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Sample records for interferon-alpha maintenance treatment

  1. 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

  2. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    PubMed

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  3. Rapid progression to cardiac tamponade in Erdheim-Chester disease despite treatment with interferon alpha.

    PubMed

    Nakhleh, Afif; Slobodin, Gleb; Elias, Nizar; Bejar, Jacob; Odeh, Majed

    2016-07-01

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis with heterogeneous clinical manifestations. The most common presentation is bone pains typically involving the long bones. Approximately 75% of the patients develop extraskeletal involvement. Cardiac involvement is seen in up to 45% of the patients, and although, pericardial involvement is the most common cardiac pathology of this rare disease, cardiac tamponade due to ECD has been very rarely reported. We describe a case of a patient found to have ECD with multi-organ involvement and small pericardial effusion, which progressed to cardiac tamponade despite treatment with interferon alpha.

  4. Effective treatment with interferon-alpha in chronic recurrent multifocal osteomyelitis.

    PubMed

    Andersson, R

    1995-10-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of unknown etiology characterized by multiple osteomyelitic changes in the predominantly metaphysial regions of long bones. It was first described by Giedon et al. in 1972. Cultures for all known microorganisms are negative. Pain is the most common symptom, and sometimes soft tissue swelling is present. Patients are usually treated with nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids and respond, at least partly, to these treatments. CRMO is most commonly seen in children and is in the majority of cases self-limiting but has a protracted course of several years. Some patients have a more prolonged disease period, as in the patient reported here. Treatment with corticosteroids in children has the risk of causing growth retardation as a potential adverse effect, and alternative treatments are of great interest. In the actual paper, a successful treatment with interferon-alpha 2b in a 34-year-old man with CRMO is presented.

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

    PubMed

    Fernandez-Sainz, I; Ramanathan, P; O'Donnell, V; Diaz-San Segundo, F; Velazquez-Salinas, L; Sturza, D F; Zhu, J; de los Santos, T; Borca, M V

    2015-09-01

    Interferon-alpha (IFNα) can effectively inhibit or abort a viral infection within the host. It has been reported that IFN induction and production is hindered during classical swine fever virus (CSFV) infection. Most of those studies have been performed in vitro, making it difficult to elucidate the actual role of IFNs during CSFV infection in swine. Here, we report the effect of IFNα treatment (delivered by a replication defective recombinant human adenovirus type 5, Ad5) in swine experimentally infected with highly virulent CSFV strain Brescia. Treatment with two different subtypes of IFNα delayed the appearance of CSF-related clinical signs and virus replication although it did not prevent lethal disease. This is the first report describing the effect of IFNα treatment during CSFV infection in swine.

  6. Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia

    PubMed Central

    Drazilova, Sylvia; Janicko, Martin; Kristian, Pavol; Schreter, Ivan; Kucinsky, Branislav; Kozlej, Marek; Hockickova, Ivana; Jarcuska, Peter

    2016-01-01

    Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response. PMID:26858755

  7. Use of intralesional interferon-alpha for the treatment of recalcitrant oral warts in patients with AIDS: a report of 4 cases.

    PubMed

    Lozada-Nur, F; Glick, M; Schubert, M; Silverberg, I

    2001-12-01

    Four human immunodeficiency virus-positive homosexual men with 2- to 4.5-year histories of recurrent oral warts that had failed to respond to conventional surgical and other treatment modalities were offered treatment with interferon-alpha. All had multiple or large oral warts, 3 had skin warts, 2 had a history of anal warts, and 1 had penile lesions. All 4 patients were treated with a combination of intralesional and subcutaneous interferon-alpha. Adverse side effects were dose-related, mild, and transient; they included flulike symptoms (3 patients), hair loss and tachycardia (1 patient), and transient changes in the white blood cell count. All patients responded to therapy and remained free of disease up to 42 months. Intralesional injection with interferon-alpha appears to provide excellent clinical control for recurrent, multiple, and extensive oral warts in the human immunodeficiency virus-positive population, and is a useful adjunct to initial surgical removal of oral warts.

  8. [Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report].

    PubMed

    Bassetti, Bil Randerson; Trés, Eduardo Sturzeneker; Ciríaco, Jovana Gobbi Marchesi; Pinto Neto, Lauro Ferreira Silva

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  9. Interferon-alpha treatment induces depression-like behaviour accompanied by elevated hippocampal quinolinic acid levels in rats.

    PubMed

    Fischer, Christina Weide; Eskelund, Amanda; Budac, David P; Tillmann, Sandra; Liebenberg, Nico; Elfving, Betina; Wegener, Gregers

    2015-10-15

    Immunotherapy with the cytokine interferon-alpha (IFN-α) can induce symptoms of depression, and it is likely that the tryptophan-kynurenine pathway may be involved in this regard. In this study we investigated the effects of IFN-α on depression-like behaviour and central metabolites of the tryptophan-kynurenine pathway in rats. Secondly, we explored the modulating effects of an antidepressant (imipramine) and anti-inflammatory drug (celecoxib) on IFN-α-induced behavioural and pathophysiological changes in the brain. The following treatment groups were used: Control (saline), IFN-α (6×10(4)IU/kg s.c.), IFN-α+imipramine or IFN-α+celecoxib. Drugs were administered daily for 1 week. IFN-α treatment induced depression-like behaviour by increasing immobility in the forced swim test (FST), and decreased tryptophan levels in the brain. There was a trend for an increased kynurenine/tryptophan ratio, indicative of indoleamine 2,3-dioxygenase (IDO) activation, and increased quinolinic acid in the hippocampus. Imipramine decreased immobility in the FST, but did not reverse the IFN-α-induced changes in the tryptophan-kynurenine pathway. There was a trend for celecoxib to decrease immobility and to reverse the IFN-α-induced increase in the kynurenine/tryptophan ratio. Thus, our study provides further evidence for IFN-α-induced depression-like behaviour through central changes of the tryptophan-kynurenine pathway.

  10. 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

  11. Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis].

    PubMed

    Di Ciommo, V; Russo, P; Ravà, L; Caprino, L

    2003-05-01

    Children with chronic hepatitis C may be ideal candidates for treatment with interferon alpha (IFNalpha) as they have liver disease at an early stage. However, adverse drug reactions need to be considered. The aim of this study was to conduct a systematic review of literature on interferon therapy of chronic hepatitis C in children, and to perform a meta-analysis of pooled data. A computerized search gave 18 articles on IFNalpha therapy in children with chronic hepatitis C; after exclusion of uncontrolled trials and of trials including patients with comorbidities, data from two studies could be pooled (48 patients). The outcomes assessed were biochemical, defined as normalization of alanine transaminase, and virologic, defined as HCV-RNA loss, both sustained at 24 months after enrollment. Results of the studies were homogenous. Risk difference was 37% (95%CI: 12.9-61) in favour of IFNalpha treated children for sustained biochemical response, and 36.8% (95%CI: 14.3-59.3) in favour of treated children for sustained HCV clearance, respectively. The differences were highly significant (P = 0.007 and P = 0.004, respectively). The histological end-point, as well as side-effects, could not be analysed, due to lack of data. This review identifies the poor methodology of the majority of the published trials. The study provides support for the efficacy of IFNalpha in improving both biochemical and virologic outcomes in chronic hepatitis C in children, but evidence is confined to these surrogate end-points.

  12. Clinical improvement and normalized Th1 cytokine profile in early and long-term interferon-alpha treatment in a suspected case of hyper-IgE syndrome.

    PubMed

    Benninghoff, Ulrike; Cattaneo, Federica; Aiuti, Alessandro; Flores-D'Arcais, Alberto; Gelmetti, Carlo; Viscardi, Matteo; Callegaro, Luciano; Mirolo, Massimiliano; Ambrosi, Alessandro; Roncarolo, Maria Grazia; Bacchetta, Rosa

    2008-09-01

    We are reporting on a 7-months-old boy with suspected hyper-IgE syndrome, presenting with a therapy resistant severe eczema and an overall reduction of in vitro cytokine production. Interferon-alpha (IFN-alpha) treatment resulted in a marked and stable clinical improvement and normalization of in vitro T-cell cytokine production, indicating a valid therapeutic potential of IFN-alpha as immunomodulating drug.

  13. Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma.

    PubMed Central

    Dillman, R. O.; Shea, W. M.; Tai, D. F.; Mahdavi, K.; Barth, N. M.; Kharkar, B. R.; Poor, M. M.; Church, C. K.; DePriest, C.

    2001-01-01

    Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patients with recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This trial was conducted to determine the clinical effects of IFN-alpha2a and CRA when given concurrently with radiation therapy to patients with high-grade glioma. Newly diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3 to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4 times a day for 5 days per week during the delivery of partial brain radiation therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy during the 7-week period. Use of the antiepileptic phenytoin was prohibited after observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated with a high rate of dermatologic toxicity not seen in a previous study with concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to 81 years) were enrolled between August 1996 and October 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tumor prior to this therapy; 50% were asymptomatic when treatment was initiated. The planned 7-week course of concurrent therapy was completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a median overall survival of 9.3 months and a 1-year survival rate of 42%. There was no improvement in survival compared with a similar group of 19 patients treated with concurrent IFN-alpha2a and radiation therapy in a

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

    PubMed Central

    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 co-infected 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 1 and 4 cannot be the final step in development of effective treatments in patients with HCV/HIV co-infection. PMID:17722274

  15. Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

    PubMed

    Bell, H; Hellum, K; Harthug, S; Maeland, A; Ritland, S; Myrvang, B; von der Lippe, B; Raknerud, N; Skaug, K; Gutigard, B G; Skjaerven, R; Prescott, L E; Simmonds, P

    1997-01-01

    Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

  16. Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes

    PubMed Central

    O'Bryan, Joel M.; Potts, James A.; Bonkovsky, Herbert L.; Mathew, Anuja; Rothman, Alan L.

    2011-01-01

    Background Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes. Methods/Principal Findings Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNα group for an additional 3.5 years. Significant telomere loss in naïve T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8+CD45RA+CD57+ memory T cells and an inverse correlation of alanine aminotransferase levels with naïve CD8+ T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index. Conclusions/Significance Sustained interferon-alpha treatment increased telomere loss in naïve T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined. PMID:21829595

  17. 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.

  18. 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.

  19. Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6.

    PubMed

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

    2013-07-01

    Cross-sectional studies have found that an elevated ratio of arachidonic acid to omega-3 fatty acid is associated with depression, and controlled intervention studies have found that decreasing this ratio through administration of omega-3 fatty acids can alleviate depressive symptoms. Additionally, arachidonic acid and omega-3 fatty acids have opposing effects on inflammatory signaling. Exogenous administration of the inflammatory cytokine interferon-alpha (IFN-α) can trigger a depressive episode in a subset of vulnerable people, though associated risk factors remain poorly understood. Using a within-subject prospective design of 138 subjects, we examined whether baseline long-chain omega-3 (docosahexaenoic acid - DHA; eicosapentaenoic acid - EPA) and omega-6 (arachidonic acid - AA; di-homo-gamma-linolenic acid - DGLA) fatty acid status was associated with depression vulnerability in hepatitis C patients treated with IFN-α. Based on the literature, we had specific a priori interest in the AA/EPA+DHA ratio. Lower baseline DHA predicted depression incidence (p=0.04), as did elevated DGLA (p=0.02) and an elevated AA/EPA+DHA ratio (p=0.007). The AA/EPA+DHA ratio predicted depression even when controlling for other critical variables such as sleep quality and race. A higher AA/EPA+DHA ratio was positively associated with both increasing Montgomery-Asperg Depression Rating Scores over time (F=4.0; p<0.05) as well as interleukin-6 levels (F=107.4; p<0.05) but not C-reactive protein. Importantly, omega-3 and omega-6 fatty acid status was not associated with sustained viral response to IFN-α treatment. These prospective data support the role of fatty acid status in depression vulnerability and indicate a potential role for omega-3 fatty acids in the prevention of inflammation-induced depression.

  20. A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-alpha2a as first line treatment in metastatic melanoma.

    PubMed

    Vihinen, Pia P; Hernberg, Micaela; Vuoristo, Meri-Sisko; Tyynelä, Kristiina; Laukka, Marjut; Lundin, Johan; Ivaska, Johanna; Pyrhönen, Seppo

    2010-08-01

    Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon alpha-2a (IFN-alpha2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m days 1-5 every 4 weeks) and IFN-alpha2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab+/-IFN-alpha2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed > or =3 months after the last bevacizumab-DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.

  1. Complete remission of multiple myeloma after autoimmune hemolytic anemia: possible association with interferon-alpha.

    PubMed

    Gesundheit, Benjamin; Zelig, Orly; Shapira, Michael Y; Ackerstein, Aliza; Avgil, Meytal; Or, Reuven

    2007-06-01

    A patient with multiple myeloma (MM) was being maintained on human recombinant interferon-alpha (INF-alpha) after VAD and autologous bone marrow transplantation (pretreated with melphalan). An episode of immune thrombocytopenia and (Coombs positive) autoimmune hemolytic anemia (AIHA) was noted while on maintenance INF-alpha, which remitted when it was withdrawn. Following this event, he achieved a state of stable disease that persists (more than 3 years) with no specific myeloma treatment. This sequence of events suggests a relationship between an immunological reaction induced by INF-alpha and the prolonged phase of stable disease.

  2. Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost-effective treatment modality in Asian Indian patients

    PubMed Central

    Kaliki, Swathi; Singh, Swati; Iram, Sadiya; Tripuraneni, Dharani

    2016-01-01

    Purpose: The purpose was to study the efficacy of interferon alpha 2b (INF α2b) in the treatment of ocular surface squamous neoplasia (OSSN) and analyze its cost-effectiveness in India. Study Design: This was a retrospective study of thirty patients with OSSN treated with topical INF α2b (1 MIU/cc) ± perilesional INF α2b (5 MIU/cc). Results: The tumor involved cornea (n = 9, 30%), conjunctivo-limbal-corneal surface (n = 19, 63%), or bulbar conjunctiva (n = 2, 7%). The mean basal dimension of the tumor was 16 mm. The tumors belonged to Tis (n = 6, 20%) or T3 (n = 24, 80%) based on the American Joint Committee Classification, 7th edition. In the six patients with Tis, three cycles of topical INF α2b were used for immunoprevention. In the remaining 24 patients, INF α2b was advised for immunoreduction, but served as immunotherapy with 100% tumor regression in 22 (92%) cases, and resulted in 95% immunoreduction in 2 (6%) cases. Complete tumor regression by immunotherapy (n = 22) was achieved with a mean number of three topical INF α2b cycles and two perilesional injections. All these 22 patients received three additional topical INF α2b cycles after complete tumor regression. For immunoreduction (n = 2), both patients received six cycles of topical INF α2b which was three perilesional INF α2b injections. The mean total treatment cost per patient with INF α2b was INR 9164 ($US 137). Based on maximum basal diameter of tumor at presentation, the mean total treatment cost per patient with INF α2b was INR 4866 ($US 73) for eyes with microscopic evidence of tumor residue (n = 6), INR 9607 ($US 143) for tumors ≤10 mm (n = 13), and INR 10,985 ($US 164) for tumors >10 mm (n = 11), with two patients needing additional surgical excision for complete tumor control. Conclusion: INF α2b can be used for immunoreduction, immunotherapy, or immunoprevention of OSSN. INF α2b is a cost-effective treatment modality for OSSN at an average total treatment cost of INR 9164 ($US

  3. Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients.

    PubMed

    Conill, Carlos; Jorcano, Sandra; Domingo-Domènech, Josep; Marruecos, Jordi; Vilella, Ramón; Malvehy, Josep; Puig, Susana; Sánchez, Marcelo; Gallego, Rosa; Castel, Teresa

    2007-10-01

    Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.

  4. Human leukocyte interferon-alpha in a hydrophilic cream versus in a gel for the treatment of genital herpes in males: a placebo-controlled, double-blind, comparative study.

    PubMed

    Syed, T A; Ahmadpour, O A; Ahmad, S A; Ahmad, S H

    1997-09-01

    The aim of this double-blind, placebo-controlled, comparative study was to differentiate the clinical efficacy and tolerability of human leukocyte interferon-alpha incorporated (2 x 10(6) IU/g) in a hydrophilic cream and in a gel to heal males afflicted with first episodes of genital herpes. Patients (n = 60), aged 18-40 years (mean 23.2) with culture-confirmed diagnosis of herpes genitalis were randomized to three parallel groups. Each patient was allocated a precoded 40-g tube, containing either preparation or placebo. Cream or gel was applied three times daily for 5 consecutive days. The duration of the active treatment was two weeks. Patients were examined after 48 hours in initial treatment, and thereafter two times a week. A reepithelialized lesion with some residual erythema was recorded as healed. The study demonstrated that patients treated with leukocyte interferon-alpha cream had both significantly shorter mean duration of lesions than gel and placebo recipients (5.3 days vs. 8 days, 13 days respectively; p < 0.001) and a higher number of healed patients (80% vs. 55%, 20% respectively; p < 0.001). Of the 60 patients, 49 (82%) complained of no drug-related side effects. Eleven patients predominantly in the cream/gel groups reported non-objective transitory increase in their body temperature (> 38 degrees C) with moderate headache, malaise and myalgia. The study was followed-up for 24 months after the first day of the treatment, and out of 31/60 cured patients, 4 had a relapse after 18 months. In conclusion the study affirmed that human leukocyte interferon-alpha (2 x 10(6) IU/g) in a hydrophilic cream is more efficacious than its incorporation in gel or placebo, thus suggesting that leukocyte interferon-alpha in a hydrophilic cream, with a profile of non-objective mild to moderate drug-induced indications, may be considered an alternative and effective treatment modality to cure male patients afflicted with first episodes of genital herpes.

  5. 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

  6. 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.

  7. [Interferon alpha-2b modified with polyethylene glycol].

    PubMed

    Wu, Yingxin; Zhai, Yanqin; Lei, Jiandu; Ma, Guanghui; Su, Zhiguo

    2008-09-01

    In order to obtain a more stable PEGylated interferon alpha-2b, and prolong its half life, interferon alpha-2b (IFN alpha-2b) was modified with monomethoxy polyethylene glycol propionaldehyde (mPEG-ALD) 20000. It was found that the optimized reaction condition for the maximum bioactivity and highest PEGylation degree of the mono PEGylated interferon alpha-2b was as follows: in 20 mmol/L, pH 6.5, citric acid and sodium dihydrogen phosphate buffer, the concentration of IFN alpha-2b was 4 mg/mL, and the molar ratio of PEG/IFN alpha-2b was 8:1, and the reaction time was 20 h at 4 degrees C. Under the optimized reaction condition, the mono PEGylation degree reached to 55%. Ion exchange chromatography was used to separate and purify mono PEGylated interferon alpha-2b from the reaction mixture. The purity of mono PEGylated interferon alpha-2b was higher than 97% characterized by HPLC. The bioactivity of the mono PEGylated interferon alpha-2b was 13.4% of the native IFN alpha-2b, while its half life in SD rat is much longer than the native IFN alpha-2b. The mono PEGylated interferon alpha-2b is also stable in aqueous.

  8. Dual onset of type 1 diabetes mellitus and Graves' disease during treatment with pegylated interferon alpha-2b and ribavirin for chronic hepatitis C.

    PubMed

    Hayashi, Masayuki; Kataoka, Yuko; Tachikawa, Kazushige; Koguchi, Hiroki; Tanaka, Hiroshi

    2009-11-01

    Currently, a combination therapy of pegylated (PEG) interferon (IFN) alpha-2b and ribavirin are being widely used for the treatment of chronic hepatitis C (CHC). We describe here a case of dual onset of type 1 DM accompanied by ketoacidosis, and Graves' disease during the combination therapy via the autoimmune process.

  9. Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

    PubMed Central

    Li, Ming-Hui; Zhang, Lu; Qu, Xiao-Jing; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Liu, Ru-Yu; Hu, Lei-Ping; Li, Zhen-Zhen; Hua, Wen-Hao; Song, Shu-Jing; Xie, Yao

    2017-01-01

    Background: Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1–3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72–96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss. PMID:28229987

  10. The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C

    PubMed Central

    Keshvari, Maryam; Alavian, Seyed Moayed; Behnava, Bita; Pouryasin, Ali; Sharafi, Heidar

    2016-01-01

    Background: A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). Materials and Methods: In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing. Results: Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients’ body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study. Conclusion: IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients. PMID:27904617

  11. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.

    PubMed

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki

    2017-01-01

    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

  12. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus

    PubMed Central

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C. Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki

    2017-01-01

    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients. PMID:28253324

  13. 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

  14. Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin--a review.

    PubMed

    Andrade, Luis Jesuíno de Oliveira; Atta, Ajax Mercês; D'Almeida Junior, Argemiro; Paraná, Raymundo

    2008-04-01

    Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

  15. Chronic hepatitis B with type I diabetes mellitus and autoimmune thyroiditis development during interferon alpha therapy.

    PubMed

    Kose, Sukran; Gozaydin, Ayhan; Akkoclu, Gulgun; Ece, Gulfem

    2012-04-13

    Interferon alpha is a molecule frequently used in the treatment of chronic hepatitis B, C, and D, with immunomodulatory and antiviral activity. It is also used in some cancer types. It has been widely claimed that interferon alpha triggers autoimmunity, with its broad adverse effect profile. Here we present the case of a 29-year-old male patient with chronic hepatitis B diagnosis who developed type 1 diabetes mellitus and autoimmune thyroiditis during treatment with interferon alfa-2b. Within four months of initiation of treatment with interferon alfa-2b, the patient presented to our clinic with dry mouth, urinary frequency (8 to 10 times per day), drinking plenty of water, night time urination, and tiredness. He was admitted to the clinic when his fasting blood glucose level was detected to be high. After examinations, the patient was diagnosed with type 1 diabetes and autoimmune thyroiditis and began to receive treatment with insulin and propranolol. Fasting blood glucose levels were controlled and thyroid hormones decreased to normal levels within one month after the treatments began. For patients who will receive treatment with interferon alpha, especially those individuals with chronic hepatitis, pancreatic autoantibodies should be checked and close monitoring should be performed as there may be glucose tolerance impairment in patients with high titers. In addition, follow-up with thyroid function tests should be performed prior to and during the treatment.

  16. Linear IgA bullous dermatosis induced by interferon-alpha 2a.

    PubMed

    Kocyigit, P; Akay, B N; Karaosmanoglu, N

    2009-07-01

    Linear Ig A bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder with linear deposits of IgA along the basement membrane zone. Its cause is unclear, although it appears to have an immune-mediated basis. Idiopathic, systemic disorder-related, and rarely drug-induced forms of LABD have been described. We describe a case of LABD associated with interferon-alpha 2A used for the treatment of Kaposi's sarcoma.

  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.

  18. Oropharyngeal pemphigus in a patient with chronic hepatitis C during interferon alpha-2a therapy.

    PubMed

    Marinho, R T; Johnson, N W; Fatela, N M; Serejo, F S; Glória, H; Raimundo, M O; Velosa, J F; Ramalho, F J; Moura, M C

    2001-07-01

    There are a few reports in the literature concerning pemphigus induced by interferon given for hepatitis C. We present the case of a 28-year-old woman with post-transfusional chronic hepatitis C who developed ulcers and vesicles on her tongue, cheeks, posterior oropharynx and vocal cords 5 months after beginning treatment with recombinant interferon alpha-2a. The direct and indirect immunofluorescence was diagnostic of pemphigus vulgaris. The drug was promptly withdrawn; the patient was medicated with prednisolone and azathioprine and recovered only 3 months later. Although there are several publications describing the occurrence of other autoimmune diseases in patients receiving interferon alpha therapy, this is the first report of a pemphigus induced by interferon in hepatitis C patients involving oropharyngeal and laryngeal mucosae without cutaneous involvement.

  19. 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

  20. Psoriasis exacerbated by interferon-alpha in a patient with chronic myeloid leukemia.

    PubMed

    Ladoyanni, E; Nambi, R

    2005-01-01

    Interferon-alpha can exacerbate existing psoriasis and induce de novo psoriasis and psoriatic arthritits. The exact underlying mechanism is not very well understood. It is not a contraindication to treat patients with pre-existing psoriasis with interferon-alpha. In these patients interferon-alpha should be used with care and only if the potential benefits justify the potential risk. Control of psoriasis prior to initiation of interferon-alpha and simultaneous antipsoriatic therapy while on interferon-alpha are essential. We would like to report a 61-year-old male patient with stable psoriasis for over 20 years, who experienced exacerbation of his psoriasis after receiving interferon-alpha for chronic myeloid leukemia. The association between the interferon-alpha therapy and the exacerbation of his psoriasis was only recognized on rechallenge at the stage he was referred to our department.

  1. 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

  2. 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

  3. 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.

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

    PubMed

    Moreno, M G; Muriel, P

    1995-08-08

    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.

  5. Expression of bioactive porcine interferon-alpha in Lactobacillus casei.

    PubMed

    Ma, Shi-jie; Li, Kun; Li, Xin-Sheng; Guo, Xiao-Qing; Fu, Peng-Fei; Yang, Ming-Fan; Chen, Hong-Ying

    2014-09-01

    In this study, we constructed an expression cassette containing the inducible lac promoter and the secretion signal from an S-layer protein of Lactobacillus brevis for the expression of porcine interferon-alpha (IFN-α) in Lactobacillus casei (Lb. casei). Reverse-transcriptase PCR verified the presence of porcine IFN-α mRNA in the recombinant Lb. casei. The porcine IFN-α protein expressed in the recombinant Lb. casei was identified by both Western blot analysis and ELISA. We used various pH values and induction times to optimize the yield of IFN-α, and found that induction with 0.8% lactose for 16 h under anaerobic conditions produced the highest concentrations of IFN-α. Furthermore, the activity of porcine IFN-α in the cultural supernatant was evaluated on ST cells infected with pseudorabies virus. The results revealed that porcine IFN-α inhibited virus replication in vitro. The findings of our study indicate that recombinant Lb. casei producing porcine IFN-α has great potential for use as a novel oral antiviral agent in animal healthcare.

  6. Use of recombinant human interferon alpha-2a in the management of a dog with epitheliotropic lymphoma.

    PubMed

    Tzannes, Sophia; Ibarrola, Patricia; Batchelor, Daniel J; Burrow, Rachel D; Blackwood, Laura

    2008-01-01

    An 8-year-old, mixed-breed dog with preputial epitheliotropic lymphoma was initially treated with cyclophosphamide, vincristine, and prednisolone. A short-term partial response was followed by disease progression after 4 weeks. Recombinant human interferon alpha-2a was administered starting at week 7. The interferon therapy resulted in rapid resolution of clinical signs and a 10-week disease-free interval. The lymphoma recurred at 17 weeks and did not respond to rescue chemotherapy. Additional oral lesions were treated with localized radiotherapy followed by increased dosages of interferon. This additional interferon treatment resulted in another 12 weeks of stable disease.

  7. 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

  8. The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

    PubMed

    Chen, P-J; Hwang, Y; Lin, C G-J; Wu, Y-J; Wu, L S-H

    2008-04-01

    Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

  9. Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.

    PubMed

    Yang, Chen; Zhao, Xinhao; Sun, Dakang; Yang, Leilei; Chong, Chang; Pan, Yu; Chi, Xiumei; Gao, Yanhang; Wang, Moli; Shi, Xiaodong; Sun, Haibo; Lv, Juan; Gao, Yuanda; Zhong, Jin; Niu, Junqi; Sun, Bing

    2016-01-01

    TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNα) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNα therapy. During the first 24 h following the initiation of IFNα treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNα-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNα treatment and plays an important role in controlling HCV replication in vitro.

  10. Ubiquitination of tissue transglutaminase is modulated by interferon alpha in human lung cancer cells.

    PubMed Central

    Esposito, Carla; Marra, Monica; Giuberti, Gaia; D'Alessandro, Anna Maria; Porta, Raffaele; Cozzolino, Anna; Caraglia, Michele; Abbruzzese, Alberto

    2003-01-01

    The addition of 2500 i.u./ml interferon alpha (IFNalpha) for 48 h induced apoptosis, and caused an approx. 4-fold increase in the activity and expression of tissue transglutaminase (tTG), in human lung cancer H1355 cells. However, the increase in mRNA levels for tTG was just 1.6-fold. On the basis of these data, we investigated whether tTG levels may be regulated through regulation of its degradation via ubiquitination. It was found that 2500 i.u./ml IFNalpha induced a time-dependent decrease in tTG ubiquitination. On the other hand, addition of the proteasome inhibitor lactacystin led to accumulation of the ubiquitinated form of the enzyme and to a consequent increase in its expression. Treatment of the cells with the two agents combined antagonized the accumulation of the ubiquitinated isoforms of tTG induced by lactacystin and caused a potentiation of tTG expression. Moreover, the tTG inducer retinoic acid was also able to cause increased expression and ubiquitination of tTG in H1355 cells. The addition of monodansylcadaverine (a tTG inhibitor) to IFNalpha-treated H1355 cells completely antagonized growth inhibition and apoptosis induced by the cytokine. In conclusion, we demonstrate for the first time that tTG is ubiquitinated and degraded by a proteasome-dependent pathway. Moreover, IFNalpha can, at least in part, induce apoptosis through the modulation of this pathway. PMID:12401132

  11. Emerging Therapies for Systemic Lupus Erythematosus - Focus on Targeting Interferon-alpha

    PubMed Central

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

    2012-01-01

    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. PMID:22525889

  12. The antiviral effect of human interferon alpha is dependent on phosphoinositide-derived messengers.

    PubMed

    Cernescu, C; Constantinescu, S N; Baltă, F; Popescu, L M

    1988-01-01

    Neomycin the putative blocker of membrane polyphosphoinositide hydrolysis, inhibited the antiviral activity of human interferon alpha, when tested on human quiescent fibroblasts challenged with vesicular stomatitis virus. The anti-interferon effect of neomycin could be correlated in terms of dose dependence for both neomycin (0.05-1 mM) and interferon (100-5,000 IU/ml). The results suggest that the antiviral activity of interferon alpha depends on diacylglycerol formation. Indeed, the synthetic diacylglycerol (50 microM) was as effective as 100 IU/ml interferon in inducing the antiviral state.

  13. 78 FR 46593 - Prospective Grant of Start-up Exclusive License: Kits for the Detection of Human Interferon-Alpha...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ...-2008/0), titled ``Compositions for Detecting Human Interferon- Alpha Subtypes and Methods of Use'', to... HUMAN SERVICES National Institutes of Health Prospective Grant of Start-up Exclusive License: Kits for the Detection of Human Interferon-Alpha Subtypes and Allotypes AGENCY: National Institutes of...

  14. EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. The EORTC Genitourinary Group.

    PubMed Central

    De Mulder, P. H.; Oosterhof, G.; Bouffioux, C.; van Oosterom, A. T.; Vermeylen, K.; Sylvester, R.

    1995-01-01

    In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded. PMID:7841054

  15. 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...

  16. Long-term efficacy and safety of interferon-alpha-2B in patients with mumps orchitis.

    PubMed

    Yapanoglu, Turgut; Kocaturk, Huseyin; Aksoy, Yilmaz; Alper, Fatih; Ozbey, Isa

    2010-12-01

    The aim of this study was to determine long-term efficacy and safety subcutaneous injection of interferon-alpha-2B in patients with mumps orchitis in terms of testicular volume and other testicular functions. Mumps orchitis was evaluated in 37 patients. Patients were hospitalized and administered 1 × 3,000,000 IU subcutaneous injection of interferon-alpha-2B daily for 7 days. The testicular volumes of all the patients were measured by ultrasonography in the 18th month following treatment termination. The testes volumes were evaluated by descriptive statistics as percentages. Patients were divided into three groups according to testes volumes and differences between the involved and non-involved testicles. Group I included patients with normal testes volume (> 12 ml) and a difference between testes of less than 2 ml or 20%; Group II (atrophic groups) included patients with testes volume of less than 12 ml; and Group III (hypotrophic groups) included patients with testes volume of greater than 12 ml and a difference between testes of more than 2 ml or 20%. Groups were compared in terms of results of semen analysis and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Patients' ages ranged between 17 and 41 years (mean: 28.3 years). A total of nine atrophy cases were identified. Sixteen patients were determined to have hypotrophic testes with a difference of 2-10 ml or 20% between the involved and non-involved testicles, despite the absence of testicular atrophy. A comparison of groups revealed that sperm density, total sperm count, total motile sperm count, and motility percentage were significantly higher in Group I than in the other groups, while serum FSH and LH levels were lower in Group I than in the other groups. Although the use of interferon-alpha-2B appears to prevent testicular atrophy and protect testicular function, it leads to a considerable difference in the volume between testicles and a significant loss of testicular

  17. Interferon alpha impairs insulin production in human beta cells via endoplasmic reticulum stress.

    PubMed

    Lombardi, Angela; Tomer, Yaron

    2017-02-23

    Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4. Intriguingly, IFNα treatment did not impair GSIS but significantly decreased insulin production in both human islets and EndoC-βH1 cells. Furthermore, IFNα decreased the expression of both proinsulin convertase 1 and proinsulin convertase 2, suggesting an altered functional state of the beta cells characterized by a slower proinsulin-insulin conversion. Pretreatment of both human islets and EndoC-βH1 cells with chemical chaperones 4-phenylbutyric acid and tauroursodeoxycholic acid completely prevented IFNα effects, indicating an ER stress-mediated impairment of insulin production. We demonstrated for the first time that IFNα elicits ER stress in human beta cells providing a novel mechanistic role for this virus-induced cytokine in the development of T1D. Compounds targeting molecular processes altered in ER-stressed beta cells could represent a potential therapeutic strategy to prevent IFNα-induced beta cell dysfunction in the early onset of T1D.

  18. Influence of carbohydrates on the stability and structure of a hyperglycosylated human interferon alpha mutein.

    PubMed

    Ceaglio, Natalia; Etcheverrigaray, Marina; Kratje, Ricardo; Oggero, Marcos

    2010-08-01

    Protein physical and chemical instability is one of the major challenges in the development of biopharmaceuticals during every step of the process, ranging from production to final delivery. This is particularly applicable to human recombinant interferon alpha-2b (rhIFN-alpha2b), a pleiotropic cytokine currently used worldwide for the treatment of various cancer and chronic viral diseases, which presents a poor stability in solution. In previous studies, we have demonstrated that the introduction of four N-glycosylation sites in order to construct a heavily glycosylated IFN variant (4N-IFN) resulted in a markedly prolonged plasma half-life which was reflected in an enhanced therapeutic activity in mice in comparison with the commercial non-glycosylated rhIFN-alpha2b (NG-IFN). Herein, we evaluated the influence of glycosylation on the in vitro stability of 4N-IFN towards different environmental conditions. Interestingly, the hyperglycosylated cytokine showed enhanced stability against thermal stress, acid pH and repetitive freeze-thawing cycles in comparison with NG-IFN. Besides, microcalorimetric analysis indicated a much higher melting temperature of 4N-IFN, also demonstrating a higher solubility of this variant as denoted by the absence of precipitation at the end of the experiment, in contrast with the NG-IFN behaviour. Furthermore, far-UV circular dichroism (CD) spectrum of 4N-IFN was virtually superimposed with that of NG-IFN, indicating that the IFN structure was not altered by the addition of carbohydrate moieties. The same conclusion could be inferred from limited proteolysis studies. Our results suggest that glycoengineering could be a useful strategy for protecting rhIFN-alpha2b from inactivation by various external factors and for overcoming aggregation problems during the production process and storage.

  19. Pegylated protein encapsulated multivesicular liposomes: a novel approach for sustained release of interferon alpha.

    PubMed

    Vyas, S P; Rawat, M; Rawat, A; Mahor, S; Gupta, P N

    2006-07-01

    Hepatitis C viral chemotherapy suffers from a relatively short half-life of the interferon alpha-2a (IFN alpha). To address this issue, we investigated the effects of polyethylene glycol modification and their subsequent encapsulation in multivesicular liposomes (MVLs), on the release properties of IFN alpha. In the present study, interferon-alpha was conjugated with methoxy-polyethylene glycol (mPEG, MW 5000). Prepared IFN alpha-mPEG5000 conjugate (IFN alpha-mPEG5000) was purified with size exclusion chromatography. The relative in vitro anti-viral activity of pegylated interferon alpha-2a was found to 87.9% of the unmodified IFN alpha. Pegylated IFN alpha encapsulated multivesicular liposomes were prepared by double emulsification technique followed by evaporation of organic solvents from chloroform ether spherules suspended in water. Prepared MVLs were then characterized for shape, size, vesicle count, encapsulation efficiency, and in vitro release rate. In process stability studies of pegylated IFN alpha protein exhibited better stability when exposed to chloroform: diethyl ether (1:1 ratio) mixture as well as variable vortexing time as compared to native IFN alpha. Relatively high percentage of encapsulation of protein ( approximately 75%) was achieved. In vitro release profile of pegylated IFN alpha-mPEG5000 containing MVLs in the PBS showed lower initial burst release with sustained and incomplete release over a period of 1 week. In contrast, native IFN alpha entrapped MVLs were observed as higher initial burst release, i.e., nearly 35% followed by almost complete release. The results confirmed the possibility of multivesicular liposomes as a long-acting or sustained-release delivery system using a combination of pegylation and encapsulation technique for controlled delivery of interferon alpha.

  20. The effects of pegylated interferon--alpha2B on mumps orchitis.

    PubMed

    Pal, Goutam

    2013-09-01

    To evaluate the effects of pegylated Interferon--alpha2B on mumps orchitis, 80 patients suffering from mumps orchitis, were randomly assigned into 2 groups of 40 patients each. In the first group patients received pegylated interferon--alpha2B and the other group did not, acting as controls. All were confirmed by mumps IgM (ELISA) and evaluated by testis size, semen analysis and hormone level. In the first group, the symptoms resolved within average 2.2 days and testicular size returned to normal within average 5.3 days but in 2nd group, those returned to normal within average 5.7 days and 10.2 days respectively. In the 1st group, oligospermia was detected in 11 patients and subsequently returned to normal in all patients and there was no testicular atrophy. In the 2nd group oligospermia was detected in 13 patients and were persistently low in 3 patients and testicular atrophy detected in 2 patients. The results indicated the beneficial role of pegylated interferon--alpha2B in preventing infertility from mumps orchitis.

  1. Definition of the interferon-alpha receptor-binding domain on the TYK2 kinase.

    PubMed

    Yan, H; Piazza, F; Krishnan, K; Pine, R; Krolewski, J J

    1998-02-13

    Interferons and cytokines modulate gene expression via a simple, direct signaling pathway containing receptors, JAK tyrosine kinases, and STAT transcription factors. The interferon-alpha pathway is a model for these cascades. Two receptors, IFNaR1 and IFNaR2, associate exclusively in a constitutive manner with two JAK proteins, TYK2 and JAK1, respectively. Defining the molecular interface between JAK proteins and their receptors is critical to understanding the signaling pathway and may contribute to the development of novel therapeutics. This report defines the IFNaR1 interaction domain on TYK2. In vitro binding studies demonstrate that the amino-terminal half of TYK2, which is approximately 600 amino acids long and contains JAK homology (JH) domains 3-7, comprises the maximal binding domain for IFNaR1. A fragment containing amino acids 171-601 (JH3-6) also binds IFNaR1, but with reduced affinity. Glutathione S-transferase-TYK2 fusion proteins approximating either the JH6 or JH3 domain affinity-precipitate IFNaR1, suggesting that these are major sites of interaction within the larger binding domain. TYK2 amino acids 1-601 act in a dominant manner to inhibit the transcription of an interferon-alpha-dependent reporter gene, presumably by displacing endogenous TYK2 from the receptor. This same fragment inhibits interferon-alpha-dependent tyrosine phosphorylation of TYK2, STAT1, and STAT2.

  2. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.

    PubMed

    Nestle, Frank O; Conrad, Curdin; Tun-Kyi, Adrian; Homey, Bernhard; Gombert, Michael; Boyman, Onur; Burg, Günter; Liu, Yong-Jun; Gilliet, Michel

    2005-07-04

    Psoriasis is one of the most common T cell-mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis.

  3. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.

  4. Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

    SciTech Connect

    Andersson, G.; Lundgren, E.; Ekre, H.P. )

    1991-02-01

    Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity.

  5. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo

    PubMed Central

    Lavender, Kerry J.; Gibbert, Kathrin; Peterson, Karin E.; Van Dis, Erik; Francois, Sandra; Woods, Tyson; Messer, Ronald J.; Gawanbacht, Ali; Müller, Janis A.; Münch, Jan; Phillips, Katie; Race, Brent; Harper, Michael S.; Guo, Kejun; Lee, Eric J.; Trilling, Mirko; Hengel, Hartmut; Piehler, Jacob; Verheyen, Jens; Wilson, Cara C.; Santiago, Mario L.

    2016-01-01

    ABSTRACT Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-α2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1 in vitro. We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-α14 subtype has very potent anti-HIV-1 activity whereas IFN-α2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-α14, but not IFN-α2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1-induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-α14 but not IFN-α2. Whereas ineffective IFN-α2 therapy was associated with CD8+ T cell activation, successful IFN-α14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL+ NK cells. These results identify IFN-α14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-α14 to reduce both viremia and proviral loads in vivo suggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-α subtype should be evaluated against the specific virus being treated. IMPORTANCE The naturally occurring antiviral protein IFN-α2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely

  6. Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.

    PubMed

    Young, A M; Marsden, J; Goodman, A; Burton, A; Dunn, J A

    2001-01-01

    Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 patients were randomized between April 1995 and April 1998. Differences in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.

  7. 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.

  8. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system.

    PubMed

    Bonaccorso, Stefania; Marino, Valentina; Puzella, Antonella; Pasquini, Massimo; Biondi, Massimo; Artini, Marco; Almerighi, Cristiana; Verkerk, Robert; Meltzer, Herbert; Maes, Michael

    2002-02-01

    There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the

  9. Reduced interferon-alpha production by Epstein-Barr virus transformed B-lymphoblastoid cell lines and lectin-stimulated lymphocytes in congenital dyserythropoietic anaemia type I.

    PubMed

    Wickramasinghe, S N; Hasan, R; Smythe, J

    1997-08-01

    The concentrations of interferon-alpha (IFN-alpha) in supernatants from cultures of Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines derived from seven patients with congenital dyserythropoietic anaemia (CDA) type I were below the 95% confidence limits for those derived from six healthy subjects. In contrast, the concentrations of IFN-alpha in supernatants from cultures of EBV-transformed lymphoblastoid cell lines derived from four patients with other types of CDA and four patients with hereditary sideroblastic anaemia were normal. Supernatants from cultures of peripheral blood lymphocytes stimulated with phytohaemagglutinin or pokeweed mitogen contained less IFN-alpha when the cells were derived from patients with CDA type I than when derived from healthy subjects. Since patients with CDA type I show a substantial haematological response to treatment with IFN-alpha, the data suggest that impaired IFN-alpha production may be an important pathogenetic mechanism in CDA type I.

  10. 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.

  11. Human leukocyte interferon-alpha in cream for the management of genital herpes in Asian women: a placebo-controlled, double-blind study.

    PubMed

    Syed, T A; Lundin, S; Cheema, K M; Kahlon, R C; Khayyami, M; Ahmad, S A; Ahmad, S H; Kahlon, B M; Kahlon, A M

    1995-03-01

    This double-blind, placebo-controlled study examined the clinical efficacy and tolerance of human leukocyte interferon-alpha (2 x 10(6) IU/g) in hydrophilic cream to cure patients afflicted with first episodes of genital herpes. Sixty patients aged 18-40 years (mean 24.5) with culture-confirmed herpes simplex genitalis, bearing 755 lesions (mean 12.6) were randomized to active and placebo groups. Patients joined the study within 7 days (mean 4.1) of the manifestation of lesions. Each patient was given a precoded 40-g tube containing placebo/active preparation with instructions on self-application of the trial medication to their lesions three times daily for 5 consecutive days (max. 15 topical applications per week). Patients were examined three times a week to evaluate clinical efficacy and other beneficial effects. A reepithelialized lesion with some residual erythema was recorded as healed. Patients resolved during the active treatment period (1-4 weeks) were spared further therapy and were requested to visit us as scheduled for posttreatment control after 16 weeks. From the remaining patients empty tubes were collected, and similarly coded replacement tubes were given to continue the treatment (in total 160 tubes were used). Patients treated with leukocyte interferon-alpha cream had significantly shorter mean duration of viral shedding/healing than placebo recipients, (6.2 days vs. 15 days; P < 0.01); thus the number of healed patients was 25/30 (83.3%) vs. 5/30 (17%; P < 0.001. Of the 60 patients 49 (81.6%) complained no drug-related side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. A quantitative assessment of depression and thyroid dysfunction secondary to interferon-alpha therapy in patients with hepatitis C.

    PubMed

    Loftis, J M; Wall, J M; Linardatos, E; Benvenga, S; Hauser, P

    2004-01-01

    The most effective treatment for hepatitis C virus (HCV) is interferon-alpha (IFN) therapy in combination with ribavirin. Although symptoms of depression are among the most common side effects of IFN therapy in treating patients with HCV, the mechanisms by which IFN produces these neuropsychiatric side effects remain unclear. In the brain, IFNs are involved in a number of regulatory functions, including but not limited to regulation of the endocrine system via the hypothalamic-pituitary-adrenal and -thyroid axes. The purpose of this study was to assess the effect of IFN therapy on thyroid function and to characterize the relationship between thyroid dysfunction and major depressive disorder during IFN therapy in patients with hepatitis C. Thirty-three patients with HCV were administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I Disorders (SCID) and completed the Beck Depression Inventory (BDI). Patients were on IFN for an average of 6 to 12 months depending on their viral genotype. Serum samples were collected at baseline, during and after IFN therapy, and measured for free thryoxine (FT4) and TSH levels. Patients who developed IFN-induced depression were treated with selective serotonin reuptake inhibitor antidepressants. Only one patient developed transient IFN-induced overt hypothyroidism, but he did not develop depression. Analysis of variance showed that there were no significant differences in either FT4 or TSH serum levels between patients who developed major depressive disorder (MDD) (no.= 10) during IFN therapy and those who did not (no.=23). These results illustrate the frequency and severity of depressive symptoms associated with IFN therapy and the apparent absence of a relationship between IFN-induced MDD and changes in thyroid function.

  13. Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study.

    PubMed Central

    Punt, C. J.; van Herpen, C. M.; Jansen, R. L.; Vreugdenhil, G.; Muller, E. W.; de Mulder, P. H.

    1997-01-01

    High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis. PMID:9231931

  14. Combination of OK432 and human interferon-alpha for treating viral-induced diabetes mellitus in mice.

    PubMed

    Kanda, T; Kogure, S; Nara, M; Tsukui, S; Utsugi, T; Tomono, S; Kawazu, S; Nagai, R; Kobayashi, I

    1998-01-26

    We investigated the therapeutic effects of OK432 (picibanil; CAS39325-1-4), an immunomodulator that is derived from the Su strain of Streptococcus pyogenes. This agent was administered alone or combined with human interferon-alpha in a murine model of insulin-dependent diabetes mellitus. Interferon-alpha inhibits viral replication, reducing the incidence of virus-induced IDDM. Groups of DBA/2 mice (N = 25 per group) received an intraperitoneal injection of OK432 and interferon-alpha daily for 16 d beginning 1 d after inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). The dose of OK432 was one clinical unit (corresponding to 0.1 mg dried cells) per mouse, and that of interferon-alpha was 1 x 10(4) u/g. The animals were killed at random at 3 or 7 d after inoculation with EMCV. The survival rate of mice treated with the combination of OK432 and with interferon-alpha was significantly greater than that of the non-treated infected control animals (P < 0.01). Fasting levels of blood glucose were significantly lower in the mice administered the combination, than in the controls, both on day 3 (68 +/- 21 mg/dl vs. 270 +/- 135 mg/dl, P < 0.01) and on day 7 (101 +/- 29 mg/dl vs. 219 +/- 112 mg/dl, P < 0.01). Serum levels of insulin were significantly higher in the treated mice than in the controls (65 +/- 5 vs. 55 +/- 1 microU/ml, P < 0.05). However, in the mice treated with OK432 or interferon-alpha alone, the survival rate and the blood level of glucose and insulin did not differ from those of infected controls. Natural killer (NK) cell activity was significantly higher in the mice treated with the drug combination than in the controls on both days evaluated: day 3, 65 +/- 5 vs. 55 +/- 1%, n = 3, P < 0.05; day 7, 44 +/- 3 vs. 22 +/- 8%, n = 3, P < 0.05). Serum levels of murine interferon in the treated mice exceeded those in controls on both days evaluated (day 3, 671 U/ml vs. 442 U/ml; day 7, 57 U/ml vs. 43 U/ml). There were no significant

  15. Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells

    PubMed Central

    Eguchi, K.; Kawakami, A.; Nakashima, M.; Ida, H.; Sakito, S.; Matsuoka, N.; Terada, K.; Sakai, M.; Kawabe, Y.; Fukuda, T.; Ishimaru, T.; Kurouji, K.; Fujita, N.; Aoyagi, T.; Maeda, K.; Nagataki, S.

    1992-01-01

    We investigated whether interferon-gamma (IFN-γ), interferon-alpha (IFN-α) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-γ (rIFN-γ), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-α and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-α and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-γ, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-γ. These results suggest that IFN-α and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells. PMID:1606729

  16. 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

  17. Expression of biologically active human interferon alpha 2 in Aloe vera.

    PubMed

    Lowther, William; Lorick, Kevin; Lawrence, Susan D; Yeow, Wen-Shuz

    2012-12-01

    Methods necessary for the successful transformation and regeneration of Aloe vera were developed and used to express the human protein, interferon alpha 2 (IFNα2). IFNα2 is a secreted cytokine that plays a vital role in regulating the cellular response to viral infection. Transgenic plants were regenerated from callus cultures initiated from zygotic embryos. Expression of the IFNA2 transgene in transformed plants was confirmed by RT-PCR and IFNα2 protein was detected by immunoblot analysis. Human A549 cells treated with transgenic aloe extracts for 6 h induced expression of the interferon stimulated gene 54, indicating activation of the IFN signaling pathway. The biological activity of the aloe produced IFNα2 was assessed using an antiviral assay with A549 cells treated with extracts from both the rind and pulp fractions of the shoot and subsequently infected with the lytic encephalomyocarditis virus. The highest level of activity attributable to recombinant IFNα2 was determined to be 625 IU/mg of total soluble protein (TSP) in the rind and 2,108 IU/mg TSP in the pulp. Two daughter plants that vegetatively budded during the course of this study were also confirmed to express IFNα2. These results confirm that Aloe vera is capable of expressing a human protein with biological activity, and that a secreted protein targeting the apoplast can be detected in the pulp fraction of the plant.

  18. 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

  19. 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.

  20. Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.

    PubMed

    Chakrabarti, D; Huang, X; Beck, J; Henrich, J; McFarland, N; James, R F; Stewart, T A

    1996-10-01

    The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

  1. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus.

    PubMed

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo

    2014-10-01

    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  2. 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.

  3. 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

  4. Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-alpha.

    PubMed

    Hung, W C; Chuang, L Y

    1999-05-01

    Although interferon-alpha (IFN-alpha) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-alpha by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-alpha in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-alpha-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21WAF-1, and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-alpha in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer.

  5. Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice

    PubMed Central

    1991-01-01

    Antigens and infectious agents that stimulate interferon alpha(IFN- alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN- alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells. PMID:1940796

  6. 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

  7. T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.

    PubMed

    Arizcorreta, A; Márquez, M; Fernández-Gutiérrez, C; Guzmán, E Pérez; Brun, F; Rodríguez-Iglesias, M; Girón-González, J A

    2006-11-01

    Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a

  8. 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

  9. 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.

  10. Knowledge and stigma regarding methadone maintenance treatment among personnel of methadone maintenance treatment and non-methadone maintenance treatment addiction facilities in Israel.

    PubMed

    Shidlansik, Lia; Adelson, Miriam; Peles, Einat

    2017-01-01

    Stigma attached to methadone maintenance treatment is very common. The objective of the current article is to evaluate the presence of stigma and its relation to the extent of knowledge about methadone maintenance treatment. The authors conducted a survey among methadone maintenance treatment and non-methadone maintenance treatment addiction therapists from different treatment centers in Israel, including methadone maintenance treatment clinics (Ministry of Health) and non-methadone maintenance treatment addiction facilities (Ministry of Social Services), using an anonymous questionnaire about methadone maintenance treatment stigma and knowledge. There were 63 therapists from methadone maintenance treatment clinics (63%) and 46 therapists from the social services department (SSD) non-methadone maintenance treatment addiction facilities (9.2%) who responded. Methadone maintenance treatment versus social services department personnel were older (42.7 ± 12.8 versus 37.5 ± 8.2 years; p = 0.03), with fewer females (48 versus 75%; p = 0.006), and 50% were social workers compared to 100% social workers in the SSD group (p < 0.0005). Stigma score was lower among methadone maintenance treatment personnel compared to the social services department personnel (3 ± 2.5 versus 5.0 ± 3.5; p = 0.0001), while the knowledge score about methadone maintenance treatment was higher among the methadone maintenance treatment personnel (10.3 ± 2.9 versus 7.7 ± 2.8; p < 0.0005). The difference in both the stigma and knowledge scores remained significant after controlling for age, gender, and profession. There was a negative correlation between the stigma and knowledge scores among both the methadone maintenance treatment (R = -0.5, p < 0.0005) and the social services department personnel (R = -0.33, p = 0.03). These results revealed a significant correlation between the presence of stigma and the extent of education and knowledge about methadone maintenance treatment, with ignorance

  11. [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.

  12. Emergence of occult minority genotype 2b hepatitis C infection in an HIV-1-co-infected patient treated for genotype 5a HCV infection with 48 weeks of pegylated-interferon-alpha 2b and ribavirin.

    PubMed

    Buckton, A J; Kulasegaram, R; Ngui, S L; Fisher, M; James, R; Rangarajan, S; Teo, C G

    2007-09-01

    An HIV-1/hepatitis C virus (HCV) co-infected patient with haemophilia received a 48-week course of pegylated interferon-alpha-2b and ribavirin therapy for genotype 5a HCV infection. Virological response was achieved at week 24. At the end of treatment, HCV RNA in serum was detected and identified to belong to genotype 2b, rather than genotype 5a. A sensitive method for identifying minority HCV genotypes in pre-treatment serum showed genotype 2b HCV carriage prior to treatment. Sequencing the interferon sensitivity-determining region of the HCV NS5A gene obtained from pre-, intra- and post-treatment sera revealed emergence of quasispecies bearing R-->K and M-->A/T mutations at codons 2222 and 2223, respectively. Occult presence of minority HCV subpopulations and their acquisition of mutations following therapy can result in poor treatment outcome.

  13. 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.

  14. NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

    PubMed Central

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

    2016-01-01

    A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+ CD107+ NK cells. In addition, the increase in NKp30+ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy. PMID:27941937

  15. A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans.

    PubMed

    Schiller, J H; Hank, J; Storer, B; Borchert, A A; Moore, K H; Albertini, M; Bechhofer, R; Wesley, O; Brown, R R; Bastin, A M

    1993-03-15

    Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression

  16. 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.,...

  17. MULTIPLEX PCR ASSAY FOR DETECTION OF HUMAN SOMATOTROPIN AND INTERFERON ALPHA2b GENES IN PLANT MATERIAL.

    PubMed

    Gerasymenko, I M; Mazur, M G; Sheludko, Y V; Kuchuk, N V

    2015-01-01

    Using transgenic plants as factories for production of physiologically active human proteins arouses special concern because occasional escape of such transgenes into environment may cause health problems. Creation of plant varieties producing pharmaceutically valuable proteins should be accompanied by development of detection methods suitable for controlling the transgene behavior. Here we describe a multiplex PCR protocol for revealing of two human genes (encoding growth hormone and interferon alpha2b) that have been successfully introduced into plant genomes. The primer pair designed for detection of human growth hormone coding sequence amplifies fragments of different size from the full-length gene in the human genome and the intronless coding sequence usually used for plant transformation. Application of this primer pair may be recommended for ruling out false positive results due to sample contamination with human DNA. Such a control may be useful also in PCR analysis during establishing of transgenic plants carrying genes of human origin.

  18. Effectiveness of maintenance treatments for nonsmall cell lung cancer

    PubMed Central

    Eadens, Matthew J; Robinson, Steven I; Price, Katharine AR

    2011-01-01

    Maintenance therapy for advanced nonsmall cell lung cancer has shown some clinical benefit for patients by improving progression-free survival and, to a lesser extent, overall survival. Two main strategies exist for maintenance therapy, ie, continuation and switch maintenance. Continuation maintenance involves the continued use of one of the induction drugs beyond 4–6 cycles of initial treatment. Switch maintenance utilizes a third agent initiated after first-line chemotherapy. Both cytotoxic agents and targeted agents have been studied. Switch maintenance therapy with pemetrexed in nonsquamous tumors and erlotinib appear to show the most clear clinical benefit. Continuation maintenance with bevacizumab has shown improvement in progression-free survival. Data concerning the role of cetuximab for maintenance is conflicting. Toxicity, quality of life, and cost are important confounding issues that need to be considered. Several ongoing Phase III trials are investigating strategies to improve on the current agents as well as testing promising new therapies. PMID:28210116

  19. CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs.

    PubMed

    Shiow, Lawrence R; Rosen, David B; Brdicková, Nadezda; Xu, Ying; An, Jinping; Lanier, Lewis L; Cyster, Jason G; Matloubian, Mehrdad

    2006-03-23

    Naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. During immune responses, the egress process can be shut down transiently. When this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. Several mediators of the innate immune system are known to cause shutdown, including interferon alpha/beta (IFN-alpha/beta) and tumour necrosis factor, but the mechanism has been unclear. Here we show that treatment with the IFN-alpha/beta inducer polyinosine polycytidylic acid (hereafter 'poly(I:C)') inhibited egress by a mechanism that was partly lymphocyte-intrinsic. The transmembrane C-type lectin CD69 was rapidly induced and CD69-/- cells were poorly retained in lymphoid tissues after treatment with poly(I:C) or infection with lymphocytic choriomeningitis virus. Lymphocyte egress requires sphingosine 1-phosphate receptor-1 (S1P1), and IFN-alpha/beta was found to inhibit lymphocyte responsiveness to S1P. By contrast, CD69-/- cells retained S1P1 function after exposure to IFN-alpha/beta. In coexpression experiments, CD69 inhibited S1P1 chemotactic function and led to downmodulation of S1P1. In a reporter assay, S1P1 crosslinking led to co-crosslinking and activation of a CD69-CD3zeta chimaera. CD69 co-immunoprecipitated with S1P1 but not the related receptor, S1P3. These observations indicate that CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-alpha/beta, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs.

  20. Evaluation of the effects of omega-3 & interferon alpha-2b administration on partial bladder outlet obstruction in a rat model

    PubMed Central

    Firat, Fatih; Uluocak, Nihat; Erdemir, Fikret; Atilgan, Dogan; Markoc, Fatma; Parlaktas, Bekir Suha; Yasar, Adem

    2016-01-01

    Background & objectives: In bladder outlet obstruction-induced rat models, the transforming growth factor-beta (TGF-β) and collagen ratios have been shown to be increased. Increased TGF-β leads to fibrosis. In this study, the effect of omega-3 and interferon alpha-2b (IFN α-2b) was investigated on oxidative stress, inflammation and fibrosis in bladder structure in a partial bladder outlet obstruction (PBOO) rat model. Methods: A total of 35 male Wistar albino rats, weighing 300-350 g, were used in the study. The rats were randomly divided into five groups. At the end of the experimental period, bladders were harvested from all the rats, and pathological analysis of the rat bladder tissues was performed. In addition, investigations were carried out with enzymatic and non-enzymatic antioxidant systems to study the antioxidant properties of omega-3 fatty acid and IFN alpha-2b. Results: Increased bladder weight in the PBOO group, in comparison to the control group, was decreased by the administration of omega-3 and IFN α-2b (P=0.002). Significantly higher superoxide dismutase (SOD) levels were detected in group 2 in comparison to the control group. It was also detected that serum SOD, glutathione peroxidase and nitric oxide (NO) levels were significantly higher in group 2 when compared to the control group (P<0.05). In the pathologic evaluation, group 2 showed significantly increased inflammation and fibrosis compared to the control group. Omega-3 treatment significantly decreased inflammation. It was shown that IFN α-2b application partially decreased inflammation. Interpretation & conclusions: The results of the present study showed that in addition to the standard primary approaches to prevent the damage to the upper urinary tract secondary to PBOO, omega-3 fatty acid and IFN α-2b could be beneficial as adjunct treatment in clinical practice. However, this needs to be further investigated with prospective, randomized clinical trials with larger sample sizes

  1. Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha.

    PubMed

    Quiroga, J A; Martin, J; Pardo, M; Carreño, V

    1994-11-01

    To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.

  2. Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells

    PubMed Central

    Tsaur, Igor; Hudak, Lukasz; Makarević, Jasmina; Juengel, Eva; Mani, Jens; Borgmann, Hendrik; Gust, Kilian M; Schilling, David; Bartsch, Georg; Nelson, Karen; Haferkamp, Axel; Blaheta, Roman A

    2015-01-01

    A significant proportion of men diagnosed with prostate cancer (PCa) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid (VPA), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (IFNα) on PCa cell growth and dissemination capacity were investigated. For that purpose, the human PCa cell lines, PC-3, DU-145 and LNCaP were treated with the combined regimen or separate single agents. Cell growth was investigated by the MTT dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin α and β subtypes were investigated by flow cytometry, western blotting and RT-PCR. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal-regulated kinases (ERK)1/2 activation were also assessed. The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients. PMID:25808196

  3. 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

  4. [Management of opioid maintenance treatments when analgesic treatments are required].

    PubMed

    Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund

    2013-01-01

    Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient.

  5. Chitosan oligomers as potential and safe absorption enhancers for improving the pulmonary absorption of interferon-alpha in rats.

    PubMed

    Yamada, Keigo; Odomi, Masaaki; Okada, Naoki; Fujita, Takuya; Yamamoto, Akira

    2005-11-01

    Effects of chitosan oligomers on pulmonary absorption of interferon-alpha (IFN) were examined by means of an in vivo pulmonary absorption experiment. Chitosan oligomers used in this study were chitosan dimer, tetramer, hexamer, and water-soluble (WS) chitosan. A significant increase in serum IFN concentrations was observed after intratracheal administration of IFN with these oligomers. Of these chitosan oligomers, 0.5% w/v chitosan hexamer appeared to be more effective in enhancing the pulmonary absorption of IFN than other oligomers at the same concentration, and the AUC value of IFN with chitosan hexamer increased 2.6-fold as compared with the control. On the other hand, chitosan polymers, which have relatively high molecular weights (22-96 kDa), were not effective in enhancing the pulmonary absorption of IFN due to their low solubility in water. Additionally, the effect of different concentrations (0.1%-1% w/v) of chitosan hexamer on the pulmonary absorption of IFN was studied. Of these different concentrations of chitosan hexamers, the highest AUC value of IFN was obtained in the presence of 0.5% w/v chitosan hexamer. Furthermore, chitosan oligomers did not cause any membrane damage to the rat pulmonary tissues, as determined by leakage of protein and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid. Therefore, these findings indicated that the use of chitosan oligomers would be a promising approach for improving of the pulmonary absorption of biologically active peptides including IFN.

  6. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    PubMed

    McCormick, C; Freshney, R I; Speirs, V

    1995-02-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  7. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    PubMed Central

    McCormick, C.; Freshney, R. I.; Speirs, V.

    1995-01-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified. PMID:7841035

  8. 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.

  9. Refolding of recombinant human interferon alpha-2a from Escherichia coli by urea gradient size exclusion chromatography.

    PubMed

    Gao, F; Shi, L; Xu, L X

    2013-01-01

    Protein refolding is still a puzzle in the production of recombinant proteins expressed as inclusion bodies (IBs) in Escherichia coli. Gradient size exclusion chromatography (SEC) is a recently developed method for refolding of recombinant proteins in IBs. In this study, we used a decreasing urea gradient SEC for the refolding of recombinant human interferon alpha-2a (rhLFNalpha-2a) which was overexpressed as IBs in E. coli. In chromatographic process, the denatured rhLFNalpha-2a would pass along the 8.0-3.0 M urea gradient and refold gradually. Several operating conditions, such as final concentration of urea along the column, gradient length, the ratio of reduced to oxidized glutathione and flow rate were investigated, respectively. Under the optimum conditions, 1.2 x 10(8) IU/mg of specific activity and 82% mass recovery were obtained from the loaded 10 ml of 1.75 mg/ml denatured protein, and rhLFNalpha-2a was also purified during this process with the purity of higher than 92%. Compared with dilution method, urea gradient SEC was more efficient for the rhl FNalpha-2a refolding in terms of specific activity and mass recovery.

  10. Effect of recombinant human interferon-alpha A/D on in vivo murine tumor cell growth.

    PubMed

    Uno, K; Shimizu, S; Inaba, K; Kitaura, M; Nakahira, K; Kato, T; Yamaguchi, Y; Muramatsu, S

    1988-05-01

    We investigated the effect of human recombinant interferon-alpha A/D A/D-IFN), which is known to delay the growth of murine tumor cells, on the growth of S1 and R1 subline cells of murine Meth A fibrosarcoma in the peritoneal cavity of mice. In vitro growth of S1 cells was sensitive to, and that of R1 cells was resistant to, the direct effect of A/D-IFN, as with murine natural IFN-alpha/beta, which was used originally to isolate these sublines. In vivo, however, the growth of not only S1 cells but also R1 cells was suppressed by the administration of A/D-IFN, and the survival time of tumor-bearing mice was prolonged. Although A/D-IFN had a direct effect on S1 cells in vivo, R1 cells were susceptible only to the indirect effect via the host cells. Macrophages (M phi) harvested from the peritoneal cavity of A/D-IFN-treated mice bearing ascitic R1 cells were very effective in suppressing the in vitro growth of R1 cells; those from non-R1-bearing A/D-IFN-treated mice were less effective. The results of in vitro experiments indicate that M phi are very probably activated by the synergism of A/D-IFN and M phi diameter-activating factor(s) produced by lymphoid cells in tumor-bearing mice.

  11. Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas.

    PubMed Central

    Singh, R K; Gutman, M; Bucana, C D; Sanchez, R; Llansa, N; Fidler, I J

    1995-01-01

    We investigated the influence of interferons alpha, beta, and gamma (IFN-alpha, -beta, and -gamma) on the production of basic fibroblast growth factor (bFGF) by human renal carcinoma cells. The human renal carcinoma cell metastatic line SN12PM6 was established in culture from a lung metastasis and SN12PM6-resistant cells were selected in vitro for resistance to the antiproliferative effects of IFN-alpha or IFN-beta. IFN-alpha and IFN-beta, but not IFN-gamma, down-regulated the expression of bFGF at the mRNA and protein levels by a mechanism independent of their antiproliferative effects. Down-regulation of bFGF required a long exposure (> 4 days) of cells to low concentrations (> 10 units/ml) of IFN-alpha or IFN-beta. The withdrawal of IFN-alpha or IFN-beta from the medium permitted SN12PM6-resistant cells to resume production of bFGF. The incubation of human bladder, prostate, colon, and breast carcinoma cells with noncytostatic concentrations of IFN-alpha or IFN-beta also produced down-regulation of bFGF production. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7753843

  12. Interferon-alpha-induced destructive thyroiditis followed by Graves' disease in a patient with chronic hepatitis C: a case report.

    PubMed

    Kim, Bu Kyung; Choi, Young Sik; Park, Yo Han; Lee, Sang Uk

    2011-12-01

    Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-α) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-α therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-α (pegIFN-α) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-α and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-α therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-α therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-α therapy and remained weakly positive after IFN-α therapy was discontinued.

  13. Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction.

    PubMed

    Law, Anna Hing-Yee; Lee, Davy Chun-Wai; Yuen, Kwok-Yung; Peiris, Malik; Lau, Allan Sik-Yin

    2010-07-01

    Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-alpha expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.

  14. Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

    PubMed

    Mangiarotti, P; Moulin, F; Palmer, P; Ravilly, S; Raymond, J; Gendrel, D

    1999-06-01

    The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

  15. 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.

  16. [Influence of small doses human interferon-alpha intranasal injection on behavior of rats of different age].

    PubMed

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

    2007-01-01

    Behavior of young (3-4 month old) and ageing (12-15 month old) rats was studied during chronic intranasal application of low doses (10 ME or 350 ME) of human interferon-alpha (HIA). In ageing rats HIA did not affect dynamics (days 0th, 8th and 16th) of (a) locomotive and (b) investigative activity in the "open field" test and in two-side defensive conditioning, and (c) decreased anxiety ("open field", "light-darkness" test). In young rats HIA (a) increased locomotive activity by 16th day (it decreased in control), (b) investigative activity did not change (in control it decreased by 8th day; "open field" test), (c) anxiety decreased in the "open field" and increased in "light-darkness" tests, (d) development of conditioned reflex improved (during 2nd learning session in 5 days after the first one). Thus, small doses of HIA differently affected behavior of rats depending on the age and experimental situation. However, both HIA doses changed rats' behavior in the same direction. We suggest that chronic low doses of HIA can regulate different aspects of behavior, but not suppress activity as it is commonly thought. This regulation can be performed via modulation of neuro-immuno-endocrine complex.

  17. Use of interferon-alpha in laryngeal papillomatosis: eight years of the Cuban national programme.

    PubMed

    Deuñas, L; Alcantud, V; Alvarez, F; Arteaga, J; Benítez, A; Bopuza, M; Carniege, L; Cartaya, B; Comas, C; Cotayo, R; Escobar, H; Fernández, H; Fernández, M; Fernández, R; García, M; Iznaga, N; la O, F; Márquez, J; Nordet, D; Pérez, J; Quintero, J; Redonavich, A; Robeleco, M; Rodríguez, H; Strander, H

    1997-02-01

    Laryngeal papillomatosis is one of the first diseases where interferon (IFN) was found to be effective. In 1983, a programme for the treatment of all such cases started in Cuba. Up to December 1991, 125 patients (92 children, 33 adults) have been treated: 102 with leucocyte IFN-alpha, 12 with recombinant IFN-alpha-2b, and 11 have received both preparations. Case management consisted of surgical removal of the lesions followed by an IFN schedule starting with 10(5) IU/kg of weight in children or 6 x 10(6) IU in adults, i.m. daily. The dose was progressively reduced, as long as no relapses occurred. At the end of the one-year schedule the doses were reduced to 5 x 10(4) IU/kg in children or 3 x 10(6) IU in adults, weekly. If there was a relapse, it was removed surgically and the patient returned to a higher dose level. Most cases (89; 71 per cent) have not relapsed after the treatment; 60 of them have been followed for more than three years. In those with relapses, the frequency of recurrence decreased in all but four patients. The treatment seemed to be more effective if initiated less than three months after the disease onset. The tracheostomy could be removed in five out of seven patients who needed it before the IFN treatment and was necessary in only three new cases during IFN treatment. In two of these, decannulation was possible later on. In a total of 14 patients relapses persisted after several cycles of IFN treatment. They were considered resistant to such treatment. No severe side effects were reported. The most frequent ones were fever, drowsiness, increased bronchial secretion, chills and headache. The establishment of this programme has maintained the disease under control in Cuba.

  18. 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)

  19. Tolerability and activity of a new recombinant interferon-alpha B/D hybrid in patients with HIV-1 infection.

    PubMed

    Frissen, P H; Brinkman, K; Ten Napel, C H; van der Ende, I M; van Buuren, I A; Boucher, C A; Reiss, P; Lange, J M

    1996-04-01

    The maximum tolerated dose (MTD) and toxicity profile of a new recombinant interferon-alpha B/D hybrid (IFN-alpha B/D) in HlV-1-infected patients were determined in an outpatient, dose-escalating study with dose groups of three patients: 16, 32, 48, 64, 96 and 112 million international units (MIU) three times weekly subcutaneously during 12 weeks. The MTD was the last dose level just below the dose level at which more than one patient experienced > or = grade 3 toxicity. The study also searched for preliminary evidence of efficacy of IFN-alpha B/D. Sixteen HIV-1-infected patients with CD4 cell counts > or = 200/mm3 were enrolled: eight were asymptomatic and eight had symptomatic disease. Two patients were excluded as a result of protocol violations. Five patients (36 per cent; one at each tested dose level) discontinued prematurely due to side effects. One patient was lost to follow-up. Twelve patients (87 per cent) experienced > or = grade 2 toxicity. Toxicity > or = grade 3 occurred in none of three patients assigned to 16 MIU, one of five assigned to 32 MIU (fatigue), one of three assigned to 48 MIU (haemorrhagic colitis) and two of three assigned to 64 MIU (fatigue). One patient (48 MIU) had reversible cardiomegaly. Progressive weight loss was experienced by 12 of 14 participants. Serum HIV-1 p24 antigen declined in nine of 11 antigenaemic patients (seven persistently > 50 per cent) without a clear dose-response relationship. CD4 percentages showed no consistent pattern and T cell reactivity diminished. The tolerability and toxicity profile of IFN-alpha B/D appear to be fairly similar to that of other types of IFN-alpha.

  20. Mass spectrometric characterization of the isoforms in Escherichia coli recombinant DNA-derived interferon alpha-2b.

    PubMed

    Liu, Yan-Hui; Wylie, David; Zhao, Jia; Cure, Raymond; Cutler, Collette; Cannon-Carlson, Susan; Yang, Xiaoyu; Nagabhushan, Tattanahalli L; Pramanik, Birendra N

    2011-01-01

    The isoforms Iso-2, Iso-3, and Iso-4 of Escherichia coli-derived recombinant human interferon alpha-2b (rhIFN α-2b), generated by posttranslational modifications of the protein during fermentation, present a major problem in terms of purification and the yield of the drug substance. We report here the structural characterization of these isoforms by mass spectrometry (MS) methods. An extensive MS study was conducted on Iso-4, which is composed of up to 75% of the in-process IFN, and on the native rhIFN α-2b. The trypsin-digested peptide mixtures generated from the two samples were analyzed by liquid chromatography (LC)-MS, and targeted peptides were further studied by LC-tandem MS (triple quadrupole mass spectrometer), high-resolution MS(n) (LTQ Orbitrap), and matrix-assisted laser desorption/ionization MS (MALDI-MS). The structure of Iso-4 was elucidated as a novel pyruvic acid ketimine derivative of the N-terminal cysteine (Cys1) of IFN α-2b, where the disulfide bond between Cys1 and Cys98 was fully reduced and the other disulfide bond pair, Cys29-ss-Cys138, was partially reduced. Similarly, Iso-2 was identified as a correctly disulfide-folded rhIFN α-2b with acetylation on Cys1, and Iso-3 was identified as an S-glutathionylated form (Cys98) of partially reduced rhIFN α-2b that was pyruvated on Cys1. Based on the characterization work, a reproducible conversion procedure was successfully implemented to convert Iso-4 to rhIFN α-2b.

  1. Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.

    PubMed

    Czimmer, Jozsef; Király, Ágnes; Szabó, Imre Laszlo; Mózsik, Gyula; Sütő, Gabor

    2013-01-01

    Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

  2. [Interferon-alpha toxicity and reversible bilateral optical neuropathy: a timely withdrawal of the drug].

    PubMed

    Pérez-Carro, G; Fernández-Alonso, R; González-Diéguez, M L; Rodríguez-García, M; Junceda-Moreno, J

    2014-04-01

    Clinical case A patient with chronic, painless, bilateral loss of vision, after significant intake of interferon (IFNα) and ribavirina due to liver transplant. Ocular fundus is normal. A suspected retrobulbar optic neuropathy is confirmed by a prolongation of the latency of the patient's visual evoked potential. There being no prior record of risk factors and with the patient's systemic analysis giving normal results, the clinical improvement and the electro-physiological tests conducted after the drug was withdrawn point to interferon as negatively affecting the bilateral optic nerve. Discussion Interferon-α is used in the treatment of viral and neoplastic illnesses. Currently the drug is formulated as Interferon alfa pegilado (IFNα-p) in order to reduce toxicity and increase tolerance. The most common secondary effects are flu symptoms, asthenia and weigh loss. Affected ocular tissue is rare and optic neuropathy is also an infrequent complication: retinopathy at the beginning of treatment is, however, more frequent. The most widely accepted hypothesis as to the cause of toxicity is the presence of circulating immune complexes. It is, therefore, essential for ophthalmologists to be aware of the toxicity of this drug in order to be able to withdraw it in good time, thus preventing potentially irreversible sight loss.

  3. KIR2DS2 as predictor of thrombocytopenia secondary to pegylated interferon-alpha therapy.

    PubMed

    Rivero-Juarez, A; Gonzalez, R; Frias, M; Manzanares-Martín, B; Rodriguez-Cano, D; Perez-Camacho, I; Gordon, A; Cuenca, F; Camacho, A; Pineda, J A; Peña, J; Rivero, A

    2016-03-15

    Our aim was to evaluate the killer cell immunoglobulin-like receptors (KIRs) as a marker for the development of thrombocytopenia secondary to Peg-interferon (IFN) therapy in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. Patients were naive to HCV treatment, receiving a first course of Peg-IFN/Ribavirin combination therapy. Total platelet count (cells ml(-1)) was determined at each visit, determining platelet decline from baseline to weeks 1, 2, 4, 8 and 12 after starting therapy. The end point of the study was development of thrombocytopenia, defined as a platelet count of <1 50 000 cells ml(-1). Fifty-eight HIV/HCV co-infected patients were included in the study, of whom 20 (34.4%) developed thrombocytopenia. The absence of KIR2DS2 was associated with higher and faster rate of thrombocytopenia (54.2% vs 22.5%; P=0.012; 6.6 vs 10.3 weeks; P=0.008). The absence of KIR2DS2 was associated with a greater decline in platelet count and development of thrombocytopenia during Peg-IFN treatment in HIV/HCV co-infected patients.The Pharmacogenomics Journal advance online publication, 15 March 2016; doi:10.1038/tpj.2016.19.

  4. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

  5. Effects of pegylated interferon alpha-2a on hepatitis-C-virus-associated glomerulonephritis.

    PubMed

    Sugiura, Tokio; Yamada, Takuji; Kimpara, Yuri; Fujita, Naoya; Goto, Kenji; Koyama, Norihisa

    2009-01-01

    Hepatitis C virus (HCV) infection leads to chronic liver disease, but it has also been associated with extrahepatic manifestations. Membranoproliferative glomerulonephritis (MPGN) is the most common renal disease associated with HCV. Although renal disease related to HCV in adults has been well studied, it has not been well studied in children because it is rare. A recent study found that antiviral therapy was effective for adult patients with HCV-associated MPGN. We report a 9-year-old girl with HCV-associated MPGN. Her HCV genotype was 1b, and her virus load was high. The first renal biopsy showed mesangial proliferation and partial double contours of the basement membrane on light microscopy and immunofluorescence staining with immunoglobulin (Ig) M, IgG, and C3. The patient was successfully treated with pegylated interferon (IFN) alpha-2a monotherapy. The antiviral therapy was generally well tolerated. After antiviral therapy, a sustained virological response-defined as negative HCV ribonucleic acid (RNA) at least 24 weeks after antiviral treatment-was achieved, the proteinuria disappeared, and the second renal biopsy showed improvement.

  6. Interferons alpha and gamma induce p53-dependent and p53-independent apoptosis, respectively.

    PubMed

    Porta, Chiara; Hadj-Slimane, Reda; Nejmeddine, Mohamed; Pampin, Mathieu; Tovey, Michael G; Espert, Lucile; Alvarez, Sandra; Chelbi-Alix, Mounira K

    2005-01-20

    Type I interferon (IFN) enhances the transcription of the tumor suppressor gene p53. To elucidate the molecular mechanism mediating IFN-induced apoptosis, we analysed programmed cell death in response to type I (IFNalpha) or type II (IFNgamma) treatment in relation to p53 status. In two cell lines (MCF-7, SKNSH), IFNalpha, but not IFNgamma, enhanced apoptosis in a p53-dependent manner. Furthermore, only IFNalpha upregulated p53 as well as p53 target genes (Noxa, Mdm2 and CD95). The apoptotic response to IFNalpha decreased in the presence of ZB4, an anti-CD95 antibody, suggesting that CD95 is involved in this process. When p53 was inactivated by the E6 viral protein or the expression of a p53 mutant, IFNalpha-induced apoptosis and p53 target genes upregulation were abrogated. Altogether these results demonstrate that p53 plays a pivotal role in the IFNalpha-induced apoptotic response. IFNalpha-induced PML was unable to recruit p53 into nuclear bodies and its downregulation by siRNA did not alter CD95 expression. In contrast, IFNgamma-induced apoptosis is p53-independent. CD95 and IFN-regulatory factor 1 (IRF1) are directly upregulated by this cytokine. Apoptotic response to IFNgamma is decreased in the presence of ZB4 and strongly diminished by IRF1 siRNA, implicating both CD95 and IRF1 in IFNgamma-induced apoptotic response. Taken together, these results show that in two different cell lines, IFNalpha and IFNgamma, induce p53-dependent -independent apoptosis, respectively.

  7. Compliance with maintenance treatment in bipolar disorder.

    PubMed

    Keck, P E; McElroy, S L; Strakowski, S M; Bourne, M L; West, S A

    1997-01-01

    Studies of compliance with pharmacologic treatment in patients with bipolar disorder have primarily involved outpatients receiving lithium. To date, very little data addresses the rates of noncompliance in patients with bipolar disorder treated with other available mood stabilizers (e.g. divalproex, carbamazepine). One hundred and forty patients initially hospitalized for a bipolar disorder, manic or mixed episode, were evaluated prospectively over 1 year to assess their compliance with pharmacotherapy. Compliance was assessed by a clinician-administered questionnaire, using information from the patient, treaters, and significant others. Seventy-one patients (51%) were partially or totally noncompliant with pharmacologic treatment during the 1-year followup period. Noncompliance was significantly associated with the presence of a comorbid substance use disorder. Denial of need was the most common reason cited for noncompliance. Compliance was associated with being male and Caucasian and with treatment with combined lithium and divalproex or with this combination and an antipsychotic. Noncompliance with pharmacotherapy remains a substantial problem in the treatment of patients with bipolar disorder.

  8. The biological properties, assay, and standardization of interferon-alpha: a need for a WHO collaborative study.

    PubMed

    Mire-Sluis, A R; Gaines Das, R; Zoon, K; Padilla, A; Thorpe, R; Meager, A

    1996-08-01

    Interferon-alpha (IFN-alpha) exists as a range of closely related, biologically active proteins and has been the subject of extensive research and clinical investigation. Standardization of IFN-alpha and the uniform reporting of IFN-alpha activity in International Units (IU) is critical to preclinical research and the clinical development of IFN-alpha products as therapeutic agents. Currently, several different IFN-alpha-containing reference preparations, established as World Health Organization (WHO) International Standards (IS) for particular IFN-alpha proteins (mixtures or single molecular species) are available for assay calibration. Nevertheless, the heterogeneous nature of IFN-alpha has raised standardization issues relating to the activity of individual IFN-alpha proteins, hence-forth termed subtypes, in the various biologic assays used for determining IFN-alpha levels. These issues include the question of parallelism of dose-response curves among particular IFN-alpha subtypes and different, naturally produced IFN-alpha subtype mixtures, for example, leukocyte IFN-alpha, and the applicability of IU of IFN-alpha activity defined by antiviral assays to alternative biologic assays, for example, antiproliferative assays. To address such issues, a WHO Consultative Group on Cytokine Standardization requested that the National Institute for Biological Standards and Control (NIBSC) and the Centre for Biologics Evaluation and Research (CBER) organize an international collaborative study to compare the activities and relative potencies of the several available IFN-alpha preparations, including those derived from human cells containing mixtures of IFN-alpha subtypes and those derived by rDNA methods containing single IFN-alpha subtypes, in different assays. To date, 111 participants in 32 countries have been recruited to the study and have agreed to assay a total of 17 different natural and recombinant IFN-alpha preparations or a defined subset thereof in specific in

  9. 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…

  10. [Effects of human and rat interferons-alpha on the behavior of rats of different ages. Comparative study of the homology of amino acid sequences].

    PubMed

    Loseva, E V; Loginova, N A; Nekliudov, V V; Mats, V N; Kurskaia, O V; Pasikova, N V

    2009-01-01

    Effects of chronic intranasal administration of human and rat interferons alpha on feeding and defensive behavior of rats were studied. Natural leukocyte human interferon "Lokferon" (a mixture of alpha interferon subtypes) and recombinant rat interferon alpha of the first subtype were used in the dose of 350 ME per rat daily. In addition, using the databases NCBI and EBI, we quantitatively estimated homology of amino-acid sequences between different subtypes of human and rat interferons. Both human (mostly in young rats) and rat interferons (mostly in old rats) increased rat feeding behavior after food conditioning to an audio tone. In old (but not in young) rats, both human and rat interferons worsened the ability of time interval assessment. In young (but not old) rats, both interferon kinds improved avoidance conditioning. The degree of homology between different human and rat interferons varied from 72% to 77%. Thus, generally, the effects of rat and human alpha interferons (350 ME) on rat conditioning were similar. This may be due to high degree of homology of amino-acid sequences between the two interferons.

  11. Interferon-alpha preserves erythrocyte and hepatocyte ATPase activities from liver damage induced by prolonged bile duct ligation in the rat.

    PubMed

    Muriel, P

    1995-01-01

    Interferons have been used to treat chronic hepatitis owing to their antiviral properties. However, now interferons are recognized to inhibit collagen production. Because fibrosis has been associated with liver damage and dysfunction, the effects of interferon-alpha 2b on biliary obstruction-induced cirrhosis were investigated. Obstructive jaundice was induced in male Wistar rats (ca. 200 g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-alpha 2b (IFN-alpha; 1000 000 IU per rat) was administered subcutaneously daily after surgery. The animals were sacrificed after 4 weeks of bile duct ligation (BDL) or sham operation. Bilirubins and serum enzyme activities of alkaline phosphatase and gamma-glutamyl transpeptidase (determined as markers of liver damage) increased several-fold after BDL. Erythrocyte and hepatocyte plasma membrane Na+/K+- and Ca2+-ATPase activities decreased significantly in the BDL group. Administration of IFN-alpha to BDL rats resulted in a partial normalization of serum markers of liver damage. The normal activity of both ATPases on erythrocyte and hepatocyte plasma membranes was completely preserved by IFN-alpha. It is concluded that interferons possess interesting hepatoprotective effects not related to their antiviral properties but probably associated with their antifibrogenic effect.

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

    PubMed

    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.

  13. Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2'-5' oligoadenylate synthetase in peritoneal macrophages.

    PubMed Central

    Gresser, I; Vignaux, F; Belardelli, F; Tovey, M G; Maunoury, M T

    1985-01-01

    Injection of conventional or axenic weanling mice with potent sheep or goat antibody to mouse interferon alpha/beta resulted in a decrease in the basal level of 2-5A synthetase in resting peritoneal macrophages and rendered these cells permissive for vesicular stomatitis virus. There was a good inverse correlation between the level of 2-5A synthetase in peritoneal macrophages and the permissivity of these cells for vesicular stomatitis virus. The peritoneal macrophages of 1- and 2-week-old mice had low levels of 2-5A synthetase and were permissive for vesicular stomatitis virus, whereas at 3 weeks (and after) there was a marked increase in the level of 2-5A synthetase in peritoneal macrophages, and these cells were no longer permissive for vesicular stomatitis virus. We suggest that low levels of interferon alpha or beta or both are produced in normal mice, and that this interferon contributes to host defense by inducing and maintaining an antiviral state in some cells. PMID:2981340

  14. 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

  15. The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin.

    PubMed

    Glas, J; Török, H P; Simperl, C; König, A; Martin, K; Schmidt, F; Schaefer, M; Schiemann, U; Folwaczny, C

    2003-07-01

    Unlike in HIV, homozygosity for a 32-bp deletion (Delta 32) of the chemokine receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C (HCV). Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. The present study sought to confirm the association between HCV and the Delta 32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-alpha-2a and ribavirin. Sixty-two patients with HCV and 119 healthy unrelated controls were genotyped for the Delta 32 mutation. For the correlation between the Delta 32 mutation and response to therapy, only patients (n = 59) who completed 6 months of combination therapy as part of a prospective study were evaluated. The Delta 32 mutation was not observed in increased frequency in HCV. Furthermore, a significant difference of the HCV load or aminotransferase concentrations was not observed in carriers versus noncarriers of the Delta 32 mutation. After stratification for potentially confounding factors such as gender or HCV genotype, a significant difference was also not detected with respect to treatment outcome. These observations argue strongly against a role of CCR5 for susceptibility to HCV infection or response to combination therapy.

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... detoxification and maintenance treatment programs. 2.34 Section 2.34 Public Health PUBLIC HEALTH SERVICE... detoxification and maintenance treatment programs. (a) Definitions. For purposes of this section: Central... information about individuals applying for maintenance treatment or detoxification treatment for the...

  17. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  18. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  19. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  20. Multifocal papillomavirus epithelial hyperplasia: successful treatment with CO2 laser therapy combined with interferon alpha-2b.

    PubMed

    Akyol, Aynur; Anadolu, Rana; Anadolu, Yücel; Ekmekci, Pelin; Gürgey, Erbak; Akay, Nisa

    2003-09-01

    Human papilloma virus (HPV) infections of the oral mucosa presents with various clinical and histopathologic features in relation with the causative HPV type and chronicity and the extent of the infection.1 The entity is known by several names based on histopathologic variations such as focal epithelial hyperplasia, oral florid papillomatosis, verrucous hyperplasia, oral florid verrucosis, and Ackerman's tumor. In recent years, the term multifocal papillomavirus epithelial hyperplasia (MPVEH) has been proposed to define the variant that usually occurs in childhood and is characterized by diffuse confluent papillomatous lesions in the oral mucosa.1 Despite the lesions' benign appearance, early diagnosis and therapy of MPVEH is essential because of its high capacity for progression and its tendency for malign degeneration.

  1. 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.

  2. [Obtaining of ScFv-CBD fusion protein and its application for affinity purification of recombinant human interferon alpha2b].

    PubMed

    Hil'chuk, P V; Okuniev, O V; Pavlova, M V; Irodov, D M; Horbatiuk, O B

    2006-01-01

    The gene of ScFv-CBD-fusion protein has been designed using the DNA sequences encoding of single-chain antibody (ScFv) against human interferon alpha2b (IFN-alpha2b) and cellulose-binding domain (CBD) from Clostridium thermocellum cellulosome. Biosynthesis of ScFv-CBD utilizing high-productive Escherichia coli system was carried out and the accumulation of target protein in bacterial inclusion bodies was shown. After the purification of the inclusion bodies and their subsequent in vitro refolding the soluble ScFv-CBD-fusion protein was directly immobilized on cellulose by bioaffinity coupling. The possibility to obtain the preparative quantities of ScFv-CBD in biologically-active form using different refolding schemes was accurately investigated in the paper. The general applicability of biologically immobilized ScFv-CBD-fusion proteins for affinity purification of recombinant IFN-alpha2b is shown.

  3. Concomitant Interferon Alpha Stimulation and TLR3 Activation Induces Neuronal Expression of Depression-Related Genes That Are Elevated in the Brain of Suicidal Persons

    PubMed Central

    Trippler, Martin; Lutterbeck, Melanie; Liu, Zijian J.; Truebner, Kurt; Bajanowski, Thomas; Gerken, Guido; Hermann, Dirk M.; Schlaak, Joerg F.

    2013-01-01

    We have previously identified 15 genes that are associated with the development of severe depressive side effects during the standard therapy with interferon alpha and ribavirin in the peripheral blood of hepatitis C virus infected patients. An enhanced expression of these genes was also found in the blood of psychiatric patients suffering severe depressive episode. Herein, we demonstrate that the same depression-related interferon-inducible genes (DRIIs) are also upregulated in post-mortem brains of suicidal individuals. Using cultured mouse hippocampal and prefrontal neurons we show that costimulation with murine IFN (mIFN) and the TLR3 agonist poly(I:C) promotes the expression of the described DRIIs, at the same time inducing pro-inflammatory cytokine expression through Stat1 and Stat3 activation, promoting neuronal apoptosis. Consequently, the upregulation of selective DRIIs, production of inflammatory cytokines and inhibition of neuronal plasticity may be involved in the pathogenesis of IFN-associated depression. PMID:24391741

  4. A serial ¹⁸FDG-PET study of a patient with SSPE who had good prognosis by combination therapy with interferon alpha and ribavirin.

    PubMed

    Ohya, Takashi; Yamashita, Yushiro; Shibuya, Ikuhiko; Hara, Munetsugu; Nagamitsu, Shinichiro; Kaida, Hayato; Kurata, Seiji; Ishibashi, Masatoshi; Matsuishi, Toyojiro

    2014-07-01

    We describe a 15-year-old girl with subacute sclerosing panencephalitis (SSPE) in stage II who was treated with isoprinosine, intraventricular interferon alpha (IFN-α), and ribavirin for 3 years. She is alive at three years from onset and studies at school with the assistance of a special educational teacher. To assess residual brain function, serial (18)FDG-positron emission tomography (PET) was performed three times to measure cortical metabolism: at onset, a year later, and three years later. At onset, PET study revealed preserved glucose metabolism of the cerebral cortex. In serial PET study, glucose metabolism of the cerebral cortex was also preserved even after three years. Although SSPE is a progressive disease of the neuronal system, and typically leads to death in approximately 2-3 years, the neurological prognosis of our case was good. We consider that combination therapy in the very early stage without hypometabolism in the cerebral cortex may be effective for SSPE.

  5. Cure of mice with established metastatic friend leukemia cell tumors by a combined therapy with tumor cells expressing both interferon-alpha 1 and herpes simplex thymidine kinase followed by ganciclovir.

    PubMed

    Santodonato, L; Ferrantini, M; Gabriele, L; Proietti, E; Venditti, M; Musiani, P; Modesti, A; Modica, A; Lupton, S D; Belardelli, F

    1996-01-01

    Transduction of the murine interferon-alpha (IFN-alpha) gene into various malignant mouse tumor cells has resulted in the loss of tumorigenicity and an acquired capacity to induce long-lasting antitumor immunity following their injection into immunocompetent syngeneic mice. In the present study, we investigated the effectiveness of IFN-alpha-producing tumor cells in the therapy of mice with established mouse tumors. In DBA/2 mice bearing subcutaneous (s.c.) Friend erythroleukemia cell (FLC) tumors, we found that to achieve some antitumor response (i) it was necessary to inject high numbers of IFN-alpha-producing FLC, which occasionally lead to the formation of slowly growing tumors; and, that (ii) repeated injections of irradiated IFN-alpha-FLC did not result in any antitumor effect. The therapeutic potential of IFN-alpha-producing FLC rendered sensitive to ganciclovir (GCV), by transfer of the herpes simplex virus thymidine kinase (tk) gene, was investigated. Complete tumor rejection and cure was observed in > or = 70% of the animals after injection of high numbers (10(7)) of IFN-alpha-producing tk-expressing tumor cells followed 4 days later by repeated GCV treatments, whereas only a slight increase in survival time was obtained after administration of control tk-expressing tumor cells (not producing IFN) and GCV. Tumor rejection was associated with a dramatic destruction of tumor tissue and with the subsequent development of a potent and long-lasting antitumor immunity. No therapeutic effect was observed in immunosuppressed nude mice. These data indicate that this approach may represent an effective and safe therapeutic strategy for antitumor cytokine gene therapy.

  6. Optimising pharmacological maintenance treatment for COPD in primary care.

    PubMed

    Jones, Rupert; Østrem, Anders

    2011-03-01

    Chronic obstructive pulmonary disease (COPD) is a multi-faceted disease that is a major cause of morbidity and mortality worldwide, and is a significant burden in terms of healthcare resource utilisation and cost. Despite the availability of national and international guidelines, and effective, well-tolerated pharmacological treatments, COPD remains substantially under-diagnosed and under-treated within primary care. As COPD is both preventable and treatable there is an urgent need to raise the awareness and profile of the disease among primary care physicians and patients. Increasing evidence suggests that initiation of long-acting bronchodilator treatment at an early stage can significantly improve the patient's long-term health and quality of life (QoL). Recent large-scale trials in COPD have confirmed the longterm benefits of maintenance treatment with long-acting bronchodilators. A wide range of benefits have been shown in selected patient groups including improved lung function and QoL, reduced exacerbations and, in some studies, delayed disease progression and improved survival. In this review, we consider recent developments in our understanding of COPD, including current and emerging pharmacological treatment options, and identify steps for optimising early diagnosis and pharmacological treatment of COPD within the primary care environment.

  7. Association between gene variants and response to buprenorphine maintenance treatment.

    PubMed

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

    2014-01-30

    A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and

  8. 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

  9. Pain Among High-Risk Patients on Methadone Maintenance Treatment.

    PubMed

    Voon, Pauline; Hayashi, Kanna; Milloy, M-J; Nguyen, Paul; Wood, Evan; Montaner, Julio; Kerr, Thomas

    2015-09-01

    The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches.

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. 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.

  13. Efficient production of canine interferon-alpha in silkworm Bombyx mori by use of a BmNPV/Bac-to-Bac expression system.

    PubMed

    Na, Zhao; Huipeng, Yao; Lipan, Lan; Cuiping, Cao; Umashankar, M L; Xingmeng, Lu; Xiaofeng, Wu; Bing, Wang; Weizheng, Cui; Cenis, J L

    2008-02-01

    We exploited the silkworm Bombyx mori for the production of recombinant canine interferon-alpha (CaIFN-alpha). The recombinant baculovirus harboring canine interferon gene was rapidly generated by the BmNPV/Bac-to-Bac system that was recently developed. In B. mori-derived cell lines, the expression of the recombinant protein reached maximal levels around 72-96 h post-infection. For the isolation of the expressed recombinant protein from B. mori larvae, the whole bodies of the infected larvae were homogenized, and the expressed protein was purified by affinity chromatography. Based on the fact that the recombinant CaIFN-alpha showed two bands on the sodium dodecyl sulfate polyacrylamide gel electrophoresis pattern, the expressed protein was thought to be glycosylated. The rCaIFN-alpha yield was about 528 microg per larva, showing that the expression in silkworm was successful. Furthermore, the recombinant protein was proven to be able to inhibit the infection of Madin-Darby canine kidney cells by the vesicular stomatitis virus, indicating that it is biologically active in vitro. The method established in this study provides an efficient way to produce a large amount of CaIFN-alpha and paves the way for further utilization of this protein as a therapeutic agent or vaccine adjuvant in dogs.

  14. In situ precipitation and vacuum drying of interferon alpha-2a: development of a single-step process for obtaining dry, stable protein formulation.

    PubMed

    Kumar, Vineet; Sharma, Vikas K; Kalonia, Devendra S

    2009-01-21

    Feasibility studies were performed to develop a process for obtaining stable dry protein formulations based on in situ polyethylene glycol (PEG)-induced precipitation and vacuum drying of interferon alpha-2a (IFNalpha2a) solution in a vial. Using a laboratory scale freeze dryer, the process was carried out in two phases: first, protein solution containing PEG was concentrated to achieve protein precipitation, and second, remaining water was removed by further reducing the chamber pressure. Drying conditions, i.e. temperature and pressure, and solution composition were selected to ensure maximal precipitation (solubility of IFNalpha2a), to achieve precipitation without boiling, and to ensure stability. Dried formulations were subjected to stability studies (40 degrees C). Concentration and precipitation could be achieved at a fast rate by utilizing pressures slightly above the vapor pressure of water. Fluorescence and circular dichroism (CD) studies showed that precipitated IFNalpha2a maintained its native structure. Fourier transform infrared spectroscopy (FTIR) studies showed that IFNalpha2a when dried in the presence of trehalose, maintained its secondary structure. Trehalose also prevented formation of aggregates during drying. Moisture contents of 1% (w/w) were achieved within 48 h of drying. Dry formulation containing 1:20:100 (w/w) IFNalpha2a:trehalose:mannitol was stable against aggregation and oxidation (6% oxidized at 40 degrees C, 6 months). Stability profile was comparable to a similar lyophilized formulation.

  15. Influence of bovine serum albumin on the secondary structure of interferon alpha 2b as determined by far UV circular dichroism spectropolarimetry.

    PubMed

    Johnston, Michael J W; Nemr, Kayla; Hefford, Mary A

    2010-03-01

    Many therapeutic biologics are formulated with excipients, including the protein excipient human serum albumin (HSA), to increase stability and prevent protein aggregation and adsorption onto glass vials. One biologic formulated with albumin is interferon alpha-2b (IFN alpha-2b). As is the case with other therapeutic biologics, the increased structural complexity of IFN alpha-2b compared to a small molecule drug requires that both the correct chemical structure (amino acid sequence) and also the correct secondary and tertiary structures (3 dimensional fold) be verified to assure safety and efficacy. Although numerous techniques are available to assess a biologic's primary, secondary and tertiary structures, difficulties arise when assessing higher order structure in the presence of protein excipients. In these studies far UV circular dichroism spectropolarimetry (far UV-CD) was used to determine the secondary structure of IFN alpha-2b in the presence of a protein excipient (bovine serum albumin, BSA). We demonstrated that the secondary structure of IFN alpha-2b remains mostly unchanged at a variety of BSA to IFN alpha-2b protein ratios. A significant difference in alpha helix and beta sheet content was noted when the BSA to IFN alpha-2b ratio was 5:1 (w/w), suggesting a potential conformational change in IFN alpha-2b secondary structure when BSA is in molar excess.

  16. 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.

  17. 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.

  18. 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.

  19. 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…

  20. The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms.

    PubMed

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads; Kjær, Lasse; Stauffer Larsen, Thomas; Bjerrum, Ole Weis; Kruse, Torben A; Hasselbalch, Hans Carl

    2017-08-01

    Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients.

  1. 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.

  2. Methadone Maintenance: Some Treatment Programs are Not Effective; Greater Federal Oversight Needed

    DTIC Science & Technology

    1990-03-01

    Mr. Chairman: In response to your request, we reviewed the activities of a number of methadone maintenance treatment programs. This report focuses on...the (1) extent of drug use by patients in methadone maintenance treatment programs; (2) the goals, objectives, and approaches of the treatment...treatment programs and the status of proposed regulations to allow methadone to be dispensed without counseling or other supportive services that are

  3. Interferon-resistant Daudi cells are deficient in interferon-alpha-induced ISGF3 alpha activation, but remain sensitive to the interferon-alpha-induced increase in ISGF3 gamma content.

    PubMed

    Dron, M; Tovey, M G

    1993-10-01

    Low levels of the transcription factor ISGF3 alpha were detected in the cytoplasm and nucleus of untreated Daudi cells, which increased markedly following interferon (IFN) treatment. In contrast no ISGF3 alpha was detected in an IFN-resistant clone of Daudi cells, DIF8, and only low levels were detected in these cells after IFN-alpha treatment. High levels of ISGF3 were produced in vitro, however, by the addition of ISGF3 alpha to extracts of IFN-treated DIF8 cells, indicating that IFN is unable to produce substantial amounts of functional ISGF3 alpha in DIF8 cells. A second clone of IFN-resistant Daudi cells, DIF3, also exhibited defective ISGF3 alpha production, which was restored to normal in the subclone DIF3REV5 that had reverted to high IFN sensitivity. Thus, the antiproliferative effect of IFN on Daudi cells and derived clones is closely related to the level of ISGF3 present in the nucleus of these cells. IFN-alpha, however, also enhances the content of ISGF3 gamma in IFN-resistant cells as well as certain proteins of unknown function, raising the possibility that a second pathway of IFN-alpha signal transduction, distinct from the ISGF3 pathway, remains functional in both DIF8 and DIF3 cells.

  4. Preparation of bioactive interferon alpha-loaded polysaccharide nanoparticles using a new approach of temperature-induced water phase/water-phase emulsion.

    PubMed

    Liu, Guang; Xu, Dong; Jiang, Mier; Yuan, Weien

    2012-01-01

    The aim of this study was to develop a temperature-induced polyethylene glycol (PEG) water phase/polysaccharide water-phase emulsion approach for preparing interferon alpha-2b (IFNα-2b)-loaded polysaccharide nanoparticles. IFNα-2b was first added to a mixture of an aqueous solution of PEG and polysaccharide. The mixture solution was stirred in a magnetic stirrer at a rate of 2000 rpm for 45 seconds at 0°C ± 0.5°C. The solution was then prefrozen at different temperatures. The polysaccharide and IFNα-2b partitioned in the polysaccharide phase were preferentially separated out as the dispersed phase from the mixture solution during the prefreezing process. Then the prefrozen sample was freeze-dried to powder form. In order to remove the PEG, the powder was washed with dichloromethane. Once IFNα-2b was loaded into the polysaccharide nanoparticles, these nanoparticles could gain resistance to vapor-water and water-oil interfaces to protect IFNα-2b. The antiviral activity of the polysaccharide nanoparticles in vitro was highly preserved (above 97%), while the antiviral activity of IFNα-2b-loaded polysaccharide nanoparticles using the control water-in-oil-in-water method was only 71%. The antiviral activity of the IFNα-2b from blood samples was also determined on the basis of the activity to inhibit the cytopathic effects of the Sindbis virus on Follicular Lymphoma cells (FL). The antiviral activity in vivo was also highly preserved (above 97%). These polysaccharide nanoparticles could be processed to different formulations according to clinical requirements.

  5. A strategy for high-level expression of soluble and functional human interferon alpha as a GST-fusion protein in E. coli.

    PubMed

    Rabhi-Essafi, Imen; Sadok, Amine; Khalaf, Noureddine; Fathallah, Dahmani M

    2007-05-01

    Escherichia coli is the most extensively used host for the production of recombinant proteins. However, most of the eukaryotic proteins are typically obtained as insoluble, misfolded inclusion bodies that need solubilization and refolding. To achieve high-level expression of soluble recombinant human interferon alpha (rhIFNalpha) in E. coli, we have first constructed a recombinant expression plasmid (pGEX-hIFNalpha2b), in which we merged the hIFNalpha2b cDNA with the glutathione S-transferase (GST) coding sequence downstream of the tac-inducible promoter. Using this plasmid, we have achieved 70% expression of soluble rhIFNalpha2b as a GST fusion protein using E. coli BL21 strain, under optimized environmental factors such as culture growth temperature and inducer (IPTG) concentration. However, release of the IFN moiety from the fusion protein by thrombin digestion was not optimal. Therefore, we have engineered the expression cassette to optimize the amino acid sequence at the GST-IFN junction and to introduce E. coli preferred codon within the thrombin cleavage site. We have used the engineered plasmid (pGEX-Delta-hIFNalpha2b) and the modified E. coli trxB(-)/gor(-) (Origami) strain to overcome the problem of removing the GST moiety while expressing soluble rhIFNalpha2b. Our results show the production of soluble and functional rhIFNalpha2b at a yield of 100 mg/l, without optimization of any step of the process. The specific biological activity of the purified soluble rhIFNalpha2b was equal to 2.0 x 10(8) IU/mg when compared with the WHO IFNalpha standard. Our data are the first to show that high yield production of soluble and functional rhIFNalpha2b tagged with GST can be achieved in E. coli.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22762137

  7. Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in institutionalized elderly individuals.

    PubMed

    Launay, Odile; Grabar, Sophie; Bloch, Frédéric; Desaint, Corinne; Jegou, David; Lallemand, Christophe; Erickson, Robert; Lebon, Pierre; Tovey, Michael G

    2008-07-29

    A randomized double-blind placebo-controlled study was conducted to determine the effect of sublingual administration of IFNalpha on the immune response to influenza vaccination in elderly institutionalized individuals. Sublingual administration of 10 million IU of IFNalpha immediately prior to vaccination, reduced the geometric mean haemagglutination inhibitory (HAI) and IgG2 circulating antibody titers, and the secretory IgA (sIgA) response in saliva, to the New York strain of influenza A virus, 21 days post-vaccination, without detectable drug-related local or systemic toxicity. IFN treatment did not inhibit the immune response to the other components of the vaccine; the New Caledonia strain of influenza A virus, or the Jiangsu strain of influenza B virus. At the dose tested sublingual administration of IFNalpha reduces the immune response to influenza vaccination in elderly institutionalized individuals.

  8. Exploiting hepatitis C virus activation of NFkappaB to deliver HCV-responsive expression of interferons alpha and gamma.

    PubMed

    Matskevich, A A; Strayer, D S

    2003-10-01

    Chronic infection with hepatitis C virus (HCV) may lead to liver failure and hepatocellular carcinoma. Current treatment for HCV includes high systemic doses of interferonalpha (IFNalpha), which is effective in less than half of patients and may have severe side effects. We designed conditional IFNalpha and IFNgamma expression constructs to be triggered by HCV-induced activation of NFkappaB, and delivered these using highly efficient recombinant Tag-deleted SV40-derived vectors. NFkappaB activates the HIV-1NL4-3 long terminal repeat (HIVLTR) as a promoter, which accounts for the conditional transgene expression. Human hepatocyte lines and primary rat hepatocytes (PRH) were transduced with SV[HIVLTR](IFN) vectors, and transfected with HCV cDNA. Production of human and murine IFNalpha and IFNgamma in cytosol and culture supernatants was measured. HCV activated the HIVLTR to produce and secrete IFNs, and did so largely through the NFkappaB binding sites of the HIVLTR. Levels of IFNs secreted, and the magnitude of induction in response to HCV, were greater in hepatocyte lines than in primary cultured hepatocytes. However, even in the latter, supernatant IFNalpha concentrations achieved by this approach were similar to therapeutic serum concentrations sought in systemic IFNalpha-treated patients. In coculture studies, secreted IFNalpha activated its cognate response elements in untransduced cells, suggesting that its potential inhibitory effects on HCV may not be limited to transduced cells. Although HCV replication in culture is difficult to assess, HCV-induced IFNalpha production demonstrably reduced HCV transcription. Conditional expression of IFNs within the liver may represent an attractive approach to therapy of severe chronic HCV infection that could avoid the side effects of systemic treatment regimens.

  9. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in cancer patients receiving radiotherapy

    PubMed Central

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

    2015-01-01

    This research aimed to find out the impact of ionizing radiations on the hIFNα-2b gene of radiotherapy treated cancer patients. The gene hIFNα-2b synthesizes a protein which is an important anticancerous and antiviral protein. The cancer patients (breast, lung, thyroid, oral and prostate) who were undergoing a radiotherapy treatment were selected. A molecular analysis was performed for DNA isolation and gene amplification through PCR, to identify gene mutations. Further, by bioinformatics tools we concluded that how mutations identified in gene sequences have led to the alterations in the hINFα-2b protein in radiotherapy receiving cancer patients. The 32% mutations in the hINFα-2b gene were identified and all were frameshift mutations. Radiotherapy can impact the immune system and cancer patients may modulate their immunity. Understaning the mechanisms of radiotherapy-elicited immune response may be helpful in the development of those therapeutic interventions that can enhance the efficacy of radiotherapy. PMID:26396921

  10. Weight-based dosing of pegylated interferon-alpha in chronic hepatitis C: just a marketing 'gag'?

    PubMed

    Ferenci, P

    2003-09-01

    Today medical-scientific data are diluted by the marketing strategies of the biomedical industry making it difficult for practising physicians to decide what is correct or wrong. One typical example is the use of pegylated interferons for treatment of chronic hepatititis C. In this report the arguments pro and contra weight-based dosing are critically discussed. The factors contributing to success or failure to eradicate the virus are manifold, and include the sensitivity of the virus to interferon, viral genotype, age, gender stage of fibrosis, presence or absense of steatosis. Weight by itself plays just a minor role. The impact of weight-based dosing in general is overestimated and certainly not needed when 40 kD branched PEG-IFNalpha2a with a restricted volume of distribution is used. Whether weight-based dosing of 12 kD linear PEG-IFNalpha2b provides any benefit over a flat dose of the drug remains to be studied.

  11. Successful interferon-alpha 2b therapy for unremitting warts in a patient with DOCK8 deficiency.

    PubMed

    Al-Zahrani, Daifulah; Raddadi, Ali; Massaad, Michel; Keles, Sevgi; Jabara, Haifa H; Chatila, Talal A; Geha, Raif

    2014-07-01

    The autosomal recessive form of the Hyper IgE syndrome (AR-HIES) with dedicator of cytokinesis 8 (DOCK8) deficiency is associated with difficult to treat persistent viral skin infections, including papilloma virus infection. Type I interferons play an important role in the defense against viruses. We examined the effect of therapy with IFN-α 2b in an 11-year old boy with DOCK8 deficiency due to a homozygous splice donor site mutation in DOCK8 intron 40. His unremitting warts showed dramatic response to IFN-α 2b therapy. Immunological studies revealed decreased circulating plasmacytoid dendritic cells (pDCs) and profound deficiency of IFN-α production by his peripheral blood mononuclear cells in response to treatment with CpG oligonucleotides. These findings indicate that underlying pDC deficiency and impaired IFN-α production may predispose to chronic viral infections in DOCK8 deficiency. IFN-α 2b therapy maybe useful in controlling recalcitrant viral infections in these patients.

  12. 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

  13. Cognitive-Behavioral Analysis System of Psychotherapy as a Maintenance Treatment for Chronic Depression

    ERIC Educational Resources Information Center

    Klein, Daniel N.; Santiago, Neil J.; Vivian, Dina; Blalock, Janice A.; Kocsis, James H.; Markowitz, John C.; McCullough, James P., Jr.; Rush, John A.; Trivedi, Madhukar H.; Arnow, Bruce A.; Dunner, David L.; Manber, Rachel; Rothbaum, Barbara; Thase, Michael E.; Keitner, Gabor I.; Miller, Ivan W.; Keller, Martin B.

    2004-01-01

    Although the efficacy of maintenance pharmacotherapy for the prevention of recurrence in major depressive disorder (MDD) is well documented, few studies have tested the efficacy of psychotherapy as a maintenance treatment. The authors examined the efficacy of the cognitive-behavioral analysis system of psychotherapy (CBASP) as a maintenance…

  14. 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

  15. Maintenance hormonal and chemotherapy treatment in metastatic breast cancer: a systematic review.

    PubMed

    Rossi, Sabrina; Schinzari, Giovanni; Basso, Michele; Strippoli, Antonia; Dadduzio, Vincenzo; D'Argento, Ettore; Cassano, Alessandra; Barone, Carlo

    2016-05-01

    Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression-free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine.

  16. Clinical outcome of combined immunotherapy with interferon-alpha and low-dose interleukine-2 for Japanese patients with metastatic renal cell carcinoma.

    PubMed

    Miyake, Hideaki; Kurahashi, Toshifumi; Takenaka, Atsushi; Inoue, Taka-aki; Fujisawa, Masato

    2009-01-01

    The objective of this study was to retrospectively investigate clinical outcomes of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) in Japanese patients with metastatic renal cell carcinoma (RCC). This study included a total of 52 patients with metastatic RCC who were treated by combined immunotherapy with IFN-alpha and low-dose IL-2 following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (5 to 6 million U/d) three times per week and intravenous injection of IL-2 (1.4 million U/d) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. In this series, complete response and partial response were achieved in 1 and 11 patients, respectively; however, the remaining 20 and 20 patients were diagnosed as showing stable disease and progressive disease, respectively. Of several parameters examined, presence of metastases at diagnosis and C-reactive protein (CRP) level were significantly associated with response to this combined therapy. The 1-, 3-, and 5-year cancer-specific survival rates of these 52 patients were 80.4%, 51.7%, and 38.8%, respectively. Furthermore, cancer-specific survival was significantly associated with performance status, presence of metastases at diagnosis, metastatic organ and CRP level on univariate analysis; however, only performance status and presence of metastases at diagnosis appeared to be independent predictors of cancer-specific death by multivariate analysis. Toxicities related to this therapy were generally mild and tolerable, limited to World Health Organization (WHO) grade 1 or 2 in the majority of patients. Collectively, these findings suggest that combined immunotherapy with IFN-alpha and low-dose IL-2 could achieve comparatively acceptable oncological outcomes in patients with metastatic RCC; however, other therapeutic options

  17. 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

  18. 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…

  19. 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…

  20. Role of Maintenance Rituximab (Rituxan) Therapy In the Treatment of Follicular Lymphoma

    PubMed Central

    Fowler, Nathan H.

    2011-01-01

    Although follicular lymphoma remains incurable, recent advances in first-line therapy have resulted in improved response rates and response duration. Maintenance therapy with rituximab (Rituxan) after induction treatment with rituximab alone or chemotherapy in combination with or without rituximab has resulted in further improvement in progression-free survival in both treatment-naive and previously treated patients. Efficacy results from the large phase 3, randomized Primary Rituximab and Maintenance (PRIMA) trial in the first-line setting have dem onstrated significant improvements in progression-free survival, in the rate of patients achieving complete remission, and in the proportion of patients remaining in complete remission using maintenance rituximab. The use of maintenance therapy is also under study in additional hematological malignancies, including diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Clinical investigation is ongoing to address the optimal duration of maintenance therapy and the question of whether re-treatment upon disease progression is as beneficial as maintenance for follicular lymphoma. PMID:22346327

  1. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... narcotic drug in decreasing doses to an individual in order to reduce or eliminate adverse physiological or psychological effects incident to withdrawal from the sustained use of a narcotic drug. (3) Maintenance treatment means the dispensing of a narcotic drug in the treatment of an individual for dependence...

  2. 38 CFR 1.478 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... narcotic drug in decreasing doses to an individual in order to reduce or eliminate adverse physiological or psychological effects incident to withdrawal from the sustained use of a narcotic drug. (3) Maintenance treatment means the dispensing of a narcotic drug in the treatment of an individual for dependence...

  3. 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…

  4. 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)

  5. Comparison of Behavioral Treatment Conditions in Buprenorphine Maintenance

    PubMed Central

    Ling, Walter; Hillhouse, Maureen; Ang, Alfonso; Jenkins, Jessica; Fahey, Jacqueline

    2013-01-01

    Background and aims The Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid-dependent individuals with buprenorphine; however no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of 4 behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence. Design After a 2-week buprenorphine induction/stabilization phase, participants were randomized to 1 of 4 behavioral treatment conditions provided for 16 weeks: Cognitive Behavioral Therapy (CBT=53); Contingency Management (CM=49); both CBT and CM (CBT+CM=49); and no additional behavioral treatment (NT=51). Setting Study activities occurred at an outpatient clinical research center in Los Angeles, California, USA. Participants Included were 202 male and female opioid-dependent participants. Measurements Primary outcome was opioid use, measured as a proportion of opioid-negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use, and adverse events. Findings No group differences in opioid use were found for the behavioral treatment phase (Chi-square=1.25, p=0.75), for a second medication-only treatment phase, or at weeks 40 and 52 follow-ups. Analyses revealed no differences across groups for any secondary outcome. Conclusion There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiates users seeking treatment. PMID:23734858

  6. Adherence to Buprenorphine Maintenance Treatment in Opioid Dependence Syndrome: A Case Control Study

    PubMed Central

    Bandawar, Mrunal; Kandasamy, Arun; Chand, Prabhat; Murthy, Pratima; Benegal, Vivek

    2015-01-01

    Background: Opioid Use disorders are emerging as a serious public health concern in India. Opioid substitution treatment is one of the emerging forms of treatment in this population which needs more evidence to increase its availability and address prejudices towards the same. Materials and Methods: This is a case control study with retrospective design reviewing the charts of patients with opioid dependence syndrome registered between January 2005 to December 2012. Adherence to treatment was the outcome variable assessed in this study. Results: The odds of the Buprenorphine Maintenance Treatment (BMT) group remaining in treatment is 4.5 (P < 0.005) times more than Naltrexone Maintenance Treatment (NMT) group and 7 times (P < 0.001) more than Psychosocial intervention (PST) alone group. Discussion: We believe that these study findings will help in reducing the prejudice towards BMT and encourage further research in this field. Conclusion: BMT has a better adherence rate than other treatments in opioid use disorders. PMID:26664083

  7. A retrospective study to compare improvement of implant maintenance by Medical Treatment Model

    PubMed Central

    Maruo, Katsuichiro; Singh, Kamleshwar; Shibata, Sadahiko; Sugiura, Go; Kumagai, Takashi; Tamaki, Katsushi; Jain, Jyoti

    2016-01-01

    Background: Study comparing the improvement of implant maintenance is limited. Clinicians must be aware of implant maintenance to improve long-term success of implant. Aims: The aim of this retrospective study was to evaluate whether the Medical Treatment Model (MTM), which is a comprehensive treatment, includes initial risk assessment, lifestyle instructions, such as diet and habits, and a customized maintenance program to improve implant prognosis. Materials and Methods: Patients who were comprehensively treated were included and divided into two groups, test and control groups. The test group included patients who started treatment with MTM, whereas control group included patients who started treatment without MTM introduction. Moreover, subsequently, compliance with maintenance, occurrence of biological complications, and implant failure were evaluated. Results: About 199 patients with 515 implants were analyzed in the control group and 38 patients with 59 implants in the test group. In the control and test groups, the percentages of patients in the four compliance categories were, respectively, 73.9% and 89.5% for excellent compliance, 7.0% and 7.9% for good compliance, 14.6% and 0% for fair compliance, and 4.5% and 2.6% for poor compliance. There was a statistically significant difference in the compliance with periodontal and implant maintenance between the test and control groups (P = 0.029). Conclusions: Within the limitation of this study, MTM significantly enhanced the compliance of patients treated with implants. PMID:27994406

  8. 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…

  9. Retention in publicly funded methadone maintenance treatment in two Western States.

    PubMed

    Deck, Dennis; Carlson, Matthew J

    2005-01-01

    This study examined individual and system characteristics associated with retention in methadone maintenance treatment among Medicaid-eligible adults in treatment for opiate use in Oregon and Washington. Logistic regression was used to examine the contributions of predisposing, need, and enabling characteristics on 365 day retention in methadone maintenance treatment. Older patients, patients with a history of methadone maintenance treatment, and persons with stable Medicaid eligibility had higher rates of retention than did patients with disabilities, polysubstance users, and those with an arrest record. In Oregon, which delivers methadone maintenance treatment through managed care, retention rose sharply from 28% to 51% between 1994 and 1998 and then leveled off. During the same time period, retention in Washington State grew from 28% to 34%. The higher rates of retention in Oregon, in part, can be explained by differences in service delivery influenced by financing. Faced with long waiting lists, Washington providers were more than twice as likely to administratively discharge patients for rule violations as their Oregon counterparts. Given the importance of retention, policies and practices that influence retention should be carefully considered. Because Medicaid eligibility has a dramatic impact on retention, policies that help extend eligibility or stabilize eligibility among individuals actively engaged in treatment should be carefully considered.

  10. 78 FR 62427 - TRICARE; Removal of the Prohibition To Use Addictive Drugs in the Maintenance Treatment of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... opioid treatment services. Medication assisted treatment, to include drug maintenance involving... medical evidence, this exclusion of medication assisted treatment of substance use dependence utilizing a... medications like buprenorphine and naloxone when used for either prolonged ambulatory detoxification...

  11. Increased antiviral activity of microscale-purified HuIFN alpha 8 (human interferon alpha 8) over HuIFN alpha 2b in Hep-2 cells challenged with Mengo virus.

    PubMed

    García, Julio César Sánchez; Ariza, Alejandro Miranda; Lasa, Alexis Musacchio; González, Luis Javier; Perez, Vladimir Besada

    2007-11-01

    Human proteins are not routinely expressed at high levels in Escherichia coli for, among other reasons, different codon usage. Several purification procedures have been applied to recover recombinant proteins for further biological characterization. However, the vast majority involve costly chromatography procedures. In the present study, both (Hu)IFN(alpha 2b) (human interferon alpha 2b) and (Hu)IFN(alpha 8) were expressed efficiently in E. coli BL21-codonplus-RIL. Subsequently, both recombinant proteins were purified to homogeneity by passive elution from reverse-stained SDS/PAGE gels, a cost-effective purification procedure. After purification, both recovered proteins were biologically active. The (Hu)IFN(alpha 8) subtype induced 1.46-fold more antiviral activity than (Hu)IFN(alpha 2b) using Hep-2 human laryngeal carcinoma cell challenged with Mengo virus.

  12. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder.

    PubMed

    Popovic, Dina; Reinares, Maria; Goikolea, Jose Manuel; Bonnin, Caterina Mar; Gonzalez-Pinto, Ana; Vieta, Eduard

    2012-05-01

    Over one half of bipolar patients have been reported to be more prone to either depressive or manic relapses. This study aimed to define profiles of drugs used for maintenance treatment of bipolar disorder (BD) by the means of Polarity Index. Polarity Index is a new metric indicating the relative antimanic versus antidepressive preventive efficacy of drugs. Polarity Index was retrieved by calculating Number Needed to Treat (NNT) for prevention of depression and NNT for prevention of mania ratio, as emerging from the results of randomized placebo-controlled trials. Included trials were randomized and double blind, with a minimal duration of 24 weeks, assessing effectiveness of a mood stabilizer or antipsychotic drug alone or in combination with a mood stabilizing agent versus a placebo comparator in BD maintenance treatment. Polarity Index value above 1.0 indicates a relative greater antimanic prophylactic efficacy, number below 1.0 a relative greater antidepressive efficacy. The polarity index for the drugs used in maintenance therapy for bipolar disorder was 12.09 for risperidone, 4.38 for aripiprazole, 3.91 for ziprasidone, 2.98 for olanzapine, 1.39 for lithium, 1.14 for quetiapine, and 0.40 for lamotrigine. Polarity index of valproate and oxcarbazepine may not be reliable due to the failure of their maintenance trials. The polarity index provides a measure of how much antidepressant versus antimanic a drug is in bipolar disorder prophylaxis, and may guide the choice of maintenance therapy in bipolar patients.

  13. Laterality, frequency and replication of rTMS treatment for chronic tinnitus: pilot studies and a review of maintenance treatment

    PubMed Central

    Mennemeier, M.; Munn, T.; Allensworth, M.; Lenow, J.K.; Brown, G.; Allen, S.; Dornhoffer, J.; Williams, D.K.

    2012-01-01

    This manuscript reports on findings of three open label, pilot studies and it reviews studies using rTMS as a maintenance treatment for any disorder. The first pilot study examined whether a patient’s original treatment response to 1 Hz rTMS over temporal cortex could be replicated by stimulating a homologous region of the opposite hemisphere. The second study examined whether a patient’s response to 1Hz rTMS could be replicated by applying 10 Hz rTMS over the same treatment site. The third study applied a 3-day course of maintenance rTMS, either at 1 or 10 Hz, when subjects indicated that the benefit of their last course of treatment was waning. Patients with bilateral subjective tinnitus of at least 6 months duration were recruited from a prior, sham controlled study with treatment crossover that applied 1Hz rTMS over temporal cortex. Both treatment responders and non-responders were recruited. Results indicated, first, that the original treatment response, both positive and negative, is replicated after stimulating a homologous region of the opposite hemisphere; second, patients respond similarly to 1 and 10 Hz stimulation of the same treatment site (an exception was one patient who initially failed 1 Hz stimulation but responded positively to 10 Hz stimulation); and, third, maintenance rTMS had a sustained and additive benefit for tinnitus among treatment responders. Conclusions are that rTMS-induced effects on tinnitus are neither hemisphere specific nor frequency dependent; although, different frequencies of rTMS may have greater potency for a given subject. Maintenance treatment is a well tolerated approach with demonstrated feasibility for managing chronic tinnitus in persons who respond positively to an initial course of treatment. PMID:22486989

  14. Implant maintenance treatment and peri-implant health.

    PubMed

    Howe, Mark-Steven

    2017-03-01

    Data sourcesMedline (PubMed), Embase, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases and a manual search of the Journal of Dental Research, Journal of Clinical Periodontology, Journal of Periodontology and the International Journal of Periodontics and Restorative Dentistry from January 2014 to February 2015.Study selectionProspective, retrospective, randomised or not, case-controlled or case series trials showing the incidence or recurrence of peri-implant disease plus or minus PIMT over more than six months.Data extraction and synthesisThree reviewers independently selected studies and abstracted data with two reviewers assessing study quality using the Newcastle-Ottawa Scale (NOS). A multivariate binomial regression was used to examine the data.ResultsThirteen studies were included with ten contributing to the meta-analysis. The average quality assessment score (NOS) was 5.3 out of a possible nine, only one paper achieved eight. At patient level mucositis ranged from 18.5-74.2% and peri-implantitis from 8-28%, with significant effects being seen for treatment (z= -14.36, p<0.001). Mucositis was affected by history of periodontitis and mean PIMT at implant and patient levels, respectively. For peri-implantitis there were also significant effects of treatment (z = -16.63, p<0.001). Increased peri-implantitis was observed for patients with a history of periodontal disease. (z=3.76, p<0.001). Implants under PIMT have 0.958 the incident event compared to those with no PIMT.ConclusionsWithin the limitations of the present systematic review it can be concluded that implant therapy must not be limited to placement and restoration of dental implants, but to the implementation of PIMT to potentially prevent biological complications and heighten the long-term success rate. Although it must be tailored to a patients risk profiling, our findings suggest reason to claim a minimum recall PIMT interval of five to six

  15. 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…

  16. Severe periodontitis is inversely associated with coffee consumption in the maintenance phase of periodontal treatment.

    PubMed

    Machida, Tatsuya; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Takeuchi, Noriko; Maruyama, Takayuki; Mizutani, Shinsuke; Kataoka, Kota; Kawabata, Yuya; Morita, Manabu

    2014-10-21

    This cross-sectional study addressed the relationship between coffee consumption and periodontitis in patients during the maintenance phase of periodontal treatment. A total of 414 periodontitis patients in the maintenance phase of periodontal treatment completed a questionnaire including items related to coffee intake and underwent periodontal examination. Logistic regression analysis showed that presence of moderate/severe periodontitis was correlated with presence of hypertension (Odds Ratio (OR) = 1.99, p < 0.05), smoking (former, OR = 5.63, p < 0.01; current, OR = 6.81, p = 0.076), number of teeth present (OR = 0.89, p < 0.001), plaque control record ≥20% (OR = 1.88, p < 0.05), and duration of maintenance phase (OR = 1.07, p < 0.01). On the other hand, presence of severe periodontitis was correlated with smoking (former, OR = 1.35, p = 0.501; current, OR = 3.98, p < 0.05), coffee consumption (≥1 cup/day, OR = 0.55, p < 0.05), number of teeth present (OR = 0.95, p < 0.05), and bleeding on probing ≥ 20% (OR = 3.67, p < 0.001). There appears to be an inverse association between coffee consumption (≥1 cup/day) and prevalence of severe periodontitis in the maintenance phase of periodontal treatment.

  17. Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals

    PubMed Central

    Tetrault, Jeanette M.; Fiellin, David A.

    2013-01-01

    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. PMID:22235870

  18. 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

  19. 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)

  20. The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among methadone maintenance treatment patients.

    PubMed

    Potik, David; Peles, Einat; Abramsohn, Yahli; Adelson, Miriam; Schreiber, Shaul

    2014-01-01

    The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among patients in methadone maintenance treatment (MMT) was examined by the Vulnerable Attachment Style Questionnaire (VASQ), the Symptom Checklist-90 (SCL-90), and drug abuse urine tests. After six years, retention in treatment and repeated urine test results were studied. Patients with vulnerable attachment style (a high VASQ score) had higher rates of drug abuse and higher psychopathology levels compared to patients with secure attachment style, especially on the interpersonal sensitivity, anxiety, hostility, phobic anxiety, and paranoid ideation scales. Drug abstinence at baseline was related to retention in treatment and to higher rates of drug abstinence after six years in MMT, whereas a vulnerable attachment style could not predict drug abstinence and retention in treatment. Clinical Implications concerning treatment of drug abusing populations and methodological issues concerning the VASQ's subscales are also discussed.

  1. Effect of CBT on Depressive Symptoms in Methadone Maintenance Patients Undergoing Treatment for Hepatitis C

    PubMed Central

    Ramsey, Susan E.; Engler, Patricia A.; Stein, Michael D.; Brown, Richard A.; Cioe, Patricia; Kahler, Christopher W.; Promrat, Kittichai; Rose, Jennifer; Anthony, Jennifer; Solomon, David A.

    2011-01-01

    To examine the efficacy of a cognitive-behavioral intervention (CBT) to prevent depression among methadone maintenance patients undergoing antiviral treatment for hepatitis C (HCV), 29 patients beginning HCV treatment were randomized to CBT or standard care (SC). Study participants did not meet criteria for major depressive disorder at the time of study recruitment. CBT did not result in less depression-related antiviral treatment failure, better adherence to antiviral treatment, or better HCV RNA outcomes. There were no significant treatment group differences on depressive symptoms over time. The CBT group did display a greater and more consistent decline in both BDI-II and HAM-D scores over time (d=.85 on the BDI-II; d=.72 on the HAM-D). PMID:21743837

  2. 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.

  3. Nursing Strategies for Patients with Chronic Renal Failure Undergoing Maintenance Hemodialysis Treatment by Arteriovenous Fistula

    PubMed Central

    QIN, Hong Yan; JIA, Ping; LIU, Hui

    2016-01-01

    Background: We aimed to analyze the effect of nursing strategies on patients with chronic renal failure (CRF) undergoing maintenance hemodialysis (MHD) treatment by puncturing on arteriovenous fistula (AVF). Methods: Ninety-two patients with chronic renal failure undergoing maintenance hemodialysis (MHD) between Jan 2014 and Jan 2015 were included in the study (all undergoing AVF, dialysis for 2–3 sessions per week, 4–5 h per session) and randomly divided into control group and observation group. Patients in control group were given standard nursing care and patients in observation group were given professional nursing of internal fistula. The complication rate and dysfunction rate during internal fistula perioperative period, fistula usage time and effect on life quality of patients of these two groups were compared (during 18-month follow-up). Results: The complication rate and dysfunction rate during internal fistula perioperative period of the observation group were significantly lower than that of the control group, and the difference was statistically significant (P<0.05). The median time of internal fistula usage was significantly prolonged, and the health index, emotion index and psychology index quality-of-life in the observation group were significantly higher than that of the control group (P<0.05). Conclusion: Professional nursing strategies of internal fistula can prolong service time, decrease complications and improve life quality for patients undergoing maintenance hemodialysis treatment via arteriovenous fistula. PMID:27957433

  4. 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

  5. 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

  6. Pharmacological agents under research for the maintenance treatment in bipolar disorder.

    PubMed

    Dimitrakopoulos, S; Konstantakopoulos, G

    2015-01-01

    The treatment of bipolar disorder is a current challenge for clinicians and despite progress in psychopharmacology, options remain limited and results are often unsatisfactory. Current research focuses on finding new pharmaceutical agents for all phases of bipolar disorder, i.e. mania, bipolar depression and maintenance. Particularly, relapse prevention and longterm stabilization is a major therapeutic target. Combination treatment and polypharmacy are the most common choices concerning relapse prevention. Furthermore, during maintenance phase patients often experience residual mood symptoms, cognitive deficits and functional decline, which altogether illustrate the inadequate effectiveness of existing treatments and the need for new, targeted, effective and safe treatments for bipolar disorder. This review focuses on active agents for maintenance treatment in bipolar disorder investigated during the last 5 years. The compounds under investigation have been tried or tested either as monotherapy or as an add-on treatment in clinical trials that have progressed up to phase 3 or in preclinical models of bipolar disorder. While awaiting the completion of many ongoing studies, the results so far indicate that paliperidone and pregabalin may have a position in the maintenance treatment of bipolar disorder. Additionally, dextromethorphan, which acts primarily as a NMDA antagonist, may be an interesting compound for further study. However, results on memantine, another NMDA antagonist, were not encouraging. The effects of omega-3 fatty acids and cytidine were not superior to placebo, although they both have neurotrophic and neuroprotective properties. Eslicarbazepine, which has antiepileptic action, provided some evidence of efficacy as monotherapy. Regarding preclinical studies in experimental models, the pharmacological agents under investigation seem to follow the neurobiological pathways related to mechanism of action of lithium, which is still the "golden standard

  7. 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

  8. Clinical significance of TT virus (TTV) infection in chronic hepatitis C patients with high dose interferon-alpha therapy in Taiwan: re-evaluated by using new set of TTV primers.

    PubMed

    Dai, Chia Yen; Yu, Ming Lung; Lin, Zu Yau; Chen, Shinn Cherng; Hsieh, Ming Yen; Lee, Li Po; Hou, Nei Jen; Hsieh, Ming Yuh; Wang, Liang Yen; Tsai, Jung Fa; Chuang, Wan Long; Chang, Wen Yu

    2003-10-01

    BACKGROUND: The clinical significance of TT virus (TTV) coinfection in chronic hepatitis C (CHC) patients and influence of TTV viremia on hepatitis C virus (HCV) response to high dose interferon-alpha therapy in Taiwan were investigated. MATERIALS AND METHODS: Total 102 HCV RNA-positive CHC patients were enrolled. TTV DNA (using polymerase chain reaction primers derived from 5' non-coding region and open reading frame 2), alanine aminotransferase (ALT), GB virus-C/hepatitis G virus (GBV-C/HGV) RNA, anti-E2 antibody, genotype and RNA levels of HCV were tested. RESULTS: The prevalence of TTV DNA was 51.0%. The mean age of TTV viremic CHC patients was significant higher than non-viremic ones (P<0.05). HCV sustained viral response (SVR) was achieved in 42 (41.2%) patients. Based on multivariate regression analyses, SVR were significantly associated with low pretreatment HCV RNA levels, HCV genotype non-1b and high pretreatment levels of ALT but not TTV viremia. CONCLUSIONS: TTV viremia is highly prevalent among Taiwanese CHC patients and related to increased ages. Neither severity of liver disease nor replication and genotype distribution of HCV was affected by concurrent TTV infection. With high HCV SVR rate associated with pretreatment HCV RNA and ALT levels and HCV genotype, TTV viremia did not influence the HCV response.

  9. Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.

    PubMed Central

    Khan, K D; Shuai, K; Lindwall, G; Maher, S E; Darnell, J E; Bothwell, A L

    1993-01-01

    The murine Ly-6A/E gene is transcriptionally induced in cells exposed to interferon alpha/beta or gamma (IFN-alpha/beta or IFN-gamma). Analysis of the 5' flanking sequence using reporter plasmids that contain upstream elements of the Ly-6E gene has previously identified an approximately 850-base-pair IFN-responsive region that lacked an IFN-alpha-stimulated response element (ISRE), the element present and required for an IFN-alpha response of a number of genes. Analysis by deletion and stable transfection of the IFN-responsive region of the Ly-6E promoter has defined an 80-base-pair region containing an IFN-gamma activation site (GAS) but no ISRE that allows IFN-gamma and IFN-alpha inducibility of the Ly-6E gene. As tested by specific antiserum, a 91-kDa protein known to be activated in IFN-alpha- or IFN-gamma-treated cells binds to the GAS element from the Ly-6E promoter. The 91-kDa protein exists as an inactive cytoplasmic precursor and depends on tyrosine phosphorylation for its activation. Thus the same 91-kDa protein appears to act in the signal transduction pathways of both types of IFN for the Ly-6-A/E gene. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:7688129

  10. Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma

    PubMed Central

    Aguiar-Bujanda, David; Blanco-Sánchez, María Jesús; Hernández-Sosa, María; Galván-Ruíz, Saray; Hernández-Sarmiento, Samuel

    2015-01-01

    Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL), both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life. PMID:26604821

  11. Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly.

    PubMed

    Bump, G M; Mulsant, B H; Pollock, B G; Mazumdar, S; Begley, A E; Dew, M A; Reynolds, C F

    2001-01-01

    Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.

  12. Accelerated second-line or maintenance chemotherapy versus treatment at disease progression in NSCLC.

    PubMed

    Velez, Michel; Belalcazar, Astrid; Domingo, Gelenis; Blaya, Marcelo; Raez, Luis E; Santos, Edgardo S

    2010-04-01

    For many decades, the use of chemotherapy as second-line therapy in non-small-cell lung cancer relied upon disease progression. Several studies have shown that four to six cycles of chemotherapy administered as front-line therapy treatment offers a survival advantage to patients; however, further chemotherapy beyond this initial treatment was more associated with side effects and no benefit in survival. Until 2009, second-line treatment for lung cancer was well established for three therapeutic agents: docetaxel, pemetrexed and erlotinib. Currently, the timeframe to use these agents has been challenged by two large randomized clinical trials in which pemetrexed (JMEN trial) and erlotinib (Sequential Tarceva in Unresectable NSCLC [SATURN] trial) were used as 'maintenance' therapy and shown to impact progression-free survival and overall survival. This review focuses on the actual dilemma that medical oncologists face in clinical practice in terms of when and to whom maintenance therapy should be applied or if the 'watch and wait' approach prior to start second-line therapy is still advisable.

  13. 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.

  14. 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.

  15. Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period.

    PubMed

    Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu

    2016-12-01

    Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models.Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients' sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period.Only VKSTT (partial regression coefficient -1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period.After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10-120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration.

  16. Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period

    PubMed Central

    Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu

    2016-01-01

    Abstract Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models. Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients’ sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period. Only VKSTT (partial regression coefficient −1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period. After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10–120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration. PMID:28002326

  17. Adolescent and young adult heroin patients: drug use and success in methadone maintenance treatment.

    PubMed

    Kellogg, Scott; Melia, Dorothy; Khuri, Elizabeth; Lin, Amy; Ho, Ann; Kreek, Mary Jeanne

    2006-01-01

    This study examined the impact of methadone maintenance treatment on an inclusive group of adolescent and young adult opiate-dependent patients, ages 15-23, admitted over a 6-year period, during their first year in the program. Retention in treatment was the primary outcome variable, and at 12 months, 48% were still in treatment. The findings were: (a) a stepwise discriminant function analysis revealed that patients who consistently used heroin were at a greater risk of leaving treatment within the first 12 months; (b) the use of cocaine was an indicator of higher levels of heroin use in those who reached the one-year mark; (c) among patients who stayed in treatment for one year, there was a significant reduction in heroin use, a trend toward a reduction in cocaine use, and no significant impact on benzodiazepine use; and (d) the group that stayed in treatment was slightly younger than the group that left before the first year ended. There were no gender or ethnic differences between the two groups. Suggestions for interventions that might improve treatment outcome are presented.

  18. Severe anorexia nervosa, co-occurring major depressive disorder and electroconvulsive therapy as maintenance treatment: a case report

    PubMed Central

    2009-01-01

    Introduction It is difficult to treat patients who, in addition to having severe anorexia nervosa, also have severe symptoms of major depressive disorder and a tendency for impulsive acting out behaviour. Our case report considers the feasibility of maintenance electroconvulsive therapy in such complicated cases. Case presentation This is a case report of a woman with anorexia nervosa and co-morbid severe major depressive disorder who was treated with electroconvulsive therapy as a maintenance treatment. The maintenance electroconvulsive therapy was conducted without immediate complications. It had a positive effect on the patient's depressive symptoms and lability and her general wellbeing, although some cognitive deficits were observed. Conclusion The maintenance electroconvulsive therapy seemed to support recovery in a case of refractory anorexia nervosa and a tendency for labile mood. The symptoms of co-occurring major depressive disorder were partly relieved and maintenance electroconvulsive therapy had some positive effect on weight gain. PMID:20062609

  19. Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment.

    PubMed

    Housová, J; Wilczek, H; Haluzík, M M; Kremen, J; Krízová, J; Haluzík, M

    2005-01-01

    Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.

  20. Predictors of retention in community-based methadone maintenance treatment program in Pearl River Delta, China

    PubMed Central

    2013-01-01

    Background The aims were to identify predictors of treatment retention in methadone maintenance treatment (MMT) clinics in Pearl River Delta, China. Methods Retrospective longitudinal study. Participants: 6 MMT clinics in rural and urban area were selected. Statistical analysis: Stratified random sampling was employed, and the data were analyzed using Kaplan-Meier survival curves and life table method. Protective or risk factors were explored using Cox’s proportional hazards model. Independent variables were enrolled in univariate analysis and among which significant variables were analyzed by multivariate analysis. Results A total of 2728 patients were enrolled. The median of the retention duration was 13.63 months, and the cumulative retention rates at 1,2,3 years were 53.0%, 35.0%, 20.0%, respectively. Multivariate Cox analysis showed: age, relationship with family, live on support from family or friends, income, considering treatment cost suitable, considering treatment open time suitable, addiction severity (daily expense for drug), communication with former drug taking peer, living in rural area, daily treatment dosage, sharing needles, re-admission and history of being arrested were predictors for MMT retention. Conclusions MMT retention rate in Guangdong was low and treatment skills and quality should be improved. Meanwhile, participation of family and society should be encouraged. PMID:23497263

  1. Sleep Disorders in Methadone Maintenance Treatment Volunteers and Opium-dependent Patients

    PubMed Central

    Khazaie, Habibolah; Najafi, Farid; Ghadami, Mohammad Rasoul; Azami, Atena; Nasouri, Marzieh; Tahmasian, Masoud; Khaledi-Paveh, Behnam

    2016-01-01

    Background The relationship between substance use and sleep is bidirectional. Substance use directly causessleep disturbances, and sleep problems are a critical factor in substance-use relapse. Methods This study evaluated sleep disorders in 65 methadone maintenance treatment (MMT) patients, and61 opium-dependent patients who did not receive any treatment between September 2011 and July 2012 inKermanshah, Iran. Both groups filled out the Pittsburgh Sleep Quality Index (PSQI) and Global SleepAssessment Questionnaire (GSAQ). Findings Sleep disorders were remarkably similar in both groups: 78.5% of MMT patients and 87.7% ofopium-dependent patients suffered from sleep problems. Sleep disorders in the opium-dependent groupwere remarkably higher and more prominent. Conclusion Compared to opium, MMT does not have as many negative effects on sleep and is more effectivein mitigating sleep problems. PMID:27882205

  2. 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

  3. Interferon-alpha regulates the dynamic balance between human activated regulatory and effector T cells: implications for antiviral and autoimmune responses.

    PubMed

    Golding, Amit; Rosen, Antony; Petri, Michelle; Akhter, Ehtisham; Andrade, Felipe

    2010-09-01

    An adequate effector response against pathogens and its subsequent inactivation after pathogen clearance are critical for the maintenance of immune homeostasis. This process involves an initial phase of T-cell effector (Teff) activation followed by the expansion of regulatory T cells (Tregs), a unique cell population that limits Teff functions. However, significant questions remain unanswered about the mechanisms that regulate the balance between these cell populations. Using an in vitro system to mimic T-cell activation in human peripheral blood mononuclear cells (PBMC), we analysed the patterns of Treg and Teff activation, with special attention to the role of type I interferon (IFN-I). Interestingly, we found that IFN-alpha, either exogenously added or endogenously induced, suppressed the generation of CD4(+) FoxP3(HI )IFN-gamma(Neg) activated Tregs (aTregs) while simultaneously promoting propagation of CD4(+) FoxP3(Low/Neg )IFN-gamma(Pos) activated Teffs (aTeffs). We also showed that IFN-alpha-mediated inhibition of interleukin (IL)-2 production may play an essential role in IFN-alpha-induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN-alpha, we investigated systemic lupus erythematosus (SLE). Plasma from patients with SLE was found to contain IFN-I activity that suppressed aTreg generation. Furthermore, anti-CD3 activated SLE PBMCs exhibited preferential expansion of aTeffs with a very limited increase in aTreg numbers. Together, these observations support a model whereby a transient production of IFN-alpha (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN-alpha may tip the aTeff:aTreg balance towards aTeffs and autoimmunity.

  4. Safety of Interferon Alpha-2a in Patients with Severe Ophthalmic Behçet's Disease: Response to Bielefeld et al.'s Letter.

    PubMed

    Ghembaza, Mohammed El Amine; Lounici, Ali

    2017-01-12

    Thyroid dysfunction is a common and severe side-effect encountered in up to 40% of patients treated with IFN-alpha-2a. The main two mechanisms by which IFN-alpha-2a induces thyroid dysfunction can be categorized as autoimmune and non-autoimmune disease. In the first subgroup, thyroid antibodies are found before treatment initiation, and then patients develop thyroiditis. In the second subgroup, IFN-alpha-2a induces thyroiditis by a direct cytotoxic effect on the thyroid gland; in this case, thyroid antibodies are usually negative. To avoid such complications, patients should undergo routine thyroid screening (thyroid-stimulating hormone and thyroid antibodies) prior to IFN-alpha-2a initiation, during the treatment period, and 6 months after treatment withdrawal.

  5. Results of therapy with interferon alpha and cyclic combination chemotherapy in patients with philadelphia chromosome positive chronic myelogenous leukemia in early chronic phase.

    PubMed

    Giles, F J; Kantarjian, H; O'Brien, S; Rios, M B; Cortes, J; Beran, M; Koller, C; Keating, M; Talpaz, M

    2001-04-01

    The objective of the study was to investigate the toxicity and efficacy of cyclic combination therapy offered to patients with Ph-positive CML having a sub-optimal response to IFN-alpha. Patients in early chronic phase CML were treated with IFN-alpha at 5MU/m(2) daily. Patients who did not achieve cytogenetic response after 6 months of IFN-alpha therapy, or Ph-suppression to less than 35% Ph-positive cells (partial cytogenetic response) after 12 months of therapy were offered cyclic intensive chemotherapy every 6 months, with IFN-alpha maintenance between cycles. The initial 3 cycles included daunorubicin, vincristine, cytosine arabinoside (ara-C) and prednisone (DOAP). Later cycles were given with cyclophosphamide replacing daunorubicin (COAP). Of 74 patients treated, 61 (82%) achieved complete hematologic response (CHR): 51 (69%) had a cytogenetic response, which was major (Ph < 35%) in 31 (42%), and complete in 23 (31%). Fifty-five patients (74%) achieved CHR by 6 months of therapy, 38 (69%; 51% of total) with a cytogenetic response - 13 (24%) had a major cytogenetic response. Seventeen patients received at least 1 course of DOAP therapy. Median survival of the overall cohort of patients was 120 months. With a median follow-up of 145 months (103+ to 155+ months), 40 patients (54%) have died. The median duration of cytogenetic response was 35 months (range 3 to 149+ months) and the estimated 10-year cytogenetic response rate was 37%. A durable complete cytogenetic response was observed in 16 patients (20%) with a median duration of 139+ months (range 12+ to 149+ months), 11 of them (15%) are now off IFN-alpha therapy for a median of 57+ months (range 12+ to 128+ months). The projected 10-year survival was 50% for the study group versus 35% for 208 patients who received other IFN-alpha based regimens at the MD Anderson Cancer Center (p<.01). In conclusion, the addition of intensive chemotherapy may improve survival in patients with CML who have not obtained an

  6. Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4⁺ T cells from patients with GI malignancy.

    PubMed

    Mundy-Bosse, Bethany L; Young, Gregory S; Bauer, Todd; Binkley, Elaine; Bloomston, Mark; Bill, Matthew A; Bekaii-Saab, Tanios; Carson, William E; Lesinski, Gregory B

    2011-09-01

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33(+)HLADR(-)CD11b(+)CD15(+) and CD33(+)HLADR(-/low)CD14(+) MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33(+)HLADR(-)CD15(+) MDSC (P = 0.008) and IL-10 with CD33(+)HLADR(-)CD15(-) MDSC (P = 0.002). The percentage of CD15(+) and CD15(-) but not CD14(+) MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4(+) T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4(+) subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33(+)HLADR(-)CD15(-) MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33(+)HLADR(-/low)CD14(+) subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  7. Zuclopenthixol decanoate in maintenance treatment of schizophrenic outpatients. Minimum effective dose and corresponding serum levels.

    PubMed

    Solgaard, T; Kistrup, K; Aaes-Jørgensen, T; Gerlach, J

    1994-05-01

    23 schizophrenic outpatients in maintenance treatment with zuclopenthixol decanoate were included in a study aimed at finding the minimum effective dose and corresponding serum concentration of zuclopenthixol. Every three months the dose was gradually reduced until prodromal symptoms appeared, indicative of an incipient relapse. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn to determine the serum concentration. This dose reduction principles proved feasible. Only one patient had a clear-cut relapse. The condition of the remaining patients was acceptably maintained by a dose increase. The minimum effective dose of zuclopenthixol was 200 mg/2 weeks (range 60-400), with a serum concentration of 22 nmol/l (7.1-69.7). There was a significant correlation between the administered dose and the corresponding serum level of the drug (r = 0.66, P < 0.01). A trend towards a positive correlation was found between the serum level at the minimum effective dose and the BPRS score (r = 0.42, P < 0.1). No correlation was found between the serum level and the side-effects or length of neuroleptic treatment. It is concluded that routine serum drug monitoring is hardly indicated in the long-term depot-neuroleptic treatment of schizophrenic patients. A strategy aiming at continually seeking the lowest effective dose on the basis of clinical parameters appears more appropriate, especially in case of depot-neuroleptic treatment.

  8. 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

  9. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Name of substance; (2) Strength of substance; (3) Dosage form; (4) Date dispensed; (5) Adequate... maintained in a dispensing log at the narcotic treatment program site and will be maintained in compliance with § 1304.22 without reference to § 1304.03. (c) All sites which compound a bulk narcotic...

  10. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Name of substance; (2) Strength of substance; (3) Dosage form; (4) Date dispensed; (5) Adequate... maintained in a dispensing log at the narcotic treatment program site and will be maintained in compliance with § 1304.22 without reference to § 1304.03. (c) All sites which compound a bulk narcotic...

  11. Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study

    PubMed Central

    Samaan, Zainab; Bawor, Monica; Dennis, Brittany B; Plater, Carolyn; Varenbut, Michael; Daiter, Jeffrey; Worster, Andrew; Marsh, David C; Tan, Charlie; Desai, Dipika; Thabane, Lehana; Pare, Guillaume

    2014-01-01

    Introduction Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study. Discussion This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff. PMID:25187714

  12. Phase III trial of chemotherapy using 5-fluorouracil and streptozotocin compared with interferon alpha for advanced carcinoid tumors: FNCLCC-FFCD 9710.

    PubMed

    Dahan, Laetitia; Bonnetain, Frank; Rougier, Philippe; Raoul, Jean-Luc; Gamelin, Eric; Etienne, Pierre-Luc; Cadiot, Guillaume; Mitry, Emmanuel; Smith, Denis; Cvitkovic, Frédérique; Coudert, Bruno; Ricard, Floriane; Bedenne, Laurent; Seitz, Jean-François

    2009-12-01

    The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1-5) and recombinant IFN-alpha-2a (3 MU x 3 per week). Primary endpoint was progression-free survival (PFS). From February 1998 to June 2004, 64 patients were included. The two arms were well matched for median age, sex ratio, PS 0-1, previous chemotherapy, surgery, or radiotherapy. The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN (hazard ratio=0.75 (0.41-1.36)). Overall survival (OS), tolerance, and effects on carcinoid symptoms were not significantly different. Despite a trend in favor of IFN, there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild.

  13. 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.

  14. Methadone maintenance treatment in Spain: the success of a harm reduction approach

    PubMed Central

    Fonseca, Francina; Castillo, Claudio; Domingo-Salvany, Antonia

    2013-01-01

    Abstract Problem During the 1980s, Spain had very strict laws limiting access to opioid agonist maintenance treatment (OAMT). Because of this, mortality among people who used illicit opioids and other illicit drugs was high. Spain was also the European country with the highest number of cases of acquired immunodeficiency syndrome transmitted through illicit drug injection. Approach The rapid spread of human immunodeficiency virus (HIV) infection among people using heroin led to a shift from a drug-free approach to the treatment of opioid dependence to one focused on harm reduction. A substantial change in legislation made it possible to meet public health needs and offer OAMT as part of harm reduction programmes in the public health system, including prisons. Local setting Legislative changes were made throughout the country, although at a different pace in different regions. Relevant changes Legal changes facilitated the expansion of OAMT, which has achieved a coverage of 60%. A parallel reduction in the annual incidence of HIV infection has been reported. Reductions in morbidity and mortality and improved health-related quality of life have been described in patients undergoing OAMT. Lessons learnt The treatment of opioid dependence has been more heavily influenced by moral concepts and prejudices that hinder legislation and interfere with the implementation of OAMT than by scientific evidence. To fulfil public health needs, OAMT should be integrated in harm reduction programmes offered primarily in public facilities, including prisons. Longitudinal studies are needed to detect unmet needs and evaluate programme impact and suitability. PMID:23554526

  15. 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

  16. Interferons alpha, beta, gamma each inhibit hepatitis C virus replication at the level of internal ribosome entry site-mediated translation.

    PubMed

    Dash, Srikanta; Prabhu, Ramesh; Hazari, Sidhartha; Bastian, Frank; Garry, Robert; Zou, Weiping; Haque, Salima; Joshi, Virendra; Regenstein, Fredric G; Thung, Swan N

    2005-06-01

    Interferon (IFN)-alpha is the standard therapy for the treatment of chronic hepatitis C, but the mechanisms underlying its antiviral action are not well understood. In this report, we demonstrated that IFN-alpha, -beta and -gamma inhibit replication of the hepatitis C virus (HCV) in a cell culture model at concentrations between 10 and 100 IU/ml. We demonstrated that the antiviral actions each of each these IFNs are targeted to the highly conserved 5' untranslated region of the HCV genome, and that they directly inhibit translation from a chimeric clone between full-length HCV genome and green fluorescent protein (GFP). This effect is not limited to HCV internal ribosome entry site (IRES), since these IFNs also inhibit translation of the encephalomyocardititis virus (EMCV) chimeric mRNA in which GFP is expressed by IRES-dependent mechanisms (pCITE-GFP). These IFNs had minimal effects on the expression of mRNAs from clones in which translation is not IRES dependent. We conclude that IFN-alpha, -beta and -gamma inhibit replication of sub-genomic HCV RNA in a cell culture model by directly inhibiting two internal translation initiation sites of HCV- and EMCV-IRES sequences present in the dicistronic HCV sub-genomic RNA. Results of this in vitro study suggest that selective inhibition of IRES-mediated translation of viral polyprotein is a general mechanism by which IFNs inhibits HCV replication.

  17. Oligoclonal CD8+ T-cell expansion in patients with chronic hepatitis C is associated with liver pathology and poor response to interferon-alpha therapy.

    PubMed

    Manfras, Burkhard J; Weidenbach, Hans; Beckh, Karl-Heinz; Kern, Peter; Möller, Peter; Adler, Guido; Mertens, Thomas; Boehm, Bernhard O

    2004-05-01

    The role of CD8(+) T lymphocytes in chronic hepatitis C virus (HCV) infection and in liver injury with subsequent development of fibrosis and cirrhosis is poorly understood. To address this question, we performed a follow-up study including 27 chronically HCV-infected individuals. We determined clonality and phenotypes of circulating CD8(+) T cells employing TCRBV spectratyping. Antigen specificity was tested by rMHC-peptide tetramer staining and stimulation with recombinant HCV antigens. In addition, T-cell clonality and phenotypes were followed during the variable clinical response of interferon- (IFN) alpha treatment. We could demonstrate that CD8(+) T-cell expansions were significantly associated with liver fibrosis and cirrhosis. Likewise, increased oligoclonality of circulating CD8(+) T cells in chronic HCV infection was identified as an indicator for poor clinical response to IFN-alpha therapy. Moreover, we also found that IFN-alpha therapy enhanced the differentiation of CD8(+) T cells towards a late differentiation phenotype (CD28(-) CD57(+)). In cases of virus elimination the disappearance of expanded terminally differentiated CD8(+) cells was observed. Thus, this study identifies an association of clonal expansions of circulating CD8(+) T cells with liver pathology and provides a possible explanation for the fact that response to IFN-alpha therapy diminishes with the duration of infection.

  18. Interferon-alpha, -beta and -gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: modulation by peroxisome proliferator-activated receptor-gamma agonists.

    PubMed

    Antonelli, Alessandro; Ferrari, Silvia Martina; Fallahi, Poupak; Ghiri, Emiliano; Crescioli, Clara; Romagnani, Paola; Vitti, Paolo; Serio, Mario; Ferrannini, Ele

    2010-06-01

    It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process.

  19. Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorder.

    PubMed

    Bobo, William V; Shelton, Richard C

    2010-11-01

    Poor adherence to pharmacotherapy during maintenance-phase treatment of bipolar disorder is a common occurrence, exposing patients to a high risk of illness relapses, rehospitalization and other negative outcomes. In view of this, there has been a reawakening of interest in the potential of long-acting injectable antipsychotic medications to improve treatment outcome during bipolar maintenance therapy. Indeed, long-acting injectable medications have practical advantages of assuring delivery of medication at a prescribed dose, and perhaps also making it easier to monitor adherence, at least to the long-acting drug. However, there are important limitations to the long-term use of depot typical neuroleptics in patients with bipolar disorder, including risk of extrapyramidal side effects and tardive dyskinesia, which may exceed that of patients with schizophrenia, and the potential for treatment-emergent exacerbation of depressive symptoms. Long-acting injectable risperidone (RLAI) has recently been approved for maintenance treatment in patients with bipolar I disorder. Evidence supporting the use of RLAI for this indication consists of several nonrandomized, open-label studies; one randomized, open-label trial; and two adequately powered randomized, double-blind trials. In general, these studies have shown RLAI to be effective for the prevention of relapse or hospitalization during bipolar maintenance treatment. In the double-blind studies, RLAI was associated with reduced relapse rates, increased time to relapse and greater control of clinical symptoms during maintenance treatment following initial stabilization, compared with oral medication treatment or placebo injection. RLAI appeared to be more effective for preventing manic/mixed episodes than depressive episodes. RLAI showed good tolerability across studies; however, dose-related extrapyramidal effects, sedation, weight gain and prolactin elevation may occur during long-term treatment. Responder

  20. Combination of interferon alpha with either Ara-C or ATRA in vitro reduces the selective action of interferon against CML CFU-GM.

    PubMed

    Marley, S B; Davidson, R J; Goldman, J M; Gordon, M Y

    2000-08-01

    Although interferon (IFN)-alpha has no specific inhibitory effect on the plating efficiency of granulocyte-macrophage colony-forming cells (CFU-GM) from patients with chronic myeloid leukaemia (CML), it does selectively inhibit the replating ability (secondary colony formation) of CML CFU-GM. Thus, amplification of CFU-GM may be a target for IFN-alpha and other agents used in the treatment of CML. Here we examined whether cytarabine (Ara-C) or all-trans retinoic acid (ATRA) exert similar effects and whether they might in combination with IFN-alpha enhance its efficacy. We found that Ara-C preferentially inhibits the formation of CML CFU-GM compared to normal CFU-GM, but this inhibition was not increased by addition of IFN-alpha. When Ara-C was added to cultures containing IFN-alpha, the inhibition of replating by CML progenitors was abrogated. ATRA increased significantly the plating efficiency of normal CFU-GM. The addition of IFN-alpha to ATRA had no effect on CML or normal colony numbers. However, addition of ATRA to cultures containing IFN-alpha reversed the selective inhibition of CML CFU-GM replating seen in cultures containing IFN-alpha alone. In four IFN-alpha/Ara-C experiments, secondary CML patient-derived colonies were examined by fluorescence in situ hybridisation (FISH). All of them were Ph chromosome positive. No significant effects on CFU-GM production were observed when CML primitive haemopoietic progenitor cells were investigated in a delta (delta) assay. Thus we conclude that combining IFN-alpha with Ara-C or ATRA neutralises the effect of IFN-alpha on CML CFU-GM. This observation provides a rationale for treating patients with alternating courses of IFN-alpha and Ara-C or ATRA, rather than giving either of these two agents in combination with IFN-alpha.

  1. 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

  2. Experimental model of pulmonary metastasis treatment with IFNalpha.

    PubMed

    Martínez, Cristina; Vicente, Vicente; Yáñez, M Josefa; García, Juana M; Canteras, Manuel; Alcaraz, Miguel

    2005-07-08

    Melanoma shows the high rates of mortality, preferentially by metastasis, and the failure of chemotherapy. We inoculated 30 B16F10 Swiss mice with 5 x 10(5) melanocytes. The mice were then inoculated with 150,000; 300,000; 600,000 and 1,200,000 IU/mouse of interferon alpha. A count of the metastatic nodules of the lung surface and the microscopic study were made by image analysis on five histological sections, calculating the implantation percentage and tumoral growth and invasion index. Treatment with the three highest doses of interferon alpha resulted in a dose-dependent reduction of the number of metastatic nodules and invaded area. A correlation existing between the parameters studied and the different antitumoral effects observed.

  3. Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial

    PubMed Central

    Yeeles, Ksenija; Bremner, Stephen; Lauber, Christoph; Eldridge, Sandra; Ashby, Deborah; David, Anthony S; O’Connell, Nicola; Forrest, Alexandra; Burns, Tom

    2013-01-01

    Objective To test whether offering financial incentives to patients with psychotic disorders is effective in improving adherence to maintenance treatment with antipsychotics. Design Cluster randomised controlled trial. Setting Community mental health teams in secondary psychiatric care in the United Kingdom. Participants Patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder, who were prescribed long acting antipsychotic (depot) injections but had received 75% or less of the prescribed injections. We randomly allocated 73 teams with a total of 141 patients. Primary outcome data were available for 35 intervention teams with 75 patients (96% of randomised) and for 31 control teams with 56 patients (89% of randomised). Interventions Participants in the intervention group were offered £15 (€17; $22) for each depot injection over a 12 month period. Participants in the control condition received treatment as usual. Main outcome measure The primary outcome was the percentage of prescribed depot injections given during the 12 month intervention period. Results 73 teams with 141 consenting patients were randomised, and outcomes were assessed for 131 patients (93%). Average baseline adherence was 69% in the intervention group and 67% in the control group. During the 12 month trial period adherence was 85% in the intervention group and 71% in the control group. The adjusted effect estimate was 11.5% (95% confidence interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of ≥95%, which was achieved in 28% of the intervention group and 5% of the control group (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003). Although differences in clinician rated clinical improvement between the groups failed to reach statistical significance, patients in the intervention group had more favourable subjective quality of life ratings (β=0.71, 95% confidence interval 0.26 to 1.15, P=0.002). The number of admissions

  4. 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

  5. Sirolimus as maintenance treatment in an infant with life-threatening multiresistant pure red cell anemia/autoimmune hemolytic anemia.

    PubMed

    Miano, Maurizio; Poggi, Vincenzo; Banov, Laura; Fioredda, Francesca; Micalizzi, Concetta; Svahn, Johanna; Montobbio, Giovanni; Gallicola, Federica; Molinari, Angelo C; Parasole, Rosanna; Petruzziello, Fara; Fischer, Alain; Calvillo, Michaela; Dufour, Carlo

    2014-04-01

    A 9-month-old boy with life-threatening multiresistant pure red cell anemia/autoimmune hemolytic anemia within the frame of a possible, undiagnosed immune-mediated disease was initially treated with prednisone. Further-line therapies of the following 7 relapses included immunoglobulins, rituximab, cyclophosphamide, and alentuzumab followed by other maintenance treatments as cyclosporine, methotrexate, and mycophenolate. After all the administered therapies failed, the patient was successfully treated by splenectomy followed by fludarabine and then sirolimus as maintenance treatment. Relapses might have been caused by the lack of a complete debulking of triggering cells and/or ineffective maintenance therapy. Splenectomy and sirolimus may have played a complementary role in the management of both situations.

  6. Stuck in limbo: illicit drug users’ experiences with opioid maintenance treatment and the relation to recovery

    PubMed Central

    Sagvaag, Hildegunn

    2016-01-01

    Objective The objective of this article is to gain insight into how individuals who frequent open illicit drug scenes experience opioid maintenance treatment (OMT) and investigate how this appears to affect their recovery processes. Method By means of the ethnographic method, one of the researchers spent time in an open illicit drug scene over a 1-year span, and gathered data on individuals who frequent the scene on a regular basis, and their experiences with OMT. The data are based on field notes and audiotaped interviews. Findings Four themes emerged as relevant for the participants’ experiences with OMT: 1) the loss of hope, 2) trapped in OMT, 3) substitution treatment is not enough, and 4) stigmatization of identity. Conclusion The participants found the OMT to be overruling and degrading. Several of the individuals from the illicit drug scene are part of the OMT programme, but as the treatment does not remove painful emotions, they supplement OMT with illegal substances, violate the OMT regulations, and run the risk of being excluded from the programme. In fear of losing the replacement opioid, they conceal parts of the addiction they seek treatment for and end up lying and cheating instead of exploring strategies for reducing and managing the addiction. The patients’ relation to the OMT personnel is negatively affected by the need to hide a large portion of their issues. The result is a feeling of hopelessness, increased stigmatization, lack of control and being trapped between two worlds—in limbo, an intermediate state which interferes with the recovery process. PMID:27765141

  7. 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

  8. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    PubMed

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia.

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

    PubMed

    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

    2010-12-01

    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.

  10. 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

  11. 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

  12. 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…

  13. Maintenance treatment after induction therapy in non-small cell lung cancer: latest evidence and clinical implications

    PubMed Central

    Gentzler, Ryan D.

    2014-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC. Therapies that have been studied in this setting in randomized trials to date include chemotherapy and molecularly targeted agents. Following the development of multiple new agents that show activity in NSCLC and have a tolerable side-effect profile, there has been increasing interest in utilizing them to maintain response to initial therapy after treatment with platinum-based doublets. Two effective strategies have evolved: continuation and switch maintenance. Despite improvements in progression-free survival and often overall survival on multiple clinical trials, there remains considerable controversy around this treatment paradigm. Here, we briefly outline the evolution of this treatment strategy and examine the available data, including recently updated data from the PARAMOUNT, AVAPERL, and PointBreak maintenance trials. Ultimately, the decision to use maintenance chemotherapy requires a nuanced discussion between the patient and physician that adequately assesses benefits of prolonged therapy and impact in terms of toxicity, quality of life, and financial cost. PMID:24381656

  14. Changes in somatic disease incidents during opioid maintenance treatment: results from a Norwegian cohort study

    PubMed Central

    Brekke, Mette; Gossop, Michael; Lindbaek, Morten; Reinertsen, Even; Thoresen, Magne; Waal, Helge

    2011-01-01

    Objectives To examine the effect of opioid maintenance treatment (OMT) on somatic morbidity in a cohort of OMT patients. Design Retrospective cohort study. Setting OMT programme in two Norwegian counties. Participants 200 OMT patients, participation rate 71.2%. Main outcome measures Incidence rates (IR) before, during and after OMT for acute/subacute hospital-treated somatic disease incidents (drug-related, non-drug-related, injuries) and rates for inpatient days and outpatient treatment contacts. Results IR for drug-related hospital treatment episodes were 76% lower during compared to before OMT (before versus during incidence rate ratio (IRR) 4.2 (95% CI 2.9 to 6.2), p<0.001) and 11 times higher after compared to during OMT (after versus during IRR 11.1 (6.6 to 18.5), p<0.001). For non-drug-related treatment episodes, IR were 35% higher during than before OMT (before versus during IRR 0.7 (0.6 to 1.0), p=0.02) and 32% higher after compared to during OMT (IRR 1.4 (0.9 to 2.2), p=0.15), while injuries showed little change according to OMT status. Although patients with on-going drug-taking during OMT showed less reduction in drug-related hospital-treated incidents during treatment than patients not using illicit drugs, the quartile with most drug-taking showed a significant reduction (before versus during IRR 3.6 (2.4 to 5.3)). Patients who had experienced cessation of OMT showed a significant reduction in drug-related treatment episodes during OMT (before versus during IRR 1.7 (1.0 to 2.9)), although less than patients without OMT interruptions (before versus during IRR 6.1 (3.6 to 10.6)), and a significant increase after OMT cessation compared with during OMT (IRR 5.4 (3.0 to 9.7)). Conclusion Acute/subacute drug-related somatic morbidity is reduced during compared to before OMT. This was also found for patients with on-going drug-taking during OMT. However, acute drug-related health problems show an increase after OMT cessation, and this is a matter of concern

  15. 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.

  16. 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

  17. Depression, suicidal ideation, and related factors of methadone maintenance treatment users in Guangzhou, China

    PubMed Central

    Zhang, Xiao; Xu, Huifang; Gu, Jing; Lau, Joseph T.F.; Hao, Chun; Zhao, Yuteng; Davis, Alissa; Hao, Yuantao

    2017-01-01

    Mental health problems are prevalent among drug users. Methadone maintenance treatment (MMT) is an evidence-based effective treatment for drug addiction; however, there are few studies investigating depression, suicidal ideation, and their related factors among MMT users. In this cross-sectional study, 648 MMT users were recruited from six MMT clinics in Guangzhou, China. Data were collected through face-to-face interviews by trained interviewers. Of all participants, 270 (42.7%) exhibited probable depression (Depression Subscale of the Chinese short version of Depression, Anxiety, and Stress Scale (DASS-D), score ≥ 10) and 99 (15.3%) reported having suicidal ideation in the last six months. After adjusting for significant socio-demographic characteristics, all studied variables, including drug use history, social support, family support for MMT use, and satisfaction toward MMT services were significantly associated with both probable depression and suicidal ideation in the last six months. Furthermore, depression fully mediated the associations between drug use history, satisfaction toward MMT services, and suicidal ideation. In the final multivariate models, probable depression was associated with social support (OR = 0.88, 95% CI = 0.83–0.93) and satisfaction toward MMT services provided by doctors (OR = 0.59, 95% CI = 0.40–0.86), while for suicidal ideation, social support (OR = 0.85, 95% CI = 0.78–0.92) and probable depression (OR = 5.94, 95% CI = 3.39–10.42) were significant. The findings suggest that there are unmet mental health needs among MMT users. For countries with limited resources of psychological services, mental health care toward MMT users should be implanted into current health care settings and incorporate components such as social support, family’s understanding of MMT, and service satisfaction. PMID:26839180

  18. Resilience associated with mental health problems among methadone maintenance treatment patients in Guangzhou, China.

    PubMed

    Jiao, Mingxu; Gu, Jing; Xu, Huifang; Hao, Chun; Lau, Joseph T F; Mo, Phoenix; Liu, Di; Zhao, Yuteng; Zhang, Xiao; Babbitt, Andrew; Hao, Yuantao

    2017-05-01

    A considerable proportion of methadone maintenance treatment (MMT) clients have experienced mental health problems (e.g., depression and anxiety), and poor mental health status is associated with HIV-related risk behaviors and treatment drop-out. Resilience is known to be a protective factor for mental health problems but is not studied among MMT clients in China. This study aimed to explore the relationship between resilience and mental health problems (depression, anxiety and stress) among clients of community-based MMT clinics in China. A total of 208 MMT clients completed the face-to-face interview conducted at 4 of 11 MMT clinics in Guangzhou. The Chinese short version of Depression Anxiety Stress Scale (DASS-21) was used to assess the presence of depressive, anxiety and stress symptoms, and the Connor-Davidson Resilience Scale (CD-RISC) was used to measure resilience. Logistic regression models were fit in data analyses. Of all participants, 12.8%, 19.5% and 8.3% had depression, anxiety and stress, respectively. The mean resilience score was 57.6 (SD = 15.9). In the univariate analyses, resilience was negatively associated with two studied mental health problems (depression and anxiety, ORu = 0.96 and 0.96, p < .01). In multivariate models adjusting for both background and other psycho-social factors, resilience was independently associated with probable depression (ORa = 0.97, 95% CI: 0.93-0.99) and anxiety (ORa = 0.96, 95% CI: 0.94-0.99). Resilience was independently associated with depression and anxiety. As resilience is changeable, interventions targeting mental health problems of MMT users should consider resilience as an important part in the designing of such interventions.

  19. Metabolic syndrome in patients enrolled in a clinical trial of aripiprazole in the maintenance treatment of bipolar I disorder

    PubMed Central

    Kemp, David E; Calabrese, Joseph R; Tran, Quynh-Van; Pikalov, Andrei; Eudicone, James M; Baker, Ross A

    2013-01-01

    Objectives To compare the effects of maintenance treatment with aripiprazole or placebo on the incidence of metabolic syndrome in bipolar disorder. Methods Patients with bipolar I disorder were stabilized on aripiprazole for 6–18 weeks prior to double-blind randomization to aripiprazole or placebo for 26 weeks. The rate of metabolic syndrome in each group was calculated at maintenance phase baseline (randomization) and endpoint for evaluable patients using an LOCF approach. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Results At entry into the maintenance phase, overall 45/125 patients (36.0%) met criteria for metabolic syndrome. Mean changes in the five components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure and glucose) from baseline to Week 26 were small except for a meaningful reduction in triglycerides (placebo −18.9 mg/dL; aripiprazole −11.5 mg/dL). By the end of the maintenance phase (endpoint, LOCF), 5/18 placebo-treated patients (27.8%) and 4/14 aripiprazole-treated patients (28.6%) no longer met metabolic syndrome criteria. The proportion of patients with metabolic syndrome was similar in the placebo and aripiprazole groups both at baseline and Week 26. There were no significant changes in any of the individual components of metabolic syndrome between aripiprazole- and placebo-treated patients during maintenance phase treatment. Conclusions The prevalence of metabolic syndrome in patients with bipolar disorder is higher than commonly reported in the general population. The effect of 26 weeks of treatment with aripiprazole on the incidence of metabolic syndrome and its components was similar to placebo. PMID:20492838

  20. 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

  1. THE IMPACT OF LOW-THRESHOLD METHADONE MAINTENANCE TREATMENT ON MORTALITY IN A CANADIAN SETTING

    PubMed Central

    Nolan, Seonaid; Hyashi, Kanna; Milloy, M-J; Kerr, Thomas; Dong, Huiru; Lima, Viviane Dias; Lappalainen, Leslie; Montaner, Julio; Wood, Evan

    2015-01-01

    Background Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the setting’s universal medical insurance plan. Methods Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with timedependent variables. Results Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1 – 3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR] = 0.73, 95% CI: 0.61 – 0.88). Conclusions While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use. PMID:26455554

  2. Long-term safety and tolerability of aripiprazole once-monthly in maintenance treatment of patients with schizophrenia.

    PubMed

    Fleischhacker, W Wolfgang; Sanchez, Raymond; Johnson, Brian; Jin, Na; Forbes, Robert A; McQuade, Robert; Baker, Ross A; Carson, William; Kane, John M

    2013-07-01

    The aim of this study was to evaluate the safety and tolerability of aripiprazole once-monthly (ARI-OM) for the maintenance treatment of schizophrenia. This long-term, pivotal study had four phases: oral conversion (phase 1, 4-6 weeks); oral stabilization (phase 2, 4-12 weeks); ARI-OM stabilization with coadministration of oral aripiprazole in the first 2 weeks (phase 3, 12-36 weeks); and a 52-week, randomized [phase 4, ARI-OM vs. placebo (2 : 1)], double-blind, maintenance phase. Safety was assessed across study phases by the time of first onset of adverse events, as were objective measures of extrapyramidal symptoms, fasting metabolic parameters, and body weight. Patient enrollment was phase 1=633; phase 2=710, of whom 210 entered phase 2 directly; phase 3=576; and phase 4=403 (ARI-OM, n=269; placebo, n=134). Adverse events (>5%) in any phase were insomnia, headache, anxiety, akathisia, increase in weight, injection-site pain, and tremor. Headache, somnolence, and nausea had a peak first onset within 4 weeks of treatment initiation. The incidence of extrapyramidal symptoms was similar in all phases. There were no unexpected changes in weight or shifts in fasting metabolic parameters across all study phases. ARI-OM had a safety and tolerability profile comparable with oral aripiprazole in maintenance treatment of schizophrenia.

  3. Somatic health among heroin addicts before and during opioid maintenance treatment: a retrospective cohort study

    PubMed Central

    Skeie, Ivar; Brekke, Mette; Lindbæk, Morten; Waal, Helge

    2008-01-01

    Background The long-term impact of opioid maintenance treatment (OMT) on morbidity and health care utilization among heroin addicts has been insufficiently studied. The objective of this study was to investigate whether health care utilization due to somatic disease decreased during OMT, and if so, whether the reduction included all kinds of diseases and whether a reduction was related to abstinence from drug use. Methods Cohort study with retrospective registration of somatic disease incidents (health problems, acute or sub-acute, or acute problems related to chronic disease, resulting in a health care contact). Medical record data were collected from hospitals, Outpatients' Departments, emergency wards and from general practitioners (GPs) and prospective data on substance use during OMT were available from 2001 onwards. The observation period was five years before and up to five years during OMT. The cohort consisted of 35 out of 40 patients who received OMT between April 1999 and January 2005 in a Norwegian district town. Statistical significance concerning changes in number of incidents and inpatient and outpatient days during OMT compared with the pre OMT period was calculated according to Wilcoxon signed rank test. Significance concerning pre/during OMT changes in disease incidents by relation to the type of health service contacts, as well as the impact of ongoing substance use during OMT on the volume of contacts, was calculated according to Pearson chi-square and Fisher's exact tests. Results 278 disease incidents were registered. There was a reduction in all incidents by 35% (p = 0.004), in substance-related incidents by 62% (p < 0.001) and in injection-related incidents by 70% (p < 0.001). There was an insignificant reduction in non-fatal overdose incidents by 44% (p = 0.127) and an insignificant increase in non-substance-related incidents by 13% (p = 0.741). Inpatient and outpatient days were reduced by 76% (p = 0.003) and 46% (p = 0.060), respectively

  4. Evaluation of Serum Adiponectin Concentrations Among Drug Abusers on Methadone Maintenance Treatment

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra; Yousefi, Maryam

    2013-01-01

    Background: Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory. Objectives: The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts. Materials and Methods: Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects with a mean age of 35 ± 9.5 years were enrolled in the study. Addicts were treated with methadone at (40 to 120 mg/d) for six months. Measurement of anthropometric parameters, serum adiponectin, and biochemical parameter levels, were assessed in the addicts, before and after six months of MMT, but only once in the healthy controls. Results: The mean basal serum adiponectin level was not significantly lower in the drug abuser group compared to the healthy subjects (P > 0.05). After six months of MMT, the mean serum adiponectin level of the drug addicts was not significantly different from their mean baseline level or that of the healthy subjects (P > 0.05). However, the mean baseline serum adiponectin level was significantly lower in overweight/obese addicts when compared to underweight patients and healthy individuals (P < 0.001). After six months of MMT, the mean level of serum adiponectin increased significantly in the underweight subjects compared to the normal weight and overweight/obese subjects (P < 0.0001) and the control group (P < 0.001). Adiponectin concentration was correlated inversely with body mass index and positively correlated with waist circumference and serum high-density lipoprotein levels. Conclusions: This study showed that MMT did not markedly alter the concentration of serum adiponectin in drug abusers. However, in regard to the variations in the serum lipid profiles and anthropometric parameters, the findings

  5. 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

  6. 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…

  7. 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

  8. Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune-mediated neuropathies.

    PubMed

    Gallia, Francesca; Balducci, Claudia; Nobile-Orazio, Eduardo

    2016-06-01

    High-dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25-60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.

  9. 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

  10. [Treatment of viral hepatitis C].

    PubMed

    Chassany, O

    1996-12-14

    Viral hepatitis C is a serious public health problem in France by the number of infected patients, the evolutive profile and by the lack of fully efficient therapeutics. However, the risk of developing cirrhosis and hepatocellular carcinoma may not be so high as it has been stated until now. Interferon alpha is at the present time, the only approved drug for the treatment of chronic hepatitis C. Its efficiency on criteria such as normalization of aminotransferases values or negativation of viremia is obtained in less than 25% of patients. The present recommendation is to use 3 MU of interferon alpha, 3 times per week during 12 months. While interferon leads to improvement of histologic lesions, it is not yet proved that a treatment by interferon can reduce, years after, the incidence of cirrhosis and hepatocellular carcinoma. No therapeutic strategy has been defined yet for the frequent situations of "no response", relapses or presence of factors that reduce the efficacy of treatment (high initial viremia level, genotype 1b, cirrhosis). It is possible that the course of patients having low or no elevation of aminotransferases and/or minimal histologic lesions, is good without any treatment. The efficacy of interferon alone appears insufficient. Thus trials in progress concern associations of antiviral drugs such as vidarabine. In lack of vaccine, preventive treatment is essential and depends upon knowledge of conditions of transmission of the virus. Transmission through blood and intravenous drug addiction represent 60 to 70% of cases of hepatitis C.

  11. 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

  12. 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

  13. 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

  14. 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, 2010 CFR

    2010-07-01

    ... costs shall be based upon past experience for existing treatment works or some other rational method... 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...

  15. Periodontal maintenance.

    PubMed

    Tan, A E S

    2009-09-01

    The main goal of periodontal therapy is to establish an oral environment compatible with periodontal health by the physical disruption of the plaque biofilm and adjunctive chemical means if required. Implicit in this objective is the ongoing requirement of detection and interception of new and recurrent disease, which continues at selected intervals for the life of the dentition after the initial ("active") phase of periodontal treatment. This concept of ongoing periodontal maintenance therapy has been embraced as the mandatory requirement for favourable periodontal outcomes based on institutional clinical trials and in practice-based studies in various parts of the world. This review examines the ramifications of periodontal maintenance therapy based upon a multi-level assessment of logistic issues and risk factors at three levels: (1) The patient level - treatment time; patient attendance compliance; and homecare measures, antiseptics/antibiotics and smoking. (2) The level of the individual tooth - tooth loss; and evaluation of success versus survival. (3) The level of each tooth surface ("site") - probing depth, loss of attachment and bleeding on probing; and changes in clinical attachment levels. In spite of the diversity of studies conducted, there is agreement on the efficacy of periodontal maintenance therapy when compared with studies on untreated populations and in treated cases that were not maintained.

  16. Serum-Infliximab Trough Levels in 45 Children with Inflammatory Bowel Disease on  Maintenance Treatment

    PubMed Central

    Rolandsdotter, Helena; Marits, Per; Sundin, Ulf; Wikström, Ann-Charlotte; Fagerberg, Ulrika L.; Finkel, Yigael; Eberhardson, Michael

    2017-01-01

    The role of trough serum infliximab (s-IFX) and antibodies toward IFX (ATI) during maintenance treatment remains unclear in children. The aim of the present study was to investigate trough s-IFX and ATI to identify any correlation with inflammatory activity and clinical response in a pediatric inflammatory bowel disease (IBD) cohort. We investigated the s-IFX trough levels in pediatric IBD patients (n = 45) on maintenance IFX treatment. Ninety-three blood samples were collected and demographics, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and albumin were recorded. The mean s-IFX trough level was 5.2 µg/mL. The mean trough s-IFX level was significantly higher in the samples taken during remission (7.2 µg/mL) compared to active disease (4.5 µg/mL, p < 0.05). The trough s-IFX levels correlated with ESR, CRP, and albumin. S-IFX was undetectable in eight of the patients, all with positive ATI and active disease. Surprisingly, clinical and biochemical remission was observed at only 26 of the 93 visits. The correlation between dose variations and changes in trough s-IFX was not evident. In line with studies in adults, the s-IFX trough levels correlated with response to infliximab. PMID:28272355

  17. 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…

  18. Electronic Monitoring of Medication Adherence in Early Maintenance Phase Treatment for Pediatric Leukemia and Lymphoma: Identifying Patterns of Nonadherence

    PubMed Central

    Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R.; Muriel, Anna

    2015-01-01

    Objective To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7–19 years diagnosed with ALL or LBL across 6 centers. Results The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Conclusions Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. PMID:24365698

  19. Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

    PubMed Central

    Lee, Hsin-Ya; Li, Jih-Heng; Sheu, Yuh-Ling; Tang, Hsin-Pei; Chang, Wei-Chiao; Tang, Tze-Chun; Yeh, Yi-Chun; Wang, Shing-Yaw; Liu, Ray-H.

    2013-01-01

    This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs), and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP) in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI) program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP. PMID:24455721

  20. Moving toward personalized medicine in the methadone maintenance treatment program: a pilot study on the evaluation of treatment responses in Taiwan.

    PubMed

    Lee, Hsin-Ya; Li, Jih-Heng; Sheu, Yuh-Ling; Tang, Hsin-Pei; Chang, Wei-Chiao; Tang, Tze-Chun; Yeh, Yi-Chun; Wang, Shing-Yaw; Liu, Ray-H

    2013-01-01

    This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs), and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP) in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI) program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP.

  1. 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.

  2. Employment-Based Abstinence Reinforcement as a Maintenance Intervention for the Treatment of Cocaine Dependence: A Randomized Controlled Trial

    PubMed Central

    DeFulio, Anthony; Donlin, Wendy D.; Wong, Conrad J.; Silverman, Kenneth

    2009-01-01

    Context: Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective: Determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design: Participants (N=128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly, and developed needed job skills during the first six months were hired as operators in a data entry business and randomly assigned to an employment only (Control, n = 24) or abstinence-contingent employment (n = 27) group. Setting: A nonprofit data entry business. Participants: Unemployed welfare recipients who persistently used cocaine while enrolled in methadone treatment in Baltimore. Intervention: Abstinence-contingent employment participants received one year of employment-based contingency management, in which access to employment was contingent on provision drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main Outcome Measure: Cocaine-negative urine samples at monthly assessments across one year of employment. Results: During the one-year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment only participants (79.3% and 50.7%, respectively; p = 0.004, OR = 3.73, 95% CI = 1.60 – 8.69). Conclusions: Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance

  3. Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol

    PubMed Central

    2014-01-01

    Background Use of methadone for the treatment of opioid addiction is an effective harm-reduction approach, although variability in treatment outcomes among individuals has been reported. Men and women with opioid addiction have been known to differ in factors such as opioid use patterns and characteristics at treatment entry; however, little has been reported about differences in methadone treatment outcomes between men and women. Therefore, we present a protocol for a systematic review which aims to provide a summary of existing literature on sex differences in outcomes of methadone treatment for opioid addiction. Methods/Design Electronic search of PubMed/MEDLINE, EMBASE, PsycINFO, and CINAHL databases will be conducted using a priori defined search strategy. Two authors (MB and BBD) will independently screen potential articles for eligibility using pre-determined inclusion and exclusion criteria and extract key information using a data extraction form designed for this study. Discrepancies will be resolved using a third party (ZS). The primary outcome will be sex differences in response to treatment defined as abstinence from illicit opioid use. We will also assess sex differences in treatment outcomes including treatment retention, remission status post-treatment, polysubstance abuse, methadone dose, drug-related adverse events, health status, psychological status, mortality, criminal activity, high risk sexual behavior, social support/relations, and employment. A meta-analysis will be conducted if possible; risk of bias and overall quality of evidence will be assessed to determine confidence in the estimates. Discussion We anticipate that this review will highlight how men and women differ in methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting. Systematic review registration PROSPERO CRD42013006549 PMID:24887111

  4. 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.

  5. Maintenance of access as demand for substance use disorder treatment grows.

    PubMed

    Frakt, Austin B; Trafton, Jodie; Pizer, Steven D

    2015-08-01

    Due to the Affordable Care Act and other recent laws and regulations, funding for substance use disorder (SUD) treatment is on the rise. In the 2000s, the Veterans Health Administration (VA) implemented several initiatives that increased funding for SUD treatment during a period of growth in demand for it. A key question is whether access to and intensity of treatment kept pace or declined. Using VA SUD treatment funding data and patient-level records to construct performance measures, we studied the relationship between funding and access during the VA expansion. Overall, we observed an increase in access to and intensity of VA SUD care associated with increased funding. The VA was able to increase funding for and expand the population to which it offered SUD treatment without diminishing internal access and intensity.

  6. 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.

  7. 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, 2013 CFR

    2013-07-01

    ... 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 to... are set forth in subpart E (40 CFR part 35). (b) Authority. The authority for establishment of...

  8. 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, 2011 CFR

    2011-07-01

    ... 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 to... are set forth in subpart E (40 CFR part 35). (b) Authority. The authority for establishment of...

  9. Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone.

    PubMed

    Wedekind, Dirk; Jacobs, Stefan; Karg, Iris; Luedecke, Christel; Schneider, Udo; Cimander, Konrad; Baumann, Pierre; Ruether, Eckart; Poser, Wolfgang; Havemann-Reinecke, Ursula

    2010-03-01

    Sixty D,L- or L-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower D,L- (P<0.05) and L-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower L-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of D,L- (and L-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, L-, but not D,L-methadone seems to be more effective in reducing additional heroin abuse.

  10. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy.

    PubMed Central

    Morgan, A G; McAdam, W A; Pacsoo, C; Darnborough, A

    1982-01-01

    One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%). PMID:7042486

  11. Benzodiazepine use among patients in heroin-assisted vs. methadone maintenance treatment: findings of the German randomized controlled trial.

    PubMed

    Eiroa-Orosa, Francisco José; Haasen, Christian; Verthein, Uwe; Dilg, Christoph; Schäfer, Ingo; Reimer, Jens

    2010-12-01

    Benzodiazepine (BZD) use has been found to be associated with poorer psychosocial adjustment, higher levels of polydrug use and more risk-taking behaviors among opioid dependent patients. The aim of this paper is to analyze the correlation between BZD use, BZD prescription and treatment outcome among participants in the German trial on heroin-assisted treatment. 1015 patients who participated in the study comparing heroin-assisted and methadone maintenance treatment (HAT & MMT) for 12 months were included in the analysis. Analyses were carried out to assess the association of treatment outcome with baseline BZD use, with ongoing BZD use and with different patterns of BZD prescription. Baseline BZD use correlated with lower retention rates but not with poorer outcome. Ongoing BZD use correlated with poorer outcomes. Significantly better outcomes were found in the course of phobic anxiety symptomatology for those with regular prescription of BZD. The percentage of BZD positive urine tests decreased more in HAT than in MMT. Poorer outcome for benzodiazepine users may be mediated by a higher severity of addiction. Cautious prescribing of benzodiazepines may be beneficial due to the reduction of overall illicit use.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. User Charge Revenues for Wastewater Treatment Plants--Insufficient to Cover Operation and Maintenance.

    DTIC Science & Technology

    1981-12-02

    future successful operation of costly treatment facilities may be in jeopardy, and the Nation’s clean water goals may not be achieved. (See pp. 8 to...considers reauthorizing the Clean Water Act in 1982. (See p. 5.) USER CHARGE SYSTEMS ARE INADEQUATE Eighteen of 36 municipalities GAO reviewed were not...addresses water pollution?1 How is the clean water objective to be -achieved? 2 * How is the program to be monitored and enforced? 3 How are treatment

  17. 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.

  18. [Induction and maintenance treatment of acute myelogenous leukemia in adults by sequential use of combination chemotherapy (author's transl)].

    PubMed

    Fülle, H H

    1977-04-15

    The therapeutic regimens for acute myelogenous leukemia in 2 different periods of time will be described with comparison of their results. A. 28 adults were treated with cytosine arabinoside and 6-thioguanine only. Thereby, 28% complete and 16% partial remissions were achieved. The mean duration of the complete remissions was 23 weeks. The mean survival time of the patients with complete remission amounted to 53 weeks B. 46% complete and 12% partial remissions were obtained in 37 patients treated with cytosine arabinoside and 6-thioguanine doubling the dosage of the above mentioned regimen followed by 3 cycles of TRAP (and COAP). Using a maintenance therapy with modified TRAP, COAP, and POMP cycles the complete remissions lasted 47 weeks at an average. The mean survival time of patients with complete remission was 87 weeks after start of treatment.

  19. 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

  20. Effects of Sodium Benzoate Treatment in Combination with An Extinction Training on the Maintenance of Cocaine-Supported Memory.

    PubMed

    Tsai, Yi-Ni; Tzeng, Wen-Yu; Cherng, Chianfang G; Liao, Tien You; Wu, Hsin-Hua; Lin, Jie-Kuan; Yu, Lung

    2016-02-29

    Activation of N-methyl-D-aspartate (NMDA) receptor can facilitate the extinction of various maladaptive memories. Sodium benzoate (NaB) has been known to enhance a naturally occurring full agonist on the glycine binding site of the NMDA receptor. This study aimed to test whether systemic NaB treatment can affect the extinction of a cocaine-supported memory, the cocaine-induced conditioned place preference (CPP). Following the establishment of the cocaine (10 mg/kg/conditioning × 3)-induced CPP, an extinction protocol, consisting of two consecutive extinction training bouts at an 8-h interval, was used. NaB (500 mg/kg) or an equivalent volume of saline was given immediately following each extinction training bout to test the modulating effect of NaB on the maintenance of cocaine-induced CPP. Moreover, NaB was bilaterally micro-infused into the medial prefrontal cortex (mPFC) to validate the involvement of this brain region in mediating systemic NaB treatment-produced effect on cocaine-induced CPP. Systemic (500 mg/kg) and intra-mPFC (10 μg/side) NaB treatment significantly decreased subsequent cocaine-induced CPP magnitude, although the NaB treatment or the extinction training alone did not affect such CPP magnitude. It was of importance to note that systemic or intra-mPFC NaB delivery did not affect mouse locomotor activity in the retests. These results, taken together, suggest that NaB treatment in combination with the extinction training may facilitate the extinction of the cocaine-supported memory. Moreover, systemic NaB treatment exerts such effects, at least in part, via its effect in the mPFC.

  1. 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

  2. 77 FR 72752 - Opioid Drugs in Maintenance and Detoxification Treatment of Opiate Addiction; Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... Combination as Used in Approved Opioid Treatment Medications AGENCY: Substance Abuse and Mental Health...--Buprenorphine: A Guide for Nurses.'' SAMHSA also sponsors continuing medical education seminars for nurses on... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH...

  3. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss

    PubMed Central

    Iepsen, E W; Lundgren, J; Dirksen, C; Jensen, J-EB; Pedersen, O; Hansen, T; Madsbad, S; Holst, J J; Torekov, S S

    2015-01-01

    Background: Recent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain. Methods: In a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance. Results: Soluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml−1 (−3.0 (95% confidence interval (CI)=−0.5 to −5.5)), P<0.001 and free leptin index decrease was 43% smaller; −62±15 vs −109±20 (−47 (95% CI=−11 to −83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (−2.3 kg (95% CI=−0.6 to −4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=−0.6 to −1)), P<0.001. Fasting glucose was decreased by an additional −0.2±0.1 mmol l−1 in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l−1 to the level before weight loss (−0.5mmol l−1 (95% CI=−0.1 to −0.9)), P<0.005. Meal response of peptide

  4. Multilevel Predictors of Concurrent Opioid Use during Methadone Maintenance Treatment among Drug Users with HIV/AIDS

    PubMed Central

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

    2012-01-01

    Background Ongoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy. Methods We analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations. Results Over 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR = 0.97 for 1 year increase), had economic dependents (AOR = 0.33), or were referred to TB treatment (AOR = 0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment. Conclusion These findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and

  5. [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.

  6. The role of anxiety in the development, maintenance, and treatment of childhood aggression.

    PubMed

    Granic, Isabela

    2014-11-01

    The majority of aggressive children exhibit symptoms of anxiety, yet none of our developmental models of aggression incorporate the role of anxiety, and our treatments ignore this comorbidity. This article outlines a novel theoretical model that specifies three hypotheses about comorbid anxious and aggressive children: (a) unpredictable parenting induces anxiety in children that in turn triggers aggressive behavior; (b) prolonged periods of anxiety deplete children's capacity to inhibit impulses and trigger bouts of aggression, and aggression in turn functions to regulate levels of anxiety; and (c) minor daily stressors give rise to anxiety while cognitive perseveration maintains anxious moods, increasingly disposing children to aggress. Little or no research has directly tested these hypotheses. Extant research and theory consistent with these claims are herein reviewed, and future research designs that can test them specifically are suggested. The clinical implications most relevant to the hypotheses are discussed, and to improve the efficacy of treatments for childhood aggression, it is proposed that anxiety may need to be the primary target of treatment.

  7. Can Assessment of Disease Burden Prior to Changes in Initial COPD Maintenance Treatment Provide Insight into Remaining Unmet Needs? A Retrospective Database Study in UK Primary Care.

    PubMed

    Landis, Sarah H; Wurst, Keele; Le, Hoa Van; Bonar, Kerina; Punekar, Yogesh S

    2017-02-01

    This retrospective cohort study aimed to assess treatment patterns over 24 months amongst patients with chronic obstructive pulmonary disease (COPD), initiating a new COPD maintenance treatment, and to understand clinical indicators of treatment change. Patients included in the study initiated a long-acting β2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), or a combination of LABA and an inhaled corticosteroid (ICS/LABA) between January 1, 2009, and November 30, 2013, as recorded in the United Kingdom Clinical Practice Research Datalink (UK CPRD). Treatment modifications (switching or adding maintenance treatments) over 24 months were assessed, and patient characteristics, disease burden, medication and healthcare resource use during the 30 days before treatment modification were evaluated. The cohort comprised 17,258 patients [LABA (8%), LAMA (39%) and ICS/LABA (54%)] with similar age, body mass index and dyspnoea distribution. LABA users were more likely than LAMA users to add a maintenance therapy. Distinct patterns of treatment augmentations were noted, whereby LABA users typically received dual therapy before moving to triple therapy, while LAMA users moved to triple therapy by directly adding an ICS/LABA. Exacerbation events immediately prior to treatment change were not frequently recorded; however, the need for rescue short-acting medication and assessment of dyspnoea in the 30 days prior to the treatment change suggest that dyspnoea is a remaining unmet need driving therapy change.

  8. 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.

  9. First year survival of patients on maintenance dialysis treatment in Poland

    PubMed Central

    Brodowska-Kania, Dorota; Rymarz, Aleksandra; Gibin´ski, Krzysztof; Kiełczewska, Julia; Smoszna, Jerzy; Saracyn, Marek; Szamotulska, Katarzyna; Niemczyk, Stanisław

    2015-01-01

    ABSTRACT 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

  10. Maintenance of CO2 level in a BLSS by controlling solid waste treatment unit

    NASA Astrophysics Data System (ADS)

    Dong, Yingying; Li, Leyuan; Liu, Hong; Fu, Yuming; Xie, Beizhen; Hu, Dawei; Liu, Dianlei; Dong, Chen; Liu, Guanghui

    A bioregenerative life support system (BLSS) is an artificial closed ecosystem for providing basic human life support for long-duration, far-distance space explorations such as lunar bases. In such a system, the circulation of gases is one of the main factor for realizing a higher closure degree. O2 produced by higher plants goes to humans, as well as microorganisms for the treatment of inedible plant biomass and human wastes; CO2 produced by the crew and microorganisms is provided for plant growth. During this process, an excessively high CO2 level will depress plant growth and may be harmful to human health; and if the CO2 level is too low, plant growth will also be affected. Thus, keeping the balance between CO2 and O2 levels is a crucial problem. In this study, a high-efficiency, controllable solid waste treatment unit is constructed, which adopts microbial fermentation of the mixture of inedible biomass and human wastes. CO2 production during the fermentation process is controlled by adjusting fermentation temperature, aeration rate, moisture, etc., so as to meet the CO2 requirement of plants

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

    PubMed

    Venkatraman, Srikanth; Bogen, Stéphane 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

    2006-10-05

    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.

  16. 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.

  17. 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

  18. Effectiveness of Paliperidone Palmitate vs. Haloperidol Decanoate for Maintenance Treatment of Schizophrenia: A Randomized Clinical Trial

    PubMed Central

    McEvoy, Joseph P.; Byerly, Matthew; Hamer, Robert M.; Dominik, Rosalie; Swartz, Marvin S.; Rosenheck, Robert A.; Ray, Neepa; Lamberti, J. Steven; Buckley, Peter F.; Wilkins, Tania M.; Stroup, T. Scott

    2014-01-01

    Importance Long-acting injectable (LAI) antipsychotics are used to reduce medication non-adherence and subsequent relapse in schizophrenia-spectrum disorders. The relative effectiveness of LAI versions of second-generation (atypical) and older antipsychotics has not been assessed. Objective To compare the effectiveness of the second-generation LAI antipsychotic paliperidone palmitate (PP) to the older LAI antipsychotic haloperidol decanoate (HD). Design, Setting, and Participants Multisite, double-blind, randomized clinical trial conducted at 22 clinical research sites in the U.S. The 311 randomized patients (PP=157, HD=154) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a LAI antipsychotic. Interventions Intramuscular injections of HD 25–200 mg or PP 39–234 mg every month for up to 24 months. Main Outcome Measures Efficacy failure, which reflected inadequate control of psychopathology by the study medication, as determined by a blinded adjudication committee. Key secondary outcomes were common adverse effects of antipsychotic medications. Results There was no statistically significant difference in the rate of efficacy failure for PP compared to HD (adjusted hazard ratio 0.98, 95% confidence interval [CI] 0.65–1.47). On average, patients on PP gained and those on HD lost weight; after six months the least squares mean weight change on PP was +2.17 kg (1.25 to 3.09) and on HD was −0.96 kg (−1.88 to −0.04). Patients taking PP had significantly greater increases in serum prolactin (men 34.56 µg/L (29.75 to 39.37) vs. 15.41 (10.73 to 20.08), p<0.001; women 75.19 (63.03 to 87.36) vs. 26.84 (13.29 to 40.40), p<0.001). Patients taking HD had significantly larger increases in global ratings of akathisia (0.73 [0.59 to 0.87] vs. 0.45 [0.31 to 0.59], p=0.006). Conclusions and Relevance Among adults with schizophrenia or schizoaffective disorder, treatment with

  19. Maintenance interventions for overweight or obese children and adolescents who participated in a treatment program: study protocol for a systematic review

    PubMed Central

    2014-01-01

    Background Childhood overweight and obesity are associated with significant health consequences. Early and successful treatment of this public health issue is necessary. Although several intervention programs for children result in weight loss or stabilisation in the short term, preventing relapse after weight loss remains an important challenge. Weight loss maintenance approaches in childhood are thought to be promising, but a structured overview of these maintenance interventions is lacking. The aim of the systematic review described in this protocol is to provide an overview of reports published about maintenance interventions in childhood overweight and obesity following initial treatment, in order to guide future directions in the development of maintenance programs for childhood obesity. Methods/design The electronic databases PubMed, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO, Scopus, and SocINDEX will be searched for this review. Reference lists of eligible study reports will be scanned for relevant references. Article selection including risk of bias assessment will be performed independently in an unblinded standardised manner by three authors. All reports describing a maintenance intervention in overweight or obese children with a mean or median age of <18 years who have followed a treatment program, regardless of the type of intervention, will be included. Data extraction will be performed using a predesigned pilot-tested data extraction sheet that covers participant characteristics, details about the treatment preceding the maintenance intervention, and the maintenance intervention itself. Body mass index standard deviation score (BMI-SDS or BMI-Z-score) will be used to compare studies. If possible, a meta-analysis will be performed using the inverse-variance random-effects method. Studies that are not included in the meta-analysis will be described in a narrative way in tables and/or in the text. Discussion This systematic review will

  20. Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine

    PubMed Central

    Nanda, Kavinderjit; Moss, Alan C

    2012-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine available are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System® (MMX) technology (Cosmo SpA, Milan, Italy) is an oral (1.2 g), once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda® or Mezavant®, Shire Pharmaceuticals Inc, Wayne, PA). In clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced and maintained clinical remission in patients with active mild-to-moderate UC. The overall safety profile of MMX mesalamine is similar to other oral mesalamine formulations. The use of such once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy. PMID:22888278

  1. 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.

  2. Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

    PubMed

    Meini, Milo; Moncini, Marco; Daini, Laura; Giarratana, Tania; Scaramelli, Daniela; Chericoni, Silvio; Stefanelli, Fabio; Rucci, Paola

    2015-08-05

    This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

  3. The cost-effectiveness and budget impact of Vietnam's methadone maintenance treatment programme in HIV prevention and treatment among injection drug users.

    PubMed

    Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Nguyen, Long Thanh; Vu, Phu Xuan; Mills, Steve; Houston, Stan; Jacobs, Philip

    2012-01-01

    We analysed the cost-effectiveness and budget impact of the methadone maintenance treatment (MMT) programme in HIV prevention and treatment among injection drug users (DUs) in Vietnam. The costs and health outcomes of providing MMT for opioid-dependent DUs versus non-MMT were estimated using a decision analytical model. Probabilistic sensitivity analysis using Monte Carlo simulation was conducted to justify uncertainties of model parameters simultaneously. The incremental cost-effectiveness ratio (ICER) of MMT in HIV prevention was US$3324 per one averted HIV case. The decision model showed that the cost-effectiveness ratio of MMT and non-MMT strategies was US$480 and US$204 per 1 quality-adjusted life year (QALY), equivalent to 0.43 and 0.18 times the gross domestic product per capita (GDPpc). The ICER for MMT versus non-MMT strategy was US$1964, approximately 1.76 times the GDPpc/QALY, classifying MMT as a cost-effective intervention. At the willingness to pay threshold of three times the GDPpc, the probability of MMT and non-MMT strategies being cost-effective was 80.3 and 19.7%, respectively. The budget impact of scaling up MMT from 2011 to 2015 will be US$97 million for 65% coverage or US$49 million for treating 80,000 DUs. The results indicated that MMT was cost-effective in HIV prevention and treatment among DUs who were opioid dependent.

  4. Utilization and outcomes of detoxification and maintenance treatment for opioid dependence in publicly-funded facilities in California, US: 1991-2012*

    PubMed Central

    Nosyk, Bohdan; Li, Libo; Evans, Elizabeth; Urada, Darren; Huang, David; Wood, Evan; Rawson, Richard; Hser, Yih-Ing

    2015-01-01

    Background California treats the largest population of opioid dependent individuals in the US and is among a small group of states that applies regulations for opioid treatment that are more stringent than existing federal regulations. We aim to characterize changes in patient characteristics and treatment utilization over time, and identify determinants of successful completion of detoxification and MMT retention in repeated attempts. Methods State-wide administrative data was obtained from California Outcome Measurement System during the period: January 1st, 1991 to March 31st, 2012. Short-term detoxification treatment and long-term maintenance treatment, primarily with methadone, was available to study participants. Mixed effects regression models were used to define determinants of successful completion of the detoxification treatment protocol (as classified by treatment staff) and duration of maintenance treatment. Results The study sample consisted of 237,709 unique individuals and 885,971 treatment episodes; 83.7% were detoxification treatment episodes in 1994, dropping to 40.5% in 2010. Among individuals accessing only detoxification, the adjusted odds of success declined with each successive attempt (vs. 1st attempt: 2nd: OR: 0.679; 95% CI (0.610, 0.755); 3rd: 0.557 (0.484, 0.641); 4th: 0.526 (0.445, 0.622); 5th: 0.407 (0.334, 0.497); ≥6th: 0.339 (0.288, 0.399). For those ever accessing maintenance treatment, later subsequent attempts were longer in duration, and those with two or more prior attempts at detoxification had marginally longer subsequent maintenance episodes (hazard ratio: 0.97; 95% CI: 0.95, 0.99). Finally, only 10.9% of all detoxification episodes were followed by admission into maintenance treatment within 14 days. Conclusions This study has revealed high rates of detoxification treatment for opioid dependence in California throughout the study period, and decreasing odds of success in repeated attempts at detoxification. PMID:25110333

  5. Prevalence of HIV, hepatitis B, C and G virus infections among injecting drug users on methadone maintenance treatment in Maribor.

    PubMed

    Baklan, Zvonko; Gorisek, Jelka Rebersek; Poljak, Mario; Pisec, Andrej

    2004-01-01

    The prevalence of human immunodeficiency virus (HIV) infection and hepatitis B, C, and G virus infections was determined in a selected group of 40 intravenous drug addicts on methadone maintenance treatment. No drug addict was infected with HIV. Seven drug addicts (17.5%) had serologic markers of hepatitis B infection but only one among them (2.5%) exhibited signs of active infection. 16 drug addicts (40%) had serologic markers of hepatitis C infection and 13 (32.5%) of them had an active infection with positive viral tests. 22 addicts (55%) had signs of hepatitis G infection, 9 (22.5%) of them had signs of active infection and 13 (32.5%) had signs of past infection. Addicts infected with the hepatitis B and C viruses were older and had also been taking drugs longer than those who were not infected with these two viruses. The proportion of those susceptible to infection with hepatitis B (70%) is high, reflecting a low prevalence of this disease and at the same time revealing the failure of preventive measures and the unacceptably low vaccination rate.

  6. Symptom Burden and Quality of Life in Patients with Follicular Lymphoma undergoing Maintenance Treatment with Rituximab Compared with Observation

    PubMed Central

    Walker, Mark S.; Stepanski, Edward J.; Reyes, Carolina; Satram-Hoang, Sacha; Houts, Arthur C.; Schwartzberg, Lee S.

    2011-01-01

    Background: The impact on health related quality of life (HRQoL) of rituximab maintenance (R-M) versus observation (OBS) after induction for treatment of follicular lymphoma (FL) is unclear. Methods: We reviewed the charts of 137 patients (53% female, 87% White, age 61.0 ± 12.4 years) who received either R-M (n = 53) or OBS (n = 84) after chemotherapy induction for newly diagnosed FL at community oncology practices within the US. Patients (65% with advanced disease; 48% with a high FLIPI score [3–5]) had completed ≥1 Patient Care Monitor HRQoL survey in the period following front-line therapy, and were excluded if they had progressed during front-line therapy. Results: Linear mixed models showed that postinduction, most symptoms were stable, with patients on R-M reporting HRQoL that was equal to that reported by OBS patients. Conclusions: Among R-M patients, receipt of rituximab was associated with improved psychological symptoms. PMID:23556084

  7. Methadone Maintenance Treatment Participant Retention and Behavioural Effectiveness in China: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Lei; Chow, Eric P. F.; Zhuang, Xun; Liang, Yanxian; Wang, Yafei; Tang, Caiyun; Ling, Li; Tucker, Joseph D.; Wilson, David P.

    2013-01-01

    Background Methadone maintenance treatment (MMT) has been scaled up by the Chinese government alongside persistent compulsory drug user detention, but the extent to which detention interferes with MMT is unknown. The study systematically reviews Chinese MMT retention rates, reasons for drop out, and behavioural changes. Method Chinese and English databases of literature are searched for studies reporting retention rates, drug use and sexual behaviours among MMT participants in China between 2004 and 2013. The estimates are summarized through a systematic review and meta-analysis. Results A total of 74 studies representing 43,263 individuals are included in this analysis. About a third of MMT participants drop out during the first three months of treatment (retention rate 69.0% (95% CI 57.7-78.4%)). Police arrest and detention in compulsory rehabilitation was the most common cause of drop out, accounting for 22.2% of all those not retained. Among retained participants, changing unsafe drug use behaviours was more effective than changing unsafe sexual behaviours. At 12 months following MMT initiation, 24.6% (15.7-33.5%) of MMT participants had a positive urine test, 9.3% (4.7-17.8%) injected drugs and only 1.1% (0.4-3.0%) sold sex for drugs. These correspond to 0.002 (<0.001-0.011), 0.045 (0.004-0.114) and 0.209 (0.076-0.580) times lower odds than baseline. However, MMT participants did not have substantial changes in condom use rates. Conclusion MMT is effective in drug users in China but participant retention is poor, substantially related to compulsory detention. Reforming the compulsory drug user detention system may improve MMT retention and effectiveness. PMID:23922668

  8. 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

  9. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy.

    PubMed

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed; Aggerholm, Anni; Antunovic, Petar; Astermark, Jan; Bernell, Per; Engström, Lena-Maria; Kjeldsen, Lars; Linder, Olle; Nilsson, Lars; Olsson, Anna; Holm, Mette S; Tangen, Jon M; Wallvik, Jonas; Oberg, Gunnar; Hokland, Peter; Jacobsen, Sten E; Porwit, Anna; Hellström-Lindberg, Eva

    2010-08-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.

  10. 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.

  11. Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: post-intervention outcomes

    PubMed Central

    DeFulio, Anthony; Silverman, Kenneth

    2011-01-01

    Aims Due to the chronicity of cocaine dependence, practical and effective maintenance interventions are needed to sustain long-term abstinence. We sought to assess the effects of long-term employment-based reinforcement of cocaine abstinence after discontinuation of the intervention. Design Participants who initiated sustained opiate and cocaine abstinence during a 6-month abstinence reinforcement and training program worked as data entry operators and were randomly assigned to a group that could work independent of drug use (Control, n = 24), or an abstinence-contingent employment (n = 27) group that was required to provide cocaine- and opiate-negative urine samples to work and maintain maximum rate of pay. Setting A nonprofit data entry business. Participants Unemployed welfare recipients who persistently used cocaine while in methadone treatment. Measurements Urine samples and self-reports were collected every six months for 30 months. Findings During the employment year, abstinence-contingent employment participants provided significantly more cocaine-negative samples than controls (82.7% and 54.2%; P = .01, OR = 4.61). During the follow-up year, the groups had similar rates of cocaine-negative samples (44.2% and 50.0%; P = .93), and HIV-risk behaviors. Participants’ social, employment, economic, and legal conditions were similar in the two groups across all phases of the study. Conclusions Employment-based reinforcement effectively maintains long-term cocaine abstinence, but many patients relapse to use when the abstinence contingency is discontinued, even after a year of abstinence-contingent employment. Relapse could be prevented in many patients by leaving employment-based abstinence reinforcement in place indefinitely, which could be facilitated by integrating it into typical workplaces. PMID:21226886

  12. 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.

  13. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China’s National Methadone Maintenance Treatment Program

    PubMed Central

    Rou, Keming; Zhao, Yan; Cao, Xiaobin; Luo, Wei; Liu, Enwu; Wu, Zunyou

    2016-01-01

    Background Hepatitis C virus (HCV) is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT) program. Methods Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution. Results Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17–8.52, p<0.0001) and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96–2.06, p<0.0001). Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001). Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012. Conclusions The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China. PMID:26906025

  14. 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

  15. Association between improvement in depression, reduced benzodiazepine (BDZ) abuse, and increased psychotropic medication use in methadone maintenance treatment (MMT) patients.

    PubMed

    Schreiber, Shaul; Peles, Einat; Adelson, Miriam

    2008-01-01

    We had evaluated the depressive symptoms severity of 75 former heroin addicts in methadone maintenance treatment (MMT) using the 21-item Hamilton rating scale for depression (21-HAM-D) and re-assessed 63 of them 1.6+/-0.3 years later. The second mean 21-HAM-D score was lower than the first (11.8+/-8.4 versus 17.4+/-6.2, p<0.0005). Benzodiazepine (BDZ) abuse was lower although not significantly (p=0.06) during the month preceding the second analysis (32/63, 50.8%) than the month preceding the first one (40/63, 63.5%). Psychotropic medication usage was higher at the second assessment than at the first one (50/63, 79.4% versus 27/63, 42.9%, p<0.0005). 21-HAM-D score reduced significantly over time among 13 "no psychotropic medication" patients (13.5+/-6.3 versus 6.8+/-6.8, p=0.005) and in 27 who started medication following the first assessment (19.3+/-3.8 versus 11.0+/-8.4, p<0.0005), but not in those who were already taking any medication before the first assessment (17.7+/-7.0 versus 15.0+/-8.0, p=n.s). 21-HAM-D score reduced in all BDZ groups but scores were still highest in the 32 patients who continued BDZ abuse (19.4+/-5.6 versus 15.2+/-7.7) followed by 14 who stopped it (16.8+/-6.4 versus 9.6+/-9.1) and were lowest in 17 patients who never abused BDZ (14.2+/-5.2 versus 7.2+/-6.4) (repeated measured, time and group effect, each p<0.0005). Predictors for being depressed at follow-up were pre-existing depression only. Stopping BDZ abuse and starting psychotropic treatment was associated with a reduction of depressive symptoms among MMT patients.

  16. 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

  17. 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.

  18. 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…

  19. 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…

  20. Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus/hepatitis B virus-coinfected individuals for whom interferon-alpha and lamivudine therapy have failed.

    PubMed

    Ristig, Maria B; Crippin, Jeffrey; Aberg, Judith A; Powderly, William G; Lisker-Melman, Mauricio; Kessels, Lisa; Tebas, Pablo

    2002-12-15

    A significant proportion of human immunodeficiency virus (HIV) infected patients are coinfected with hepatitis B virus (HBV). Currently available treatments for chronic hepatitis B (interferon [IFN]-alpha and lamivudine [3TC]) have limited long-term utility because of side effects or of the development of resistance. Tenofovir disoproxil fumarate (TDF) is a nucleotide analog with excellent activity in vitro against HBV, which is also active against 3TC-resistant HBV variants. In this 24-week pilot study, the anti-HBV activity of TDF was prospectively evaluated in a cohort of 6 HIV coinfected subjects for whom 3TC and IFN therapy had previously failed. At baseline, all patients were taking 3TC or FTC and were hepatitis B surface antigen and hepatitis B e antigen positive; 4 had cirrhosis. Baseline HBV load was 7.95 log(10) copies/mL. By weeks 12 and 24, HBV load had decreased by 3.1 log(10) copies/mL and 4.3 log(10) copies/mL, respectively. There was a transient increase of transaminases after the initiation of treatment. No patient developed HBe antibodies. TDF is a very promising drug for the treatment of chronic hepatitis B in HIV-infected individuals.

  1. 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

  2. Maintenance Therapy with Partially Hydrolyzed Guar Gum in the Conservative Treatment of Chronic Anal Fissure: Results of a Prospective, Randomized Study

    PubMed Central

    Izzo, Giuseppe; Di Martino, Natale; Renzi, Adolfo

    2014-01-01

    Purpose. This study was designed to evaluate the role of maintenance therapy with partially hydrolyzed guar gum (PHGG) after topical application of glyceryl trinitrate (GTN) in the conservative treatment of chronic anal fissure (CAF). Methods. From all the patients with CAF observed during the study period, 165 subjects with healed CAF after standard therapy with topical GTN 0.4% ointment were randomized to receive (group II) or not (group I) maintenance therapy with PHGG for 10 months. Clinical and manometric followup was carried out 6 and 12 months after treatment. Results. At six-month followup, median visual analogue scale score was significantly higher in group I if compared with group II. The success and recurrence rate at 12-month followup were, respectively, 38.3% (28/73) in group I versus 58.5% (41/70) in group II (P = 0.019; Fisher's exact test) and 30.2% (13/43) in group I versus 14.5% (7/48) in group II (P = 0.0047; Fisher's exact test). Conclusion. The maintenance therapy with PHGG in patients with healed CAF after chemical sphincterotomy by topical application of GTN 0.4% ointment seems associated with a significant reduction of recurrence rate and with a significant increase of success rate at 12-month followup. PMID:25089280

  3. Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma.

    PubMed Central

    Johnston, S. R.; Constenla, D. O.; Moore, J.; Atkinson, H.; A'Hern, R. P.; Dadian, G.; Riches, P. G.; Gore, M. E.

    1998-01-01

    The purpose of this study was to evaluate in a randomized phase II trial the efficacy and toxicity of combination biochemotherapy compared with chemotherapy alone in patients with metastatic melanoma. Sixty-five patients with metastatic melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3), DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n = 35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s. (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9 MU (days 1-3). Evidence for immune activation was determined by flow cytometric analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up to six courses depending on response. The overall response rate of BCDT with IL-2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12-46%) with eight PRs; the median durations of response were 2.8 months and 2.5 months respectively. Sites of response were similar in both groups. There was no difference between the two groups in progression-free survival or overall survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant lymphopenia, evidence of immune activation was indicated by a significant rise in the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells) subsets, without any change in the percentage of CD4 or CD4 T-cell subsets. Toxicity assessment revealed a significantly higher incidence of severe thrombocytopenia in patients treated with combination chemotherapy than with chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu-like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous IL-2 and IFNalpha to

  4. Functional Genetic Polymorphisms in CYP2C19 Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort

    PubMed Central

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C.H.; Chang, Yao-Sheng

    2013-01-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations. PMID:24016178

  5. Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

    PubMed

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

    2013-10-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

  6. Rational-Emotive, Self-Instructional, and Behavioral Assertion Training: Enhancing the Generalization and Maintenance of Treatment Gains.

    ERIC Educational Resources Information Center

    Carmody, Timothy P.

    A sample of 63 subassertive adults participated in four 90-minute sessions of group assertion training. The treatment components of challenging maladaptive cognitions and learning self-instructions were examined by comparing Rational-Emotive, Self-Instructional, and Behavioral Assertion Training. A delayed-treatment control group was also…

  7. 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

  8. The Effectiveness of Group Family Training About the Principles of Harm Reduction Approach on Marital Satisfaction of Spouses of Patients Under Methadone Maintenance Treatment.

    PubMed

    Hojjat, Seyed Kaveh; Rezaei, Mahdi; Hatami, Seyed Esmaeil; Kohestani, Mina; Norozi Khalili, Mina

    2017-01-02

    One of the most important problems in treatment of drug dependence is the cooperation of the patient's family. Many families do not look at drug dependence as a chronic and relapsing disorder and expect a quick and definite recovery of the disease. These families, including wives, are unfamiliar with the concept of harm reduction as a realistic approach. The aim of this study was to educate the spouses of patients undergoing methadone maintenance treatment (MMT) on the different aspects of harm reduction approach and assess the impact of this training on marital satisfaction and relapse rate. This study was a pretest-posttest study with control group. The sample consisted of 50 MMT patients and their wives in private methadone maintenance treatment clinics in the city of Bojnurd, located in the northeastern region of Iran. The experimental group received eight group training sessions run by a psychiatrist. The content of the training sessions was based on harm reduction programs for families of patients with high-risk behaviors. Two groups are compared in terms of marital satisfaction and relapse rate. A paired t test was used to compare changes before and after the training. The results of this study showed that harm reduction education and efforts for changing wives' views toward MMT are effective in increasing their marital satisfaction. However, the conducted training showed no effect on relapse rate in the six-month follow-up. Regarding the fact that this type of training has not been paid enough attention in the national protocol, the proposed training program of this research can be considered in MMT clinics.

  9. Change in body image and psychological well-being during behavioral obesity treatment: Associations with weight loss and maintenance.

    PubMed

    Palmeira, António L; Branco, Teresa L; Martins, Sandra C; Minderico, Cláudia S; Silva, Marlene N; Vieira, Paulo N; Barata, José T; Serpa, Sidónio O; Sardinha, Luís B; Teixeira, Pedro J

    2010-06-01

    This study reports on outcomes from a behavioral obesity treatment program, evaluating if treatment-related changes in body image and psychological well-being are predictors of weight change during treatment and after follow-up. Participants were 142 overweight/obese women (BMI=30.2+/-3.7kg/m(2); age=38.3+/-5.8 years) participants in a behavioral treatment program consisting of a 4-month treatment period and a 12-month follow-up. Psychosocial variables improved during treatment and these changes were correlated with 4-month weight reduction. Short-term changes in body size dissatisfaction (p=.002) and mood (p=.003) predicted long-term weight loss. Additional results suggest that there might be a predictive role of short-term changes in body size dissatisfaction and self-esteem on long-term weight loss after accounting for initial weight change (p<.028). We conclude that, along with weight changes, cognitive and affect-related processes influenced during obesity treatment may be related long-term success, in some cases independently of initial weight loss.

  10. Older adults prescribed methadone: a review of the literature across the life span from opiate initiation to methadone maintenance treatment.

    PubMed

    Doukas, Nick

    2014-01-01

    Professionals currently working with methadone patients are facing challenges with the rise of polydrug use, HIV and Hepatitis epidemics, and treating a large volume of individuals who are older than ever before, presenting for the first time in their 50's, 60's and 70's. There have been two literature reviews conducted on this older population, but they can only provide a snap-shot view on the later stage of life of this unique group. A longitudinal literature review of the long-term opiate abuser who has transitioned into opiate replacement therapy will provide depth and illustrate the complexity of interrelated factors that have been affected throughout their life span. This paper reviews the literature conducted on opiate addicts from their earlier stages of substance use to older adulthood where many have chosen to enter into a methadone maintenance program. The paper will also take a biopsychosocial approach when reviewing the literature because of how these three domains are deeply affected and interrelated with this population.

  11. Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis: results of the CARE study.

    PubMed

    Qunibi, Wajeh Y; Nolan, Charles R

    2004-09-01

    Most patients with end-stage renal disease develop hyperphosphatemia because their dietary intake exceeds phosphorus elimination by intermittent thrice-weekly dialysis. Inadequately treated hyperphosphatemia plays a central role in the pathogenesis of secondary hyperparathyroidism and extraosseous calcification. Moreover, in the last 15 years, this biochemical abnormality has become increasingly important following the publication of two epidemiologic studies that demonstrated an association between elevated serum phosphorus and increased mortality risk in patients with end-stage renal disease. As a result, the National Kidney Foundation Kidney Disease Outcome and Quality Initiative (K/DOQI) Bone Metabolism and Chronic Kidney Disease Guidelines recommend that serum phosphorus levels be maintained between 3.5 and 5.5 mg/dL. Unfortunately, cross-sectional studies have shown a mean serum phosphorus of 6.2 mg/dL in the maintenance hemodialysis population in the United States. An alarming 60% of patients have serum phosphorus in excess of the 5.5 mg/dL level recommended by K/DOQI guidelines. In order to achieve this new target for serum phosphorus, the most efficacious and cost-effective phosphate binders currently available should be utilized. In this review, we discuss the results of the Calcium Acetate Renagel Evaluation (CARE study), which clearly demonstrated the superiority of calcium acetate over sevelamer hydrochloride for controlling serum phosphorus and calcium-phosphate product to the levels recommended by the K/DOQI guidelines.

  12. Low-dose add-on memantine treatment may improve cognitive performance and self-reported health conditions in opioid-dependent patients undergoing methadone-maintenance-therapy

    PubMed Central

    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

  13. 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.

  14. 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…

  15. Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction?

    PubMed

    Koester, S; Anderson, K; Hoffer, L

    1999-12-01

    In addition to the numerous heroin users who voluntarily enter methadone treatment as a way to free themselves from illicit drug addiction and those ordered to do so by the courts, there are a large number of opioid users who enter methadone treatment with other objectives in mind. These include shorter-term goals that users do not necessarily equate with complete heroin abstinence. In this paper we report the results of a qualitative study designed to identify and describe the motivations active heroin users have for entering methadone treatment, and to suggest that many of these short-term methadone episodes may operate as self-prescribed attempts at risk reduction, and act as pilot tests for users considering or anticipating entering treatment to quit the use of illicit drugs. We argue that heroin users' motivations, perceptions about methadone, and the strategies they devise for adapting methadone treatment for their own needs should be recognized for their value in reducing the multiple risks associated with drug use.

  16. 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

  17. 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

  18. Alcoholics Anonymous and Relapse Prevention as Maintenance Strategies After Conjoint Behavioral Alcohol Treatment for Men: 18-Month Outcomes

    ERIC Educational Resources Information Center

    McCrady, Barbara S.; Epstein, Elizabeth E.; Kahler, Christopher W.

    2004-01-01

    Ninety men with alcohol problems and their female partners were randomly assigned to 1 of 3 outpatient conjoint treatments: alcohol behavioral couples therapy (ABCT), ABCT with relapse prevention techniques (RP/ABCT), or ABCT with interventions encouraging Alcoholics Anonymous (AA) involvement (AA/ABCT). Couples were followed for 18 months after…

  19. Programmed Stuttering Treatment for Children: Comparison of Two Establishment Programs through Transfer, Maintenance, and Follow-Up.

    ERIC Educational Resources Information Center

    Ryan, Bruce P.; Ryan, Barbara Van Kirk

    1995-01-01

    Two operant speech treatment programs for establishing fluent speech--Delayed Auditory Feedback and Gradual Increase in Length and Complexity of Utterance--were compared, with 24 elementary-secondary level students. Both programs produced important improvement in fluency in a reasonable time period and resulted in similar levels of transfer and…

  20. Effect of different frequencies of preventive maintenance treatment on dental caries: five-year observations in general dentistry patients.

    PubMed

    Rosén, Birgitta; Olavi, Göran; Birkhed, Dowen; Edvardsson, Stig; Egelberg, Jan

    2004-10-01

    A long-term study in adults at a public dental clinic in Sweden was initiated to evaluate the relative effectiveness of prophylactic treatments on the progression of dental caries and periodontal discase. With treatments scheduled every 3rd, 6th, 12th or 18th month, this report presents results on caries for the 3-month, 6-month and 18-month groups, and evaluates the impact of various caries-related risk factors. Caries increment over approximately 5 years was determined by adding clinical and radiographic findings of manifest primary and secondary caries during the study. Overall caries activity among all 105 participating individuals was low to moderate. No significant differences for caries on any of the various tooth surfaces or for total caries were observed among the three groups. Multiple regression analysis with 5-year caries increment as dependent variable showed that the following factors had a statistically significant association with caries increment: percentage filled surfaces at baseline examination, dietary score, plaque score, and number of mutans streptococci and lactobacilli in saliva. Non-significant factors included number of preventive treatments provided during the 5-year interval. The results of this long-term trial suggest that preventive treatments as often as every 3 6 months may not be justified in the case of patients with low to moderate caries activity.

  1. A comparison of HCV antibody testing in drug-free and methadone maintenance treatment programs in the United States.

    PubMed

    Strauss, Shiela M; Astone, Janetta M; Jarlais, Don Des; Hagan, Holly

    2004-03-08

    Drug treatment programs are uniquely situated to screen patients for antibodies for hepatitis C virus (HCV), an infectious disease that has reached epidemic proportions among drug users. This paper compares the accessibility and patients' use of opportunities for HCV antibody testing in a large sample of methadone and drug-free treatment programs (N=256) in the US, and reports programs' recent changes and future plans concerning it. Results indicate that almost all methadone and about two-thirds of drug-free programs in the sample provided HCV antibody screening to at least some patients in 2001. While about two-thirds of the methadone and close to one-third of the drug-free programs offered this service to all patients, these programs report that only about 3/5 of their patients actually provided specimens for testing for HCV antibodies. Some drug treatment programs were planning to increase the availability and accessibility of HCV antibody screening, but others were planning to cut back on these services, primarily due to limited resources. These results can inform policymakers who advocate for increased HCV antibody screening in drug treatment programs about the current level and future plans for implementing these services, illuminating where resources and motivational efforts need to be targeted.

  2. 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…

  3. Assessing the efficacy of 2 years of maintenance treatment with venlafaxine extended release 75–225 mg/day in patients with recurrent major depression: a secondary analysis of data from the PREVENT study

    PubMed Central

    Kornstein, Susan G.; Kocsis, James H.; Ahmed, Saeeduddin; Thase, Michael; Friedman, Edward S.; Dunlop, Boadie W.; Yan, Bing; Pedersen, Ron; Ninan, Philip T.; Li, Thomas; Keller, Martin

    2013-01-01

    The objective of this study was to evaluate the long-term efficacy of venlafaxine extended release (ER) ≤225 mg/ day in patients with recurrent major depressive disorder (MDD). In this double-blind trial, outpatients with recurrent MDD (N=1096) were randomized to 10 weeks of acute-phase treatment with venlafaxine ER (75–300 mg/ day) or fluoxetine (20–60 mg/day) followed by a 6-month continuation phase and two consecutive 12-month maintenance phases. At the start of each maintenance period, venlafaxine ER responders were randomized to double-blind venlafaxine ER or placebo. In this analysis, data from responders to acute and continuation treatment were analyzed during the combined maintenance phases while receiving venlafaxine ER ≤225 mg/day. Failure to maintain response was defined as an increase in maintenance dose to 300 mg/day or recurrence. Differences were calculated using Kaplan–Meier methods and compared using log-rank tests. Continuation-phase responders (n =114) receiving venlafaxine ER ≤225 mg/ day comprised the analysis population (venlafaxine ER: n= 55; placebo: n= 59). The estimated probability for remaining well across 24 months of maintenance treatment was 67% for venlafaxine ER and 41% for placebo (P = 0.007). Venlafaxine ER effectively maintained response at doses ≤225 mg/day for up to 2.5 years in patients with recurrent MDD. The findings are consistent with those of the full data set. PMID:18854724

  4. Changes in Millon Clinical Multiaxial Inventory scores among opiate addicts as a function of retention in methadone maintenance treatment and recent drug use.

    PubMed

    Calsyn, D A; Wells, E A; Fleming, C; Saxon, A J

    2000-05-01

    The Millon Clinical Multiaxial Inventory (MCMI) was administered to 144 men and 86 women within 1 month of admission to methadone maintenance treatment and was readministered 18 months following admission. Based on prior research, we hypothesized there would be significant decreases on scales measuring affective disturbance, anxiety, and social isolation and little change in scales measuring antisocial and narcissistic traits. In addition, it was hypothesized that changes on the MCMI would be related to retention in treatment and illicit drug use during the interim between initial assessment and follow-up. Data were analyzed using a multivariate analysis of variance (MANOVA) for repeated measures. There was an overall decrease in MCMI scores, indicating less psychopathology between initial assessment and follow-up. MCMI scales did not change as a function of retention status, but decreases in MCMI scale scores were greater for subjects who were light drug users in the 6 months prior to the follow-up compared to heavy users. Inspection of individual MCMI scales supported our hypothesis; there were decreases on scales measuring affective disturbance, anxiety, and social isolation, but not on scales measuring antisocial and narcissistic traits.

  5. Psychological and behavioural factors associated with long-term weight maintenance after a multidisciplinary treatment of uncomplicated obesity.

    PubMed

    Buscemi, Silvio; Castellini, Giovanni; Batsis, John A; Ricca, Valdo; Sprini, Delia; Galvano, Fabio; Grosso, Giuseppe; Rosafio, Giuseppe; Caravello, Marzia; Rini, Giovam Battista

    2013-12-01

    Obesity is a multifactorial syndrome and the likelihood of success of a medical nutritional treatment (MNT) over the long term is low. As psychological and behavioural factors have an important role in both pathogenesis and the treatment of obesity, these issues were investigated in individuals with obesity who reported a long-term success or a failure in terms of weight loss following a MNT. Eighty-eight individuals of an original cohort of 251 subjects were re-evaluated 10 years after a MNT with cognitive-behavioural approach for uncomplicated obesity. Fifty-three participants were classified as failure (body weight change ≥0.5 kg) and 35 as a success (10-year body weight change <0.5 kg) of the MNT. Prior to the beginning of the weight-management program, both the Dieting Readiness Test (DRT) and the Hospital Anxiety and Depression Scale (HADS) were administered. At a 10-year follow-up after the MNT, self-reported questionnaires were administered: quality of life was assessed by the Obesity Related Well-Being (ORWELL 97) questionnaire, eating attitudes and behaviours by the Eating Disorder Examination Questionnaire (EDE-Q), the Binge Eating Scale (BES) investigated the presence and severity of binge eating and the Symptom Checklist (SCL 90-R) was used to identify the psychopathological distress. The scores of the ORWELL 97 items concerning symptoms (P = 0.005), discomfort (P = 0.03) and the total score (P = 0.02) were significantly lower in the success group. The depression score of the HADS was positively correlated with the percentage of body weight change observed 10 years after the MNT (r = 0.22; P = 0.045). The scores of the shape concern (EDE-Q) (r = 0.35; P = 0.013) and of the discomfort (ORWELL 97) (r = 0.36; P = 0.012) were significantly correlated with the percentage of body weight change 10 years after the MNT. In conclusion, this study is in agreement with the possibility that the psychological quality of life is associated even with modest amounts

  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. 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

  8. Clinical study of Shengxuening tablet combined with rHuEPO for the treatment of renal anemia of maintenance hemodialysis patients.

    PubMed

    Cheng, Xin; Yu, Guojun; Hu, Jiangping; Xu, Xuefeng; Luo, Fang; Shen, Ping; Zhang, Guosheng; Yang, Ning

    2016-07-01

    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.

  9. Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays.

    PubMed

    Spanbauer, A C; Casseday, S; Davoudzadeh, D; Preston, K L; Huestis, M A

    2001-10-01

    Heroin, with a plasma half-life of approximately 5 min, is rapidly metabolized to 6-acetylmorphine (6-AM). 6-AM, a specific marker for heroin use, which also has a short half-life of only 0.6 h, is detected in urine for only a few hours after heroin exposure. Ingestion of poppy seeds and/or licit opiate analgesics can produce positive urine opiate tests. This has complicated the interpretation of positive opiate results and contributed to the decision to raise opiate cutoff concentrations and to require 6-AM confirmation in federally mandated workplace drug-testing programs. Microgenics Corp. has developed the CEDIA 6-AM assay, a homogeneous enzyme immunoassay for semiquantitative determination of 6-AM in human urine, in addition to its CEDIA DAU opiate assay. Urine specimens were collected 3 times per week from 27 participants enrolled in a clinical research trial evaluating a contingency management treatment program for heroin and cocaine abuse. Of the 1377 urine specimens screened, 261 (18.9%) were positive for opiates at > or = 300 ng/mL, 153 (11.1%) were positive for opiates at > or = 2000 ng/mL, and 55 (4.0%) were positive for 6-AM at > or = 10 ng/mL. For opiate-positive screens > or = 300 and > or = 2000 ng/mL, 91.3% and 80.8% confirmed positive for morphine or codeine at the respective gas chromatography-mass spectrometry (GC-MS) cutoffs. All specimens screening positive for 6-AM also confirmed positive by GC-MS at > or = 10 ng/mL. Increasing the opiate screening and confirmation cutoffs for the federal workplace drug-testing program resulted in 8% fewer opiate-positive tests; however, recent heroin use was not affected by this change.

  10. Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials

    PubMed Central

    Majer, Istvan M.; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten

    2015-01-01

    Background Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. Objective This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. Data sources A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Study selection Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extraction Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data synthesis Data were analyzed by applying a mixed treatment comparison competing risks model

  11. Maintenance Business Plans.

    ERIC Educational Resources Information Center

    Adams, Matt

    2002-01-01

    Discusses maintenance business plans, statements which provide accountability for facilities maintenance organizations' considerable budgets. Discusses the plan's components: statement of plan objectives, macro and detailed description of the facility assets, maintenance function descriptions, description of key performance indicators, milestone…

  12. Maintenance Management Update.

    ERIC Educational Resources Information Center

    Sternloff, Robert E.

    1987-01-01

    Current trends in park maintenance are overviewed, including maintenance impact statements, avoidance of cost through efficient use and national resource conservation, horticultural accomplishments that influence maintenance management, and vandalism prevention. (CB)

  13. Evaluation of a low-threshold/high-tolerance methadone maintenance treatment clinic in saint john, new brunswick, Canada: one year retention rate and illicit drug use.

    PubMed

    Christie, Timothy K S; Murugesan, Alli; Manzer, Dana; O'Shaughnessey, Michael V; Webster, Duncan

    2013-01-01

    Objective. To report the one-year retention rate and the prevalence of illicit opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT) methadone maintenance treatment (MMT) clinic located in Saint John, New Brunswick, Canada. Methods. A description of the LTHT MMT clinic is provided. The one-year retention rate was determined by collecting data on patients who enrolled in the LTHT MMT clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit drug use was determined using a randomly selected retrospective cohort of 84 participants. For each participant the results of six consecutive urine tests for the most recent three months were compared to the results of the first six consecutive urine tests after program entry. Results. The one-year retention rate was 95%, 67% of the cohort achieved abstinence from illicit opioids and an additional 13% abstained from cocaine use. Conclusion. The novel feature of the LTHT MMT clinic is that patients are not denied methadone because of lack of ancillary services. Traditional comprehensive MMT programs invest the majority of financial resources in ancillary services that support the biopsychosocial model, whereas the LTHT approach utilizes a medical model and directs resources at medical management.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Pediatric hepatitis B treatment

    PubMed Central

    Inui, Ayano; Fujisawa, Tomoo

    2017-01-01

    Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts’ opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection. PMID

  19. Activation of AMPK protects against hydrogen peroxide-induced osteoblast apoptosis through autophagy induction and NADPH maintenance: new implications for osteonecrosis treatment?

    PubMed

    She, Chang; Zhu, Lun-qing; Zhen, Yun-fang; Wang, Xiao-dong; Dong, Qi-rong

    2014-01-01

    Elevated hydrogen peroxide (H2O2) causes osteoblast dysfunction and apoptosis, serving as an important contributor to the development of osteonecrosis. Here we aimed to understand the role of AMP-activated protein kinase (AMPK) in the process. We observed a high level of AMPK activation in surgery isolated patients' osteonecrosis tissues. In cultured osteoblastoma MG63 cells, H2O2 stimulation induced significant AMPK activation, oxidative stress, cell death and apoptosis. Inhibition of AMPK by its inhibitor (compound C) or by shRNA-mediated knockdown dramatically enhanced H2O2-induced MG63 cell apoptosis, while over-expression of AMPK in HEK-293 cells alleviated H2O2-induced cell damage. These results confirmed that H2O2-activated AMPK is pro-cell survival. We observed that H2O2 induced protective autophagy in MG63 cells, and AMPK-dependent Ulk1 activation and mTORC1 (mTOR complex 1) inactivation might involve autophagy activation. Further, AMPK activation inhibited H2O2-induced oxidative stress, probably through inhibiting NADPH (nicotinamide adenine dinucleotide phosphate) depletion, since more NADPH depletion and oxidative stress were induced by H2O2 in AMPK deficient MG63 cells. Finally, we observed a significant AMPK activation in H2O2-treated primary cultured and transformed (MC3T3-E1) osteoblasts, and AMPK inhibitor compound C enhanced death by H2O2 in these cells. Based on these results, we concluded that H2O2-induced AMPK activation is pro-survival and anti-apoptosis in osteoblasts. Autophagy induction and NADPH maintenance are involved in AMPK-mediated pro-survival effects. AMPK might represent a novel molecular target for osteonecrosis treatment.

  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. Establishing maintenance performance indicators

    SciTech Connect

    Baca, B.

    1994-10-01

    Maintenance Performance Indicators (PI) specify where the maintenance department is and which direction it is going allowing for a quick and accurate assessment of the performance of the Maintenance Management Program (MMP). Establishing PI`s for the maintenance department will allow a measure of productivity and a means of feedback for methods improvement. Effective performance of the maintenance department directly effects plant profitability. Improvements in the quality and productivity of the maintenance work force will significantly reduce maintenance costs. The level of performance attained by the maintenance work force is usually guessed at. Guessing will not identify areas needing improvement or help to initiate a corrective action. Maintenance PI`s are required for maintenance departments whose goal is to control maintenance costs while increasing productivity. The application of basic statistical methods will allow a maintenance department to know where they are and which direction they are going. The data presented in this paper is a representation of indicators used in industry as well as developed indicators to establish a complete maintenance performance indicator program. The methodology used in developing this program can be used as a way to manage a cost effective maintenance management program.

  2. 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

  3. Situation-specific factors predicting nonadherence to methadone maintenance treatment: a cross-sectional study using the case-crossover design in Guangzhou, China.

    PubMed

    Gu, Jing; Xu, Huifang; Lau, Joseph T F; Chen, Long; Wang, Zixin; Hao, Chun; Hao, Yuantao

    2014-01-01

    Methadone maintenance treatment (MMT) is a key risk reduction measure for controlling HIV transmission among drug users. Studies using traditional methods exist to distinguish between drop outs and nondrop outs. However, many nondrop outs use MMT discontinuously and no study has identified situation-specific factors predicting their showing or not showing up. This study used a case-crossover design comparing situation-specific factors appearing on the last episode of attendance versus those of the last episode of nonattendance. A total of 133 participants were recruited from two MMT clinics in Guangzhou, China. Participants were asked separately whether various situation-specific factors existed in the last episodes of nonattendance and attendance of MMT. Matched odds ratios (ORs) based on conditional logistic regression analysis were presented. The results showed that the participants attended the MMT clinics on average for 25 days in the last month. Situation-specific factors significantly predicting nonattendance included: (1) physical and mental health status: in illness (OR = 33.0, P < 0.001), in a bad mood (OR = 7.5, P < 0.001), and occurrence of an unhappy event (OR = 18.0, P < 0.001); (2) other engagement: work engagement (OR = 40.0, P < 0.001), trip to other places (OR = 83.0, P < 0.001), and social activities (OR = 10.0, P = 0.012); (3) interpersonal relationship: conflicts with family (OR = 19.0, P = 0.004); and (4) structural situational factors: financial difficulty (OR = 19.0, P = 0.004) and worrying about police arrest (OR = 12.0, P = 0.003). Other factors such as interaction with drug users and heroin use were marginally significant, while reduced methadone dosage was nonsignificant. Interventions to improve MMT adherence need to consider situation-specific factors. Ancillary psychosocial services should be integrated with current MMT; MMT should also provide more flexible services to the clients. Furthermore, efforts should be taken to build up

  4. Pharmacokinetic-pharmacodynamic modeling of mood and withdrawal symptoms in relation to plasma concentrations of methadone in patients undergoing methadone maintenance treatment.

    PubMed

    Shiran, Mohammad-Reza; Lennard, Martin S; Iqbal, Mohammad-Zafar; Lagundoye, Olawale; Seivewright, Nicholas; Tucker, Geoffrey T; Rostami-Hodjegan, Amin

    2012-10-01

    The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers' concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT). Eighty-eight regular subjects at the Sheffield Care Trust Substance Misuse Services were studied. Samples of blood and urine were collected before the daily dose of methadone. Blood samples were taken up to 5 hours after dose. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by liquid chromatography-mass spectrometry. The Total Mood Disturbance Score (TMDS), the Objective Opioid Withdrawal Scale (OOWS), and the Subjective Opioid Withdrawal Scale (SOWS) were used as measures of mood and withdrawal. Population pharmacokinetic/pharmacodynamic analysis and subsequent multiple regression analysis were used to determine the factors influencing the pharmacodynamic effects of methadone. Significant decreases (P ≤ 0.04) were observed in the scores for the TMDS, SOWS, and OOWS for 5 hours after methadone dosage. The TMDS had returned to baseline by 10 hours after dose (P = 0.98), at which time the SOWS remained significantly below baseline (P = 0.001). Multiple regression analysis revealed that 33% of the overall variation in unbound (R)-methadone EC50 was explained by 3 variables, namely CYP3A activity (9%), age (16%), and sex (8%). Age also accounted for 8% and 9% of the variation in total (rac)- and (R)-methadone EC50. The present study has confirmed that the duration of mood change in the present study was shorter than the effect of methadone in stabilizing withdrawal symptoms. Thus, it is likely that a once-daily dose of methadone, albeit effective for preventing withdrawal, may not be sufficient to improve mood in some patients. Finally, it was established that CYP3A

  5. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma.

    PubMed

    Rini, Brian I; McDermott, David F; Hammers, Hans; Bro, William; Bukowski, Ronald M; Faba, Bernard; Faba, Jo; Figlin, Robert A; Hutson, Thomas; Jonasch, Eric; Joseph, Richard W; Leibovich, Bradley C; Olencki, Thomas; Pantuck, Allan J; Quinn, David I; Seery, Virginia; Voss, Martin H; Wood, Christopher G; Wood, Laura S; Atkins, Michael B

    2016-01-01

    Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.

  6. 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

  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. 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…

  9. Microform Reader Maintenance.

    ERIC Educational Resources Information Center

    Hall, Hal W.; Michaels, George H.

    1985-01-01

    Describes experiences in organizing a program of microform reader and reader/printer maintenance at Texas A & M's Sterling C. Evans Library and offers guidelines for regular machine maintenance and repair. Guidelines discussed relate to maintenance philosophy, general machine cleaning, troubleshooting, service contracts, supplies,…

  10. 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…

  11. 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)…

  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,…

  13. Maintenance Management System

    DTIC Science & Technology

    1990-06-01

    maintenance opera- tions. d. Available national maintenance management system (MMS) software be utilized to develop the planning, organizing...portland cement concrete pavements to level and realign faulted areas between slabs or craks within the slab by grinding the high side. MAINTENANCE ITEM

  14. 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).

  15. Benefits of the intermittent use of 6-mercaptopurine and methotrexate in maintenance treatment for low-risk acute lymphoblastic leukemia in children: randomized trial from the Brazilian Childhood Cooperative Group--protocol ALL-99.

    PubMed

    Brandalise, Silvia R; Pinheiro, Vitória R; Aguiar, Simone S; Matsuda, Eduardo I; Otubo, Rosemary; Yunes, José A; Pereira, Waldir V; Carvalho, Eny G; Cristofani, Lilian M; Souza, Marcelo S; Lee, Maria L; Dobbin, Jane A; Pombo-de-Oliveira, Maria S; Lopes, Luiz F; Melnikoff, Katharina N T; Brunetto, Algemir L; Tone, Luiz G; Scrideli, Carlos A; Morais, Vera L L; Viana, Marcos B

    2010-04-10

    PURPOSE To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. PATIENTS AND METHODS Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MTX (200 mg/m(2) every 3 weeks; group 2, n = 272). RESULTS The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P = .28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2). CONCLUSION The intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

  16. A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer

    PubMed Central

    2012-01-01

    Background Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research. Methods This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs). Results A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the

  17. 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.

  18. Role of Carbamazepine in the Symptomatic Treatment of Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature

    PubMed Central

    Ravikumar, Sandhya; Crawford, John Ross

    2013-01-01

    We describe the clinical presentation and clinical course of subacute sclerosing panencephalitis in a 13-year-old previously healthy boy who recently immigrated to the United States from Iraq. He presented with macular retinopathy, followed by progressive myoclonus and encephalopathy. After extensive workup, a diagnosis of subacute sclerosing panencephalitis was suspected by the presence of period epileptiform discharges on electroencephalogram and confirmed by elevated measles titers in the cerebrospinal fluid. Combination immunomodulatory therapy with isoprinosine, ribavirin, and intra-Ommaya interferon alpha did not result in clinical improvement. Within days following the administration of carbamazepine, there was remarkable improvement in the myoclonus and he was able to ambulate independently for a period of 4 months at which time he unfortunately progressed to a vegetative state. This case highlights the importance of carbamazepine as a potential first line symptomatic treatment of subacute sclerosing panencephalitis and provides a review of the literature on the subject. PMID:23533854

  19. Operation and Maintenance Resources for Small Drinking Water Systems

    EPA Pesticide Factsheets

    These documents and tools provide information on identifying treatment technologies that remove multiple contaminants, schedules for maintenance tasks and checklists, and logs for easily recording findings.

  20. Examining maintenance responsibilities.

    PubMed

    Lam, K C

    2001-06-01

    This paper has examined the important responsibilities of the two organisations involved in the provision of maintenance service for the vital building services in many of our highly serviced buildings. The issues raised could be put to beneficial use in both clients and maintenance providers. All in all, the clients should work closely with their maintenance providers. Engineering services in buildings will not perform satisfactorily and efficiently if both parties do not work together and understand the maintenance tasks based on a business partnering mode. Put forward is the view that the management of the activities involved in the operation and maintenance process is a "shared commitment/involvement" between the client and the maintenance provider. It is obvious that many factors can influence the continued effectiveness of a quality maintenance scheme set up by client and provider. Some of these factors are: Change in key personnel Updates in technology Amendments to engineering practice Implementation of legislative requirements Changes in operation by client or provider Change of use of building Passage of time These factors must be fully reviewed by both parties from time to time, and necessary actions taken. A cooperative team working relationship and improved communication should be fostered by the client and his provider for the best management of services maintenance. This arrangement will contribute to better building services systems with continuous improvement; improved value for clients and higher return for the maintenance provider.

  1. [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.

  2. Methadone maintenance: some client opinions.

    PubMed

    Brown, B S; Benn, G J; Jansen, D R

    1975-06-01

    The authors found similar attitudes toward methadone and methadone treatment programs in 75 detoxification and 115 methadone maintenance clients. Both groups expressed considerable ambivalence--although they viewed methadone as capable of helping them end their herioin addiction, they were concerned about possible methadone dependence and about side effects, both real and imagined. The authors stress the societal context of such concern and suggest that, althought they are not easily allayed, limiting the duration of methadone maintenace from the outset of treatment may be an ameliorative factor.

  3. 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…

  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. Maintenance of School Gymnasiums.

    ERIC Educational Resources Information Center

    Finchum, R. N.

    1965-01-01

    Procedures are suggested that may be helpful to those responsible for the operation and maintenance of school buildings and gymnasiums. Most schools with gymnasiums utilize them for both instructional and sports purposes. Maintenance of the multipurpose gym are discussed under four subject areas--(1) floors, (2) lighting, (3) sanitation, and (4)…

  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…

  7. 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. Final rule.

    PubMed

    2016-11-02

    This 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. An interim final rule is in effect. 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 rule includes procedures to assist beneficiaries in transferring covered prescriptions to the mail order pharmacy program.

  8. 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

    2015-08-06

    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.

  9. 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

  10. Multiple papillomavirus-associated epidermal hamartomas and squamous cell carcinomas in situ in a dog following chronic treatment with prednisone and cyclosporine.

    PubMed

    Callan, Mary Beth; Preziosi, Diane; Mauldin, Elizabeth

    2005-10-01

    A 4-year-old, spayed female toy fox terrier developed multiple epidermal hamartomas and squamous cell carcinomas in situ following chronic immunosuppressive therapy with prednisone and cyclosporine for management of an immune-mediated nonregenerative anaemia. Immunohistochemical staining was positive for papillomavirus antigen within both benign (n = 19) and malignant (n = 8) cutaneous lesions that developed during a 3-year period of observation, with positive staining most often seen in keratinocytes in the granular cell layer. Treatment of the papillomavirus infection with interferon-alpha was discontinued after 2 weeks because of diarrhoea and a further increase in liver enzymes. The cutaneous lesions of this dog persisted and new lesions developed during the year following discontinuation of both cyclosporine and prednisone. This is the first reported case of papillomavirus-associated squamous cell carcinoma in situ developing in a dog following chronic administration of cyclosporine and prednisone.

  11. Treatment of psoriasis and long-term maintenance using 308 nm excimer laser, clobetasol spray, and calcitriol ointment: a case series.

    PubMed

    Wong, Jillian W; Nguyen, Tien V; Bhutani, Tina; Koo, John Y M

    2012-08-01

    Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.

  12. Hydroxychloroquine: a multifaceted treatment in lupus.

    PubMed

    Costedoat-Chalumeau, Nathalie; Dunogué, Bertrand; Morel, Nathalie; Le Guern, Véronique; Guettrot-Imbert, Gaëlle

    2014-06-01

    The efficacy of antimalarials, especially hydroxychloroquine (HCQ), in preventing systemic lupus erythematosus (SLE) flares is well demonstrated. However, many studies show that the percentage of SLE patients treated with HCQ remains low. By blocking the toll-like receptor 7 and 9 in plasmacytoid dendritic cells, HCQ inhibits interferon-alpha production which plays a crucial role in SLE pathogenesis. In addition to reducing damage accrual in SLE patients, HCQ appears to protect against the occurrence of diabetes, thrombotic events, and dyslipidemia. As a consequence, some studies have suggested that HCQ, which is inexpensive, has a protective effect on survival in SLE patients. Thanks to the pharmacokinetic properties of HCQ (long half-life) and to the availability of its blood assay, very low or undetectable blood HCQ concentrations are a valuable marker of non-adherence to treatment, thus adding a new benefit to HCQ prescriptions. The main side effect of HCQ is retinal toxicity. This complication is very rare, but may be potentially severe, thus requiring regular screening. Retinal toxicity remains the only absolute contra-indication of HCQ in adult SLE patients. Other contra-indications are few and rare. During pregnancy and breast-feeding, HCQ continuation is not only allowed but recommended. In conclusion, the risk/benefit ratio of HCQ is excellent. Many now believe that all SLE patients should be offered this treatment.

  13. 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.

  14. Factors Influencing Army Maintenance

    DTIC Science & Technology

    1989-01-01

    ARI Research Note 89-11 (N 00 Factors Influencing Army Maintenance LOloD Debra C. Evans and J. Thomas Roth Applied Science Associates, Inc. for...1.2.7 .2.7.C.1 11. TITLE (Include Security ClassifIcarIon) Factors Influencing Army Maintenance i2. FERSONAL AuTtiOR(S) Evans, Debra C., and Roth, J...y • ’ Factors and variables that influence maintenance for systems and related manpower, per- sonnel, and training (MPT) characteristics were

  15. 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

  16. 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.

  17. 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)

  18. 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)

  19. 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)

  20. 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)

  1. 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.

  2. 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)

  3. 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.

  4. FGD maintenance guidelines. Volume 2: FGD maintenance information. Final report

    SciTech Connect

    Davidson, L.N.; Miller, G.P.; Wedig, C.P.

    1986-07-01

    The ''FGD Maintenance Guidelines'' was written to fill the need for maintenance information that applies specifically to flue gas desulfurization (FGD) systems. Previously there was no single source of data describing FGD maintenance. Usually maintenance managers relied on suppliers' operating and maintenance manuals, past FGD experience, or procedures from other areas of a power plant. There are two volumes in the Guidelines intended to assist utility personnel in planning and performing maintenance for FGD systems. Different aspects of maintenance are emphasized in each volume. Volume 1, FGD Maintenance Programs, provides guidance for supervisory personnel involved in planning maintenance. It describes the utility industry's experience with FGD maintenance programs, a procedure for organizing and managing maintenance programs, and ways to design FGD systems for maintainability. The section about implementing a maintenance program contains a detailed example to illustrate the procedure, based on experience of an actual operating FGD system. Volume 2, FGD Maintenance Information, has practical information, useful in understanding FGD systems and their maintenance needs. It describes the major types of FGD systems operating in the US and typical maintenance associated with each. Also, in this volume, there is information about maintenance needs and procedures for the most common types of FGD equipment. 21 refs., 48 figs., 3 tabs.

  5. 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

  6. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

    PubMed

    Hoffman, Sarah R; Le, Tam; Lockhart, Alexandre; Sanusi, Ayodeji; Dal Santo, Leila; Davis, Meagan; McKinney, Dana A; Brown, Meagan; Poole, Charles; Willame, Corinne; Smith, Jennifer S

    2017-01-25

    A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

  7. Lamivudine and interferon versus lamivudine monotherapy for HBeAg-positive hepatitis B treatment: a meta-analysis of randomized, controlled trials.

    PubMed

    Rudin, Dan

    2007-01-01

    The suboptimal outcomes of current chronic hepatitis B treatments have prompted the notion of combination therapy as a means of augmenting the therapeutic response. In this study, investigators compared lamivudine monotherapy versus its combination with conventional or pegylated interferon-alpha, pooling data from all pertinent randomized controlled studies into the meta-analysis. The studies were evaluated for methodologic quality and heterogeneity. Rates of sustained virologic and biochemical responses and of hepatitis B e antigen clearance and seroconversion were used as primary efficacy measures. Quantitative metaanalyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. Analysis yielded greater sustained virologic, biochemical, and seroconversion rates with the addition of conventional (odds ratio [OR]=4.5, 95% confidence interval [CI]=2.2-9.4, P<.001; OR=2.1, 95% CI=1.3-3.2, P=.002; and OR=2.6, 95% CI=1.4-4.8, P=.001, respectively) and pegylated (OR=2.0, 95% CI=1.1-3.6, P=.02; OR=1.8, 95% CI=1.3-2.6, P<.001; and OR=1.6, 95% CI=1.1-2.3, P=.03, respectively) interferon-alpha to lamivudine, with the former also yielding greater hepatitis B e antigen clearance rates (OR=2.6, 95% CI=1.3-5.2, P=.008). As previous studies suggested that pegylated interferon monotherapy and its combination with lamivudine were comparable, the use of this combination is not justified. In contrast, when conventional interferon-a is used, its combination with lamivudine should be considered.

  8. 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…

  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. Are methadone counselors properly equipped to meet the palliative care needs of older adults in methadone maintenance treatment? Implications for training.

    PubMed

    Doukas, Nick

    2014-01-01

    Today's methadone patients differ greatly from those of the past. Because of the rise of polydrug use and the HIV and hepatitis epidemics, treatment has become much more complex, which multiply the concerns and complexities of treatment. Patients entering methadone programs are also more commonly presenting at ages well into their 50s, 60s, and 70s; and this phenomenon of high rates continues to grow. The majority of these individuals in treatment have presented with a number of significant comorbid medical conditions that will progress and eventually lead to death. This aging cohort must be approached with a modified treatment plan that focuses on management and promoting healthy aging, while attending to their maximum delay of illness, disease, and disability. This article argues that it is necessary for counselors working with this group to adopt a palliative care philosophy. This article also makes recommendations in areas that counselors need to be knowledgeable and skilled in to provide appropriate palliative services specific to this aging population with multiple needs as they near end of life.

  11. Sustained treatment effect in attention-deficit/hyperactivity disorder: focus on long-term placebo-controlled randomized maintenance withdrawal and open-label studies.

    PubMed

    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.

  12. Prolonged remission maintenance in acute myeloid leukaemia.

    PubMed

    Spiers, A S; Goldman, J M; Catovsky, D; Costello, C; Galton, D A; Pitcher, C S

    1977-08-27

    Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

  13. Prolonged remission maintenance in acute myeloid leukaemia.

    PubMed Central

    Spiers, A S; Goldman, J M; Catovsky, D; Costello, C; Galton, D A; Pitcher, C S

    1977-01-01

    Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia. PMID:268229

  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. 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).

  16. Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study.

    PubMed

    Guslandi, M

    1999-11-01

    Patients with mild to moderate active colitis who are treated with mesalazine plus transdermal nicotine reportedly suffer fewer relapses than patients treated with mesalazine plus oral prednisone. A long-term follow-up period was carried out to confirm this. Thirty patients with remission of distal colitis after therapy with the above treatment schedules were monitored for 12 months (Rachmilewitz' activity index plus endoscopy). Relapsed patients were retreated in a cross-over fashion. After 12 months recurrences were observed in 14 of 15 patients initially treated with steroids and in 7 of 15 subjects who were had received transdermal nicotine (P = 0.007, Fisher's test). A higher proportion of relapsed patients from the prednisone group, after successful retreatment with nicotine patches, remained in remission after 6 months (20%) than relapsed patients who switched to steroid treatment (57%). Our present results confirm the concept that nicotine-induced remission of ulcerative colitis lasts longer than that obtained by oral corticosteroids.

  17. Previous Midlife Oestradiol Treatment Results in Long-Term Maintenance of Hippocampal Oestrogen Receptor α Levels in Ovariectomised Rats: Mechanisms and Implications for Memory.

    PubMed

    Black, K L; Witty, C F; Daniel, J M

    2016-10-01

    Ovariectomised rats that have received previous administration of oestradiol in midlife display enhanced cognition and increased hippocampal levels of oestrogen receptor (ER)α months after oestradiol treatment ended compared to ovariectomised controls. The present study aimed to investigate the mechanisms by which ERα levels are maintained following midlife oestradiol exposure and the role of ERα in memory in ageing females in the absence of circulating oestrogens. Unliganded ERα has increased interaction with the ubiquitin ligase, C-terminus of Hsc-70 interacting protein (CHIP), leading to increased degradation of the receptor. In our first experiment, we tested the hypothesis that midlife oestradiol exposure in ovariectomised rats results in decreased interaction between CHIP and hippocampal ERα, leading to increased levels of ERα. Middle-aged rats were ovariectomised and received oestradiol or vehicle implants. After 40 days, implants were removed. One month later, rats were killed and hippocampi were processed for whole protein western blotting and co-immunoprecipitation, in which ERα was immunoprecipitated from lysate. As expected, ERα protein expression was increased in rats previously treated with oestradiol compared to vehicle-treated rats. In rats treated with oestradiol, there was a decrease in CHIP-ERα interaction, suggesting that previous oestradiol treatment reduces interaction, slowing the degradation of ERα. In a second experiment, we determined the impact on memory of antagonism of ER in the absence of circulating oestrogens. Rats were ovariectomised and implanted with oestradiol capsules. Capsules were removed after 40 days. Rats received chronic i.c.v. infusion of ER antagonist, ICI 182 780, or artificial cerebrospinal fluid vehicle and were tested on a spatial memory radial-maze task. Rats treated with ICI 182 780 had significantly worse performance (more errors). These experiments provide evidence that previous midlife oestradiol

  18. 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…

  19. 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.

  20. [Preventive maintenance of repeated ischemic insults].

    PubMed

    Gavrilenko, A V; Kuklin, A V; Kravchenko, A A; Agafonov, I N

    2008-01-01

    In the review we offer analysis of the effectiveness of carotid endarterectomy in treatment of post-functional apoplexy or stroke patients. Published results of the researches specify possible efficiency of carotid endarterectomy in preventive maintenance against repeated apoplectic attack or strokes. Yet the criteria of usage and execution of the carotid endarterectomy are still to be discussed.

  1. 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…

  2. 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…

  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. 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…

  5. 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.

  6. 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,…

  7. 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…

  8. Playground Inspection & Maintenance.

    ERIC Educational Resources Information Center

    Leeds, Gerard

    People today demand a safer work environment and a safer play environment for children. Accidents such as broken arms are no longer accepted as an inevitable part of growing up. This paper presents recommendations for the maintenance of safe playground areas and equipment, covering three main areas: (1) inspections, which should follow a specified…

  9. 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…

  10. 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)

  11. 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.

  12. 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,…

  13. 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

  14. 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…

  15. 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.

  16. Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials.

    PubMed

    Malczewski, Agnieszka; Marshall, Andrea; Payne, Miranda J; Mao, Lili; Bafaloukos, Dimitrios; Si, Lu; Pectasides, Dimitrios; Fountzilas, George; Guo, Jun; Gogas, Helen; Middleton, Mark R

    2016-01-01

    Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.K., Greek, and Chinese randomized trials. All patients were randomized either to IFN-α-2b 15-20 MIU/m(2) IV daily 5 days per week for 4 weeks (IV) or to the same regimen followed by IFN-α-2b 9-10 MIU/m(2) administered three times per week for 48 weeks (IV and SC). Allowing for dose interruptions and reductions, an equivalent total dose of IFN-α-2b was delivered in all three studies. We assessed whether IV was noninferior to IV and SC in terms of relapse-free survival (RFS) and investigated tumor and patient characteristics that impacted on outcomes. Median follow-up of 716 stage IIB-IIIC patients was 5.4 years. Noninferiority of IV compared to IV and SC could not be conferred for RFS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.89-1.52; noninferior P = 0.17). Stage (P < 0.0001), site (acral vs. other, P < 0.0001), and Breslow thickness (P = 0.02) were significant predictors of RFS. The HR for death was 1.13 for IV compared to IV and SC, (95% CI 0.91-1.39). Stage (P < 0.0001) and Breslow thickness (P = 0.001) were significant independent predictors of OS. The available data suggest that where adjuvant high-dose interferon is being considered there is no evidence to deviate from the year long regimen described in the Eastern Cooperative Oncology Group and Intergroup studies.

  17. 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

  18. Study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence: the PREVENT trial

    PubMed Central

    2010-01-01

    Background Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. We need to develop psychological therapies that prevent depressive relapse/recurrence. A recently developed treatment, Mindfulness-based Cognitive Therapy (MBCT, see http://www.mbct.co.uk) shows potential as a brief group programme for people with recurring depression. In two studies it has been shown to halve the rates of depression recurring compared to usual care. This trial asks the policy research question, is MBCT superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and, secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question asks is an increase in mindfulness skills the key mechanism of change? Methods/Design The design is a single blind, parallel RCT examining MBCT vs. m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT plus ADM-tapering with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Depressive relapse/recurrence over two years is the primary outcome variable. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre/post-treatment and a qualitative study of service users' views and experiences. Discussion If the

  19. 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

  20. Terminal automation system maintenance

    SciTech Connect

    Coffelt, D.; Hewitt, J.

    1997-01-01

    Nothing has improved petroleum product loading in recent years more than terminal automation systems. The presence of terminal automation systems (TAS) at loading racks has increased operational efficiency and safety and enhanced their accounting and management capabilities. However, like all finite systems, they occasionally malfunction or fail. Proper servicing and maintenance can minimize this. And in the unlikely event a TAS breakdown does occur, prompt and effective troubleshooting can reduce its impact on terminal productivity. To accommodate around-the-clock loading at racks, increasingly unattended by terminal personnel, TAS maintenance, servicing and troubleshooting has become increasingly demanding. It has also become increasingly important. After 15 years of trial and error at petroleum and petrochemical storage and transfer terminals, a number of successful troubleshooting programs have been developed. These include 24-hour {open_quotes}help hotlines,{close_quotes} internal (terminal company) and external (supplier) support staff, and {open_quotes}layered{close_quotes} support. These programs are described.

  1. CFB refractory maintenance

    SciTech Connect

    Johnson, R.C.

    1994-12-31

    The CFB maintenance manager has to make rapid-fire decisions regarding refractory maintenance during short or unscheduled turnarounds. This presentation offers a hands-on approach to expedient refractory failure analyses with specific repair recommendations. Photographs of most typical CFB refractory failures and their structural repairs are discussed. The most reliable repairs can be expected by using the latest state-of-the-art refractory materials and installation techniques. Refractory materials are consumable; therefore minor repairs should always be conducted at the first opportunity; this will preclude future major repairs. During a short or unscheduled outage, major repairs should be confined to the specific structural repair site; the removal of good, serviceable refractory is unnecessary under these conditions.

  2. Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO® and OTEMTO® studies: a subgroup analysis by age

    PubMed Central

    Ferguson, Gary T; Karpel, Jill P; Clerisme-Beaty, Emmanuelle; Grönke, Lars; Voß, Florian; Buhl, Roland

    2016-01-01

    Background Increasing age is associated with poor prognosis in patients with COPD. Objective This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years. Methods In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO only). This analysis used the approved doses of tiotropium + olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George’s Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0–3) response, and trough FEV1 response. Results A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO. FEV1 AUC0–3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 μg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups. SGRQ scores generally improved with tiotropium + olodaterol 5/5 μg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO. In all age groups receiving tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved. Conclusion No differences were noted in relative responses to treatment or safety when

  3. 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.

  4. Management Aspects of Software Maintenance.

    DTIC Science & Technology

    1984-09-01

    TRADITIONAl METHODS ..... ............. 50 C. PARAMETRIC MODELS ..... .............. 53 D. ESTIMATING MAINTENANCE COSTS ... ......... 57 1. Planning...maintenance. 10 10A 4 7he extensive research dcne cn software development and on the management of the development process is only ncw begin- ning to...and external factors. C. GENEEAL PROCEDURE The procedure used was to research literature concerning software maintenance. Particular emphasis was

  5. 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…

  6. 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…

  7. 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.

  8. Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up.

    PubMed

    Evangelopoulos, M E; Andreadou, E; Koutsis, G; Koutoulidis, V; Anagnostouli, M; Katsika, P; Evangelopoulos, D S; Evdokimidis, I; Kilidireas, C

    2017-01-15

    Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate. All patients were found positive for NMO IgG. All patients (three with NMO and two with NMOSD, 1 patient with recurrent optic neuritis and 1 patient with recurrent myelitis) had received rituximab treatment for six years. One patient with NMOSD received cyclophosphamide prior to rituximab while two were misdiagnosed as multiple sclerosis and had received interferon treatment. All received rituximab infusion of 375mg/m(2) once per week for 4weeks and then every two months for the first two years and then every six months. B-cell counts were measured every two months and were kept in almost undetectable levels. No relapse was noted during the treatment period while EDSS score was improved in all patients. No severe adverse effects occurred during RTX treatment. Rituximab treatment on NMO and NMOSD patients showed significant improvement in disability and relapse-rate without any significant adverse effects.

  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. 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.

  11. [Formulation of an oral solid dosage form containing human interferon-alpha].

    PubMed

    Kristo, Katalin; Bajdik, János; Márki, Arpád; Eros, István; Falkay, György; Hödi, Klára

    2008-01-01

    The main objective of this study was to process the human alpha-interferon for the solid dosage form. The first step was the preparation of the intermediate product for the tablet making. Fluid bed apparatus with top spray method was applied for the layering of powdered cellulose with human alpha-interferon solutions. The intermediate product was compressed into tablet and an enteric solvent coating of the tablets was made in a fluid bed apparatus with Wurster method. The physical parameters were detected. These fitted the Ph. Eur. and the mechanical properties of the tablets were appropriate for coating in fluid bed apparatus. The tablets agree with the requirements of Ph. Eur. and the active agent was not dissolved in gastric juice. An animal test was also performed. The human alpha-interferon in the blood of the animals was detected with ELISA method. The human alpha-interferon specific kit was used. The active ingredient dissolved from the tablets was absorbed from the ileum. The solid dosage form containing human alpha-interferon was prepared; this can make oral application of human alpha-interferon possible.

  12. The role of interferon alpha in initiation of type I diabetes in the NOD mouse.

    PubMed

    Li, Qing; McDevitt, Hugh O

    2011-07-01

    Type 1 diabetes (T1D) is an autoimmune disease in both humans and the nonobese diabetic (NOD) mouse, in which the insulin-producing-cells of the pancreatic islets are destroyed by a beta islet cell-specific T cell immune response. We recently reported that interferon (IFN)-α is an early trigger of the T1D process in NOD mice. Here, we show that extensive blockade of IFN-α action by a monoclonal antibody specific to IFN-α receptor 1 results in nearly complete prevention of T1D in NOD mice. Whether professional IFN-α producing cells, plasmacytoid dendritic cells (pDCs), are responsible for the initiation of T1D has been unclear. Here we demonstrate that depletion of pDCs in NOD mice by a specific mAb given at 15-25 days of age significantly delays the onset and decreases the incidence of T1D. These findings indicate that pDC and pDC-derived IFN-α are the prime initiators of the pathogenesis of T1D in NOD mice.

  13. Phorbol esters potentiate the induction of class I HLA expression by interferon alpha.

    PubMed Central

    Erusalimsky, J D; Kefford, R F; Gilmore, D J; Milstein, C

    1989-01-01

    We have studied the effect of phorbol esters on the induction of class I histocompatibility antigen (HLA) expression by interferons (IFNs) in the T-cell line MOLT-4 and in the MOLT-4 mutant YHHH. Addition of IFN-alpha to phorbol 12,13-dibutyrate-pretreated MOLT-4 cells causes a greater than 20-fold increase in the expression of class I HLA, as compared to a 4- to 7-fold IFN-alpha-induced increase in control cells. Pretreatment with phorbol 12,13-dibutyrate does not alter the class I HLA response to IFN-gamma or the responses of other IFN-induced genes. This effect of phorbol 12,13-dibutyrate reproduces in MOLT-4 cells the phenotype of the mutant YHHH, which also displays a selective enhanced class I HLA response to IFN-alpha. Pretreatment of YHHH with phorbol 12,13-dibutyrate does not affect any of the responses induced by IFN. These findings suggest the existence of a phorbol ester-sensitive factor, inducible in MOLT-4 and constitutively expressed or modified in YHHH, which operates in the pathway of induction of class I HLA by IFN-alpha but not in the pathway used by IFN-gamma. Images PMID:2494657

  14. 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.

  15. 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

  16. Relative resistance of HIV-1 founder viruses to control by interferon-alpha

    PubMed Central

    2013-01-01

    Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNα2 (22 U/ml) was lower than that for IFNβ (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNα2 and IFNβ, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNα than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions The establishment of systemic HIV-1 infection by relatively IFNα-resistant founder viruses lends strong support to the hypothesis that IFNα plays an important role in the control of HIV-1 replication during the earliest stages of infection, prior to systemic viral spread. These findings suggest that it may be possible to harness the antiviral activity of type 1 IFNs in prophylactic and potentially also therapeutic strategies to combat HIV-1 infection. PMID:24299076

  17. Morphine inhibits intrahepatic interferon- alpha expression and enhances complete hepatitis C virus replication.

    PubMed

    Li, Yuan; Ye, Li; Peng, Jin-Song; Wang, Chuan-Qing; Luo, Guang-Xiang; Zhang, Ting; Wan, Qi; Ho, Wen-Zhe

    2007-09-01

    Heroin addicts are a high-risk group for hepatitis C virus (HCV) infection and the development of chronic HCV disease. We thus examined whether morphine, the active metabolite of heroin, has the ability to inhibit intrahepatic interferon (IFN)- alpha expression, facilitating HCV replication in human hepatocytes. Morphine inhibited intrahepatic IFN- alpha expression, which was associated with an increase in HCV replication in hepatocytes. Moreover, morphine compromised the anti-HCV effect of recombinant IFN- alpha . Investigation of the mechanism responsible for the morphine action revealed that morphine inhibited expression of IFN regulatory factor 5 in the hepatocytes. In addition, morphine suppressed the expression of p38, an important signal-transducing molecule involved in IFN- alpha -mediated anti-HCV activity. These findings indicate that morphine plays a cofactor role in facilitating HCV persistence in human hepatocytes.

  18. Multiplex pcr assay for detection of human interferon alpha2b gene in transgenic plants.

    PubMed

    Gerasymenko, I M; Sakhno, L O; Mazur, M G; Sheludko, Y V

    2012-01-01

    During the last decade interferons are regarded as potent candidates for generation of plant-based edible vaccines because of broad spectrum of antiviral activities and adjuvant properties. Establishment and certification of numerous interferon producing plant systems requests development of fast and efficient multiplex PCR protocol for the transgene detection in GM plants. Here we represent a protocol for simultaneous amplification in one assay of fragments of hIFN alpha 2b gene and two control genes, namely virD1 of Agrobacterium tumefaciens and conservative region of plant actin gene.

  19. Phorbol esters potentiate the induction of class I HLA expression by interferon. alpha

    SciTech Connect

    Erusalimsky, J.D.; Kefford, R.F.; Gilmore, D.J.; Milstein, C. )

    1989-03-01

    The authors have studied the effect of phorbol esters on the induction of class I histocompatibility antigen (HLA) expression by interferons (IFNs) in the T-cell line MOLT-4 and in the MOLT-4 mutant YHHH. Addition of IFN-{alpha} to phorbol 12,13-dibutyrate-pretreated MOLT-4 cells causes a >20-fold increase in the expression of class I HLA, as compared to a 4- to 7-fold IFN-{alpha}-induced increase in control cells. Pretreatment with phorbol 12,13-dibutyrate does not alter the class I HLA response to IFN-{gamma} or the responses of other IFN-induced genes. This effect of phorbol 12,13-dibutyrate reproduces in MOLT-4 cells the phenotype of the mutant YHHH, which also displays a selective enhanced class I HLA response to IFN-{alpha}. Pretreatment of YHHH with phorbol 12,13-dibutyrate does not affect any of the responses induced by IFN. These findings suggest the existence of a phorbol ester-sensitive factor, inducible in MOLT-4 and constitutively expressed or modified in YHHH, which operates in the pathway of induction of class I HLA by IFN-{alpha} but not in the pathway used by IFN-{gamma}.

  20. 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. ...

  1. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    PubMed

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

  2. Adherence to Chronic Hepatitis C Treatment Regimen: First Report From a Referral Center in Iran

    PubMed Central

    Ravi, Saeedeh; Nasiri Toosi, Mohsen; Karimzadeh, Iman; Ahadi-Barzoki, Mehdi; Khalili, Hossein

    2013-01-01

    Background Various aspects of adherence to HCV treatment such as frequency, risk factors as well as causes of non-adherence, and its real role in clinical and virological outcome of the infected patients have remained largely unknown. Objectives The current study aimed to evaluate patients’ adherence to anti-HCV medications in Iran. Materials and Methods From October 2010 to March 2011, socio-demographic characteristics, features of HCV infection, clinical properties, and habitual history of 190 patients were collected. Adherence of each patient to anti-HCV medications was determined at months 1, 3, and 6 of treatment by self-reporting and pill or empty ampoule counting. Adherence to anti-HCV treatment regimen was determined based on the 80/80/80 rule. Results Adherence rate to interferon, ribavirin, or a combination of them over the first 6 months of therapy in Iranian HCV patients measured by both methods of self-reporting and pill counting were 35.4-65.8%, 46.3-56.8%, and 28.4-51.1%, respectively. Delay in receiving new prescription, financial issues, and adverse drug reactions were the most common causes of non-adherence in the patients. Adherence to ribavirin was identified as an independent predictor of achieving the end of treatment response, or sustained virological response. Conclusions The rate of adherence to interferon and ribavirin varied significantly according to the method of calculation. Over the treatment course, adherence to interferon alpha and ribavirin, each or their combination, diminished significantly. PMID:24032043

  3. 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.

  4. Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder: protocol for a systematic review and meta-analysis

    PubMed Central

    Prajapati, Asta R; Wilson, Jonathan

    2016-01-01

    Introduction Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. Methods and analysis The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy. Ethics and dissemination Ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and

  5. Parameter on periodontal maintenance. American Academy of Periodontology.

    PubMed

    2000-05-01

    The American Academy of Periodontology has developed the following parameter on Periodontal Maintenance. Periodontal maintenance is an integral part of periodontal therapy for patients with a history of inflammatory periodontal diseases. Patients should be informed of the disease process, therapeutic alternatives, potential complications, expected results, and their responsibility in treatment. Consequences of no treatment should be explained. Failure to comply with a periodontal maintenance program may result in recurrence or progression of the disease process. Given this information, patients should then be able to make informed decisions regarding their periodontal therapy.

  6. Paranal maintenance and CMMS experience

    NASA Astrophysics Data System (ADS)

    Montano, Nelson

    2004-10-01

    During the last four years of operations, low technical downtime has been one of the relevant records of the Paranal Observatory. From the beginning of the Very Large Telescope (VLT) project, European Southern Observatory (ESO) has considered the implementation of a proper maintenance strategy a fundamental point in order to ensure low technical down time and preserve the Observatory's assets. The implementation of the maintenance strategy was based on the following aspects: - Strong maintenance sense during the design stage. Line Replacement Unit (LRU) concept, standardization and modularity of the Observatory equipment - Creation of a dedicated team for Maintenance - The implementation of a Computerized Maintenance Management System After four operational years, the result of these aspects has exceeded the expectations; the Observatory has been operating with high availability under a sustainable strategy. The strengths of the maintenance strategy have been based on modern maintenance concepts applied by regular production companies, where any minute of down time involves high cost. The operation of the actual Paranal Maintenance System is based mainly on proactive activities, such as regular inspections, preventive maintenance (PM) and predictive maintenance (PdM) plans. Nevertheless, it has been necessary to implement a strong plan for corrective maintenance (CM). The Spare Parts Strategy has also been an important point linked to the Maintenance Strategy and CMMS implementation. At present, almost 4,000 items related to the Observatory spare parts are loaded into the CMMS database. Currently, we are studying the implementation of a Reliability Centered Maintenance (RCM) project in one of our critical systems The following document presents the actual status of the Paranal Maintenance Strategy and which have been the motivations to implement the established strategy.

  7. Qualitative Maintenance Experience Handbook

    DTIC Science & Technology

    1975-10-20

    rdme hinge nonression springn. 7. Rem~ove 3 nuts, 1w- ashers , and bolts holding hinge pin halvers together. 8. Remove piD pin senuring iury strut and...bolt, nut. i,, asher , and pin. ONSTALLATTON: I. Reverse )’F -emov,,I. P. Aotuator is pr c-ad;Iusted to lenth and probably does not need adjust 3. TI...time in that syst-m and also permits malfunctions to be induces in a system not directly associated with the maintenance. [ ITI I - ___ ~ JaI , FLIGHT

  8. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  9. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., preventive maintenance, rebuilding, and alterations. 43.3 Section 43.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.3 Persons authorized to perform maintenance, preventive maintenance, rebuilding,...

  10. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  11. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., preventive maintenance, rebuilding, and alterations. 43.3 Section 43.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.3 Persons authorized to perform maintenance, preventive maintenance, rebuilding,...

  12. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  13. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., preventive maintenance, rebuilding, and alterations. 43.3 Section 43.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.3 Persons authorized to perform maintenance, preventive maintenance, rebuilding,...

  14. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., preventive maintenance, rebuilding, and alterations. 43.3 Section 43.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.3 Persons authorized to perform maintenance, preventive maintenance, rebuilding,...

  15. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  16. 14 CFR 43.9 - Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in..., PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.9 Content, form, and disposition of maintenance, preventive maintenance, rebuilding, and alteration records (except inspections performed in accordance...

  17. 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…

  18. Towards automated traceability maintenance.

    PubMed

    Mäder, Patrick; Gotel, Orlena

    2012-10-01

    Traceability relations support stakeholders in understanding the dependencies between artifacts created during the development of a software system and thus enable many development-related tasks. To ensure that the anticipated benefits of these tasks can be realized, it is necessary to have an up-to-date set of traceability relations between the established artifacts. This goal requires the creation of traceability relations during the initial development process. Furthermore, the goal also requires the maintenance of traceability relations over time as the software system evolves in order to prevent their decay. In this paper, an approach is discussed that supports the (semi-) automated update of traceability relations between requirements, analysis and design models of software systems expressed in the UML. This is made possible by analyzing change events that have been captured while working within a third-party UML modeling tool. Within the captured flow of events, development activities comprised of several events are recognized. These are matched with predefined rules that direct the update of impacted traceability relations. The overall approach is supported by a prototype tool and empirical results on the effectiveness of tool-supported traceability maintenance are provided.

  19. Maintenance and supply options

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The object of the Maintenance and Supply Option was to develop a high level operational philosophy related to maintenance and supply operations and incorporate these concepts into the Lunar Base Study. Specific products to be generated during this task were three trade studies and a conceptual design of the Logistic Supply Module. The crew size study was performed to evaluate crew sizes from the baseline size of four to a crew size of eight and determine the preferred crew size. The second trade study was to determine the impact of extending surface stay times and recommend a preferred duration of stay time as a function of crew, consumables, and equipment support capabilities. The third trade study was an evaluation of packaging and storage methods to determine the preferred logistics approach to support the lunar base. A modified scenario was developed and served as the basis of the individual trade studies. Assumptions and guidelines were also developed from experience with Apollo programs, Space Shuttle operations, and Space Station studies. With this information, the trade studies were performed and a conceptual design for the Logistic Supply Module was developed.

  20. Operation and Maintenance of Water Pollution Control Facilities: A WPCF White Paper.

    ERIC Educational Resources Information Center

    Hill, William R.; And Others

    1979-01-01

    Presented are the recommendations of the Water Pollution Control Federation for operation and maintenance consideration during the planning design, construction, and operation of wastewater treatment facilities. (CS)