest increase to 116% of baseline, however without a significant effect on plasmin generation, as reflected by plasma levels of plasmin-alpha 2-antiplasmin complexes. IFN-alpha had no effect on the plasma levels of thrombin-antithrombin III (TAT) complexes. We conclude that despite considerable effects on endothelial cells, IFN-alpha does not significantly alter the coagulant-fibrinolytic balance, although the occurrence of such changes under pathological circumstances is not excluded.

  18. Interferon-alpha: a therapeutic target in systemic lupus erythematosus.

    PubMed

    Crow, Mary K

    2010-02-01

    The long history of elevated interferon (IFN)-alpha in association with disease activity in patients who have systemic lupus erythematosus (SLE) has assumed high significance in the past decade, with accumulating data strongly supporting broad activation of the type I IFN pathway in cells of patients who have lupus, and association of IFN pathway activation with significant clinical manifestations of SLE and increased disease activity based on validated measures. In addition, a convincing association of IFN pathway activation with the presence of autoantibodies specific for RNA-binding proteins has contributed to delineation of an important role for Toll-like receptor activation by RNA-containing immune complexes in amplifying innate immune system activation and IFN pathway activation. Although the primary triggers of SLE and the IFN pathway remain undefined, rapid progress in lupus genetics is helping define lupus-associated genetic variants with a functional relationship to IFN production or response in patients. Together, the explosion of data and understanding related to the IFN pathway in SLE have readied the lupus community for translation of those insights to improved patient care. Patience will be needed to allow collection of clinical data and biologic specimens across multiple clinical centers required to support testing of IFN activity, IFN-inducible gene expression and chemokine gene products as candidate biomarkers. Meanwhile, promising clinical trials are moving forward to test the safety and efficacy of monoclonal antibody inhibitors of IFN-alpha. Other therapeutic approaches to target the IFN pathway may follow close behind.

  19. Interferon-alpha genes from Bos and Bubalus bubalus.

    PubMed

    Shi, Xiju; Xia, Chun; Pan, Baoliang; Wang, Ming

    2006-01-01

    Interferon-a genes were cloned from six breeds of three species of two genera (three Chinese native cattle breeds of yellow cattle, wild yak and HuanHu domestic yak, one European breed of Holstein cow, and two water buffalo breeds of FuAn water buffalo and FuZhong water buffalo) by direct PCR. The PCR products were directly inserted into the expression vector to be sequenced and expressed. Sequence analysis showed that IFN-a genes of six clones were composed of 498 nucleotides, encoding a mature polypeptide with 166 amino acids. Compared with the published BoIFN-a subtypes, the IFN-a gene of Holstein cow had only one point mutation with the BoIFN-aA subtype. The IFN-a gene of yellow cattle was similar to the BoIFN-aD subtype with amino acid identity of 97.0% and may be considered as a new subtype, namely, BoIFN-aD1. The other four IFN-a genes, cloned from wild yak and HuanHu domestic yak, FuAn water buffalo, and FuZhong water buffalo, represented four new subtypes, namely, BoIFN-aI, BoIFN-aJ, BuIFN-a1, and BuIFN-a2, respectively. Each of the six clones was expressed in E. coli with molecular weight of approximately 20 kDa by SDS-PAGE and Western blot analyses. Antiviral activity assays showed that the six recombinant IFN-a (rIFN-a) all exhibited 1,000 times higher antiviral activity in the MDBK/VSV cell line than in the CEF/VSV one. Moreover, the rIFN-as could inhibit infectious bovine rhinotracheitis virus replication in the MDBK cell line using CPE inhibition method. The results suggested that rIFN-as a potential agent for clinical application against virus diseases in cattle industry.

  20. Maintenance treatment of chronic schizophrenic patients. A study with the long-acting thioxanthene derivative, cis(Z)-clopenthixol decanoate-sordinol depot.

    PubMed

    Dom, R; De Mesmaecker, L; van den Broucke, M; van Hest, T; Baro, F

    1978-04-01

    The clinical effect of clopenthixol decanoate has been assessed in a 5-month controlled including 21 hospitalized chronic schizophrenic patients. The ratings were done with BPRS, NOSIE 30, the two psychological tests of WAIS and Grübaum, and the rating scale of Simpson & Angus to assess extrapyramidal side effects. Clopenthixol decanoate was found an effective and long-acting antipsychotic compound with few autonomic and neurological side effects. Compared with previous maintenance treatment it also showed a positive influence on depression and facilitation of the social adaptation of the patients.

  1. Assessing the cost-effectiveness of medical treatments in acid-related diseases. The Markov chain approach applied to a comparison between intermittent and maintenance treatment of reflux esophagitis.

    PubMed

    Stålhammar, N O

    1993-01-01

    Escalating medical costs have made it increasingly important to carry out economic evaluations of drug therapy. In the area of acid-related diseases, much of the current interest is focused on comparisons between omeprazole and H2 receptor antagonists. After having discussed the basic methodology used in these analyses, viz. the decision-tree analysis, this paper presents an extension of this methodology, the Markov chain approach, which is more appropriate for analyses of longer time periods. Thereafter, this methodology is used to analyze the cost-effectiveness of omeprazole in intermittent versus maintenance treatment of reflux esophagitis. The cost data are from Sweden and the time period studied is one year. It is found that maintenance treatment provides 63 more healthy days per year at an extra direct cost of SEK 40 per day. From a sensitivity analysis it is concluded that the cost-effectiveness of intermittent versus maintenance treatment is mainly determined by the probability of relapse when off treatment, the severity of the symptoms in the case of a relapse and the value to the patient of a healthy day, i.e. a day free from reflux esophagitis. PMID:8171303

  2. Effects of Adapalene-Benzoyl Peroxide Combination Gel in Treatment or Maintenance Therapy of Moderate or Severe Acne Vulgaris: A Meta-Analysis

    PubMed Central

    Zhou, Rongying

    2014-01-01

    Background An antibiotic-free, fixed-dose combination gel with adapalene (A) 0.1% and benzoyl peroxide (BPO) 2.5% has been developed for treatment of acne vulgaris. Objective To compare the clinical outcomes of A-BPO combination gel with vehicle gel for treatment or maintenance therapy of patients with acne vulgaris. Methods An electronic search of the database PubMed (1966 to September 2012), Embase (1984 to September 2012), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2012) was undertaken to identify relevant studies. Main clinical outcomes were success rate, treatment-related adverse events (AEs), AEs leading to discontinuation, satisfaction with the effectiveness, and overall satisfaction. Results Six studies were finally included in this meta-analysis. The A-BPO group yielded better clinical outcomes regarding the success rate (p<0.00001), satisfaction with the effectiveness of treatment (p=0.005), and overall satisfaction (p=0.005) compared to the vehicle group. The incidence of treatment-related AEs in the A-BPO group was comparable with that of vehicle group (p=0.09), while the A-BPO group was associated with a slightly increase in the incidence of AEs leading to discontinuation when compared with the vehicle group (p=0.02). Conclusion A-BPO combination gel yields better clinical outcomes including success rate, satisfaction with the effectiveness, and overall satisfaction compared to vehicle gel, despite an increased incidence of AEs leading to discontinuation. The A-BPO combination agent most likely contributes to the treatment of moderate acne vulgaris rather than severe acne vulgaris, but it may be useful in maintenance therapy of patients with severe acne vulgaris. PMID:24648685

  3. A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.

    PubMed

    Wasdell, Michael B; Jan, James E; Bomben, Melissa M; Freeman, Roger D; Rietveld, Wop J; Tai, Joseph; Hamilton, Donald; Weiss, Margaret D

    2008-01-01

    The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy. PMID:18078449

  4. Blockade of morphine-induced behavioral sensitization by a combination of amisulpride and RB101, comparison with classical opioid maintenance treatments

    PubMed Central

    Cordonnier, L; Sanchez, M; Roques, B P; Noble, F

    2007-01-01

    Background and purpose: Maintenance treatments with methadone or buprenorphine are more or less efficient procedures for helping heroin addicts to stop or reduce drug abuse. Another approach to treat opiate dependence could be to target the endogenous opioid system by enhancing the effects of enkephalins by protecting them from enzymic degradation by the dual peptidase inhibitor RB101. Experimental approach: As chronic treatment with the dopamine D2 antagonist amisulpride facilitates RB101-induced behavioral effects, we chose in this study to treat mice previously sensitized to the hyperlocomotor effects induced by morphine with a combination of amisulpride and RB101. Key results: Expression of morphine-induced locomotor sensitization was abolished after combined treatment with amisulpride (20 mg.kg−1, i.p.) and RB101 (80 mg.kg−1, i.p.), whereas these drugs were not effective when used alone. We then compared these results with the effects of amisulpride combined with buprenorphine (0.1 mg.kg−1, i.p.) or methadone (2.5 mg.kg−1, i.p.) upon morphine-induced behavioral sensitization. Whereas the combination of amisulpride and buprenorphine partially blocked the expression of morphine sensitization, amisulpride+methadone was not effective in this paradigm. Conclusions and implications: The combination of amisulpride+RB101 appears to be very efficient in blocking the expression of morphine-induced behavioral sensitization. This could reflect a reinstatement of a balance between the function of the dopamine and opioid systems and could represent a new approach in maintenance treatments for opiate addiction. PMID:17351659

  5. Effectiveness of Relapse Prevention Cognitive-Behavioral Model in Opioid-Dependent Patients Participating in the Methadone Maintenance Treatment in Iran

    PubMed Central

    PASHAEI, Tahereh; SHOJAEIZADEH, Davoud; RAHIMI FOROUSHANI, Abbas; GHAZITABATABAE, Mahmoud; MOEENI, Maryam; RAJATI, Fatemeh; M RAZZAGHI, Emran

    2013-01-01

    Background: To evaluate the effectiveness of a relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) in Iran. Methods: The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies (INCAS). Participants were randomized into two groups: educational intervention group (N=46) and control group (N=46). The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instrument. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. Results: While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 (P<0.01). Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 (P<.03), 0.31 (P<.02), and 0.13 (P<.02) respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group Conclusion: Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance. PMID:26056645

  6. RATE OF ADHERENCE TO AND FACTORS ASSOCIATED WITH METHADONE MAINTENANCE TREATMENT PROGRAM (MMTP) COMPLIANCE AMONG INJECTING DRUG USE PATIENTS IN NEPAL.

    PubMed

    Sharma, Vikas; Chamroonswasdi, Kanittha; Srisorrachatr, Suwat

    2016-03-01

    We conducted a survey to determine the rate of adherence to and factors associated with compliance with a methadone maintenance treatment program (MMTP) among injecting drug users in Nepal. We conducted face-to-face structured interviews with 165 methadone treatment patients aged 20-54 years during 5-20 April 2015. Data analysis included percentages, means, standard deviations, chi-square tests and multiple logistic regression analysis. Seventy-two point one percent of respondents had good adherence to a MMTP. Multiple logistic regression with 81.8% prediction showed respondents without a previous history of relapse were 2.7 times more likely to adhere to the MMTP than those with a history of relapse [Adjusted OR = 2.772; 95% Confidence interval (CI): 1.163-6.605]. Respondents with a good knowledge of the MMTP 9.4 times more likely to be adherent to the MMTP than those with a poor to fair knowledge of the MMTP (Adjusted OR = 9.464; 95% CI: 3.873-23.126). The likelihood of MMTP adherence was 4.5 times more likely when methadone treatment services were available than those where the availability of methadone treatment services were low to moderate (Adjusted OR = 4.553; 95% CI: 1.883-11.008). Knowledge and availability of MMTP need to be improved in the study area in Nepal.

  7. Low-dose add-on memantine treatment may improve cognitive performance and self-reported health conditions in opioid-dependent patients undergoing methadone-maintenance-therapy.

    PubMed

    Chang, Yun-Hsuan; Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Po See; Wang, Tzu-Yun; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-01-01

    An important interaction between opioid and dopamine systems has been indicated, and using opioids may negatively affect cognitive functioning. Memantine, a medication for Alzheimer's disease, increasingly is being used for several disorders and maybe important for cognitive improvement. Opioid-dependent patients undergoing methadone-maintenance-therapy (MMT) and healthy controls (HCs) were recruited. Patients randomly assigned to the experimental (5 mg/day memantine (MMT+M) or placebo (MMT+P) group: 57 in MMT+M, 77 in MMT+P. Those completed the cognitive tasks at the baseline and after the 12-week treatment were analyzed. Thirty-seven age- and gender-matched HCs, and 42 MMT+P and 39 MMT+M patients were compared. The dropout rates were 49.4% in the MMT+P and 26.3% in the MMT+M. Both patient groups' cognitive performances were significantly worse than that of the HCs. After the treatment, both patient groups showed improved cognitive performance. We also found an interaction between the patient groups and time which indicated that the MMT+M group's post-treatment improvement was better than that of the MMT+P group. Memantine, previously reported as neuroprotective may attenuate chronic opioid-dependence-induced cognitive decline. Using such low dose of memantine as adjuvant treatment for improving cognitive performance in opioid dependents; the dose of memantine might be a worthy topic in future studies. PMID:25989606

  8. Low-dose add-on memantine treatment may improve cognitive performance and self-reported health conditions in opioid-dependent patients undergoing methadone-maintenance-therapy.

    PubMed

    Chang, Yun-Hsuan; Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Po See; Wang, Tzu-Yun; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-05-19

    An important interaction between opioid and dopamine systems has been indicated, and using opioids may negatively affect cognitive functioning. Memantine, a medication for Alzheimer's disease, increasingly is being used for several disorders and maybe important for cognitive improvement. Opioid-dependent patients undergoing methadone-maintenance-therapy (MMT) and healthy controls (HCs) were recruited. Patients randomly assigned to the experimental (5 mg/day memantine (MMT+M) or placebo (MMT+P) group: 57 in MMT+M, 77 in MMT+P. Those completed the cognitive tasks at the baseline and after the 12-week treatment were analyzed. Thirty-seven age- and gender-matched HCs, and 42 MMT+P and 39 MMT+M patients were compared. The dropout rates were 49.4% in the MMT+P and 26.3% in the MMT+M. Both patient groups' cognitive performances were significantly worse than that of the HCs. After the treatment, both patient groups showed improved cognitive performance. We also found an interaction between the patient groups and time which indicated that the MMT+M group's post-treatment improvement was better than that of the MMT+P group. Memantine, previously reported as neuroprotective may attenuate chronic opioid-dependence-induced cognitive decline. Using such low dose of memantine as adjuvant treatment for improving cognitive performance in opioid dependents; the dose of memantine might be a worthy topic in future studies.

  9. Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder With or Without Agoraphobia? A Randomized Controlled Clinical Trial

    PubMed Central

    White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

    2012-01-01

    Objective To examine the possibility that maintenance cognitive behavior therapy (M–CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either nine monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. Results M–CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up (MFU). Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-MFU (HR = 1.15, p < .01). Conclusions M–CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome in PD/A. PMID:23127290

  10. RATE OF ADHERENCE TO AND FACTORS ASSOCIATED WITH METHADONE MAINTENANCE TREATMENT PROGRAM (MMTP) COMPLIANCE AMONG INJECTING DRUG USE PATIENTS IN NEPAL.

    PubMed

    Sharma, Vikas; Chamroonswasdi, Kanittha; Srisorrachatr, Suwat

    2016-03-01

    We conducted a survey to determine the rate of adherence to and factors associated with compliance with a methadone maintenance treatment program (MMTP) among injecting drug users in Nepal. We conducted face-to-face structured interviews with 165 methadone treatment patients aged 20-54 years during 5-20 April 2015. Data analysis included percentages, means, standard deviations, chi-square tests and multiple logistic regression analysis. Seventy-two point one percent of respondents had good adherence to a MMTP. Multiple logistic regression with 81.8% prediction showed respondents without a previous history of relapse were 2.7 times more likely to adhere to the MMTP than those with a history of relapse [Adjusted OR = 2.772; 95% Confidence interval (CI): 1.163-6.605]. Respondents with a good knowledge of the MMTP 9.4 times more likely to be adherent to the MMTP than those with a poor to fair knowledge of the MMTP (Adjusted OR = 9.464; 95% CI: 3.873-23.126). The likelihood of MMTP adherence was 4.5 times more likely when methadone treatment services were available than those where the availability of methadone treatment services were low to moderate (Adjusted OR = 4.553; 95% CI: 1.883-11.008). Knowledge and availability of MMTP need to be improved in the study area in Nepal. PMID:27244967

  11. Acute and maintenance electroconvulsive therapy for treatment of severely disabling obsessive-compulsive symptoms in a patient with Asperger syndrome.

    PubMed

    Nilsson, Björn M; Ekselius, Lisa

    2009-09-01

    We report successful treatment with electroconvulsive therapy of a comorbid condition including severe obsessive-compulsive symptoms and hypochondriacal delusions in a 38-year-old man with Asperger syndrome. His condition deteriorated into a severely disabled chronic state that was refractory to different pharmacological and psychological treatments but was completely reversed after electroconvulsive therapy. Although typical obsessive-compulsive symptoms were predominant, the case also exhibits differences compared with regular obsessive-compulsive disorder regarding onset and course that are discussed in the report.

  12. Harm reduction, methadone maintenance treatment and the root causes of health and social inequities: An intersectional lens in the Canadian context

    PubMed Central

    2011-01-01

    Background Using our research findings, we explore Harm Reduction and Methadone Maintenance Treatment (MMT) using an intersectional lens to provide a more complex understanding of Harm Reduction and MMT, particularly how Harm Reduction and MMT are experienced differently by people dependent on how they are positioned. Using the lens of intersectionality, we refine the notion of Harm Reduction by specifying the conditions in which both harm and benefit arise and how experiences of harm are continuous with wider experiences of domination and oppression; Methods A qualitative design that uses ethnographic methods of in-depth individual and focus group interviews and naturalistic observation was conducted in a large city in Canada. Participants included Aboriginal clients accessing mainstream mental health and addictions care and primary health care settings and healthcare providers; Results All client-participants had profound histories of abuse and violence, most often connected to the legacy of colonialism (e.g., residential schooling) and ongoing colonial practices (e.g., stigma & everyday racism). Participants lived with co-occurring illness (e.g., HIV/AIDS, Hepatitis C, PTSD, depression, diabetes and substance use) and most lived in poverty. Many participants expressed mistrust with the healthcare system due to everyday experiences both within and outside the system that further marginalize them. In this paper, we focus on three intersecting issues that impact access to MMT: stigma and prejudice, social and structural constraints influencing enactment of peoples' agency, and homelessness; Conclusions Harm reduction must move beyond a narrow concern with the harms directly related to drugs and drug use practices to address the harms associated with the determinants of drug use and drug and health policy. An intersectional lens elucidates the need for harm reduction approaches that reflect an understanding of and commitment to addressing the historical, socio

  13. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

    PubMed Central

    Carrera, Fernando; Lok, Charmaine E.; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F.E.; Canaud, Bernard; Kerr, Peter G.; Macdougall, Iain C.; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C.

    2010-01-01

    Background. Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. Methods. Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11–13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50–53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. Results. Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. Conclusions. Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa

  14. Concurrent Heroin Use and Correlates among Methadone Maintenance Treatment Clients: A 12-Month Follow-up Study in Guangdong Province, China

    PubMed Central

    Luo, Xiaofeng; Zhao, Peizhen; Gong, Xiao; Zhang, Lei; Tang, Weiming; Zou, Xia; Chen, Wen; Ling, Li

    2016-01-01

    Objective: To assess concurrent heroin use and correlates among Methadone Maintenance Treatment (MMT) clients in Guangdong Province, China. Method: Demographic and drug use data were collected with a structured questionnaire, and MMT information was obtained from the MMT clinic registration system in Guangdong. Human immunodeficiency virus (HIV-) and hepatitis C virus (HCV) infected status and urine morphine results were obtained from laboratory tests. Logistic regressions were employed to investigate the factors associated with concurrent heroin use. Results: Among the 6848 participants, 75% continued using heroin more than once during the first 12 months after treatment initiation. Concurrent heroin use was associated with inharmonious family relationship (OR (odds ratio) = 1.49, 95% CI (confidence intervals): 1.24–1.78), HIV positivity (OR = 1.25, 95% CI: 1.01–1.55), having multiple sex partners (OR = 1.34, 95% CI: 1.07–1.69), having ever taken intravenous drugs (OR = 0.81, 95% CI: 0.69–0.95), higher maintenance dose (OR = 1.13, 95% CI: 1.01–1.28) and poorer MMT attendance (OR<20% = 1.32, 95% CI: 1.13–1.53; OR20%– = 1.33, 95% CI: 1.14–1.54; OR50%– = 1.69, 95% CI: 1.44–2.00). Among those who used heroin concurrently, the same factors, and additionally being older (OR35– = 1.26, 95% CI: 1.11–1.43; OR≥45 = 1.63, 95% CI: 1.30–2.05) and female (OR = 1.60, 95% CI: 1.28–2.00), contribute to a greater frequency of heroin use. Conclusions: Concurrent heroin use was prevalent among MMT participants in Guangdong, underscoring the urgent needs for tailored interventions and health education programs for this population. PMID:27005649

  15. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    ERIC Educational Resources Information Center

    Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

    2012-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

  16. Maintenance Sessions Prolong Cigarette Abstinence.

    ERIC Educational Resources Information Center

    Brandon, Thomas H.; And Others

    Recent smoking treatment programs have shifted emphasis from initial cessation rates to long-term abstinence, with aversion therapy and coping response training having had the most success. A smoking cessation treatment consisting of rapid smoking and behavioral counseling was supplemented with two maintenance treatments. After completing the…

  17. Criminal convictions among dependent heroin users during a 3-year period prior to opioid maintenance treatment: a longitudinal national cohort study.

    PubMed

    Bukten, Anne; Skurtveit, Svetlana; Stangeland, Per; Gossop, Michael; Willersrud, Astrid B; Waal, Helge; Havnes, Ingrid; Clausen, Thomas

    2011-12-01

    This study investigates frequency and types of criminal convictions among a national sample of heroin users during a 3-year period prior to opioid maintenance treatment (OMT). All heroin users (N = 3,789) in Norway who applied for and were eligible for OMT (1997-2003) were included. The OMT records were cross-linked to Norwegian crime statistics. During observation, 24,478 convictions were recorded among 60.9% of the sample. Differences of criminal convictions were found within the group; a large proportion (39.1%) had no convictions, whereas 10% of the sample was responsible for 37.8% of all convictions. Convictions for acquisitive crimes and drug crimes were the most common. Variations in the cohort's individual crime sequences were found. The heavy involvement of heroin users with the criminal justice system provides an opportunity to intervene with dependent offenders. Coordination between treatment providers and police or courts can play an important role in improving outcomes through better access to treatment.

  18. Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; In the light of completed trials.

    PubMed

    Korkmaz, Taner; Seber, Selcuk; Basaran, Gul

    2016-02-01

    Late and recurrent stage ovarian cancer has a high mortality and low response rate to therapy beyond first line treatment. Although first line platinum/taxane based regimens have a satisfactory response rate eventually in most cases disease recurrence is common and second-line treatments are not curative. Delaying progression or recurrence is the main goal of current ongoing clinical studies by means of establishing an effective maintenance regimen with acceptable toxicity profile. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. Over the past several years, the idea of prolongation of therapy for ovarian cancer has garnered clinical attention and academic debate. As a result of a greater understanding of the molecular pathways involved in carcinogenesis and tumor growth, a large number of potential therapeutic targets have been identified and drugs to block receptors, ligands or pathways are being developed. Currently, numerous clinical trials with targeted agents have just been completed or are ongoing involving patients achieving a complete or durable response after first-line and beyond the first line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of progression-free survival and overall survival. PMID:26603345

  19. Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge

    PubMed Central

    Gowen, Brian B.; Ennis, Jane; Bailey, Kevin W.; Vest, Zachary; Scharton, Dionna; Sefing, Eric J.; Turner, Jeffrey D.

    2014-01-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity. PMID:24662673

  20. Photodynamic therapy as adjunct to non-surgical periodontal treatment in patients on periodontal maintenance: a randomized controlled clinical trial.

    PubMed

    Chondros, Panos; Nikolidakis, Dimitris; Christodoulides, Nicos; Rössler, Ralf; Gutknecht, Norbert; Sculean, Anton

    2009-09-01

    Recent preclinical and clinical data have suggested the potential benefit of photodynamic therapy (PDT) in the treatment of periodontitis. However, currently, there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis. The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy. Twenty-four patients receiving regularly supportive periodontal therapy were randomly treated with either subgingival scaling and root planing followed by a single episode of PDT (test) or subgingival scaling and root planing alone (control). The following parameters were evaluated at baseline and at 3 months and 6 months after therapy: full mouth plaque score (FMPS), full mouth bleeding score (FMBS), bleeding on probing (BOP) at experimental sites, probing pocket depth (PPD), gingival recession (REC), and clinical attachment level (CAL). Primary outcome variables were changes in PPD and CAL. Microbiological evaluation of Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythensis (T.f.), Treponema denticola (T.d.), Peptostreptococcus micros (P.m.), Fusobacterium nucleatum (F.n.), Campylobacter rectus (C.r.), Eubacterium nodatum (E.n.), Eikenella corrodens (E.c.), and Capnocytophaga species (C.s.) was also performed at baseline and at 3 months and 6 months after therapy, using a commercially available polymerase chain reaction test. No differences in any of the investigated parameters were observed at baseline between the two groups. At 3 months and 6 months after treatment, there were no statistically significant differences between the groups in terms of PPD, CAL and FMPS. At 3 months and 6 months, a statistically significantly higher improvement of BOP was found in the test group. At 3 months after therapy

  1. Phosphate Treatment Strongly Inhibits New Arbuscule Development But Not the Maintenance of Arbuscule in Mycorrhizal Rice Roots.

    PubMed

    Kobae, Yoshihiro; Ohmori, Yoshihiro; Saito, Chieko; Yano, Koji; Ohtomo, Ryo; Fujiwara, Toru

    2016-05-01

    Phosphorus (P) is a crucial nutrient for plant growth, but its availability to roots is limited in soil. Arbuscular mycorrhizal (AM) symbiosis is a promising strategy for improving plant P acquisition. However, P fertilizer reduces fungal colonization (P inhibition) and compromises mycorrhizal P uptake, warranting studies on the mechanistic basis of P inhibition. In this study, early morphological changes in P inhibition were identified in rice (Oryza sativa) using fungal cell wall staining and live-cell imaging of plant membranes that were associated with arbuscule life cycles. Arbuscule density decreased, and aberrant hyphal branching was observed in roots at 5 h after P treatment. Although new arbuscule development was severely inhibited, preformed arbuscules remained intact and longevity remained constant. P inhibition was accelerated in the rice pt11-1 mutant, which lacks P uptake from arbuscule branches, suggesting that mature arbuscules are stabilized by the symbiotic P transporter under high P condition. Moreover, P treatment led to increases in the number of vesicles, in which lipid droplets accumulated and then decreased within a few days. The development of new arbuscules resumed within by 2 d. Our data established that P strongly and temporarily inhibits new arbuscule development, but not intraradical accommodation of AM fungi. PMID:26979330

  2. Investigation of Repeat Client Drop-Out and Re-Enrolment Cycles in Fourteen Methadone Maintenance Treatment Clinics in Guangdong, China

    PubMed Central

    Zhang, Di; Li, Xiaoling; Zhao, Peizhen; Ling, Li

    2015-01-01

    Objective Client adherence is vital for effective methadone maintenance treatment (MMT). This study explores the pattern and associated factors of client adherence, drop-out and re-enrolment in the Chinese MMT programme over the period of 2006–2013. Methods This retrospective study was conducted in 14 MMT clinics in Guangdong Province, China. We employed Kaplan-Meier survival analysis to estimate the rates of drop-out and re-enrolment of MMT clients and multivariate Cox regression to identify associated factors. Results Among 1,512 study participants, 79% have experienced ‘drop-out’ during the 7-year study period. However, 82% ‘dropped-out’ clients resumed treatment at a later time. Low education level (junior high or below versus otherwise, HR = 1.21, 1.05–1.40), low methadone dosage in the first treatment episode (<50 ml versus ≥50 ml, HR = 1.84, 1.64–2.06) and higher proportion of positive urine test (≥50% versus<50%, HR = 3.72, 3.30–4.20) during the first treatment episode were strong predictors of subsequent drop-outs of the participants. Among the ‘dropped-out’ clients, being female (HR = 1.40, 1.23–1.60), being married (HR = 1.19, 1.09–1.30), and having a higher proportion of positive urine tests in the first treatment episode (≥50% versus<50%, HR = 1.35, 1.20–1.51) had greater likelihood of subsequent re-enrolment in MMT. Clients receiving lower methadone dosage (first treatment episode <50 ml versus ≥50 ml, HR = 1.12, 1.03–1.23; the last intake before drop-out <50 ml versus ≥50 ml, HR = 1.16, 1.04–1.30) were also more likely to re-enrol. Conclusion Persistent cycling in-and-out of clients in MMT programmes is common. Insufficient dosage and higher proportion of positive urine samples in the first treatment episode are the key determinants for subsequent client drop-out and re-enrolment. Interventions should target clients in their early stage of treatment to improve retention in the long term. PMID:26484772

  3. Sexual Abuse and its Relation to Chronic Pain among Women from a Methadone Maintenance Clinic versus a Sexual Abuse Treatment Center.

    PubMed

    Peles, Einat; Seligman, Zivya; Bloch, Miki; Potik, David; Sason, Anat; Schreiber, Shaul; Adelson, Miriam

    2016-01-01

    To determine the effect of sexual abuse history on chronic pain and its relation to opioid addiction and methadone maintenance treatment (MMT), we studied current women MMT patients, and women patients from a sexual abuse treatment center with no history of opioid addiction. Questionnaires included Chronic Pain, Chronic Severe Pain, the Yale-Brown Obsessive Compulsive Scale, the Dissociative Experiences Scale (DES), and the Structured Interview for Disorders of Extreme Stress (complex-PTSD). Chronic severe pain was most prevalent among sexually abused women with no history of opioid addiction (64% of 25), followed by sexually abused MMT women (30.9% of 68), and MMT women with no history of sexual abuse (25% of 8, p = 0.01). Pain severity correlated with dissociation and complex-PTSD scores. The sexually abused non-MMT women had higher rates of high dissociation scores (DES ≥ 30) and complex-PTSD, but fewer obsessive-compulsive disorder symptoms (scored ≥16) than the MMT sexually abused women. Chronic pain was found to be highly prevalent among sexually abused women, independent of being methadone-maintained with an addiction history. The high known prevalence of chronic pain among MMT patients, which may be attributable to opioid-induced hyperalgesia, may partially reflect the sexual abuse history, and should be targeted in future studies evaluating pain indices. PMID:27430532

  4. Sexual Abuse and its Relation to Chronic Pain among Women from a Methadone Maintenance Clinic versus a Sexual Abuse Treatment Center.

    PubMed

    Peles, Einat; Seligman, Zivya; Bloch, Miki; Potik, David; Sason, Anat; Schreiber, Shaul; Adelson, Miriam

    2016-01-01

    To determine the effect of sexual abuse history on chronic pain and its relation to opioid addiction and methadone maintenance treatment (MMT), we studied current women MMT patients, and women patients from a sexual abuse treatment center with no history of opioid addiction. Questionnaires included Chronic Pain, Chronic Severe Pain, the Yale-Brown Obsessive Compulsive Scale, the Dissociative Experiences Scale (DES), and the Structured Interview for Disorders of Extreme Stress (complex-PTSD). Chronic severe pain was most prevalent among sexually abused women with no history of opioid addiction (64% of 25), followed by sexually abused MMT women (30.9% of 68), and MMT women with no history of sexual abuse (25% of 8, p = 0.01). Pain severity correlated with dissociation and complex-PTSD scores. The sexually abused non-MMT women had higher rates of high dissociation scores (DES ≥ 30) and complex-PTSD, but fewer obsessive-compulsive disorder symptoms (scored ≥16) than the MMT sexually abused women. Chronic pain was found to be highly prevalent among sexually abused women, independent of being methadone-maintained with an addiction history. The high known prevalence of chronic pain among MMT patients, which may be attributable to opioid-induced hyperalgesia, may partially reflect the sexual abuse history, and should be targeted in future studies evaluating pain indices.

  5. Reduction of Fusarium rot and maintenance of fruit quality in melon using eco-friendly hot water treatment.

    PubMed

    Sui, Yuan; Droby, Samir; Zhang, Danfeng; Wang, Wenjie; Liu, Yongsheng

    2014-12-01

    Significant losses in harvested fruit can be directly attributable to decay fungi and quality deterioration. Hot water treatment (HWT) has been demonstrated to be an effective and economic environment-friendly approach for managing postharvest decay and maintaining fruit quality. In this study, the effects of HWT (45 °C for 10, 15, 20, and 25 min) on in vitro growth of Fusarium oxysporum, in vivo Fusarium rot, and natural decay of melon were investigated. HWT inhibited spore germination and germ tube elongation of F. oxysporum. Protein impairment and ATP consumption triggered by HWT contributed to the inhibitory effect. Results of in vivo studies showed that HWT effectively controlled Fusarium rot and natural decay of melon. Correspondingly, HWT induced a significant increase in content of total phenolic compounds and lignin of melon. These findings indicate that the effects of HWT on Fusarium rot may be associated with the direct fungal inhibition and the elicitation of defense responses in fruit. Importantly, HWT used in this study had beneficial effects on fruit quality as well. HWT may represent an effective non-chemical approach for management of postharvest Fusarium rot.

  6. Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study

    PubMed Central

    Marston, Louise; Walters, Kate; Geddes, John R.; King, Michael; Osborn, David P. J.

    2016-01-01

    Background There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine. Methods and Findings We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64–3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45–0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45–0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47–0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40–0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29–0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09–0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13–0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10–0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14–0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07

  7. Treatment of major depressive disorder and dysthymic disorder with antidepressants in patients with comorbid opiate use disorders enrolled in methadone maintenance therapy: a meta-analysis.

    PubMed

    Pedrelli, Paola; Iovieno, Nadia; Vitali, Mario; Tedeschini, Enrico; Bentley, Kate H; Papakostas, George I

    2011-10-01

    Depression and opiate-use disorders (abuse, dependence) often co-occur, each condition complicating the course and outcome of the other. It has been recommended that clinicians prescribe antidepressant therapy for mood symptoms in patients with active substance-use disorders, but whether antidepressants are effective in this specific population is not entirely clear. Therefore, the aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with comorbid opiate-use disorders currently in methadone maintenance treatment (MMT). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the treatment of MDD/DD in patients with comorbid opiate-use disorders currently in MMT. The search was limited to articles published between January 1, 1980, and June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in our analysis (n = 317 patients). We found no statistically significant difference in response rates between antidepressant and placebo therapy in trials of MDD/DD patients with comorbid opiate-use disorders currently in MMT (risk ratio for response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no difference in the depressive outcome of patients with comorbid opiate-use disorders on MMT whether they are on medication or placebo. Future studies examining the effectiveness of antidepressants while controlling for several variables such as psychosocial treatment and assessing the specific classes of antidepressants are needed.

  8. Clinical study of Shengxuening tablet combined with rHuEPO for the treatment of renal anemia of maintenance hemodialysis patients

    PubMed Central

    CHENG, XIN; YU, GUOJUN; HU, JIANGPING; XU, XUEFENG; LUO, FANG; SHEN, PING; ZHANG, GUOSHENG; YANG, NING

    2016-01-01

    The aim of the present study was to investigate the clinical effects of Shengxuening tablet (silkworm excrement) combined with recombinant human erythropoietin (rHuEPO) for the treatment of renal anemia of maintenance hemodialysis (MHD) patients. Seventy-two MHD patients with renal anemia were included in the study and randomly divided into the control (n=34) and observation (n=38) groups. Patients in the control group were treated by hypodermic injection of 100–150 U/(kg·w) rHuEPO and patients in the observation group were treated by rHuEPO + 1.0 g t.i.d. p.o. Shengxuening tablet. The two groups were assisted by conventional treatments including iron, folic acid, vitamin B12 and L-carnitine. After 3 and 6 months, improvement of anemia was compared. After 3 months, the hemoglobin, hematocrit, serum ferritin and transferrin saturation levels of the observation group were significantly higher than those of the control group (p<0.05). In addition, C-reactive protein and superoxide dismutase levels of the observation group were significantly lower than those of the control group (p<0.05). After 6 months, indices of the observation group were ameliorated while the improvement of control group was not obvious, and indices of the observation group were significantly higher than those of the control group (p<0.05). Consumption of rHuEPO in the observation group was significantly less than that of the control group, and the total effective rate was significantly higher than that of the control group (p<0.05). In conclusion, Shengxuening tablet combined with rHuEPO was safe and effective for the treatment of renal anemia of MHD patients. PMID:27347032

  9. Recommendations from the Spanish Oncology Genitourinary Group for the treatment of metastatic renal cancer.

    PubMed

    Bellmunt, Joaquim; Calvo, Emiliano; Castellano, Daniel; Climent, Miguel Angel; Esteban, Emilio; García del Muro, Xavier; González-Larriba, José Luis; Maroto, Pablo; Trigo, José Manuel

    2009-03-01

    For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.

  10. Methadone maintenance treatment program in prisons from the perspective of medical and non-medical prison staff: a qualitative study in Iran

    PubMed Central

    Moradi, Ghobad; Farnia, Marzieh; Shokoohi, Mostafa; Shahbazi, Mohammad; Moazen, Babak; Rahmani, Khaled

    2015-01-01

    Background: As one of the most important components of harm reduction strategy for high-risk groups, following the HIV epidemics, Methadone Maintenance Treatment (MMT) has been initiated in prisoners since 2003. In this paper, we aimed to assess the advantages and shortcomings of the MMT program from the perspective of people who were involved with the delivery of prison healthcare in Iran. Methods: On the basis of grounded theory and through conducting 14 Focus Group Discussions (FGDs), 7 FGDs among physicians, consultants, experts, and 7 FGDs among directors and managers of prisons (n= 140) have been performed. The respondents were asked about positive and negative elements of the MMT program in Iranian prisons. Results: This study included a total of 48 themes, of which 22 themes were related to advantages and the other 26 were about shortcomings of MMT programs in the prisons. According to participants’ views "reduction of illegal drug use and high-risk injection", "reduction of potentially high-risk behaviors" and "making positive attitudes" were the main advantages of MMT in prisons, while issues such as "inaccurate implementation", "lack of skilled manpower" and "poor care after release from prison" were among the main shortcomings of MMT program. Conclusions: MMT program in Iran’s prisons has achieved remarkable success in the field of harm reduction, but to obtain much more significant results, its shortcomings and weaknesses must be also taken into account by policy-makers. PMID:26340487

  11. Rapid determination of methadone and its major metabolite in biological fluids by gas-liquid chromatography with thermionic detection for maintenance treatment of opiate addicts.

    PubMed

    Chikhi-Chorfi, N; Pham-Huy, C; Galons, H; Manuel, N; Lowenstein, W; Warnet, J M; Claude, J R

    1998-11-01

    A rapid gas-liquid chromatographic assay is developed for the quantification of methadone (Mtd) and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in biological fluids of opiate addicts. After alkaline extraction from samples with lidocaine hydrochloride as internal standard, Mtd and EDDP are separated on SP-2250 column at 220 degrees C and detected with a thermionic detector. The chromatographic time is about 6 min. The relative standard deviations (R.S.D.) of Mtd and EDDP standards are between 1.5 and 5.5%. Most drugs of abuse (morphine, codeine, narcotine, cocaine, benzoylecgonine, cocaethylene, dextropropoxyphene etc) are shown not to interfere with this technique. The method has been applied to study the levels of Mtd and EDDP metabolite in serum, saliva and urine of patients under maintenance treatment for opiate dependence. EDDP levels were found higher than those of Mtd in urine samples from four treated patients, but lower in serum and undetectable in saliva. However, Mtd concentrations were higher in saliva than in serum.

  12. Effects of modified atmosphere packing and honey dip treatments on quality maintenance of minimally processed grape cv. Razaki (V. vinifera L.) during cold storage.

    PubMed

    Sabır, Ali; Sabır, Ferhan K; Kara, Zeki

    2011-06-01

    Increasing pressure in food conservation sector to replace chemical applications has urged researchers to focus on studying new strategies of extending the postharvest life of produces. In such efforts, numerous materials have been tested for their effectiveness as well as suitability in organic consumption. In this study, effects of modified atmosphere packing (MAP) and honey solution dip on maintenance of quality of minimally processed table grape cv. Razaki were investigated. During the storage at 0 °C with relative humidity of 90%, MAP, honey dip, and their combined applications significantly retarded the weight loss of berries that retained about 2 mm of cap stem. Soluble solid contents of all berries slightly increased, while their acid amounts decreased, resulting in consecutive rises of maturity index. With respect to the sensory score, calculated as mean of ten panelists, honey treatment alone was ranked the highest while control berries had significantly lower value. Overall, MAP, honey solution dip or their combination significantly maintained the general quality of minimally processed grape by delaying quality loss and berry decay. Therefore, honey solution dip yielded promising results to use as an edible organic coating barrier to moisture and resist to water vapor diffusion during the cold storage, offering a good adherence to berry surface. PMID:23572752

  13. Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial.

    PubMed

    Katzman, Martin A; Brawman-Mintzer, Olga; Reyes, Efren B; Olausson, Bengt; Liu, Sherry; Eriksson, Hans

    2011-01-01

    The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) following open-label run-in (4-8 weeks) and open-label stabilization (≥ 12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio=0.19 (95% confidence interval 0.12-0.31; P<0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P<0.001) and Q-LES-Q (P<0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine.

  14. Cross-sectional study of the severity of self-reported depressive symptoms in heroin users who participate in a methadone maintenance treatment program

    PubMed Central

    WU, Yafei; YAN, Shiyan; BAO, Yanping; LIAN, Zhi; QU, Zhi; LIU, Zhimin

    2016-01-01

    Background Methadone maintenance treatment (MMT) is widely recognized as an effective method of combatting narcotic addiction. MMT reduces heroin withdrawal symptoms and, thus, makes it possible to provide the psychological and social support that is essential to the rehabilitation of drug users. Aim Compare the severity of depressive symptoms in heroin users who are currently receiving MMT to that of heroin users who are not receiving MMT. Methods We administered the 13-item version of the Beck Depression Inventory (BDI-13) and a demographic history form to 929 heroin users who had been receiving MMT at nine methadone treatment clinics in three Chinese cities for an average of 9 months and to 238 heroin users who had enrolled in a MMT program at the centers but had not yet begun MMT. Results Seventy-nine percent (188/238) of the untreated individuals reported depressive symptoms compared to 68% (628/929) of the individuals receiving MMT (χ2=11.69, p<0.001). The median (interquartile range) BDI score in the untreated group was 10.4 (7.9-11.4) compared to 8.0 (5.7-11.6) in the MMT group (Z=2.75, p=0.006). In the MMT group, there was a negative correlation between the severity of reported depressive symptoms and the duration of participation in the MMT program (rs=-0.24, Z=2.88, p=0.004). Multivariate linear regression analysis showed that after adjusting for all demographic variables the treated group still had less severe depressive symptoms than the untreated group. After adjusting for the effect of MMT treatment, depressive symptoms were more severe in heroin users who self-reported poor family relationships (standardized regression coefficient β=0.118, t=6.56, p<0.001) and in those who were divorced (β=0.120, t=3.73, p<0.001). Conclusions Moderate to severe depressive symptoms are common in heroin users. MMT is associated with lower levels of depressive symptoms in heroin users, but prospective randomized controlled trials are needed to determine whether or

  15. Cross-sectional study of the severity of self-reported depressive symptoms in heroin users who participate in a methadone maintenance treatment program

    PubMed Central

    WU, Yafei; YAN, Shiyan; BAO, Yanping; LIAN, Zhi; QU, Zhi; LIU, Zhimin

    2016-01-01

    Background Methadone maintenance treatment (MMT) is widely recognized as an effective method of combatting narcotic addiction. MMT reduces heroin withdrawal symptoms and, thus, makes it possible to provide the psychological and social support that is essential to the rehabilitation of drug users. Aim Compare the severity of depressive symptoms in heroin users who are currently receiving MMT to that of heroin users who are not receiving MMT. Methods We administered the 13-item version of the Beck Depression Inventory (BDI-13) and a demographic history form to 929 heroin users who had been receiving MMT at nine methadone treatment clinics in three Chinese cities for an average of 9 months and to 238 heroin users who had enrolled in a MMT program at the centers but had not yet begun MMT. Results Seventy-nine percent (188/238) of the untreated individuals reported depressive symptoms compared to 68% (628/929) of the individuals receiving MMT (χ2=11.69, p<0.001). The median (interquartile range) BDI score in the untreated group was 10.4 (7.9-11.4) compared to 8.0 (5.7-11.6) in the MMT group (Z=2.75, p=0.006). In the MMT group, there was a negative correlation between the severity of reported depressive symptoms and the duration of participation in the MMT program (rs=-0.24, Z=2.88, p=0.004). Multivariate linear regression analysis showed that after adjusting for all demographic variables the treated group still had less severe depressive symptoms than the untreated group. After adjusting for the effect of MMT treatment, depressive symptoms were more severe in heroin users who self-reported poor family relationships (standardized regression coefficient β=0.118, t=6.56, p<0.001) and in those who were divorced (β=0.120, t=3.73, p<0.001). Conclusions Moderate to severe depressive symptoms are common in heroin users. MMT is associated with lower levels of depressive symptoms in heroin users, but prospective randomized controlled trials are needed to determine whether or

  16. Pharmacogenomics of methadone maintenance treatment.

    PubMed

    Somogyi, Andrew A; Barratt, Daniel T; Ali, Robert L; Coller, Janet K

    2014-05-01

    Methadone is the major opioid substitution therapy for opioid dependence. Dosage is highly variable and is often controlled by the patient and prescriber according to local and national policy and guidelines. Nevertheless many genetic factors have been investigated including those affecting its metabolism (CYP2B6-consistent results), efflux transport (P-gp-inconsistent results), target μ-opioid receptor (μ-opioid receptor-inconsistent results) and a host of other receptors (DRD2) and signaling elements (GIRK2 and ARRB2; not replicated). None by themselves have been able to substantially explain dosage variation (the major but not sole end point). When multiple genes have been combined such as ABCB1, CYP2B6, OPRM1 and DRD2 a greater contribution to dosage variation was found but not as yet replicated. As stabilization of dosage needs to be made rapidly, it is imperative that larger internationally based studies be instigated so that genetic contribution to dosage can be properly assessed, which may or may not tailor to different ethnic groups and each country's policy towards an outcome that benefits all.

  17. High Prevalence of HIV, HCV and Tuberculosis and Associated Risk Behaviours among New Entrants of Methadone Maintenance Treatment Clinics in Guangdong Province, China

    PubMed Central

    Chen, Wen; Zou, Xia; Ling, Li

    2013-01-01

    Background Methadone maintenance treatment (MMT) has been available in Guangdong province, China since 2006. This study aims to estimate the prevalence levels of HIV, Hepatitis C (HCV), Tuberculosis (TB) and their co-infections and associated demographic and risk behaviours among MMT entrants. Method A total of 2296 drug users at the time of their MMT enrolment were recruited from four clinics during 2006-2011. Participants’ demographic characteristics, infection status and self-reported high-risk drug-use and sexual behaviours were surveyed. Log-linear contingency analysis was employed to investigate the demographic and behavioural differences between gender and drug-user type, while multivariate regression analysis was used to identify the associated factors of HIV, HCV and TB infections. Results Female drug users demonstrate significantly higher frequency of daily drug consumption (Log-linear contingency analysis, G2=10.86, p=0.013) and higher proportion of having had sex in the past three months (G2=30.22, p<0.001) than their male counterparts. Among injecting drug users, females also inject (χ2=16.15, p=0.001) and share syringes (χ2=13.24, p=0.004) more frequently than males. Prevalence of HIV, HCV and TB among MMT entrants are 6.3%, 78.7% and 4.4% respectively. Co-infections of HIV/HCV, HIV/TB, HCV/TB and HIV/HCV/TB reportedly infect 5.6%, 0.5%, 3.8% and 0.3% of study participants. Infection risks of HIV, HCV and TB are consistently associated with increasing length of drug use, injecting drugs, financial dependence and reduced sexual activities. Conclusion Injecting drug use is the major contributing factor in prevalence levels of HIV, HCV and TB among MMT entrants. Female drug users are more disadvantaged in their social status and risk-taking in their drug use behaviours than males. PMID:24116185

  18. The Effect of Methadone-Maintenance Therapy With and Without Interactive Treatment on Improving Emotion-Regulation Strategies and Resilience Among Opiate-Dependent Clients

    PubMed Central

    Hoseiny, Hadis; Jadidi, Mohsen; Habiballah Nataj, Leila; Saberi- Zafarghandi, Mohammad Bagher

    2015-01-01

    Background: Due to the chronic and recurrent nature of addiction, many people who quit drug addiction may slip back into the pattern of using drugs shortly after the detoxification period. Emotion-regulation strategies and resilience play an important role in preventing the recurrences of substance abuse. Objectives: This study aimed to compare the effects of methadone-maintenance therapy (MMT) and interactive therapy (a combination of MMT and cognitive-behavioral therapy) on improving emotion-regulation strategies and resilience among opiate-dependent clients. Patients and Methods: This pretest-posttest quasi-experimental study was performed on 60 patients with substance abuse admitted to Methadone Addiction Treatment Centers and Detox Centers in Sari within three months of therapy for their addiction (from October to December 2013). Then, the participants were randomly assigned to two different groups (n = 30) were examined in two groups of 30 people targeted to be available in the selected population. Participants in all three groups, before and after the intervention, filled out the questionnaires of Schutte emotional intelligence scale and Connor-Davidson resiliency questionnaire. Data were analyzed using the analysis of covariance method. Results: The results showed that an interactive therapy would be significantly more effective than the MMT on improving emotion-regulation strategies and promoting the resilience level among opiate-dependent clients. Moreover, the results showed that cognitive- behavior therapy combined with MMT may improve emotion-regulation strategies, and promote the amount of resiliency and recovery. Conclusions: The cognitive-behavior therapy combined with MMT can improve emotion-regulation strategies and resiliency and thus prevent the substance-abuse relapse. PMID:25821751

  19. Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain.

    PubMed

    Banz, Kurt; Bischoff, Helge; Brunner, Matthias; Chouaid, Christos; de Castro Carpeño, Javier; de Marinis, Filippo; Grossi, Francesco; Vergnenègre, Alain; Walzer, Stefan

    2011-12-01

    Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain. Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed. Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates. Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile. PMID:21592611

  20. Cryogenics maintenance strategy

    NASA Astrophysics Data System (ADS)

    Cruzat, Fabiola

    2012-09-01

    ALMA is an interferometer composed of 66 independent systems, with specific maintenance requirements for each subsystem. To optimize the observation time and reduce downtime maintenance, requirements are very demanding. One subsystem with high maintenance efforts is cryogenics and vacuum. To organize the maintenance, the Cryogenic and Vacuum department is using and implementing different tools. These are monitoring and problem reporting systems and CMMS. This leads to different maintenance approaches: Preventive Maintenance, Corrective Maintenance and Condition Based Maintenance. In order to coordinate activities with other departments the preventive maintenance schedule is kept as flexible as systems allow. To cope with unavoidable failures, the team has to be prepared to work under any condition with the spares on time. Computerized maintenance management system (CMMS) will help to manage inventory control for reliable spare part handling, the correct record of work orders and traceability of maintenance activities. For an optimized approach the department is currently evaluating where preventive or condition based maintenance applies to comply with the individual system demand. Considering the change from maintenance contracts to in-house maintenance will help to minimize costs and increase availability of parts. Due to increased number of system and tasks the cryo team needs to grow. Training of all staff members is mandatory, in depth knowledge must be built up by doing complex maintenance activities in the Cryo group, use of advanced computerized metrology systems.

  1. Maintenance Research. Report 6. Maintenance Training.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Highways, Baton Rouge.

    The main objective of the training research phase of the maintenance management study was to develop and test training methods suitable for highway maintenance supervisors. Supervisors were trained by one of five different methods (lecture, group discussion, programed instruction, programed workshops, audiovisual instruction). The report documents…

  2. Methadone maintenance treatment programme reduces criminal activity and improves social well-being of drug users in China: a systematic review and meta-analysis

    PubMed Central

    Sun, Hua-Min; Li, Xiao-Yan; Chow, Eric P F; Li, Tong; Xian, Yun; Lu, Yi-Hua; Tian, Tian; Zhuang, Xun; Zhang, Lei

    2015-01-01

    Objective Methadone maintenance treatment (MMT) has been implemented in China since 2004 and has expanded into a nationwide programme. This study aims to evaluate changes in social functioning, family relations and drug-related criminal behaviour among MMT clients in China. Design Systematic review and meta-analysis. Methods Both English and Chinese literature databases, including PubMed, Chongqing VIP Chinese Science and Technology Journals Database (CQVIP), China National Knowledge Infrastructure (CNKI) and Wanfang Data, were comprehensively searched over the period 2004–2014 for studied indicators. Study selection, quality assessment and data extraction were conducted according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Statement. Meta-analyses were conducted using Comprehensive Meta-Analysis Biostat software. Results Thirty-eight articles were included in this review (1 in English and 37 in Chinese). The self-reported arrest rate decreased from 13.1% (95% CI 9.1% to 18.5%) at baseline to 3.4% (95% CI 1.5% to 7.7%) and 4.3% (95% CI 1.6% to 11.4%) after 6 and 12 months of MMT intervention, respectively. The rate of drug selling decreased from 7.6% (95% CI 3.8% to 14.8%) at baseline to 1.9% (95% CI 0.6% to 6.2%) and 3.0% (95% CI 1.0% to 8.9%) after 6 and 12 months of intervention, respectively. Similarly, the rates of selling sex for drugs and drug-related crime decreased from 5.3% (95% CI 2.4% to 11.1%) and 9.9% (95% CI 6.8% to 14.2%) at baseline to 1.1% (95% CI 0.5% to 2.3%) and 3.4% (95% CI 2.5% to 4.5%) at 6 months, then to 0.8% (95% CI 0.3% to 1.9%) and 3.4% (95% CI 0.8% to 13.1%) at 12 months after treatment initiation, respectively. In contrast, the rate of employment of clients and the proportion of clients having a good relationship with their family increased substantially from 26.4% (95% CI 22.9% to 30.1%) and 37.9% (95% CI 32.0% to 44.2%) to 41.6% (95% CI 36.6% to 48.0%) and 59.6% (95% CI 48.1% to 70

  3. The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China

    PubMed Central

    2014-01-01

    Background HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China. Methods Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users. Results A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran’s I was 0.3015, 0.3449, and 0.3155, respectively (P < 0.0001). Both the geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different. Conclusion HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent

  4. [Development of Hospital Equipment Maintenance Information System].

    PubMed

    Zhou, Zhixin

    2015-11-01

    Hospital equipment maintenance information system plays an important role in improving medical treatment quality and efficiency. By requirement analysis of hospital equipment maintenance, the system function diagram is drawed. According to analysis of input and output data, tables and reports in connection with equipment maintenance process, relationships between entity and attribute is found out, and E-R diagram is drawed and relational database table is established. Software development should meet actual process requirement of maintenance and have a friendly user interface and flexible operation. The software can analyze failure cause by statistical analysis.

  5. [Development of Hospital Equipment Maintenance Information System].

    PubMed

    Zhou, Zhixin

    2015-11-01

    Hospital equipment maintenance information system plays an important role in improving medical treatment quality and efficiency. By requirement analysis of hospital equipment maintenance, the system function diagram is drawed. According to analysis of input and output data, tables and reports in connection with equipment maintenance process, relationships between entity and attribute is found out, and E-R diagram is drawed and relational database table is established. Software development should meet actual process requirement of maintenance and have a friendly user interface and flexible operation. The software can analyze failure cause by statistical analysis. PMID:27066680

  6. Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder with or without Agoraphobia? A Randomized Controlled Clinical Trial

    ERIC Educational Resources Information Center

    White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

    2013-01-01

    Objective: We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method: Participants were all patients (N = 379) who…

  7. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    PubMed

    Heigener, David F; Pereira, José Rodrigues; Felip, Enriqueta; Mazal, Juraj; Manzyuk, Lyudmila; Tan, Eng Huat; Merimsky, Ofer; Sarholz, Barbara; Esser, Regina; Gatzemeier, Ulrich

    2015-06-01

    The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.

  8. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group.

    PubMed

    Pulczynski, Elisa J; Kuittinen, Outi; Erlanson, Martin; Hagberg, Hans; Fosså, Alexander; Eriksson, Mikael; Nordstrøm, Marie; Østenstad, Bjørn; Fluge, Øystein; Leppä, Sirpa; Fiirgaard, Bente; Bersvendsen, Hanne; Fagerli, Unn-Merete

    2015-04-01

    The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18-75 years were eligible. Thirty-nine patients aged 18-65 years and 27 patients aged 66-75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%-47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%-61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64-75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730). PMID:25480497

  9. A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Ammonium Lactate Lotion 12% and Halobetasol Propionate Ointment 0.05% in the Treatment and Maintenance of Psoriasis.

    PubMed

    Emer, Jason J; Frankel, Amylynne; Sohn, Andrew; Lebwohl, Mark

    2011-02-01

    Consensus recommends a gradual reduction in the frequency or steroid potency of topical corticosteroids following clinical improvement in the treatment of psoriasis, although no established guidelines have been developed. The authors sought to evaluate a combination regimen in the treatment and maintenance of psoriasis. Patients with mild-to-moderate psoriasis were enrolled (n=55) in a randomized, double-blind, placebo-controlled study using ammonium lactate lotion and halobetasol ointment. Those with initial improvement of target plaques after two weeks of combination treatment twice daily were randomized to a maintenance phase (n=41). Patients applied ammonium lactate lotion twice daily everyday and either placebo ointment (n=20) or steroid ointment (n=21) twice daily on weekends only. Forty-one of 55 patients (74.6%) were rated as "clear" (0) or "almost clear" (1) after two weeks of combination treatment. In the maintenance phase, the probability of physician global assessment worsening at six weeks in the steroid group was only 10 percent while in the placebo group the probability rose to 75 percent (p<0.0001). The probability of physician global assessment worsening climbed to 100 percent by 14 weeks in the placebo group while only increasing to 29 percent in the steroid group (p<0.0001). Twelve patients at study termination still had not worsened. Worsening of the physician global assessment index was more likely (HR 7.8 [2.84, 21.43]) in the placebo group than in the steroid group (p<0.0001). No cutaneous side effects, such as steroid atrophy or irritation, were noted. Combination treatment effectively cleared plaque psoriasis initially, and ammonium lactate twice daily everyday with weekend-only applications of halobetasol ointment effectively sustained the initial improvement for a significantly longer period of time when compared with placebo without demonstrating any significant side effects, such as steroid atrophy.

  10. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group.

    PubMed

    Pulczynski, Elisa J; Kuittinen, Outi; Erlanson, Martin; Hagberg, Hans; Fosså, Alexander; Eriksson, Mikael; Nordstrøm, Marie; Østenstad, Bjørn; Fluge, Øystein; Leppä, Sirpa; Fiirgaard, Bente; Bersvendsen, Hanne; Fagerli, Unn-Merete

    2015-04-01

    The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18-75 years were eligible. Thirty-nine patients aged 18-65 years and 27 patients aged 66-75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%-47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%-61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64-75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730).

  11. Facilities maintenance handbook

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This handbook is a guide for facilities maintenance managers. Its objective is to set minimum facilities maintenance standards. It also provides recommendations on how to meet the standards to ensure that NASA maintains its facilities in a manner that protects and preserves its investment in the facilities in a cost-effective manner while safely and efficiently performing its mission. This handbook implements NMI 8831.1, which states NASA facilities maintenance policy and assigns organizational responsibilities for the management of facilities maintenance activities on all properties under NASA jurisdiction. It is a reference for facilities maintenance managers, not a step-by-step procedural manual. Because of the differences in NASA Field Installation organizations, this handbook does not assume or recommend a typical facilities maintenance organization. Instead, it uses a systems approach to describe the functions that should be included in any facilities maintenance management system, regardless of its organizational structure. For documents referenced in the handbook, the most recent version of the documents is applicable. This handbook is divided into three parts: Part 1 specifies common definitions and facilities maintenance requirements and amplifies the policy requirements contained in NMI 8831. 1; Part 2 provides guidance on how to meet the requirements of Part 1, containing recommendations only; Part 3 contains general facilities maintenance information. One objective of this handbook is to fix commonality of facilities maintenance definitions among the Centers. This will permit the application of uniform measures of facilities conditions, of the relationship between current replacement value and maintenance resources required, and of the backlog of deferred facilities maintenance. The utilization of facilities maintenance system functions will allow the Centers to quantitatively define maintenance objectives in common terms, prepare work plans, and

  12. Defer Maintenance, Invite Disaster

    ERIC Educational Resources Information Center

    Bowman, William W.

    1977-01-01

    An AGB- and NACUBO-sponsored survey showed that "wish lists" are accumulating overdue major maintenance projects because energy costs are consuming physical plant budgets. Problem areas are discussed: budget "guesstimation," preventive maintenance, deferred maintenance inventory, the APPA accounting format, resource allocation, and inflation.…

  13. Light Vehicle Preventive Maintenance.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This correspondence course, originally developed for the Marine Corps, is designed to instruct students in the performance of preventive maintenance on motor vehicles. Instructional materials are presented in three chapters as follows: (1) Major Maintenance Areas (maintenance system, tires, batteries, cooling systems, and vehicle lubrication; (2)…

  14. Asphalt in Pavement Maintenance.

    ERIC Educational Resources Information Center

    Asphalt Inst., College Park, MD.

    Maintenance methods that can be used equally well in all regions of the country have been developed for the use of asphalt in pavement maintenance. Specific information covering methods, equipment and terminology that applies to the use of asphalt in the maintenance of all types of pavement structures, including shoulders, is provided. In many…

  15. Assessment and Treatment of Deviant Behavior in Children - Section Four: Evaluation of Three Experimental and One Control Strategy in Facilitating Generalization and Maintenance of Treatment Effects Following Two Months of Treatment in a Token Economy. Final Report.

    ERIC Educational Resources Information Center

    Walker, Hill M.; Buckley, Nancy K.

    The document is section four of a six part report on the assessment and treatment of deviant behavior in children. The effects of three experimental strategy were investigated to facilitate generalization of treatment effects following 2 months in a token economy classroom. Forty four subjects were assigned to one of three experimental strategies,…

  16. Innovation for maintenance technology improvements

    NASA Technical Reports Server (NTRS)

    Shives, T. R. (Editor); Willard, W. A. (Editor)

    1982-01-01

    A group of 34 submitted entries (32 papers and 2 abstracts) from the 33rd meeting of the Mechanical Failures Prevention Group whose subject was maintenance technology improvement through innovation. Areas of special emphasis included maintenance concepts, maintenance analysis systems, improved maintenance processes, innovative maintenance diagnostics and maintenance indicators, and technology improvements for power plant applications.

  17. Status of fusion maintenance

    SciTech Connect

    Fuller, G.M.

    1984-01-01

    Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission.

  18. Hepatitis E virus infection: Epidemiology and treatment implications

    PubMed Central

    Lee, Ga Young; Poovorawan, Kittiyod; Intharasongkroh, Duangnapa; Sa-nguanmoo, Pattaratida; Vongpunsawad, Sompong; Chirathaworn, Chintana; Poovorawan, Yong

    2015-01-01

    Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable. PMID:26568916

  19. Industrial Maintenance Strategies

    SciTech Connect

    Sajjad Akbar

    2006-07-01

    Industrial plants have become more complex due to technological advancement. This has made the task of maintenance more difficult. The maintenance costs in terms of resources and downtime loss are so high that maintenance function has become a critical factor in a plant's profitability. Industry should devote as much forethought to the management of maintenance function as to production. Maintenance has grown from an art to a precise, technical engineering science. Planning, organizing scheduling and control of maintenance using modern techniques pays dividends in the form of reduced costs and increased reliability. The magnitude and the dimension of maintenance have multiplied due to development in the engineering technologies. Production cost and capacities are directly affected by the breakdown time. Total operating cost including the maintenance cost plays an important role in replacement dimension. The integrated system approach would bring forth the desired results of high maintenance standards. The standards once achieved and sustained, would add to the reliability of the plan and relieve heavy stresses and strains on the engineering logistic support. (author)

  20. [Medical Equipment Maintenance Methods].

    PubMed

    Liu, Hongbin

    2015-09-01

    Due to the high technology and the complexity of medical equipment, as well as to the safety and effectiveness, it determines the high requirements of the medical equipment maintenance work. This paper introduces some basic methods of medical instrument maintenance, including fault tree analysis, node method and exclusive method which are the three important methods in the medical equipment maintenance, through using these three methods for the instruments that have circuit drawings, hardware breakdown maintenance can be done easily. And this paper introduces the processing methods of some special fault conditions, in order to reduce little detours in meeting the same problems. Learning is very important for stuff just engaged in this area.

  1. Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/TRICARE: Refills of Maintenance Medications Through Military Treatment Facility Pharmacies or National Mail Order Pharmacy Program. Interim final rule.

    PubMed

    2015-08-01

    This interim final rule implements Section 702 (c) of the Carl Levin and Howard P. "Buck" McKeon National Defense Authorization Act for Fiscal Year 2015 which states that beginning October 1, 2015, the pharmacy benefits program shall require eligible covered beneficiaries generally to refill non-generic prescription maintenance medications through military treatment facility pharmacies or the national mail-order pharmacy program. Section 702(c) of the National Defense Authorization Act for Fiscal Year 2015 also terminates the TRICARE For Life Pilot Program on September 30, 2015. The TRICARE For Life Pilot Program described in Section 716 (f) of the National Defense Authorization Act for Fiscal Year 2013, was a pilot program which began in March 2014 requiring TRICARE For Life beneficiaries to refill non-generic prescription maintenance medications through military treatment facility pharmacies or the national mail-order pharmacy program. TRICARE for Life beneficiaries are those enrolled in the Medicare wraparound coverage option of the TRICARE program. This interim rule includes procedures to assist beneficiaries in transferring covered prescriptions to the mail order pharmacy program. This regulation is being issued as an interim final rule in order to comply with the express statutory intent that the program begin October 1, 2015. Public comments, however, are invited and will be considered for possible revisions to this rule for the second year of the program. PMID:26248388

  2. Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/TRICARE: Refills of Maintenance Medications Through Military Treatment Facility Pharmacies or National Mail Order Pharmacy Program. Interim final rule.

    PubMed

    2015-08-01

    This interim final rule implements Section 702 (c) of the Carl Levin and Howard P. "Buck" McKeon National Defense Authorization Act for Fiscal Year 2015 which states that beginning October 1, 2015, the pharmacy benefits program shall require eligible covered beneficiaries generally to refill non-generic prescription maintenance medications through military treatment facility pharmacies or the national mail-order pharmacy program. Section 702(c) of the National Defense Authorization Act for Fiscal Year 2015 also terminates the TRICARE For Life Pilot Program on September 30, 2015. The TRICARE For Life Pilot Program described in Section 716 (f) of the National Defense Authorization Act for Fiscal Year 2013, was a pilot program which began in March 2014 requiring TRICARE For Life beneficiaries to refill non-generic prescription maintenance medications through military treatment facility pharmacies or the national mail-order pharmacy program. TRICARE for Life beneficiaries are those enrolled in the Medicare wraparound coverage option of the TRICARE program. This interim rule includes procedures to assist beneficiaries in transferring covered prescriptions to the mail order pharmacy program. This regulation is being issued as an interim final rule in order to comply with the express statutory intent that the program begin October 1, 2015. Public comments, however, are invited and will be considered for possible revisions to this rule for the second year of the program.

  3. Halt Runaway Maintenance Costs.

    ERIC Educational Resources Information Center

    Trotter, Andrew

    1988-01-01

    To keep expensive computer software and hardware functioning requires good housekeeping, some protective equipment, ground rules, and supervision. Schools can arrange microcomputer maintenance through service agreements with computer manufacturers, pay-as-you-go service from local computer stores, or setting up their own maintenance and repair…

  4. Progressive Planned Maintenance.

    ERIC Educational Resources Information Center

    Lewis, Mary Jo; Jacobs, Richard S.

    A planned maintenance system, which was implemented at Washington State University (WSU), uniquely integrates functions of equipment inventory, scheduling, time reporting, project management, materials inventory, and billing. Management now has immediate access to equipment data, maintenance status, and costs. Staff requirements are readily…

  5. Fixing Maintenance Productivity.

    ERIC Educational Resources Information Center

    Fickes, Michael

    2003-01-01

    Describes how one university's facility managers use Nextel communications technology in conjunction with a Famis Software maintenance management system to improve the productivity of its maintenance technicians. The system uses a wireless Internet connection to automate the flow of work order information to and from technicians. The key to these…

  6. Maintenance Trades Guidelines

    ERIC Educational Resources Information Center

    Weidner, Theodore J.

    2008-01-01

    In 2002, APPA published "Maintenance Staffing Guidelines for Educational Facilities," the first building maintenance trades staffing guideline designed to assist educational facilities professionals with their staffing needs. addresses how facilities professionals can determine the appropriate size and mix of their organization. Contents include…

  7. Maximizing Hard Floor Maintenance.

    ERIC Educational Resources Information Center

    Steger, Michael

    2000-01-01

    Explains the maintenance options available for hardwood flooring that can help ensure long life cycles and provide inviting spaces. Developing a maintenance system, knowing the type of traffic that the floor must endure, using entrance matting, and adhering to manufacturers guidelines are discussed. Daily, monthly or quarterly, and long-term…

  8. The demedicalization of methadone maintenance.

    PubMed

    Rosenbaum, M

    1995-01-01

    The institution of methadone maintenance as a treatment modality for heroin addiction in the mid-1960s was part of the growing medicalization of social problems in the United States. The definition of deviance as "sickness" rather than "badness" set the stage for America's first harm-reduction strategy. By the 1970s methadone maintenance was seen as a way to reduce drug-related crime, and federally funded programs proliferated. Accompanying methadone's phenomenal expansion was increased regulation, bureaucratization, and criticism. The early 1980s brought the Reagan era, fiscal austerity, the new "just say no" abstinence morality, and demedicalization of methadone maintenance. By the time needle-sharing was recognized as a major contributing factor in the spread of HIV, methadone had been transformed into a largely fee-for-service, short-term, begrudgingly tolerated treatment modality. Ironically, while other countries were able to use methadone to curb the spread of AIDS, the United States refused to facilitate its expansion, and in fact impeded it. To the frustration of proponents and consumers, this original harm-reduction tool, with the potential to impact the epidemic, was demedicalized and remains marginalized. PMID:7562261

  9. Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review.

    PubMed

    Räßler, F; Lukács, J; Elsner, P

    2016-09-01

    Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well-designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions. PMID:27357601

  10. Maintenance Process Strategic Analysis

    NASA Astrophysics Data System (ADS)

    Jasiulewicz-Kaczmarek, M.; Stachowiak, A.

    2016-08-01

    The performance and competitiveness of manufacturing companies is dependent on the availability, reliability and productivity of their production facilities. Low productivity, downtime, and poor machine performance is often linked to inadequate plant maintenance, which in turn can lead to reduced production levels, increasing costs, lost market opportunities, and lower profits. These pressures have given firms worldwide the motivation to explore and embrace proactive maintenance strategies over the traditional reactive firefighting methods. The traditional view of maintenance has shifted into one of an overall view that encompasses Overall Equipment Efficiency, Stakeholders Management and Life Cycle assessment. From practical point of view it requires changes in approach to maintenance represented by managers and changes in actions performed within maintenance area. Managers have to understand that maintenance is not only about repairs and conservations of machines and devices, but also actions striving for more efficient resources management and care for safety and health of employees. The purpose of the work is to present strategic analysis based on SWOT analysis to identify the opportunities and strengths of maintenance process, to benefit from them as much as possible, as well as to identify weaknesses and threats, so that they could be eliminated or minimized.

  11. Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

    SciTech Connect

    Gerber, Nicolas U.; Hoff, Katja von; Resch, Anika; Ottensmeier, Holger; Kwiecien, Robert; Faldum, Andreas; Matuschek, Christiane; Hornung, Dagmar; Bremer, Michael; Benesch, Martin; Pietsch, Torsten; Warmuth-Metz, Monika; Kuehl, Joachim; Rutkowski, Stefan; Kortmann, Rolf D.

    2014-07-15

    Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

  12. Four-Year Maintenance Treatment With Adalimumab in Patients with Moderately to Severely Active Ulcerative Colitis: Data from ULTRA 1, 2, and 3

    PubMed Central

    Colombel, Jean-Frederic; Sandborn, William J; Ghosh, Subrata; Wolf, Douglas C; Panaccione, Remo; Feagan, Brian; Reinisch, Walter; Robinson, Anne M; Lazar, Andreas; Kron, Martina; Huang, Bidan; Skup, Martha; Thakkar, Roopal B

    2014-01-01

    OBJECTIVES: The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis (UC) has been reported up to week 52 from the placebo-controlled trials ULTRA (Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab) 1 and 2. Up to 4 years of data for adalimumab-treated patients from ULTRA 1, 2, and the open-label extension ULTRA 3 are presented. METHODS: Remission per partial Mayo score, remission per Inflammatory Bowel Disease Questionnaire (IBDQ) score, and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208. Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline. Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing, respectively. As observed, last observation carried forward (LOCF) and nonresponder imputation (NRI) were used to report efficacy. Adverse events were reported for any adalimumab-treated patient. RESULTS: A total of 600/1,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies. Of these, 199 patients remained on adalimumab after 4 years of follow-up. Rates of remission per partial Mayo score, remission per IBDQ score, mucosal healing, and corticosteroid discontinuation at week 208 were 24.7%, 26.3%, 27.7% (NRI), and 59.2% (observed), respectively. Of the patients who were followed up in ULTRA 3 (588/1,094), a total of 360 patients remained on adalimumab 3 years later. Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6% and 59.9% of patients, respectively (NRI). Adverse event rates were stable over time. CONCLUSIONS: Remission, mucosal healing, and improved quality of life were maintained in patients with moderately to

  13. Maintenance information: value added?

    SciTech Connect

    Tomlingson, P.D.

    2005-11-01

    A study of how well the mining industry uses information management systems for maintenance suggests there's plenty of room for improvement. The article presents results of a study of 13 mining and mineral processing operations over a four year period combined with a questionnaire completed by 91 attendees at seminars. None of the organizations had a well-defined, documented maintenance program and consequently were not able to use information effectively. Packaged information system providers did not recognise that industrial maintenance organizations had different information needs.

  14. Automating Preventive Maintenance.

    ERIC Educational Resources Information Center

    Oshier, Michael J.

    1984-01-01

    Describes the following aspects of the State University of New York-Brockport's preventive maintenance computerization project: (1) software selection, (2) project implementation; and (3) problems and benefits of the system. (MCG)

  15. Timpani Repair and Maintenance.

    ERIC Educational Resources Information Center

    Combs, F. Michael

    1980-01-01

    Rather than focusing on specific brands of timpani, these guidelines for repair cover mechanical problems of a general nature: pedals, dents, unclear tone, and squeaking. Preventive maintenance is discussed. (Author/SJL)

  16. Automated preventive maintenance program

    NASA Technical Reports Server (NTRS)

    Cea, E. J.; Grieger, T. H.

    1971-01-01

    Maintenance program which is concise and inexpensive to operate adapts to almost any system that has a FORTRAN compiler. Program operates on a stored data base with an output consisting of scheduling information and various management reports.

  17. Carpet Maintenance Guide.

    ERIC Educational Resources Information Center

    Griffin, William R.

    1999-01-01

    Discusses ways to make carpet maintenance in schools easier and effective for keeping carpeted areas in schools attractive and long lasting. Covers cleaning tips for basic spills, ideas for staying on top of stains, and suggestions for eliminating odors. (GR)

  18. [Medical Equipment Maintenance Methods].

    PubMed

    Liu, Hongbin

    2015-09-01

    Due to the high technology and the complexity of medical equipment, as well as to the safety and effectiveness, it determines the high requirements of the medical equipment maintenance work. This paper introduces some basic methods of medical instrument maintenance, including fault tree analysis, node method and exclusive method which are the three important methods in the medical equipment maintenance, through using these three methods for the instruments that have circuit drawings, hardware breakdown maintenance can be done easily. And this paper introduces the processing methods of some special fault conditions, in order to reduce little detours in meeting the same problems. Learning is very important for stuff just engaged in this area. PMID:26904890

  19. Getting into Motorcycle Maintenance

    ERIC Educational Resources Information Center

    Mosher, Lynn

    1978-01-01

    This article tells how to start a high school course in motorcycle maintenance and includes names and addresses of some motorcycle manufacturers and a list of needed tools, equipment, and materials. (MF)

  20. Computerized Fleet Maintenance.

    ERIC Educational Resources Information Center

    Cataldo, John J.

    1985-01-01

    The Computerized Fleet Maintenance (CFM) program of a New York school district has major component areas of garage operation, vehicle replacement, and fuel consumption. CFM detects high expenditures and provides the rationale for bus replacement. (MLF)

  1. Care and Maintenance.

    ERIC Educational Resources Information Center

    Hampton, Carolyn H.; Hampton, Carol D.

    1979-01-01

    The classroom care and maintenance of terrestrial isopods is described. Includes illustrations of isopod external anatomy, a potato trap for collecting isopods, and a constructed habitat for raising isopods. (MA)

  2. Woodwind Instrument Maintenance.

    ERIC Educational Resources Information Center

    Sperl, Gary

    1980-01-01

    The author presents a simple maintenance program for woodwind instruments which includes the care of tendon corks, the need for oiling keys, and methods of preventing cracks in woodwind instruments. (KC)

  3. Remote Maintenance Monitoring

    NASA Technical Reports Server (NTRS)

    Owens, Richard C.; Simkins, Lorenz; Rochette, Donn

    1990-01-01

    Automated system gives new life to aging network of computers. Remote maintenance monitoring system developed to diagnose problems in large distributed computer network. Consists of data links, displays, controls, software, and more than 200 computers. Uses sensors to collect data on failures and expert system to examine data, diagnose causes of failures, and recommend cures. Designed to be retrofitted into launch processing system at Kennedy Space Center. Reduces downtime, lowers workload and expense of maintenance, and makes network less dependent on human expertise.

  4. Maintenance of remission following 2 years of standard treatment then dose reduction with abatacept in patients with early rheumatoid arthritis and poor prognosis

    PubMed Central

    Westhovens, Rene; Robles, Manuel; Ximenes, Antonio Carlos; Wollenhaupt, Jurgen; Durez, Patrick; Gomez-Reino, Juan; Grassi, Walter; Haraoui, Boulos; Shergy, William; Park, Sung-Hwan; Genant, Harry; Peterfy, Charles; Becker, Jean-Claude; Murthy, Bindu

    2015-01-01

    Objectives To evaluate maintenance of response while reducing intravenous abatacept dose from ∼10 mg/kg to ∼5 mg/kg in patients with early rheumatoid arthritis (RA) who achieved disease activity score (DAS)28 (erythrocyte sedimentation rate, ESR) <2.6. Methods This 1-year, multinational, randomised, double-blind substudy evaluated the efficacy and safety of ∼10 mg/kg and ∼5 mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS28 (ESR) <2.6 at year 2 of the AGREE study. The primary outcome was time to disease relapse (defined as additional disease-modifying antirheumatic drugs, ≥2 courses high-dose steroids, return to open-label abatacept ∼10 mg/kg, or DAS28 (C reactive protein) ≥3.2 at two consecutive visits). Results 108 patients were randomised (∼10 mg/kg, n=58; ∼5 mg/kg, n=50). Three and five patients, respectively, discontinued, and four per group returned to open-label abatacept. Relapse over time and the proportion of patients relapsing were similar in both groups (31% (∼10 mg/kg) vs 34% (∼5 mg/kg); HR: 0.87 (95% CI 0.45 to 1.69)). Mean steady-state trough serum concentration for the ∼10 mg/kg group was 20.3–24.1 µg/mL, compared with 8.8–12.0 µg/mL for the ∼5 mg/kg group. Conclusions This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS28 (ESR) <2.6 after ≥1 year on abatacept (∼10 mg/kg). Trial registration number NCT00989235. PMID:25550337

  5. Low maintenance hydrocarbon soil & groundwater

    SciTech Connect

    Seabolt, L.K. Jr.; Ryckman, M.D.

    1995-12-31

    This paper illustrates practical methods to control remedial system life cycle costs for pump and treat and biovent systems through the use of low maintenance treatment systems. Cost control factors will be illustrated through the presentation of three case histories: a groundwater free product recovery system at an Air Force P.O.L. (Petroleum, Oil, and Lubricant) storage area, a free product recovery and bioventing system at a beverage fleet distribution facility, and a free product recovery and ventilation system at a publication facility.

  6. Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004–2009

    PubMed Central

    Haroldsen, Candace; Carter, Marjorie E.; LaFleur, Joanne

    2015-01-01

    We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV) infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA) facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001). For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness. PMID:26167690

  7. Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009.

    PubMed

    Gundlapalli, Adi V; Nelson, Richard E; Haroldsen, Candace; Carter, Marjorie E; LaFleur, Joanne

    2015-01-01

    We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV) infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA) facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001). For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness. PMID:26167690

  8. Sustained treatment effect in attention-deficit/hyperactivity disorder: focus on long-term placebo-controlled randomized maintenance withdrawal and open-label studies

    PubMed Central

    Goodman, David W

    2013-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists throughout life. Approximately two-thirds of patients with a childhood diagnosis of ADHD continue to experience clinically significant symptoms into adulthood. Nevertheless, most of these individuals consider themselves “well,” and a vast majority discontinue medication treatment during adolescence. As evidence concerning the adult presentation of ADHD becomes more widely accepted, increasing numbers of physicians and patients will face decisions about the benefits and risks of continuing ADHD treatment. The risks associated with psychostimulant pharmacotherapy, including abuse, dependence, and cardiovascular events, are well understood. Multiple clinical trials demonstrate the efficacy of psychostimulants in controlling ADHD symptoms in the short term. Recent investigations using randomized withdrawal designs now provide evidence of a clinically significant benefit with continued long-term ADHD pharmacotherapy and provide insight into the negative consequences associated with discontinuation. Because many patients lack insight regarding their ADHD symptoms and impairments, they may place a low value on maintaining treatment. Nevertheless, for patients who choose to discontinue treatment, physicians can remain a source of support and schedule follow-up appointments to reassess patient status. Medication discontinuation can be used as an opportunity to help patients recognize their most impairing symptoms, learn and implement behavioral strategies to cope with ADHD symptoms, and understand when additional supportive resources and the resumption of medication management may be necessary. PMID:23576871

  9. The Maintenance Effect of Cognitive-Behavioural Treatment Groups for the Chinese Parents of Children with Intellectual Disabilities in Melbourne, Australia: A 6-Month Follow-Up Study

    ERIC Educational Resources Information Center

    Wong, D. F. K.; Poon, A.; Kwok, Y. C. Lai

    2011-01-01

    Background: Caring for a child with intellectual disability can be stressful. No data on the longer-term effects of cognitive-behavioural treatment (CBT) on parents from a Chinese-speaking background who have children with intellectual disabilities are available in the literature. This study attempted to fill this research gap by examining the…

  10. Sex-Related Differences in Self-Reported Neurocognitive Impairment among High-Risk Cocaine Users in Methadone Maintenance Treatment Program

    PubMed Central

    Shrestha, Roman; Huedo-Medina, Tania B; Copenhaver, Michael M

    2015-01-01

    BACKGROUND Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. METHODS The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients’ awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. RESULTS Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. CONCLUSIONS These findings suggest that cocaine users enter into treatment with a range of NCI – with women having significantly more neurocognitive deficits than men – that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients. PMID:25861219

  11. Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema.

    PubMed

    Matera, Maria Gabriella; Sanduzzi, Alessandro; Alfano, Roberto; Cazzola, Mario

    2016-06-01

    Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma). PMID:26998725

  12. Rituximab: Recommendations of the French Vasculitis Study Group (FVSG) for induction and maintenance treatments of adult, antineutrophil cytoplasm antibody-associated necrotizing vasculitides.

    PubMed

    Charles, Pierre; Bienvenu, Boris; Bonnotte, Bernard; Gobert, Pierre; Godmer, Pascal; Hachulla, Éric; Hamidou, Mohamed; Harlé, Jean-Robert; Karras, Alexandre; Lega, Jean-Christophe; Le Quellec, Alain; Mahr, Alfred D; Mouthon, Luc; Papo, Thomas; Puéchal, Xavier; Pugnet, Gregory; Samson, Maxime; Sibilia, Jean; Terrier, Benjamin; Vandergheynst, Frederick; Guillevin, Loïc

    2013-10-01

    Increasing rituximab prescription for ANCA-associated necrotizing vasculitides justifies the publication of recommendations for clinicians. Rituximab is approved in the United States to induce and maintain remission. In Europe, rituximab was recently approved for remission induction. However, governmental agencies' approvals cannot replace clinical practice guidelines. Herein, the French Vasculitis Study Group Recommendations Committee, comprised of physicians with extensive experience in the treatment of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

  13. Building Maintenance, Management, and Budgeting.

    ERIC Educational Resources Information Center

    Pawsey, M. R.

    1982-01-01

    Australian methods and formulas for funding building maintenance and management are outlined and found to be haphazard. Discussed are: ultimate costs of deferred maintenance, major plant replacements, life cycle costing, types of maintenance programs (including full preventive maintenance), use of computer programs for planning, and organization…

  14. Reliability Centered Maintenance - Methodologies

    NASA Technical Reports Server (NTRS)

    Kammerer, Catherine C.

    2009-01-01

    Journal article about Reliability Centered Maintenance (RCM) methodologies used by United Space Alliance, LLC (USA) in support of the Space Shuttle Program at Kennedy Space Center. The USA Reliability Centered Maintenance program differs from traditional RCM programs because various methodologies are utilized to take advantage of their respective strengths for each application. Based on operational experience, USA has customized the traditional RCM methodology into a streamlined lean logic path and has implemented the use of statistical tools to drive the process. USA RCM has integrated many of the L6S tools into both RCM methodologies. The tools utilized in the Measure, Analyze, and Improve phases of a Lean Six Sigma project lend themselves to application in the RCM process. All USA RCM methodologies meet the requirements defined in SAE JA 1011, Evaluation Criteria for Reliability-Centered Maintenance (RCM) Processes. The proposed article explores these methodologies.

  15. Maintenance simulation: Software issues

    SciTech Connect

    Luk, C.H.; Jette, M.A.

    1995-07-01

    The maintenance of a distributed software system in a production environment involves: (1) maintaining software integrity, (2) maintaining and database integrity, (3) adding new features, and (4) adding new systems. These issues will be discussed in general: what they are and how they are handled. This paper will present our experience with a distributed resource management system that accounts for resources consumed, in real-time, on a network of heterogenous computers. The simulated environments to maintain this system will be presented relate to the four maintenance areas.

  16. The Effect of Combination Antiviral Therapy in the Treatment of Hepatitis C on the Occurrence of Depressive Disorder in Patients Treated for Hepatitis C in the Republic of Srpska

    PubMed Central

    Banjac, Visnja; Zivlak-Radulovic, Nera; Miskovic, Mirjana

    2016-01-01

    Background: The current standard treatment of chronic hepatitis C in Bosnia and Herzegovina consists of pegylated interferon alpha in combination with ribavirin. Interferon therapy has many psychiatric side effects, with depressive symptomatology being most prominent. The aim of the study was to establish the frequency and severity of depression in patients with chronic hepatitis C during two months of the aforementioned therapy. Subjects and Methods: The overall sample consisted of 46 subjects, divided into three subgroups, aged 18 to 65. The study population consisted of subjects treated for chronic hepatitis C (n = 15), subjects infected but not treated for chronic hepatitis C (n = 15), and healthy controls (n = 16). The assessment and level of depression were based on the Structural clinical interview (SCID), Montgomery-Asberg Depression Rating Scale and Zung Self-Rating Depression Scale. The assessments were conducted before interferon therapy (on the day 0), after 4 and 8 weeks of therapy. Results: Regarding its frequency, MADRS scoring showed that the number of depressed subjects receiving therapy increased after 8 weeks (46.7%). There was statistical significance between the subgroups after 4 and 8 weeks. Likewise, the ZUNG scale showed that the number of depressed subjects receiving therapy increased after 8 weeks (73.3%). There was statistical significance between the subgroups on the day 0, after 4 and 8 weeks. Conclusions: Depression was significantly more frequent in chronic hepatitis C subjects treated with interferon alpha in combination with ribavirin than in subjects in the group without therapy. Mild depression was most prevalent. PMID:27147788

  17. Psychiatric treatment considerations with direct acting antivirals in hepatitis C

    PubMed Central

    2013-01-01

    Background Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications. Methods We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies. Results Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized. Conclusions Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy. PMID:23672254

  18. Erdheim–Chester disease: from palliative care to targeted treatment

    PubMed Central

    Graziani, Giorgio; Podestà, Manuel A.; Cucchiari, David; Reggiani, Francesco; Ponticelli, Claudio

    2014-01-01

    Erdheim–Chester disease (ECD) is a life-threatening multi-systemic non-Langerhans histiocytosis with cardiovascular complications as the leading cause of death. ECD affects the kidneys in up to 30% of cases, with fibrotic tissue deposition in the perirenal fat and renal hilum. Diagnosis is usually based on histological analysis of the pathologic tissue, which typically shows xanthogranulomatous infiltrates of foamy CD68+/CD1a- histiocytes surrounded by fibrosis. A consistent percentage of patients affected by ECD develop renal failure and hypertension as a consequence of renal artery stenosis and hydronephrosis. These conditions have been generally treated with the placement of stents and nephrostomies that frequently led to disappointing outcomes. Before the introduction of interferon-alpha (IFNα) treatment, the mortality rate was as high as 57% in the long term. Recent studies have granted new insights into the pathogenesis of ECD, which seems to bear a dual component of clonal and inflammatory disease. These advances led to use specific therapies targeting either the oncogenes (BRAFV600E) or the effectors of the immune response implicated in ECD (IL-1, TNFα). Drugs such as anakinra (recombinant human IL-1 receptor antagonist), infliximab (monoclonal antibody against TNFα) and vemurafenib (inhibitor of mutant BRAF) showed promising results in small single-centre series. Although larger trials will be needed to address the impact of these drugs on ECD prognosis and to select the most effective treatment, targeted therapies hold the premises to drastically change the outcome of this condition. PMID:25852907

  19. Community Maintenance Programs for Sexual Offenders

    ERIC Educational Resources Information Center

    Youssef, Carollyne

    2013-01-01

    While optimism regarding the treatment of sexual offenders has increased over the past couple of decades, research into the factors that assist offenders in maintaining therapeutic changes remains in the dark. Maintenance programs for offenders, while theoretically appearing to have a solid place in offender rehabilitation, surprisingly have not…

  20. ICD Complex Operations and Maintenance Plan

    SciTech Connect

    Gibson, P. L.

    2007-06-25

    This Operations and Maintenance (O&M) Plan describes how the Idaho National Laboratory (INL) conducts operations, winterization, and startup of the Idaho CERCLA Disposal Facility (ICDF) Complex. The ICDF Complex is the centralized INL facility responsible for the receipt, storage, treatment (as necessary), and disposal of INL Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) remediation waste.

  1. Stabilization Pond Operation and Maintenance Manual.

    ERIC Educational Resources Information Center

    Sexauer, Willard N.; Karn, Roger V.

    This manual provides the waste stabilization pond operator with the basics necessary for the treatment of wastewater in stabilization ponds. The material is organized as a comprehensive guide that follows the normal operation and maintenance procedures from the time the wastewater enters the left station until it leaves the pond. A comprehensive…

  2. A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod.

    PubMed

    Tyring, S K; Arany, I; Stanley, M A; Tomai, M A; Miller, R L; Smith, M H; McDermott, D J; Slade, H B

    1998-08-01

    Imiquimod, an immune response modifier, has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus (HPV). To identify the molecular mechanism(s) by which condylomata acuminata clear during topical treatment with imiquimod, wart skin biopsies were taken from patients before treatment, at treatment week 6, and at the end of treatment. Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products. Wart clearance was associated with evidence of tissue production of interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha. Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins. Thus, topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins.

  3. Floors: Care and Maintenance.

    ERIC Educational Resources Information Center

    Post Office Dept., Washington, DC.

    Guidelines, methods and policies regarding the care and maintenance of post office building floors are overviewed in this handbook. Procedures outlined are concerned with maintaining a required level of appearance without wasting manpower. Flooring types and characteristics and the particular cleaning requirements of each type are given along with…

  4. Computerized Fleet Maintenance.

    ERIC Educational Resources Information Center

    Cataldo, John J.

    The computerization of school bus maintenance records by the Niskayuna (New York) Central School District enabled the district's transportation department to engage in management practices resulting in significant savings. The district obtains computer analyses of the work performed on all vehicles, including time spent, parts, labor, costs,…

  5. School Maintenance Needs

    ERIC Educational Resources Information Center

    Erickson, Paul W.

    2011-01-01

    The United States is full of schools built in the 1950s and 60s that supported the boomer school-age enrollment increase. These schools, once beacons of the neighborhood, are 50 to 60 years old and susceptible to becoming the community "eyesore." Budgeting for maintenance was fairly systematic for school districts for the first 10 to 20 years…

  6. Electrical Maintenance Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 30 units to consider for use in a tech prep competency profile for the occupation of electrical maintenance technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific…

  7. Diesel Vehicle Maintenance Competencies.

    ERIC Educational Resources Information Center

    Braswell, Robert; And Others

    Designed to provide a model set of competencies, this manual presents tasks which were identified by employers, employees, and teachers as important in a postsecondary diesel vehicle maintenance curriculum. The tasks are divided into seven major component areas of instruction: chassis and suspension, diesel engines, diesel fuel, electrical,…

  8. CH Packaging Maintenance Manual

    SciTech Connect

    Washington TRU Solutions

    2002-01-02

    This procedure provides instructions for performing inner containment vessel (ICV) and outer containment vessel (OCV) maintenance and periodic leakage rate testing on the following packaging seals and corresponding seal surfaces using a nondestructive helium (He) leak test. In addition, this procedure provides instructions for performing ICV and OCV structural pressure tests.

  9. Preventive Maintenance Process

    NASA Technical Reports Server (NTRS)

    Ciaruffoli, Veronica; Bramley, Craig; Matteson, Mike

    2001-01-01

    The Preventive Maintenance (PM) program at Stennis Space Center (SSC) evolved from an ineffective and poorly organized state to a highly organized state in which it became capable of tracking equipment, planning jobs with man hour estimates, and supporting outsourcing. This viewgraph presentation traces the steps the program took to improve itself.

  10. Home Maintenance Manual.

    ERIC Educational Resources Information Center

    Richmond, Jim; And Others

    This manual, written especially for the Navajo and Hopi Indian Relocation Commission, is a simply worded, step-by-step guide to home maintenance for new homeowners. It can be used for self-study or it can serve as instructional material for a training class on home ownership. The manual is organized in nine sections that cover the following…

  11. Maintenance Crisis vs Solutions.

    ERIC Educational Resources Information Center

    Haggard, Susie

    Industrial maintenance in Northeast Georgia is facing an acute crisis. Contributing factors are economic development that is depleting the work force, aging of the population, downsizing of the military, and lack of technical school graduates. Solutions to the crisis fall into three categories: short-term, mid-term, and long-term. For short-term…

  12. Industrial Mechanical Maintenance.

    ERIC Educational Resources Information Center

    Hendrix, Laborn J.

    This manual was developed to assist teachers in Oklahoma in preparing students for industrial mechanical maintenance. The materials in this teacher's guide are organized in 14 units of instruction covering the following four areas: receiving and setting equipment; equipment hookup and operation; equipment layout, anchoring, and setup; and…

  13. Floors: Selection and Maintenance.

    ERIC Educational Resources Information Center

    Berkeley, Bernard

    Flooring for institutional, commercial, and industrial use is described with regard to its selection, care, and maintenance. The following flooring and subflooring material categories are discussed--(1) resilient floor coverings, (2) carpeting, (3) masonry floors, (4) wood floors, and (5) "formed-in-place floors". The properties, problems,…

  14. Care and Maintenance.

    ERIC Educational Resources Information Center

    Hampton, Carol D.; Hampton, Carolyn H.

    1980-01-01

    Described is a method for bringing the sea into the classroom by setting up a saltwater aquarium. Included is selection of an aquarium, filtering systems, water (whether natural salt or synthetic sea salts), bottom materials, setting up an aquarium, system stabilization, stocking an aquarium, and maintenance of the aquarium. (DS)

  15. Operations and maintenance philosophy

    SciTech Connect

    DUNCAN, G.P.

    1999-10-28

    This Operations and Maintenance (O&M) Philosophy document is intended to establish a future O&M vision, with an increased focus on minimizing worker exposure, ensuring uninterrupted retrieval operations, and minimizing operation life-cycle cost. It is intended that this document would incorporate O&M lessons learned into on-going and future project upgrades.

  16. Horticulture: Grounds Maintenance Employee.

    ERIC Educational Resources Information Center

    Sims, James; And Others

    The unit of individualized learning activities is designed to provide training in grounds maintenance. The materials in the unit are divided into two sections. The developmental or preliminary phase (15 pages) is for use by the instructor and includes brief descriptions of the job and of the student population, along with listings of the specific…

  17. Grounds Maintenance Evaluation.

    ERIC Educational Resources Information Center

    Chesapeake Public Schools, VA. Office of Program Evaluation.

    The Grounds Shop of the Chesapeake Public School Division (Virginia) Department of School Plants was evaluated in 1995-96. The goals of the grounds maintenance program are to provide safe and attractive grounds for students, parents, and staff of the school district. The evaluation examined the extent to which these goals are being met by using…

  18. IMWG consensus on maintenance therapy in multiple myeloma

    PubMed Central

    Durie, Brian G. M.; McCarthy, Philip; Palumbo, Antonio; San Miguel, Jésus; Barlogie, Bart; Morgan, Gareth; Sonneveld, Pieter; Spencer, Andrew; Andersen, Kenneth C.; Facon, Thierry; Stewart, Keith A.; Einsele, Hermann; Mateos, Maria-Victoria; Wijermans, Pierre; Waage, Anders; Beksac, Meral; Richardson, Paul G.; Hulin, Cyrille; Niesvizky, Ruben; Lokhorst, Henk; Landgren, Ola; Bergsagel, P. Leif; Orlowski, Robert; Hinke, Axel; Cavo, Michele; Attal, Michel

    2012-01-01

    Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established. PMID:22271445

  19. Preventive Maintenance. Training Module 3.320.2.77.

    ERIC Educational Resources Information Center

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document is an instructional module package prepared in objective form for use by an instructor familiar with preventive maintenance methods and procedures in a water or wastewater treatment system. Included are objectives, instructor guides, and student handouts. This module includes concepts of preventive maintenance, setting up a record…

  20. 40 CFR 35.2206 - Operation and maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Operation and maintenance. 35.2206 Section 35.2206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2206 Operation and maintenance. (a) The grantee must...

  1. Methadone Medical Maintenance: An Early 21st-Century Perspective.

    PubMed

    Novick, David M; Salsitz, Edwin A; Joseph, Herman; Kreek, Mary Jeanne

    2015-01-01

    Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians' offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended. PMID:26110221

  2. Interferon-alpha inhibits murine macrophage transforming growth factor-beta mRNA expression.

    PubMed

    Dhanani, S; Huang, M; Wang, J; Dubinett, S M

    1994-06-01

    Transforming growth factor-beta (TGF-beta), a multifunctional polypeptide is produced by a wide variety of cells and regulates a broad array of physiological and pathological functions. TGF-beta appears to play a central role in pulmonary fibrosis and may contribute to tumor-associated immunosuppression. Alveolar macrophages are a rich source of TGF-beta and are intimately involved in lung inflammation. We therefore chose to study TGF-beta regulation in murine alveolar macrophages as well as an immortalized peritoneal macrophage cell line (IC-21). Murine macrophages were incubated with cytokines to evaluate their role in regulating TGF-beta mRNA expression. We conclude that IFN-alpha downregulates TGF-beta mRNA expression in murine macrophages. PMID:8088926

  3. Sensitive radioimmunoassay for detection of antibodies to recombinant human interferon-alpha A

    SciTech Connect

    Palleroni, A.V.; Trown, P.W.

    1986-12-01

    A radioimmunoassay (RIA) for the detection of antibodies to recombinant human leukocyte interferon A (rHuIFN-alpha A) in human serum has been developed and validated against the standard antiviral neutralization bioassay (ANB). The assay measures the binding of /sup 125/I-labeled rHuIFN-alpha A to immunoglobulins in serum. Aliquots of patients' sera are incubated with /sup 125/I-rHuIFN-alpha A and the complexes formed between antibodies in the sera and the /sup 125/I-rHuIFN-alpha A are precipitated with goat anti-human IgG serum. The radioactivity in the immune precipitate is a measure of the quantity of antibody (if present) in the serum. The sensitivity of this RIA is 5 ng of IgG/ml of serum.

  4. Percutaneous absorption of interferon-alpha by self-dissolving micropiles.

    PubMed

    Ito, Yukako; Saeki, Atsushi; Shiroyama, Keiji; Sugioka, Nobuyuki; Takada, Kanji

    2008-04-01

    To ascertain the pharmaceutical usefulness of self-dissolving micropiles (SDMPs) containing interferon (IFN), two types of SDMPs were prepared using chondroitin sulfate and dextran as the base. After percutaneous administration of 5000 IU/kg IFN-alpha2b SDMP to rats, serum IFN levels were measured for 6 h. The peak serum IFN level, maximum drug concentration (Cmax), and the time when serum IFN level reaches to Cmax, time to reach maximum concentration (Tmax), were 8.2+/-0.5 IU/ml and 1.2+/-0.1 h, respectively, for chondroitin SDMP. For dextran SDMP, Cmax and Tmax were 3.1+/-0.4 IU/ml and 3.3+/-0.3 h, respectively. AUC of chondroitin SDMP was 1.5 times greater than that of dextran SDMP. Bioavailabilities (BAs) of IFN were 378.3% for chondroitin SDMP and 255.9% for dextran SDMP that were larger than 100%. The BA of IFN from subcutaneous (s.c.) injection solution was 320.9%. The relative BAs of IFN SDMPs against s.c. injection solution were 117.8% for chondroitin SDMP and 79.9% dextran SDMP. An in vitro release experiment suggested the faster release rate of IFN from chondroitin SDMP, 57.3% at 5 min, than dextran SDMP, 32.6% at 5 min. Chondroitin SDMP containing IFN showed good stability for 3 months and no damage to the administered rat skin.

  5. Effects of interferon-alpha (IFN-alpha) administration on leucocytes in healthy humans.

    PubMed

    Corssmit, E P; Heijligenberg, R; Hack, C E; Endert, E; Sauerwein, H P; Romijn, J A

    1997-02-01

    Plasma concentrations of IFN-alpha are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-alpha has anti-inflammatory properties. To study the effects of IFN-alpha on leucocyte subsets and activation and on cytokines, we administered IFN-alpha (rhIFN-alpha2b; 5 x 10(6) U/m2) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in circulating leucocytes and parameters for neutrophil and monocyte activation. After administration of IFN-alpha, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-alpha administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-alpha. IFN-alpha significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma concentrations of soluble TNF receptors p55 and p75 increased after IFN-alpha administration. We conclude that IFN-alpha induces multiple alterations in the distribution and functional properties of leucocytes. IFN-alpha exerts pro- as well as anti-inflammatory effects within the cytokine network.

  6. Anti-viral effect of interferon-alpha on bovine viral diarrhea virus.

    PubMed

    Sentsui, H; Takami, R; Nishimori, T; Murakami, K; Yokoyama, T; Yokomizo, Y

    1998-12-01

    To get basic information to control persistent virus infection among domestic animals by cytokines, the antiviral activity of four natural human cytokines against bovine viral diarrhea virus (BVDV) was evaluated. Normal bovine peripheral blood mononuclear leukocytes (PBML) and fetal bovine muscular cells (FBMC) were treated with varying doses of human interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta. The antiviral activity in treated cells was measured by the titration of virus infectivity in comparison with non-treated controls. IFN-alpha significantly suppressed virus growth in both PBML and FBMC. The growth of two cytopathogenic and two noncytopathogenic strains was suppressed in the presence of more than 10(3) u/ml of IFN-alpha. Addition of either TNF-alpha or TNF-beta to IFN-alpha did not potentiate the suppressive effect. IFN-alpha also suppressed the replication of BVDV in PBML from cattle persistently infected with BVDV.

  7. Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions

    PubMed Central

    Liu, Chien-Cheng; Gao, Yong-Jing; Luo, Hao; Berta, Temugin; Xu, Zhen-Zhong; Ji, Ru-Rong; Tan, Ping-Heng

    2016-01-01

    It is well known that interferons (IFNs), such as type-I IFN (IFN-α) and type-II IFN (IFN-γ) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytokine, IFN-γ drives neuropathic pain by inducing microglial activation in the spinal cord. However, little is known about the role of IFN-α in regulating pain sensitivity and synaptic transmission. Strikingly, we found that IFN-α/β receptor (type-I IFN receptor) was expressed by primary afferent terminals in the superficial dorsal horn that co-expressed the neuropeptide CGRP. In the spinal cord IFN-α was primarily expressed by astrocytes. Perfusion of spinal cord slices with IFN-α suppressed excitatory synaptic transmission by reducing the frequency of spontaneous excitatory postsynaptic current (sEPSCs). IFN-α also inhibited nociceptive transmission by reducing capsaicin-induced internalization of NK-1 and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial dorsal horn neurons. Finally, spinal (intrathecal) administration of IFN-α reduced inflammatory pain and increased pain threshold in naïve rats, whereas removal of endogenous IFN-α by a neutralizing antibody induced hyperalgesia. Our findings suggest a new form of neuronal-glial interaction by which IFN-α, produced by astrocytes, inhibits nociceptive transmission in the spinal cord. PMID:27670299

  8. Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function.

    PubMed

    Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

    2016-08-01

    Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

  9. Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function

    PubMed Central

    Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

    2016-01-01

    ABSTRACT Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

  10. Cytotoxic activity of interferon alpha induced dendritic cells as a biomarker of glioblastoma

    NASA Astrophysics Data System (ADS)

    Mishinov, S. V.; Stupak, V. V.; Tyrinova, T. V.; Leplina, O. Yu.; Ostanin, A. A.; Chernykh, E. R.

    2016-08-01

    Dendritic cells (DCs) are the most potent antigen presenting cells that can play direct role in anti-tumor immune response as killer cells. DC tumoricidal activity can be stimulated greatly by type I IFN (IFNα and IFNβ). In the present study, we examined cytostatic and cytotoxic activity of monocyte-derived IFNα-induced DCs generated from patients with brain glioma and evaluated the potential use of these parameters in diagnostics of high-grade gliomas. Herein, we demonstrated that patient DCs do not possess the ability to inhibit the growth of tumor HEp-2 cell line but low-grade and high-grade glioma patients do not differ significantly in DC cytostatic activity. However, glioma patient DCs are characterized by reduced cytotoxic activity against HEp-2 cells. The impairment of DC cytotoxic function is observed mainly in glioblastoma patients. The cytotoxic activity of DCs against HEp-2 cells below 9% is an informative marker for glioblastomas.

  11. Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha.

    PubMed

    Toma, S; Yamashiro, T; Arakaki, S; Shiroma, J; Maeshiro, T; Hibiya, K; Sakamoto, N; Kinjo, F; Tateyama, M; Fujita, J

    2009-07-01

    Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti-retroviral therapy. HCV-related liver disease is more severe in HIV-infected patients than in non-HIV-infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down-regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin-selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose-dependently repressed HCV replication at low concentrations (IC(50), 9.88 micromol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 micromol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.

  12. Proposed SOLCOST maintenance activities

    SciTech Connect

    1980-01-01

    This document provides a short description of work that has been accomplished to date and work in progress. A discussion of the program status as it is currently configured follows and finally proposed work by Solar Environmental Engineering Company (SEEC) in its most recently signed contract with the Department of Energy (DOE) is given. Early statements are designed to give the reader a good background so that the suggested SOLCOST maintenance activities will be more easily understood.

  13. Flight Crew Health Maintenance

    NASA Technical Reports Server (NTRS)

    Gullett, C. C.

    1970-01-01

    The health maintenance program for commercial flight crew personnel includes diet, weight control, and exercise to prevent heart disease development and disability grounding. The very high correlation between hypertension and overweight in cardiovascular diseases significantly influences the prognosis for a coronary prone individual and results in a high rejection rate of active military pilots applying for civilian jobs. In addition to physical fitness the major items stressed in pilot selection are: emotional maturity, glucose tolerance, and family health history.

  14. Simple maintenance for dramatic effect.

    PubMed

    Wells, Scott; Collen, Mark

    2012-08-01

    In an article which first appeared in print in the March 2012 issue of The Australian Hospital Engineer, based on a presentation given at the Institute of Hospital Engineering Australia's 2009 National Conference, Scott Wells, energy manager, Engineering & Building Services, at Royal Brisbane Women's Hospital, and Mark Collen, a district account manager, Engineering and Process Development Division, at water treatment specialist, Nalco, discuss how sound, regular, and thorough, maintenance and cleaning of hospital air-handing units will not only enhance their operating efficiency, but will also help reduce airborne infection risk in the healthcare facilities they serve. They also detail practical measures taken at hospitals in Queensland to reduce the energy consumption of air-handling equipment. PMID:22984738

  15. PREVENTIVE MAINTENANCE. HONEYWELL PLANNING GUIDE.

    ERIC Educational Resources Information Center

    Honeywell, Inc., Minneapolis, Minn.

    THIS HONEYWELL PAMPHLET DISCUSSES SOME ASPECTS OF PREVENTIVE MAINTENANCE OF AUTOMATIC CONTROLS, HEATING, VENTILATING, AND AIR CONDITIONING, AND COMPARES IN-PLANT WITH CONTRACT SERVICE, CONCLUDING THAT CONTRACT SERVICE IS PREFERABLE AND DESCRIBING A NUMBER OF MAINTENANCE PLANS WHICH THEY FURNISH. PREVENTIVE MAINTENANCE PROVIDES--(1) MORE EFFICIENT…

  16. AUTOMOTIVE DIESEL MAINTENANCE. PROGRAM OUTLINE.

    ERIC Educational Resources Information Center

    Human Engineering Inst., Cleveland, OH.

    INFORMATIONAL TOPICS COVERED IN THE TEXT MATERIALS AND SELF-INSTRUCTIONAL BRANCH PROGRAMED TRAINING FILMS FOR A 2-YEAR, 55 MODULE PROGRAM IN AUTOMOTIVE DIESEL MAINTENANCE ARE GIVEN. THE 30 MODULES FOR "AUTOMOTIVE DIESEL MAINTENANCE 1" ARE AVAILABLE AS VT 005 655 - VT 005 684, AND THE 25 MODULES FOR "AUTOMOTIVE DIESEL MAINTENANCE 2" ARE AVAILABLE…

  17. Refining the maintenance techniques for Interlocking Concrete Paver GIs

    EPA Science Inventory

    Surface clogging adversely affects the performance of Interlocking Concrete Pavements (ICP) by reducing their ability to infiltrate stormwater runoff. The clogging rate is a function of pavement type, traffic loading, surrounding physical environment and maintenance treatments. ...

  18. General aviation avionics equipment maintenance

    NASA Technical Reports Server (NTRS)

    Parker, C. D.; Tommerdahl, J. B.

    1978-01-01

    Maintenance of general aviation avionics equipment was investigated with emphasis on single engine and light twin engine general aviation aircraft. Factors considered include the regulatory agencies, avionics manufacturers, avionics repair stations, the statistical character of the general aviation community, and owners and operators. The maintenance, environment, and performance, repair costs, and reliability of avionics were defined. It is concluded that a significant economic stratification is reflected in the maintenance problems encountered, that careful attention to installations and use practices can have a very positive impact on maintenance problems, and that new technologies and a general growth in general aviation will impact maintenance.

  19. The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment

    PubMed Central

    Wang, Si-Tien; Huang, Hui; Ba-Mancini, Abbie; Shi, Hongliang; Chen, Kristina; Korves, Caroline; Dhawan, Ravinder; Cakana, Andrew; van de Velde, Helgi; Corzo, Deyanira; Duh, Mei Sheng

    2013-01-01

    The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99–06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99–06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R. PMID:23299777

  20. Interventions for Weight Reduction: Facing the Maintenance Problem

    ERIC Educational Resources Information Center

    Anderson, Drew A.; Simmons, Angela M.; Milnes, Suzanne M.

    2005-01-01

    Behavioral treatments are perhaps the cornerstone of modern obesity treatment. Maintenance of weight lost via behavioral treatments has been less than hoped for, however. Weight regain is the result of complex interactions between physiological, behavioral, cognitive, and environmental factors; in this paper we review some of these factors and…