Science.gov

Sample records for chronic clozapine treatment

  1. Serum antimuscarinic activity during clozapine treatment.

    PubMed

    de Leon, Jose; Odom-White, Aruby; Josiassen, Richard C; Diaz, Francisco J; Cooper, Thomas B; Simpson, George M

    2003-08-01

    This study attempts: (1) to verify that serum antimuscarinic activity is related to clozapine dose, and more importantly to clozapine plasma concentrations; (2) to explore whether norclozapine has serum antimuscarinic activity; (3) to explore whether antimuscarinic activity is related to clozapine side effects; and (4) to compare the serum antimuscarinic activities of clozapine with those of antiparkinsonian drugs and other antipsychotics. In 39 patients participating in a double-blind clozapine study, the [3H]QNB assay was used to measure serum antimuscarinic activity: (1) on baseline medications; (2) after a 4-week haloperidol trial; (3) after a 16-week clozapine trial of either 100, 300, or 600 mg/d; and (4) after 1 or 2 consecutive 16-week clozapine trials with remaining doses in nonresponders. Clozapine levels predicted serum antimuscarinic activity better than clozapine dose. At the end of the 1st clozapine trial, the correlation with the levels explained 69% of the variance of serum antimuscarinic activity (r = 0.83, P < 0.001, N = 34). Clozapine levels were good predictors of serum antimuscarinic activity only in patients taking 300 or 600 mg/d. After correcting for clozapine levels, the within-subject correlation between norclozapine levels and serum antimuscarinic activity was relatively high and significant (r = 0.54, F = 26.7, df = 1.65, P < 0.001). Constipation was significantly associated with higher serum antimuscarinic activity during the 1st clozapine trial. Clozapine was associated with clearly higher antimuscarinic activity than other antipsychotics or low doses of antiparkinsonians. In vitro studies and new clinical studies are needed to verify whether norclozapine may significantly contribute to antimuscarinic activity during clozapine treatment. PMID:12920408

  2. Clozapine

    MedlinePlus

    Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... dispose of any leftover rinse water. Clozapine controls schizophrenia but does not cure it. It may take ...

  3. Clozapine for treatment of aggression in non-psychotic adolescents.

    PubMed

    Kumar, Tarun; Kathpal, Archana; Demer, James

    2016-08-01

    Use of Second Generation Antipsychotics (SGAs) in children and adolescents has grown more significantly in recent years. Clozapine has shown good results for the treatment of aggression in adult population but no case has been reported about the use of clozapine for treatment of aggression in non-psychotic adolescents. We present cases of 2 adolescents in which clozapine was used primarily to treat their aggressive behavior and suicidal ideation. PMID:27520908

  4. Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.

    PubMed

    Poyraz, Cana Aksoy; Özdemir, Armağan; Sağlam, Nazife Gamze Usta; Turan, Şenol; Poyraz, Burç Çağrı; Tomruk, Nesrin; Duran, Alaattin

    2016-06-01

    The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia. PMID:26433727

  5. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia

    PubMed Central

    Cipriani, Andrea; Boso, Marianna; Barbui, Corrado

    2014-01-01

    Background Although clozapine has been shown to be the treatment of choice in people with schizophrenia that are resistant to treatment, one third to two thirds of people still have persistent positive symptoms despite clozapine monotherapy of adequate dosage and duration. The need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine is the most common reason for simultaneously prescribing a second antipsychotic drug in combination with clozapine. Objectives To determine the efficacy and tolerability of various clozapine combination strategies with antipsychotics in people with treatment resistant schizophrenia. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and MEDLINE (up to November 2008). We checked reference lists of all identified randomised controlled trials and requested pharmaceutical companies marketing investigational products to provide relevant published and unpublished data. Selection criteria We included only randomised controlled trials recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. Data collection and analysis Two review authors independently extracted data and resolved disagreement by discussion with third member of the team. When insufficient data were provided, we contacted the study authors. Main results Three small (range of number of participants 28 to 60) randomised controlled trials were included in the review. Even though results from individual studies did not find that one combination strategy is better than the others, the methodological quality of included studies was too low to allow authors to use the collected data to answer the research question correctly. Authors’ conclusions In this review we considered the risk of bias too high because of

  6. Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

    PubMed Central

    Voulgari, Christina; Giannas, Raphael; Paterakis, Georgios; Kanellou, Anna; Anagnostopoulos, Nikolaos; Pagoni, Stamata

    2015-01-01

    Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy. PMID:25755670

  7. Is There a Role for Clozapine in the Treatment of Children and Adolescents?

    ERIC Educational Resources Information Center

    Findling, Robert L.; Frazier, Jean A.; Gerbino-Rosen, Ginny; Kranzler, Harvey N.; Kumra, Sanjiv; Kratochvil, Christopher J.

    2007-01-01

    This article presents responses to the question of whether clozapine is ever appropriate to use in the pediatric population. Among others, Jean A. Frazier also agreed that clozapine is appropriate for use in the pediatric population. Clozapine has truly revolutionized the treatment of refractory patients with schizophrenia at any age. This agent…

  8. Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia.

    PubMed

    Üçok, Alp; Çikrikçili, Uğur; Karabulut, Sercan; Salaj, Ada; Öztürk, Meliha; Tabak, Öznur; Durak, Rümeysa

    2015-09-01

    The aim of this retrospective chart-review study was to investigate the relationship between delayed commencement of clozapine and the level of response in treatment-resistant schizophrenia (TRS). We included 162 patients with schizophrenia who used clozapine. The mean delay until starting clozapine after fulfillment of the TRS criteria was 29 months. The delay was shorter in those who gained benefit from clozapine (P=0.04), those who were treated in a specialized psychosis outpatient unit (P=0.01), and in men (P=0.009), and it correlated with age (P<0.001). The delay in starting clozapine and the maximum clozapine dose were independent contributors toward the response to clozapine in the logistic regression analysis. Moreover, of those who gained considerable benefit from clozapine, the patients were younger (P=0.01), the duration of illness before clozapine treatment was shorter (P=0.001), and the numbers of adequate antipsychotic trials before the use of clozapine were fewer (P=0.05). Our findings suggest that efforts aimed at reducing the delay for starting clozapine may increase the effectiveness of clozapine in TRS. PMID:26163875

  9. Clozapine Treatment of Childhood-Onset Schizophrenia: Evaluation of Effectiveness, Adverse Effects, and Long-Term Outcome

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Vermani, Anoop; Greenstein, Deanna K.; Bobb, Aaron J.; Spencer, Edgar P.; Clasen, Liv S.; Tossell, Julia W.; Stayer, Catherine C.; Gochman, Peter A.; Lenane, Marge C.; Rapoport, Judith L.; Gogtay, Nitin

    2007-01-01

    Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other…

  10. Does clozapine decrease smoking?

    PubMed

    de Leon, Jose; Diaz, Francisco J; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2005-06-01

    McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients. PMID:15951089

  11. Ivabradine, a novel treatment for clozapine-induced sinus tachycardia: a case series

    PubMed Central

    Brook, Jennifer; Dixon, Thomas; Gaughran, Fiona; Shergill, Sukhi; Melikian, Narbeh; MacCabe, James H.

    2014-01-01

    Objectives: Clozapine is the most efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by intolerability. Sinus tachycardia is a common adverse event associated with clozapine use, which may lead to the premature discontinuation of clozapine. Traditionally, β blockers are used to treat clozapine-associated tachycardia, though problems with intolerability and ineffectiveness can limit their utility. Methods: In this article, we present two cases of patients with treatment-resistant schizophrenia who developed symptomatic tachycardia associated with clozapine therapy. Results: We demonstrate that the novel heart rate controlling agent ivabradine can be effectively and safely used to control the heart rate and to allow for continued treatment with clozapine. Conclusion: This is the first report in the literature demonstrating that ivabradine appears to be a well tolerated agent, which should be considered as a symptomatic treatment of clozapine-induced tachycardia if the use of a β blocker fails due to a lack of response or intolerability. PMID:25057344

  12. Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

    PubMed Central

    Harrison, Rebecca N.S.; Murray, Robin M.; Lee, Sang Hyuck; Paya Cano, Jose; Dempster, David; Curtis, Charles J.; Dima, Danai; Gaughran, Fiona; Breen, Gerome

    2016-01-01

    Objectives Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK. Methods A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders. Results Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs. Conclusion Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments. PMID:27315048

  13. Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

    PubMed

    Ahmed, Mohamed; Cannon, Dara M; Scanlon, Cathy; Holleran, Laurena; Schmidt, Heike; McFarland, John; Langan, Camilla; McCarthy, Peter; Barker, Gareth J; Hallahan, Brian; McDonald, Colm

    2015-09-01

    Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity. PMID:25829144

  14. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports

    PubMed Central

    Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

    2016-01-01

    Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176

  15. Prevalence of tardive dyskinesia in chronic male inpatients with schizophrenia on long-term clozapine versus typical antipsychotics.

    PubMed

    Ye, Minjie; Tang, Wei; Liu, Linjing; Zhang, Feixue; Liu, Jiahong; Chen, Yuanling; Chen, Da Chun; Tan, Yun Long; Yang, Fu De; Hong Xiu, Mei; Hui, Li; Lv, Meng Han; Soares, Jair C; Zhang, Xiang Yang

    2014-11-01

    This study aimed to examine the prevalence and clinical associated variables of tardive dyskinesia (TD) in a large sample of Chinese inpatients with schizophrenia on long-term treatment with clozapine versus typical antipsychotics. A total of 584 male inpatients with schizophrenia on long-term clozapine (n=341) or typical antipsychotic (n=243) treatment were evaluated using the Abnormal Involuntary Movement Scale (AIMS). The patient's psychopathology was assessed using the Positive and Negative Syndrome Scale. The overall prevalence of TD was 44.5%, with rates of 48.7% in the clozapine group and 38.7% in the typical antipsychotic group (P=0.017). The AIMS score was significantly lower in typical than in clozapine groups (P<0.005). A multiple regression analysis showed that the following variables were significantly associated with the AIMS score: clozapine versus typical medication (P=0.008), Positive and Negative Syndrome Scale negative subscore (P=0.017), and age (P=0.04). There are significant differences in the prevalence and clinical correlates of TD in schizophrenia treated with clozapine versus typical antipsychotics. PMID:24803102

  16. Clozapine Treatment of Psychosis Associated with Velo-Cardio-Facial Syndrome: Benefits and Risks

    ERIC Educational Resources Information Center

    Gladston, S.; Clarke, D. J.

    2005-01-01

    Clozapine is licensed for the treatment of psychotic illnesses resistant to other antipsychotic medications. Velo-cardio-facial syndrome (VCFS) is associated with a vulnerability to psychotic illness that may be resistant to treatment with conventional typical and atypical antipsychotics. A 32-year-old man with intellectual disability (ID) and a…

  17. An evaluation of subjective experiences, effects and overall satisfaction with clozapine treatment in a UK forensic service

    PubMed Central

    Qurashi, Inti; Chu, Simon; Duffy, Chris; Husain, Nusrat; Chaudhry, Imran

    2015-01-01

    Objectives: Patients prescribed clozapine were surveyed to assess (a) the effects, both positive and adverse, and overall satisfaction with clozapine in comparison to previously prescribed antipsychotics and (b) the relative significance of effects experienced, both positive and adverse, in terms of impact on subjective well-being. Methods: A total of 56 male patients prescribed clozapine at a forensic psychiatric hospital were surveyed using a 27-item questionnaire. All patients had been prescribed clozapine for a minimum of 3 months. Respondents were asked to rate effects and satisfaction with clozapine treatment in comparison with previously prescribed antipsychotic medication on a five-point scale. Respondents were also asked to rate effects experienced with clozapine treatment in terms of impact on subjective well-being on a five-point scale. Results: A total of 89% of respondents reported greater satisfaction with clozapine than with previously prescribed antipsychotic medication. A majority of patients reported positive effects in terms of an improvement in their quality of life (68%) and social abilities (52%) with clozapine in comparison with previously prescribed antipsychotics. Nocturnal hypersalivation (84%) and weight gain (57%) were the most common adverse effects. Hedonic responses were assessed for each effect in order to determine the associated subjective experiences. The most positive hedonic responses were for quality of life, mood and alertness. In terms of adverse impact on subjective well-being, nocturnal hypersalivation ranked highest. Conclusions: Patients in a UK forensic sample are largely satisfied with clozapine treatment. The subjective effects of clozapine treatment should be taken into account by clinicians when assessing response. This may provide an opportunity to highlight the positive changes and prioritize management of the most undesirable adverse effects, which is likely to promote compliance and improve longer term treatment

  18. Impairment of left ventricular function early in treatment with clozapine: a preliminary study.

    PubMed

    Curto, Martina; Comparelli, Anna; Ciavarella, Giuseppino M; Gasperoni, Carlotta; Lionetto, Luana; Corigliano, Valentina; Uccellini, Arianna; Mancinelli, Iginia; Ferracuti, Stefano; Girardi, Paolo; Baldessarini, Ross J

    2015-09-01

    This preliminary prospective study evaluated cardiac status in 15 treatment-resistant schizophrenia patients (aged 18-55 years) without evidence of cardiovascular disease. Patients underwent clinical assessment, blood tests, ECG, and echocardiography before and during clozapine treatment for 4 weeks as doses increased from 25 to 100 mg/day. Serum concentrations of high-sensitivity C-reactive protein, troponin-I, brain natriuretic peptide, and clozapine+norclozapine were assayed at week 3; ECG and echocardiography were repeated at week 4. At moderate serum drug concentrations (124 ng/ml), the heart rate increased by 10% and high-sensitivity C-reactive protein levels were slightly elevated, but troponin-I and brain natriuretic peptide levels were not elevated. Echocardiographic indices indicated declining left ventricular (LV) diastolic and systolic function in 60-80% of participants, with an increase in systolic pulmonary artery pressure, A-wave velocity, and LV myocardial performance index by 16-24% in 60-80% of participants and a decrease in the E/A ratio by 29% in 73% of participants - all uncorrelated with drug concentrations. Early treatment with moderate doses of clozapine was associated with subclinical but substantial decreases in LV functioning in surprisingly high proportions of participants. Studies with more participants, higher drug doses, and long-term follow-up are needed to confirm and determine the course of the observed abnormalities and to evaluate their relationship with rare clinical cardiotoxicity associated with clozapine. PMID:26049674

  19. Heat stroke during long-term clozapine treatment: should we be concerned about hot weather?

    PubMed

    Hoffmann, Maurício Scopel; Oliveira, Lucas Mendes; Lobato, Maria Inês Rodrigues; Belmonte-de-Abreu, Paulo

    2016-03-01

    Objective To describe the case of a patient with schizophrenia on clozapine treatment who had an episode of heat stroke. Case description During a heat wave in January and February 2014, a patient with schizophrenia who was on treatment with clozapine was initially referred for differential diagnose between systemic infection and neuroleptic malignant syndrome, but was finally diagnosed with heat stroke and treated with control of body temperature and hydration. Comments This report aims to alert clinicians take this condition into consideration among other differential diagnoses, especially nowadays with the rise in global temperatures, and to highlight the need for accurate diagnosis of clinical events during pharmacological intervention, in order to improve treatment decisions and outcomes. PMID:27074342

  20. The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

    PubMed Central

    Wu, Ming-Kung; Chung, Weilun; Wu, Ching-Kuan; Tseng, Ping-Tao

    2015-01-01

    Introduction: Stevens–Johnson syndrome (SJS) is a severe adverse drug reaction that can result in disability and mortality. SJS is defined as having a widespread distribution throughout the whole body surface area with <10% extent of skin detachment and skin lesions. Some drugs, such as carbamazepine, have been reported to have a greater correlation to SJS. Although clozapine use has been mentioned as a risk factor for development of SJS, no report has clearly described the features of SJS as a reaction to clozapine use. Herein, we report the case of a patient presenting SJS after long-term clozapine treatment. Case report: Mr A was a 54-year-old male with a diagnosis of chronic schizophrenia. He was hospitalized in a mental institute and received clozapine 200 mg/day for 2 years, without discomfort or drug side effects. He developed acute-onset mouth edema, multiple oral and ocular ulcers, oral and ocular mucosa swelling, and multiple erythematous skin rashes over his entire body and extremities with hypertension and high fever. SJS was diagnosed after referral to a general hospital. Results The SJS subsided under supportive treatment. Conclusion Accumulated lymphocytes and macrophages in the epidermis and elevated TNF-α might cause an immune reaction and apoptosis and result in the clinical presentation of SJS. Clozapine is believed to modulate the immunologic reaction, and therefore might induce SJS through immunomodulation. This case highlights the importance of considering the possibility of SJS resulting from the use of drugs for which there are no reports of such a severe complication. PMID:25914536

  1. Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response.

    PubMed

    Hwang, Rudi; Shinkai, Takahiro; De Luca, Vincenzo; Ni, Xingqun; Potkin, Steven G; Lieberman, Jeffrey A; Meltzer, Herbert Y; Kennedy, James L

    2007-09-01

    Dopamine D1 receptors (D1) in the prefrontal cortex have been implicated in the modulation of cognitive processes as well as both positive and negative symptoms of schizophrenia. Therefore pharmacologic agents with potent D1 effects such as clozapine may influence the symptoms of schizophrenia (SCZ). Genetic variation in the D1 receptor gene (DRD1) may help to explain some of the variability in patient response to antipsychotics (APs). This study investigates the effect of four single nucleotide polymorphisms (SNPs) in DRD1 on clozapine response in two distinct SCZ populations (Caucasian and African American) refractory or intolerant to conventional APs. This study included 183 Caucasian and 49 African American schizophrenics diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (revised third or fourth edition). Genotyping was determined by 5'-exonuclease fluorescence assays. Within each population genotype, allele, allele +/- and haplotype frequencies were compared against dichotomous and quantitative measures of treatment response. Linkage disequilibrium analysis was also performed. In the Caucasian sample, no associations were observed for individual SNP tests. However, a rare three-marker haplotype predicted poor response. In the African American sample, the rs265976 variant and another three-marker haplotype were associated with cLozapine response. Although we did not find an association between the rs4532 SNP (-48 A/G, recognized by a DdeI restriction cut site) and cLozapine response as reported by Potkin et al. (2003), a trend in the same direction was observed as well. Our findings suggest that the rs4532 SNP may have a small effect if any. Further studies in larger, independent samples are required to validate these findings. PMID:17092969

  2. Asymptomatic left ventricular dysfunction with long-term clozapine treatment for schizophrenia: a multicentre cross-sectional cohort study

    PubMed Central

    Chow, V; Yeoh, T; Ng, A C C; Pasqualon, T; Scott, E; Plater, J; Whitwell, B; Hanzek, D; Chung, T; Thomas, L; Celermajer, D S; Kritharides, L

    2014-01-01

    only independent predictors of impaired GLS. Conclusions Asymptomatic mild LV impairment is common in patients with schizophrenia receiving long-term clozapine treatment and is associated with neutrophilia and low HDL-C. PMID:25332789

  3. Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging

    PubMed Central

    2005-01-01

    Many neuroimaging studies of schizophrenia have shown abnormalities in the frontal cortex, limbic system, basal ganglia, temporal and parietal lobes. These findings are not specific or consistent enough to build up a coherent theory of the origin of the brain abnormality in schizophrenia. This paper describes a state-of-the-art approach of SPECT to correlate neuropsychological evaluation. PANSS scores and different brain focal abnormalities of two groups of patients receiving Clozapine and classical antipsychotic treatments were observed. A total of 20 drug-free patients, actively psychotic schizophrenic, were selected according to the DSM-IV criteria. Pre-Post-treatment was designed using PANSS and 99mTc- ECD-SPECT to assess regional Cerebral Blood Flow (rCBF). The results showed that after treatment, differences in PANSS scores were significant in both groups, with superior scores resulting from the Clozapine therapy. Results were supported by SPECT, which showed a greater improvement in the Clozapine group. Both positive and negative symptoms were improved with Clozapine as well. Before treatment, hypofrontality was the most common (85%) finding, whereas after treatment hypofrontality was mostly cleared. However, in some areas like temporal and caudate, hyperfrontality was induced. Negative symptoms showed linkage to hypofrontality in both groups before and after treatment, and both positive and negative symptoms were improved more with Clozapine therapy than with classical treatment. PMID:15968344

  4. Retrospective review of clozapine in the treatment of patients with autism spectrum disorder and severe disruptive behaviors.

    PubMed

    Beherec, Laurène; Lambrey, Simon; Quilici, Gwendoline; Rosier, Antoine; Falissard, Bruno; Guillin, Olivier

    2011-06-01

    Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 ± 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs. PMID:21508854

  5. [Clozapine withdrawal. A review].

    PubMed

    Szafrański, T; Gmurkowski, K

    1999-01-01

    The article describes the symptoms of withdrawal of clozapine and their possible causes as well as research on switching from clozapine to another antipsychotic drug. A computerised search was conducted using MEDLINE (1966-1997) to retrieve reports of clozapine withdrawal. Fifteen case reports and sixteen withdrawal studies (only one of them double-blind and two single-blind) were identified. Clozapine multi-receptors profile seems to be responsible for withdrawal symptoms--several specific mechanisms are suggested: cholinergic supersensitivity, dopaminergic supersensivity, special role of D4 receptors, possibilities of serotonergic, noradrenergic and GABA-ergic involvement. Risk of relapse after withdrawal of clozapine seems to be greater than after withdrawal of classical neuroleptics. Some patients might become de novo neuroleptic resistant for at least several weeks after withdrawal. Therefore, clozapine should be stopped only due to strong clinical indications, and if only possible, the withdrawal should be slow (50 mg/week). To prevent relapse of psychosis some experts advocate starting new antipsychotic drugs in therapeutic dosage before withdrawal of clozapine is completed. In case of emergency, when clozapine (high dosage) must be withdrawn immediately, patient must be hospitalised and cholinergics might be considered to prevent, cholinergic rebound". There are no established guidelines which antipsychotic to choose after withdrawal of clozapine. In general, classical antipsychotics are ineffective. Thioridazine is suggested because of its prominent anticholinergic activity, but there is no clinical evidence of advantage of this treatment in comparison to classical drugs. Risperidon and especially olanzapine are promising possibilities, but initial data are disappointing. Benzamides might be another possibility but clinical data are scarce. These important issues require further studies. PMID:10786215

  6. Chronic Myeloproliferative Neoplasms Treatment

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  7. Granulocyte colony stimulating factor (G-CSF) can allow treatment with clozapine in a patient with severe benign ethnic neutropaenia (BEN): a case report.

    PubMed

    Spencer, Benjamin W J; Williams, Hugh R J; Gee, Siobhan H; Whiskey, Eromona; Rodrigues, Joseph P; Mijovic, Aleksandar; MacCabe, James H

    2012-09-01

    Clozapine is the treatment of choice for treatment-resistant schizophrenia, but it is associated with a risk of neutropaenia and agranulocytosis. Clozapine use is regulated by mandatory blood monitoring in the UK, requiring cessation of treatment should the absolute neutrophil count (ANC) drop below specified values. Benign reductions in the ANC in non-white populations are common, and this can preclude a patient from receiving treatment with clozapine. A diagnosis of benign ethnic neutropaenia can reduce these treatment restrictions (UK specific), but the degree of neutropaenia can be significant enough to still prevent treatment. In this report, we show that response to granulocyte colony stimulating factor (G-CSF) may be quite variable and difficult to predict, but with careful monitoring it can be used to increase the ANC count and allow continued treatment with clozapine. PMID:22719015

  8. Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

    PubMed Central

    Singh, Aakanksha; Grover, Sandeep; Malhotra, Pankaj; Varma, Subhash C.

    2016-01-01

    Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozapine and this has very rarely been linked to human leukocyte-antigen haplotypes vulnerability. In this report we review the existing data on late onset agranulocytosis with clozapine and describe the case of a young man, who developed agranulocytosis with clozapine after 35 months of treatment and was found to have genetic vulnerability in form of being positive for HLA DR4. This case highlights underlying autoimmune immune mechanism in clozapine-induced agranulocytosis and the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with genetic vulnerability to develop this condition. PMID:27121434

  9. An open study of clozapine in the treatment of resistant schizophrenia.

    PubMed

    Desai, N; Jain, V; Ghalsasi, S; Dalvi, M; Kelkar, S

    1999-10-01

    This open study was undertaken to assess the efficacy of clozapine in resistant schizophrenics, its side effects and safety profile and the mean dose required. Sample consisted of 28 patients who had been previously treated with neuroleptics and ECTs. A special proforma was prepared for recording the psychopathology and side effect profile. The complete blood count, differential count and BPRS scores were recorded weekly for a period of 3 months. Within 1 month of treatment on a dose range of 100-200 mg/day a 25%-50% decline in the BPRS score was noticed, the mean dose required was 241 mg/day. Sedation and sialorrhoea constituted the commonest side effects in 90% patients. No case of agranulocytosis was reported. The implications of the study are discussed. PMID:21430808

  10. An Unusual Case of Delirium after Restarting Clozapine

    PubMed Central

    Khanra, Sourav; Sethy, Rati Ranjan; Munda, Sanjay Kumar; Khess, Christoday Raja Jayant

    2016-01-01

    Clozapine is a gold standard medication and drug of choice in refractory schizophrenia. Among many of its fatal side effects, delirium is less reported and inconsistently recognized by clinicians. We here present a case of delirium which emerged during retreatment with clozapine in a patient of paranoid schizophrenia. A patient diagnosed with paranoid schizophrenia, was restarted on clozapine after he left medications and became symptomatic. He was delirious on 22nd day after clozapine was restarted. Clozapine was stopped and the patient was managed with standard treatment for delirium. After one week interval, clozapine was restarted. Delirium was not noted till 6 weeks of his hospital stay. Clozapine induced central anticholinergic toxicity or clozapine induced seizure might cause delirium in index case. Limited literature exist delirium with clozapine. Clinicians must have high index of suspicion to detect delirium during clozapine therapy. More researches should focus to explore the association between delirium and clozapine. PMID:26792049

  11. Combining Clozapine and Talk Therapies.

    ERIC Educational Resources Information Center

    Mulroy, Kevin

    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. This paper reviews articles concerning clozapine therapy. It considers its benefits and dangers in various situations, and how it can be successfully combined with talk therapies. Studies are reviewed concerning patients in outpatient clinics, partial hospitalization…

  12. Does the Addition of a Second Antipsychotic Drug Improve Clozapine Treatment?

    PubMed Central

    Barbui, Corrado; Signoretti, Alessandra; Mulè, Serena; Boso, Marianna; Cipriani, Andrea

    2009-01-01

    In patients with schizophrenia who do not have an optimal response to clozapine, it remains unclear if there is an evidence base to support a second antipsychotic in combination with clozapine. The present systematic review was therefore carried out to determine the efficacy of various clozapine combination strategies with antipsychotics. Relevant studies were located by searching the Cochrane Schizophrenia Group Trials Register, Medline, and Embase (up to November 2007). Only studies randomly allocating patients to clozapine plus another antipsychotic vs clozapine monotherapy were included. The search yielded 21 studies suitable for reanalysis. In 3 trials, clozapine was combined with a phenothiazine, in 8 trials with a benzamide, and in the remaining trials with risperidone. While the majority of randomized trials were not double blind, 6 studies were double-blind placebo-controlled trials. A total of 14 randomized open studies significantly favored clozapine combination strategy in terms of mean difference (random effect standardized mean difference [SMD] = −0.80, 95% confidence interval [CI] = −1.14 to −0.46); however, data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy in terms of mean difference (SMD = −0.12, 95% CI = −0.57 to 0.32). In terms of percentage of patients failing to show an improvement, a total of 10 randomized open studies significantly favored clozapine combination strategy (random effect relative risk [RR] = 0.64, 95% CI = 0.42 to 0.97), but data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy (RR = 0.91, 95% CI = 0.75 to 1.11). We conclude that the evidence base supporting a second antipsychotic in addition to clozapine in partially responsive patients with schizophrenia is weak. This weak evidence indicates modest to absent benefit. PMID:18436527

  13. EEG hemispheric asymmetry as a predictor and correlate of short-term response to clozapine treatment in schizophrenia.

    PubMed

    Knott, V; Labelle, A; Jones, B; Mahoney, C

    2000-07-01

    In search of early neuroleptic response predictors in schizophrenia, functional interhemispheric and intrahemispheric asymmetry indices, derived from spectrally analyzed resting electroencephalographic (EEG) activity, were examined in 17 schizophrenic patients prior to open label treatment with the atypical neuroleptic clozapine. Compared to EEG asymmetry indices derived from a normative data bank, patients exhibited significant interhemispheric (left greater than right) and intrahemispheric (anterior greater than posterior) deviations in delta, theta, alpha and beta frequency bands. Intrahemispheric indices were positively correlated with clinical ratings of positive symptoms and global psychopathology. Clozapine-induced improvements in positive and negative symptoms and global psychopathology symptom ratings were related to pretreatment intrahemispheric asymmetry only, with relationships varying with symptom, recording region and frequency band. The results are discussed in relation to the neurobiology of schizophrenia and the utility of EEG as an informative predictor of treatment response. PMID:10923202

  14. A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome.

    PubMed

    Zimbron, Jorge; Khandaker, Golam M; Toschi, Chiara; Jones, Peter B; Fernandez-Egea, Emilio

    2016-09-01

    Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine. PMID:27496573

  15. Metformin for treatment of clozapine-induced weight gain in adult patients with schizophrenia: a meta-analysis

    PubMed Central

    LIU, Zhengrong; ZHENG, Wei; GAO, Shuai; QIN, Zhisong; LI, Guannan; NING, Yuping

    2015-01-01

    Background Long-term use of clozapine for individuals with schizophrenia carries a high risk for developing metabolic abnormalities, especially clozapine-induced weight gain. Previous studies suggest that metformin can decrease clozapine-induced weight gain, but the sample sizes of most of these studies are relatively small. Methods We identified randomized controlled trials (RCTs) published prior to December 15, 2015 about the use of metformin to treat clozapine-induced weight gain in adults with schizophrenia by searching several English-language and Chinese-language databases. Two independent researchers did the screening and data extraction. We used Revman 5.3 to conduct the meta-analyses, assessed the risk of bias (RoB), and assessed the strength of the evidence using the Cochrane Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). Results Six studies with a pooled sample of 207 treatment-group patients and 207 control-group patients were included —— three double-blind, placebo-controlled RCTs and three RCTs that did not use placebo controls and were not blinded. The meta-analysis found that compared to the control condition, patients receiving metformin experienced significantly greater reductions in body weight (mean difference [MD]=-2.89 kg, 95% CI: -4.20 to -1.59 kg) and body mass index (BMI) (MD=-0.81, 95% CI: -1.16 to -0.45), but there was no significant difference between the groups in the prevalence of side effects. Based on the GRADE scale, the strength of the evidence for the change in weight outcome was ‘moderate’ and that for the change in BMI outcome was ‘high’, but the strength of evidence about differences in side effects between groups was ‘low’ or ‘very low’. Conclusions Adjunctive treatment with metformin appears to be effective for treating clozapine-induced weight gain and elevations in BMI in adult patients with schizophrenia. However, the quality of the evidence about the safety of this treatment

  16. Risks and Benefits of Rapid Clozapine Titration

    PubMed Central

    Lochhead, Jeannie D.; Nelson, Michele A.; Schneider, Alan L.

    2016-01-01

    Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia. PMID:27403276

  17. Clozapine in Three Individuals with Mild Mental Retardation and Treatment-Refractory Psychiatric Disorders.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1994-01-01

    Although clozapine is a drug specifically approved for people with schizophrenia, it has not been systematically evaluated with dually diagnosed individuals having mental retardation. This article reviews the drug's use in the general population, discusses potential difficulties in prescribing it for individuals with mental retardation, and…

  18. Late Onset Clozapine Induced Agranulocytosis

    PubMed Central

    Velayudhan, Rajmohan; Kakkan, Sushil

    2014-01-01

    Agranulocytosis is defined as an absolute neutrophil count less than 100/mm3 in association with infectious disease. The risk of agranulocytosis is 0.38% of all clozapine treated cases and there is a relatively lesser incidence in Indian population. The risk of clozapine-induced agranulocytosis and neutropenia is highest in the first 6 months and higher in the initial 18 months after the onset of treatment. There have been very few reports of neutropenia and agranulocytosis after this period. There have so far been no reports of late onset clozapine induced agranulocytosis has been reported from India. A case of late onset clozapine induced agranulocytosis with possible mechanism of the same is reported. PMID:25336778

  19. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

    PubMed Central

    Nosè, Michela; Accordini, Simone; Artioli, Paola; Barale, Francesco; Barbui, Corrado; Beneduce, Rossella; Berardi, Domenico; Bertolazzi, Gerardo; Biancosino, Bruno; Bisogno, Alfredo; Bivi, Raffaella; Bogetto, Filippo; Boso, Marianna; Bozzani, Alberto; Bucolo, Piera; Casale, Marcello; Cascone, Liliana; Ciammella, Luisa; Cicolini, Alessia; Cipresso, Gabriele; Cipriani, Andrea; Colombo, Paola; Dal Santo, Barbara; De Francesco, Michele; Di Lorenzo, Giorgio; Di Munzio, Walter; Ducci, Giuseppe; Erlicher, Arcadio; Esposito, Eleonora; Ferrannini, Luigi; Ferrato, Farida; Ferro, Antonio; Fragomeno, Nicoletta; Parise, Vincenzo Fricchione; Frova, Maria; Gardellin, Francesco; Garzotto, Nicola; Giambartolomei, Andrea; Giupponi, Giancarlo; Grassi, Luigi; Grazian, Natalia; Grecu, Lorella; Guerrini, Gualtiero; Laddomada, Francesco; Lazzarin, Ermanna; Lintas, Camilla; Malchiodi, Francesca; Malvini, Lara; Marchiaro, Livio; Marsilio, Alessandra; Mauri, Massimo Carlo; Mautone, Antonio; Menchetti, Marco; Migliorini, Giuseppe; Mollica, Marco; Moretti, Daniele; Mulè, Serena; Nicholau, Stylianos; Nosè, Flavio; Occhionero, Guglielmo; Pacilli, Anna Maria; Pecchioli, Stefania; Percudani, Mauro; Piantato, Ennio; Piazza, Carlo; Pontarollo, Francesco; Pycha, Roger; Quartesan, Roberto; Rillosi, Luciana; Risso, Francesco; Rizzo, Raffella; Rocca, Paola; Roma, Stefania; Rossattini, Matteo; Rossi, Giuseppe; Rossi, Giovanni; Sala, Alessandra; Santilli, Claudio; Saraò, Giuseppe; Sarnicola, Antonio; Sartore, Francesca; Scarone, Silvio; Sciarma, Tiziana; Siracusano, Alberto; Strizzolo, Stefania; Tansella, Michele; Targa, Gino; Tasser, Annamarie; Tomasi, Rodolfo; Travaglini, Rossana; Veronese, Antonio; Ziero, Simona

    2009-01-01

    Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol

  20. Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments.

    PubMed

    O'Connor, William T; O'Shea, Sean D

    2015-06-01

    Schizophrenia disease models are necessary to elucidate underlying changes and to establish new therapeutic strategies towards a stage where drug efficacy in schizophrenia (against all classes of symptoms) can be predicted. Here we summarise the evidence for a GABA dysfunction in schizophrenia and review the functional neuroanatomy of five pathways implicated in schizophrenia, namely the mesocortical, mesolimbic, ventral striopallidal, dorsal striopallidal and perforant pathways including the role of local GABA transmission and we describe the effect of clozapine on local neurotransmitter release. This review also evaluates psychotropic drug-induced, neurodevelopmental and environmental disease models including their compatibility with brain microdialysis. The validity of disease models including face, construct, etiological and predictive validity and how these models constitute theories about this illness is also addressed. A disease model based on the effect of the abrupt withdrawal of clozapine on GABA release is also described. The review concludes that while no single animal model is entirely successful in reproducing schizophreniform symptomatology, a disease model based on an ability to prevent and/or reverse the abrupt clozapine discontinuation-induced changes in GABA release in brain regions implicated in schizophrenia may be useful for hypothesis testing and for in vivo screening of novel ligands not limited to a single pharmacological class. PMID:25585121

  1. Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant bipolar mania: case series

    PubMed Central

    Turan, Şenol; Demirel, Ömer Faruk; Usta Sağlam, Nazife Gamze; Yıldız, Nazım; Duran, Alaattin

    2015-01-01

    Treatment of severe and refractory manic episodes in hospital settings can occasionally be very difficult. In particular, severely excited patients showing aggressive, hostile, impulsive behaviours frequently require physical restraint and seclusion, high doses of antipsychotics and benzodiazepines, and sometimes, electroconvulsive therapy. Hospital stay is generally prolonged and such patients cause great emotional distress for other patients in the ward and clinical staff involved in their care. Here we report on three patients with a diagnosis of bipolar disorder and one patient with a diagnosis of schizoaffective disorder bipolar subtype, all of whom were hospitalized for severe manic episodes with psychotic features. These patients were extremely difficult to manage in the ward as no response could be obtained in the first week of treatment despite high doses of antipsychotics and benzodiazepine administration. The introduction and rapid titration of clozapine proved remarkably effective and was well tolerated in the acute management of these patients. We observed that clozapine had a superior and fast mood stabilization effect with rapid titration and could be extremely helpful in the management of such patients. PMID:26301080

  2. Clozapine and Fever: A Case of Continued Therapy With Clozapine.

    PubMed

    Bruno, Valentina; Valiente-Gómez, Alicia; Alcoverro, Oscar

    2015-01-01

    Clozapine is a major atypical antipsychotic drug used in treatment-resistant schizophrenia (Patel and Allin. Ther Adv Psychopharmacol 2011;1:25-29). It interferes with dopamine binding to D1, D2, D3, and D5 receptors but has high affinity to D4. It also has an anticholinergic effect and antagonizes α-adrenergic, histaminergic, and serotoninergic receptors (Oerther and Ahlenius. J Pharmacol Exp Ther 2000;292:731-736). Clozapine has proved effective in treating positive and negative symptoms in patients with refractory schizophrenia, thus accounting for its frequent use. Despite its effectiveness, this drug is not without its adverse effects. The most well known is agranulocytosis. There are, however, many others, such as myocarditis, aspiration pneumonia, ileus, fever, hyperglycemia, hyperlipidemia, hypertriglycemia, tachycardia, and weight gain, among others (Bruijnzeel et al. Asian J Psychiatr 2014;11:3-7). Fever induced by clozapine is a common phenomenon (Lowe et al. Ann Pharmacother 2007;41:1700-1704), which usually occurs in the first 4 weeks of treatment, and its prevalence oscillates from 0.5% and 55%, depending on the study (Jeong et al. Schizophr Res 2002;56:191-193; Young et al. Schizophr Bull 1998;24:381-390). The fever lasts for 2.5 days on average, and unless the treatment is discontinued, it generally abates between day 8 and 16 of treatment (Kohen et al. Ann Pharmacother 2009;43:143-146). There are several different theories about the physiopathological mechanism; it could be a variation of malignant neuroleptic syndrome, an infection secondary to neutropenia, and allergic reaction or the emergence of the immunomodulating effect of clozapine. Some case reports in the bibliography have shown that patients in treatment with clozapine can develop a mild leukocytosis, but the presence of other concurrent symptoms, which indicate infection, is not common (Tham and Dickson. J Clin Psychiatry 2002;63:880-884). The theory of an allergic reaction is

  3. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities.

    PubMed

    Whiskey, Eromona; Taylor, David

    2007-01-01

    Clozapine remains the antipsychotic of choice for refractory schizophrenia despite its propensity for serious blood disorders. When neutropenia or agranulocytosis occur in people taking clozapine, cessation of treatment is mandated and relapse often results. Because such patients are usually unresponsive to other antipsychotics, many clinicians consider restarting clozapine, despite the risks involved. However, the risks of clozapine rechallenge vary according to the cause and nature of the blood dyscrasia. Neutropenia can arise because of factors unrelated or indirectly related to clozapine treatment. These include benign ethnic neutropenia, concomitant drug therapy, co-existing medical conditions and drug interactions. In such cases, clozapine may be restarted if non-clozapine causes of neutropenia are identified and eliminated, although concurrent treatment with lithium (to induce leukocytosis) is sometimes necessary. Close monitoring of the patient is essential because it is rarely possible to completely rule out the contribution of clozapine to the blood dyscrasia and because lithium does not protect against clozapine-related agranulocytosis. In cases of clozapine-induced neutropenia (as distinct from agranulocytosis, which may have a different pathology) rechallenge may also be considered and, again, lithium co-therapy may be required. Where clozapine is clearly the cause of agranulocytosis, rechallenge should not be considered or undertaken unless there are very exceptional circumstances (severe and prolonged relapse following clozapine discontinuation). In these cases, re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring. Granulocyte colony-stimulating factor is likely to be required as co-therapy, given the very high likelihood of recurrence. Uncertainty over the likely cause of blood dyscrasia in people taking clozapine, coupled with uncertainty over the mechanism by which clozapine causes both

  4. The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study.

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

    Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as having Benign Ethnic Neutropenia. None of the Benign Ethnic Neutropenia-registered patients discontinued treatment for haematological reasons. To optimize clozapine treatment and improve long-term outcomes, a significantly greater proportion of Black patients should be registered as having Benign Ethnic Neutropenia. PMID:20305043

  5. Clozapine safety, 40 years later.

    PubMed

    Raja, Michele; Raja, Silvia

    2014-01-01

    Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review. PMID:24809463

  6. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao

    2016-01-01

    This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I(2) = 62%), separating the two groups as early as weeks 1-2 with an SMD of -0.58 (p<0.00001; I(2) = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4-9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6-16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4-11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2-5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. PMID:27285996

  7. Generic clozapine: a cost-saving alternative to brand name clozapine?

    PubMed

    Tse, Gordon; Thompson, Deborah; Procyshyn, Ric M

    2003-01-01

    As a consequence of its prevalence, early onset and chronicity, schizophrenia imposes clinical and economic impediments to healthcare practitioners and society alike. Among the many antipsychotics available to treat the symptoms of this devastating illness, clozapine has emerged and differentiated itself from the others as the agent most efficacious for the treatment of refractory patients. Since the patent for Clozaril (Novartis) expired in 1998, three manufacturers of generic clozapine have submitted abbreviated new drug applications to the US FDA for review and approval to market a generic clozapine product. In each case, the US FDA deemed the generic formulations to be bioequivalent to the brand name Clozaril. Apart from case reports, industry-sponsored studies have been conducted comparing Clozaril with two generic formulations. In one case, a generic formulation of clozapine manufactured by Creighton Products Corporation (formerly a subsidiary [generic house] of Sandoz Pharmaceuticals) was found to be bioequivalent to Clozaril. On the other hand, studies (sponsored by Novartis) have challenged the bioequivalence, therapeutic equivalence and interchangeability between Clozaril and a generic formulation manufactured by Zenith Goldline Pharmaceuticals (now IVAX Corporation). The IVAX Corporation-sponsored studies refuted these claims citing data from two patient registry database studies and one small clinical trial. Apart from a single in-house bioequivalence study, no further investigations have been conducted with a third generic formulation manufactured by Mylan Pharmaceutical. Although the clinical significance of the above discrepancy is obvious, what is less than obvious is the pharmacoeconomic implications that arises from this debate. Clearly, if the brand name and generic formulations are 'truly' bioequivalent, then the cost savings realised would be the difference in acquisition cost. On the other hand, if the various formulations are not

  8. Systematic Review of Clozapine Cardiotoxicity.

    PubMed

    Curto, Martina; Girardi, Nicoletta; Lionetto, Luana; Ciavarella, Giuseppino M; Ferracuti, Stefano; Baldessarini, Ross J

    2016-07-01

    Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse effects, including myocarditis and cardiomyopathy. Given their clinical importance, we systematically reviewed research on adverse cardiac effects of clozapine, aiming to improve estimates of their incidence, summarize features supporting their diagnosis, and evaluate proposed monitoring procedures. Incidence of early (≤2 months) myocarditis ranges from <0.1 to 1.0 % and later (3-12 months) cardiomyopathy about 10 times less. Diagnosis rests on relatively nonspecific symptoms, ECG changes, elevated indices of myocardial damage, cardiac MRI findings, and importantly, echocardiographic evidence of developing ventricular failure. Treatment involves stopping clozapine and empirical applications of steroids, diuretics, beta-blockers, and antiangiotensin agents. Mortality averages approximately 25 %. Safety of clozapine reuse remains uncertain. Systematic studies are needed to improve knowledge of the epidemiology, avoidance, early identification, and treatment of these adverse effects, with effective and practicable monitoring protocols. PMID:27222142

  9. Treatment of chronic urticaria.

    PubMed

    Jurakić Toncić, Ruzica; Lipozencić, Jasna; Marinović, Branka

    2009-01-01

    Urticaria is a disorder characterized by rapid onset of localized swelling of the skin or mucosa, called wheals or urtica. According to frequency and duration, urticaria can be divided into acute and chronic type. Chronic urticaria is any type of urticaria occurring every day or twice per week, lasting longer than 6 weeks. Chronic urticaria is a common disorder and estimated prevalence is 1% of the population. Also, it is not rare in childhood. The pathogenesis of chronic urticaria has not yet been completely understood. Chronic urticaria is a heterogeneous group of disorders, and according to the etiology and cause, several groups of chronic urticaria are distinguished, i.e. autoimmune, pseudoallergic, infection-related, physical urticaria, vasculitis urticaria and idiopathic urticaria. Treatment and management of chronic urticaria can be non-pharmacological and pharmacological, and sometimes it is not possible to control the disease with antihistamines only, which are considered to be the mainstay of treatment. In severe cases of chronic urticaria, especially if autoimmunity has been proven, several authors describe different modules of immunomodulation: cyclosporine, cyclophosphamide, mycophenolate-mofetil, omalizumab, plasmapheresis, systemic corticosteroids, and immunoglobulin therapy. This article primarily addresses the treatment of chronic idiopathic and autoimmune urticaria. PMID:20021986

  10. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S.; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P.; Seiner, Stephen J.; Xiang, Yu-Tao

    2016-01-01

    This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. Trial registration CRD42014006689 (PROSPERO). PMID:27285996

  11. Successful rechallenge with clozapine following ‘red alert’

    PubMed Central

    Toni-Uebari, Thelma K; Rees, John

    2013-01-01

    A case is presented of a 23-year-old lady with treatment-resistant schizoaffective disorder who had responded well to treatment with clozapine. Fifteen months after satisfactory use of clozapine she had ‘red alerts’ from routine haematological monitoring indicating neutropenia. Clozapine was discontinued and she was admitted to the psychiatric hospital to manage the aftermath of discontinuing clozapine and start alternative treatment with other antipsychotics. Her mental health rapidly deteriorated. Adequate trials with amisulpride, haloperidol, olanzapine and flupenthixol decanoate yielded little improvement in her clinical state. After 9 months of non-response to other antipsychotic medications, she was rechallenged with clozapine, followed by improvement in her mental state. She was eventually discharged home after 14 months of hospitalisation in a stable mental state. She remained mentally stable in the community on clozapine for 18 months after rechallenge, with no further red alerts. PMID:23345473

  12. [Chronic migraine: treatment].

    PubMed

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A. PMID:22532241

  13. Neuroleptic-resistant schizophrenic patients treated by clozapine: clinical evolution, plasma and red blood cell clozapine and desmethylclozapine levels.

    PubMed

    Aymard, N; Baldacci, C; Leyris, A; Smagghe, P O; Tribolet, S; Vacheron, M N; Viala, A; Caroli, F

    1997-01-01

    The aim of this open study was to determine a more rational therapeutic approach for psychotic patients treated with clozapine for several months, using measurement of plasma and red blood cell levels (P, RBC) of clozapine (cloza) and N-desmethylclozapine (descloza), the major metabolite of clozapine, which has been reported to be less active but more toxic (agranulocytosis) than clozapine itself. The RBC concentration may be considered as more representative of the free fraction drug. The study concerned 7 patients suffering from chronic paranoid schizophrenia according to the DSM-IV criteria. All of them were treatment-refractory schizophrenic inpatients (4 men, 3 women, mean age +/- SD: 38.2 +/- 8.4 years; mean duration of illness +/- SD: 14.4 +/- 5.1 years). They had received at least two different neuroleptics, for 6 weeks, before entering the study. Treatment started in our hospitalization unit with clozapine 25 mg up to a maximum of 900 mg/d (mean stabilized daily dose +/- SD: 507 +/- 211 mg and mean daily dose per kg: 6.91 +/- 3.08 mg). Clinical evaluations (Quality of Life Scale: QLS), regular blood monitoring and biological samples were conducted at the same time, weekly for 18 weeks and then monthly (duration of the study: 4 to 38 months; mean +/- SD: 12.9 +/- 11.5 months). Plasma and RBC (after lysis) levels were determined by reversed phase HPLC and UV detection after extraction with hexane. All the patients improved very quickly after the first week of treatment and six were able to leave the hospitalization unit and start outpatient care such as daily hospitalization, returning home or in sheltered accommodation. With the following plasma (P) and RBC levels: mean cloza +/- SD: (P = 294 +/- 146 ng/ml; RBC = 110 +/- 82 ng/ml) and mean descloza +/- SD: (P = 173 +/- 106 ng/ml; RBC = 76 +/- 54 ng/ml); none of the seven patients developed agranulocytosis. The blood levels, ensuring better surveillance, have a predictive value for clinical improvement. A

  14. Worldwide Differences in Regulations of Clozapine Use.

    PubMed

    Nielsen, Jimmi; Young, Corina; Ifteni, Petru; Kishimoto, Taishiro; Xiang, Yu-Tao; Schulte, Peter F J; Correll, Christoph U; Taylor, David

    2016-02-01

    Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended. PMID:26884144

  15. Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population.

    PubMed

    Xu, Q; Wu, X; Li, M; Huang, H; Minica, C; Yi, Z; Wang, G; Shen, L; Xing, Q; Shi, Y; He, L; Qin, S

    2016-08-01

    Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61. PMID:26282453

  16. Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: Analysis of the CATIE Phase 2E data

    PubMed Central

    Nakajima, Shinichiro; Takeuchi, Hiroyoshi; Fervaha, Gagan; Plitman, Eric; Chung, Jun Ku; Caravaggio, Fernando; Iwata, Yusuke; Mihashi, Yukiko; Gerretsen, Philip; Remington, Gary; Mulsant, Benoit; Graff-Guerrero, Ariel

    2014-01-01

    Background The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Interventions Effectiveness phase 2E. Methods Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models. Results No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone. Conclusion The present findings suggest clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE. PMID:25556080

  17. An Initiative to Improve Clozapine Prescribing in New York State.

    PubMed

    Carruthers, Jay; Radigan, Marleen; Erlich, Matthew D; Gu, Gyojeong; Wang, Rui; Frimpong, Eric Y; Essock, Susan M; Olfson, Mark; Castillo, Enrico G; Miller, Gregory A; Sederer, Lloyd I; Stroup, T Scott

    2016-04-01

    Clozapine remains the only medication approved for treatment-resistant schizophrenia. But underuse is the norm. In 2010, the New York State Office of Mental Health began a multifaceted initiative to promote the evidence-based use of clozapine. From 2009 to 2013, in the absence of a well-funded pharmaceutical marketing campaign, the proportion of new clozapine trials among all new outpatient antipsychotic trials increased 40% among adult New York Medicaid recipients with a diagnosis of schizophrenia. The largest gains occurred in state-operated clinics. New York's experience demonstrates the feasibility of making clozapine more accessible to patients who stand to benefit most. PMID:26725299

  18. Helping clozapine help: a role for support groups.

    PubMed

    Zita, David F; Goethe, John

    2002-01-01

    A successful clozapine support group operates from the principle that the drug is most successful when the person takes it as prescribed. The likelihood of initial and ongoing collaboration with treatment is increased when the tangible gains of the treatment can be experienced in the self and demonstrated in others. Clozapine support groups can advance the goals of collaboration and recovery. PMID:12047011

  19. Treatment Option Overview (Chronic Myeloproliferative Neoplasms)

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  20. Treatment Options for Chronic Myeloproliferative Neoplasms

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  1. Hematological Adverse Events in Clozapine-Treated Children and Adolescents

    ERIC Educational Resources Information Center

    Gerbino-Rosen, Ginny; Roofeh, David; Tompkins, D. Andrew; Feryo, Doug; Nusser, Laurie; Kranzler, Harvey; Napolitano, Barbara; Frederickson, Anne; Henderson, Inika; Rhinewine, Joe; Kumra, Sanjiv

    2005-01-01

    Objective: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and…

  2. The Use of Clozapine in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Thalayasingam, S.; Alexander, R. T.; Singh, I.

    2004-01-01

    There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region. A retrospective file-review of patients treated in these…

  3. Clozapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2014-01-01

    Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. Main results The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation

  4. Medical management of patients on clozapine: A guide for internists.

    PubMed

    Lundblad, Wynne; Azzam, Pierre N; Gopalan, Priya; Ross, Clinton A

    2015-08-01

    Clozapine was approved by the US Food and Drug Administration in 1989 for the management of treatment-resistant schizophrenia, and has since proven to reduce symptom burden and suicide risk, increase quality of life, and reduce substance use in individuals with psychotic disorders. Nevertheless, clozapine's psychiatric benefits have been matched by its adverse effect profile. Because they are likely to encounter medical complications of clozapine during admissions or consultations for other services, hospitalists are compelled to maintain an appreciation for these iatrogenic conditions. The authors outline common (eg, constipation, sialorrhea, weight gain) and serious (eg, agranulocytosis, seizures, myocarditis) medical complications of clozapine treatment, with internist-targeted recommendations for management, including indications for clozapine discontinuation. PMID:25809850

  5. Clozapine Rechallenge After Neutropenia or Leucopenia.

    PubMed

    Prokopez, Cintia R; Armesto, Arnaldo R; Gil Aguer, María F; Balda, María V; Papale, Rosa M; Bignone, Inés M; Daray, Federico M

    2016-08-01

    To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia. PMID:27232877

  6. Increasing the clozapine: norclozapine ratio with co-administration of fluvoxamine to enhance efficacy and minimize side effects of clozapine therapy.

    PubMed

    Légaré, Nancy; Grégoire, Claire-Anne; De Benedictis, Luigi; Dumais, Alexandre

    2013-06-01

    Although clozapine is the only antipsychotic agent to have demonstrated superior efficacy in treatment-refractory schizophrenia, one- to two-thirds of patients do not respond adequately despite acceptable dosages and plasma levels. Moreover, a significant number of patients stop the therapy for various reasons, including its side effects, many of which are thought to be related to its active metabolite, norclozapine. However, combining clozapine with the SSRI antidepressant fluvoxamine decreases norclozapine formation by inhibiting the CYP450 1A2 isoenzyme. Lowering norclozapine levels in this way while maintaining therapeutic clozapine levels increases the clozapine: norclozapine ratio; the potential benefits include both a reduction of such side effects as sedation, weight gain, metabolic disturbances, and neutropenia, and an increase in efficacy. The optimal ratio of clozapine to norclozapine has not yet been defined, but a ratio of two or more implies that saturation of clozapine metabolism has been reached. We hypothesize that co-administration of clozapine and fluvoxamine at dosages that will produce therapeutic plasma levels of clozapine and a clozapine: norclozapine ratio of two or more will increase efficacy and tolerability of clozapine therapy in treatment-resistant schizophrenic patients. PMID:23490199

  7. Genetic and Clinical Factors Affecting Plasma Clozapine Concentration

    PubMed Central

    Edman, Gunnar; Bertilsson, Leif; Hukic, Dzana Sudic; Lavebratt, Catharina; Eriksson, Sven V.; Ösby, Urban

    2015-01-01

    Objective: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. Method: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. Results: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100–2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10–0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. Conclusions: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine. PMID:26137357

  8. Factors predicting use of laxatives in outpatients stabilized on clozapine

    PubMed Central

    Bailey, Loren; Varma, Seema; Ahmad, Nina; Gee, Siobhan; Taylor, David M.

    2015-01-01

    Constipation is a common and sometimes fatal side effect of clozapine treatment. In this study, we aimed to identify factors associated with clozapine-induced constipation. Data on 202 outpatients stabilized on clozapine treatment were collected. Of these, 71 patients (35%) had a current prescription for laxatives (a proxy for the presence of constipation). Mean clozapine dose was 400.4 mg/day in those prescribed laxatives and 390.1 mg/day in those not prescribed laxatives (p = 0.67), while mean clozapine plasma concentration was 0.53 mg/l and 0.49 mg/l, respectively (p = 0.29). Patients using laxatives had on average 29% higher norclozapine concentrations (mean = 0.34 mg/l) than those who did not use laxatives (mean = 0.27 mg/l; p = 0.046). Laxative use was more common in female patients (49.1%) than male patients (29.1%; p < 0.01). Prescribers should be vigilant for constipation at any dose or plasma concentration of clozapine and should be mindful that male patients may be undertreated. Norclozapine concentrations may predict clozapine-induced constipation. PMID:26557981

  9. Factors predicting use of laxatives in outpatients stabilized on clozapine.

    PubMed

    Bailey, Loren; Varma, Seema; Ahmad, Nina; Gee, Siobhan; Taylor, David M

    2015-10-01

    Constipation is a common and sometimes fatal side effect of clozapine treatment. In this study, we aimed to identify factors associated with clozapine-induced constipation. Data on 202 outpatients stabilized on clozapine treatment were collected. Of these, 71 patients (35%) had a current prescription for laxatives (a proxy for the presence of constipation). Mean clozapine dose was 400.4 mg/day in those prescribed laxatives and 390.1 mg/day in those not prescribed laxatives (p = 0.67), while mean clozapine plasma concentration was 0.53 mg/l and 0.49 mg/l, respectively (p = 0.29). Patients using laxatives had on average 29% higher norclozapine concentrations (mean = 0.34 mg/l) than those who did not use laxatives (mean = 0.27 mg/l; p = 0.046). Laxative use was more common in female patients (49.1%) than male patients (29.1%; p < 0.01). Prescribers should be vigilant for constipation at any dose or plasma concentration of clozapine and should be mindful that male patients may be undertreated. Norclozapine concentrations may predict clozapine-induced constipation. PMID:26557981

  10. Clozapine-Related EEG Changes and Seizures: Dose and Plasma-Level Relationships

    PubMed Central

    Varma, Seema; Bishara, Delia; Besag, Frank M. C.; Taylor, David

    2011-01-01

    Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 μg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 μg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where

  11. Clozapine-induced stuttering: an estimate of prevalence in the west of Ireland

    PubMed Central

    Gallagher, Anne; Sharma, Kapil; Ali, Tariq; Lewis, Elizabeth; Murray, Ivan; Hallahan, Brian

    2015-01-01

    Objectives: Clozapine is the most effective treatment available for treatment-resistant schizophrenia; however, it is also associated with a large array of adverse effects that limits its tolerability. A number of previous case reports have noted an association between clozapine and stuttering, however the rate of this possible adverse effect is yet to be established. Methods: In this paper, we present six cases of patients treated with clozapine who developed stuttering. Results: Clozapine was associated with stuttering in 0.92% of individuals treated with clozapine in the region. Clozapine-induced stuttering was associated with an increase in treatment dose or with dose titration at initiation of clozapine in five individuals, with dose reduction or slower dose titration associated with a cessation of stuttering in these cases. Conclusions: This is the largest case series to date examining clozapine-induced stuttering and indicates that clozapine-induced stuttering is a relatively common adverse effect that can be managed by a slower titration of clozapine dosage or a modest reduction in dose in most cases. PMID:26301079

  12. Effect of Adenine on Clozapine-induced Neutropenia in Patients with Schizophrenia: A Preliminary Study

    PubMed Central

    Takeuchi, Ippei; Kishi, Taro; Hanya, Manako; Uno, Junji; Fujita, Kiyoshi; Kamei, Hiroyuki

    2015-01-01

    Objective This study examined the utility of adenine for preventing clozapine-induced neutropenia. Methods This retrospective study examined the effect of adenine on clozapine-induced neutropenia in patients with treatment-resistant schizophrenia and was conducted at Okehazama Hospital in Japan from July 2010 to June 2013. Adenine was available for use from June 2011 onwards. Twenty-one patients started receiving clozapine treatment from July 2010 to April 2011 (the pre-adenine adoption group), and 47 patients started receiving it from May 2011 to June 2013 (the post-adenine adoption group). The effects of adenine were assessed based on changes in the patients’ leukocyte counts and the frequency of treatment discontinuation due to clozapine-induced neutropenia. Results Sixty-eight patients were treated with clozapine from July 2010 to June 2013. Of the 21 patients in the pre-adenine adoption group, 4 discontinued treatment due to clozapine-induced neutropenia, whereas only 2 of the 47 patients in the post-adenine adoption group discontinued treatment. The frequency of treatment discontinuation due to clozapine-induced neutropenia was significantly lower in post-adenine adoption group than in the pre-adenine adoption group (p=0.047). Conclusion Adenine decreased the frequency of treatment discontinuation due to clozapine-induced neutropenia. Our data suggest that combined treatment with clozapine and adenine is a safe and effective strategy against treatment-resistant schizophrenia. PMID:26243842

  13. Weight gain during a double-blind multidosage clozapine study.

    PubMed

    de Leon, Jose; Diaz, Francisco J; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2007-02-01

    Possible variables associated with weight gain during clozapine treatment include dosing, treatment duration, baseline body mass index (BMI), sex, and plasma norclozapine concentrations. Weight gains during a double-blind, randomized clozapine study using 100-, 300-, and 600-mg/d doses were analyzed. It was hypothesized that weight gain was associated with baseline BMI, clozapine dosing, and demographic factors. The possible contribution of plasma clozapine and norclozapine concentrations was explored. Fifty treatment-refractory schizophrenia patients were randomized to 100-, 300-, or 600-mg/d doses of clozapine for a 16-week, double-blind treatment in a research ward. Nonresponsive patients went onto a second and/or a third 16-week, double-blind treatment at the other doses. Weights of patients were measured every week. During the first clozapine treatment, weight gain varied across 3 baseline BMI categories (normal-weight patients [4.1 kg, P < 0.001], overweight patients [2.6 kg, P = 0.05], and obese patients [0.36 kg, not significant]) and according to dosing (600 mg/d [4.4 kg], 300 mg/d [2.6 kg], and 100 mg/d [1.3 kg]). Sex had no effect after controlling for baseline BMI and dose, but the African-American race had a strong significant effect despite the small number of African Americans (n = 6). At the end of the first clozapine treatment, plasma norclozapine concentration was not significantly correlated with weight gain in the total sample (r = 0.16, P = 0.32, n = 43), but seems to be strongly correlated in nonsmokers. Despite its limitations, this study indicates that baseline BMI, dosing, and, possibly, the African-American race may be major determinants of clozapine-induced weight gain. PMID:17224708

  14. Electroencephalographic Abnormalities in Clozapine-Treated Patients: A Cross-Sectional Study

    PubMed Central

    Goyal, Nishant; Desarkar, Pushpal; Nizamie, Haque

    2011-01-01

    The objective of our study was to examine the electroencephalogram (EEG) abnormalities associated with clozapine treatment. It was a cross-sectional study on 87 psychiatric patients on clozapine treatment. 32 channel digital EEG was recorded and analysed visually for abnormalities. EEG abnormalities were observed in 63.2% of patients. Both slowing and epileptiform activities were noted in 41.4% of patients. The EEG abnormalities were not associated with dose or duration of clozapine exposure. PMID:22216049

  15. Clozapine-induced dysphagia with secondary substantial weight loss.

    PubMed

    Osman, Mugtaba; Devadas, Vekneswaran

    2016-01-01

    Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight. PMID:27543610

  16. Clozapine-induced myoclonus: a case report and review of the literature

    PubMed Central

    Osborne, Ian J.; McIvor, Ronan J.

    2015-01-01

    We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full tonic–clonic seizure. Clozapine treatment can result in a range of seizure-like activity, the most well-known being tonic–clonic seizures. This case highlights the importance of recognizing and treating clozapine-induced myoclonus, as it can herald the onset of a full seizure, even at low serum clozapine levels. We highlight the variety of ways myoclonus can present clinically and suggest treatment options. PMID:26834968

  17. Use of Clozapine for Borderline Personality Disorder: A Case Report

    PubMed Central

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-01-01

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  18. Use of Clozapine for Borderline Personality Disorder: A Case Report.

    PubMed

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-05-31

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  19. [Neurosurgical treatment of chronic pain].

    PubMed

    Fontaine, Denys

    2013-06-01

    Neurosurgical treatment of pain is based on 3 concepts: 1) lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (cordotomy, radicotomy...), they are indicated to treat morphine-resistant cancer pain; 2) neuromodulation techniques try to decrease pain by reinforcing inhibitory mechanisms, using chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation...) to treat chronic neuropathic pain; 3) intrathecal infusion of analgesics (morphine, ziconotide), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, patients with severe and chronic pain, refractory to all other treatments. PMID:23923757

  20. Chronic Pruritus: Clinics and Treatment

    PubMed Central

    Grundmann, Sonja

    2011-01-01

    Chronic pruritus, one of the main symptoms in dermatology, is often intractable and has a high impact on patient's quality of life. Beyond dermatologic disorders, chronic pruritus is associated with systemic, neurologic as well as psychologic diseases. The pathogenesis of acute and chronic (>6 weeks duration) pruritus is complex and involves in the skin a network of resident (e.g., sensory neurons) and transient inflammatory cells (e.g., lymphocytes). In the skin, several classes of histamine-sensitive or histamine-insensitve C-fibers are involved in itch transmission. Specific receptors have been discovered on cutaneous and spinal neurons to be exclusively involved in the processing of pruritic signals. Chronic pruritus is notoriously difficult to treat. Newer insights into the underlying pathogenesis of pruritus have enabled novel treatment approaches that target the pruritus-specific pathophysiological mechanism. For example, neurokinin-1 antagonists have been found to relieve chronic pruritus. PMID:21738356

  1. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. PMID:24141084

  2. Clozapine: Its Impact on Aggressive Behavior among Children and Adolescents with Schizophrenia.

    ERIC Educational Resources Information Center

    Kranzler, Harvey; Roofeh, David; Gerbino-Rosen, Ginny; Dombrowski, Carolyn; McMeniman, Marjorie; DeThomas, Courtney; Frederickson, Anne; Nusser, Laurie; Bienstock, Mark D.; Fisch, Gene S.; Kumra, Sanjiv

    2005-01-01

    Objective: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.X) at Bronx Children's Psychiatric Center. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of…

  3. Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine

    SciTech Connect

    Husain, Zaheed; Almeciga, Ingrid; Delgado, Julio C.; Clavijo, Olga P.; Castro, Januario E.; Belalcazar, Viviana; Pinto, Clara; Zuniga, Joaquin; Romero, Viviana; Yunis, Edmond J. . E-mail: edmond_yunis@dfci.harvard.edu

    2006-08-01

    Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 {mu}M) in the presence of 0.1 mM H{sub 2}O{sub 2} demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60 cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis.

  4. Behavioral effects of clozapine: Involvement of trace amine pathways in C. elegans and M. musculus

    PubMed Central

    Karmacharya, Rakesh; Lynn, Spencer K.; Demarco, Sarah; Ortiz, Angelica; Wang, Xin; Lundy, Miriam Y.; Xie, Zhihua; Cohen, Bruce M.; Miller, Gregory M.; Buttner, Edgar A.

    2011-01-01

    Clozapine is an antipsychotic medication with superior efficacy in treatment-refractory schizophrenia. The molecular basis of clozapine’s therapeutic profile is not well understood. We studied behavioral effects of clozapine in Caenorhabditis elegans to identify novel pathways that modulate clozapine’s biological effects. Clozapine stimulated egg laying in C. elegans in a dose-dependent manner. This effect was clozapine-specific, as it was not observed with exposure to a typical antipsychotic, haloperidol or an atypical antipsychotic, olanzapine. A candidate gene screen of biogenic amine neurotransmitter systems identified signaling pathways that mediate this clozapine-specific effect on egg laying. Specifically, we found that clozapine-induced increase in egg laying requires tyramine biosynthesis. To test the implications of this finding across species, we explored whether trace amine systems modulate clozapine’s behavioral effects in mammals by studying trace amine-associated receptor 1 (TAAR1) knockout mice. Clozapine increased pre-pulse inhibition (PPI) in wild-type mice. This increase in PPI was abrogated in TAAR1 knockout mice, implicating TAAR1 in clozapine-induced PPI enhancement. In transfected mammalian cell lines, we found no TAAR activation by antipsychotics, suggesting that modulation of trace amine signaling in mice does not occur directly at the receptor itself. In summary, we report a heretofore-unknown role for trace amine systems in clozapine-mediated effects across two species: C. elegans and mice. PMID:21529784

  5. [Neurosurgical treatment of chronic pain].

    PubMed

    Fontaine, D; Blond, S; Mertens, P; Lanteri-Minet, M

    2015-02-01

    Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications. PMID:25681114

  6. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

    PubMed

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  7. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence

    PubMed Central

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m2 and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m2. Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  8. Training in a Clozapine Clinic for Psychiatry Residents: A Plea and Suggestions for Implementation

    ERIC Educational Resources Information Center

    Freudenreich, Oliver; Henderson, David C.; Sanders, Kathy M.; Goff, Donald C.

    2013-01-01

    Objective: The authors sought to develop a model educational clinic and curriculum for psychiatric residents, to increase knowledge and comfort about clozapine prescribing. This matters because clozapine is an important evidence-based treatment for refractory schizophrenia that remains underutilized in clinical practice. Method: This is a…

  9. The Use of Clozapine among Individuals with Intellectual Disability: A Review

    ERIC Educational Resources Information Center

    Singh, Ashvind N.; Matson, Johnny L.; Hill, B. D.; Pella, Russell D.; Cooper, Christopher L.; Adkins, Angela D.

    2010-01-01

    Clozapine has been approved in the United States since 1990 for refractory or treatment resistant schizophrenia in the general population. However, as with many other antipsychotic medications, it is being prescribed for reasons other than those indicated. Among individuals with intellectual disabilities, clozapine is increasingly being prescribed…

  10. Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients with Persistent Symptoms

    PubMed Central

    Kelly, Deanna L.; Sullivan, Kelli M.; McEvoy, Joseph P; McMahon, Robert P.; Wehring, Heidi J.; Liu, Fang; Warfel, Dale; Vyas, Gopal; Richardson, Charles M.; Fischer, Bernard A.; Keller, William R.; Mathew Koola, Maju; Feldman, Stephanie; Russ, Jessica C.; Keefe, Richard S.; Osing, Jennifer; Hubzin, Leeka; August, Sharon; Walker, Trina M.; Buchanan, Robert W.

    2015-01-01

    Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10 week, double blind placebo-controlled trial. Primary outcomes tested were positive and cognitive symptoms, while avolition, anxiety/depression and negative symptoms were secondary outcomes. Methods Schizophrenia and schizoaffective participants (N=52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily) (N=29) or placebo (N=23). Results Brief Psychiatric Rating Scale (BPRS) psychosis factor (p=0.098, effect size ES=0.39) and BPRS total score (p=0.075, effect size 0.55) were not significant. A ≥30% change in total BPRS symptoms was observed in 7/28 (25%) among minocycline and 1/23 (4%) among placebo participants, respectively (p=0.044). Global cognitive function (MATRICS Consensus Cognitive Battery, MCCB) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (p=0.03), with significant improvement in working memory favoring minocycline (p=0.023, ES 0.41). The SANS total score did not differ, but significant improvement in avolition with minocycline was noted (p=0.012, ES=0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (p=0.028, ES=0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared to placebo. Conclusion Minocycline’s effect on the MCCB composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings. PMID:26082974

  11. Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study.

    PubMed

    Schneider, Carolina; Papachristou, Efstathios; Wimberley, Theresa; Gasse, Christiane; Dima, Danai; MacCabe, James H; Mortensen, Preben Bo; Frangou, Sophia

    2015-06-01

    Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS. PMID:25769917

  12. The Effect of Race-Ethnicity on Clozapine Outcomes among Medicaid Beneficiaries with Schizophrenia

    PubMed Central

    Horvitz-Lennon, Marcela; Donohue, Julie M.; Lave, Judith R.; Alegria, Margarita; Normand, Sharon-Lise T.

    2013-01-01

    Objective Effectiveness trials have confirmed the superiority of clozapine in the treatment of schizophrenia, but little is known about whether the drug’s superiority holds across racial-ethnic groups. This study examined the effect of race-ethnicity on the effectiveness of clozapine relative to other antipsychotics among patients in maintenance antipsychotic treatment. Methods Black, Latino, and white Florida Medicaid beneficiaries with schizophrenia receiving maintenance treatment with clozapine or other antipsychotic medications during 7/1/00-6/30/05 were identified. Cox proportional hazard regression models were used to estimate associations of clozapine, race-ethnicity, and their interaction, with time to discontinuation for any cause, our primary measure of effectiveness. Results The study cohort included 20,122 episodes of treatment with clozapine (3.7%) and other antipsychotics (96.3%), with 23% black and 36% Latino. Unadjusted analyses suggested that Latinos continue on clozapine longer than whites, while they and blacks discontinue other antipsychotics sooner than whites. Adjusted analyses using 749 propensity score matched sets of clozapine and other antipsychotic users indicated that risk of discontinuation was lower for clozapine users (RR = .45, 95% CI = .39 – .52), an effect that was not moderated by race-ethnicity. Times to discontinuation were longer for clozapine users. Overall risk of antipsychotic discontinuation was higher for blacks (RR =1.56, CI = 1.27 – 1.91), and Latinos (RR = 1.23, CI = 1.02 – 1.48). Conclusions This study confirmed clozapine’s superior effectiveness and did not find evidence that race-ethnicity modifies this effect. These findings heighten the need for efforts to increase clozapine use, particularly among minority groups. PMID:23242347

  13. Clozapine's Effect on Recidivism Among Offenders with Mental Disorders.

    PubMed

    Mela, Mansfield; Depiang, Gu

    2016-03-01

    Mental disorder is associated with criminal reoffending, especially violent acts of offending. Features of mental disorder, psychosocial stresses, substance use disorder, and personality disorder combine to increase the risk of criminal recidivism. Clozapine, an atypical antipsychotic, is indicated in the treatment of patients with psychotic disorders. This article is the report of a community follow-up study of a matched control of those treated with clozapine (n = 41) and those treated with other antipsychotics (n = 21). Rates of reoffending behavior in the general, nonviolent, violent, and sexual categories were calculated after two years of follow-up. Although not statistically significant, the two-year criminal conviction rates of those treated with other antipsychotics in all offense categories except sexual reoffending were two-fold higher than in those treated with clozapine. The time from release to the first offense and crime-free time in the community were significantly longer in the clozapine group. By prolonging the time it takes from release to first offense, clozapine confers additional crime-reduction advantages. PMID:26944747

  14. Clozapine Can Be the Good Option in Resistant Mania.

    PubMed

    Arafat, S M Yasir; Rahman, S M Atikur; Haque, Md Maruful; Shah, Mohsin Ali; Algin, Sultana; Nahar, Jhunu Shamsun

    2016-01-01

    Bipolar mood disorder is a mental disorder with a lifetime prevalence rate of about 1% in the general population and there are still a proportion of individuals who suffer from bipolar mood disorders that are resistant to standard treatment. Reporting clozapine responsive mania that was not responding to two previous consecutive atypical antipsychotics and one typical antipsychotic was aimed at. A 17-year-old male manic patient was admitted into the psychiatry inpatient department and was nonresponsive to Risperidone 12 mg daily for 4 weeks, Olanzapine 30 mg daily for 3 weeks, and Haloperidol 30 mg daily for 3 weeks, along with valproate preparation 1500 mg daily. He was started on clozapine as he was nonresponsive to Lithium in previous episodes and did not consent to starting Electroconvulsive Therapy (ECT). He responded adequately to 100 mg clozapine and 1500 mg valproate preparation and remission happened within 2 weeks of starting clozapine. Clozapine can be a good option for resistant mania and further RCT based evidences will strengthen the options in treating resistant mania. PMID:27525148

  15. Clozapine Can Be the Good Option in Resistant Mania

    PubMed Central

    Haque, Md. Maruful; Shah, Mohsin Ali; Algin, Sultana; Nahar, Jhunu Shamsun

    2016-01-01

    Bipolar mood disorder is a mental disorder with a lifetime prevalence rate of about 1% in the general population and there are still a proportion of individuals who suffer from bipolar mood disorders that are resistant to standard treatment. Reporting clozapine responsive mania that was not responding to two previous consecutive atypical antipsychotics and one typical antipsychotic was aimed at. A 17-year-old male manic patient was admitted into the psychiatry inpatient department and was nonresponsive to Risperidone 12 mg daily for 4 weeks, Olanzapine 30 mg daily for 3 weeks, and Haloperidol 30 mg daily for 3 weeks, along with valproate preparation 1500 mg daily. He was started on clozapine as he was nonresponsive to Lithium in previous episodes and did not consent to starting Electroconvulsive Therapy (ECT). He responded adequately to 100 mg clozapine and 1500 mg valproate preparation and remission happened within 2 weeks of starting clozapine. Clozapine can be a good option for resistant mania and further RCT based evidences will strengthen the options in treating resistant mania. PMID:27525148

  16. Gene polymorphisms potentially related to the pharmacokinetics of clozapine: a systematic review.

    PubMed

    Krivoy, Amir; Gaughran, Fiona; Weizman, Abraham; Breen, Gerome; MacCabe, James H

    2016-07-01

    Clozapine is currently the ultimate effective therapy for otherwise treatment-refractory schizophrenia. However, the drug is also associated with many adverse effects, some of them potentially fatal. Thus, there is an unmet need to predict clinical response to clozapine. As the pharmacokinetics of clozapine vary considerably between and within individuals, there may be an association between genetic polymorphisms and clozapine plasma concentration and consequently, clinical response. We have reviewed studies that have investigated the association between clozapine metabolic pathways related to genes polymorphisms in relation to plasma clozapine concentration and clinical response. Overall, most of the studies reported negative results. The only gene polymorphism that has been found to be associated with clozapine plasma concentration and response was the ABCB1 gene, which codes for transmembrane transporters expressed in the bowel mucosa, blood-brain barrier, kidney and liver. More prospective longitudinal studies are needed to elucidate the possible role of the ABCB1 polymorphism and transmembrane transporters in clozapine pharmacokinetics and clinical response. PMID:25563806

  17. [Behavioral treatment for chronic insomnia].

    PubMed

    Adachi, Yoshiko; Yamagami, Toshiko

    2002-01-01

    The efficacy of non-pharmacological intervention for chronic insomnia has been proven by several meta-analytic reviews, an NIH report, an American Academy of Sleep Medicine review, and numerous clinical trials. Behavior therapy for chronic insomnia consists of relaxation, stimulus control, sleep restriction, cognitive restructuring and sleep hygiene education, which has produced reliable and durable changes in total sleep time, sleep onset latency, number and duration of awakening. These studies also showed that the post-treatment effect of behavior therapy is equal to that of hypnotic therapy, and that these effects were maintained for 6 months on follow-up assessment. Elderly insomniac patients would gain considerable benefit from behavioral treatments because there are no adverse physical effects as there are from pharmacological therapy. The authors present the basic theory, techniques of behavior therapy for insomnia, and the results of two important key meta-analytic reviews. Any behavioral approach such as convenient education, self-care enhancement by bibliotherapy, and individual face-to-face counseling, seem to be fruitful not only for American but also Japanese insomnia patients. Nonetheless, there are no currently actual intervention studies using behavior therapy in Japan. We have discussed the methodology of intervention study and published a behavioral self-help manual for people with sleep problems. Development of a behavioral approach to chronic insomnia seemed to be very beneficial and a useful contribution to mental health services. PMID:12373807

  18. Clozapine-Induced Myocarditis: A Case Report of an Adolescent Boy with Intellectual Disability

    PubMed Central

    Aboueid, Lila; Toteja, Nitin

    2015-01-01

    Background. Although known for its efficacy in treatment-resistant schizophrenia, the usage of clozapine has been limited due to concerns over potential adverse effects. Myocarditis, one potential fatal complication, can develop at any point during treatment but has been most commonly observed 2-3 weeks after clozapine initiation. Objective. A case of acute clozapine-induced myocarditis is described, highlighting the history, onset, and treatment course of presentation. There is a need to raise awareness of this potential complication, especially in the pediatric population. Results. 17-year-old Puerto Rican boy, with history of schizophrenia, disorganized type (treatment resistant), and intellectual disability, developed myocarditis on the thirteenth day following clozapine commencement. Initial presenting symptoms included tachycardia, lethargy, and vague gastrointestinal distress. Patient fully recovered after supportive medical care and clozapine discontinuation. Conclusions. Myocarditis is a known potential complication of clozapine initiation; however, due to its limited usage in the pediatric population, reported cases are limited. There is a need to establish evidence-based monitoring guidelines for clozapine usage, particularly in the pediatric population where the presentation may be atypical and clinical suspicion may be overlooked. PMID:26266072

  19. Treatment of chronic venous insufficiency.

    PubMed

    Rathbun, Suman W; Kirkpatrick, Angelia C

    2007-04-01

    Chronic venous insufficiency (CVI) results from venous hypertension secondary to superficial or deep venous valvular reflux. Treatment modalities are aimed at reducing venous valvular reflux, thereby inhibiting the ensuing pathologic inflammatory process. Compression therapy using pumps, bandaging, and/or graded compression stockings is the mainstay of treatment for CVI. Compression therapy has been shown to be effective in reducing venous hypertension retarding the development of inflammation and pathologic skin changes. Pharmacologic agents such as diuretics and topical steroid creams reduce swelling and pain short term but offer no long-term treatment advantage. Herbal supplements may reduce the inflammatory response to venous hypertension, but are not licensed by the US Food and Drug Administration, and vary in their efficacy, quality, and safety. However, several randomized controlled trials using the herbal horse chestnut seed extract containing aescin have shown short-term improvement in signs and symptoms of CVI. Endovascular and surgical techniques aimed at treatment of primary and secondary venous valvular reflux have been shown to improve venous hemodynamics promoting healing of venous ulcers and improving quality of life. The newer endovascular treatments of varicose veins using laser, radiofrequency ablation, and chemical foam sclerotherapy show some promise. PMID:17484814

  20. The Effect of Clozapine on Hematological Indices: A 1-Year Follow-Up Study.

    PubMed

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Powell, Valerie; Bhaloo, Amaal; Bies, Robert; Remington, Gary

    2015-10-01

    Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations. PMID:26267420

  1. Glutamatergic Neurometabolites in Clozapine-Responsive and -Resistant Schizophrenia

    PubMed Central

    Goldstein, Meghan Elizabeth; Anderson, Valerie Margaret; Pillai, Avinesh; Kydd, Robert R.

    2015-01-01

    Background: According to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated. Methods: Proton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects. Results: Group differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η2 = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η2 = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected). Conclusions: Total glutamate + glutamine levels

  2. Knowledge of Psychiatric Nurses About the Potentially Lethal Side-Effects of Clozapine.

    PubMed

    De Hert, Marc; De Beugher, Annelien; Sweers, Kim; Wampers, Martien; Correll, Christoph U; Cohen, Dan

    2016-02-01

    Clozapine is an antipsychotic with superior efficacy in treatment refractory patients, and has unique anti-suicidal properties and a low propensity to cause extrapyramidal side-effects. Despite these advantages, clozapine utilization is low. This can in part be explained by a number of potentially lethal side effects of clozapine. Next to psychiatrists nurses play a crucial role in the long-term management of patients with schizophrenia. It is therefore important that nurses know, inform and monitor patients about the specific side-effects of clozapine. A recent study of psychiatrists published in 2011 has shown that there was a gap in the knowledge about side-effects of clozapine. The knowledge about side-effects of clozapine in nurses has never been studied. This cross-sectional study evaluated the knowledge base regarding the safety of clozapine, and its potential mediators, of psychiatric nurses in 3 psychiatric hospitals in Belgium with a specifically developed questionnaire based on the literature and expert opinion (3 clozapine experts). A total of 85 nurses completed the questionnaire. The mean total score was 6.1 of a potential maximum score of 18. Only 3 of the 18 multiple choice knowledge questions were answered correctly by more than 50% of nurses. Only 24.9% of participants passed the test (>50% correct answers). Nurses working on psychosis units were more likely to pass the test (xx.y% vs yy.z%, p=0.0124). There was a trend that nurses with a lower nursing diploma were more likely to fail the test (p=0.0561). Our study clearly identifies a large gap in the basic knowledge of psychiatric nurses about clozapine and its side-effects. Knowledge could be increased by more emphasis on the topic in nurse's training curricula as well as targeted onsite training. Only 23.5% of participants indicate that there was sufficient information in their basic nursing training. PMID:26804506

  3. Clinical management of clozapine patients in relation to efficacy and side-effects.

    PubMed

    Naber, D; Holzbach, R; Perro, C; Hippius, H

    1992-05-01

    Medical charts of 480 schizophrenic in-patients (581 treatments) were analysed to evaluate the efficacy and side-effects of clozapine. Clozapine treatment lasted for mean 49 (s.d. 38) days. Of the sample, 11.0% showed worsening or no change, 31.5% slight improvement, 53.0% marked improvement and 4.5% almost total reduction of symptoms. At least one major side-effect occurred in 68.0% of patients. A combination of clozapine with classical neuroleptics, antidepressants, benzodiazepines or lithium is tolerated by most patients, but increases the incidence of some side-effects. Clozapine treatment had to be discontinued because of severe side-effects in 8.6% of patients. In 81 schizophrenic out-patients, clozapine significantly reduced the days of in-patient treatment and number of hospital readmissions. Two patients developed leucopenia but had no complications after clozapine withdrawal. This study indicates a satisfactory benefit/risk ratio and compliance in most of the patients. PMID:1358128

  4. Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats.

    PubMed

    Tian, Dan-Dan; Wang, Wei; Wang, Hua-Ning; Sze, Stephen Cho Wing; Zhang, Zhang-Jin

    2016-01-01

    Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-drug interactions, which were rarely reported when antipsychotics were included. This study aims to determine whether the concomitant use of these herbal medicines affects the pharmacokinetic characteristics of CLZ in rat models. Rats were given a single or multiple intraperitoneal injections of 10 mg/kg CLZ, either alone or with individual herbal water extracts administered orally. CLZ and its two inactive metabolites, norclozapine and clozapine N-oxide, were determined by high-performance liquid chromatography/tandem mass spectrometry. In the acute treatment, the formation of both metabolites was reduced, while no significant change was observed in the CLZ pharmacokinetics for any of the herbal extracts. In the chronic treatment, none of the four herbal extracts significantly influenced the pharmacokinetic parameters of CLZ and its metabolites. Renal and liver functions stayed normal after the 11-day combined use of herbal medicines. Overall, the four herbs had limited interaction effect on CLZ pharmacokinetics in the acute and chronic treatment. Herb-drug interaction includes both pharmacokinetic and pharmacodynamic mechanisms. This result gives us a hint that pharmacodynamic herb-drug interaction, instead of pharmacokinetic types, may exist and need further confirmation. PMID:27240333

  5. Chronic migraine: risk factors, mechanisms and treatment.

    PubMed

    May, Arne; Schulte, Laura H

    2016-08-01

    Chronic migraine has a great detrimental influence on a patient's life, with a severe impact on socioeconomic functioning and quality of life. Chronic migraine affects 1-2% of the general population, and about 8% of patients with migraine; it usually develops from episodic migraine at an annual conversion rate of about 3%. The chronification is reversible: about 26% of patients with chronic migraine go into remission within 2 years of chronification. The most important modifiable risk factors for chronic migraine include overuse of acute migraine medication, ineffective acute treatment, obesity, depression and stressful life events. Moreover, age, female sex and low educational status increase the risk of chronic migraine. The pathophysiology of migraine chronification can be understood as a threshold problem: certain predisposing factors, combined with frequent headache pain, lower the threshold of migraine attacks, thereby increasing the risk of chronic migraine. Treatment options include oral medications, nerve blockade with local anaesthetics or corticoids, and neuromodulation. Well-defined diagnostic criteria are crucial for the identification of chronic migraine. The International Headache Society classification of chronic migraine was recently updated, and now allows co-diagnosis of chronic migraine and medication overuse headache. This Review provides an up-to-date overview of the classification of chronic migraine, basic mechanisms and risk factors of migraine chronification, and the currently established treatment options. PMID:27389092

  6. Lessons Learned and Questions Raised by an Atypical Case of Clozapine-Induced Myocarditis.

    PubMed

    Earnshaw, Charles H; Powell, Lucy; Haeney, Owen

    2016-01-01

    A Caucasian male in his early twenties suffering from treatment resistant schizophrenia was started on clozapine. After three days he developed tachycardia, a common side effect of clozapine induction. He had one temperature spike (38.9°C) on day ten after induction but remained clinically well. An ECG and blood tests were normal. Due to persistent tachycardia and an episode of collapse whilst seated on day 12, he was admitted to hospital for further investigation. A diagnosis of myocarditis was confirmed as a result of elevated cardiac enzyme levels and an echocardiogram. Following withdrawal of clozapine, supportive management, and initiation of cardiac medication, the patient made a successful recovery. He will be followed up with the cardiology team to ensure that his heart function returns to normal. Given the incidence of clozapine-induced myocarditis, the associated mortality risk, and diagnostic difficulties, this case raises questions about whether a formal system for identifying myocarditis should be adopted. PMID:27478671

  7. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis.

    PubMed

    Shirazi, Ayala; Stubbs, Brendon; Gomez, Lucia; Moore, Susan; Gaughran, Fiona; Flanagan, Robert J; MacCabe, James H; Lally, John

    2016-01-01

    Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6-37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91-4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID:27271593

  8. The novel use of clozapine in an adolescent with borderline personality disorder

    PubMed Central

    Hill, Simon Alastair

    2014-01-01

    Background: Clozapine has been used to good effect in the treatment of adults with borderline personality disorder, but there is scant evidence of it being used in an adolescent population with these difficulties. Methods: Clozapine was trialled in an adolescent with a clinical presentation consistent with an emerging borderline personality disorder. Results: There was a large reduction in the number of incidents involving abuse to staff, or harm to self, in the 8 weeks after commencing clozapine therapy, compared with the 8 weeks prior, and also a large reduction in the number of episodes of the use of seclusion in the 13 weeks after commencing clozapine therapy, compared with the 13 weeks prior. The young person was also able to be reintegrated in to the ward environment once established on clozapine therapy, which had not been possible full-time, for a whole year prior. Conclusions: Although limited by involving just one adolescent, this very preliminary data does nonetheless suggest that clozapine may have a role in treating adolescents with emerging borderline personality disorder when other treatment options have been exhausted. PMID:25083274

  9. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

    PubMed Central

    Shirazi, Ayala; Stubbs, Brendon; Gomez, Lucia; Moore, Susan; Gaughran, Fiona; Flanagan, Robert J.; MacCabe, James H.; Lally, John

    2016-01-01

    Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID:27271593

  10. Easing Chronic Pain: Better Treatments and Medications

    MedlinePlus

    ... Bar Home Current Issue Past Issues Easing Chronic Pain: Better Treatments and Medications Past Issues / Fall 2007 ... this page please turn Javascript on. What Is Pain? You know it at once. It may be ...

  11. Management and treatment of chronic urticaria (CU).

    PubMed

    Maurer, M; Church, M K; Gonçalo, M; Sussman, G; Sánchez-Borges, M

    2015-06-01

    Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU. PMID:26053292

  12. The diagnosis and treatment of chronic migraine.

    PubMed

    Weatherall, Mark W

    2015-05-01

    Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine. PMID:25954496

  13. The diagnosis and treatment of chronic migraine

    PubMed Central

    2015-01-01

    Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine. PMID:25954496

  14. Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice.

    PubMed

    Wohkittel, Christopher; Gerlach, Manfred; Taurines, Regina; Wewetzer, Christoph; Unterecker, Stefan; Burger, Rainer; Schreck, Diana; Mehler-Wex, Claudia; Romanos, Marcel; Egberts, Karin

    2016-08-01

    Information on dose- and concentration-related clinical effects of clozapine treatment in children and adolescents is scarce. This study aimed to examine the relationship between dose, serum concentration, and clinical outcome as well as the influencing factors thereof in paediatric patients treated with clozapine. Data from a routine Therapeutic Drug Monitoring (TDM) service between 2004 and 2014 were studied in 68 patients, aged 11-18 years. Severity of illness, therapeutic effectiveness and adverse drug reactions (ADRs) were assessed by standardized means. A relationship between the daily dose (mean 319 mg, 4.9 mg/kg) and serum concentration (mean 387 ng/ml) of clozapine was found with the variation in dose explaining 30 % of the variability in clozapine serum concentrations. Also gender contributed to the variability, however, no influence of age or concomitant medications was detected. Furthermore, a significant association was found between clozapine serum concentration and the occurrence of ADRs. Patients without ADRs had a lower mean serum concentration than those with mild (261.4 vs 407.3 ng/ml, P = 0.018) and moderate ADRs (261.4 vs 416.3 ng/ml, P = 0.028). As clozapine was estimated to be effective in lower blood concentrations, guidance on a possibly lower therapeutic range of clozapine serum levels in paediatric patients is provided. With ADRs increasing under higher concentrations, TDM is strongly recommended in paediatric clozapine therapy for individualized dosing. Dose adjustment in females also might be reasonable according to gender-related differences in serum concentrations. However, regarding the limitations of this study results should be validated in larger studies with more standardized designs. PMID:27221285

  15. Case Report. Prevention of Clozapine-Induced Granulocytopenia/Agranulocytosis with Granulocyte-Colony Stimulating Factor (G-CSF) in an Intellectually Disabled Patient with Schizophrenia

    ERIC Educational Resources Information Center

    Rajagopal, G.; Graham, J. G.; Haut, F. F. A.

    2007-01-01

    Background: While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery. Method: In this case…

  16. Behavioral effects of sertindole, risperidone, clozapine and haloperidol in Cebus monkeys.

    PubMed

    Casey, D E

    1996-03-01

    Extrapyramidal side effects (EPS) are major limitations to neuroleptic treatment of psychoses. To evaluate further the behavioral characteristics of the novel antipsychotic agents, a wide range of single intramuscular doses of sertindole (0.1-2.5 mg/kg IM), risperidone (0.01-0.25 mg/kg IM), clozapine (1.0-25.0 mg/kg IM), and haloperidol (0.01-0.25 mg/kg IM) were blindly evaluated at weekly intervals in Cebus monkeys previously sensitized to neuroleptics. All drugs except clozapine produced dystonia and parkinsonian symptoms, but haloperidol and risperidone were 50-100 times more potent than sertindole in producing EPS. Sertindole, risperidone and haloperidol had no significant sedative effects, whereas clozapine produced dose related sedation. Risperidone, clozapine and haloperidol but not sertindole decreased locomotor activity. Sertindole, risperidone and clozapine had a calming effect at doses below the EPS threshold, unlike haloperidol. Sertindole has many behavioral effects in nonhuman primates that are similar to those seen with the new antipsychotics, risperidone and clozapine, which suggests a favorable antipsychotic benefit/risk ratio in the clinic, especially regarding EPS. PMID:8935808

  17. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms.

    PubMed

    Leung, Jonathan G; Palmer, Brian A

    2016-01-01

    One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS). OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of "violent delusions." However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD) was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient's obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS. PMID:27313938

  18. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms

    PubMed Central

    2016-01-01

    One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS). OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of “violent delusions.” However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD) was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient's obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS. PMID:27313938

  19. The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

    PubMed Central

    Yadav, Prem N; Abbas, Atheir I; Farrell, Martilias S; Setola, Vincent; Sciaky, Noah; Huang, Xi-Ping; Kroeze, Wesley K; Crawford, LaTasha K; Piel, David A; Keiser, Michael J; Irwin, John J; Shoichet, Brian K; Deneris, Evan S; Gingrich, Jay; Beck, Sheryl G; Roth, Bryan L

    2011-01-01

    Clozapine, by virtue of its absence of extrapyramidal side effects and greater efficacy, revolutionized the treatment of schizophrenia, although the mechanisms underlying this exceptional activity remain controversial. Combining an unbiased cheminformatics and physical screening approach, we evaluated clozapine's activity at >2350 distinct molecular targets. Clozapine, and the closely related atypical antipsychotic drug olanzapine, interacted potently with a unique spectrum of molecular targets. This distinct pattern, which was not shared with the typical antipsychotic drug haloperidol, suggested that the serotonergic neuronal system was a key determinant of clozapine's actions. To test this hypothesis, we used pet1−/− mice, which are deficient in serotonergic presynaptic markers. We discovered that the antipsychotic-like properties of the atypical antipsychotic drugs clozapine and olanzapine were abolished in a pharmacological model that mimics NMDA-receptor hypofunction in pet1−/− mice, whereas haloperidol's efficacy was unaffected. These results show that clozapine's ability to normalize NMDA-receptor hypofunction, which is characteristic of schizophrenia, depends on an intact presynaptic serotonergic neuronal system. PMID:21048700

  20. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for chronic lymphocytic leukemia What`s new in chronic lymphocytic leukemia research and treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  1. Treatment of Refractory Chronic Urticaria

    PubMed Central

    Mehta, Aayushi; Godse, Kiran; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot

    2015-01-01

    Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature. PMID:26120147

  2. Can valproic acid be an inducer of clozapine metabolism?

    PubMed Central

    Diaz, Francisco J.; Eap, Chin B.; Ansermot, Nicolas; Crettol, Severine; Spina, Edoardo; de Leon, Jose

    2014-01-01

    Introduction Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that 1) VPA is a net inducer of clozapine metabolism, and 2) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14% to 39%) after controlling for confounding variables including smoking (35% lower, 28% to 56%). Discussion Prospective studies are needed to definitively establish that VPA may 1) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and 2) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism. PMID:24764199

  3. [Local invasive treatment of chronic pain].

    PubMed

    Medvedeva, L A; Zagorul'ko, O I; Gnezdilov, A V

    2014-01-01

    The literature on methods of invasive local treatment of chronic pain was analyzed. We reviewed 14 publications including meta-analyses and systematic reviews. The use of regional anesthesia conducted by anesthesiologists in pain clinics demonstrated the evidence based efficacy of different types of peridural injections of local anesthetics with steroids in patients with root pain syndromes at cervical and lumbar levels. Therapeutic blockades of the occipital nerve is effective method of treatment of cervicogenic and cluster headache as well as occipital nerve neuralgia. There are clear indications of the efficacy of local injections in primary chronic cephalgia (migraine and headache of tension). The possibility of the abortion of the pain information flow in peripheral nociceptive pathways and, as a consequence, breaking the vicious circle is emphasized. Issues on the efficacy of local injections at trigger points in the treatment of chronic pain are highlighted. PMID:24874319

  4. Dopamine dynamics during emotional cognitive processing: Implications of the specific actions of clozapine compared with haloperidol.

    PubMed

    Kawano, Masahiko; Oshibuchi, Hidehiro; Kawano, Takaaki; Muraoka, Hiroyuki; Tsutsumi, Takahiro; Yamada, Makiko; Inada, Ken; Ishigooka, Jun

    2016-06-15

    Clozapine has improved efficacy relative to typical antipsychotics in schizophrenia treatment, particularly regarding emotional symptoms. However, the mechanisms underlying its therapeutic benefits remain unclear. Using a methamphetamine-sensitised rat model, we measured changes in dopamine levels in the amygdalae in response to a fear-conditioned cue, serving as a biochemical marker of emotional cognitive processing disruption in psychosis, for analysing the biochemical mechanisms associated with the clinical benefits of clozapine. We also compared how clozapine and haloperidol affected basal dopamine levels and phasic dopamine release in response to the fear-conditioned cue. Extracellular dopamine was collected from the amygdalae of freely moving rats via microdialysis and was analysed by high-performance liquid chromatography. Clozapine or haloperidol was injected during microdialysis, followed by exposure to the fear-conditioned cue. We analysed the ratio of change in dopamine levels from baseline. Haloperidol treatment increased the baseline dopamine levels in both non-sensitised and sensitised rats. Conversely, clozapine only increased the basal dopamine levels in the non-sensitised rats, but not in the sensitised rats. Although both antipsychotics attenuated phasic dopamine release in both the non-sensitised and sensitised rats, the attenuation extent was greater for clozapine than for haloperidol under both dopaminergic conditions. Our findings indicate that stabilized dopamine release in the amygdalae is a common therapeutic mechanism of antipsychotic action during emotional processing. However, the specific dopaminergic state-dependent action of clozapine on both basal dopamine levels and stress-induced dopamine release may be the underlying mechanism for its superior clinical effect on emotional cognitive processing in patients with schizophrenia. PMID:27085900

  5. Response to clozapine in a clinically identifiable subtype of schizophrenia

    PubMed Central

    Butcher, Nancy J.; Fung, Wai Lun Alan; Fitzpatrick, Laura; Guna, Alina; Andrade, Danielle M.; Lang, Anthony E.; Chow, Eva W. C.; Bassett, Anne S.

    2015-01-01

    Background Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples. Aims To determine whether patients with a well-established genetic subtype of schizophrenia show a different response profile to the antipsychotic clozapine than those with idiopathic schizophrenia. Method We retrospectively studied the long-term safety and efficacy of clozapine in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS group) and half matched for age and clinical severity but molecularly confirmed to have no pathogenic copy number variant (idiopathic group). Results Both groups showed similar clinical improvement and significant reductions in hospitalisations, achieved at a lower median dose for those in the 22q11.2DS group. Most common side-effects were similarly prevalent between the two groups, however, half of the 22q11.2DS group experienced at least one rare serious adverse event compared with none of the idiopathic group. Many were successfully retried on clozapine. Conclusions Individuals with 22q11.2DS-schizophrenia respond as well to clozapine treatment as those with other forms of schizophrenia, but may represent a disproportionate number of those with serious adverse events, primarily seizures. Lower doses and prophylactic (for example anticonvulsant) management strategies can help ameliorate side-effect risks. This first systematic evaluation of antipsychotic response in a genetic subtype of schizophrenia provides a proof-of-principle for personalised medicine and supports the utility of clinical genetic testing in schizophrenia. PMID:25745132

  6. Diagnosis and treatment of chronic ankle pain.

    PubMed

    Wukich, Dane K; Tuason, Dominick A

    2011-01-01

    The differential diagnosis for chronic ankle pain is quite broad. Ankle pain can be caused by intra-articular or extra-articular pathology and may be a result of a traumatic or nontraumatic event. A detailed patient history and physical examination, coupled with judicious selection of the appropriate imaging modalities, are vital in making an accurate diagnosis and providing effective treatment. Chronic ankle pain can affect all age groups, ranging from young athletes to elderly patients with degenerative joint and soft-tissue disorders. It has been estimated that 23,000 ankle sprains occur each day in the United States, representing approximately 1 sprain per 10,000 people per day. Because nearly one in five ankle injuries result in chronic symptoms, orthopaedic surgeons are likely to see patients with chronic ankle pain. Many patients with chronic ankle pain do not recall any history of trauma. Reviewing the management of the various disorders that can cause chronic ankle pain will help orthopaedic surgeons provide the best treatment for their patients. PMID:21553785

  7. Consumer access to clozapine in Australia: how does this compare to New Zealand and the United Kingdom?

    PubMed Central

    Mcmillan, Sara S.

    2016-01-01

    Background: Clozapine is an antipsychotic medication used in treatment resistant schizophrenia. However, clozapine is associated with a significant adverse effect profile and extensive monitoring is required to optimise consumer safety. Traditionally, clozapine can only be prescribed by a psychiatrist and dispensed at a hospital or hospital affiliated pharmacy in Australia. These restrictions could result in significant treatment burden for consumers taking clozapine. Objective: To identify (1) the different models of supply that exist for people living in the community taking clozapine in Australia and compare to those in New Zealand and the United Kingdom, and (2) explore how these supply models may impact on consumer burden from the perspective of professionals involved in the supply of clozapine. Method: Key informants were interviewed (n=8) from Australia, New Zealand and the United Kingdom regarding how consumers, who lived in the community, accessed clozapine. Data were analysed and led to the development of four clozapine supply models. These four models were further validated by an online survey of a wider sample (n=30). Data were analysed thematically and via simple descriptive statistics. Results: Clozapine supply varied depending on location. A secondary care model was utilised in the United Kingdom compared to a community based (primary care) model in New Zealand; Australia utilised a mixture of both secondary and primary care. A key theme from all study participants was that community pharmacy should be utilised to dispense clozapine to consumers living in the community, provided adequate training and safeguards are in place. It was noted that the utilisation of community pharmacies could improve access and flexibility, thereby reducing treatment burden for these consumers. Conclusion: There are predominately two models for supply of clozapine to consumers living in the community in Australia, New Zealand and the United Kingdom. One model utilises

  8. Chronic Hepatitis E Virus Infection and Treatment

    PubMed Central

    Kamar, Nassim; Izopet, Jacques; Dalton, Harry R.

    2013-01-01

    It is now well accepted that hepatitis E virus (HEV) infection can induce chronic hepatitis and cirrhosis in immunosuppressed patients. Chronic genotype-3 HEV infections were first reported in patients with a solid-organ transplant. Thereafter, cases of chronic HEV infection have been reported in patients with hematological disease and in those who are human immunodeficiency virus (HIV)-positive. HEV-associated extra-hepatic manifestations, including neurological symptoms, kidney injuries, and hematological disorders, have been also reported. In transplant patients, reducing the dosage of immunosuppressive drugs allows the virus to be cleared in some patients. In the remaining patients, as well as hematological patients and patients who are HIV-positive, anti-viral therapies, such as pegylated interferon and ribavirin, have been found to be efficient in eradicating HEV infection. This review summarizes our current knowledge of chronic HEV infection, its treatment, and the extra-hepatic manifestations induced by HEV. PMID:25755487

  9. Probiotics in the treatment of chronic rhinoconjunctivitis and chronic rhinosinusitis.

    PubMed

    Kramer, Matthias F; Heath, Matthew D

    2014-01-01

    Chronic rhinitis and rhinosinusitis (CRS) are relevant health conditions affecting significant percentages of the western population. They are frequently coexisting and aggravating diseases. Both are chronic, noninfectious, and inflammatory conditions sharing to a certain extent important pathophysiologic similarities. Beneficial effects of probiotics are long known to mankind. Research is beginning to unravel the true nature of the human microbiome and its interaction with the immune system. The growing prevalence of atopic diseases in the developed world led to the proposition of the "hygiene hypothesis." Dysbiosis is linked to atopic diseases; probiotic supplementation is able to alter the microbiome and certain probiotic strains have immunomodulatory effects in favour of a suppression of Th-2 and stimulation of a Th1 profile. This review focuses on randomized, double-blind, placebo-controlled trials investigating clinical parameters in the treatment of chronic rhinitis and CRS. An emerging number of publications demonstrate beneficial effects using probiotics in clinical double-blind placebo-controlled (dbpc) trials in allergic rhinitis (AR). Using probiotics as complementary treatment options in AR seems to be a promising concept although the evidence is of a preliminary nature to date and more convincing trials are needed. There are no current data to support the use of probiotics in non-AR or CRS. PMID:24872820

  10. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature.

    PubMed

    Kulkarni, Ranganath R

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  11. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature

    PubMed Central

    Kulkarni, Ranganath R.

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  12. Clozapine

    MedlinePlus

    ... mL, use the larger (9 mL) oral syringe. Fill the oral syringe with by air by drawing back the plunger. Then insert the open tip of ... the adaptor in the bottle. Place the cap back on the bottle and turn it ... warm tap water after each use. Fill a cup with water and place the tip ...

  13. Clozapine reinitiation following a “red result” secondary to chemotherapy

    PubMed Central

    Munshi, Tariq; Mazhar, Mir; Hassan, Tariq

    2013-01-01

    We describe a case of a patient whose clozapine was discontinued after a “red result” following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases, manufacturers grant permission, on compassionate grounds, for clozapine to be continued or reinitiated following assessment by their consultant hematologist. Other than a recent case report, there is not much literature surrounding this medical issue. However, since the two leading causes of mortality in schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence. Clinicians are reluctant to prescribe clozapine in view of its side-effect profile, despite its proven efficacy for managing treatment-resistant schizophrenia. The alternative is to prescribe two antipsychotics to manage symptoms. This approach may be associated with increased side effects, and evidence for actual benefits is scant. The consequences were disastrous in this case, as the individual not only relapsed following clozapine discontinuation, but the therapy for this treatable form of lymphoma had to be delayed. He was eventually admitted to an inpatient unit after having been stable for 15 years. We managed to stabilize him with olanzapine and aripiprazole which enabled the heme-oncology group to resume R-CHOP therapy with filgrastim (granulocyte colony-stimulating factor). Even so, he continued to exhibit severe psychotic symptoms, with religious delusions and auditory hallucinations. We therefore applied for permission to rechallenge him on clozapine. Permission was granted when protocol conditions were met, and reinitiation went without any adverse events. The patient’s symptoms showed improvement within a few weeks, and the other antipsychotics were discontinued once clozapine was titrated up to 300 mg. The decision to reinitiate clozapine following a red result is not to be taken lightly, but needs to be considered in terms of

  14. Oral ciprofloxacin for treatment of chronic osteomyelitis.

    PubMed

    Yamaguti, A; Trevisanello, C; Lobo, I M; Carvalho, M C; Bortoletto, M L; Silva, M L; Brasil Filho, R; Levi, G C; Mendonça, J S

    1993-01-01

    Seventeen adult patients with chronic osteomyelitis were treated with oral ciprofloxacin, 750 mg twice daily. Treatment ranged from 28 to 254 days. Efficacy was considered to be good, based upon clinical resolution observed in 13 patients (76%). Clinical and microbiological failure was observed in 3 patients (18%), and there was one case of reinfection. Tolerance was very satisfactory, since the adverse reactions were mild and transitory; these occurred in 7 patients (41%), being cutaneous rash in 4 patients and diarrhoea in 3 patients. No patient had to discontinue treatment. Thus, oral ciprofloxacin may be useful option for the prolonged treatment of chronic osteomyelitis, provided that it is always associated with surgical debridement. Due to the probable development of ciprofloxacin resistance in the S. aureus multiresistant strain, already observed in two patients in the present investigation, it is suggested that for the treatment of such infections another drug with antistaphylococcal activity should be associated with the ciprofloxacin. PMID:8354592

  15. Diagnosis and treatment for chronic migraine.

    PubMed

    Moriarty, Maureen; Mallick-Searle, Theresa

    2016-06-19

    Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs. PMID:27203455

  16. Diagnosis and treatment for chronic migraine

    PubMed Central

    Moriarty, Maureen; Mallick-Searle, Theresa

    2016-01-01

    Abstract: Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs. PMID:27203455

  17. Levothyroxine Augmentation in Clozapine Resistant Schizophrenia: A Case Report and Review.

    PubMed

    Seddigh, Ruohollah; Azarnik, Somayeh; Keshavarz-Akhlaghi, Amir-Abbas

    2015-01-01

    There are many reports that show different thyroid abnormalities in schizophrenia without clear establishment of their role in etiology and treatment outcome of schizophrenia. Among these reports, there are only a few that consider a role for thyroid hormones as augmenting agents in the treatment with antipsychotic drugs. This case report outlines symptom subsidence of a patient with clozapine refractory paranoid schizophrenia and normal thyroid function who added levothyroxine to clozapine and found that symptoms of psychosis returned once levothyroxine was discontinued. Although this observation needs to be confirmed in controlled clinical trials, we aimed to discuss possible hypothesized mechanisms underlying this observation. PMID:26078905

  18. Pivmecillinam treatment of chronic urinary tract infection.

    PubMed

    Kalager, T; Bøe, E; Digranes, A; Høisaether, P; Solberg, C O

    1978-01-01

    Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections. PMID:204581

  19. Chronic idiopathic urticaria: treatment with omalizumab.

    PubMed

    Naaman, Sandra; Sussman, Gordon

    2014-01-01

    Chronic idiopathic urticaria (CIU) is a common autoimmune skin condition characterized by spontaneously recurring hives for 6 weeks or longer. The new terminology used for CIU in most countries including Canada is chronic spontaneous urticaria (CSU). CSU is associated with significant psychosocial morbidity with a markedly negative impact on overall quality of life. Conventional approaches with antihistamines, even at high doses, is effective in about 50% of patients suffering from CSU. A new treatment option, omalizumab, a humanized monoclonal antibody against the Fc domain of IgE, has undergone the scrutiny of randomized research studies evaluating the efficacy in CSU. This editorial reviews mechanisms of action of omalizumab, efficacy, cost and potential side effect profile. Omalizumab has emerged as a very promising treatment option for patients with CSU. Future research is necessary to establish standardized protocols related to dosing as well as monitoring possible adverse effects of long-term treatment. PMID:25807072

  20. [Chronic myelogenous leukemia: diagnosis and treatment].

    PubMed

    Demeter, Judit; Poros, Anna; Bödör, Csaba; Horváth, Laura; Masszi, Tamás

    2016-09-01

    Chronic myelogenous leukemia is a clonal myeloproliferative neoplasm caused by reciprocal translocation involving chromosomes 9 and 22 resulting in the expression of a constitutively activated BCR-ABL1 tyrosine kinase that leads to the malignant transformation of the hematopoietic stem cells. The condition was previously known as a relentlessly progressive disease, but the treatment was revolutionalized by the efficacy of tyrosine kinase inhibitors. Therapeutic success is thus currently determined by the depth of molecular response achieved on therapy. Multiple tyrosine kinase agents are available even for the first line treatment. This guideline summarizes current focal points of the treatment of chronic myelogenous leukemia specific to Hungary and provides definitions for optimal molecular responses in this condition. Orv. Hetil., 2016, 157(37), 1459-1468. PMID:27615196

  1. Evaluation and Treatment of Chronic Meningitis

    PubMed Central

    Zunt, Joseph R.

    2014-01-01

    Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications. PMID:25360204

  2. [A treatment method for chronic parenchymatous parotitis].

    PubMed

    Ivasenko, P I; Lobastov, A Iu; Potashov, D A; Distergova, O V; Shadevskiĭ, V M; Krivinskiĭ, A K

    1993-01-01

    A method for therapy of chronic parenchymatous parotitis is suggested supplementing dimethyl sulfoxide. As reported, the parotid glands produce parotin, an insulin-like substance, whose production is reduced in chronic parotitis; hence, short-acting insulin administered in microdoses was chosen for therapy. To potentiate local insulin effect and increase the sensitivity of oral mucosa peripheral receptors to it a 5% calcium pantothenate solution was used. This method was used in the treatment of 42 patients with chronic parenchymatous parotitis aged 23 to 62. The method is effective, it can be easily used by the patients themselves, and there are virtually no contraindications against such therapy. The authors have applied for inventors' certificate, the priority certificate is No. 4836436/14 as of June 27, 1990. PMID:8236296

  3. Effects of clozapine on sleep measures and sleep-associated changes in growth hormone and cortisol in patients with schizophrenia.

    PubMed

    Lee, J H; Woo, J I; Meltzer, H Y

    2001-09-20

    There have been limited reports on the effect of the atypical anti-psychotic agent clozapine on sleep measures and hormone secretion. The goal of this study was to determine the type, rate, and extent of changes in sleep measures and nighttime secretion of growth hormone (GH) and cortisol during clozapine treatment. Five schizophrenic patients (age: 32.4+/-7.4) and five age- and sex-matched normal subjects (age: 33.0+/-5.1) underwent nocturnal polysomnography (NPSG) before clozapine therapy (S1), and during early and late clozapine therapy (S2 and S3). Serum GH and cortisol levels were monitored during each NPSG. NPSG findings showed that the mean total sleep time, sleep efficiency, and duration of awakening were increased at S2, and maintained until S3. The mean amounts of stage 2 sleep at S2 and S3 increased significantly compared with that of S1. In unmedicated schizophrenic patients, the mean plasma GH level in rapid eye movement sleep was lower than during the waking stage, and the mean level of plasma cortisol was higher during the waking stage. Plasma cortisol levels did not differ between control subjects and patients at any time, but clozapine treatment decreased plasma cortisol levels at S2 compared with S1 and S3. Plasma GH levels were unchanged by clozapine treatment. Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy. These effects were maintained through at least 7 weeks of therapy. However, clozapine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients. PMID:11549404

  4. Insight into mechanism of in vitro insulin secretion increase induced by antipsychotic clozapine: role of FOXA1 and mitochondrial citrate carrier.

    PubMed

    Menga, A; Infantino, V; Iacobazzi, F; Convertini, P; Palmieri, F; Iacobazzi, V

    2013-08-01

    The use of clozapine and other antipsychotic drugs is known to be associated with a number of adverse metabolic side effects, including diabetes mellitus. These side effects could be, at least in part, the result of impaired islet cell function and abnormal insulin secretion, although the underlying mechanisms are unknown. The aim of this study is the identification of targets for clozapine related to the abnormal insulin secretion. We identify a specific activation of the transcriptional factor FOXA1, but not FOXA2 and FOXA3, by clozapine in HepG2 cells. Clozapine enhances FOXA1 DNA-binding and its transcriptional activity, increasing mitochondrial citrate carrier gene expression, which contains a FOXA1 site in its promoter. Haloperidol, a conventional antipsychotic drug, does not determine any increase of FOXA1 gene expression. We also demonstrate that clozapine upregulates FOXA1 and CIC gene expression in INS-1 cells only at basal glucose concentration. In addition, we find that abnormal insulin secretion in basal glucose conditions could be completely abolished by FOXA1 silencing in INS-1 cells treated with clozapine. The identification of FOXA1 as a novel target for clozapine may shed more light to understand molecular mechanism of abnormal insulin secretion during clozapine treatment. PMID:22959654

  5. Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis

    PubMed Central

    Leung, Janni; Russell, Anthony W.; Wysoczanski, Daniel; Kisely, Steve

    2016-01-01

    Background Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine’s impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. Methods We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group’s trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. Results Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. Conclusions Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. Trial Registration PROSPERO registration number: CRD42015029723 PMID:27304831

  6. Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis – a case report

    PubMed Central

    Oke, Vikram; Schmidt, Frances; Bhattarai, Bikash; Basunia, Md; Agu, Chidozie; Kaur, Amrit; Enriquez, Danilo; Quist, Joseph; Salhan, Divya; Gayam, Vijay; Mungikar, Prajakta

    2015-01-01

    Clozapine is the preferred antipsychotic used for the treatment of resistant schizophrenia with suicidal ideation. The drug is started at a low dose and gradually increased to a target dose of 300–450 mg/day. It is well known to cause agranulocytosis and neutropenia. Several cases of fatal sepsis have been reported in neutropenic patients and emphasis is placed on monitoring for agranulocytosis; however, clozapine also causes intestinal hypomotility and constipation, which if unrecognized can lead to intestinal obstruction, bowel necrosis, and intra-abdominal sepsis. Reduced behavioral pain reactivity in schizophrenics may alter the ability to express pain, potentially leading to a delay in the presentation for medical attention. We report a case of fatal intra-abdominal sepsis secondary to an unrecognized case of clozapine-related constipation. PMID:26392790

  7. Chronic hepatitis B: Advances in treatment

    PubMed Central

    Santantonio, Teresa Antonia; Fasano, Massimo

    2014-01-01

    Treatment of chronic hepatitis B (CHB) has markedly improved in the last 15 years due to the availability of direct antivirals which greatly increase therapeutic options. Currently, there are two classes of agents licensed for CHB treatment: standard or pegylated interferon alpha (IFN or Peg-IFN) and five nucleoside/nucleotide analogues (NAs). Long-term treatment with NAs is the treatment option most often used in the majority of CHB patients. Entecavir and tenofovir, the most potent NAs with high barrier to resistance, are recommended as first-line monotherapy by all major treatment guidelines and can lead to long-lasting virological suppression, resulting in histological improvement or reversal of advanced fibrosis and reduction in disease progression and liver-related complications. In this review, we focus on current treatment strategies of chronic hepatitis B and discuss the most recent efficacy and safety data from clinical trials and real life clinical practice. Recent findings of response-guided approaches are also discussed. PMID:24868322

  8. Challenges in the Treatment of Chronic Wounds

    PubMed Central

    Frykberg, Robert G.; Banks, Jaminelli

    2015-01-01

    Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use. PMID:26339534

  9. Chronic rhinosinusitis and emerging treatment options

    PubMed Central

    Piromchai, Patorn; Kasemsiri, Pornthep; Laohasiriwong, Supawan; Thanaviratananich, Sanguansak

    2013-01-01

    This review describes the epidemiology and various treatments in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Evidence for short-term use of systemic corticosteroids has been shown to be favorable in CRSwNP, but still limited in CRSsNP. Topical corticosteroids improve symptom scores in both CRS subgroups. The role of microbes in CRS is still controversial. Culture-directed antibiotics are recommended for CRSsNP with exacerbation. Long-term use of low dosage antibiotics is recommended for CRSsNP for their anti-inflammatory effects. Other emerging treatment options are also discussed. PMID:23785241

  10. Chronic fatigue syndrome: aetiology, diagnosis and treatment

    PubMed Central

    Avellaneda Fernández, Alfredo; Pérez Martín, Álvaro; Izquierdo Martínez, Maravillas; Arruti Bustillo, Mar; Barbado Hernández, Francisco Javier; de la Cruz Labrado, Javier; Díaz-Delgado Peñas, Rafael; Gutiérrez Rivas, Eduardo; Palacín Delgado, Cecilia; Rivera Redondo, Javier; Ramón Giménez, José Ramón

    2009-01-01

    Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome. PMID:19857242

  11. Hypnosis treatment for chronic low back pain.

    PubMed

    Tan, Gabriel; Fukui, Tenley; Jensen, Mark P; Thornby, John; Waldman, Karen L

    2010-01-01

    Chronic low back pain (CLBP) is a significant healthcare problem, and many individuals with CLBP remain unresponsive to available interventions. Previous research suggests that hypnosis is effective for many chronic pain conditions; however, data to support its efficacy for CLBP are outdated and have been limited primarily to case studies. This pilot study indicated that a brief, 4-session standardized self-hypnosis protocol, combined with psycho-education, significantly and substantially reduced pain intensity and pain interference. Significant session-to-session improvements were also noted on pain ratings and mood states; however, follow-up data suggest that these benefits may not have been maintained across time in this sample. These findings need to be replicated and confirmed in a larger clinical trial, which could also assess the long-term effects of this treatment. PMID:20183738

  12. Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Bobb, Aaron J.; Gogtay, Nitin; Stevens, Hanna; Greenstein, Deanna K.; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas; Gochman, Peter A.; Sharp, Wendy S.; Mattai, Anand; Lenane, Marge C.; Yanovski, Jack A.; Rapoport, Judith L.

    2005-01-01

    Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls…

  13. Treatment options for chronic mucocutaneous candidiasis.

    PubMed

    van de Veerdonk, Frank L; Netea, Mihai G

    2016-07-01

    Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a rare and severe primary immunodeficiency that is characterized by mucocutaneous fungal infection, autoimmunity, cerebral aneurysms, and oropharyngeal and esophageal cancer. Recently, it was discovered that STAT1 mutations are responsible for AD-CMC. These mutations lead to the inability of STAT1 to be dephosphorylated, resulting in hyperphosphorylation, increased binding to the DNA, and gain of function (GOF) effects on STAT1 signaling. Furthermore, a characteristic feature of AD-CMC patients is deficiency in the T-helper 17 (Th17) responses, which is believed to be the immunological cause of the mucocutaneous fungal infection. No targeted treatment other than lifelong antifungal prophylaxis exists for AD-CMC. However, the discovery of the genetic and immunological defects makes it now possible to explore new treatment strategies. This review will discuss immunomodulatory treatment options that can be explored in patients with STAT1 GOF mutations. PMID:27161991

  14. Treatment of stable chronic obstructive pulmonary disease.

    PubMed

    Rennard, Stephen I

    Chronic obstructive pulmonary disease (COPD) is a readily diagnosable disorder that responds to treatment. Smoking cessation can reduce symptoms and prevent progression of disease. Bronchodilator therapy is key in improvement of lung function. Three classes of bronchodilators-beta agonists, anticholinergics, and theophylline-are available and can be used individually or in combination. Inhaled glucocorticoids can also improve airflow and can be combined with bronchodilators. Inhaled glucocorticoids, in addition, might reduce exacerbation frequency and severity as might some bronchodilators. Effective use of pharmacotherapy in COPD needs integration with a rehabilitation programme and successful treatment of co-morbidities, including depression and anxiety. Treatment for stable COPD can improve the function and quality of life of many patients, could reduce admissions to hospital, and has been suggested to improve survival. PMID:15337408

  15. Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study

    PubMed Central

    Every-Palmer, Susanna; Nowitz, Mike; Stanley, James; Grant, Eve; Huthwaite, Mark; Dunn, Helen; Ellis, Pete M.

    2016-01-01

    Background Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to ‘gastrointestinal hypomotility’, gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative. Methods Using standardized radiopaque marker (‘Metcalf’) methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age. Outcomes For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors. Interpretation Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine. PMID:27077119

  16. A common action of clozapine, haloperidol, and remoxipride on D1- and D2-dopaminergic receptors in the primate cerebral cortex.

    PubMed

    Lidow, M S; Goldman-Rakic, P S

    1994-05-10

    The potencies of the major neuroleptics used in the treatment of schizophrenia, including haloperidol and remoxipride, correlate with their ability to bind D2-dopaminergic receptors in subcortical structures. On the other hand, the neuroleptic clozapine has a low affinity for these sites, and the pharmacological basis of its beneficial action is less clear. We have found that chronic treatment with clozapine, haloperidol, and remoxipride up-regulates D2 receptors in specific cortical areas of the rhesus monkey frontal, parietal, temporal, and occipital lobes. Of particular interest, all three neuroleptics down-regulated D1 receptors in prefrontal and temporal association regions--the two areas most often associated with schizophrenia. This latter finding raises the possibility that down-regulation of D1 receptors in prefrontal and temporal cortex may be an important component of the therapeutic response to neuroleptic drugs. Further, the common effects of three neuroleptics with different pharmacological profiles in the cerebral cortex is consistent with the idea that this structure is a major therapeutic target in the treatment of schizophrenia. PMID:8183912

  17. Valacyclovir treatment of chronic fatigue in adolescents.

    PubMed

    Henderson, Theodore A

    2014-01-01

    Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished mood, and reduced activity, all symptoms having extensive diagnostic overlaps with depression. Studies have linked chronic viral infections with CFS, and antiviral therapy has effectively treated CFS in adult patients. In a retrospective case series, 15 adolescents and preteens referred to the author for treatment-resistant depression or mood disorder were evaluated and found to have met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been diagnosed in the past with CFS, the majority had a current diagnosis of depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text Revision (DSM-IV TR) criteria for depression were not met in all patients, although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the Children's Depression Inventory (CDI) were below the cutoff for depression in all but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained and sleep was evaluated with sleep logs. All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir. This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study's data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection. PMID:24445302

  18. Expectations predict chronic pain treatment outcomes.

    PubMed

    Cormier, Stéphanie; Lavigne, Geneviève L; Choinière, Manon; Rainville, Pierre

    2016-02-01

    Accumulating evidence suggests an association between patient pretreatment expectations and numerous health outcomes. However, it remains unclear if and how expectations relate to outcomes after treatments in multidisciplinary pain programs. The present study aims at investigating the predictive association between expectations and clinical outcomes in a large database of chronic pain patients. In this observational cohort study, participants were 2272 patients treated in one of 3 university-affiliated multidisciplinary pain treatment centers. All patients received personalized care, including medical, psychological, and/or physical interventions. Patient expectations regarding pain relief and improvements in quality of life and functioning were measured before the first visit to the pain centers and served as predictor variables. Changes in pain intensity, depressive symptoms, pain interference, and tendency to catastrophize, as well as satisfaction with pain treatment and global impressions of change at 6-month follow-up, were considered as treatment outcomes. Structural equation modeling analyses showed significant positive relationships between expectations and most clinical outcomes, and this association was largely mediated by patients' global impressions of change. Similar patterns of relationships between variables were also observed in various subgroups of patients based on sex, age, pain duration, and pain classification. Such results emphasize the relevance of patient expectations as a determinant of outcomes in multimodal pain treatment programs. Furthermore, the results suggest that superior clinical outcomes are observed in individuals who expect high positive outcomes as a result of treatment. PMID:26447703

  19. What's New in Chronic Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for chronic myeloid leukemia What`s new in chronic myeloid leukemia research and treatment? Studies ... such as cyclosporine or hydroxychloroquine, with a TKI. New drugs for CML Because researchers now know the ...

  20. [Surgical treatment of chronic thromboembolic pulmonary hypertension].

    PubMed

    Mercier, Olaf; Fadel, Elie; Mussot, Sacha; Fabre, Dominique; Ladurie, François-Leroy; Angel, Claude; Brenot, Philippe; Riou, Jean-Yves; Bourkaib, Riad; Lehouerou, Daniel; Musat, Andy; Stephan, François; Rohnean, Adéla; Jaïs, Xavier; Humbert, Marc; Sitbon, Olivier; Simonneau, Gérald; Dartevelle, Philippe

    2014-09-01

    Chronic thromboembolic pulmonary hypertension is a rare but underdiagnosed disease. The development of imaging played a crucial role for the screening and the decision of operability over the past few years. Indeed, chronic thromboembolic pulmonary hypertension is the only type of pulmonary hypertension with a potential curative treatment: pulmonary endarterectomy. It is a complexe surgical procedure performed under cardiopulmonary bypass with deep hypothermia and circulatory arrest. The aim of the procedure is to completely remove the scar tissue inside the pulmonary arteries down to the segmental and sub-segmental levels. Compared to lung transplantation, which carries a postoperative mortality of 15-20% and a 5-year survival of 50%, pulmonary endarterectomy is a curative treatment with a postoperative mortality of less than 3%. However, lung transplantation remains an option for young patients with inoperable distal disease or after pulmonary endarterectomy failure. Considering that medical history of deep venous thrombosis or pulmonary embolism is lacking in 25 to 50%, the diagnosis of chronic thromboembolic pulmonary hypertension remains challenging. The lung V/Q scan is useful for the diagnosis showing ventilation and perfusion mismatches. Lesions located at the level of the pulmonary artery, the lobar or segmental arteries may be accessible to surgical removal. The pulmonary angiogram with the lateral view and the pulmonary CT scan help to determine the level of the intravascular lesions. If there is a correlation between the vascular obstruction assessed by imaging and the pulmonary resistance, pulmonary endarterectomy carries a postoperative mortality of less than 3% and has a high rate of success. If the surgery is performed at a later stage of the disease, pulmonary arteriolitis developed mainly in unobstructed territories and participated in the elevated vascular resistance. At this stage, postoperative risk is higher. PMID:25154908

  1. [Surgical treatment of chronic idiopathic constipation].

    PubMed

    Menguy, R; Chey, W

    We review current experience with surgical treatment of severe constipation due to primary inertia of the colon. Over the last 10 years, we have operated 18 patients (14 females and 4 males) with severe constipation. The surgical procedure was either nearly total colonectomy with ascending colon/rectum anastomosis (8 cases) or total colonectomy with ileorectal anastomosis (9 cases). In one patient, coloproctectomy was performed with an ileoanal anastomosi. Indications for surgery were based on results of barium emena and functional evaluation of defecation. Results were satisfactory in all patients. In several patients however, we noted that the motility of other levels of the digestive tract was also impaired. Colonectomy was introduced as a treatment for chronic constipation nearly a century ago and although very few indications have been retained in the recent this procedure has now become an acceptable surgical approach in a limited number of well-though-out cases. PMID:7729199

  2. Other Phenotypes and Treatment of Chronic Rhinosinusitis.

    PubMed

    Naclerio, Robert M; Baroody, Fuad M

    2016-01-01

    Chronic rhinosinusitis (CRS) is difficult to define, partly because the disease recognized by clinicians is both heterogeneous and the endpoint of different pathophysiologic, genetic, and environmental interactions. For this article, we define CRS as symptoms lasting more than 3 months combined with an imaging study showing inflammation in the sinuses. This article comments on some factors that are believed to influence the expression of CRS. These factors include anatomic abnormalities, immotile cilia, age, allergic sensitization, immune deficiency, dental infections, gastrointestinal reflux, smoking, biofilm, and the microbiome. Other factors are discussed in other sections. The article concludes with an overview of treatment. In brief, nasal steroids and large volume nasal irrigations are the first line of treatment for this inflammatory disease. Antibiotics are used when infections are thought to contribute. Oral steroids are frequently used in severe disease. Endoscopy and sinus computed tomography scans are used when surgery is contemplated. PMID:27393776

  3. Immunodeficiency in chronic sinusitis: recognition and treatment.

    PubMed

    Stevens, Whitney W; Peters, Anju T

    2015-01-01

    Chronic rhinosinusitis (CRS) is estimated to affect over 35 million people. However, not all patients with the diagnosis respond to standard medical and surgical treatments. Although there are a variety of reasons a patient may be refractory to therapy, one possible etiology is the presence of an underlying immunodeficiency. This review will focus on the description, recognition, and treatment of several antibody deficiencies associated with CRS, including common variable immunodeficiency (CVID), selective IgA deficiency, IgG subclass deficiency, and specific antibody deficiency (SAD). The diagnosis of antibody deficiency in patients with CRS is important because of the large clinical implications it can have on sinus disease management. CVID is treated with immunoglobulin replacement, whereas SAD may be managed symptomatically and sometimes with prophylactic antibiotics and/or immunoglobulin replacement. PMID:25785751

  4. Pharmacological treatment of chronic obstructive pulmonary disease

    PubMed Central

    Montuschi, Paolo

    2006-01-01

    None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. PMID:18044097

  5. Successful Treatment of Chronic Donor Site Pain

    PubMed Central

    Yanow, Jennifer H; Lorenzo, Luigi Di; Worosilo, Sharon C; Pappagallo, Marco

    2015-01-01

    Introduction: This is a case presentation of a 45-year-old male with chronic donor site pain following autologous iliac crest bone harvest successfully treated with superior cluneal nerve blockade. Donor site pain following autologous bone harvest is a common postoperative complication of lumbar fusion procedures that can cause significant morbidity and diminish quality of life, even in the context of an otherwise successful surgery. Dysfunction of the superior cluneal nerves is an etiology of this chronic pain. The patient’s medical history, attempted treatments, and literature were reviewed. Case Presentation: A 45-year-old male with a six year history of severe pain over the right iliac crest following an otherwise successful lumbar laminectomy and fusion underwent two sets of superior cluneal nerve blocks, with sustained relief of more than 80% at seven months follow up. Conclusions: Donor site pain following autologous iliac crest bone harvest is a common surgical complication that is often resistant to conservative treatments such as physical therapy and oral medications. Blockade of the superior cluneal nerves is a safe and technically simple procedure that may result in long-term pain relief, obviating the need to consider more invasive options. PMID:26587399

  6. [Clozapine intoxication: theoretical aspects and forensic-medical examination ].

    PubMed

    Shigeev, S V; Ivanova, N A; Ivanov, S V

    2013-01-01

    This literature review is focused on diagnostics of acute clozapine intoxication with the fatal outcome. According to the Russian authors, clozapine intoxication ranks first in the structure of criminal poisoning and accounted for 99.7% of all the cases that occurred in Moscow during the period from 2003 to 2006. Toximetric investigations of clinical manifestations of clozapine intoxication revealed that the threshold clozapine concentration in blood is 0.12 ± 0.06 mg/I, the critical and lethal concentrations are 1.01 ± 0.2 mg/I and 3.5 ± 1.5 mg/I respectively. Autopsy on corpses of the victims of clozapine intoxication showed that most clozapine-induced pathological changes have a non-specific character (including largely circulatory disorders and dystrophic changes in parenchymatous organs). Clozapine poisoning is associated with the lengthening of QT-interval on ECG; at the values in excess of 500 ms, the risk of severe arrhythmia and sudden death significantly increases. Clozapine intake may lead to the development of potentially fatal myocarditis (the so-called clozapine-associated eosinophilic myocardium) in somatically healthy subjects. Foreign researchers report the possibility of a post-mortem increase of blood clozapine content compared with its antemortem level. They also showed that simultaneous use of substances stimulating activity of cytochrome P-450 enzymes (ethyl alcohol, finlepsin, fenitrin, nicotine) and clozapine accelerates metabolism and thereby reduces clozapine concentration in blood. It is concluded that comprehensive investigations of clozapine intoxication are needed taking into consideration pathomorphological changes induced by this agent, its potential interaction with other factors influencing human body, and the results of forensic chemical expertise of the fatal cases. PMID:25474921

  7. Treatment of chronic HCV genotype 1 coinfection.

    PubMed

    Boesecke, Christoph; Rockstroh, Jürgen K

    2015-09-01

    Several all-oral direct-acting antiviral (DAA) combination therapies including two fixed-dose combinations (FDCs) have been recently licensed for treatment of hepatitis C virus (HCV) genotype 1 infection. Results of pivotal trials with these new compounds are now also available in human immunodeficiency virus (HIV)/HCV-coinfected patients, highlighting that, in the DAA era, differences no longer do exist in efficacy between HCV-monoinfected and HIV/HCV-coinfected patients. This review will give an overview of the key DAA-containing studies in HIV/HCV genotype 1 coinfection and give guidance on how and when these should be used in clinical practice. Simplified DAA-based and potentially interferon-free HCV therapy regimens are characterized by smaller pill burden, better tolerability, shorter treatment durations, and higher cure rates. With first pilot studies in HCV treatment-naive and treatment-experienced persons with HCV/HIV coinfection demonstrating sustained virological response rates above 95 %, interferon (IFN)-free DAA combinations should be considered the new standard of care for chronic HCV. Per both European and US treatment guidelines, HCV treatment indications and DAA drug selection in HIV-coinfected patients are no longer different from HCV-monoinfected patients as cure rates in HCV-monoinfected and HCV-coinfected patients are superimposable. Drug-drug interactions with the new DAAs and concomitant antiretroviral therapy, however, have to be checked carefully prior to selecting DAAs due to commonly shared metabolization pathways. In countries with access to the new DAAs, interferon-free DAA combination therapy for HCV genotype 1 infection is strongly recommended. Agents should be selected based upon HCV genotype and according to current guidelines. Potential drug-drug interactions between HIV antiretrovirals and HCV therapy need to be checked, and if necessary, combination antiretroviral therapy (cART) has to be adapted to the respective HCV therapy

  8. Discriminative stimulus properties of 1.25mg/kg clozapine in rats: Mediation by serotonin 5-HT2 and dopamine D4 receptors.

    PubMed

    Prus, Adam J; Wise, Laura E; Pehrson, Alan L; Philibin, Scott D; Bang-Andersen, Benny; Arnt, Jørn; Porter, Joseph H

    2016-10-01

    The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug discrimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects. The present study was conducted to elucidate the receptor-mediated stimulus properties that form this clozapine discriminative cue by testing selective receptor ligands in rats trained to discriminate a 1.25mg/kg dose of clozapine from vehicle in a two choice drug discrimination task. Full substitution occurred with the 5-HT2A inverse agonist M100907 and the two preferential D4/5-HT2/α1 receptor antagonists Lu 37-114 ((S)-1-(3-(2-(4-(1H-indol-5-yl)piperazin-1-yl)ethyl)indolin-1-yl)ethan-1-one) and Lu 37-254 (1-(3-(4-(1H-indol-5-yl)piperazin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one). Partial substitution occurred with the D4 receptor antagonist Lu 38-012 and the α1 adrenoceptor antagonist prazosin. Drugs selective for 5-HT2C, 5-HT6 muscarinic, histamine H1, and benzodiazepine receptors did not substitute for clozapine. The present findings suggest that 5-HT2A inverse agonism and D4 receptor antagonism mediate the discriminative stimulus properties of 1.25mg/kg clozapine in rats, and further confirm that clozapine produces a complex compound discriminative stimulus. PMID:27502027

  9. A Questionnaire-based Study of the Views of Schizophrenia Patients and Psychiatric Healthcare Professionals in Japan about the Side Effects of Clozapine

    PubMed Central

    Takeuchi, Ippei; Hanya, Manako; Uno, Junji; Amano, Yuhei; Fukai, Keiko; Fujita, Kiyoshi; Kamei, Hiroyuki

    2016-01-01

    Objective It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. Methods Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. Results Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. Conclusion Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan. PMID:27489383

  10. Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

    PubMed Central

    Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

    2006-01-01

    Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

  11. EEG alterations in patients treated with clozapine in relation to plasma levels.

    PubMed

    Haring, C; Neudorfer, C; Schwitzer, J; Hummer, M; Saria, A; Hinterhuber, H; Fleischhacker, W W

    1994-02-01

    It is well known that psychotropic drugs can induce EEG alterations. Dose dependence seems established; however, there are no data concerning the impact of plasma levels. The authors investigated the influence of clozapine plasma levels on the frequency of EEG alterations. Data from 29 inpatients (18 male, 11 female, 31.7 +/- 10.2 years) receiving clozapine in a dose range between 25 and 600 mg were collected prospectively. There was no psychotropic or anticholinergic comedication. All patients had normal EEGs before taking clozapine. Fifteen patients showed pathological changes (group 2) and 14 no changes (group 1). Discriminant analysis showed that EEG changes are dependent on plasma levels (P = 0.0009, plasma levels in group 1 mean 81.6 ng/ml, +/- SD 64.6, in group 2 235.7 ng/ml, +/- 169.8). A total of 72.4% of the patients were correctly classified as having either pathological EEG changes or none by this analysis. Variables such as dose, age, sex, weight and duration of treatment were not statistically relevant. It can therefore be suggested that clozapine plasma levels are a valid indicator for the appearance of electrophysiological reactions. PMID:7846212

  12. Chronic thromboembolic pulmonary hypertension: Medical treatment

    PubMed Central

    Ozsu, Savas; Cinarka, Halit

    2013-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is responsible for significant levels of morbidity and mortality. The estimated cumulative incidence of CTEPH is 2-4% among patients presenting with acute pulmonary thromboembolism. Currently, at the time of CTEPH diagnosis, 37.9% of the patients in an international registry were receiving at least one pulmonary arterial hypertension (PAH)-targeted therapy. Advanced medical therapy is considered in patients with inoperable disease, as a bridge to pulmonary endarterectomy or in those with persistent or recurrent pulmonary hypertension. PAH-specific medical therapies include endothelin receptor antagonists, phosphodiesterase inhibitors, and prostacyclin analogues. The present article will focus on recent developments in the pharmacological treatment of CTEPH. PMID:24015333

  13. [Treatment of chronic bovine endometritis and factors for treatment success].

    PubMed

    Feldmann, M; Tenhagen genannt Emming, S; Hoedemaker, M

    2005-01-01

    In a controlled field trial, 178 dairy cows with chronic endometritis and at least 21 days in lactation were randomly assigned to four different treatment groups: prostaglandin F2alpha intramuscularly (PG, 5 mg dinoprost (5 ml Dinolytic), n = 51), intrauterine antibiotics (AB; 400 mg ampicillin + 800 oxacillin (20 ml Totocillin), n = 49), intrauterine antiseptics (AS; 100 ml 4% Lotagen, n = 50); control (C, no initial treatment, n = 28). Before treatment, uterine swabs for bacteriologic examination and blood samples for determination of serum progesterone concentrations were collected. Two weeks following the first treatment, cows were reexamined. In case no clinical cure was diagnosed, treatment was repeated and control cows were treated for the first time with one of the three treatments mentioned above. The four treatment groups did not differ with respect to the clinical cure or reproductive performance. Therefore, factors that might have an influence on clinical cure and fertility were evaluated. With increasing duration of lactation, the clinical cure after a single treatment increased significantly over all treatment groups from 59.5% (treatment before day 42 postpartum) to 79.6% (treatment following day 42 postpartum) (P < 0.05). Within the PG group, a statistically significantly higher cure rate after a single treatment and first service conception rate and a lower pregnancy index were obtained when the treatment was performed following day 42 postpartum (P < 0.05). This was not the case in the other treatment groups. A retarded involution of the uterus based on the size had a negative effect on clinical cure over all groups (first treatment clinical cure: 68.2% (small uteri) vs 44.4% (large uteri); P < 0.05). Within groups, this effect was also detected, but only as a trend (P > 0.05). Isolation of Arcanobacterium (A.) pyogenes negatively influenced first treatment clinical cure over all treatment groups (79.0% vs 31.5%) and within treatment groups (P < 0

  14. A systematic review of the evidence of clozapine's anti-aggressive effects.

    PubMed

    Frogley, Catherine; Taylor, David; Dickens, Geoff; Picchioni, Marco

    2012-10-01

    Reducing the risk of violent and aggressive behaviour in patients with schizophrenia remains a clinical priority. There is emerging evidence to suggest that the second-generation antipsychotic, clozapine, is effective at reducing this risk in patients with schizophrenia and some evidence to suggest that it may be best in selected patients. We conducted a systematic literature search in March 2011 of all prospective and retrospective studies, which investigated clozapine's anti-aggressive effects in a variety of mental disorders. The review identified six animal studies, four randomized controlled trials, 12 prospective non-controlled studies and 22 retrospective studies, with four case studies. We found considerable evidence in support of clozapine's ability to reduce violent and aggressive behaviour. Clozapine's anti-aggressive effect was most commonly explored in patients with schizophrenia, with less evidence available for other psychiatric disorders, including borderline personality disorder, autistic spectrum disorders, post-traumatic stress disorder, bipolar disorder and learning disability. There was mixed evidence to address the question of whether or not clozapine was any more effective than other antipsychotics. In the case of schizophrenia, there was evidence to suggest that clozapine's anti-aggressive effect was more marked particularly in those with treatment-resistant illness. Its anti-aggressive effects appeared to be 'specific', being to some extent greater than both its more general antipsychotic and sedative effects. There were significant methodological inconsistencies in the studies we identified, particularly surrounding patient recruitment criteria, the definition and measurement of violence and the lack of randomized, controlled trials. Data on therapeutic monitoring were also limited. Clozapine can reduce violence and persistent aggression in patients with schizophrenia and other psychiatric disorders. It may offer an advantage over other

  15. Treatment refractory schizophrenia: how should we proceed?

    PubMed

    Sharif, Z A

    1998-01-01

    A substantial portion of schizophrenic patients demonstrate suboptimal response to conventional antipsychotics. These agents are primarily effective in the treatment of psychotic symptoms; their efficacy in other domains of psychopathology such as negative symptoms, chronic aggressive behavior, and cognitive deficits, is limited or non-existent. In this group of refractory patients, the novel atypical antipsychotic clozapine has demonstrated robust efficacy, with response rates approaching 60% after twelve weeks of treatment. Efficacy of clozapine extends to symptom domains other than psychosis, including negative symptoms, mood stabilization, aggressive behavior and compulsive water drinking. Several novel agents, each of which shares some, but not all, of the preclinical and clinical characteristics that make clozapine so unique, have been introduced in the last 4 years. These agents demonstrate a broader spectrum of efficacy and an improved side effect profile in non-refractory patients. Initial data on their efficacy in refractory patients suggests that olanzapine does not achieve overall superior efficacy in this patient population compared to conventional agents although there is some evidence of relatively greater efficacy in negative symptoms and aggressivity. Several studies suggest that the efficacy of risperidone is superior to that of conventional agents in refractory patients. Preliminary conclusions are not possible for quetiapine because of a paucity of data in the literature. The literature supports a risperidone trial prior to a clozapine trial in a treatment algorithm for refractory patients because of its more favorable risk/benefit profile. PMID:9793107

  16. Metabolism of clozapine by neutrophils. Possible implications for clozapine-induced agranulocytosis.

    PubMed

    Uetrecht, J P

    1992-01-01

    Many types of adverse drug reactions appear to involve reactive metabolites which, by their very nature, usually have short biological half-lives. Therefore, reactive metabolites formed by neutrophils, or neutrophil precursors in the bone marrow, would seem more likely to be responsible for drug-induced agranulocytosis than metabolites formed in the liver. We have found that several drugs associated with a relatively high incidence of drug-induced agranulocytosis are metabolised by activated neutrophils to chemically reactive metabolites. In preliminary experiments with clozapine, we found that clozapine was metabolised by neutrophils. It also reacted with hypochlorous acid, the principal oxidant generated by neutrophils, to form a reactive intermediate. This intermediate has a half-life of 1 minute in buffer, but reacts very rapidly with glutathione. We believe that this intermediate is a nitrenium ion. Such a metabolite could be responsible for clozapine-induced agranulocytosis, either by direct toxicity or through an immune-mediated mechanism. PMID:1503678

  17. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients. PMID:27284847

  18. Vigabatrin: rational treatment for chronic epilepsy.

    PubMed Central

    Ring, H A; Heller, A J; Farr, I N; Reynolds, E H

    1990-01-01

    Vigabatrin is a selective, irreversible suicide inhibitor of GABA transaminase and thus increases brain and CSF GABA. In 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti-convulsant drugs, the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48.2% reduction in seizure frequency. Twenty patients who had exhibited a 50% or more reduction in frequency of one or more seizure types entered an eight week double-blind placebo controlled phase. Patients on vigabatrin maintained a 54.7% reduction of seizure frequency, whereas those on placebo showed an 18.6% increase in seizure frequency, a highly significant difference between the two groups. In the open phase, seven patients were withdrawn due to unacceptable and reversible adverse events. The commonest side effects were drowsiness, depression and mood instability, and headaches. Vigabatrin is a potentially valuable new treatment for chronic epilepsy, especially partial seizures with or without secondary generalisation. PMID:2292696

  19. Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

    SciTech Connect

    Shaikh, S.; Collier, D.A.; Sham, P.

    1995-12-18

    We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine`s action being at D4 receptors. 28 refs., 1 fig., 3 tabs.

  20. Effective physical treatment for chronic low back pain.

    PubMed

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future. PMID:15062718

  1. Evaluation and treatment of chronic digital ischemia.

    PubMed Central

    Wilgis, E F

    1981-01-01

    Forty-two patients were evaluated and treated during the past five years at the Union Memorial Hospital Hand Center with the diagnosis of chronic digital ischemia. These patients with this syndrome, manifested by pain, severe cold intolerance and occasional tip ulceration, all were failures of conventional conservative treatment of vasodilators, tobacco abstinence and beta blocking agents. The evaluation consisted of first ruling out large vessel disease by noninvasive techniques of angiography. The patients underwent a variety of noninvasive diagnostic tests including Doppler examination, pulse volume recordings with cold stress, radioisotope scanning of the digital circulation and peripheral sympathetic block of the digital nerves. Treatment included direct microvascular reconstruction of the distal ulnar or radial artery and palmar arch, in ten patients, thermal biofeedback, in 22 patients and a new surgical procedure-digital sympathectomy, in ten patients, involving 18 digits. Eight of ten patients with palmar arch reconstruction improved with seven of ten having patent vein grafts. Thermal biofeedback has been helpful in 20 patients. Testing shows that an increase in digital perfusion can be initiated by all patients. However, only 70% can achieve this improvement. Digital sympathectomy consists of isolating the terminal branches of the sympathetic nerves which travel with the peripheral nerves, dividing these branches and stripping the adventitia of the digital arteries. Eight of nine patients have the experienced improvement in digital circulation, as manifested by pulse volume recordings after operation and radioisotope studies. Pain is substantially alleviated and the ulcers healed. All of these patients responded before operation to the digital nerve block with measured increased in digital perfusion. PMID:7247519

  2. The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study.

    PubMed

    Machielsen, Marise Wj; Veltman, Dick J; van den Brink, Wim; de Haan, Lieuwe

    2014-07-01

    Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and are associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this comorbid group. However, little is known about the mechanisms underlying the assumed superiority of clozapine. We compared the effects of clozapine and risperidone on attentional bias, subjective craving and associated regional brain activity in patients with schizophrenia and CUD. Overall, 36 patients with schizophrenia and 19 healthy controls were included. Patients were randomised to antipsychotic treatment with clozapine or risperidone. At baseline and after 4 weeks of medication use, regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging. Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop, while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop. A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop. These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone. PMID:24646809

  3. FDA changes clozapine monitoring guidelines: Implications for worldwide practice.

    PubMed

    Bastiampillai, Tarun; Gupta, Arun; Allison, Stephen

    2016-06-01

    US FDA decision to change their clozapine monitoring guidelines in 2015 for the first time. The changes proposed are as follows: lowering the neutrophil count before ceasing clozapine from 1.5 to 1.0×10(9)/l, allowing the potential for re-challenge following severe neutropenia (<1.0×10(9)/l) and allowing those with benign ethnic neutropenia the opportunity to be commenced on clozapine. These changes will allow a greater number of patients with schizophrenia in USA to be continued on clozapine. In our correspondence we summarize the evidence that support these changes. The FDA changes will likely have impact on clozapine monitoring protocols in other countries. PMID:27208449

  4. Establishing the characteristics of an effective pharmacogenetic test for clozapine-induced agranulocytosis

    PubMed Central

    Verbelen, M; Collier, D A; Cohen, D; MacCabe, J H; Lewis, C M

    2015-01-01

    Clozapine is the only evidence-based therapy for treatment-resistant schizophrenia, but it induces agranulocytosis, a rare but potentially fatal haematological adverse reaction, in less than 1% of users. To improve safety, the drug is subject to mandatory haematological monitoring throughout the course of treatment, which is burdensome for the patient and one of the main reasons clozapine is underused. Therefore, a pharmacogenetic test is clinically useful if it identifies a group of patients for whom the agranulocytosis risk is low enough to alleviate monitoring requirements. Assuming a genotypic marker stratifies patients into a high-risk and a low-risk group, we explore the relationship between test sensitivity, group size and agranulocytosis risk. High sensitivity minimizes the agranulocytosis risk in the low-risk group and is essential for clinical utility, in particular in combination with a small high-risk group. PMID:25732907

  5. Chronic orchialgia: Review of treatments old and new

    PubMed Central

    Tojuola, Bayo; Layman, Jeffrey; Kartal, Ibrahim; Gudelogul, Ahmet; Brahmbhatt, Jamin; Parekattil, Sijo

    2016-01-01

    Introduction: Chronic orchialgia is historically and currently a challenging disease to treat. It is a diagnostic and therapeutic challenge for physicians. Conservative therapy has served as the first line of treatment. For those who fail conservative therapy, surgical intervention may be required. We aim to provide a review of currently available surgical options and novel surgical treatment options. Methods: A review of current literature was performed using PubMed. Literature discussing treatment options for chronic orchialgia were identified. The following search terms were used to identify literature that was relevant to this review: Chronic orchialgia, testicular pain, scrotal content pain, and microsurgical denervation of the spermatic cord (MDSC). Results: The incidence of chronic orchialgia has been increasing over time. In the USA, it affects up to 100,000 men per year due to varying etiologies. The etiology of chronic orchialgia can be a confounding problem. Conservative therapy should be viewed as the first line therapy. Studies have reported poor success rates. Current surgical options for those who fail conservative options include varicocelectomy, MDSC, epididymectomy, and orchiectomy. Novel treatment options include microcryoablation of the peri-spermatic cord, botox injection, and amniofix injection. Conclusion: Chronic orchialgia has been and will continue to be a challenging disease to treat due to its multiple etiologies and variable treatment outcomes. Further studies are needed to better understand the problem. Treatment options for patients with chronic orchialgia are improving. Additional studies are warranted to better understand the long-term durability of this treatment options. PMID:26941490

  6. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells.

    PubMed

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100μM) and doxorubicin (0.2µM) decreased the cell survival rate, but olanzapine (1-100µM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. PMID:27368152

  7. Easing Chronic Pain: Better Treatments and Medications

    MedlinePlus

    ... can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period ... flow and oxygen to muscles and relieve stress. Psychological methods These include counseling, hypnosis, and cognitive-behavioral ...

  8. [Current issues on the treatment of chronic constipation].

    PubMed

    Hong, Kyoung Sup; Jung, Kee Wook; Lee, Tae Hee; Lee, Bong Eun; Park, Sun-Young; Shin, Jeong Eun; Kim, Seong-Eun; Park, Kyung Sik; Choi, Suck Chei

    2014-09-25

    Chronic constipation is a very common clinical problem with its prevalence of up to 14% in the general population. It is not a life-threatening disease, but since patient's satisfaction to the treatment is known to be as low as 50%, chronic constipation still remains a clinically challenging problem. Fortunately, many new treatments have been introduced or are to be introduced in the near future. This article will review the basic concepts and the results of recent studies on the new treatments for chronic constipation. PMID:25252863

  9. Chronic hepatitis C: latest treatment options.

    PubMed

    Iosue, Kathleen

    2002-04-01

    The most common chronic bloodborne infection in the United States, hepatitis C virus (HCV) is the most frequent reason for liver transplantation. Unfortunately, most infected individuals don't realize they're HCV positive and only discover the disease after severe liver damage has occurred. Here, update your knowledge on the epidemiology, transmission and risk factors, diagnosis, clinical presentation, and management of chronic HCV. Insight on counseling and quality of life issues for infected patients is also included. PMID:11984417

  10. Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP-induced deficits in reversal learning in the two-lever operant task in male Sprague Dawley rats.

    PubMed

    de Bruin, N M W J; van Drimmelen, M; Kops, M; van Elk, J; Wetering, M Middelveld-van de; Schwienbacher, I

    2013-05-01

    Reasoning and problem solving deficits have been reported in schizophrenic patients. In the present study, we have tested rats in a two-lever reversal learning task in a Skinner box to model these deficits. In other studies using the Skinner box, atypical antipsychotics fully reversed phencyclidine (PCP)-induced impairments in reversal learning which is in contrast to clinical observations where antipsychotics lack the ability to fully reverse cognitive deficits in schizophrenia. Therefore, it can be argued that the outcome of these tests may lack predictive value. In the present study, after training on a spatial discrimination between two levers, rats were exposed to a reversal of the previously learned stimulus-response contingency during 5 days. We first investigated the effects of sub-chronic treatment with the non-competitive N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801) and PCP on reversal learning and extinction in male Sprague Dawley rats. Subsequently, we studied the effects of different PCP treatment regimes. Then, we investigated whether the atypical antipsychotics risperidone and clozapine and the 5-hydroxytryptamine6 (5-HT6) antagonist GSK-742457 could reverse the PCP-induced deficits. All drugs were administered subcutaneously (s.c.). MK-801 did not impair reversal learning, while PCP (1.0 and 2.0 mg/kg) induced a clear deficit in reversal learning. Both compounds, however, disrupted extinction at all tested doses. Risperidone and clozapine were both ineffective in significantly ameliorating the PCP-induced deficit in reversal learning which fits well with the clinical observations. The lowest dose of clozapine (1.25 mg/kg) had an intermediate effect in ameliorating the deficit in reversal learning induced by PCP (not different from control or PCP-treated rats). The lowest dose of GSK-742457 (0.63 mg/kg) fully reversed the PCP-induced deficits while the higher dose (5.0 mg/kg) had an intermediate effect. PMID:23384714

  11. Encapsulation of clozapine in polymeric nanocapsules and its biological effects.

    PubMed

    Łukasiewicz, Sylwia; Szczepanowicz, Krzysztof; Podgórna, Karolina; Błasiak, Ewa; Majeed, Nather; Ogren, Sven Ove Ögren; Nowak, Witold; Warszyński, Piotr; Dziedzicka-Wasylewska, Marta

    2016-04-01

    Clozapine is an effective atypical antipsychotic drug that unfortunately exhibits poor oral bioavailability. Moreover, the clinical use of the compound is limited because of its numerous unfavorable and unsafe side effects. Therefore, the aim of the present study was the development of a new nanocarrier for a more effective clozapine delivery. Here, clozapine was encapsulated into polymeric nanocapsules (NCs). Polyelectrolyte multilayer shells were constructed by the technique of sequential adsorption of polyelectrolytes (LbL) using biocompatible polyanion PGA (Poly-L-glutamic acid, sodium salt) and polycation PLL (poly-L-lysine) on clozapine-loaded nanoemulsion cores. Pegylated external layers were prepared using PGA-g-PEG (PGA grafted by PEG (polyethylene glycol)). Clozapine was successfully loaded into the PLL-PGA nanocarriers (CLO-NCs) with an average size of 100 nm. In vitro analysis of the interactions of the CLO-NCs with the cells of the mononuclear phagocytic system (MPS) was conducted. Cell biocompatibility, phagocytosis potential, and cellular uptake were studied. Additionally, the biodistribution and behavioral effects of the encapsulated clozapine were also studied. The results indicate that surface modified (by PEG grafting) polymeric PLL-PGA CLO-NCs are very promising nanovehicles for improving clozapine delivery. PMID:26774571

  12. The surgical treatment of chronic intestinal ischemia.

    PubMed Central

    Eklof, B; Hoevels, J; Ihse, I

    1978-01-01

    The mortality in acute intestinal ischemia is high, and 50% of such patients have previous attacks of abdominal angina due to chronic intestinal ischemia. Vascular reconstruction is remarkably successful in relieving the symptoms of chronic intesintal ischemia and for this reason angiographic examination is recommended in all patients in whom chronic intestinal ischemia is suspected. If the diagnosis is established by arteriography with appropriate supporting evidence, vascular reconstruction should be performed. Images Fig. 1a and b. Fig. 2a and b. Fig. 3b and c. Fig. 4a. Fig. 4b. Fig. 5b. Fig. 6. Fig. 7a. Fig. 7b and c. Fig. 8a and b. Fig. 9a. Fig. 9b. Fig. 9c. PMID:637591

  13. Medication Treatment Efficacy and Chronic Orofacial Pain.

    PubMed

    Clark, Glenn T; Padilla, Mariela; Dionne, Raymond

    2016-08-01

    Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (β-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful. PMID:27475515

  14. Clozapine-Induced Obsessive-Compulsive Symptoms in Schizophrenia: A Critical Review

    PubMed Central

    Schirmbeck, Frederike; Zink, Mathias

    2012-01-01

    Obsessive-compulsive disorder (OCD) is rarely associated with schizophrenia, whereas 20 to 30% of schizophrenic patients, suffer from comorbid obsessive-compulsive symptoms (OCS). So far no single pathogenetic theory convincingly explained this fact suggesting heterogeneous subgroups. Based on long-term case observations, one hypothesis assumes that second-onset OCS in the course of schizophrenia might be a side effect of second generation antipsychotics (SGA), most importantly clozapine (CLZ). This review summarizes the supporting epidemiological and pharmacological evidence: Estimations on prevalence of OCS increase in more recent cross-sectional studies and in later disease stages. Longitudinal observations report the de novo-onset of OCS under clozapine treatment. This association has not been reported with first generation antipsychotics (FGA) or SGAs with mainly dopaminergic mode of action. Finally, significant correlations of OCS-severity with duration of treatment, dose and serum levels suggest clozapine-induced OCS. However, supposed causal interactions need further verifications. It is also unclear, which neurobiological mechanisms might underlie the pathogenetic process. Detailed genotypic and phenotypic characterizations of schizophrenics with comorbid OCS regarding neurocognitive functioning and activation in sensitive tasks of functional magnetic imaging are needed. Multimodal large-scaled prospective studies are necessary to define patients at risk for second-onset OCS and to improve early detection and therapeutic interventions. PMID:22942882

  15. Hormonal and Metabolic Effects of Olanzapine and Clozapine Related to Body Weight in Rodents

    PubMed Central

    Albaugh, Vance L.; Henry, Cathy R.; Bello, Nicholas T.; Hajnal, Andras; Lynch, Susan L.; Halle, Beth; Lynch, Christopher J.

    2009-01-01

    Objective To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Research Methods and Procedures Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Results Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting ~24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical anti-psychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. Discussion A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge. PMID:16493121

  16. Evaluation and treatment of chronic hand conditions.

    PubMed

    Darowish, Michael; Sharma, Jyoti

    2014-07-01

    Hand and wrist problems are frequently the cause of patients' complaints in the primary care setting. Common problems include hand numbness, pain, loss of motion, or unexplained masses in the hand. Many problems can be successfully managed or treated with nonoperative measures. This article focuses on commonly encountered causes of chronic hand pain. PMID:24994053

  17. Treatment of chronic diarrhoea: loperamide versus ispaghula husk and calcium.

    PubMed

    Qvitzau, S; Matzen, P; Madsen, P

    1988-12-01

    Twenty-five patients with chronic diarrhoea were included in an open, randomized crossover trial comparing the effect of loperamide with ispaghula and calcium. Nineteen patients completed both treatments. Before treatment the median number of daily stools was 7 (range, 4-13), stool consistency was loose in all, and urgency was present in 16 out of 19 patients. Both treatments halved stool frequency, but with regard to urgency and stool consistency ispaghula and calcium was significantly better. A combination of ispaghula and calcium seems to be a cheap and effective alternative to conventional treatment of chronic diarrhoea. Moreover, side effects were minimized. PMID:3074458

  18. Evidence-based Management Strategies for Treatment of Chronic Wounds

    PubMed Central

    Werdin, Frank; Tennenhaus, Mayer; Schaller, Hans-Eberhardt; Rennekampff, Hans-Oliver

    2009-01-01

    The care and management of patients with chronic wounds and their far-reaching effects challenge both the patient and the practitioner. Further complicating this situation is the paucity of evidence-based treatment strategies for chronic wound care. After searching both MEDLINE and Cochrane databases, we reviewed currently available articles concerning chronic wound care. Utilizing this information, we have outlined a review of current, evidence-based concepts as they pertain to the treatment of chronic wounds, focusing on fundamental treatment principles for the management of venous, arterial, diabetic, and pressure ulcers. Individualized treatment options as well as general wound management principles applicable to all varieties of chronic wounds are described. Classification and treatment guidelines as well as the adoption of the TIME acronym facilitate an organized conceptional approach to wound care. In so doing, individual aspects of generalized wound care such as debridement, infection, and moisture control as well as attention to the qualities of the wound edge are comprehensively evaluated, communicated, and addressed. Effective adjuvant agents for the therapy of chronic wounds including nutritional and social support measures are listed, as is a brief review of strategies helpful for preventing recurrence. An appreciation of evidence-based treatment pathways and an understanding of the pathophysiology of chronic wounds are important elements in the management of patients with chronic wounds. To achieve effective and long-lasting results, a multidisciplinary approach to patient care, focused on the education and coordination of patient, family as well as medical and support staff can prove invaluable. PMID:19578487

  19. Berberine inhibits SREBP-1-related clozapine and risperidone induced adipogenesis in 3T3-L1 cells.

    PubMed

    Hu, Yueshan; Kutscher, Eric; Davies, Gareth E

    2010-12-01

    Weight gain is a common and potentially serious complication associated with the treatment of second generation antipsychotics such as clozapine and risperidone. Increased peripheral adipogenesis via the SREBP-1 pathway could be one critical mechanism responsible for antipsychotic drug-induced weight gain. Berberine, a botanical alkaloid, has been shown in our previous studies to inhibit adipogenesis in cell and animal models. MTT was used to determine the cytotoxic effects of clozapine and risperidone in combination with berberine. Differentiation of 3T3-L1 cells was monitored by Oil-Red-O staining and the expression of SREBP-1 and related proteins was determined by real-time RT-PCR and western blotting. The results showed that neither clozapine nor risperidone, alone or in combination with berberine had significant effects on cell viability. Eight days treatment with 15 μM clozapine increased adipogenesis by 37.4% and 50 μM risperidone increased adipogenesis by 26.5% during 3T3-L1 cell differentiation accompanied by increased SREBP-1, PPARγ, C/EBPα, LDLR and Adiponectin gene expression. More importantly, the addition of 8 μM berberine diminished the induction of adipogenesis almost completely accompanied by down-regulated mRNA and protein expression levels of SREBP-1-related proteins. These encouraging results may lead to the use of berberine as an adjuvant to prevent weight gain during second generation antipsychotic medication. PMID:20564506

  20. Evaluation and treatment of chronic cough.

    PubMed

    Terasaki, Genji; Paauw, Douglas S

    2014-05-01

    Chronic cough is a frustrating and common problem, resulting in significant psychological and physical sequelae as well as enormous financial costs in terms of health care expense and time lost from work. Decreased QoL and depression are common. However, using a systematic approach, including assessing whether the patient uses ACE-I and cigarettes, excluding the presence of red flags and risk factors for life-threatening diseases, and obtaining and normal chest radiograph, more than 90% of cases of chronic cough are diagnosed as being caused by UACS, asthma, or GERD. It is recommended to address these conditions sequentially, starting with UACS. Nonasthmatic eosinophilic bronchitis and pertussis infections are unrecognized by primary care providers and should be considered after UACS, asthma, and GERD have been addressed. Finally, cough hypersensitivity syndrome is a new area of research and has been hypothesized to be the underlying factor in many cases of chronic cough, regardless of the inciting factor. More clinical research is needed to further elucidate the cough reflex pathway and the factors involved in modulating its sensitivity, which may eventually lead to new antitussive therapeutics. PMID:24758953

  1. Ghosts in the Machine. Interoceptive Modeling for Chronic Pain Treatment.

    PubMed

    Di Lernia, Daniele; Serino, Silvia; Cipresso, Pietro; Riva, Giuseppe

    2016-01-01

    Pain is a complex and multidimensional perception, embodied in our daily experiences through interoceptive appraisal processes. The article reviews the recent literature about interoception along with predictive coding theories and tries to explain a missing link between the sense of the physiological condition of the entire body and the perception of pain in chronic conditions, which are characterized by interoceptive deficits. Understanding chronic pain from an interoceptive point of view allows us to better comprehend the multidimensional nature of this specific organic information, integrating the input of several sources from Gifford's Mature Organism Model to Melzack's neuromatrix. The article proposes the concept of residual interoceptive images (ghosts), to explain the diffuse multilevel nature of chronic pain perceptions. Lastly, we introduce a treatment concept, forged upon the possibility to modify the interoceptive chronic representation of pain through external input in a process that we call interoceptive modeling, with the ultimate goal of reducing pain in chronic subjects. PMID:27445681

  2. Ghosts in the Machine. Interoceptive Modeling for Chronic Pain Treatment

    PubMed Central

    Di Lernia, Daniele; Serino, Silvia; Cipresso, Pietro; Riva, Giuseppe

    2016-01-01

    Pain is a complex and multidimensional perception, embodied in our daily experiences through interoceptive appraisal processes. The article reviews the recent literature about interoception along with predictive coding theories and tries to explain a missing link between the sense of the physiological condition of the entire body and the perception of pain in chronic conditions, which are characterized by interoceptive deficits. Understanding chronic pain from an interoceptive point of view allows us to better comprehend the multidimensional nature of this specific organic information, integrating the input of several sources from Gifford's Mature Organism Model to Melzack's neuromatrix. The article proposes the concept of residual interoceptive images (ghosts), to explain the diffuse multilevel nature of chronic pain perceptions. Lastly, we introduce a treatment concept, forged upon the possibility to modify the interoceptive chronic representation of pain through external input in a process that we call interoceptive modeling, with the ultimate goal of reducing pain in chronic subjects. PMID:27445681

  3. Are clozapine blood dyscrasias associated with concomitant medications?

    PubMed

    Demler, Tammie Lee; Trigoboff, Eileen

    2011-04-01

    Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are

  4. Are Clozapine Blood Dyscrasias Associated with Concomitant Medications?

    PubMed Central

    Demler, Tammie Lee

    2011-01-01

    Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are

  5. Current treatment of choice for chronic hepatitis C infection

    PubMed Central

    Yasin, Tareq; Riley, Thomas R; Schreibman, Ian R

    2011-01-01

    More than three million Americans have chronic hepatitis C infection, and the disease remains one of the most common blood-borne infections in the US. Treatment is focused on the chronic form of the disease, because the acute one tends to be self-limiting. In this article, we review the recent literature regarding the most effective therapy against hepatitis C infection, to confirm the current treatment of choice for the disease. We conclude that combination therapy with pegylated interferon and ribavirin remains the initial treatment of choice. New research focusing on adjuvant therapies, such as protease and polymerase inhibitors, has yielded early data that appear to be promising. PMID:21694905

  6. Treatment of a Case Example with PTSD and Chronic Pain

    ERIC Educational Resources Information Center

    Shipherd, Jillian C.

    2006-01-01

    This commentary reviews the case of GH, a survivor of a road traffic collision, who has chronic pain and posttraumatic stress disorder (PTSD). The case formulation, assessment strategy, and treatment plan are informed by the relevant experimental literature and empirically supported treatments using a cognitive behavioral perspective. Given this…

  7. Chronic pruritus--pathogenesis, clinical aspects and treatment.

    PubMed

    Metz, M; Ständer, S

    2010-11-01

    Chronic pruritus is a major symptom in numerous dermatological and systemic diseases. Similar to chronic pain, chronic pruritus can have a dramatic impact on the quality of life and can worsen the general condition of the patient considerably. The pathogenesis of itch is diverse and involves a complex network of cutaneous and neuronal cells. In recent years, more and more itch-specific mediators and receptors, such as interleukin-31, gastrin-releasing peptide receptor or histamine H4 receptor have been identified and the concept of itch-specific neurons has been further characterized. Understanding of the basic principles is important for development of target-specific treatment of patients with chronic pruritus. In this review, we summarize the current knowledge about the pathophysiological principles of itch and provide an overview about current and future treatment options. PMID:20846147

  8. Treatment algorithm for chronic lateral ankle instability

    PubMed Central

    Giannini, Sandro; Ruffilli, Alberto; Pagliazzi, Gherardo; Mazzotti, Antonio; Evangelisti, Giulia; Buda, Roberto; Faldini, Cesare

    2014-01-01

    Summary Introduction: ankle sprains are a common sports-related injury. A 20% of acute ankle sprains results in chronic ankle instability, requiring surgery. Aim of this paper is to report the results of a series of 38 patients treated for chronic lateral ankle instability with anatomic reconstruction. Materials and methods: thirty-eight patients were enrolled in the study. Seventeen patients underwent a surgical repair using the Brostrom-modified technique, while the remaining underwent anatomic reconstruction with autologous or allogenic graft. Results: at a mean follow-up of 5 years the AOFAS score improved from 66.1 ± 5.3 to 92.2 ± 5.6. Discussion: the findings of this study confirm that anatomic reconstruction is an effective procedure with satisfactory subjective and objective results which persist at long-term follow-up along with a low complication rate. No differences, in term of clinical and functional outcomes, were observed between the Brostrom-modified repair and the anatomic reconstruction technique. Level of evidence: level IV. PMID:25767783

  9. Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies

    PubMed Central

    Wachholtz, Amy; Gonzalez, Gerardo; Boyer, Edward; Naqvi, Zafar N; Rosenbaum, Christopher; Ziedonis, Douglas

    2011-01-01

    Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain. PMID:24474854

  10. Cinnarizine in the treatment of chronic asthma.

    PubMed Central

    Emanuel, M B; Chamberlain, J A; Whiting, S; Rigden, B G; Craven, A H

    1979-01-01

    1 Cinnarizine, an inhibitor of calcium ion transport across smooth muscle cell membrane, has been shown to exert an anti-asthmatic effect in patients with chronic asthma. 2 It is postulated that antagonism to calcium ion transport across the mast cell membrane may cause the compound to have a pharmacological effect similar to sodium cromoglycate. 3 Cinnarizine is orally active and its therapeutic effect is demonstrated in a double-blind, cross-over, placebo controlled study. 4 Patient benefit was shown by a significant improvement in peak flow rate. A non-significant trend towards a reduction in symptomatic bronchodilator usage and a decrease in asthma symptom score was also shown. 5 It is concluded that cinnarizine could well prove to be the first of a new family of anti-asthmatic drugs offering a protective effect when taken systemically. PMID:367414

  11. Current concepts in diagnosis and treatment of chronic lymphocytic leukemia

    PubMed Central

    Roliński, Jacek

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed type of leukemia in Western Europe and North America, and represents about 30% of all leukemias in adults. Chronic lymphocytic leukemia is a disease of the elderly, who are often in poorer general health and burdened with multiple comorbidities. These factors affect the decision making when choosing an appropriate method of treatment. In recent years there has been significant progress in the treatment of chronic lymphocytic leukemia, first due to the introduction of immunochemotherapy with monoclonal antibodies and latterly small molecules, like tyrosine kinase inhibitors targeting B-cell receptor signaling. This article discusses the current diagnostic principles, the most important prognostic factors and therapeutic options, available in first-line treatment and in refractory/resistant disease, including high-risk CLL, both for patients with good and those with poor performance status. It also presents important novel molecules which have been evaluated in clinical trials. PMID:26793019

  12. Evaluation of treatment with carboxymethylcellulose on chronic venous ulcers*

    PubMed Central

    Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli

    2016-01-01

    BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773

  13. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  14. [Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].

    PubMed

    Fiessinger, J N; Aiach, M; Lagneau, P; Cormier, J M; Housset, E

    1975-04-20

    38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment. PMID:176733

  15. [New treatment options for chronic pruritus].

    PubMed

    Zeidler, C; Pfleiderer, B; Ständer, S

    2016-08-01

    Prevalent in 14-17 % of the population, chronic pruritus is among the most common and stressful symptoms in medicine. In spite of new findings regarding the origin and chronification of the symptom, therapy remains a great challenge. There is a lack of approved therapies that provide rapid and efficient reduction of pruritus. As a result, the affected patients suffer a long time (even months to years), and somatic (scratch lesions, super infections, sleep disorders) and psychosomatic disorders develop. Interdisciplinary cooperation with various specialists is important not just for these reasons, but also due to different etiologies of the symptom and common comorbidities. In addition, there remains a great need for uniformly devised, clinically controlled studies, recommendations and guidelines. New therapeutic approaches are currently being verified in clinical trials. This allows for future prospects of possible new and partially targeted therapies. This article provides a summary of current therapeutic options based on case series, individual randomized controlled trials and the current S2K guideline. PMID:27351559

  16. [Surgical options in the treatment of chronic venous ulcers].

    PubMed

    Stellmes, Arno; Derungs, Urs; Schmidli, Jürg; Widmer, Matthias K

    2011-03-01

    Surgery offers several options in prevention of chronic venous insufficiency and its sequelae. Both the operation on veins with valve dysfunction to reduce reflux and the elimination of obstruction in thrombosed veins aim for the reduction of venous hypertension. Elevated venous pressure, impairment of cutaneous capillaries and a chronic inflammatory process result in sclerosis of skin and subcutaneous tissue and might proceed to the fascia resulting in a chronic compartment syndrome. Non- healing chronic venous ulcers under conservative therapy for more than three months may be treated by vein-surgery, local wound care therapy like shaving and negative pressure treatment and if necessary by lowering of elevated intracompartimental pressure by fasciotomy or even fasciectomy. PMID:21360463

  17. Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia

    PubMed Central

    Chen, Yaoyu; Li, Shaoguang

    2014-01-01

    In a significant proportion of patients with chronic myeloid leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine) is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic myeloid leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic myeloid leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic myeloid leukemia who do not respond well to tyrosine kinase inhibitors. PMID:24516334

  18. Treatment of Chronic Constipation: Prescription Medications and Surgical Therapies

    PubMed Central

    Everhart, Kelly; Lacy, Brian E.

    2015-01-01

    Constipation is a highly prevalent disorder that affects people regardless of age, race, gender, or socioeconomic status. For many patients, constipation is a chronic condition that reduces quality of life. Chronic constipation also imposes a significant economic burden on the health care system. The treatment of constipation remains problematic for both patients and providers for a variety of reasons, including a lack of specificity of symptoms, an inconsistent relationship between underlying pathophysiology and symptom generation, and different and unpredictable patient responses to medications. A large number of over-the-counter agents are used to treat symptoms of constipation, although many of these agents are not effective, and data to support their use are limited and generally of poor quality. Patients referred for consultation typically have failed therapy with over-the-counter agents and require prescription medications or possibly even surgical therapy. This article discusses medical treatments and surgical options for chronic idiopathic constipation. PMID:27099579

  19. Treatment of Chronic Constipation: Prescription Medications and Surgical Therapies.

    PubMed

    Hussain, Zilla H; Everhart, Kelly; Lacy, Brian E

    2015-02-01

    Constipation is a highly prevalent disorder that affects people regardless of age, race, gender, or socioeconomic status. For many patients, constipation is a chronic condition that reduces quality of life. Chronic constipation also imposes a significant economic burden on the health care system. The treatment of constipation remains problematic for both patients and providers for a variety of reasons, including a lack of specificity of symptoms, an inconsistent relationship between underlying pathophysiology and symptom generation, and different and unpredictable patient responses to medications. A large number of over-the-counter agents are used to treat symptoms of constipation, although many of these agents are not effective, and data to support their use are limited and generally of poor quality. Patients referred for consultation typically have failed therapy with over-the-counter agents and require prescription medications or possibly even surgical therapy. This article discusses medical treatments and surgical options for chronic idiopathic constipation. PMID:27099579

  20. Gabapentin and pregabalin for the treatment of chronic pruritus.

    PubMed

    Matsuda, Kazuki M; Sharma, Divya; Schonfeld, Ariel R; Kwatra, Shawn G

    2016-09-01

    Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies. PMID:27206757

  1. [Advances in the treatment of chronic prostatitis/chronic pelvic pain syndrome].

    PubMed

    Yang, Ming-Gen; Zhao, Xiao-Kun

    2008-12-01

    So far the etiology of chronic prostatitis (PC) and particularly chronic pelvic pain syndrome (CPPS) remains to be elucidated. According to recent epidemiologic data, CP is the most common urological disease in men below 50 years and occurs in 2.5%-16.0% of the world population. Since the 1990s, researchers of many countries have carried out deeper, more extensive and larger scaled studies than ever before on the etiology, diagnosis and treatment of the disease, with the sponsorship and coordination of such international institutions as the International Prostatitis Collaborative Network (IPCN), the Chronic Prostatitis Collaborative Research Network of the National Institute of Health (NIH-CPCRN) and so on. As prevalent as multiple sclerosis, CPPS is the most common yet most poorly understood "prostatitis syndrome". This article reviews the progress in the studies of the treatment of CPPS, explores the main problems and ventures the prospects for the development in this field. PMID:19157239

  2. Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine.

    PubMed

    Chana, Gursharan; Lucero, Ginger; Salaria, Shahid; Lozach, Jean; Du, Pinyi; Woelk, Christopher; Everall, Ian

    2009-09-01

    Growing genetic evidence has implicated a role for neuregulin-1 (NRG-1) in schizophrenia pathogenesis as well as alterations in SNAP receptor (SNARE) proteins at both gene and protein levels in post-mortem investigations. In relation to a potential therapeutic mechanism for atypical antipsychotic medications, clozapine has been shown to increase both NRG-1 levels and synaptic markers in rodents. As evidence continues to mount for a potential restoration in connectivity by antipsychotic medications being a mode of efficacy we chose to examine the effects of the atypical antipsychotic clozapine and the typical antipsychotic haloperidol on NRG-1 and SNARE protein transcripts in human brain aggregates exposed to plasma levels chronically for a period of three weeks. At the end of this exposure period we performed quantitative real-time PCR to investigate the mRNA levels of NRG-1, VAMP-1 and SNAP-25. Overall we found that clozapine had the ability to upregulate NRG-1 (+3.58 fold change) and VAMP-1 (+1.92) while SNAP-25 remained unchanged. Changes for haloperidol exposed aggregates were below our cut-off of +1.5. Overall the results of our investigation lend further support to atypical antipsychotic medications having the potential to increase levels of neurotrophic and synaptic markers such as NRG-1 and VAMP-1, the former being a strong candidate susceptibility gene for schizophrenia. In the absence of frank neuronal loss in schizophrenia, restoration of neuronal and synaptic functions by atypical antipsychotics in the brains of schizophrenics maybe a key mechanism of therapeutic efficacy by re-establishing normal connectivity and functioning. PMID:19502011

  3. Vasodilator treatment for acute and chronic heart failure.

    PubMed Central

    Chatterjee, K; Parmley, W W

    1977-01-01

    The current status of the use of vasodilator drugs in the treatment of acute and chronic heart failure has been reviewed. It is apparent that vasodilator treatment can be used effectively in some patients with heart failure with a beneficial haemodynamics response, and that vasodilator agents are likely to find an important place in the management of such patients. Vasodilator treatment may be associated with complications and must be used with care. Though several nonparenteral vasodilator agents have been investigated, no ideal drug is yet available for the treatment of chronic heart failure. Nevertheless, it is probable that suitable drugs will emerge and find an important place in the management of such patients. Images PMID:884021

  4. Alitretinoin for the treatment of severe chronic hand eczema

    PubMed Central

    King, Thomas; McKenna, John; Alexandroff, Anton B

    2014-01-01

    Chronic hand eczema is a common and often debilitating condition. Alitretinoin, a 9-cis-retinoic acid and pan-retinoic acid agonist, is a new and effective systemic treatment for chronic hand eczema, which provides another treatment option. A “clear” or “almost clear” response can be achieved in up to half of patients within a 24-week course of treatment. Even higher rates of remission can be obtained with a longer duration of treatment. Alitretinoin has a favorable overall profile of adverse effects; however, female patients who are at risk of becoming pregnant should follow a strict pregnancy-prevention program due to the teratogenic effects of this drug. PMID:25525339

  5. Current diagnosis and treatment of chronic subdural haematomas

    PubMed Central

    Iliescu, IA

    2015-01-01

    A developed society is usually also characterized by an elderly population, which has a continuous percentage growth. This population frequently presents a cumulus of medical pathologies. With the development of the medication and surgical treatment of different affections, the life span has increased and the pathology of an old patient has diversified as far as the cumulus of various pathological diseases in the same person is concerned. Chronic subdural pathologies represent an affection frequently met in neurosurgery practice. Any neurosurgeon, neurologist and not only, has to be aware of the possibility of the existence of a chronic subdural haematoma, especially when the patient is old and is subjected to an anticoagulant or antiaggregant treatment, these 2 causes being by far the etiological factors most frequently met in chronic subdural haematomas. With an adequate diagnosis and treatment, usually surgical, the prognosis is favorable. Although the surgical treatment presents a categorical indication in most of the cases, the fact that there are many surgical techniques, a great relapse rate, as well as the numerous studies, which try to highlight the efficiency of a technique as compared to another, demonstrate that the treatment of these haematomas is far from reaching a consensus among the neurosurgeons. The latest conservatory treatment directions are still being studied and need many years to be confirmed. Abbreviations: CT = computerized tomography, MRI = magnetic resonance imaging PMID:26351527

  6. Treatment of chronic hepatic encephalopathy with levodopa 1

    PubMed Central

    Lunzer, Michael; James, I. M.; Weinman, J.; Sherlock, Sheila

    1974-01-01

    Three of six patients with chronic hepatic encephalopathy treated with levodopa showed a significant improvement. One patient was probably improved whilst the remaining two patients failed to show any benefit. Serial electroencephalography did not demonstrate significant changes. Treatment with levodopa was associated with an improvement in `speed-based' tasks as assessed by computerized psychometry. A significant rise in cerebral oxygen consumption was found during levodopa therapy. Gastrointestinal side effects were dose limiting. It is concluded that a therapeutic trial of levodopa in patients with chronic hepatic encephalopathy is indicated when the response to conventional therapy has been poor. PMID:4430473

  7. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine*

    PubMed Central

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D’Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  8. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine.

    PubMed

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-04-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  9. New Chronic Pain Treatments in the Outpatient Setting: Review Article.

    PubMed

    Grandhe, R; Souzdalnitski, D; Gritsenko, K

    2016-05-01

    Chronic pain is an issue encountered by many health care providers in their routine clinical practice. In addition to generalized patient suffering, this condition has significant clinical, psychological, and socioeconomic impact due to its widespread occurrence. The landscape of chronic pain management has been changing rapidly with an array of treatment innovations, better understanding of established therapies, and care coordination across specialties. In this article, we have reviewed emerging new modalities as well as transformation of established therapies by interventional, pharmacologic, rehabilitative, psychological, complimentary, and interdisciplinary approaches. PMID:27038972

  10. Glycopyrronium bromide for the treatment of chronic obstructive pulmonary disease.

    PubMed

    Riario-Sforza, Gian Galeazzo; Ridolo, Erminia; Riario-Sforza, Edoardo; Incorvaia, Cristoforo

    2015-02-01

    Glycopyrronium bromide is a new long-acting muscarinic antagonist to be used once-daily, which is approved as a bronchodilator for the symptomatic maintenance treatment of adult patients with chronic obstructive pulmonary disease (COPD). In the Glycopyrronium bromide in chronic Obstructive pulmonary disease airWays trials, treatment with inhaled glycopyrronium bromide at 50 μg once daily achieved a significantly better lung function than placebo, as measured by the trough forced expiratory volume in 1 s in patients with moderate-to-severe COPD. The lung function improvement was maintained for up to 52 weeks. Other improved indexes were dyspnea scores, health status, exacerbation rates and time of exercise endurance. Studies comparing the efficacy of glycopyrronium versus tiotropium bromide found substantial equivalence of the two drugs. Glycopyrronium was generally well tolerated. These data add inhaled glycopyrronium bromide to the treatment of patients with moderate to severe COPD as an effective once-daily LAMA. PMID:25547422

  11. Discontinuing treatment in children with chronic, critical illnesses.

    PubMed

    Mahon, M M; Deatrick, J A; McKnight, H J; Mohr, W K

    2000-03-01

    Decisions about optimal treatment for critically ill children are qualitatively different from those related to adults. Technological advances over the past several decades have resulted in myriad treatment options that leave many children chronically, critically ill. These children are often technology dependent. With new technologies and new patient populations comes the responsibility to understand how, when, and why these technologies are applied and when technology should not be used or should be withdrawn. Much has been written about ethical decision making in the care of chronically, critically ill adults and newborns. In this article, relevant factors about the care of children older than neonates are described: standards, decision makers, age of the child, and pain management. A case study is used as a mechanism to explore these issues. Dimensions of futility, discontinuing aggressive treatment, and a consideration of benefits and burdens are integrated throughout the discussion to inform nurse practitioner practice. PMID:11219897

  12. Effective Treatment of Chronic Radiation Proctitis Using Radiofrequency Ablation

    PubMed Central

    Zhou, Chao; Adler, Desmond C.; Becker, Laren; Chen, Yu; Tsai, Tsung-Han; Figueiredo, Marisa; Schmitt, Joseph M.; Fujimoto, James G.

    2009-01-01

    Endoscopic argon plasma coagulation and bipolar electrocautery are currently preferred treatments for chronic radiation proctitis, but ulcerations and strictures frequently occur. Radiofrequency ablation (RFA) has been successful for mucosal ablation in the esophagus. Here we report the efficacy of RFA with the BarRx Halo90 system in three patients with bleeding from chronic radiation proctitis. In all cases, the procedure was well tolerated and hemostasis was achieved after 1 or 2 RFA sessions. Re-epithelialization of squamous mucosa was observed over areas of prior hemorrhage. No stricturing or ulceration was seen on follow-up up to 19 months after RFA treatment. Real-time endoscopic optical coherence tomography (EOCT) visualized epithelialization and subsurface tissue microvasculature pre- and post-treatment, demonstrating its potential for follow-up assessment of endoscopic therapies. PMID:20593010

  13. The local treatment and available dressings designed for chronic wounds.

    PubMed

    Skórkowska-Telichowska, Katarzyna; Czemplik, Magdalena; Kulma, Anna; Szopa, Jan

    2013-04-01

    The great diversity of wounds and the broad range of available dressings complicate the selection of proper chronic wound treatment. Choosing the right treatment is the essential step in the healing process. In this review, we focus on chronic nonhealing ulcers, which are a critical problem in clinical practice, and current knowledge about persistent wound care. Here, we present the objectives of local treatment with description of several types of dressings and their ingredients, features, indications, and contraindications. These include hydrocolloid, alginate, hydrogel, and dextranomer dressings; polyurethane foam and membrane dressings; semipermeable polyurethane membrane dressings; and TenderWet (Hartmann, Rock Hill, SC) and flax dressings. There is also a brief section on the use of other alternative wound-healing accelerators, such as platelet-rich plasma and light-emitting diode therapy. PMID:21982060

  14. Pathogenesis and treatment of pain in patients with chronic wounds.

    PubMed

    Freedman, Gordon; Cean, Conrad; Duron, Vincent; Tarnovskaya, Alina; Brem, Harold

    2003-01-01

    Pain must be managed during treatment of a patient with a chronic wound. Failure to do so will impair the patient's ability to heal significantly. Understanding the wound's etiology is essential for designing the wound-healing protocol and implementing its pain management regimen, of which a critical part is the chronic-wound patient's self-assessed scores of pain and functionality. In this report we present a paradigm for treating all chronic wounds, which was subsequently applied to 32 consecutive patients. Our integrated-team approach to managing the treatment of wounds includes accurate evaluation of the progression of patients' pain. Directors of the pain-management team and wound team have jointly managed hundreds of patients--either hospitalized or seen in both outpatient clinical practices. The three general categories for etiologies of the 10 most common types of chronic wounds are: ischemia, neuropathy, and direct tissue damage (e.g. pressure ulcers and venous stasis ulcers). Each of these are treated with unique analgesic regimens focused on surgical/medical management of the wound: oral and parenteral medications in combinations designed to facilitate specific additive analgesic effects and nerve blocks and implantable devices for correcting underlying wound pathophysiology. Successful treatment of pain generally results in increased functional independence and improvement of the patient's quality of life. We integrated wound-care pain-management team established guidelines that delineate the causes of chronic wounds and categorize treatment options for practical clinical use. The expectation is that all pain should be resolved in all patients if both the wound-healing and pain-healthcare providers use current technologies and drugs. PMID:12931299

  15. Change in Suicidal Ideation Following Interdisciplinary Treatment of Chronic Pain

    PubMed Central

    Kowal, John; Wilson, Keith G.; Henderson, Peter R.; McWilliams, Lachlan A.

    2014-01-01

    Objectives To examine suicidal ideation in individuals with chronic pain, especially change in suicidal thinking following interdisciplinary treatment. Methods Consecutive patients (n = 250) admitted to a 4-week, group-based chronic pain management program completed measures of pain intensity, functional limitations, depressive symptoms, overall distress, pain catastrophizing, self-perceived burden, and suicidal ideation at pre- and post-treatment. Results Before treatment, 30 (12.0%) participants were classified as having a high level of suicidal ideation, 56 (22.4%) had a low level of suicidal ideation, and 164 (65.6%) reported none. Following treatment, there was a significant reduction in suicidal ideation and improvements in all other outcomes, but there were still some individuals with high (n = 22, 8.8%) or low (n = 28, 11.2%) levels at discharge. Patients with high suicidal ideation at baseline differed from those with no suicidal thinking on pre- and post-treatment measures of depression, distress, catastrophizing, and self-perceived burden, but not on pain intensity or functional limitations. Patients high in suicidal ideation endorsed greater pain catastrophizing and self-perceived burden than those low in suicidal thinking. Sustained suicidal ideation after treatment was associated with higher baseline levels of suicidal thinking and self-perceived burden to others, as well as a more limited overall response to treatment. Discussion Suicidal ideation was common in individuals with chronic pain, although mostly at a low level. Interdisciplinary treatment may result in reduced suicidal thinking; however, some patients continue to express thoughts of self-harm. Future studies could examine processes of change and interventions for treatment-resistant suicidal concerns. PMID:24281291

  16. Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Guimarães-Costa, R; Iancu Ferfoglia, R; Viala, K; Léger, J-M

    2014-10-01

    Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP. PMID:25200479

  17. Bioconcentration of two basic pharmaceuticals, verapamil and clozapine, in fish.

    PubMed

    Nallani, Gopinath C; Edziyie, Regina E; Paulos, Peter M; Venables, Barney J; Constantine, Lisa A; Huggett, Duane B

    2016-03-01

    The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 μg/L and 419 μg/L of verapamil (500 μg/L nominal) or 28.5 μg/L and 40 μg/L of clozapine (50 μg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients. PMID:26753615

  18. Prescribing clozapine and rifampicin: clinical impact of their interaction

    PubMed Central

    Parker, Caroline

    2016-01-01

    The predictable pharmacokinetic drug interaction between clozapine and rifampicin is listed in most standard reference texts but little detail is given or emphasis on its clinical significance. The interaction is based on theoretical knowledge of both drugs; to date just two case reports have been published. This article describes a third case demonstrating the significance of this interaction. This was potentially devastating for the patient who required an extended psychiatric admission. The enzyme induction was so potent that the dose of clozapine had to be increased approximately sixfold. Careful management of this significant interaction is essential for effective patient care. PMID:27280037

  19. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes

    PubMed Central

    Cassoli, Juliana S.; Iwata, Keiko; Steiner, Johann; Guest, Paul C.; Turck, Christoph W.; Nascimento, Juliana M.; Martins-de-Souza, Daniel

    2016-01-01

    Separate lines of evidence have demonstrated the involvement of N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in schizophrenia. Here, we have carried out shotgun mass spectrometry proteome analysis of oligodendrocytes treated with the NMDA receptor antagonist MK-801 to gain potential insights into these effects at the molecular level. The MK-801 treatment led to alterations in the levels of 68 proteins, which are associated with seven distinct biological processes. Most of these proteins are involved in energy metabolism and many have been found to be dysregulated in previous proteomic studies of post-mortem brain tissues from schizophrenia patients. Finally, addition of the antipsychotic clozapine to MK-801-treated oligodendrocyte cultures resulted in changes in the levels of 45 proteins and treatment with clozapine alone altered 122 proteins and many of these showed opposite changes to the MK-801 effects. Therefore, these proteins and the associated energy metabolism pathways should be explored as potential biomarkers of antipsychotic efficacy. In conclusion, MK-801 treatment of oligodendrocytes may provide a useful model for testing the efficacy of novel treatment approaches. PMID:26973466

  20. Adult chronic sleepwalking and its treatment based on polysomnography.

    PubMed

    Guilleminault, Christian; Kirisoglu, Ceyda; Bao, Gang; Arias, Viola; Chan, Allison; Li, Kasey K

    2005-05-01

    Adult sleepwalking affects 2.5% of the general population and may lead to serious injuries. Fifty young adults with chronic sleepwalking were studied prospectively. Clinical evaluation, questionnaires from patients and bed partners, and polysomnography were obtained on all subjects in comparison with 50 age-matched controls. Subjects were examined for the presence of psychiatric anxiety, depression and any other associated sleep disorder. Isolated sleepwalking or sleepwalking with psychiatric disorders was treated with medication. All other patients with other sleep disorders were treated only for their associated problem. Prospective follow-up lasted 12 months after establishment of the most appropriate treatment. Patients with only sleepwalking, treated with benzodiazepines, dropped out of follow-up testing and reported persistence of sleepwalking, as did patients with psychiatric-related treatment. Chronic sleepwalkers frequently presented with sleep-disordered breathing (SDB). All these patients were treated only for their SDB, using nasal continuous positive airway pressure (CPAP). All nasal CPAP-compliant patients had control of sleepwalking at all stages of follow-up. Non-compliant nasal CPAP patients had persistence of sleepwalking. They were offered surgical treatment for SDB. Those successfully treated with surgery also had complete resolution of sleepwalking. Successful treatment of SDB, which is frequently associated with chronic sleepwalking, controlled the syndrome in young adults. PMID:15817520

  1. Treatment of Chronic Plantar Fasciitis With Percutaneous Latticed Plantar Fasciotomy.

    PubMed

    Yanbin, Xu; Haikun, Chu; Xiaofeng, Ji; Wanshan, Yang; Shuangping, Liu

    2015-01-01

    Plantar fasciitis, the most common cause of pain in the inferior heel, accounts for 11% to 15% of all foot symptoms requiring professional care among adults. The present study reports the results of a minimally invasive surgical treatment of chronic plantar fasciitis. All patients with plantar fasciitis who had undergone percutaneous latticed plantar fasciotomy at 3 clinical sites from March 2008 to March 2009 were included in the present study. The follow-up evaluations for this treatment were conducted using the Mayo clinical scoring system. We investigated 17 patients with recalcitrant chronic plantar fasciitis who had undergone this treatment within a follow-up period of ≥13 months. All procedures were performed in the clinic with the patient under local anesthesia. No wound infections or blood vessel or nerve damage occurred. At a mean follow-up period of 16.0 ± 2.29 (range 13 to 21) months, significant improvement was seen in the preoperative mean Mayo score (from 12.06 ± 2.54 to 89.76 ± 4.28, p < .001) and no patient had developed symptom recurrence. Also, none of the patients had developed complex regional pain syndrome. All patients were able to return to regular shoe wear by 3 weeks postoperatively. The technique of plantar fasciitis with percutaneous latticed plantar fasciotomy could be a promising treatment option for patients with recalcitrant chronic plantar fasciitis. PMID:26058817

  2. The chronic syndromes after previous treatment of pituitary tumours.

    PubMed

    Romijn, Johannes A

    2016-09-01

    Ultimately, almost all patients who are appropriately treated for pituitary tumours enter a chronic phase with control or cure of hormonal excess, adequate treatment of pituitary insufficiency and relief of mass effects. This phase is associated with improvement of initial signs and symptoms, but also with the persistent consequences of the initial disease and associated treatments. Pituitary insufficiency is a common denominator in many of these patients, and is associated with a reduction in quality of life, despite adequate endocrine substitution. Hypothalamic dysfunction can be present in patients previously treated for visual impairments caused by large suprasellar adenomas, or craniopharyngiomas. In addition to hypopituitarism, these patients can have multisystem morbidities caused by altered hypothalamic function, including weight gain and disturbed regulation of sleep-wake cycles. Mortality can also be affected. Patients cured of Cushing disease or acromegaly have chronic multisystem morbidities (in the case of Cushing disease, also affecting mortality) caused by irreversible effects of the previous excesses of cortisol in Cushing disease and growth hormone and insulin-like growth factor 1 in acromegaly. In addition to early diagnosis and treatment of pituitary tumours, research should focus on the amenability of these chronic post-treatment syndromes to therapeutic intervention, to improve quality of life and clinical outcomes. PMID:27259177

  3. Chronic pain: the burden of disease and treatment innovations.

    PubMed

    Monti, S; Caporali, R

    2015-01-01

    Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Efficacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients' long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profile, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic field, particularly in the treatment of osteoarthritis and low back pain. PMID:26492961

  4. [Some practical questions on chronic stipsis treatment with prucalopride].

    PubMed

    Bellacosa, L; Cogliandro, R; Cremon, C; De Giorgio, R; Barbara, G; Stanghellini, V

    2014-03-01

    Chronic constipation is a frequent pathological condition bearing relevant socioeconomic burdens, mainly due to uncertain management and unsatisfactory response to traditional laxatives. Prucalopride is a novel enterokinetic drug, that has been demonstrated to improve bowel functions and relieve a broad spectrum of digestive symptoms in patients with severe chronic constipation who had failed to respond to various traditional laxatives. In this paper we discussed the practical aspects of chronic constipation treatment, in particular focusing on some questions about the practical use of prucalopride. Prucalopride is a potent, selective, high-affinity agonist of the 5-HT4 receptors widely expressed in the gastrointestinal tract. Unlike other 5-HT4 agonists, such as cisapride and tegaserod, it is devoid of adverse cardiovascular effects. Furthermore, it is characterized by a low potential for interactions with other drugs, due to its pharmacokinetic characteristics. Prucalopride was approved, in 2009, by the European Medicines Agency for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief, however, there are ongoing studies to extend the use of the drug even to males. PMID:24632771

  5. Clozapine prescribing in the UK: views and experience of consultant psychiatrists

    PubMed Central

    Farooq, Saeed

    2015-01-01

    Objectives: It has been repeatedly shown that clozapine is underutilized and there is delayed use of it in clinical practice. Method: An online survey was sent to 2771 consultant psychiatrists registered with the Royal College of Psychiatrists in the UK. A total of 243 responded to this survey. The survey elicited their views and experiences in using clozapine as well as to identify what may be the underlying causes for its underutilization. Results: Over 75% acknowledged that they had good training in using clozapine and about 56% had clozapine-dedicated service. However, 40.5% preferred to use several other antipsychotics prior to considering clozapine. A third felt it was not safe to start clozapine in the community and 42% had less than five patients on clozapine. Eleven possible reasons for clozapine underutilization were identified including concerns about side effects, patients not wanting to have blood tests and lack of experience or knowledge. Knowledge deficiency in certain aspects of clozapine use were identified, e.g. a third of respondents did not know that the risk of agranulocytosis changes with time, 42.7% did not think that clozapine can reduce substance use, while 20% were not aware of its benefit in reducing suicidal risk. Conclusions: Important areas of concern such as managing side effects and deficiency in evidence-based use of clozapine were identified. These can be targeted in training and professional development programme. PMID:26240748

  6. Chronic benzodiazepine treatment and cortical responses to adenosine and GABA.

    PubMed

    Mally, J; Connick, J H; Stone, T W

    1990-10-22

    The effects of chronic treatment of mice with clonazepam have been examined on the responses of neocortical slices to adenosine, 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA). Responses to these agonists were measured as changes in the depolarisation induced by N-methyl-D-aspartate (NMDA). Added to the superfusion medium diazepam blocked responses to adenosine but not 5-HT; this effect was not observed with 2-chloroadenosine or in the presence of 2-hydroxynitrobenzylthioguanosine. GABA was inactive in control slices but chronic treatment with clonazepam induced responses to GABA and enhanced responses to adenosine but not 5-HT. It is suggested that the induction of GABA responses may reflect the up-regulation of GABA receptors, but the increase of adenosine responses by clonazepam implies that there is no simple relationship between adenosine receptor binding and functional responses. PMID:1979931

  7. Treatment failure in patients with chronic Blastocystis infection.

    PubMed

    Roberts, Tamalee; Ellis, John; Harkness, John; Marriott, Deborah; Stark, Damien

    2014-02-01

    This article reports long-term infection and treatment failure in 18 symptomatic individuals infected with Blastocystis spp. Patients were initially treated with either metronidazole, iodoquinol or triple combination therapy consisting of nitazoxanide, furazolidone and secnidazole. Following treatment, resolution of clinical symptoms did not occur and follow-up testing revealed ongoing infection with the same subtype. Patients then underwent secondary treatment with a variety of antimicrobial agents but remained symptomatic with Blastocystis spp. still present in faeces. Sequencing of the SSU rDNA was completed on all isolates and four subtypes were identified in this group: ST1, ST3, ST4 and ST5. This study highlights the lack of efficacy of several commonly used antimicrobial regimens in the treatment of Blastocystis and the chronic nature of some infections. It also demonstrates the need for further research into treatment options for Blastocystis infection. PMID:24243286

  8. Neurodevelopment and chronic illness: Mechanisms of disease and treatment.

    PubMed

    Armstrong, F Daniel

    2006-01-01

    Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we are now able to observe the natural history of childhood diseases such as sickle cell anemia or HIV, or the consequences of treatment of disease such as leukemia, brain tumors, or kidney disease, we are also able to study a number of biological mechanisms that result in long-term neurocognitive impairment. While some of the neurodevelopmental outcomes can be directly linked to structural damage of the CNS, other systems (e.g., hematologic, immunologic, pulmonary) appear to play crucial indirect roles in the development of the CNS and neurocognitive abilities because of the way that they affect the course of brain development and activity of the brain across time. Important interactions between acute disease factors, biological mechanisms, age at the time of disease or treatment effect, and disruptions in patterns of development after successful treatment or management all provide support for a neurodevelopmental model of childhood chronic illness. Testing this model may make it possible to more accurately predict the timing and degree of severity of long-term neurodevelopmental consequences, provide guidance for improved treatment and prevention, and offer better understanding of neurodevelopmental disruptions that occur in other non-chronic illness related disabilities. PMID:17061286

  9. Chronic hepatitis C: This and the new era of treatment.

    PubMed

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-18

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205

  10. Chronic hepatitis C: This and the new era of treatment

    PubMed Central

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-01

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205

  11. Diagnosis and treatment of pancreatic pseudocysts in chronic pancreatitis.

    PubMed

    Aghdassi, Ali; Mayerle, Julia; Kraft, Matthias; Sielenkämper, Andreas W; Heidecke, Claus-Dieter; Lerch, Markus M

    2008-03-01

    Pancreatic pseudocysts are a well-known complication of acute or chronic pancreatitis, with a higher incidence in the latter. Diagnosis is accomplished most often by computed tomographic scanning, by endoscopic retrograde cholangiopancreatography, or by ultrasound, and a rapid progress in the improvement of diagnostic tools enables detection with high sensitivity and specificity. Different strategies contribute to the treatment of pancreatic pseudocysts: endoscopic transpapillary or transmural drainage, percutaneous catheter drainage, or open surgery. The feasibility of endoscopic drainage is highly dependent on the anatomy and topography of the pseudocyst, but provides high success and low complication rates. Percutaneous drainage is used for infected pseudocysts. However, its usefulness in chronic pancreatitis-associated pseudocysts is questionable. Internal drainage and pseudocyst resection are frequently used as surgical approaches with a good overall outcome, but a somewhat higher morbidity and mortality compared with endoscopic intervention. We therefore conclude that pseudocyst treatment in chronic pancreatitis can be effectively achieved by both endoscopic and surgical means. This review entails publications referring to the classification of pancreatic pseudocysts, epidemiology, diagnostic tools, and therapeutic options for pancreatic pseudocysts. Only full articles were considered for the review. Based on a search in PubMed, the MeSH terms "pancreatic pseudocysts and classification," "diagnosis," and "endoscopic, percutaneous, and surgical treatment" were used either alone or in combination. PMID:18376299

  12. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    PubMed

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy. PMID:24980070

  13. Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

    PubMed

    Kreinin, Anatoly; Miodownik, Chanoch; Mirkin, Vitaly; Gaiduk, Yulia; Yankovsky, Yan; Bersudsky, Yuly; Lerner, Paul P; Bergman, Joseph; Lerner, Vladimir

    2016-06-01

    Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC. PMID:27028980

  14. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy with methotrexate

    PubMed Central

    Fialho, D; Chan, Y‐C; Allen, D C; Reilly, M M; Hughes, R A C

    2006-01-01

    We discovered many reports of other immunosuppressive drugs being used in adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but none of methotrexate. As weekly low dose oral methotrexate is safe, effective, and well tolerated in other diseases, we treated 10 patients with otherwise treatment resistant CIDP. Seven showed improvement in strength by at least two points on the MRC sum score and three worsened. Only two showed an improvement in disability and both were also receiving corticosteroids. We discuss the difficulty of detecting an improvement in treatment resistant CIDP and propose methotrexate as a suitable agent for testing in a randomised trial. PMID:16543541

  15. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins

    PubMed Central

    Schaefer, Sara M.; Gottschalk, Christopher H.; Jabbari, Bahman

    2015-01-01

    Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques. PMID:26184313

  16. Antibiotic treatment and resistance in chronic wounds of vascular origin

    PubMed Central

    TZANEVA, VALENTINA; MLADENOVA, IRENA; TODOROVA, GALINA; PETKOV, DIMITAR

    2016-01-01

    Background and aim The problem of antibiotic resistance is worldwide and affects many types of pathogens. This phenomenon has been growing for decades and nowadays we are faced with a wide range of worrisome pathogens that are becoming resistant and many pathogens that may soon be untreatable. The aim of this study was to determine the resistance and antibiotic treatment in chronic wounds of vascular origin. Methods We performed a cross sectional study on a sample of patients with chronic vascular wounds, hospitalized between October 2014 and August 2015, in the Clinic of Vascular Surgery in Trakia Hospital Stara Zagora. The statistical analysis of data was descriptive, considering the p value of ≤0.05, the threshold of statistical significance. Results In the group of 110 patients, the significantly most frequent chronic wound (p<0.001) was peripheral arteriopathy (47.3%, CI95%: 38.19–56.54). Among 159 strains, 30% of patients having multiple etiology, the species most frequently isolated were Staphylococcus aureus, E.coli, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis with a significant predominance (p<0.05) of the Gram negative (55.1%). The spectrum of strains resistance included the Beta-lactams (36.4%, p<0.001), Macrolides (20%), Tetracyclines (9.1%), Aminoglycosides (8.2%) and Fluoroquinolones (4.5%). Conclusions Gram negative microorganisms were the main isolates in patients with vascular chronic wound. Significantly predominant was the resistance to the beta-lactam antibiotics. PMID:27547055

  17. Comparative oxidation of loxapine and clozapine by human neutrophils.

    PubMed

    Jegouzo, A; Gressier, B; Frimat, B; Brunet, C; Dine, T; Luyckx, M; Kouach, M; Cazin, M; Cazin, J C

    1999-01-01

    The clozapine-induced agranulocytosis could be due to the formation of a reactive intermediate formed in polymorphonuclear neutrophils and granulocyte precursors with the myeloperoxidase-hydrogen peroxide system. On the contrary, no case of agranulocytosis has been described for loxapine, an other neuroleptic drug with a very close structural analogy. We have compared the clozapine and loxapine interaction with the oxidative burst and particularly with this enzymatic complex. On the one hand, the assay of the oxidative species demonstrated a different impact for the two neuroleptics. The 50% inhibitory concentration was 92 microM for hydrogen peroxide and 40 microM for hypochlorous acid for loxapine. The loxapine target is located before the myeloperoxidase-hydrogen peroxide system in the oxidative stream, whereas clozapine diverts the chlorination pathway of the enzyme. On the other hand, the in vitro metabolism of drugs by the myeloperoxidase-hydrogen peroxide system has been investigated by mass spectrometry. Loxapine remains inert but clozapine undergoes the oxidation. The glutathione or ascorbate addition in the medium leads to a removal of the oxidation. Glutathione is able to trap the toxic intermediate and could avoid its formation. PMID:10027097

  18. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    PubMed

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment. PMID:26826992

  19. Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic Patients: A Randomized, Two-Period, Crossover Study

    PubMed Central

    Woo, Young Sup; Wang, Hee-Ryung; Yoon, Bo-Hyun; Lee, Sang-Yeol; Lee, Kwang Hun; Seo, Jeong Seok

    2015-01-01

    Objective Clozapine is the treatment of choice for refractory schizophrenia. The aim of this study was to compare the pharmacokinetics of the brand name (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in Korean schizophrenic patients. Methods A prospective, randomized, crossover study was conducted to evaluate the steady-state pharmacokinetic profiles of Clozaril and Clzapine. Schizophrenic patients were randomized to receive either the brand name or generic formulation (100 mg twice daily) for 10 days, followed by the other formulation for 10 days. Plasma samples were collected on the last day of each treatment period. Results Twenty-two of 28 patients (78.6%) completed the study. The mean Cmax,ss values for Clzapine and Clozaril were 524.62 and 551.18 ng/mL, and the mean AUC0-12 values were 4479.90 hr·ng/mL and 4724.56 hr·ng/mL, respectively. The 90% CI values for the natural logarithmically transformed Cmax,ss and AUC0-12 ratios (Clzapine to Clozaril) after a single oral dose (100 mg) were 0.934 (0.849-1.028) and 0.936 (0.869-1.008), respectively. Five patients (20.8%) among 24 patients who took Clzapine reported 11 adverse events and six adverse events were reported by four patients (15.4%) among 26 who took Clozaril; there were no significant differences on physical examination or in vital signs, ECG, and laboratory tests between groups. Conclusion Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril). PMID:26207129

  20. Systematic Review of Multidisciplinary Chronic Pain Treatment Facilities.

    PubMed

    Fashler, Samantha R; Cooper, Lynn K; Oosenbrug, Eric D; Burns, Lindsay C; Razavi, Shima; Goldberg, Lauren; Katz, Joel

    2016-01-01

    This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities. PMID:27445618

  1. Systematic Review of Multidisciplinary Chronic Pain Treatment Facilities

    PubMed Central

    Fashler, Samantha R.; Cooper, Lynn K.; Oosenbrug, Eric D.; Burns, Lindsay C.; Razavi, Shima; Goldberg, Lauren; Katz, Joel

    2016-01-01

    This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities. PMID:27445618

  2. Medium-Level Laser in Chronic Tinnitus Treatment

    PubMed Central

    Dejakum, K.; Piegger, J.; Plewka, C.; Gunkel, A.; Thumfart, W.; Kudaibergenova, S.; Goebel, G.; Kral, F.; Freysinger, W.

    2013-01-01

    The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study. PMID:24294604

  3. The neurobiology, investigation, and treatment of chronic insomnia.

    PubMed

    Riemann, Dieter; Nissen, Christoph; Palagini, Laura; Otte, Andreas; Perlis, Michael L; Spiegelhalder, Kai

    2015-05-01

    Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions. PMID:25895933

  4. Chronic type B aortic dissection: indications and strategies for treatment.

    PubMed

    Rohlffs, F; Tsilimparis, N; Diener, H; Larena-Avellaneda, A; Von Kodolitsch, Y; Wipper, S; Debus, E S; Kölbel, T

    2015-04-01

    Chronic type B aortic dissection is a distinctive condition that needs individual treatment strategies and different considerations than in therapy of acute or subacute type B aortic dissection. The most common indication for treatment of this complex disease is aneurysmal dilatation of the dissected aortic segment. While open repair of the enlarged dissected aorta remains the best option for good-risk patients and patients with connective tissue disorders in high-volume centers with respective expertise, endovascular management of chronic type B aortic dissection with postdissection aneurysms has significantly gained ground in the past years. But the concept of TEVAR with implantation of a tubular stent-graft into the thoracic aorta to seal the proximal entry tear and reroute the blood flow into the true lumen alone, is not associated with satisfactory results. This is mainly due to the sparse remodeling capacity of the aortic tissue compared to earlier stages of the disease as the aortic wall and the dissection membrane are thickened and more rigid. On the other hand, it is restricted by the most limiting factor for endovascular success in chronic type B aortic dissection: persistent false lumen perfusion. This problem also affects patients with residual dissection after surgical repair of a DeBakey type I aortic dissection or dissection after ascending aortic repair for other pathologies. Hence, it is evident that strategies to achieve endovascular false lumen occlusion are of increasing importance and novel techniques have been introduced to solve the problem of persisting false lumen flow. Thus, the evolution of a large variety of techniques to address the false lumen perfusion issue indicates that complicated chronic type B dissection involves a high diversity in clinical presentation and morphology. A large armamentarium of catheter skills as well as critical individualized treatment strategies are required to address the heterogenous morphological disease

  5. Chronic administration of antipsychotics attenuates ongoing and ketamine-induced increases in cortical γ oscillations.

    PubMed

    Anderson, Paul M; Pinault, Didier; O'Brien, Terence J; Jones, Nigel C

    2014-11-01

    Noncompetitive N-methyl-d-aspartate receptor (NMDAr) antagonists can elicit many of the symptoms observed in schizophrenia in healthy humans, and induce a behavioural phenotype in animals relevant to psychosis. These compounds also elevate the power and synchrony of gamma (γ) frequency (30-80 Hz) neural oscillations. Acute doses of antipsychotic medications have been shown to reduce ongoing γ power and to inhibit NMDAr antagonist-mediated psychosis-like behaviour in rodents. This study aimed to investigate how a chronic antipsychotic dosing regimen affects ongoing cortical γ oscillations, and the electrophysiological and behavioural responses induced by the NMDAr antagonist ketamine. Male Wistar rats were chronically treated with haloperidol (0.25 mg/kg/d), clozapine (5 mg/kg/d), LY379268 (0.3 mg/kg/d) or vehicle for 28 d, delivered by subcutaneous (s.c.) osmotic pumps. Weekly electrocorticogram (ECoG) recordings were acquired. On day 26, ketamine (5 mg/kg, s.c.) was administered, and ECoG and locomotor activity were simultaneously measured. These results were compared with data generated previously following acute treatment with these antipsychotics. Sustained and significant decreases in ongoing γ power were observed during chronic administration of haloperidol (64%) or clozapine (43%), but not of LY379268 (2% increase), compared with vehicle. Acute ketamine injection concurrently increased γ power and locomotor activity in vehicle-treated rats, and these effects were attenuated in rats chronically treated with all three antipsychotics. The ability of haloperidol or clozapine to inhibit ketamine-induced elevation in γ power was not observed following acute administration of these drugs. These results indicate that modulation of γ power may be a useful biomarker of chronic antipsychotic efficacy. PMID:24964190

  6. Cardiac effects of current treatments of chronic obstructive pulmonary disease.

    PubMed

    Lahousse, Lies; Verhamme, Katia M; Stricker, Bruno H; Brusselle, Guy G

    2016-02-01

    We review the cardiac safety of the drugs available at present for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in stable disease, focusing on inhaled long-acting muscarinic antagonists (LAMA) and long-acting β2 agonists (LABA), used either as a monotherapy or as a fixed-dose combination. We report the difficulties of, and pitfalls in, the investigation of the safety of drug treatments in COPD, which is hampered by the so-called COPD trial paradox: on the one hand, COPD is defined as a systemic disease and is frequently associated with comorbidities (especially cardiovascular comorbidities), which have an important effect on the prognosis of individual patients; on the other hand, patients with COPD and cardiovascular or other coexisting illnesses are often excluded from participation in randomised controlled clinical trials. In these trials, inhaled long-acting bronchodilators, both LAMA or LABA, or both, seem to be safe when used in the appropriate dose in adherent patients with COPD without uncontrolled cardiovascular disease or other notable comorbidities. However, the cardiac safety of LAMA and LABA is less evident when used inappropriately (eg, overdosing) or in patients with COPD and substantial cardiovascular disease, prolonged QTc interval, or polypharmacy. Potential warnings about rare cardiac events caused by COPD treatment from meta-analyses and observational studies need to be confirmed in high quality large randomised controlled trials. Finally, we briefly cover the cardiac safety issues of chronic oral drug treatments for COPD, encompassing theophylline, phosphodiesterase inhibitors, and macrolides. PMID:26794033

  7. Metabolic Disturbances, Side Effect Profile and Effectiveness of Clozapine in Adolescents

    PubMed Central

    Grover, Sandeep; Hazari, Nandita; Chakrabarti, Subho; Avasthi, Ajit

    2016-01-01

    Introduction: Data on effect of clozapine on metabolic syndrome in adolescent patients with psychosis are limited. This study aimed to evaluate the prevalence and incidence of metabolic syndrome in children and adolescents with psychotic disorders prior to clozapine and while receiving clozapine. Secondary aims were to study the effectiveness and side effect profile of clozapine. Materials and Methods: Thirteen child and adolescent patients were evaluated at baseline, 3 months, and a follow-up beyond 6 months. Assessments were made for metabolic profile, effectiveness by positive and negative syndrome scale (PANSS), and side effects. Results: Prior to starting of clozapine, the prevalence of metabolic syndrome was 23%. After 3 months on clozapine, 38.5% (5/13) patients fulfilled criteria of metabolic syndrome and further on follow-up beyond 6 months (with last observation carried forward) 46.2% (6/13) had developed metabolic syndrome. There was a significant reduction in PANSS scores at 3 months and follow-up more so in those who developed metabolic syndrome at 3 months. Among the other side effects, hypersalivation was the most common side effect (100%) followed by sedation (69%). Conclusion: Half the prevalence of metabolic syndrome in adolescents on clozapine can be attributed to other factors prior to starting of clozapine, and another half can be attributed to clozapine. Clozapine is effective in an adolescent population. PMID:27335518

  8. Individual changes in clozapine levels after smoking cessation: results and a predictive model.

    PubMed

    Meyer, J M

    2001-12-01

    Published reports document 20-40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital-wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml +/- 598.8 ng/ml) occurred upon smoking cessation (p < .034) from a baseline level of 550.2 ng/ml (+/- 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (+/- 105.2 ng/ml) for the remaining cases (p < .001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F = 34.9;p = .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events. PMID:11763003

  9. Psychological Interventions in the Treatment of Chronic Itch.

    PubMed

    Schut, Christina; Mollanazar, Nicholas K; Kupfer, Jörg; Gieler, Uwe; Yosipovitch, Gil

    2016-03-01

    Patients with chronic itch suffer from higher levels of depression and anxiety than their healthy counterparts. Furthermore, psychological factors, such as stress, are known to aggravate itch. The mere act of thinking about itching can induce the sensation. Interventions like habit reversal training and arousal reduction have been shown to have positive effects on itch relief. Yet, there is still limited data on the psychological management to control the itch scratch cycle and a description of methods suitable to address itch. In this review, we describe different psychological interventions shown to be effective in the treatment of chronic itch. We also provide suggestions based on our experience of suitable interventions for patients with different types of itch. PMID:26073701

  10. Repression predicts outcome following multidisciplinary treatment of chronic pain.

    PubMed

    Burns, J W

    2000-01-01

    This study examined whether repression predicts outcome following multidisciplinary treatment for chronic pain and whether links between anxiety and outcome are obscured by repressors. Ninety-three chronic pain patients completed a 4-week pain program. Lifting capacity, walking endurance, depression, pain severity, and activity were measured at pre- and posttreatment. Low-anxious, repressor, high-anxious, and defensive/high-anxious groups were formed from median splits of Anxiety Content (ACS) and Lie scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Significant ACS x Lie interactions were found for lifting capacity, depression, and pain severity changes. Planned comparisons showed that both repressors and high-anxious patients performed poorly on lifting capacity; repressors alone recovered poorly on depression and pain severity. Results imply that repression may interfere with the process and outcome of pain programs. PMID:10711590

  11. Pulmonary endarterectomy for the treatment of chronic thromboembolic pulmonary hypertension.

    PubMed

    Guth, Stefan; Wiedenroth, Christoph B; Kramm, Thorsten; Mayer, Eckhard

    2016-06-01

    Pulmonary endarterectomy is a curative treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). There is a growing body of evidence suggesting that not only patients with CTEPH but also patients with pulmonary arterial obstructions and mean pulmonary artery pressures < 25 mmHg should be offered surgery. In this review, the recent literature regarding pathophysiology, diagnostic methods, decision making by an expert CTEPH team, and surgical techniques will be summarized. Novel alternative treatment options for inoperable CTEPH patients will be discussed, i.e. targeted medical therapy and balloon pulmonary angioplasty. For the future the major task will be to define a clear selection process for the optimal treatment of the individual CTEPH patient. PMID:27070482

  12. [Methylprednisolone pulse in treatment of childhood chronic inflammatory demyelinating polyneuropathy].

    PubMed

    Rafai, M A; Boulaajaj, F Z; Sekkat, Z; El Moutawakkil, B; Slassi, I

    2010-09-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is rare and treatment is based primarily on intravenous immunoglobulins or oral corticosteroids. Boluses of methylprednisolone (MP) are a possible alternative. We report 3 cases of CIDP in children with good outcome after MP pulse therapy. One male (7 years of age) and 2 females (4 and 5 years of age) presented with recurring episodes of functional impotence of both lower limbs and walking impairment, partially reversible without treatment. Clinical and electrophysiological data and the analysis of the cerebrospinal fluid were compatible with CIDP. MP pulses were administered: the total number of pulses varied from 5 to 8, very satisfactory progression on the clinical and electrophysiological pattern was noted, without recurrence in the 3 cases. Childhood CIDP presents clinical, electrophysiological outcome, and prognostic particularities, recurring readily, and the outcome is good. Boluses of MP are an alternative for treatment of these neuropathies in childhood. PMID:20709511

  13. Direct Acting Antivirals for the Treatment of Chronic Viral Hepatitis

    PubMed Central

    Karayiannis, Peter

    2012-01-01

    The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.This paper aims to summarise the current state of play in treatment approaches for chonic viral hepatitis patients and future perspectives. PMID:24278700

  14. [Complex treatment of chronic periodontitis with balneopeloid therapy].

    PubMed

    Leonova, L E; Smelova, L Z; Pavlova, G A; Chernyshova, L E

    2013-01-01

    Complex investigation and treatment has been realized on 127 patients aged from 27 to 45 years with chronic generalized periodontitis. Patients were divided into two groups. In the fist group (68 patients) complex treatment included course of balneopeloid therapy with irrigation of high mineralized natural water (sanatorium "Tumentransgas" chink №1-95, Ugorsk) followed by application of sapropel mud (the Pake lake). The second group (59 patients) received only conventional periodontal treatment. Positive effect of balneopeloid therapy was identified, which was reflected in stabilizations of pathological process in the periodontal tissues in 78% of patients, as well as changes in physical and chemical properties of the oral gluid. Also the number of periodontopahogenic germs of gingival pockets was decreased. PMID:23528399

  15. Treatment compliance in chronic illness: Current situation and future perspectives.

    PubMed

    Conthe, P; Márquez Contreras, E; Aliaga Pérez, A; Barragán García, B; Fernández de Cano Martín, M N; González Jurado, M; Ollero Baturone, M; Pinto, J L

    2014-01-01

    Long-term chronic diseases have a high mortality rate around the world, affecting both genders equally. Despite improvements in the diagnosis and treatment of various health problems, lack of treatment compliance remains an obstacle to improving health and patient quality of life, and it carries a high associated socio-healthcare cost. The objectives of this study were to develop the concept of «therapeutic adherence», which includes both pharmacological compliance as well as non-pharmacological (level of agreement and patient involvement, lifestyle changes, etc.) treatments. The study also aimed to establish the clinical and socio-health impact of non-compliance, the reasons for non-compliance, and methods and strategies to improve compliance. The results of this study support therapeutic adherence as an essential goal of the healthcare system that encompasses all stakeholders involved in patient health. PMID:24816042

  16. Clozapine-associated development of second-onset obsessive compulsive symptoms in schizophrenia: impact of clozapine serum levels and fluvoxamine add-on.

    PubMed

    Gahr, M; Rehbaum, K; Connemann, B J

    2014-05-01

    Among antiserotonergic second generation antipsychotics (SGA), particularly treatment with clozapine (CLZ) is associated with the development of second-onset obsessive compulsive symptoms (OCS) in schizophrenia. However, less is known regarding the factors that increase the individual susceptibility for the development of SGA-associated second-onset OCS in schizophrenia. Here we present the case of a 29-year-old female patient with disorganized schizophrenia who exhibited OCS due to fluvoxamine-induced elevation of CLZ serum levels via inhibition of CYP 1A2 und 2C19. The severity of the observed OCS featured an association with CLZ serum levels. The case illustrates the interaction between fluvoxamine add-on and CLZ serum levels on the development of OCS in schizophrenia and emphasizes the need of regular therapeutic drug monitoring. PMID:24846087

  17. Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex.

    PubMed

    Meshul, C K; Janowsky, A; Casey, D E; Stallbaumer, R K; Taylor, B

    1992-01-01

    Perforated synapses, which contain a discontinuous density along the postsynaptic membrane, can increase or decrease in numbers following various behavioral and biochemical manipulations. We have previously established that 14-day treatment with haloperidol causes an increase in the number of perforated synapses within the caudate nucleus (dorsolateral region) but not the nucleus accumbens (Meshul and Casey 1989). This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time. We have now further examined the effects of haloperidol administration, which is associated with a high incidence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD), and assessed the effects of clozapine, which appears to have a lower potential for inducing EPS and TD. Administration of haloperidol for 2 weeks significantly increased the percentage of perforated synapses in the caudate, but not in the nucleus accumbens or layer VI of medial prefrontal cortex (MPCx). There was an increase in specific [125I]epidepride binding to D-2 receptors in the caudate nucleus and MPCx following haloperidol. Administration of clozapine for 2 weeks did not affect the percentage of perforated synapses in any of the three dopamine (DA)-rich regions that were examined. There was an increase in specific [3H]SCH 23390 binding to D-1 receptors and in specific [125I]epidepride binding to D-2 receptors only within MPCx following clozapine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1531388

  18. Efficacy of Viola odorata in Treatment of Chronic Insomnia

    PubMed Central

    Feyzabadi, Zohre; Jafari, Farhad; Kamali, Seyed Hamid; Ashayeri, Hassan; Badiee Aval, Shapour; Esfahani, Mohammad Mahdi; Sadeghpour, Omid

    2014-01-01

    Background: Insomnia is the most common sleep disorder that reduces quality of life. Objectives: Due to side effects of hypnotic drug and the increasing demand for alternative medicine substitutes, violet oil (VO) was used in this study. VO is a known medication in Iranian traditional medicine that induces sleep in insomniac patients. Patients and Methods: This study was conducted as an experimental pretest-posttest evaluation on VO efficacy in 50 patients with chronic insomnia in Iranian Traditional Medicine Clinic of Mashhad University of Medical Sciences, Mashhad, Iran. Treatment consisted of intranasal drop of VO, two drops containing 66 mg of VO in each nostril nightly before sleeping for one month. All patients were asked to complete an Insomnia Severity Index (ISI) questionnaire before the start of the trial and after one month of treatment. Results: Improvements in sleep and ISI scores were significantly greater in patients after a month receiving VO drop in comparison with before starting treatment (P < 0.05). A few patients reported some complications about VO consumption, most of which were mild and no serious adverse event was encountered. Conclusions: VO can be presented as a safe, well-tolerated, and effective herbal preparation in patients with chronic insomnia. PMID:25763239

  19. New treatments for chronic hepatitis C: an overview for paediatricians.

    PubMed

    Serranti, Daniele; Indolfi, Giuseppe; Resti, Massimo

    2014-11-21

    Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed firstly in adults. In recent years, a number of direct-acting antiviral agents (DAAs) are under development for treatment of chronic hepatitis C virus (HCV) infection. These agents block viral replication inhibiting directly one of the several steps of HCV lifecycle. DAAs are classified into several categories based on their molecular target: HCV NS3/4A protease inhibitors, HCV NS5B polymerase inhibitors and HCV NS5A inhibitors. Other promising compounds are cyclophilin A inhibitors, mi-RNA122 and IFN-λ. Several new drugs associations will be developed in the near future starting from the actual standard of care. IFN-based and IFN-free regimens are being studied in adults. In this constantly evolving scenario new drug regimens targeted and suitable for children would be possible in the next future. Especially for children, it is crucial to identify the right combination of drugs with the highest potency, barrier to resistance and the best safety profile. PMID:25473150

  20. Pharmacology of opioids in the treatment of chronic pain syndromes.

    PubMed

    Vallejo, Ricardo; Barkin, Robert L; Wang, Victor C

    2011-01-01

    The perpetual pursuit of pain elimination has been constant throughout human history and pervades human cultures. In some ways it is as old as medicine itself. Cultures throughout history have practiced the art of pain management through remedies such as oral ingestion of herbs or techniques believed to have special properties. In fact, even Hippocrates wrote about the practice of trepanation, the cutting of holes in the body to release pain. Current therapies for management of pain include the pervasive utilization of opioids, which have an extensive history, spanning centuries. There is general agreement about the appropriateness of opioids for the treatment of acute and cancer pain, but the long-term use of these drugs for treatment of chronic non-malignant pain remains controversial. The pros and cons regarding these issues are beyond the scope of this review. Instead, the purpose of this review will be directed towards the pharmacology of commonly prescribed opioids in the treatment of various chronic pain syndromes. Opium, derived from the Greek word for "juice," is extracted from the latex sap of the opium poppy (Papaverum somniferum). The juice of the poppy is the source of some 20 different alkaloids of opium. These alkaloids of opioids can be divided into 2 chemical classes: phenanthrenes (morphine, codeine, and thebaine) and benzylisoquinolines (agents that do not interact with opioid receptors). PMID:21785485

  1. Treatment Preferences for CAM in Children with Chronic Pain

    PubMed Central

    Meldrum, Marcia; Kim, Su C.; Jacob, Margaret C.; Zeltzer, Lonnie K.

    2007-01-01

    CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years ± 2.4; range = 8–18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80%) were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy), pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities. PMID:17965769

  2. Treatment Preferences for CAM in children with chronic pain.

    PubMed

    Tsao, Jennie C I; Meldrum, Marcia; Kim, Su C; Jacob, Margaret C; Zeltzer, Lonnie K

    2007-09-01

    CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years +/- 2.4; range = 8-18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80%) were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy), pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities. PMID:17965769

  3. Pharmacologic approaches for the treatment of chronic insomnia.

    PubMed

    Neubauer, David N

    2003-01-01

    Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics. PMID:14626538

  4. Chlorpromazine, clozapine and olanzapine inhibit anionic amino acid transport in cultured human fibroblasts.

    PubMed

    Marchesi, C; Dall'Asta, V; Rotoli, B M; Bianchi, M G; Maggini, C; Gazzola, G C; Bussolati, O

    2006-09-01

    We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated by system X(-) (AG) (EAAT transporters) in cultured human fibroblasts. With 30 microM chlorpromazine, transport inhibition is detectable after 3 h of treatment, maximal after 48 h (>60%), and referable to a decrease in V(max). Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X(-) (AG) since transport systems A and y(+) are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines, clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective. Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic patients. PMID:16699818

  5. [Treatment of chronic itch in systemic disease. Current standards].

    PubMed

    Mettang, T; Ständer, S; Kremer, A E

    2015-12-01

    Chronic itch (CI) is a frequent and sometimes tormenting symptom in many skin and systemic diseases. In systemic diseases, it mostly appears on primarily unaffected skin. As a sequelae of intense scratching, secondary skin lesions such as excoriations, scars, and prurigo nodularis may occur. Due to the lack of valid pathogenetic concepts and good clinical trials, the therapy of CI remains mostly symptomatic. In Europe almost all drugs used to treat CI are not approved for this indication. CI is frequent in patients with chronic kidney diseases in advanced stages. Gabapentin and pregabalin, anticonvulsants, and centrally acting calcium channel blockers have been shown to exert a profound effect in CI. Furthermore, UVB phototherapy has been proven to attenuate pruritus in uremic patients. Randomized controlled studies have recently shown that nalfurafine, a κ-opioid receptor agonist, is able to ameliorate itch in patients with uremic itch. In patients suffering from cholestatic itch, the anion exchange resin colestyramine and rifampicin are effective antipruritic drugs. Furthermore, µ-opioid receptor antagonists and sertraline may be used to alleviate CI in hepatic diseases. In refractory cases, naso-biliary drainage or albumin dialysis are effective invasive procedures. For the treatment of chronic itch in hematological diseases no controlled trials have been performed so far. The mainstay in these cases is to treat the underlying disease. PMID:26585238

  6. Endovascular Treatment of Chronic Mesenteric Ischemia: Report of Five Cases

    SciTech Connect

    Nyman, Ulf; Ivancev, Krasnodar; Lindh, Mats; Uher, Petr

    1998-07-15

    Purpose: To evaluate the midterm results of percutaneous transluminal angioplasty (PTA) and stent placement in stenotic and occluded mesenteric arteries in five consecutive patients with chronic mesenteric ischemia. Methods: Five patients with 70%-100% obliterations of all mesenteric vessels resulting in chronic mesenteric ischemia (n= 4) and as a prophylactic measure prior to abdominal aortic aneurysm repair (n= 1) underwent PTA of celiac and/or superior mesenteric artery (SMA) stenoses (n= 2), primary stenting of ostial celiac occlusions (n= 2), and secondary stenting of a SMA occlusion (n= 1; recoil after initial PTA). All patients underwent duplex ultrasonography (US) (n= 3) and/or angiography (n= 5) during a median follow-up of 21 months (range 8-42 months). Results: Clinical success was obtained in all five patients. Asymptomatic significant late restenoses (n3) were successfully treated with repeat PTA (n= 2) and stenting of an SMA occlusion (n= 1; celiac stent restenosis). Recurrent pain in one patient was interpreted as secondary to postsurgical abdominal adhesions. Two puncture-site complications occurred requiring local surgical treatment. Conclusions: Endovascular techniques may be attempted prior to surgery in cases of stenotic or short occlusive lesions in patients with chronic mesenteric ischemia. Surgery may still be preferred in patients with long occlusions and a low operative risk.

  7. Approach to the Treatment of Chronic Metabolic Acidosis in CKD.

    PubMed

    Raphael, Kalani L

    2016-04-01

    Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered. PMID:26776539

  8. Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Gozzini, Antonella; Usala, Emilio; Carella, Angelo M; Rege-Cambrin, Giovanna; Martino, Bruno; Abruzzese, Elisabetta; Albano, Francesco; Stagno, Fabio; Luciano, Luigia; D'Adda, Mariella; Bocchia, Monica; Cavazzini, Francesco; Tiribelli, Mario; Lunghi, Monia; Pia Falcone, Antonietta; Musolino, Caterina; Levato, Luciano; Venturi, Claudia; Soverini, Simona; Cavo, Michele; Alimena, Giuliana; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-06-01

    The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc. PMID:26971721

  9. [A case of chronic myeloid leukemia occurring during treatment for chronic lymphocytic leukemia].

    PubMed

    Hattori, Hideki; Kuwayama, Maki; Kotake, Takeshi; Karasuno, Takahiro

    2011-02-01

    Since the progression of chronic lymphocytic leukemia(CLL)is long and requires lengthy primary disease management, the risk of double primary cancers and secondary cancer due to treatment has become an issue in western countries with a high incidence of CLL. However, the coexistence with chronic myeloid leukemia(CML)is rare even in the West, and no cases have been reported in Japan. At this time, we would like to report a rare case of CML coexisting during the progression of CLL. The patient was a 68-year-old woman. As she had entered the advanced stage of B-cell chronic lymphocytic leukemia(B-CLL), fludarabine, a purine analog agent, was administered. Two years later, a high-granulocyte dominant white blood cell count began to appear. BCR/ABL analysis by FISH was 97. 6%positive, and the chromosomal test was t(9:22)(q34:q11), so CML was diagnosed. Coexistence of CML in CLL can mainly be classified into three types; CML preceding CLL, CLL preceding CML, and simultaneous occurrence, and the most common, as in this case, long progression CLL preceding CML. At this time, we performed a mainly bibliographical consideration according to the main occurrence type, including the possibility of secondary CML due to fludarabine. PMID:21368508

  10. Chronic urticaria: aetiology, management and current and future treatment options.

    PubMed

    Kozel, Martina M A; Sabroe, Ruth A

    2004-01-01

    Chronic urticaria is a common condition that can be very disabling when severe. A cause for chronic idiopathic urticaria (CIU) is only infrequently identified. Potential causes include reactions to food and drugs, infections (rarely) and, apart from an increased incidence of thyroid disease, uncomplicated urticaria is not usually associated with underlying systemic disease or malignancy. About one-third of patients with CIU have circulating functional autoantibodies against the high affinity IgE receptor or against IgE, although it is not known why such antibodies are produced, or how the presence of such antibodies alters the course of the disease or response to treatment. There are only a few publications relating to childhood urticaria, but it is probably similar to the adult form, except that adult urticaria is more common. The diagnosis is based on patient history and it is vital to spend time documenting this in detail. Extensive laboratory tests are not required in the vast majority of patients. Chronic urticaria resolves spontaneously in 30-55% of patients within 5 years, but it can persist for many years. Treatment is aimed firstly at avoiding underlying causative or exacerbating factors. Histamine H1 receptor antagonists remain the mainstay of oral treatment for all forms of urticaria. The newer low-sedating antihistamines desloratadine, fexofenadine, levocetirizine and mizolastine should be tried first. Sedating antihistamines have more adverse effects but are useful if symptoms are causing sleep disturbance. Low-dose dopexin is effective and especially suitable for patients with associated depression. There is controversy as to whether the addition of an histamine H2 receptor antagonist or a leukotriene antagonist is helpful. For CIU, second-line agents include ciclosporin (cyclosporine) [which is effective in approximately 75% of patients], short courses of oral corticosteroids, intravenous immunoglobulins and plasmapheresis, although the last two were

  11. Attrition and adherence in the online treatment of chronic insomnia.

    PubMed

    Hebert, Elizabeth A; Vincent, Norah; Lewycky, Samantha; Walsh, Kaitlyn

    2010-01-01

    This study examined the ability of the Theory of Planned Behavior (TPB; Ajzen, 1985) and the Transtheoretical Model of Behavior Change (TTM; Prochaska & DiClemente, 1983) to explain adherence and attrition in an online treatment program for chronic insomnia. Responses to questionnaire measures of the TPB and TTM were used to predict adherence and dropout over the subsequent 5 weeks of treatment. Results showed that there was a 17% dropout rate and that perceived behavioral control, social support, and intention to complete the program were significantly associated with adherence to sleep hygiene homework. Attrition was predicted only by symptom severity and psychiatric comorbidity. Implications are that these models should be considered to maximize adherence. PMID:20582757

  12. Psychosocial perspectives in the treatment of pediatric chronic pain

    PubMed Central

    2012-01-01

    Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize return to more developmentally appropriate physical, academic and social activities. This article will provide an overview of major psychosocial factors impacting on pediatric pain and disability, propose an explanatory model for conceptualizing the development and maintenance of pain and functional disability in medically difficult-to-explain pain syndromes, and review representative evidence-based cognitive behavioral and systemic treatment approaches for improving functioning in this pediatric population. PMID:22676345

  13. Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

    PubMed Central

    Rohon, Peter; Vondrakova, Jana; Jonasova, Anna; Holzerova, Milena; Jarosova, Marie; Indrak, Karel

    2012-01-01

    Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy. PMID:22937326

  14. Psychosocial perspectives in the treatment of pediatric chronic pain.

    PubMed

    Carter, Bryan D; Threlkeld, Brooke M

    2012-01-01

    Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize return to more developmentally appropriate physical, academic and social activities. This article will provide an overview of major psychosocial factors impacting on pediatric pain and disability, propose an explanatory model for conceptualizing the development and maintenance of pain and functional disability in medically difficult-to-explain pain syndromes, and review representative evidence-based cognitive behavioral and systemic treatment approaches for improving functioning in this pediatric population. PMID:22676345

  15. Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

    PubMed Central

    Corante, Noemí

    2016-01-01

    Abstract Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61–69, 2016.—Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment. PMID:27218284

  16. Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment.

    PubMed

    Villafuerte, Francisco C; Corante, Noemí

    2016-06-01

    Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61-69, 2016.-Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment. PMID:27218284

  17. Percutaneous Endovascular Treatment of Chronic Iliac Artery Occlusion

    SciTech Connect

    Carnevale, F. C. De Blas, Mariano; Merino, Santiago; Egana, Jose M.; Caldas, Jose G.M.P.

    2004-09-15

    Purpose: To evaluate the clinical and radiological long-term results of recanalization of chronic occluded iliac arteries with balloon angioplasty and stent placement.Methods: Sixty-nine occluded iliac arteries (mean length 8.1 cm; range 4-16 cm) in 67 patients were treated by percutaneous transluminal angioplasty and stent placement. Evaluations included clinical assesment according to Fontaine stages, Doppler examinations with ankle-brachial index (ABI) and bilateral lower extremity arteriograms. Wallstent and Cragg vascular stents were inserted for iliac artery recanalization under local anesthesia. Follow-up lasted 1-83 months (mean 29.5 months).Results: Technical success rate was 97.1% (67 of 69). The mean ABI increased from 0.46 to 0.85 within 30 days after treatment and was 0.83 at the most recent follow-up. Mean hospitalization time was 2 days and major complications included arterial thrombosis (3%), arterial rupture (3%) and distal embolization (1%). During follow-up 6% stenosis and 9% thrombosis of the stents were observed. Clinical improvement occurred in 92% of patients. Primary and secondary patency rates were 75% and 95%, respectively.Conclusion: The long-term patency rates and clinical benefits suggest that percutaneous endovascular revascularization with metallic stents is a safe and effective treatment for patients with chronic iliac artery occlusion.

  18. Chronic benzodiazepine treatment decreases spine density in cortical pyramidal neurons.

    PubMed

    Curto, Yasmina; Garcia-Mompo, Clara; Bueno-Fernandez, Clara; Nacher, Juan

    2016-02-01

    The adult brain retains a substantial capacity for synaptic reorganization, which includes a wide range of modifications from molecular to structural plasticity. Previous reports have demonstrated that the structural remodeling of excitatory neurons seems to occur in parallel to changes in GABAergic neurotransmission. The function of neuronal inhibitory networks can be modified through GABAA receptors, which have a binding site for benzodiazepines (BZ). Although BZs are among the most prescribed drugs, is not known whether they modify the structure and connectivity of pyramidal neurons. In the present study we wish to elucidate the impact of a chronic treatment of 21 days with diazepam (2mg/kg, ip), a BZ that acts as an agonist of GABAA receptors, on the structural plasticity of pyramidal neurons in the prefrontal cortex of adult mice. We have examined the density of dendritic spines and the density of axonal en passant boutons in the cingulate cortex. Although no significant changes were observed in their anxiety levels, animals treated with diazepam showed a decrease in the density of spines in the apical dendrites of pyramidal neurons. Most GFP-expressing en passant boutons in the upper layers of the cingulate cortex had an extracortical origin and no changes in their density were detected after diazepam treatment. These results indicate that the chronic potentiation of GABAergic synapses can induce the structural remodeling of postsynaptic elements in pyramidal neurons. PMID:26733301

  19. Clozapine Interaction with Phosphatidyl Inositol 3-Kinase (PI3K)/Insulin Signaling Pathway in Caenorhabditis elegans

    PubMed Central

    Karmacharya, Rakesh; Sliwoski, Gregory R.; Lundy, Miriam Y.; Suckow, Raymond F.; Cohen, Bruce M.; Buttner, Edgar A.

    2012-01-01

    Clozapine has superior and unique effects as an antipsychotic agent, but the mediators of these effects are not known. We studied behavioral and developmental effects of clozapine in Caenorhabditis elegans, as a model system to identify previously undiscovered mechanisms of drug action. Clozapine induced early larval arrest, a phenotype that was also seen with the clozapine metabolite N-desmethyl clozapine but not with any other typical or atypical antipsychotic drug tested. Mutations in the insulin receptor/daf-2 and the phosphatidyl inositol 3-kinase (PI3K)/age-1 suppressed clozapine-induced larval arrest, suggesting that clozapine may activate the insulin signaling pathway. Consistent with this notion, clozapine also increased expression of an age-1::GFP reporter. Activation of the insulin signaling pathway leads to cytoplasmic localization of the fork head transcription factor FOXO/daf-16. Clozapine produced cytoplasmic localization of DAF-16::GFP in arrested L1 larvae, in contrast to stressors such as starvation or high temperature which produce nuclear localization of DAF-16::GFP in arrested L1 larvae. Clozapine also inhibited pharyngeal pumping in C. elegans, an effect that may contribute to but did not explain clozapine-induced larval arrest. Our findings demonstrate a drug-specific interaction between clozapine and the PI3K/insulin signaling pathway in C. elegans. As this pathway is conserved across species, the results may have implications for understanding the unique effects of clozapine in humans. PMID:19322168

  20. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    PubMed Central

    Smolej, Lukáš

    2015-01-01

    Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL) in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS) in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101) is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. PMID:25691812

  1. Antiviral treatment for chronic hepatitis B in renal transplant patients

    PubMed Central

    Ridruejo, Ezequiel

    2015-01-01

    Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population. PMID:25729474

  2. Optimal treatment with boceprevir for chronic HCV infection.

    PubMed

    Maasoumy, Benjamin; Manns, Michael P

    2013-02-01

    There are 160-170 million people with chronic hepatitis C virus (HCV) infection worldwide. The marketing of protease inhibitors (PIs) has been a milestone in the history of HCV therapy. In phase III studies, up to 75% of the patients achieved a sustained virological response (SVR) after triple therapy with pegylated-interferon (PEG-IFN)-α, ribavirin (RBV) and boceprevir (BOC). However, triple regimens are more expensive and associated with drug-drug interactions (DDIs) and more adverse events (AEs). According to results in 'real-world' settings, safety seems to be limited, in particular in patients with advanced liver disease. To optimize efficacy while minimizing AEs as well as costs, the optimal treatment strategy must be determined for BOC. Optimizing treatment is based on patient selection, the most efficient treatment design, management of side effects and the challenge of DDIs. Therapy-associated risks, treatment urgency and chances of SVR must all be considered for patient selection. In addition, certain differences between the two approved PIs may help identify the ideal candidates for each HCV PI. Optimal treatment design is based on the results of phase II and III studies, in which different approaches have been tested including 'lead-in' and response-guided strategies. Treatment regimens and stopping rules recommended by the FDA and EMA should normally be followed. Still, there are some cases in which more personalized strategies may be more promising. Management of side effects is a major challenge and plays a crucial role in ensuring safety and adherence. PMID:23286841

  3. Endovascular Treatment of Chronic Mesenteric Ischemia: Results in 14 Patients

    SciTech Connect

    Chahid, Tamam; Alfidja, Agaicha T.; Biard, Marie; Ravel, Anne; Garcier, Jean Marc; Boyer, L.

    2004-11-15

    We evaluated immediate and long-term results of percutaneous transluminal angioplasty (PTA) and stent placement to treat stenotic and occluded arteries in patients with chronic mesenteric ischemia. Fourteen patients were treated by 3 exclusive celiac artery (CA) PTAs (2 stentings), 3 cases with both Superior Mesenteric Artery (SMA) and CA angioplasties, and 8 exclusive SMA angioplasties (3 stentings). Eleven patients had atheromatous stenoses with one case of an early onset atheroma in an HIV patient with antiphospholipid syndrome. The other etiologies of mesenteric arterial lesions were Takayashu arteritis (2 cases) and a postradiation stenoses (1 case). Technical success was achieved in all cases. Two major complications were observed: one hematoma and one false aneurysm occurring at the brachial puncture site (14.3%). An immediate clinical success was obtained in all patients. During a follow-up of 1-83 months (mean: 29 months), 11 patients were symptom free; 3 patients had recurrent pain; in one patient with inflammatory syndrome, pain relief was obtained with medical treatment; in 2 patients abdominal pain was due to restenosis 36 and 6 months after PTA, respectively. Restenosis was treated by PTA (postirradiation stenosis), and by surgical bypass (atheromatous stenosis). Percutaneous endovascular techniques are safe and accurate. They are an alternative to surgery in patients with chronic mesenteric ischemia due to short and proximal occlusive lesions of SMA and CA.

  4. Regression of chronic posterior leukoencephalopathy after stop of methotrexate treatment.

    PubMed

    Marcon, Gabriella; Giovagnoli, Anna Rita; Mangiapane, Paola; Erbetta, Alessandra; Tagliavini, Fabrizio; Girotti, Floriano

    2009-10-01

    Posterior reversible leukoencephalopathy (PRLE) is a neurological disorder caused by a variety of pathological conditions such as high doses or long-term low-doses of immunosuppressive therapy. PRLE associated with methotrexate (MTX) is well known but it was rarely observed in adult patients submitted to long-term low-dose administration via the oral route. Here we report the case of a patient affected by psoriasis, treated by chronic oral low-dose of MTX, who presented with limb ideomotor apraxia. Magnetic resonance (MRI) of the brain showed, on T2-weighted images, a diffuse hyperintensity involving bilaterally the white matter of the occipital, parietal and frontal lobes. MTX treatment was stopped and, at the 6-month follow-up, the neuropsychological performances was improved. Two years later, the neuropsychological profile was normal and MRI showed a regression of the white matter abnormalities. PMID:19626273

  5. Chronic radiation proctopathy: A practical review of endoscopic treatment

    PubMed Central

    Lenz, Luciano; Rohr, Rachel; Nakao, Frank; Libera, Ermelindo; Ferrari, Angelo

    2016-01-01

    Chronic radiation proctopathy (CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbid-mortality. Endoscopy has a role in the diagnosis, staging and treatment of this disease. Currently available endoscopic modalities are formalin, potassium titanyl phosphate laser, neodymium:yttrium-aluminum-garnet laser, argon laser, bipolar electrocoagulation (BiCAP), heater probe, band ligation, cryotherapy, radiofrequency ablation and argon plasma coagulation (APC). Among these options, APC is the most promising. PMID:26981189

  6. Nutritional support in the treatment of chronic hepatic encephalopathy.

    PubMed

    Milke García, María del Pilar

    2011-06-01

    The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided. PMID:22228881

  7. Chronic radiation proctopathy: A practical review of endoscopic treatment.

    PubMed

    Lenz, Luciano; Rohr, Rachel; Nakao, Frank; Libera, Ermelindo; Ferrari, Angelo

    2016-02-27

    Chronic radiation proctopathy (CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbid-mortality. Endoscopy has a role in the diagnosis, staging and treatment of this disease. Currently available endoscopic modalities are formalin, potassium titanyl phosphate laser, neodymium:yttrium-aluminum-garnet laser, argon laser, bipolar electrocoagulation (BiCAP), heater probe, band ligation, cryotherapy, radiofrequency ablation and argon plasma coagulation (APC). Among these options, APC is the most promising. PMID:26981189

  8. Treatment of chronic kidney diseases with histone deacetylase inhibitors

    PubMed Central

    Liu, Na; Zhuang, Shougang

    2015-01-01

    Histone deacetylases (HDACs) induce deacetylation of both histone and non-histone proteins and play a critical role in the modulation of physiological and pathological gene expression. Pharmacological inhibition of HDAC has been reported to attenuate progression of renal fibrogenesis in obstructed kidney and reduce cyst formation in polycystic kidney disease. HDAC inhibitors (HDACis) are also able to ameliorate renal lesions in diabetes nephropathy, lupus nephritis, aristolochic acid nephropathy, and transplant nephropathy. The beneficial effects of HDACis are associated with their anti-fibrosis, anti-inflammation, and immunosuppressant effects. In this review, we summarize recent advances on the treatment of various chronic kidney diseases with HDACis in pre-clinical models. PMID:25972812

  9. Racial Disparities in Treatment Rates for Chronic Hepatitis C

    PubMed Central

    Vutien, Philip; Hoang, Joseph; Brooks, Louis; Nguyen, Nghia H.; Nguyen, Mindie H.

    2016-01-01

    Abstract Chronic hepatitis C (CHC) disproportionately affects racial minorities in the United States (US). Although prior studies have reported lower treatment rates in Blacks than in Caucasians, the rates of other minorities remain understudied. We aimed to examine antiviral treatment rates by race and to evaluate the effect of other demographic, medical, and psychiatric factors on treatment rates. We performed a population-based study of adult CHC patients identified via ICD-9CM query from OptumInsight's Data Mart from January 2009 to December 2013. Antiviral treatment was defined by pharmaceutical claims for interferon and/or pegylated-interferon. A total of 73,665 insured patients were included: 51,282 Caucasians, 10,493 Blacks, 8679 Hispanics, and 3211 Asians. Caucasians had the highest treatment rate (10.7%) followed by Blacks (8.8%), Hispanics (8.8%), and Asians (7.9%, P < .001). Hispanics had the highest cirrhosis rates compared with Caucasians, Blacks, and Asians (20.7% vs 18.3%, 17.1%, and 14.3%, respectively). Caucasians were the most likely to have a psychiatric comorbidity (20.1%) and Blacks the most likely to have a medical comorbidity (44%). Asians were the least likely to have a psychiatric (6.4%) or medical comorbidity (26.9%). On multivariate analysis, racial minority was a significant predictor of nontreatment with odds ratios of 0.82 [confidence interval (CI): 0.74–0.90] for Blacks, 0.87 (CI: 0.78–0.96) for Hispanics, and 0.73 (CI: 0.62–0.86) for Asians versus Caucasians. Racial minorities had lower treatment rates than Caucasians. Despite fewer medical and psychiatric comorbidities and higher incomes and educational levels, Asians had the lowest treatment rates. Hispanics also had lower treatment rates than Caucasians despite having higher rates of cirrhosis. Future studies should aim to identify underlying racial-related barriers to hepatitis C virus treatment besides socioeconomic status and medical or psychiatric comorbidities

  10. Profile of omalizumab in the treatment of chronic spontaneous urticaria

    PubMed Central

    Labrador-Horrillo, Moises; Ferrer, Marta

    2015-01-01

    Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients’ health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children. PMID:26346472

  11. [Medical treatment of chronic venous disease: evolution or involution?].

    PubMed

    Agus, G B

    2011-06-01

    Chronic venous disease (CVD) is an important clinical condition with substantial epidemiological implications and socio-economic repercussions. In the Western world the consequences of its high prevalence, the costs of diagnosis and therapy, the significant loss of working hours and the repercussions on patients'quality of life are well known. Pharmacotherapy for CVD has greatly developed over the last 40 years and largely used in the symptomatic treatment of CVD together with compression therapy and to make patients more comfortable. The clinical efficacy on the symptoms (feeling of heaviness, pain, paresthesia, heat and burning sensations, night cramps, etc.) has long been confirmed by Level III, IV and V evidence, but there are now Level I and II trials on specific drugs. For the bioflavonoids double-blind, randomised trials have used micronized purified flavonoid fraction; rutosides; escin; anthocyanosides; and synthetic calcium dobesilate. It was therefore surprising some recent difficulties in the use of this important treatment in health national system in Italy. In this up-date we use the method on evidence-based medicine from the medical literature. We have started a governance and economic analysis of the problem in Italy. Particular consideration was given to the evidence set out in review, meta-analysis, guidelines and Consensus Statements in this field. The evidence for pharmacological agents in the treatment of CVD suggests today a wide use in all CEAP classes. PMID:21516076

  12. Effects of chronic buspirone treatment on cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Bergman, Jack

    2013-02-01

    Cocaine abuse and dependence is a major public health problem that continues to challenge medication-based treatment. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on both serotonin and dopamine systems. In recent preclinical studies, acute buspirone treatment reduced cocaine self-administration at doses that did not also decrease food-reinforced behavior in rhesus monkeys (Bergman et al, 2012). The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of cocaine and food. Five adult rhesus monkeys (Macaca mulatta) were trained to self-administer cocaine and food during four 1-h daily sessions under a second-order schedule of reinforcement (FR2 [VR 16:S]). Buspirone (0.32 and 0.56 mg/kg/h) was administered intravenously through one lumen of a double-lumen catheter every 20 min for 23 h each day for 7-10 consecutive days. Each buspirone treatment period was followed by saline control treatment until drug- and food-maintained responding returned to baseline levels. Buspirone significantly reduced responding maintained by cocaine, and shifted the dose-effect curve downwards. Buspirone had minimal effects on food-maintained responding. In cocaine discrimination studies, buspirone (0.1-0.32 mg/kg, IM) did not antagonize the discriminative stimulus and rate-altering effects of cocaine in four of six monkeys. These findings indicate that buspirone selectively attenuates the reinforcing effects of cocaine in a nonhuman primate model of cocaine self-administration, and has variable effects on cocaine discrimination. PMID:23072835

  13. Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: assessing for tolerance and cross-tolerance to clozapine

    PubMed Central

    Chou, Shinnyi; Davis, Collin; Jones, Sean; Li, Ming

    2014-01-01

    Neurotensin is an endogenous neuropeptide closely associated with the mesolimbic dopaminergic system and shown to possess antipsychotic-like effects. In particular, acute neurotensin receptor activation can inhibit conditioned avoidance response (CAR), attenuate phencyclidine (PCP)-induced prepulse inhibition (PPI) disruptions, and reverse PCP-induced hyperlocomotion. However, few studies have examined the long term effects of repeated neurotensin receptor activation and results are inconsistent. Since clinical administration of antipsychotic therapy often requires a prolonged treatment schedule, here we assessed the effects of repeated activation of neurotensin receptors using an NTS1 receptor selective agonist, PD149163, in 3 behavioral tests of antipsychotic activity. We also investigated whether reactivity to the atypical antipsychotic clozapine was altered following prior PD149163 treatment. Using both normal and prenatally immune activated rats generated through maternal immune activation with polyinosinic:polycytidilic acid, we tested PD149163 in CAR, PCP (1.5 mg/kg)-induced PPI disruption, and PCP (3.2 mg/kg)-induced hyperlocomotion. For each paradigm, rats were first repeatedly tested with vehicle or PD149163 (1.0, 4.0, 8.0 mg/kg, sc) along with vehicle or PCP for PPI and hyperlocomotion tests, then challenged with PD149163 after 2 drug-free days. All rats were then challenged with clozapine (5.0 mg/kg, sc). During the repeated test period, PD149163 exhibited antipsychotic-like effects in all three models. On the PD149163 challenge day, prior drug treatment only caused a tolerance effect in CAR. This tolerance in CAR was transferrable to clozapine, as it enhanced clozapine tolerance in the same group of animals. Although no tolerance effect was seen in the PD149163 challenge for the PCP-induced hyperlocomotion test, the clozapine challenge showed increased sensitivity in groups previously exposed to repeated PD149163 treatment. Our findings suggest

  14. Guidelines for the Use of Clozapine in Individuals with Developmental Disabilities

    ERIC Educational Resources Information Center

    Sabaawi, Mohamed; Singh, Nirbhay N.; de Leon, Jose

    2006-01-01

    Clozapine is the most effective antipsychotic medication currently in use, but there has been a paucity of well-controlled research on its efficacy with people with developmental disabilities. We present a set of guidelines to ensure proper utilization of clozapine in individuals with developmental disabilities, because it can offer them…

  15. Treatment of chronic dry eye: focus on cyclosporine

    PubMed Central

    Kymionis, George D; Bouzoukis, Dimitrios I; Diakonis, Vassilios F; Siganos, Charalambos

    2008-01-01

    To review the current treatment of chronic dry eye syndrome, focusing on cyclosporine A (CsA), a systematic literature search was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the use of CsA in dry eye. A manual literature search was also undertaken based on citations in the published articles. The knowledge on the pathogenesis of dry eye syndrome has changed dramatically during the last few years. Inflammation and the interruption of the inflammatory cascade seem to be the main focus of the ophthalmologic community in the treatment of dry eye, giving the anti-inflammatory therapy a new critical role. The infiltration of T-cells in the conjuctiva tissue and the presence of cytokines and proteasis in the tear fluid were the main reason introducing the use of immunomodulator agents such as corticosteroids, cyclosporine, and doxycicline in order to treat dry eye syndrome. CsA emulsion is approved by the FDA for the treatment of dry eye, while clinical trials of this agent have demonstrated efficacy and safety of CsA. CsA seems to be a promising treatment against dry eye disease. New agents focused on the inflammatory pathogenesis of this syndrome in combination with CsA may be the future in the quest of treating dry eye. More studies are needed to determine the efficacy, safety, timing, and relative cost/effect of CsA. PMID:19668437

  16. Thalidomide for the treatment of chronic refractory pruritus.

    PubMed

    Sharma, Divya; Kwatra, Shawn G

    2016-02-01

    Pruritus is a common and often times difficult to treat symptom in many dermatologic and systemic diseases. For pruritus with an inflammatory or autoimmune origin, therapies such as topical corticosteroids and antihistamines are often initiated. However, in the case that these and additional systemic therapies are ineffective, thalidomide, an immunomodulator and neuromodulator, may be a useful alternative treatment. Considerable relief of chronic pruritus has been demonstrated with thalidomide in case reports, case series, and controlled trials. Double-blind controlled studies demonstrated thalidomide's efficacy as an antipruritic agent in patients with uremic pruritus, primary biliary cirrhosis, and prurigo nodularis. In case reports, case series, and open-label trials, thalidomide significantly reduced pruritus associated with conditions such as actinic prurigo and paraneoplastic pruritus. Because of variations in study design and evaluation of antipruritic effect, it is difficult to fully understand thalidomide's role based on the evidence described to date in the medical literature. In this review, we provide an overview of the reported findings and evaluate thalidomide's utility in managing refractory pruritus in the context of its adverse risk profile. We propose that thalidomide can be an alternative or combination antipruritic treatment for patients who do not obtain enough relief from conservative therapy. PMID:26577510

  17. Fludarabine in the treatment of chronic lymphocytic leukemia: a review

    PubMed Central

    Ricci, Francesca; Tedeschi, Alessandra; Morra, Enrica; Montillo, Marco

    2009-01-01

    Fludarabine (FAMP) is the most effective and most extensively studied purine analog in indolent B-cell malignancies. Its use is indicated for first-and second-line treatment of B-cell chronic lymphocytic leukemia (B-CLL). FAMP as a single agent has produced superior response rates and progression-free survival than standard therapy with chlorambucil and alkylator-based regimen. Efficacy of FAMP may be increased by combining this purine analog with other chemotherapeutic and non-chemotherapeutic agents. FAMP and cyclophosphamide combination (FC) has shown promising results with higher overall response and complete response rates than FAMP in monotherapy, although no difference has been detected in survival. Quality of response and eradication of minimal residual disease (MRD) have been reported to be associated with prolonged survival. Eradication of MRD has been achieved by combining FC with mitoxantrone or monoclonal antibody including alemtuzumab or rituximab or both. FAMP has been widely used in non-myeloablative conditioning regimens, often combined with a variety of other cytotoxic agents, with the aim of inducing enough immunosuppression to allow successful engraftment and to exert some pretransplant anti-tumor activity. The current paper provides an overview of use of FAMP as a single agent or as a cornerstone of different therapeutic strategies for treatment of B-CLL patients. PMID:19436622

  18. Biofeedback treatment of chronic constipation: myths and misconceptions.

    PubMed

    Chiarioni, G

    2016-09-01

    Chronic constipation is a prevalent disorder with considerable impact on healthcare costs and quality of life. Most patients would respond to conservative measures in primary care. Patients with refractory constipation are commonly referred to dedicated centers for appropriate investigations and management. After testing, three main subtypes of constipation are commonly identified: normal colon transit, slow transit, and functional defecation disorders. The etiology of functional defecation disorders is consistent with maladaptive behavior, and biofeedback therapy has been considered a valuable treatment option. Being safe and only marginally invasive, retraining has been historically employed to manage all types of refractory constipation. There are a number of strongly held beliefs about biofeedback therapy that are not evidence-based. The aim of this review was to address these beliefs concerning protocols, efficacy, indications, and safety, with a special focus on the relevance of identifying patients with a functional defecation disorder who are ideal candidates for retraining. Randomized controlled trials support the effectiveness of biofeedback therapy for severe, refractory constipation due to functional defecation disorders. Limitations of the treatment are discussed, but biofeedback remains the safest option to successfully manage this hard-to-treat subtype of constipation. PMID:27450533

  19. Treatment of chronic limb spasticity with botulinum toxin A.

    PubMed Central

    Dunne, J W; Heye, N; Dunne, S L

    1995-01-01

    The purpose of this open study was to find out whether botulinum toxin A (BTX-A) relieves the signs and symptoms of chronic limb spasticity. The study comprised 40 patients, aged 12-82 years, with moderate to severe spasticity of the upper (13) or lower limbs (27) refractory to conventional physical and medical treatments. Outcome measures were clinical and blinded videotape assessments of spasticity and motor function. Electromyography guided BTX-A injections were given in one or two sessions at total doses averaging 175 U in the upper limb (range 70-270 U) and 221 U in the lower limb (range 100-500 U). Thirty four patients (85%) derived worthwhile benefit, with improved limb posture and increased range of passive motion in 31, pain reduction in 28 of 31 with pain, and improved function in 16. Side effects were limited to local and usually mild discomfort from the injections (19), symptomatic local weakness (one), and local infection (one). Preliminary experience indicates that BTX-A is a promising adjunctive treatment for selected patients with spasticity. PMID:7876859

  20. Craniosacral Therapy for the Treatment of Chronic Neck Pain

    PubMed Central

    Lauche, Romy; Cramer, Holger; Rampp, Thomas; Saha, Felix J.; Ostermann, Thomas; Dobos, Gustav

    2016-01-01

    Objectives: With growing evidence for the effectiveness of craniosacral therapy (CST) for pain management, the efficacy of CST remains unclear. This study therefore aimed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients. Materials and Methods: A total of 54 blinded patients were randomized into either 8 weekly units of CST or light-touch sham treatment. Outcomes were assessed before and after treatment (week 8) and again 3 months later (week 20). The primary outcome was the pain intensity on a visual analog scale at week 8; secondary outcomes included pain on movement, pressure pain sensitivity, functional disability, health-related quality of life, well-being, anxiety, depression, stress perception, pain acceptance, body awareness, patients’ global impression of improvement, and safety. Results: In comparison with sham, CST patients reported significant and clinically relevant effects on pain intensity at week 8 (−21 mm group difference; 95% confidence interval, −32.6 to −9.4; P=0.001; d=1.02) and at week 20 (−16.8 mm group difference; 95% confidence interval, −27.5 to −6.1; P=0.003; d=0.88). Minimal clinically important differences in pain intensity at week 20 were reported by 78% within the CST group, whereas 48% even had substantial clinical benefit. Significant between-group differences at week 20 were also found for pain on movement, functional disability, physical quality of life, anxiety and patients’ global improvement. Pressure pain sensitivity and body awareness were significantly improved only at week 8. No serious adverse events were reported. Discussion: CST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and the quality of life up to 3 months after intervention. PMID:26340656

  1. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease

    PubMed Central

    Dubovsky, Jason A.; Flynn, Ryan; Du, Jing; Harrington, Bonnie K.; Zhong, Yiming; Kaffenberger, Benjamin; Yang, Carrie; Towns, William H.; Lehman, Amy; Johnson, Amy J.; Muthusamy, Natarajan; Devine, Steven M.; Jaglowski, Samantha; Serody, Jonathan S.; Murphy, William J.; Munn, David H.; Luznik, Leo; Hill, Geoffrey R.; Wong, Henry K.; MacDonald, Kelli K.P.; Maillard, Ivan; Koreth, John; Elias, Laurence; Cutler, Corey; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Panoskaltsis-Mortari, Angela; Byrd, John C.; Blazar, Bruce R.

    2014-01-01

    Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity. Here, we evaluated whether ibrutinib could reverse established cGVHD in 2 complementary murine models, a model interrogating T cell–driven sclerodermatous cGVHD and an alloantibody-driven multiorgan system cGVHD model that induces bronchiolar obliterans (BO). In the T cell–mediated sclerodermatous cGVHD model, ibrutinib treatment delayed progression, improved survival, and ameliorated clinical and pathological manifestations. In the alloantibody-driven cGVHD model, ibrutinib treatment restored pulmonary function and reduced germinal center reactions and tissue immunoglobulin deposition. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Furthermore, ibrutinib treatment reduced activation of T and B cells from patients with active cGVHD. Our data demonstrate that B cells and T cells drive cGVHD and suggest that ibrutinib has potential as a therapeutic agent, warranting consideration for cGVHD clinical trials. PMID:25271622

  2. Treatment seeking behaviour in southern Chinese elders with chronic orofacial pain: a qualitative study

    PubMed Central

    2014-01-01

    Background Chronic orofacial pain (OFP) is common in general adult populations worldwide. High levels of psychological distress and impaired coping abilities are common among Western people with chronic OFP but limited information was found in southern Chinese people. This study aimed to explore the perceptions and experiences of community dwelling elderly people with chronic OFP symptoms and their treatment seeking behaviour in Hong Kong. Methods An exploratory qualitative interview study was conducted. Elderly people experiencing chronic OFP symptoms were invited to take part in an individual semi-structured interview. A total of 25 semi-structured interviews were performed for 25 participants. Results Pertinent issues relating to the treatment seeking behaviour emerged from the interviews, many of which were inter-related and overlapping. They were organized into three major themes: (i) Impact of chronic OFP on daily life; (ii) Personal knowledge and feeling of chronic OFP; (iii) Management of chronic OFP. The participants were found to have the intention to seek professional treatment, but there were barriers which discouraged them continuing to seek professional treatment. They also received complementary treatment for chronic OFP, such as acupuncture, massage and “chi kung”. Moreover, a wide range self-management techniques were also mentioned. On the other hand, those who did not seek professional treatment for the chronic OFP claimed that they had accepted or adapted to the pain as part of their lives. Conclusions This qualitative study observed that elderly people affected by chronic OFP symptoms in Hong Kong sought many different ways to manage their pain including traditional and complementary approaches. The role of the dentist in dealing with chronic OFP is unclear. Multiple barriers exist to accessing care for chronic OFP. The findings may be used to inform future chronic OFP management strategies in Hong Kong. PMID:24460663

  3. Chronic cough and laryngeal dysfunction improve with specific treatment of cough and paradoxical vocal fold movement

    PubMed Central

    Ryan, Nicole M; Vertigan, Anne E; Gibson, Peter G

    2009-01-01

    Rationale Chronic persistent cough can be associated with laryngeal dysfunction that leads to symptoms such as dysphonia, sensory hyperresponsiveness to capsaicin, and motor dysfunction with paradoxical vocal fold movement and variable extrathoracic airflow obstruction (reduced inspiratory airflow). Successful therapy of chronic persistent cough improves symptoms and sensory hyperresponsiveness. The effects of treatment for chronic cough on laryngeal dysfunction are not known. Objective The aim of this study was to investigate effects of therapy for chronic cough and paradoxical vocal fold movement. Methods Adults with chronic cough (n = 24) were assessed before and after treatment for chronic persistent cough by measuring quality of life, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity and fibreoptic laryngoscopy to observe paradoxical vocal fold movement. Subjects with chronic cough were classified into those with (n = 14) or without (n = 10) paradoxical vocal fold movement based on direct observation at laryngoscopy. Results Following treatment there was a significant improvement in cough related quality of life and cough reflex sensitivity in both groups. Subjects with chronic cough and paradoxical vocal fold movement also had additional improvements in extrathoracic airway hyperresponsiveness and paradoxical vocal fold movement. The degree of improvement in cough reflex sensitivity correlated with the improvement in extrathoracic airway hyperresponsiveness. Conclusion Laryngeal dysfunction is common in chronic persistent cough, where it is manifest as paradoxical vocal fold movement and extrathoracic airway hyperresponsiveness. Successful treatment for chronic persistent cough leads to improvements in these features of laryngeal dysfunction. PMID:19292930

  4. Treatment for Chronic Pain in Patients With Advanced Cancer

    ClinicalTrials.gov

    2010-11-07

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Pain; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  5. A personalized framework for medication treatment management in chronic care.

    PubMed

    Koutkias, Vassilis G; Chouvarda, Ioanna; Triantafyllidis, Andreas; Malousi, Andigoni; Giaglis, Georgios D; Maglaveras, Nicos

    2010-03-01

    The ongoing efforts toward continuity of care and the recent advances in information and communication technologies have led to a number of successful personal health systems for the management of chronic care. These systems are mostly focused on monitoring efficiently the patient's medical status at home. This paper aims at extending home care services delivery by introducing a novel framework for monitoring the patient's condition and safety with respect to the medication treatment administered. For this purpose, considering a body area network (BAN) with advanced sensors and a mobile base unit as the central communication hub from the one side, and the clinical environment from the other side, an architecture was developed, offering monitoring patterns definition for the detection of possible adverse drug events and the assessment of medication response, supported by mechanisms enabling bidirectional communication between the BAN and the clinical site. Particular emphasis was given on communication and information flow aspects that have been addressed by defining/adopting appropriate formal information structures as well as the service-oriented architecture paradigm. The proposed framework is illustrated via an application scenario concerning hypertension management. PMID:20007042

  6. Advances in the treatment of chronic myeloid leukemia.

    PubMed

    Eiring, Anna M; Khorashad, Jamshid S; Morley, Kimberly; Deininger, Michael W

    2011-01-01

    Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML), the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance. PMID:21867560

  7. Catheter venography and endovascular treatment of chronic cerebrospinal venous insufficiency.

    PubMed

    Mandato, Kenneth; Englander, Meridith; Keating, Lawrence; Vachon, Jason; Siskin, Gary P

    2012-06-01

    Multiple sclerosis (MS) is a disorder characterized by damage to the myelin sheath insulation of nerve cells of the brain and spinal cord affecting nerve impulses which can lead to numerous physical and cognitive disabilities. The disease, which affects over 500,000 people in the United States alone, is widely believed to be an autoimmune condition potentially triggered by an antecedant event such as a viral infection, environmental factors, a genetic defect or a combination of each. Chronic cerebrospinal venous insufficiency (CCSVI) is a condition characterized by abnormal venous drainage from the central nervous system that has been theorized to have a possible role in the pathogenesis and symptomatology of MS (1). A significant amount of attention has been given to this theory as a possible explanation for the etiology of symptoms related to MS patients suffering from this disease. The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. The article presented describes endovascular techniques employed to diagnose and treat patients with MS and CCSVI. PMID:22640501

  8. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis

    PubMed Central

    Shelton, Celeste A.; Whitcomb, David C.

    2014-01-01

    Opinion Statement Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants – including a new class of bicarbonate-defective mutations – and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management. PMID:24954874

  9. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis.

    PubMed

    Wilschanski, M; Miller, L L; Shoseyov, D; Blau, H; Rivlin, J; Aviram, M; Cohen, M; Armoni, S; Yaakov, Y; Pugatsch, T; Pugatch, T; Cohen-Cymberknoh, M; Miller, N L; Reha, A; Northcutt, V J; Hirawat, S; Donnelly, K; Elfring, G L; Ajayi, T; Kerem, E

    2011-07-01

    In a subset of patients with cystic fibrosis (CF), nonsense mutations (premature stop codons) disrupt production of full-length, functional CF transmembrane conductance regulator (CFTR). Ataluren (PTC124) allows ribosomal readthrough of premature stop codons in mRNA. We evaluated drug activity and safety in patients with nonsense mutation CF who took ataluren three times daily (morning, midday and evening) for 12 weeks at either a lower dose (4, 4 and 8 mg·kg(-1)) or higher dose (10, 10 and 20 mg·kg(-1)). The study enrolled 19 patients (10 males and nine females aged 19-57 yrs; dose: lower 12, higher seven) with a classic CF phenotype, at least one CFTR nonsense mutation allele, and an abnormal nasal total chloride transport. Both ataluren doses were similarly active, improving total chloride transport with a combined mean change of -5.4 mV (p<0.001), and on-treatment responses (at least -5 mV improvement) and hyperpolarisations (values more electrically negative than -5 mV) in 61% (p<0.001) and 56% (p = 0.002) of patients. CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing. Adverse clinical and laboratory findings were uncommon and usually mild. Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability. PMID:21233271

  10. TRPV1 and TRPM8 in Treatment of Chronic Cough.

    PubMed

    Millqvist, Eva

    2016-01-01

    Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician's awareness. The possibilities of modulating airway transient receptor potential (TRP) ion channels may indicate new ways to treat the persistent cough "without a reason". The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction. PMID:27483288

  11. Hsp90 Inhibitors for the Treatment of Chronic Myeloid Leukemia

    PubMed Central

    Khajapeer, Kalubai Vari; Baskaran, Rajasekaran

    2015-01-01

    Chronic myeloid leukemia (CML) is a hematological malignancy that arises due to reciprocal translocation of 3′ sequences from c-Abelson (ABL) protooncogene of chromosome 9 with 5′ sequence of truncated break point cluster region (BCR) on chromosome 22. BCR-ABL is a functional oncoprotein p210 that exhibits constitutively activated tyrosine kinase causing genomic alteration of hematopoietic stem cells. BCR-ABL specific tyrosine kinase inhibitors (TKIs) successfully block CML progression. However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue. Heat-shock proteins (Hsps) function as molecular chaperones facilitating proper folding of nascent polypeptides. Their increased expression under stressful conditions protects cells by stabilizing unfolded or misfolded peptides. Hsp90 is the major mammalian protein and is required by BCR-ABL for stabilization and maturation. Hsp90 inhibitors destabilize the binding of BCR-ABL protein thus leading to the formation of heteroprotein complex that is eventually degraded by the ubiquitin-proteasome pathway. Results of many novel Hsp90 inhibitors that have entered into various clinical trials are encouraging. The present review targets the current development in the CML treatment by availing Hsp90 specific inhibitors. PMID:26770832

  12. Treatment of horses with chronic diarrhea: immunologic status.

    PubMed

    Targowski, S P

    1976-01-01

    All chronically diarrheal horses given (orally) 2 series of treatments with normal horse serum recovered in 2 to 4 weeks. However, mild diarrhea sometimes persisted several months in the group of horses with severe diarrhea. Weight gains were approximately 35% in horses with severe diarrhea and approximately 10% in horses with mild diarrhea. Serum specimens from 12 diarrheal and 20 normal horses were examined for immunoglobulins by single radial immunodiffusion technique. Concentration of immunoglobulin A in serum of diarrheal horses was approximately 50% lower than that in serum of normal horses. By contrast, there was more immunoglobulin G in serum of diarrheal horses than in serum of normal horses. Phytohemagglutinin (PHA-M) responsiveness of blood lymphocytes showed transient suppression during the stage of severe diarrhea. The regaining of PHA-M responsiveness of lymphocytes was observed simultaneously with the recovery process. However, the responsiveness of lymphocytes in recovered horses remained markedly lower than that in normal horses. Allergic reactions in diarrheal and normal horses were studied by observing dermal response to injections of saline extracts from some of the horse feeds. A delayed hypersensitivity reaction to streptokinase-streptodornase and PHA-M was also studied. Allergic reactions to these extracts were not induced in either diarrheal or normal horses; however, inflammatory response to the extracts was approximately 50% greater in normal than in diarrheal horses. Response to intradermal injection of either streptokinase-streptodornase or PHA-M was significantly greater in normal horses than in diarrheal horses. PMID:1247193

  13. Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.

    PubMed

    Alzoubi, Karem H; Mayyas, Fadia A; Khabour, Omar F; Bani Salama, Fatima M; Alhashimi, Farah H; Mhaidat, Nizar M

    2016-07-01

    Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P < 0.05). Use of melatonin prevented memory impairment induced by SD. Furthermore, melatonin normalized SD-induced reduction in the hippocampus activity of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, melatonin enhanced the ratio of reduced to oxidized glutathione GSH/GSSG in sleep-deprived rats (P < 0.05) without affecting thiobarbituric acid reactive substance (TBARS) levels (P > 0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD. PMID:26084441

  14. [Treatment of Chronic Functional Constipation during Pregnancy and Lactation].

    PubMed

    Gharehbaghi, K; Gharehbaghi, D R; Wierrani, F; Sliutz, G

    2016-02-01

    Natural fibres (bulk-forming agents), docusate sodium (stool-softener), mineral oils (lubricant laxatives), macrogol (polyethylene glycol, PEG), sugars and sugar alcohols (osmotic laxatives) and anthraquinones and diphenolic laxatives (stimulant laxatives) seem to be safe medicaments regarding teratogenicity and lactation. The US Food and Drug Administration (FDA) risk categories for these substances taken during pregnancy and lactation are often the result of the lack of studies than of evidence-based information. So risk categories do not help in the decision-making for the right laxative. Alternative solutions such as proposals of the American College of Gastroenterology's Committee on FDA related matters, (ACG-FDA) and the Motherisk Programme try to improve decision-making. For newer compounds such as chloride-channel-activators and procinetics no data regarding safe use in pregnancy and during breast-feeding are available as yet. We suggest the use of macrogol and lactulose as the first-line therapy in treating chronic constipation during pregnancy. Macrogol shows some advantages, such as faster onset of bowel action and fewer flatulences. If this treatment does not work or starts but then stops working, we recommend in the second and third trimenon a second-line treatment with diphenolic laxatives such as bisacodyl and and sodium picosulfate. During pregnancy the decision on the application of these laxatives is largely determined by the side-effects of tenesmus associated with preterm births. During lactation we recommend macrogol (preferable to lactulose due to the lack of data), lactulose, bisacodyl and sodium picosulfate, according to the nature of the conditions. PMID:26866689

  15. Recognizing Family Dynamics in the Treatment of Chronic Fatigue Syndrome

    ERIC Educational Resources Information Center

    Sperry, Len

    2012-01-01

    Chronic fatigue syndrome (CFS) is an increasingly common chronic medical condition that affects not only patients but also their families. Because family dynamics, particularly the family life cycle, can and does influence the disease process, those providing counseling to CFS patients and their families would do well to recognize these dynamics.…

  16. Fatigue in chronic kidney disease: Definition, assessment and treatment.

    PubMed

    Zalai, Dora; Bohra, Miqdad

    2016-01-01

    Chronic fatigue--an overwhelming subjective feeling of mental or physical exhaustion--impacts patients' everyday functioning and quality of life, delays recovery after hemodialysis, and increases mortality. There are a number of factors that may perpetuate clinically significant fatigue among individuals with chronic kidney disease, including sleep disorders, depression, sedentary lifestyle, anemia, and chronic inflammation. Some of these factors (i.e., anemia and inflammation) are in the forefront of clinical attention, whereas the other contributing factors often remain unrecognized. This article provides a pragmatic overview of the definition, assessment, maintaining factors, and management of fatigue in chronic kidney disease. Given that chronic fatigue is a major determinant of patients' quality of life, nurses can bring about a fundamental improvement in patients' well-being if they recognize the most common fatigue-perpetuating factors and facilitate fatigue management interventions. PMID:27215061

  17. Plasma clozapine concentration coefficients of variation in a long-term study.

    PubMed

    Diaz, Francisco J; de Leon, Jose; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2005-01-01

    Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14), 19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9) and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3 vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations. PMID:15560958

  18. Quo Vadis Clozapine? A Bibliometric Study of 45 Years of Research in International Context

    PubMed Central

    López-Muñoz, Francisco; Sanz-Fuentenebro, Javier; Rubio, Gabriel; García-García, Pilar; Álamo, Cecilio

    2015-01-01

    We have carried out a bibliometric study about the international scientific publications on clozapine. We have used the EMBASE and MEDLINE databases, and we applied bibliometric indicators of production, as Price’s Law on the increase of scientific literature. We also calculated the participation index (PI) of the different countries. The bibliometric data have also been correlated with some social and health data from the 12 most productive countries in biomedicine and health sciences. In addition, 5607 original documents dealing with clozapine, published between 1970 and 2013, were downloaded. Our results state non-fulfilment of Price’s Law, with scientific production on clozapine showing linear growth (r = 0.8691, vs. r = 0.8478 after exponential adjustment). Seven of the 12 journals with the highest numbers of publications on clozapine have an Impact Factor > 2. Among the countries generating clozapine research, the most prominent is the USA (PI = 24.32), followed by the UK (PI = 6.27) and Germany (PI = 5.40). The differences among countries on clozapine research are significantly related to economic variables linked to research. The scientific interest in clozapine remains remarkable, although after the application of bibliometric indicators of production, a saturation point is evident in the growth of scientific literature on this topic. PMID:26404263

  19. Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment.

    PubMed

    Ferguson, Sherry A; Law, C Delbert; Sarkar, Sumit

    2015-10-01

    The chronic MPTP+probenecid treatment paradigm has been used to successfully model the neurochemical, neuropathological, and behavioral effects associated with Parkinson's disease. Here, adult male C57Bl/6 mice were injected ip with 25 mg/kg MPTP and 250 mg/kg probenecid (MPTPp) or saline twice weekly for a total of 10 injections. Behavioral assessments included motor coordination, grip strength, spatial learning/memory, locomotor activity, and anhedonia. Those assessments were repeated up to 8 weeks post-treatment. In a subsequent experiment, adult male mice were treated with saline or MPTPp as described above. One-half of each group was allowed access to 1% trehalose in the water bottle. Trehalose intake averaged 1.90-2.34 g/kg. Behavioral assessments included locomotor activity, olfaction, motor coordination, grip strength, and exploratory behavior. Those assessments were repeated 4 weeks post-treatment. The strongest MPTPp effect was hyperactivity as exhibited in the open field. This increased activity was apparent in both experiments and occurred at all time points post-treatment. Assessments of grip strength, water maze performance, olfaction, and exploratory behavior did not indicate MPTPp-related alterations. When the specifications for the motor coordination test were made somewhat easier in the second experiment, there were deficits exhibited by the MPTPp group, the MPTPp+trehalose group and the trehalose group. The addition of trehalose did not alleviate any of the MPTPp-induced behavioral alterations; however, trehalose treatment significantly attenuated the striatal decreases in DA, DOPAC, HVA and 5-HIAA. These results provide a more comprehensive description of the behavioral alterations resulting from the chronic MPTPp treatment regimen and suggest that trehalose at this concentration does not act as a complete neuroprotectant. PMID:26111725

  20. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine

    PubMed Central

    Hudson, M R; Rind, G; O'Brien, T J; Jones, N C

    2016-01-01

    Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg−1), clozapine (5 mg kg−1), olanzapine (5 mg kg−1), LY379268 (3 mg kg−1), NFPS (sarcosine, 1 mg kg−1), d-serine (1800 mg kg−1) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg−1), ketamine (5 mg kg−1) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia. PMID:27093066

  1. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine.

    PubMed

    Hudson, M R; Rind, G; O'Brien, T J; Jones, N C

    2016-01-01

    Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg(-1)), clozapine (5 mg kg(-1)), olanzapine (5 mg kg(-1)), LY379268 (3 mg kg(-1)), NFPS (sarcosine, 1 mg kg(-1)), d-serine (1800 mg kg(-1)) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg(-1)), ketamine (5 mg kg(-1)) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia. PMID:27093066

  2. α-Blockers for the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Update on Current Clinical Evidence

    PubMed Central

    Nickel, J. Curtis; Touma, Naji

    2012-01-01

    The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is multifactorial, making its treatment difficult. Multimodal therapy including α-adrenergic antagonists (α-blockers), anti-inflammatory agents, and other pain treatments may provide optimal management for CP/CPPS. Although α-blockers are the most prescribed drugs for patients with CP/CPPS, not all studies support their efficacy. A recent meta-analysis of small trials suggested that treatment with α-blockers, possibly in combination with antibacterial agents, is efficacious in relieving symptoms. Third-generation α1A blockers (silodosin, tamsulosin) may provide efficacy as well as reduced cardiovascular side effects. Future research should aim to identify potential biomarkers associated with treatment response. PMID:23526487

  3. ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine.

    PubMed

    Jaquenoud Sirot, Eveline; Knezevic, Branka; Morena, Gina Perla; Harenberg, Sabine; Oneda, Beatrice; Crettol, Séverine; Ansermot, Nicolas; Baumann, Pierre; Eap, Chin B

    2009-08-01

    To examine the genetic factors influencing clozapine kinetics in vivo, 75 patients treated with clozapine were genotyped for CYPs and ABCB1 polymorphisms and phenotyped for CYP1A2 and CYP3A activity. CYP1A2 activity and dose-corrected trough steady-state plasma concentrations of clozapine correlated significantly (r = -0.61; P = 1 x 10), with no influence of the CYP1A2*1F genotype (P = 0.38). CYP2C19 poor metabolizers (*2/*2 genotype) had 2.3-fold higher (P = 0.036) clozapine concentrations than the extensive metabolizers (non-*2/*2). In patients comedicated with fluvoxamine, a strong CYP1A2 inhibitor, clozapine and norclozapine concentrations correlate with CYP3A activity (r = 0.44, P = 0.075; r = 0.63, P = 0.007, respectively). Carriers of the ABCB1 3435TT genotype had a 1.6-fold higher clozapine plasma concentrations than noncarriers (P = 0.046). In conclusion, this study has shown for the first time a significant in vivo role of CYP2C19 and the P-gp transporter in the pharmacokinetics of clozapine. CYP1A2 is the main CYP isoform involved in clozapine metabolism, with CYP2C19 contributing moderately, and CYP3A4 contributing only in patients with reduced CYP1A2 activity. In addition, ABCB1, but not CYP2B6, CYP2C9, CYP2D6, CYP3A5, nor CYP3A7 polymorphisms, influence clozapine pharmacokinetics. PMID:19593168

  4. Assessment of treatment response in chronic constipation clinical trials

    PubMed Central

    Ervin, Claire M; Fehnel, Sheri E; Baird, Mollie J; Carson, Robyn T; Johnston, Jeffrey M; Shiff, Steven J; Kurtz, Caroline B; Mangel, Allen W

    2014-01-01

    Background While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients. Aim To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials. Methods Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patient-reported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients. Results All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall. Conclusion Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit. PMID:24940076

  5. Azithromycin buccal patch in treatment of chronic periodontitis

    PubMed Central

    Latif, Sajith Abdul; Vandana, K. L.; Thimmashetty, J.; Dalvi, Priyanka Jairaj

    2016-01-01

    Aim: This study aims to explore the clinical, microbiological, and biochemical impact of azithromycin (AZM) buccal patch in chronic generalized patients as a monotherapy as well as an adjunct to nonsurgical therapy. Materials and Methods: A parallel design was used forty periodontitis patients were randomly allocated into five groups, namely Group 1 scaling root planing (SRP) alone, Group 2 (SRP + AZM patch group), Group 3 (SRP + AZM tablet group), Group 4 (AZM patch monotherapy), and Group 5 (AZM tablet as monotherapy). Plaque index, gingival bleeding index, modified gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and 21 and 90 days. Subgingival pooled plaque sample was collected to assess periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia (Pi) by anaerobic culture method. Tumor necrosis factor alpha (TNF-α) was also evaluated at baseline and 21 days. Periodontal maintenance was performed in Group 1 until 90th day, and clinical parameter was assessed at the end of 90th day. Results: SRP + AZM tablets showed greater reduction in clinical parameters (P < 0.05) AZM as monotherapy did not offer clinical benefits over SRP. Baseline data were compared at the end, i.e., 90th day a significant reduction in plaque scores, gingival bleeding, and PPD was observed however no significant gain in the clinical attachment was observed. Conclusion: The monotherapy resulted in no improvement of periodontal parameters, microbial parameters, and TNF-α level. It is safe to use AZM + SRP as a mode of nonsurgical treatment in periodontitis patients. PMID:27127325

  6. TEV-48125 for the preventive treatment of chronic migraine

    PubMed Central

    Dodick, David W.; Krymchantowski, Abouch V.; VanderPluym, Juliana H.; Tepper, Stewart J.; Aycardi, Ernesto; Loupe, Pippa S.; Ma, Yuju; Goadsby, Peter J.

    2016-01-01

    Objective: To evaluate the onset of efficacy of TEV-48125, a monoclonal antibody against calcitonin gene-related peptide, recently shown to be effective for the preventive treatment of chronic migraine (CM) and high-frequency episodic migraine. Methods: A randomized placebo-controlled study tested once-monthly injections of TEV-48125 675/225 mg or 900 mg vs placebo. Headache information was captured daily using an electronic headache diary. The primary endpoint was change from baseline in the number of headache hours in month 3. Herein, we assess the efficacy of each dose at earlier time points. Results: The sample consisted of 261 patients. For headache hours, the 675/225-mg dose separated from placebo on day 7 and the 900-mg dose separated from placebo after 3 days of therapy (p = 0.048 and p = 0.033, respectively). For both the 675/225-mg and 900-mg doses, the improvement was sustained through the second (p = 0.004 and p < 0.001) and third (p = 0.025 and p < 0.001) weeks of therapy and throughout the study (month 3, p = 0.0386 and p = 0.0057). For change in weekly headache days of at least moderate intensity, both doses were superior to placebo at week 2 (p = 0.031 and p = 0.005). Conclusions: TEV-48125 demonstrated a significant improvement within 1 week of therapy initiation in patients with CM. Classification of evidence: This study provides Class II evidence that for patients with CM, TEV-48125 significantly decreases the number of headache hours within 3 to 7 days of injection. PMID:27281531

  7. Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2015-02-01

    New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy. PMID:25431965

  8. Formulation of budesonide mouthwash for the treatment of oral chronic graft-versus-host disease.

    PubMed

    Van Schandevyl, Guy; Bauters, Tiene

    2016-02-01

    Oral involvement is (very) common in chronic graft-versus-host disease and can cause discomfort and impairment of oral function. Budesonide, a highly potent corticosteroid with low systemic activity, can be used as a topical treatment for oral chronic graft-versus-host disease. We describe the development of a formulation of budesonide and sodium bicarbonate for use as mouthwash in patients with oral chronic graft-versus-host disease. PMID:25411262

  9. Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

    PubMed Central

    Issy, Ana Carolina; Ferreira, Frederico R.; Viveros, Maria-Paz; Del Bel, Elaine A.; Guimarães, Francisco S.

    2015-01-01

    Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were

  10. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... possible stem cell transplant (SCT) early in treatment. Second-line treatment of CLL If the initial treatment ... and combinations listed above may be options as second-line treatments. For many people who have already ...

  11. Obsessive compulsive symptoms in patients with Schizophrenia on Clozapine and with Obsessive Compulsive disorder: a comparison study.

    PubMed

    Doyle, Mairead; Chorcorain, Aoife Ni; Griffith, Eleanor; Trimble, Tim; O'Callaghan, Eadbard

    2014-01-01

    Obsessive compulsive symptoms are commonly reported in those with schizophrenia. Clozapine has previously been reported to induce, aggravate and alleviate these symptoms. It is unclear if these are similar to the symptoms experienced by those with obsessive compulsive disorder. This study describes the obsessive compulsive symptom profile of a population of patients with schizophrenia treated with clozapine (n = 62) and compares this with patients with Obsessive Compulsive Disorder (n = 35). All participants were attending an outpatient community mental health service. The Obsessive Compulsive Inventory (which measures the frequency and associated distress of a range of "behavioural" and "cognitive" symptoms), the Hospital Anxiety and Depression Scale and a demographic questionnaire were completed. In addition the schizophrenia group treated with clozapine completed the Brief Psychiatric Rating Scale. The OCD group reported significantly more symptoms for all OCI subscales compared to the clozapine group. Overall fourteen (22%) of the schizophrenia treated with clozapine group had clinically significant total OCI scores. Two (3%) had documented OCS pre clozapine. De novo OCS was reported in twelve (19%) cases. Nine (11%) had documented OC symptoms pre-clozapine while only two (3%) had symptoms after clozapine was initiated. In terms of OC symptom profile, the clozapine group scored highest on the Doubting scale, a cognitive symptom whereas the OCD group scored highest on Washing, a behavioural symptom. Both groups reported greater distress with cognitive rather than behavioural symptoms. Medication including clozapine dose was not correlated with symptom severity. Anxiety correlated highly with obsessive compulsive symptoms in the Clozapine group but not the OCD group. Within the Clozapine group, Obsessing correlated highly with Unusual Thought Content. Findings suggest that obsessive compulsive symptoms in the Clozapine group may reflect a subtype of 'schizo

  12. Comparing Chronic Pain Treatment Seekers in Primary Care versus Tertiary Care Settings

    PubMed Central

    Fink-Miller, Erin L.; Long, Dustin M.; Gross, Richard T.

    2015-01-01

    Background Patients frequently seek treatment for chronic nonmalignant pain in primary care settings. Compared with physicians who have completed extensive specialization (eg, fellowships) in pain management, primary care physicians receive much less formal training in managing chronic pain. While chronic pain represents a complicated condition in its own right, the recent increase in opioid prescriptions further muddles treatment. It is unknown whether patients with chronic pain seeking treatment in primary care differ from those seeking treatment in tertiary care settings. This study sought to determine whether patients with chronic pain in primary care reported less pain, fewer psychological variables related to pain, and lower risk of medication misuse/abuse compared with those in tertiary care. Methods Data collected from patients with chronic pain in primary care settings and tertiary care settings were analyzed for significant differences using Wilcoxon rank sum tests, Fisher exact tests, and linear regression. A host of variables among populations, including demographics, self-reported pain severity, psychological variables related to pain, and risk for opioid misuse and abuse, were compared. Results Findings suggest that primary care patients with chronic pain were similar to those in tertiary care on a host of indices and reported more severe pain. There were no significant group differences for risk of medication misuse or abuse. Conclusion It seems that primary care physicians care for a complicated group of patients with chronic pain that rivals the complexity of those seen in specialized tertiary care pain management facilities. PMID:25201929

  13. A Unified, Transdiagnostic Treatment for Adolescents with Chronic Pain and Comorbid Anxiety and Depression

    ERIC Educational Resources Information Center

    Allen, Laura B.; Tsao, Jennie C. I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

    2012-01-01

    Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional…

  14. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Braam, W.; Didden, R.; Smits, M.; Curfs, L.

    2008-01-01

    Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

  15. Ultrasound-guided pulsed radiofrequency treatment of the pudendal nerve in chronic pelvic pain.

    PubMed

    Ozkan, D; Akkaya, T; Yildiz, S; Comert, A

    2016-02-01

    Chronic pelvic pain is a condition that can be caused by pudendal neuralgia, interstitial cystitis, piriformis syndrome and neuropathy of the ilioinguinal, iliohypogastric and genitofemoral nerves. Based on three case reports this article discusses the clinical effectiveness of pulsed high-frequency radiofrequency (PRF) treatment applied to the pudendal nerve under ultrasound guidance in medicinally treated patients with chronic pelvic pain. PMID:26811947

  16. Proposal of a model for multidisciplinary treatment program of chronic migraine with medication overuse: preliminary study.

    PubMed

    Grazzi, L; Prunesti, A; Bussone, G

    2015-05-01

    The treatment of patients with chronic migraine associated with medication overuse is challenging in clinical practice; different strategies of treatment have been recently developed, multidisciplinary treatment approaches have been developed in academic headache centers. Education and support of patients are necessary to improve patients' adherence to pharmacological treatments as well as to non-pharmacological therapies. This study reports a clinical experience conducted at our Headache center with a group of female patients, suffering from chronic migraine complicated by medication overuse, treated by a multidisciplinary approach and followed for a period of 1 year after withdrawal. Results confirm the efficacy of a multifaceted treatment to manage this problematic category of patients. PMID:26017536

  17. Comparison of clozapine in nail and hair of psychiatric patients determined with LC-MS/MS.

    PubMed

    Chen, Hang; Xiang, Ping; Sun, Qi-Ran; Shen, Min

    2012-09-01

    As a keratinized material, nail recently has attracting researchers' attention in the pharmaceuticals analysis. There are comparatively limited studies concerning nail's xenobiotic determination and its mechanism. This article reported the development of a sensitive, specific and reproducible LC-MS/MS method, which could be as a foundation of other studies on drug determination in nail. It can also be regarded as the first report on organic drug in mainland China. Sixteen nail samples from volunteers, who were ingested clozapine for more than nine months, are confirmed positive after being analyzed by the method. It is found that contents of clozapine in the patients' nails are above the nanogram level. Besides, a comparative study of clozapine concentration in nails and hair was made, with a result that there exists a correlation between the two materials in terms of clozapine concentration. PMID:23227550

  18. Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study.

    PubMed

    Mattos Júnior, Francisco Moreira; Mattos, Rafael Villanova; Teixeira, Manoel Jacobsen; Siqueira, Silvia Regina Dowgan Tesseroli de; Siqueira, Jose Tadeu Tesseroli de

    2015-07-01

    The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001) and in its intensity (p < 0.001). Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics. PMID:26200051

  19. Treatment of Chronic Idiopathic Onychodystrophy with Intake of Carotene-rich Food

    PubMed Central

    Jung, Jin Young; Roh, Mi Ryung

    2008-01-01

    Background Onychodystrophy refers to the various abnormalities in nail morphology due to changes in the attachment of the nail plate, changes in nail surface or color. The treatment principle of onychodystrophy largely relies on the discovery and verification of the cause. However, preventive treatment methods offer little help to the patient due to poor compliance, and the effect of corticosteroid is only temporary. Objective To evaluate the clinical efficacy of carotene-rich food intake in chronic idiopathic onychodystrophy. Methods Ten patients with chronic idiopathic onychodystrophy were recommended to drink one or two cups of carrot juice daily. Results Patients showed improvement of onychodystrophy after drinking carrot juice twice a day for at least 4 weeks. No specific adverse effects were noted. Conclusion Since there are no reliable treatment methods for chronic idiopathic onychodystrophy, we suggest a simple and compliant treatment method consisting of taking carotene-rich food, such as carrot juice, for patients with chronic idiopathic onychodystrophy. PMID:27303149

  20. Chronic Urticaria: Indian Context—Challenges and Treatment Options

    PubMed Central

    Khan, Sujoy; Maitra, Anirban; Hissaria, Pravin; Roy, Sitesh; Padukudru Anand, Mahesh; Nag, Nalin; Singh, Harpal

    2013-01-01

    Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal) is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management. PMID:24223585

  1. Refractory chronic cough: new perspectives in diagnosis and treatment.

    PubMed

    Pacheco, Adalberto; Cobeta, Ignacio; Wagner, Carolin

    2013-04-01

    In patients with chronic cough, nearly 40% of the population does not experience definitive improvement of their cough despite correctly applying the anatomic diagnosis. In many of these patients with refractory cough, laryngeal symptoms are frequent. The region of the larynx/pharynx is configured as a bridge between the esophagus and the upper and lower respiratory tract. The association of reflux in patients with chronic cough and symptoms such as globus pharyngis, itchiness or the need to clear one's throat have recently been given attention due to the possibility of joint therapeutic intervention of the gastroesophageal reflux and larynx, both with new medications as well as with laryngeal rehabilitation therapies, with observed benefits in the disappearance of chronic cough in cases that had been previously labeled as refractory. PMID:23165122

  2. Comparison of Operant Behavioral and Cognitive-Behavioral Group Treatment for Chronic Low Back Pain.

    ERIC Educational Resources Information Center

    Turner, Judith A.; Clancy, Steve

    1988-01-01

    Assigned chronic low back pain patients to operant behavioral (OB) treatment, cognitive-behavioral (CB) treatment, or waiting-list (WL) condition. Both treatments resulted in decreased physical and psychosocial disability. OB patients' greater improvement leveled off at followup; CB patients continued to improve over the 12 months following…

  3. The classic: Chapter XVIII. Operative treatment in chronic articular ostitis. 1884.

    PubMed

    Gibney, Virgil P

    2010-02-01

    This Classic article is a reprint of the original work by Virgil P. Gibney, Chapter XVIII. Operative Treatment in Chronic Articular Ostitis. An accompanying biographical sketch of Virgil P. Gibney, MD, is available at DOI 10.1007/s11999-009-1166-2 . The Classic Article is (c)1884 and is abridged from Gibney VP. Operative treatment in chronic articular ostitis. In: The Hip and Its Diseases. New York, NY, London, UK: Bermingham & Co; 1884:388-402. PMID:19936860

  4. Bacterial flora as a cause or treatment of chronic diarrhea.

    PubMed

    Scaldaferri, Franco; Pizzoferrato, Marco; Pecere, Silvia; Forte, Fabrizio; Gasbarrini, Antonio

    2012-09-01

    Intestinal microflora can be considered an organ of the body. It has several functions in the human gut, mostly metabolic and immunologic, and constantly interacts with the intestinal mucosa in a delicate equilibrium. Chronic diarrhea is associated with an alteration of gut microbiota when a pathogen invades the gut and also in several conditions associated with intestinal mucosal damage or bowel dysfunction, as in inflammatory bowel disease, irritable bowel syndrome, or small bowel bacterial overgrowth. This article discusses the basis of gut microbiota modulation. Evidence for the efficacy of gut microbiota modulation in chronic conditions is also discussed. PMID:22917165

  5. The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders

    PubMed Central

    Hayes, Richard D.; Downs, Johnny; Chang, Chin-Kuo; Jackson, Richard G.; Shetty, Hitesh; Broadbent, Matthew; Hotopf, Matthew; Stewart, Robert

    2015-01-01

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007–2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2–0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes. PMID:25154620

  6. Regular treatment with salmeterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Cates, Matthew J

    2014-01-01

    Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular salmeterol versus placebo or regular short-acting beta2-agonists. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and FDA submissions in relation to salmeterol. The date of the most recent search was August 2011. Selection criteria We included controlled parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular salmeterol and were of at least 12 weeks’ duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second checked them. We sought unpublished data on mortality and serious adverse events. Main results The review includes 26 trials comparing salmeterol to placebo and eight trials comparing with salbutamol. These included 62,815 participants with asthma (including 2,599 children). In six trials (2,766 patients), no serious adverse event data could be obtained. All-cause mortality was higher with regular salmeterol than placebo but the increase was not significant (Peto odds ratio (OR) 1.33 (95% CI 0.85 to 2.08)). Non-fatal serious adverse events were significantly increased when regular salmeterol was compared with placebo (OR 1.15 95% CI 1.02 to 1.29). One extra serious adverse event occurred over 28 weeks for every 188 people

  7. Regular treatment with formoterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Cates, Matthew J

    2014-01-01

    Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol versus placebo or regular short-acting beta2-agonists. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was January 2012. Selection criteria We included controlled, parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular formoterol and were of at least 12 weeks’ duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second author checked them. We sought unpublished data on mortality and serious adverse events. Main results The review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline. Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when

  8. [Immunogenetic aspects of pathogenesis, prognosis and treatment of the main forms of chronic pancreatitis].

    PubMed

    Gubergrits, N B; Khodakovskii, A V; Linevskii, I V

    1996-01-01

    Immunogenetic examination comprising determination of erythrocyte antigens (ABO systems and resus-factor) and leukocytes (HLA system) using hemagglutination and compliment-dependent cytotoxicity, respectively, was performed for 138 patients with chronic recurrent pancreatitis, 52 patients with chronic pancreatitis and 456 healthy subjects. Analysis of relations between the above antigens, the disease risk, clinical and laboratory parameters, readings of ultrasound histogram and the efficacy of treatment helped discover not only provoking and protecting genes, but also some pathogenetic mechanisms involved in genetic predisposition. These findings may be used in the choice of treatment policy and to upgrade the significance of prognosis of principal forms of chronic pancreatitis. PMID:8992107

  9. Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life

    PubMed Central

    Maher, Senan; Cunningham, Aoife; O’Callaghan, Niamh; Byrne, Fintan; Mc Donald, Colm; McInerney, Shane; Hallahan, Brian

    2016-01-01

    Objectives: The objective of this study was to evaluate the prevalence and severity of clozapine-induced hypersalivation, and assess the impact hypersalivation has on global functioning. Methods: Participants attending a dedicated clozapine clinic were invited to undertake a structured interview regarding their experiences of clozapine-induced hypersalivation. Two psychometric instruments to measure hypersalivation, the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale were used. Results: Clozapine-induced hypersalivation was experienced by 92% of participants, with nocturnal hypersalivation more prevalent compared to daytime hypersalivation (85% versus 48%). Daytime drooling was severe in 18% of cases and was present on a frequent or constant basis for 20% of individuals. Hypersalivation had at least a moderate impact on the quality of life of 15% of study participants. Conclusions: Clozapine-induced hypersalivation is the most prevalent adverse effect experienced by patients treated with clozapine and negatively impacts on quality of life, particularly if daytime drooling is present. The development of further strategies to ameliorate this adverse effect is required given the demonstrated lack of success to date in managing this condition. PMID:27354906

  10. Chronic Fatigue Syndrome: Searching for the Cause and Treatment.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1989-01-01

    Chronic fatigue syndrome became known nationally in l985 with a pseudoepidemic in a Nevada resort community. Initially and erroneously linked to the Epstein-Barr virus, the cause of this puzzling syndrome and the mind-body connection are areas of controversy and research. (Author/SM)

  11. Chronic treatment with a carbon monoxide releasing molecule reverses dietary induced obesity in mice

    PubMed Central

    Hosick, Peter A; AlAmodi, Abdulhadi A; Hankins, Michael W; Stec, David E

    2016-01-01

    ABSTRACT Chronic, low level treatment with a carbon monoxide releasing molecule (CO-RM), CORM-A1, has been shown to prevent the development of obesity in response to a high fat diet. The objective of this study was to test the hypothesis that chronic, low level treatment with this CO-RM can reverse established obesity via a mechanism independent of food intake. Dietary induced obese mice were treated with CORM-A1, the inactive compound iCORM-A1, or saline every 48 hours for 30 weeks while maintained on a high fat (60%) diet. Chronic treatment with CORM-A1 resulted in a 33% decrease from initial body weight over the 30 week treatment period while treatment with iCORM and saline were associated with 18 and 25% gain in initial body weight over the same time frame. Chronic treatment with CORM-A1 did not affect food intake or activity but resulted in a significant increase in metabolism. CORM-A1 treatment also resulted in lower fasting blood glucose, improvement in insulin sensitivity and decreased heptatic steatosis. Chronic treatment with CO releasing molecules can reverse dietary induced obesity and normalize insulin resistance independent of changes in food intake or activity. These findings are likely though a mechanism which increases metabolism. PMID:27144091

  12. Extrastriatal dopamine D2 receptors: distribution, pharmacological characterization and region-specific regulation by clozapine.

    PubMed

    Janowsky, A; Neve, K A; Kinzie, J M; Taylor, B; de Paulis, T; Belknap, J K

    1992-06-01

    The distribution of dopamine D2 receptors in the rat brain was determined by quantitative autoradiography of the binding of [125I]epidepride and the effects of chronic drug administration on regulation of receptors in striatal and extrastriatal brain regions were characterized. [125I]Epidepride (2200 Ci/mmol) bound with high affinity to coronal tissue sections from the rat brain (Kd = 78 pM), and specific binding was detected in a number of discrete layers, nuclei or regions of the hippocampus, thalamus, cerebellum and other extrastriatal sites. Pharmacological analysis of radioligand binding to hippocampal and cerebellar membranes indicated binding to dopamine D2 receptors, and approximately 10% of the binding appeared to represent low affinity idazoxan-displaceable binding to alpha-2 adrenoceptors. The binding to extrastriatal regions resembled previously reported radioligand binding to dopamine D2 receptors in striatal and cortical membranes. Chronic (14 day) administration of two dopamine D2 receptor antagonists, either the typical neuroleptic haloperidol (1.5 mg/kg i.p.) or the atypical neuroleptic clozapine (30 mg/kg i.p.), caused a significant increase in the density of [125I]epidepride binding sites in the medial prefrontal cortex and parietal cortex. Only haloperidol caused a significant increase in the density of [3H]spiperone and [125I]epidepride binding sites in the striatum and a slight increase in [125I]epidepride binding sites in the hippocampus. Similar administration of amphetamine (5 mg/kg i.p.) had no significant effect on the density of dopamine D2 receptors in any brain region examined. In addition, no drug-induced changes in the characteristics of dopamine D2 receptors in discrete areas of the cerebellum were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1534844

  13. Histamine H1 receptor involvement in prepulse inhibition and memory function: Relevance for the antipsychotic actions of clozapine

    PubMed Central

    Roegge, Cindy S.; Perraut, Charles; Hao, Xin; Levin, Edward D.

    2009-01-01

    Histamine H1 blockade is one of the more prominent actions of the multi-receptor acting antipsychotic clozapine. It is currently not known how much this H1 antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine. The current studies with Sprague-Dawley rats were conducted to determine the participation of histaminergic H1 receptor subtype in sensorimotor plasticity and memory function affected by clozapine using tests of prepulse inhibition (PPI) and radial-arm maze choice accuracy. The PPI impairment caused by the glutamate antagonist dizocilpine (MK-801) was significantly attenuated by clozapine. In the current project, we found that the selective H1 antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse. In the radial-arm maze (RAM), pyrilamine, like clozapine, impaired working memory and caused a significant dose-related slowing of response. Pyrilamine, however, decreased the number of reference memory errors. We have previously shown that nicotine effectively attenuates the clozapine-induced working memory impairment, but in the current study, nicotine did not significantly alter the effects of pyrilamine on the RAM. In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the H1 antagonist pyrilamine, while pyrilamine had a mixed effect on cognition. Pyrilamine impaired working memory but improved reference memory in rats. Thus, H1 antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine. PMID:17382376

  14. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review

    PubMed Central

    Malik, Shahbaz A.; Malik, Sarah; Dowsley, Taylor F.; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus. PMID:26664756

  15. Current treatments for chronic hepatitis B virus infections.

    PubMed

    Zoulim, Fabien; Lebossé, Fanny; Levrero, Massimo

    2016-06-01

    Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) and although a prophylactic vaccine and effective antiviral therapies are available, no cure exists. Curative regimens are urgently needed because up to one million deaths per year are caused by HBV-related liver cancer and end-stage liver disease. HBV is an hepatotropic virus which belongs to the Hepadnaviridae family and replicates its DNA genome via a reverse transcriptase mechanism. Effective therapies have been developed for chronic hepatitis B (CHB) infection in the last two decades. They rely on the use of interferon alpha and its pegylated formulation, and on nucleos(t)ide analogs that inhibit viral polymerase activity. Their results are discussed in this review as well as future perspectives. PMID:27318098

  16. Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.

    PubMed

    Lafosse, Laurent; Baier, Gloria P; Leuzinger, Jan

    2005-08-01

    This article presents an all-arthroscopic technique for coracoclavicular ligament reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint dislocation. A coracoacromial ligament transfer is done to reconstruct the torn coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament is dissected from the undersurface of the acromion and is reinserted on the inferior clavicle by transosseous suture fixation. Additional wire or screw stabilization may be used. With this method, we achieve a very satisfactory reduction of the dislocated acromioclavicular joint. PMID:16086572

  17. Pathophysiology and treatment of inflammatory anorexia in chronic disease.

    PubMed

    Braun, Theodore P; Marks, Daniel L

    2010-12-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been implicated as a uniting pathogenic mechanism of cachexia and associated anorexia. One of the targets of inflammatory mediators is the central nervous system, and in particular feeding centers in the hypothalamus located in the ventral diencephalon. Current research has begun to elucidate the mechanisms by which inflammation reaches the hypothalamus, and the neural substrates underlying inflammatory anorexia. Research into these neural mechanisms has suggested new therapeutic possibilities, which have produced promising results in preclinical and clinical trials. This review will discuss inflammatory signaling in the hypothalamus that mediates anorexia, and the opportunities for therapeutic intervention that these mechanisms present. PMID:21475703

  18. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment.

    PubMed

    Kim, Jun Hyung; Kim, Mi Na; Han, Kwang-Hyub; Kim, Seung Up

    2015-04-01

    Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases (CLD) is crucial, as liver fibrosis is important in determining the prognosis of liver diseases. Currently, liver biopsy (LB) is considered the gold standard for staging liver fibrosis or cirrhosis. However, utilization of LB in clinical practice is often limited because of its invasive nature, sampling error and interobserver variability. Recently, transient elastography (TE) was introduced as a noninvasive, highly reproducible technique for assessing the degree of liver fibrosis. After extensive studies, TE is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in patients with CLD. In the past few years, the role of TE in monitoring liver stiffness and determining prognosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who are undergoing antiviral treatment has been investigated. In patients with CHB, liver stiffness values decrease with antiviral treatment. TE can also be used to predict the incidence of liver-related events during antiviral treatment. In patients with CHC, TE can be used to monitor potential regression of liver fibrosis after antiviral treatment and may predict the treatment outcome of CHC. In addition, TE is an adjunct tool for distinguishing inactive hepatitis B virus carriers from patients with chronic active hepatitis. This review article discusses the important findings from recent studies focusing on the clinical application of TE in patients with chronic viral hepatitis who are undergoing antiviral treatments. PMID:24976523

  19. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

    PubMed

    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

  20. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease

    PubMed Central

    Flowers, Mary E. D.; Sandmaier, Brenda M.; Aki, Sahika Z.; Carpenter, Paul A.; Lee, Stephanie J.; Storer, Barry E.; Martin, Paul J.

    2014-01-01

    This study was designed to characterize failure-free survival (FFS) as a novel end point for clinical trials of chronic graft-versus-host disease (GVHD). The study cohort included 400 consecutive patients who received initial systemic treatment of chronic GVHD at our center. FFS was defined by the absence of second-line treatment, nonrelapse mortality, and recurrent malignancy during initial treatment. The FFS rate was 68% at 6 months and 54% at 12 months after initial treatment. Multivariate analysis identified 4 risk factors associated with treatment failure: time interval <12 months from transplantation to initial treatment, patient age ≥60 years, severe involvement of the gastrointestinal tract, liver, or lungs, and Karnofsky score <80% at initial treatment. Initial steroid doses and the type of initial treatment were not associated with risk of treatment failure. Lower steroid doses after 12 months of initial treatment were associated with long-term success in withdrawing all systemic treatment. FFS offers a potentially useful basis for interpreting results of initial treatment of chronic GVHD. Incorporation of steroid doses at 12 months would increase clinical benefit associated with the end point. Studies using FFS as the primary end point should measure changes in GVHD-related symptoms, activity, damage, and disability as secondary end points. PMID:24876566

  1. Physical exercise as non-pharmacological treatment of chronic pain: Why and when

    PubMed Central

    Ambrose, Kirsten R.; Golightly, Yvonne M.

    2015-01-01

    Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety and sleep disturbance and are treated alone or in combination by pharmacologic and nonpharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training and movement therapies). Physical activity improves general health, disease risk and progression of chronic illnesses such as cardiovascular disease, type-2 diabetes and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly and account for physical limitations, psychosocial needs and available resources. PMID:26267006

  2. Do minimally invasive procedures have a place in the treatment of chronic low back pain?

    PubMed

    Cahana, Alex; Mavrocordatos, Philippe; Geurts, Jos W M; Groen, Gerbrand J

    2004-05-01

    Chronic low back pain is the leading cause of disability in the industrialized world. Medical and surgical treatments remain costly despite limited efficacy. The field of 'interventional pain' has grown enormously and evidence-based practice guidelines are systematically developed. In this article, the vast, complex and contradictory literature regarding the treatment of chronic low back pain is reviewed. Interventional pain literature suggests that there is moderate evidence (small randomized, nonrandomized, single group or matched-case controlled studies) for medial branch neurotomy and limited evidence (nonexperimental one or more center studies) for intradiscal treatments in mechanical low back pain. There is moderate evidence for the use of transforaminal epidural steroid injections, lumbar percutaneous adhesiolysis and spinal endoscopy for painful lumbar radiculopathy, and spinal cord stimulation and intrathecal pumps mostly after spinal surgery. In reality, there is no gold standard for the treatment of chronic low back pain, but these results appear promising. PMID:15853544

  3. Modern wound care - practical aspects of non-interventional topical treatment of patients with chronic wounds.

    PubMed

    Dissemond, Joachim; Augustin, Matthias; Eming, Sabine A; Goerge, Tobias; Horn, Thomas; Karrer, Sigrid; Schumann, Hauke; Stücker, Markus

    2014-07-01

    The treatment of patients with chronic wounds is becoming increasingly complex. It was therefore the aim of the members of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to report on the currently relevant aspects of non-interventional, topical wound treatment for daily practice. -Beside necessary procedures, such as wound cleansing and débridement, we describe commonly used wound dressings, their indications and practical use. Modern antiseptics, which are currently used in wound therapy, usually contain polyhexanide or octenidine. Physical methods, such as negative-pressure treatment, are also interesting options. It is always important to objectify and adequately treat pain symptoms which often affect these patients. Modern moist wound therapy may promote healing, reduce complications, and improve the quality of life in patients with chronic wounds. Together with the improvement of the underlying causes, modern wound therapy is an important aspect in the overall treatment regime for patients with chronic wounds. PMID:24813380

  4. [Current opportunities for treatment of chronic hepatitis C in patients with HIV co-infection].

    PubMed

    Inglot, Małgorzata; Szymczak, Aleksandra; Gasiorowski, Jacek

    2008-01-01

    Liver diseases, mainly chronic viral hepatitis, recently have become the main cause of hospitalization and death in individuals with HIV infection. As HCV infection is predominant condition in this group of patients, treatment of hepatitis C is extremely important in halting hepatic injury. Large clinical trials (APRICOT, RIBAVIC, ACTG 5071) showed satisfactory efficacy and safety of therapy with pegylated interferon alpha and ribavirin. Other trials, searching ways to improve efficacy of chronic hepatitis C treatment in HIV co-infected individuals, are still running. Management possibilities include higher doses of ribavirin and, prolonged course of treatment. The article summarizes current state of knowledge in the field of chronic hepatitis C treatment in HIV/HCV-coinfected individuals. PMID:18807485

  5. Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis

    PubMed Central

    Kamar, Nassim; Lhomme, Sébastien; Abravanel, Florence; Marion, Olivier; Peron, Jean-Marie; Alric, Laurent; Izopet, Jacques

    2016-01-01

    Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. PMID:27537905

  6. Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis.

    PubMed

    Kamar, Nassim; Lhomme, Sébastien; Abravanel, Florence; Marion, Olivier; Peron, Jean-Marie; Alric, Laurent; Izopet, Jacques

    2016-01-01

    Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. PMID:27537905

  7. Familiarizing Students with the Empirically Supported Treatment Approaches for Psychophysiological Disorders and Chronic Pain.

    ERIC Educational Resources Information Center

    Wilkins, Victoria; Chambliss, Catherine

    In training counseling students, it is increasingly important to acquaint them with the clinical research literature exploring the efficacy of particular treatments. This review of empirically supported treatments (EST's) concerning psychophysiological disorders and chronic pain is intended to facilitate the educational process. EST's, or…

  8. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    SciTech Connect

    Clow, D.W.; Hammer, R.P. Jr. )

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  9. Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

    ERIC Educational Resources Information Center

    Hunter, John A.

    2010-01-01

    Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

  10. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    PubMed

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response. PMID:26928522

  11. Treatment of Oppositional Behavior in Children of Parents with Brain Injury and Chronic Pain.

    ERIC Educational Resources Information Center

    Ducharme, Joseph M.; Davidson, Amy; Rushford, Nancy

    2002-01-01

    This case study evaluated effects of errorless compliance training on cooperation of sons of two fathers with brain injury and chronic pain. Following treatment, children displayed high levels of compliance to parent requests as well as generalization and maintenance of treatment gains. Errorless compliance training is recommended to foster…

  12. Chronic Hepatitis C Virus Infection: A Review of Current Direct-Acting Antiviral Treatment Strategies

    PubMed Central

    Zhang, Johnathan; Nguyen, Douglas; Hu, Ke-Qin

    2016-01-01

    Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents. PMID:27293521

  13. Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report

    PubMed Central

    Oneal, Brent J.; Patterson, David R.; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P.

    2009-01-01

    This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

  14. Virtual reality hypnosis in the treatment of chronic neuropathic pain: a case report.

    PubMed

    Oneal, Brent J; Patterson, David R; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P

    2008-10-01

    This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

  15. Chronic facial pain in the female patient: treatment updates.

    PubMed

    Stavropoulos, Franci; Hastie, Barbara A

    2007-05-01

    Over the past decade, gender-related differences in pain and analgesia have been examined in experimental settings with conflicting evidence on whether men and women differ in their response to pain. New advances in research have begun to investigate the influence of genetic factors in moderating sex differences in analgesic response. This article provides oral and maxillofacial surgeons with evidence-based data on the issues of chronic pain between the sexes to suggest alternative approaches to the management of pain in their male and female patients. PMID:18088882

  16. Treatment of chronic radial head dislocations in children.

    PubMed

    Belangero, W D; Livani, B; Zogaib, R K

    2007-04-01

    From 1990 to 2005 our department treated nine patients with chronic radial head dislocation by an ulnar osteotomy and indirect reduction by interosseous membrane. The patients varied in age from 2 years and 8 months to 10 years, and the time from the injury to operation ranged from 40 days to 3 years. The range of functional motion and carrying angle was restored in all nine patients, and no complications, such as recurrent dislocation, infection, or neurovascular injury were observed. This technique has proven to be a successful approach to treating such cases, with a low range of complications and good functional results. PMID:16741732

  17. Treatment of chronic migraine with intramuscular pericranial injections of onabotulinumtoxin a.

    PubMed

    Belvis, Robert; Mas, Natalia

    2014-01-01

    Chronic migraine is the most frequent and disabling complication of migraine. To date, only two drugs have been specifically analysed for the treatment of chronic migraine, topiramate and onabotulinumtoxin A, and in the evidence-based medicine categories, they have achieved level of evidence I and as such, a grade of recommendation A according to current guidelines. Following the PREEMPT paradigm, pericranial intramuscular onabotulinumtoxin A injections show a good efficacy and safety in chronic migraine patients, both in phase III randomized clinical trials and in a pooled data analyses. Onabotulinumtoxin A injections reduce the number of days of headache and migraine, they reduce the consumption of triptans and disability, and improve the quality of life of migraine patients. For these reasons, onabotulinumtoxin type A is an option as valid as topiramate for the treatment of chronic migraine. PMID:25643127

  18. 'You say treatment, I say hard work': treatment burden among people with chronic illness and their carers in Australia.

    PubMed

    Sav, Adem; Kendall, Elizabeth; McMillan, Sara S; Kelly, Fiona; Whitty, Jennifer A; King, Michelle A; Wheeler, Amanda J

    2013-11-01

    The aim of this study was to explore treatment burden among people with a variety of chronic conditions and comorbidities and their unpaid carers. The burden of living with ongoing chronic illness has been well established. However, the burden associated with proactively treating and managing chronic illness, commonly referred to as 'treatment burden', is less understood. This study helps to bridge this gap in our understanding by providing an in-depth analysis of qualitative data collected from a large sample of adults from diverse backgrounds and with various chronic conditions. Using semi-structured in-depth interviews, data were collected with a large sample of 97 participants that included a high representation of people from culturally and linguistically diverse backgrounds and indigenous populations across four regions of Australia. Interviews were conducted during May-October 2012, either face to face (n = 49) or over the telephone (n = 48) depending on the participant's preference and location. Data were analysed using an iterative thematic approach and the constant comparison method. The findings revealed four interrelated components of treatment burden: financial burden, time and travel burden, medication burden and healthcare access burden. However, financial burden was the most problematic component with the cost of treatment being significant for most people. Financial burden had a detrimental impact on a person's use of medication and also exacerbated other types of burden such as access to healthcare services and the time and travel associated with treatment. The four components of treatment burden operated in a cyclical manner and although treatment burden was objective in some ways (number of medications, and time to access treatment), it was also a subjective experience. Overall, this study underscores the urgent need for healthcare professionals to identify patients overwhelmed by their treatment and develop 'individualised' treatment

  19. Simplifying Effective Treatment of Chronic Hives in Children

    MedlinePlus

    American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

  20. Targeting cortical representations in the treatment of chronic pain: a review.

    PubMed

    Moseley, G Lorimer; Flor, Herta

    2012-01-01

    Recent neuroscientific evidence has confirmed the important role of cognitive and behavioral factors in the development and treatment of chronic pain. Neuropathic and musculoskeletal pain are associated with substantial reorganization of the primary somatosensory and motor cortices as well as regions such as the anterior cingulate cortex and insula. What is more, in patients with chronic low back pain and fibromyalgia, the amount of reorganizational change increases with chronicity; in phantom limb pain and other neuropathic pain syndromes, cortical reorganization correlates with the magnitude of pain. These findings have implications for both our understanding of chronic pain and its prevention and treatment. For example, central alterations may be viewed as pain memories that modulate the processing of both noxious and nonnoxious input to the somatosensory system and outputs of the motor and other response systems. The cortical plasticity that is clearly important in chronic pain states also offers potential targets for rehabilitation. The authors review the cortical changes that are associated with chronic pain and the therapeutic approaches that have been shown to normalize representational changes and decrease pain and discuss future directions to train the brain to reduce chronic pain. PMID:22331213

  1. [Chronic insomnia: treatment methods based on the current "3P" model of insomnia].

    PubMed

    Poluektov, M G; Pchelina, P V

    2015-01-01

    Authors consider one of the popular models of the pathogenesis of chronic insomnia--"3P" model. It explains the origin and course of insomnia on the basis of interaction of three factors: predisposing, precipitating and perpetuating. The role of each group of factors and its connection to the cerebral hyperarousal state is discussed. Different variants of cognitive-behavioral therapy and pharmacological treatment of chronic insomnia are described. PMID:26978509

  2. Habit Reversal as a Treatment for Chronic Skin Picking: A Pilot Investigation

    ERIC Educational Resources Information Center

    Teng, Ellen J.; Woods, Douglas W.; Twohig, Michael P.

    2006-01-01

    The purpose of this study was to compare the effectiveness of habit reversal (HR) to a wait-list control as a treatment for chronic skin picking in adults. Twenty-five adults with a chronic skin-picking problem were randomly assigned to a wait-list control or HR group. At pretreatment, posttreatment, and a 3-month follow-up, self-reported skin…

  3. An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

    SciTech Connect

    Pauly, J.R.; Marks, M.J.; Gross, S.D.; Collins, A.C. )

    1991-09-01

    Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the number of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.

  4. Enhancing effects of chronic lithium treatment on detour learning in chicks.

    PubMed

    Zhang, Lei; Chen, Xiaoyun; Feng, Wei; Cui, Yonghua; Xu, Shiqing; Che, Yi

    2012-07-01

    Lithium is the first line of therapeutic drugs used to treat both mania and depression in bipolar disorder.Although a body of research suggests that lithium acts as a cognitive enhancer, other animal studies suggest that lithium induces cognitive deficits. Comparatively, the effects of lithium on cognitive behaviour in these studies are inconsistent and contradictory. Further investigations in different species of animals and behavioural tasks are important to evaluate the possibility that lithium may act as a cognitive enhancer. In the present study, the chicks were treated intraperitoneally with lithium chloride (120 mg/kg), and the effects of chronic lithium treatment on chick cognitive behaviour were examined using a detour learning task.Additionally, the effects of chronic lithium treatment on BDNF messenger RNA (mRNA) expression were measured in RTPCR. We found that chronic lithium treatment(120 mg/kg) had no effect on spontaneous motor activity or weight gain of the chicks and that the chicks had a general healthy appearance, while chronic lithium treatment significantly promoted the response latency of detour learning and BDNF mRNA expression. These results suggest that chronic lithium treatment may improve cognitive function. PMID:22290294

  5. Successful medical treatment of emphysematous pyelonephritis in chronic hemodialysis.

    PubMed

    Vlachopanos, Georgios; Kassimatis, Theodoros; Zerva, Adamantia; Kokkona, Anastasia; Stavroulaki, Eirini; Zacharogiannis, Charilaos; Agrafiotis, Athanasios

    2015-10-01

    Emphysematous pyelonephritis (EPN) is a life-threatening renal infection caused by gas-producing bacteria and fungi. It usually occurs in patients with diabetes and patients with urinary tract obstruction. A combination of systemic antibiotics, percutaneous catheter drainage, or open nephrectomy is typically required to achieve cure. Because of grim prognosis, resorting to interventional methods is frequently inevitable. We report the case of a 77-year-old woman with diabetes and end-stage renal disease on chronic hemodialysis that presented with fever and left flank pain. A bubbly gas pattern inside the left kidney was demonstrated on abdominal computed tomography scan and blood cultures grew Escherichia coli. She was successfully treated solely with systemic antibiotics. This highlights the fact that prompt recognition of imaging findings associated with benign prognosis is essential for a favorable outcome. It allows for an effective management avoiding high-risk interventions, especially in frail patients with multiple comorbidities. Finally, we review all published cases of EPN in chronic dialysis patients. PMID:25643771

  6. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements

    PubMed Central

    Nicolson, Garth L.

    2014-01-01

    Loss of function in mitochondria, the key organelle responsible for cellular energy production, can result in the excess fatigue and other symptoms that are common complaints in almost every chronic disease. At the molecular level, a reduction in mitochondrial function occurs as a result of the following changes: (1) a loss of maintenance of the electrical and chemical transmembrane potential of the inner mitochondrial membrane, (2) alterations in the function of the electron transport chain, or (3) a reduction in the transport of critical metabolites into mitochondria. In turn, these changes result in a reduced efficiency of oxidative phosphorylation and a reduction in production of adenosine-5′-triphosphate (ATP). Several components of this system require routine replacement, and this need can be facilitated with natural supplements. Clinical trials have shown the utility of using oral replacement supplements, such as l-carnitine, alpha-lipoic acid (α-lipoic acid [1,2-dithiolane-3-pentanoic acid]), coenzyme Q10 (CoQ10 [ubiquinone]), reduced nicotinamide adenine dinucleotide (NADH), membrane phospholipids, and other supplements. Combinations of these supplements can reduce significantly the fatigue and other symptoms associated with chronic disease and can naturally restore mitochondrial function, even in long-term patients with intractable fatigue. PMID:26770107

  7. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  8. Neurodevelopment and Chronic Illness: Mechanisms of Disease and Treatment

    ERIC Educational Resources Information Center

    Armstrong, F. Daniel

    2006-01-01

    Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we…

  9. Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats.

    PubMed

    Muller, Alexandre P; Tort, Ana H; Gnoatto, Jussânia; Moreira, Julia D; Vinadé, Elsa R; Perry, Marcos L; Souza, Diogo O; Lara, Diogo R; Portela, Luis V

    2010-10-01

    Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of

  10. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

    PubMed Central

    Kissin, Igor

    2013-01-01

    Background For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present. PMID:23874119

  11. Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models.

    PubMed

    Brinholi, Francis Fregonesi; Farias, Carine Coneglian de; Bonifácio, Kamila Landucci; Higachi, Luciana; Casagrande, Rúbia; Moreira, Estefânia Gastaldello; Barbosa, Décio Sabbatini

    2016-07-01

    Although the etiopathogenic mechanisms of schizophrenia (SCZ) are unknown, evidences suggest that excessive free radical production or oxidative stress may be involved in the pathophysiology of SCZ. Antipsychotics are the drugs used in the treatment of SCZ but it remains controversial the impact that typical vs. atypical antipsychotics has on the oxidative stress status in SCZ patients. In vitro, the antioxidant capacity of six antipsychotics was assessed by their ability to: decrease or scavenge reactive oxygen species in the neutrophil respiratory burst; donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH); and scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS(+)). This study demonstrated that both clozapine and olanzapine have antioxidant effects, in vitro, by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS(+) assay and stabilizing the radical DPPH. Ziprasidone significantly scavenged ABTS(+) and stabilized the radical DPPH whereas risperidone significantly reduced the respiratory burst. Haloperidol and quetiapine lacked antioxidant effects. The chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs on the top of their antipsychotic mechanism of action. PMID:27261620

  12. Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches.

    PubMed

    Cadet, Jean Lud; Bisagno, Veronica

    2015-01-01

    Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users. PMID:26834649

  13. [Opinions on the prevention and treatment of chronic critical illness].

    PubMed

    An, Youzhong

    2016-07-01

    Chronic critical illness (CCI) is an inevitable result of overpopulation and aging, as well as the development of medicine. The number of CCI patients will constantly increase and become an unaffordable economic burden for families, societies and countries. CCI could be prevented by multiple measures. Firstly, doctors must know about the pathophysiology and etiology of the disease. When providing organ function support for CCI patient, we have to know and treat the cause of the disease as early as possible. Secondly, we need to precisely monitor the insults caused by the disease and/or improper host response to the disease, evaluate the organ reserve function, and predict the outcomes and life quality after discharging from hospital. In addition, it is necessary to strengthen the humanity training of health care workers, publicize the correct thanatopsis in the whole society that every life is "born to die", and define the core role of medicine as "to comfort always". PMID:27452750

  14. Treatment of chronic anterior locked glenohumeral dislocation with hemiarthroplasty

    PubMed Central

    Nicolas, Andrea Pujol; Liow, Raymond

    2014-01-01

    Restoring good shoulder function in an active patient with a chronic anterior locked dislocation of the glenohumeral joint can be challenging. This case report describes a 58-year-old active patient who presented with a very late missed locked anterior dislocation of the glenohumeral joint. He had coexisting large bony defects in the anterior glenoid and humeral head with resultant loss of motion and pain secondary to glenohumeral arthrosis. He underwent a humeral hemiarthroplasty, glenoid structural bone grafting, glenoid biological resurfacing and reinforcement of anterior capsule with the graft jacket to achieve a pain-free, stable, mobile joint with good range of movements and function. The clinical decision-making process and the surgical technique used in the management of this difficult condition are discussed.

  15. Treatment of chronic radial head dislocations in children

    PubMed Central

    Belangero, W. D.; Zogaib, R. K.

    2006-01-01

    From 1990 to 2005 our department treated nine patients with chronic radial head dislocation by an ulnar osteotomy and indirect reduction by interosseous membrane. The patients varied in age from 2 years and 8 months to 10 years, and the time from the injury to operation ranged from 40 days to 3 years. The range of functional motion and carrying angle was restored in all nine patients, and no complications, such as recurrent dislocation, infection, or neurovascular injury were observed. This technique has proven to be a successful approach to treating such cases, with a low range of complications and good functional results. PMID:16741732

  16. Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches

    PubMed Central

    Cadet, Jean Lud; Bisagno, Veronica

    2016-01-01

    Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users. PMID:26834649

  17. Effectiveness of an interdisciplinary pain management program for the treatment of chronic pelvic pain.

    PubMed

    Kames, L D; Rapkin, A J; Naliboff, B D; Afifi, S; Ferrer-Brechner, T

    1990-04-01

    Chronic pelvic pain has rarely been discussed in the pain management literature, although it is extremely common in general gynecological practice and often refractory to traditional medical and surgical therapy. A chronic pelvic pain program was developed to offer an alternative treatment approach for women for whom standard gynecological procedures were inappropriate or unsuccessful. Sixteen subjects completed the full 6-8 week interdisciplinary program, which included both somatic and behavioral therapies. Compared to a waiting list control the results showed a dramatic decrease in reported levels of pain following treatment. Anxiety and depression also decreased and psychosocial functioning improved, including return to work, increased social activities, and improved sexual activity. The outcome suggests that the interdisciplinary pain management approach is effective for the treatment of chronic pelvic pain. PMID:2352765

  18. Peripheral nerve stimulation for treatment of chronic headache: a case report.

    PubMed

    Green, Adam; Issa, Mohammed A; Kim, Chong H

    2013-01-01

    Chronic daily headaches can be debilitating. Multiple treatments have been suggested with varying degrees of success. We present a case of a 27-year-old female with greater than ten years of chronic daily headaches. The patient was evaluated at the headache clinic where she was diagnosed with complex migraine with components of occipital neuralgia. Multiple medication regimens were tried without significant benefit. The patient also underwent bilateral occipital blocks along with trigger point injections of various muscles including the semispinalis capitis with significant but limited duration of benefit. After other treatments were unsuccessful, the patient was referred to the Pain Management Center and underwent a trial of peripheral nerve stimulation with significant pain relief without complications. She then proceeded with permanent implantation of the peripheral nerve stimulator with continued pain relief. This case demonstrates the utility of peripheral nerve stimulation for the treatment of refractory chronic daily headaches and should be part of our armamentarium. PMID:24371861

  19. Anhedonia and altered cardiac atrial natriuretic peptide following chronic stressor and endotoxin treatment in mice.

    PubMed

    Wann, Boubacar Pasto; Audet, Marie-Claude; Gibb, Julie; Anisman, Hymie

    2010-02-01

    Chronic stressors and inflammatory immune activation may contribute to pathophysiological alterations associated with both major depression and cardiovascular disease. The present study, conducted in mice, assessed whether a chronic stressor of moderate severity that induced an anhedonic effect, when coupled with a bacterial endotoxin, lipopolysaccharide (LPS), additively or interactively provoked circulating and heart atrial natriuretic peptide (ANP), a potentially useful diagnostic and prognostic tool in cardiac diseases. As well, given the potential role of inflammatory processes in both depression and cardiovascular disease, we assessed pro-inflammatory mRNA expression in heart in response to the stressor and the LPS treatments. Male CD-1 mice that had been exposed to a chronic, variable stressor over 4 weeks displayed reduced sucrose consumption, possibly reflecting the anhedonic effects of the stressor. Treatment with LPS (10mug) provoked increased circulating corticosterone levels in both chronically stressed and non-stressed mice. Moreover, ANP concentrations in plasma and in the left ventricle were increased by both the stressor and the LPS treatments, as were left atrial and ventricular cytokine (interleukin-1beta; tumor necrosis factor-alpha) mRNA expression. Further, these treatments synergistically influenced the rise of plasma ANP. A link may exist between stressor-provoked depressive features (anhedonia) and immune activation, with elevated levels of ANP, a potential marker of cardiovascular disturbance. These findings are consistent with the view that chronic stressors and inflammatory immune activation may represent a common denominator subserving the frequent comorbidity between these illnesses. PMID:19604644

  20. [EFFICACY OF CYCLOFERON LINIMENT IN THE COMBINED TREATMENT OF CHRONIC GINGIVITIS IN PATIENTS WITH CHRONIC INFECTIOUS DISEASES].

    PubMed

    Soboleva, L A; Shul'dyakov, A A; Bulkina, N V

    2015-01-01

    In order to study the clinical-pathogenetic efficacy of using cycloferon liniment in the combined therapy of patients with gingivitis on the background of chronic infectious diseases (HIV infection, hepatitis C, brucellosis), medical examination and treatment of 42 patients with this diagnosis has been carried out. It is established, that the use of cycloferon liniment in the combined therapy decreases the infection load in periodontal recess and manifestation of local inflammation, normalizes the immunity indices, and reduces the level of endogenous intoxication. All these factors provide acceleration of the recuperation processes and decrease the frequency of recidivating. PMID:26591207

  1. 75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ...) (74 FR 40900, August 13, 2009). Under these regulations, a treatment IND, which permits patients... Treatment of Chronic Hepatitis C Infection in Patients With Unmet Medical Need; Public Hearing; Request for... agents (DAAs) for the treatment of chronic hepatitis C (CHC) infection in patients with unmet...

  2. Chronic treatment with antidepressant drugs and the analgesia induced by 5-methoxy-N,N-dimethyltryptamine: attenuation by desipramine.

    PubMed

    Danysz, W; Minor, B G; Post, C; Archer, T

    1986-08-01

    The effect of chronic and acute oral or intraperitoneal treatment with the antidepressant drugs, desipramine, amitriptyline, alaproclate and iprindole, upon pain thresholds in the tail flick, hot plate and shock titration tests of nociception in saline- and 5-MeODMT-treated rats was studied. Chronic desipramine treatment increased the pre-test tail flick latencies. In the saline-treated rats, chronic oral desipramine treatment increased tail flick latencies, whereas chronic oral amitriptyline treatment decreased tail flick latencies. In 5-MeODMT-treated rats, chronic oral desipramine treatment attenuated the effects of 5-MeODMT (1 mg/kg) in all three tests of nociception, whereas chronic amitriptyline caused a potentiation in the tail flick and hot plate tests. Chronic oral iprindole treatment attenuated 5-MeODMT-induced analgesia in the hot plate test. Chronic intraperitoneal desipramine treatment attenuated 5-MeODMT analgesia in the tail flick and shock titration tests. In a different chronic treatment experiment, oral desipramine treatment attenuated 5-MeODMT analgesia in the tail flick test and zimeldine did for both the tail flick and hot plate tests, whereas mianserin potentiated 5-MeODMT-induced analgesia in both the tail flick and hot plate tests. In the saline-treated rats, acute treatment with all four drugs, desipramine, amitriptyline, iprindole and alaproclate, elevated the shock thresholds, whereas in 5-MeODMT-treated rats, desipramine and amitriptyline elevated shock thresholds. Two main conclusions can be drawn: chronic desipramine caused a quite consistent attenuation of 5-MeODMT-induced analgesia and the effects of acute treatment differed strongly from that of the chronic treatment. The effects of chronic administration with these antidepressants were compared with other findings using different measures of behavioural and receptor function. PMID:3776549

  3. Chronic myelogenous leukemia in chronic phase transforming into acute leukemia under treatment with dasatinib 4 months after diagnosis.

    PubMed

    Nakamura, Yukitsugu; Tokita, Katsuya; Nagasawa, Fusako; Takahashi, Wataru; Nakamura, Yuko; Sasaki, Ko; Ichikawa, Motoshi; Mitani, Kinuko

    2016-03-01

    We report a 64-year-old woman morphologically diagnosed with chronic myelogenous leukemia in the chronic phase. Despite having achieved a complete hematological response following treatment with dasatinib, she developed lymphoblastic crisis 4 months later. Blastic cells were in a CD45-negative and SSC-low fraction, and positive for CD10, CD19, CD34, and HLA-DR expression and rearrangement in the immunoglobulin heavy chain gene. Chemotherapy using the HyperCVAD/MA regimen led to a complete cytogenetic response, and after cord blood transplantation, she obtained a complete molecular remission. However, the crisis recurred 6 months later. Another salvage therapy using L-AdVP regimen followed by nilotinib led to a complete molecular remission. Retrospective analyses using flow cytometry and polymerase chain reaction revealed a minimal blastic crisis clone present in the initial marrow in chronic phase. This case is informative as it suggests that sudden blastic crisis may occur from an undetectable blastic clone present at initial diagnosis and that leukemic stem cells may survive cytotoxic chemotherapy that eliminates most of the blastic cells. PMID:26662559

  4. [Treatment of chronic alcoholic pancreatitis with a new acid-resistant pancreatin product].

    PubMed

    Kempelen, I; Szilárd, M

    1995-09-17

    The authors summarised pathophysiology and therapy possibility of the chronic alcoholic pancreatitis. They introduce a new product of pancreatin use for treatment of chronic alcoholic pancreatitis. The aim of this prospective study was to asses the efficacy of this new drug in the treatment of chronic alcoholic pancreatitis. The treatment was carried out by new pancreatin product containing 10,000 FIP U lipase, 9000 FIP U amylase, and 500 FIP E protease. During the study 30 patients--suffering from alcoholic pancreatitis--were treated. They received, two tablets three times daily in a period of two weeks. The following parameters were observed and compared before and after the period of treatment: complaints of the patients, the characteristics of the stool (daily weight, frequency, fat contents, consistency) the change of the body weight and degree of abdominal pain. These parameters were compared using a score-system, before and after the period of treatment. The authors could analyse the data of 21 patients. It was proved that there was a significant decrease in frequency, daily weight and fat contents of the stool and in abdominal pain. There was not significant change in the body weight. The authors concluded that this new product is a good pancreatin preparation which is useful and suitable for effective treatment of chronic alcoholic pancreatitis, if the patient keeps abstinence. PMID:7566938

  5. Lack of extrapyramidal side effects predicts quality of life in outpatients treated with clozapine or with typical antipsychotics.

    PubMed

    Strejilevich, Sergio A; Palatnik, Ana; Avila, Rubén; Bustin, Julián; Cassone, Julieta; Figueroa, Soledad; Gimenez, Mariana; de Erausquin, Gabriel A

    2005-02-28

    We compared symptom severity and quality of life (QOL) in schizophrenic patients adequately treated with typical antipsychotics (TAP) or clozapine (CZP). Groups did not differ in symptom severity or QOL. Clozapine caused fewer extrapyramidal symptoms. Negative and extrapyramidal symptoms predicted QOL. Similar outcome in both groups suggests a common ceiling to antipsychotic efficacy. PMID:15741003

  6. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  7. Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases

    SciTech Connect

    Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.

    1986-07-01

    Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.

  8. EMDR: a new treatment for trauma and chronic pain.

    PubMed

    Grant, M

    2000-05-01

    EMDR (eye movement desensitization and reprocessing) is a new psychological treatment for trauma that is capable of facilitating rapid and permanent reduction in distressing thoughts and feelings (Carlson et al. 1998,Wilson et al. 1995). In addition to reduction of psychological distress, the method leads to more adaptive attitudes and functioning. The utility of the method also appears to extend beyond trauma with positive results reported in the treatment of addictions, phobias, and pain (Henry 1996, Goldstein & Feske 1994, Grant 1986). As a treatment for pain EMDR offers a method of facilitating permanent changes in how pain is experienced somatically and emotionally. Knowledge and understanding of the principles underlying EMDR can also provide a guide for more effective interventions by pain specialists. PMID:10844748

  9. Limits and possibilities experienced by nurses in the treatment of women with chronic venous ulcers.

    PubMed

    Silva, Marcelo Henrique da; Jesus, Maria Cristina Pinto de; Merighi, Miriam Aparecida Barbosa; Oliveira, Deíse Moura de

    2014-08-01

    Objective To understand the experiences and expectations of nurses in the treatment of women with chronic venous ulcers. Method Phenomenological research was based on Alfred Schütz, whose statements were obtained in January, 2012, through semi-structured interviews with seven nurses. Results The nurse reveals the difficulties presented by the woman in performing self-care, the perceived limitations in the treatment anchored in motivation, and the values and beliefs of women. It showed professional frustration because venous leg ulcer recurrence, lack of inputs, interdisciplinary work and training of nursing staff. There was an expected adherence to the treatment of women, and it emphasized the need for ongoing care, supported self-care and standard practices in treatment. Conclusion That treatment of chronic venous leg ulcers constitutes a challenge that requires collective investment, involving women, professionals, managers and health institutions. PMID:25517835

  10. Chronic thromboembolic pulmonary hypertension: time for research in pathophysiology to catch up with developments in treatment

    PubMed Central

    Toshner*, Mark

    2014-01-01

    The modern treatment era in chronic thromboembolic disease has seen significant advances in both surgical and medical treatment. One such treatment, the pulmonary endarterectomy (where established chronic organized thrombus is removed), has dramatically affected morbidity and mortality. These advances have outstripped basic research into the causes and pathophysiology of disease, which remain largely poorly understood. In this review, we will set out to explain some of the historical reasons for this, including the difficulties inherent in human studies and the lack of good animal models. We will review some of the recent advances in pathophysiology from registries and translational research, and we will summarize the treatment options, with some discussion of very recently published work, including medical and surgical treatments, both traditional and more experimental work in non-invasive techniques. PMID:24991415

  11. Mechanisms and treatment of extraosseous calcification in chronic kidney disease.

    PubMed

    Ketteler, Markus; Rothe, Hansjörg; Krüger, Thilo; Biggar, Patrick H; Schlieper, Georg

    2011-09-01

    Strong and unidirectional associations exist between the severity of cardiovascular calcifications and mortality in patients with advanced chronic kidney disease. In the past 10 years, a wealth of experimental and clinical information has been published on the key pathophysiological events that contribute to the development and progression of vascular and soft-tissue calcifications. These processes involve a sensitive balance of calcification inhibition, induction and removal. The traditional view of regarding secondary hyperparathyroidism and elevated calcium × phosphate product as the pivotal risk factors for calcification has been challenged by data demonstrating a role for other, more subtle and complex pathomechanisms. These mechanisms include the loss of endogenous calcification inhibitors, deficient clearance of calcified debris, effects of vitamin K and vitamin D, and the action of calcification inducers as in osteogenic transdifferentiation. In this Review, we describe our current knowledge of the factors involved in the passive and active regulation of extraosseous calcification processes, with an assessment of their importance as targets for future diagnostic and therapeutic interventions. PMID:21769106

  12. Protective effect of captopril against clozapine-induced myocarditis in rats: role of oxidative stress, proinflammatory cytokines and DNA damage.

    PubMed

    Abdel-Wahab, Basel A; Metwally, Metwally E; El-khawanki, Mohamed M; Hashim, Alaa M

    2014-06-01

    Clozapine (CLZ) is the most effective therapeutic alternative in the treatment of resistant schizophrenia. However, the cardiotoxicity of CLZ, particularly in young patients, has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with antioxidant properties effective in treating hypertension and heart failure. The aim of this study was to investigate the protective effect of captopril against clozapine-induced myocarditis in rats and the possible mechanisms behind this effect. The effect of captopril treatment [5 or 10mg/kg/d, injected intraperitoneally (i.p.) for 21days] on the cardiotoxic effect of coadministered CLZ (25mg/kg/d, i.p.) was assessed. Myocarditis was assessed histopathologically, immunohistochemically and biochemically. Frozen heart specimens were used to determine the amount of lipid peroxides product (MDA), nitric oxide (NO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) activity, proinflammatory cytokines (TNF-α and IL-10) and DNA degradation product(8-OHdG). Coadministration of captopril with the tested doses of CLZ decreased the histological hallmarks and biochemical markers (CK-MP and LDH) of myocarditis. In addition, captopril attenuated the effects of CLZ on oxidative stress parameters, NO and serum and cardiac 8-OHdG levels. Captopril significantly attenuated the effect of CLZ on all measured parameters in a dose-dependent manner. These results suggested that captopril exerts a protective action against CLZ-induced myocarditis. Multiple mechanisms contribute to this effect, including a decrease in cardiac oxidative stress and proinflammatory cytokines production, modulation of antioxidant status and protection from oxidative DNA damage. Hence, captopril may be effective in reducing the incidence and severity of CLZ-induced myocarditis in humans. PMID:24709159

  13. Treatment of Chronic Stuttering: Outcomes from a Student Training Clinic

    ERIC Educational Resources Information Center

    Block, Susan; Onslow, Mark; Packman, Ann; Gray, Belinda; Dacakis, Georgia

    2005-01-01

    Background: It has been suggested that one way to increase speech pathologists' confidence in working with people who stutter is to provide them with relevant and stimulating clinical experiences during their professional preparation. This paper describes a treatment programme for adults who stutter that is conducted by speech pathology students,…

  14. Chronic Kidney Disease (CKD) Treatment Burden Among Low-Income Primary Care Patients

    PubMed Central

    Kahn, Linda S.; Vest, Bonnie M.; Madurai, Nethra; Singh, Ranjit; York, Trevor R.M.; Cipparone, Charlotte W.; Reilly, Sarah; Malik, Khalid S.; Fox, Chester H.

    2015-01-01

    Objective This study explored the self-management strategies and treatment burden experienced by low income US primary care patients with chronic kidney disease. Methods Semi-structured interviews were conducted with 34 patients from two primary care practices on Buffalo’s East Side, a low-income community. Qualitative analysis was undertaken using an inductive thematic content analysis approach. We applied Normalization Process Theory (NPT) to the concept of treatment burden to interpret and categorize our findings. Results The sample was predominantly African-American (79%) and female (59%). Most patients (79%) had a diagnosis of Stage 3 CKD. Four major themes were identified corresponding to NPT and treatment burden: (1) Coherence – making sense of CKD; (2) Cognitive participation – enlisting support and organizing personal resources; (3) Collective action – self-management work; and (4) Reflexive monitoring – further refining chronic illness self-care in the context of CKD. For each component we identified barriers hindering patients’ ability to accomplish the necessary tasks. Conclusions Our findings highlight the substantial treatment burden faced by inner-city primary care patients self-managing CKD in combination with other chronic illnesses. Health care providers’ awareness of treatment burden can inform the development of person-centered care plans that can help patients to better manage their chronic illnesses. PMID:25416418

  15. [CHRONOLOGICAL APPROACH TO COMPLEX TREATMENT OF PATIENTS WITH CHRONIC CHOLECYSTITIS IN COMBINATION WITH THE OPISTHORCHIASIS].

    PubMed

    Poddubnaya, O A

    2015-01-01

    The development of new technologies of medical rehabilitation of patients with chronic cholecystitis in combination with a chronic opisthorchiasis, remains an actual problem of clinical gastroenterology. The use of a group chronobiological approach to the complex treatment of these patients including EHF-therapy allows to increase efficiency of the conducted measures. The analysis of results testified to beneficial effect of such approach on indicators of a functional condition of hepatobiliarity system and an organism in general. The positive dynamics of all studied indicators provided high thera- peutic effect (to 84.8%), and the revealed contingency of these results to features of carrying out treatment, allowed to establish their interrelation (χ² = 104.13; p = 0.0001; Kramer's V-coefficient = 0.35). It guarantees (is a predictor) receiving of high therapeutic effect (Percent Concordant of = 86.4%; the standardized coefficient = 2.54; r = 0.001) of the complex treatment including EHF-therapy with use of chronobiological approach to treatment of patients with chronic cholecystitis in combination with a chronic opisthorchiasis. The established dependences have a great practical importance and can be used in a choice of tactics of treatment of this category of patients. PMID:27214989

  16. Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.

    PubMed

    Dotta, Laura; Scomodon, Omar; Padoan, Rita; Timpano, Silviana; Plebani, Alessandro; Soresina, Annarosa; Lougaris, Vassilios; Concolino, Daniela; Nicoletti, Angela; Giardino, Giuliana; Licari, Amelia; Marseglia, Gianluigi; Pignata, Claudio; Tamassia, Nicola; Facchetti, Fabio; Vairo, Donatella; Badolato, Raffaele

    2016-03-01

    In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis. PMID:26732859

  17. Formulation and evaluation of clozapine orally disintegrating tablets prepared by direct compression.

    PubMed

    Olmez, S S; Vural, I; Sahin, S; Ertugrul, A; Capan, Y

    2013-02-01

    In this study, clozapine orally disintegrating tablets (ODTs) were prepared by direct compression method. Disintegration time, resistance to crushing of tablets, porosity, friability, dissolution tests were performed and dissolution profiles of ODTs were investigated. Morphological and interaction studies were also performed. Friability values were found to be less than 1%. All tablet formulations disintegrated within 1 min and fulfilled the 3 min disintegration time required for ODTs given in the European Pharmacopoeia. More than 85% of the labeled amount of clozapine was dissolved in 15 min from the ODTs. No interaction or changes were found between active substance and excipients. As a result of the studies, ODT formulations developed in this study can be suggested as promising formulations, which assist development and manufacturing a generic product of clozapine. PMID:23469682

  18. Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine

    PubMed Central

    Sharma, Pravesh; Davis, Jeffrey; Rachamallu, Vivekananda; Aligeti, Manish

    2016-01-01

    This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient's psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient's laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner. PMID:26904343

  19. Functional antagonistic properties of clozapine at the 5-HT3 receptor.

    PubMed

    Hermann, B; Wetzel, C H; Pestel, E; Zieglgänsberger, W; Holsboer, F; Rupprecht, R

    1996-08-23

    The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile. PMID:8780717

  20. Ziprasidone as Adjunctive Therapy in Severe Bipolar Patients Treated with Clozapine

    PubMed Central

    Bartolommei, Natalia; Pensabene, Laura; Luchini, Federica; Benvenuti, Antonella; Di Paolo, Antonello; Cosentino, Luca; Mauri, Mauro; Lattanzi, Lorenzo

    2014-01-01

    Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course. PMID:25006524

  1. Optimized Treatment and Heart Rate Reduction in Chronic Heart Failure

    PubMed Central

    Moreno, Irineu Blanco; Del Carlo, Carlos Henrique; Pereira-Barretto, Antônio Carlos

    2013-01-01

    Background Heart failure (HF) is a syndrome that leads to poor outcome in advanced forms. The neurohormonal blockade modifies this natural history; however, it is often suboptimal. Objective The aim of this study is to assess at what percentage cardiologists used to treating HF can prescribe target doses of drugs of proven efficacy. Methods A total of 104 outpatients with systolic dysfunction were consecutively enrolled, all under stabilized treatment. Demographic and treatment data were evaluated and the doses achieved were verified. The findings are shown as percentages and correlations are made between different variables. Results The mean age of patients was 64.1 ± 14.2 years, with SBP =115.4 ± 15.3, HR = 67.8 ± 9.4 bpm, weight = 76.0 ± 17.0 kg and sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI 52.9%), all received beta-blockers (BB), the most often prescribed being carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below the optimal dose and of those who received ACEI, 52.7% received an optimized dose. As for the BB, target doses were prescribed to 76.0% of them. In this group of patients, most with BB target dose, it can be seen that 36.5% had HR ≥ 70 bpm in sinus rhythm. Conclusion Cardiologists used to treating HF can prescribe target doses of ACEI and BB to most patients. Even though they receive the recommended doses, about one third of patients persists with HR > 70 bpm and should have their treatment optimized. PMID:24100693

  2. Understanding Patients’ Experiences of Treatment Burden in Chronic Heart Failure Using Normalization Process Theory

    PubMed Central

    Gallacher, Katie; May, Carl R.; Montori, Victor M.; Mair, Frances S.

    2011-01-01

    PURPOSE Our goal was to assess the burden associated with treatment among patients living with chronic heart failure and to determine whether Normalization Process Theory (NPT) is a useful framework to help describe the components of treatment burden in these patients. METHODS We performed a secondary analysis of qualitative interview data, using framework analysis, informed by NPT, to determine the components of patient “work.” Participants were 47 patients with chronic heart failure managed in primary care in the United Kingdom who had participated in an earlier qualitative study about living with this condition. We identified and examined data that fell outside of the coding frame to determine if important concepts or ideas were being missed by using the chosen theoretical framework. RESULTS We were able to identify and describe components of treatment burden as distinct from illness burden using the framework. Treatment burden in chronic heart failure includes the work of developing an understanding of treatments, interacting with others to organize care, attending appointments, taking medications, enacting lifestyle measures, and appraising treatments. Factors that patients reported as increasing treatment burden included too many medications and appointments, barriers to accessing services, fragmented and poorly organized care, lack of continuity, and inadequate communication between health professionals. Patient “work” that fell outside of the coding frame was exclusively emotional or spiritual in nature. CONCLUSIONS We identified core components of treatment burden as reported by patients with chronic heart failure. The findings suggest that NPT is a theoretical framework that facilitates understanding of experiences of health care work at the individual, as well as the organizational, level. Although further exploration and patient endorsement are necessary, our findings lay the foundation for a new target for treatment and quality improvement

  3. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    PubMed

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment. PMID:26852913

  4. A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.

    PubMed

    Gras-Miralles, Beatriz; Cremonini, Filippo

    2013-01-01

    Chronic constipation is a common disorder in the general population, with higher prevalence in the elderly, and is associated with worse quality of life and with greater health care utilization. Lubiprostone is an intestinal type-2 chloride channel activator that increases intestinal fluid secretion, small intestinal transit, and stool passage. Lubiprostone is currently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation and of irritable bowel syndrome with predominant constipation. This review outlines current approaches and limitations in the treatment of chronic constipation in the elderly and discusses the results, limitations, and applicability of randomized, controlled trials of lubiprostone that have been conducted in the general and elderly population, with additional focus on the use of lubiprostone in constipation in Parkinson's disease and in opioid-induced constipation, two clinical entities that can be comorbid in elderly patients. PMID:23439964

  5. Successful Treatment with Posaconazole of a Patient with Chronic Chagas Disease and Systemic Lupus Erythematosus

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Gállego, Montserrat; López-Chejade, Paulo Luis; Urbina, Julio A.; Gascón, Joaquim

    2010-01-01

    American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy. PMID:20348503

  6. Effective observation of treatment of chronic pharyngitis with semiconductor laser irradiation at acupuncture points

    NASA Astrophysics Data System (ADS)

    Li, Suxian; Wang, Xiaoyan; Wang, Yanrong

    1993-03-01

    The treatment of this disease with laser such as He-Ne laser, Nd:YAG laser, and CO2 laser, etc., has been applied in our country, but application of the semiconductor laser therapy has received few reports. It has many advantages, such as ting volume, steady function, simple operation (the patient can operate it by himself), no side effects, remarkable results, and it is very convenient. So the semiconductor laser can be used to treat the chronic pharyngitis with irradiation on acupunctural points. One-hundred-twenty chronic pharyngitis patients were divided into 2 groups, a laser group and a medicine group, 60 cases for each. The effective rate is 91.6% and 66.6%, respectively. Obviously the treatment of chronic pharyngitis with semiconductor laser is valuable for widespread use. The principle of the laser therapy is discussed in the last part of this paper.

  7. Older People’s Experiences of Patient-Centered Treatment for Chronic Pain: A Qualitative Study

    PubMed Central

    Teh, Carrie F.; Karp, Jordan F.; Kleinman, Arthur; Reynolds, Charles F.; Weiner, Debra K.; Cleary, Paul D.

    2010-01-01

    Introduction Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. Objective To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient–provider relationship. Design In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Results Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient–provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient–provider relationship is important to this population. Specifically, participants described the importance of “being heard” and “being understood” by providers. Conclusions As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient–provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient–provider relationship by attending to differences in patients’ willingness to engage in patient-directed care and emphasizing shared decision-making. PMID:19207235

  8. The role of ketamine in the treatment of chronic cancer pain

    PubMed Central

    ZGAIA, ARMEANA OLIMPIA; IRIMIE, ALEXANDRU; SANDESC, DOREL; VLAD, CATALIN; LISENCU, COSMIN; ROGOBETE, ALEXANDRU; ACHIMAS-CADARIU, PATRICIU

    2015-01-01

    Background and aim Ketamine is a drug used for the induction and maintenance of general anesthesia, for the treatment of postoperative and posttraumatic acute pain, and more recently, for the reduction of postoperative opioid requirements. The main mechanism of action of ketamine is the antagonization of N-methyl-D-aspartate (NMDA) receptors that are associated with central sensitization. In the pathogenesis of chronic pain and particularly in neuropathic pain, an important role is played by the activation of NMDA receptors. Although ketamine is indicated and used for the treatment of chronic cancer pain as an adjuvant to opioids, there are few clinical studies that clearly demonstrate the effectiveness of ketamine in this type of pain. The aim of this study is to analyze evidence-based clinical data on the effectiveness and safety of ketamine administration in the treatment of chronic neoplastic pain, and to summarize the evidence-based recommendations for the use of ketamine in the treatment of chronic cancer pain. Method We reviewed the literature from the electronic databases of MEDLINE, COCHRANE, PUBMED, MEDSCAPE (1998–2014), as well as chapters of specialized books (palliative care, pain management, anesthesia). Results A number of studies support the effectiveness of ketamine in the treatment of chronic cancer pain, one study does not evidence clear clinical benefits for the use of ketamine, and some studies included too few patients to be conclusive. Conclusions Ketamine represents an option for neoplasic pain that no longer responds to conventional opioid treatment, but this drug should be used with caution, and the development of potential side effects should be carefully monitored. PMID:26733743

  9. [Novel treatments for hepatitis C virus infection in chronic kidney disease].

    PubMed

    Fabrizi, Fabrizio; Messa, Piergiorgio

    2016-01-01

    Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions. PMID:27545640

  10. Randomized clinical trial for treatment of chronic nightmares in trauma-exposed adults.

    PubMed

    Davis, Joanne L; Wright, David C

    2007-04-01

    Nightmares and sleep disturbance are fundamental concerns for victims of trauma. This study examined the efficacy of a manualized cognitive-behavioral treatment (CBT) for chronic nightmares in trauma-exposed individuals via a randomized clinical trial. Participants were randomly assigned to a treatment group or wait-list control group, with 27 participants completing the treatment. At the 6-month follow-up assessment, 84% of treated participants reported an absence of nightmares in the previous week. Significant decreases were also reported in symptoms of depression and posttraumatic stress, fear of sleep, and number of sleep problems, while sleep quality and quantity improved. The present study adds to the growing literature indicating this brief CBT as a first-line treatment for trauma-exposed individuals with chronic nightmares. PMID:17427914

  11. Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.

    PubMed

    Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin

    2015-04-15

    Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831

  12. Stem cell technology for the treatment of acute and chronic renal failure

    PubMed Central

    Pino, Christopher J.; Humes, H. David

    2010-01-01

    Acute and chronic renal failure are disorders with high rates of morbidity and mortality. Current treatment is based upon conventional dialysis to provide volume regulation and small solute clearance. There is growing recognition that renal failure is a complex disease state requiring a multifactorial therapy to address the short-comings of the conventional monofactorial approach. Kidney transplantation remains the most effective treatment, however, organ availability lags far behind demand. Many key kidney functions including gluconeogenesis, ammoniagenesis, metabolism of glutathione, catabolism of important peptide hormones, growth factors, and cytokines critical to multiorgan homeostasis and immunomodulation are provided by renal tubule cells. Therefore, cell-based therapies are promising multifactorial treatment approaches. In this review, current stem cell technologies including adult stem cells, embryonic stem cells and induced pluripotent stem cells will be discussed as cell sources for the treatment of acute and chronic renal failure. PMID:20801413

  13. The chronically mentally ill group treatment for individuals with schizophrenia.

    PubMed

    Wilson, W H; Diamond, R J; Factor, R M

    1990-08-01

    Comprehensive treatment programs for individuals with schizophrenia usually include a variety of groups, many of which have concrete tasks as a focus: medication management, social skills training, meal preparation, etc. These groups can simultaneously serve more general rehabilitative purposes if leaders apply principles of group leadership which recognize the neuropathological substrate of schizophrenia and which take into account the specific interpersonal characteristics and needs of individuals who have the illness. This paper presents a framework for leading task-oriented groups for individuals with schizophrenia and give examples from a medication group in a psychosocial rehabilitation program. PMID:2208966

  14. [Mistakes and complications appearing during treatment of chronic pulpitis of the deciduos teeth in children].

    PubMed

    Gazhva, S I; Pozhitok, E S; Agafonov, G V

    2010-01-01

    On the basis of clinical data dentists' mistakes and complication appearing in treatment of chronic pulpitis of the deciduous teeth in children in private dental clinics were investigated. Causes of their occurrence were revealed and ways of their prophylaxis were suggested. PMID:20517241

  15. Differential Effects of Treatments for Chronic Depression: A Latent Growth Model Reanalysis

    ERIC Educational Resources Information Center

    Stulz, Niklaus; Thase, Michael E.; Klein, Daniel N.; Manber, Rachel; Crits-Christoph, Paul

    2010-01-01

    Objective: Psychotherapy-pharmacotherapy combinations are frequently recommended for the treatment of chronic depressive disorders. Our aim in this novel reanalysis of archival data was to identify patient subgroups on the basis of symptom trajectories and examine the clinical significance of the resultant classification on basis of differential…

  16. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

    ERIC Educational Resources Information Center

    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  17. Lesion Characteristics Related to Treatment Improvement in Object and Action Naming for Patients with Chronic Aphasia

    ERIC Educational Resources Information Center

    Parkinson, R. Bruce; Raymer, Anastasia; Chang, Yu-Ling; FitzGerald, David B.; Crosson, Bruce

    2009-01-01

    Few studies have examined the relationship between degree of lesion in various locations and improvement during treatment in stroke patients with chronic aphasia. The main purpose of this study was to determine whether the degree of lesion in specific brain regions was related to magnitude of improvement over the course of object and action naming…

  18. Treating Chronic Pain in Veterans Presenting to an Addictions Treatment Program

    ERIC Educational Resources Information Center

    Ilgen, Mark A.; Haas, Elizabeth; Czyz, Ewa; Webster, Linda; Sorrell, John T.; Chermack, Stephen

    2011-01-01

    Chronic pain and substance use disorders frequently co-occur. The pharmacological treatment of pain is complicated in individuals with substance use disorders because of the potential for abuse and diversion of many prescription pain medications. One potential approach is to use a combination of cognitive-behavioral and acceptance-based strategies…

  19. Demographic and Psycho-Social Implications for Assessment and Treatment of Chronic Pain Patients.

    ERIC Educational Resources Information Center

    Auvenshine, Dwight

    Several demographic and psychosocial variables affect assessment and treatment of chronic pain patients. The variables include demographic characteristics, life styles, family constellations, job conditions, financial status, support networks, and leisure activities. In recent years clinics and programs have emerged in a variety of configurations.…

  20. Chronic Treatment with Haloperidol Induces Deficits in Working Memory and Feedback Effects of Interval Timing

    ERIC Educational Resources Information Center

    Lustig, C.; Meck, W.H.

    2005-01-01

    Normal participants (n=5) having no experience with antipsychotic drugs and medicated participants (n=5) with clinical experience with chronic low doses of haloperidol (3-10mg/day for 2-4 months) in the treatment of neuroses were evaluated for the effects of inter-trial interval (ITI) feedback on a discrete-trials peak-interval timing procedure.…

  1. Treatment options for chronic idiopathic (immune) thrombocytopenic purpura.

    PubMed

    George, J N

    2000-01-01

    The goal of treatment for idiopathic (immune) thrombocytopenic purpura (ITP) is to prevent serious bleeding. Traditionally, corticosteroids have been used as first-line therapy followed by splenectomy. Experience with splenectomy over 60 years shows that approximately two thirds of patients achieve normal platelet counts during the initial observation, but that thrombocytopenia often recurs with longer follow-up. We know that long-term use of corticosteroids can lead to significant morbidities; there is no consensus regarding the appropriate timing or indications for splenectomy. To address the Issue of appropriate use of splenectomy, we designed a multicenter clinical trial that will randomize patients to either standard care, involving prednisone followed by splenectomy, or to a novel regimen of limited prednisone treatment followed by WinRho SDF (Nabi, Boca Raton, FL) (anti-D) therapy to maintain the platelet count in a safe range for 1 year. Anti-D can be administered easily in an outpatient setting with few side effects and can provide predictable, transient increases in platelet count. The hypothesis is that prolonged maintenance therapy with a nontoxic regimen may increase the percentage of patients who will experience a spontaneous remission from thrombocytopenia, thereby avoiding an invasive and permanent surgical procedure, splenectomy, and its potentially life-threatening sequelae. PMID:10676922

  2. [Cost-effectiveness of chronic hepatitis C treatment in Spain].

    PubMed

    Haj-Ali Saflo, Okba; Hernández Guijo, Jesús Miguel

    2009-01-01

    In this study we evaluated the pharmacologic costs of hepatitis C treatment, considering recommendations on both the duration of therapy and sustained virological response. With this aim, we analyzed relevant scientific articles published in the previous 10 years, considering the most common genotypes present in Spain. In this analysis, we estimated overall costs to be 1,636,524.58-1,761,365.73 euro and 1,794.586.39-1,917,013.73 euro with the use of pegylated interferon (PegIFN)-alpha-2a and PegIFN-alpha-2b, respectively. Sustained virological response was 59.18% and 64.58% respectively, with no significant difference between the two formulations. Finally, we assess the economic costs of the use of high-dose PegIFN-alpha-2a and ribavirin in patients with genotype 1 and treatment resistance (baseline HCV-RNA values > 800.000UI/ml, without early viral response at 12 weeks and weight > 85kg). PMID:19615787

  3. On-treatment platelet reactivity in patients with chronic obstructive pulmonary disease undergoing percutaneous coronary intervention.

    PubMed

    Campo, Gianluca; Pavasini, Rita; Pollina, Alberto; Tebaldi, Matteo; Ferrari, Roberto

    2014-01-01

    Patients with chronic obstructive pulmonary disease (COPD) show a poor prognosis after myocardial infarction (MI) and percutaneous coronary intervention (PCI). We evaluated on-treatment platelet reactivity (PR) and several gene polymorphisms related to PR in 130 patients undergoing PCI with and without COPD. Those with concomitant COPD showed higher on-treatment PR values both at the time of PCI and 1 month after. This finding may contribute to explain the poor prognosis of COPD patients after MI and PCI. PMID:23878160

  4. Chronic kidney disease-mineral and bone disorder: Guidelines for diagnosis, treatment, and management.

    PubMed

    Moschella, Carla

    2016-07-01

    Chronic kidney disease affects 23 million Americans and is associated with many complications, one of the most complex of which is mineral and bone disorder. Pathophysiologic mechanisms begin to occur early in CKD but when the glomerular filtration rate declines to <50% of normal, biochemical and bone matrix abnormalities, which vary and are multifactorial, begin to be clinically apparent. Mainstays of treatment remain management of hyperphosphatemia and prevention or treatment of secondary hyperparathyroidism. PMID:27272731

  5. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

    PubMed

    Lynch, Mary E; Campbell, Fiona

    2011-11-01

    Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required. PMID:21426373

  6. Chronic Pruritus in the Absence of Skin Disease: Pathophysiology, Diagnosis and Treatment.

    PubMed

    Pereira, Manuel P; Kremer, Andreas E; Mettang, Thomas; Ständer, Sonja

    2016-08-01

    Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients. Thus, future studies aiming to unveil the complex mechanisms underlying chronic pruritus and develop new therapeutic agents are urgently needed. PMID:27216284

  7. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

    PubMed Central

    Lynch, Mary E; Campbell, Fiona

    2011-01-01

    Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required. Linked Article This article is linked to a themed issue in the British Journal of Pharmacology on Respiratory Pharmacology. To view this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1 PMID:21426373

  8. Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease

    PubMed Central

    Alarcón de Noya, B.; Araujo-Jorge, T.; Grijalva, M. J.; Guhl, F.; López, M. C.; Ramsey, J. M.; Ribeiro, I.; Schijman, A. G.; Sosa-Estani, S.; Torrico, F.; Gascon, J.

    2014-01-01

    Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients. PMID:24247135

  9. Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

    PubMed Central

    FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

    2010-01-01

    Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

  10. Chronic lumbar spine and radicular pain: pathophysiology and treatment.

    PubMed

    Wheeler, Anthony H; Murrey, Daniel B

    2002-04-01

    The lumbar spine forms the foundation and infrastructure of an organic skyscraper equipped with the physiologic capacity to act as a crane for lifting and a crankshaft for walking. Subjected to aging like other "human machinery," the lumbar spine adapts to the wear and tear of gravity and biomechanical loading through structural and neurochemical changes. Many of the changes are maladaptive, resulting in pain, physical and functional disability, and altered neurophysiologic circuitry. Some compensatory reactions are constructive, but others cause more interference with the organism's capacity to cope. A conceptional understanding of the multifaceted structural, biomechanical, biochemical, medical, and psychosocial influences that compose this mix elucidates the complexity of applying effective treatments. PMID:11872180

  11. Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Lasserson, Toby J

    2014-01-01

    Background An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in previous Cochrane reviews. Objectives We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked manufacturers’ websites of clinical trial registers for unpublished trial data and also checked Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was January 2012. Selection criteria We included controlled, parallel-design clinical trials on patients of any age and with any severity of asthma if they randomised patients to treatment with regular formoterol versus regular salmeterol (without randomised inhaled corticosteroids), and were of at least 12 weeks’ duration. Data collection and analysis Two authors independently selected trials for inclusion in the review and extracted outcome data. We sought unpublished data on mortality and serious adverse events from the sponsors and authors. Main results The review included four studies (involving 1116 adults and 156 children). All studies were open label and recruited patients who were already taking inhaled corticosteroids for their asthma, and all studies contributed data on serious adverse events. All studies compared formoterol 12 μg versus salmeterol 50 μg twice daily. The adult studies were all comparing Foradil Aerolizer with Serevent Diskus, and the children’s study compared Oxis Turbohaler to Serevent Accuhaler. There was only one death in an adult (which was unrelated to asthma) and none in children, and there were no significant differences in non-fatal serious adverse events comparing formoterol to salmeterol in adults (Peto odds ratio (OR) 0.77; 95

  12. Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

    PubMed Central

    Garcia, Simone; Ramos, Carolina O.; Senra, Juliana F. V.; Vilas-Boas, Fabio; Rodrigues, Maurício M.; Campos-de-Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo; Soares, Milena B. P.

    2005-01-01

    Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2β, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of β1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy. PMID:15793134

  13. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations

    PubMed Central

    Müller, Martin C.; Cortes, Jorge E.; Kim, Dong-Wook; Druker, Brian J.; Erben, Philipp; Pasquini, Ricardo; Branford, Susan; Hughes, Timothy P.; Radich, Jerald P.; Ploughman, Lynn; Mukhopadhyay, Jaydip

    2009-01-01

    Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844. PMID:19779040

  14. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.

    PubMed

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2016-05-01

    The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients

  15. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children.

    PubMed

    Hathout, Yetrib; Conklin, Laurie S; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J; Morgenroth, Lauren P; Nagaraju, Kanneboyina; Heier, Christopher R; Damsker, Jesse M; van den Anker, John N; Henricson, Erik; Clemens, Paula R; Mah, Jean K; McDonald, Craig; Hoffman, Eric P

    2016-01-01

    Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes. PMID:27530235

  16. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children

    PubMed Central

    Hathout, Yetrib; Conklin, Laurie S.; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J.; Morgenroth, Lauren P.; Nagaraju, Kanneboyina; Heier, Christopher R.; Damsker, Jesse M.; van den Anker, John N.; Henricson, Erik; Clemens, Paula R.; Mah, Jean K.; McDonald, Craig; Hoffman, Eric P.

    2016-01-01

    Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes. PMID:27530235

  17. Part 2: Treatments for Chronic Gastrointestinal Disease and Gut Dysbiosis

    PubMed Central

    Bull, Matthew J.; Plummer, Nigel T.

    2015-01-01

    Part 1 of this review discussed the connection between the human gut microbiota and health. Manipulation of the intestinal microbiota holds promise as a prospective therapy for gut dysbiosis, ameliorating symptoms of gastrointestinal and systemic diseases and restoring health. The concept of probiotics has existed for more than 100 y, and modern research methods have established sound scientific support for the perceived benefits of probiotic bacteria, which mainly include Lactobacillus and Bifidobacterium genera. On the basis of these evidence-based functional approaches, dietary interventions that supplement the normal diet with probiotics or prebiotics are now considered as potentially viable alternatives or adjuncts to the use of steroids, immunosuppressants, and/or surgical interventions. Studies investigating the impact on gastrointestinal disorders, such as diarrhea, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS); and systemic metabolic diseases, such as type 2 diabetes and obesity, in response to the use of probiotics and prebiotics are reviewed. Further, fecal microbial transplantation (FMT) is discussed as an exciting development in the treatment of gut dysbiosis using microbes. PMID:26770128

  18. Thymalfasin for the treatment of chronic hepatitis C infection.

    PubMed

    Rustgi, Vinod K

    2007-09-01

    The purpose of this review article is to examine previous and ongoing studies of thymalfasin in combination with peginterferon-alpha2a and peginterferon-alpha2a plus ribavirin in difficult-to-treat hepatitis C virus (HCV) patients. The following studies will be reviewed in detail: (1) Sherman and colleagues conducted a study in 109 HCV RNA positive HVC patients comparing the combination of thymalfasin + IFN versus IFN alone versus placebo. (2) Rustgi et al. evaluated the efficacy and safety of thymalfasin and peg-IFN-alpha2a in 31 genotype 1, high viral load, HCV nonresponders in a 12-week viral kinetic study. (3) Di Bisceglie, Sherman et al. performed a study of previous HCV nonresponders being retreated with either peginterferon-alpha2a plus thymalfasin or peginterferon-alpha2a plus placebo. (4) Poo and colleagues in Mexico evaluated triple combination therapy using thymalfasin, peginterferon-alpha2a, and ribavirin for the treatment of Hispanic HCV nonresponders. PMID:17600289

  19. Part 2: Treatments for Chronic Gastrointestinal Disease and Gut Dysbiosis.

    PubMed

    Bull, Matthew J; Plummer, Nigel T

    2015-02-01

    Part 1 of this review discussed the connection between the human gut microbiota and health. Manipulation of the intestinal microbiota holds promise as a prospective therapy for gut dysbiosis, ameliorating symptoms of gastrointestinal and systemic diseases and restoring health. The concept of probiotics has existed for more than 100 y, and modern research methods have established sound scientific support for the perceived benefits of probiotic bacteria, which mainly include Lactobacillus and Bifidobacterium genera. On the basis of these evidence-based functional approaches, dietary interventions that supplement the normal diet with probiotics or prebiotics are now considered as potentially viable alternatives or adjuncts to the use of steroids, immunosuppressants, and/or surgical interventions. Studies investigating the impact on gastrointestinal disorders, such as diarrhea, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS); and systemic metabolic diseases, such as type 2 diabetes and obesity, in response to the use of probiotics and prebiotics are reviewed. Further, fecal microbial transplantation (FMT) is discussed as an exciting development in the treatment of gut dysbiosis using microbes. PMID:26770128

  20. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment

    PubMed Central

    Maxson, Julia E.; George, Tracy I.; Tyner, Jeffrey W.

    2013-01-01

    Although activation of tyrosine kinase pathways is a shared theme among myeloproliferative neoplasms, the pathogenetic basis of chronic neutrophilic leukemia (CNL) has remained elusive. Recently, we identified high-frequency oncogenic mutations in the granulocyte-colony stimulating factor receptor (CSF3R) in CNL and in some patients with atypical chronic myeloid leukemia. Inhibition of Janus kinase 2 or SRC kinase signaling downstream of mutated CSF3R is feasible and should be explored therapeutically. Herein, we discuss the potential impact of these findings for the classification and treatment of these disorders. PMID:23896413

  1. Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea, 2015 Revised Edition

    PubMed Central

    Shin, Jeong Eun; Jung, Hye-Kyung; Lee, Tae Hee; Jo, Yunju; Lee, Hyuk; Song, Kyung Ho; Hong, Sung Noh; Lim, Hyun Chul; Lee, Soon Jin; Chung, Soon Sup; Lee, Joon Seong; Rhee, Poong-Lyul; Lee, Kwang Jae; Choi, Suck Chei; Shin, Ein Soon

    2016-01-01

    The Korean Society of Neurogastroenterology and Motility first published guidelines for chronic constipation in 2005 and was updated in 2011. Although the guidelines were updated using evidence-based process, they lacked multidisciplinary participation and did not include a diagnostic approach for chronic constipation. This article includes guidelines for diagnosis and treatment of chronic constipation to realistically fit the situation in Korea and to be applicable to clinical practice. The guideline development was based upon the adaptation method because research evidence was limited in Korea, and an organized multidisciplinary group carried out systematical literature review and series of evidence-based evaluations. Six guidelines were selected using the Appraisal of Guidelines for Research & Evaluation (AGREE) II process. A total 37 recommendations were adopted, including 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 25 regarding treatments. The guidelines are intended to help primary physicians and general health professionals in clinical practice in Korea, to provide the principles of medical treatment to medical students, residents, and other healthcare professionals, and to help patients for choosing medical services based on the information. These guidelines will be updated and revised periodically to reflect new diagnostic and therapeutic methods. PMID:27226437

  2. Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

    PubMed Central

    Cortez, Karoll J.

    2015-01-01

    Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. PMID:25553238

  3. Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.

    PubMed

    Kosinska, Anna D; Liu, Jia; Lu, Mengji; Roggendorf, Michael

    2015-02-01

    Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model. PMID:25535101

  4. Angiotensin II receptor blockers: a new possible treatment for chronic migraine?

    PubMed

    Disco, Caterina; Maggioni, Ferdinando; Zanchin, Giorgio

    2015-08-01

    The objective is to suggest a possible role of different angiotensin receptor blockers in the treatment of chronic migraine, especially in hypertensive subjects. Chronic migraine is a highly disabling disorder affecting between 1.4 and 2.2 % of the general population. Despite many pharmacological and non-pharmacological treatments proposed, the results are rather discouraging. Therefore, we believe that should be highlighted all the possible therapies that may lead to an improvement of the symptomatology. Particularly, data available on efficacy of ARBs in preventing chronic migraine are poor. Methods include case reports, literature review and discussion. We report three cases recently treated with angiotensin II receptor blockers that showed a significant improvement, never previously presented with more conventional treatments, including beta blockers. In all three cases, we obtained the reversibility from a chronic migraine to an episodic. Taking a cue from this observation, we consider desirable large controlled, randomized trials to assess the effectiveness of ARBs both in CM hypertensive patients and in patients who do not require anti-hypertensive therapy; furthermore are desirable comparative studies between the various ARB inhibitors to assay any intermolecular differences in efficacy. PMID:25917398

  5. Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea, 2015 Revised Edition.

    PubMed

    Shin, Jeong Eun; Jung, Hye-Kyung; Lee, Tae Hee; Jo, Yunju; Lee, Hyuk; Song, Kyung Ho; Hong, Sung Noh; Lim, Hyun Chul; Lee, Soon Jin; Chung, Soon Sup; Lee, Joon Seong; Rhee, Poong-Lyul; Lee, Kwang Jae; Choi, Suck Chei; Shin, Ein Soon

    2016-07-30

    The Korean Society of Neurogastroenterology and Motility first published guidelines for chronic constipation in 2005 and was updated in 2011. Although the guidelines were updated using evidence-based process, they lacked multidisciplinary participation and did not include a diagnostic approach for chronic constipation. This article includes guidelines for diagnosis and treatment of chronic constipation to realistically fit the situation in Korea and to be applicable to clinical practice. The guideline development was based upon the adaptation method because research evidence was limited in Korea, and an organized multidisciplinary group carried out systematical literature review and series of evidence-based evaluations. Six guidelines were selected using the Appraisal of Guidelines for Research & Evaluation (AGREE) II process. A total 37 recommendations were adopted, including 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 25 regarding treatments. The guidelines are intended to help primary physicians and general health professionals in clinical practice in Korea, to provide the principles of medical treatment to medical students, residents, and other healthcare professionals, and to help patients for choosing medical services based on the information. These guidelines will be updated and revised periodically to reflect new diagnostic and therapeutic methods. PMID:27226437

  6. [Psychopharmaceuticals for treatment of suicidal patients and for suicide prevention].

    PubMed

    Haußmann, R; Bauer, M; Lewitzka, U; Müller-Oerlinghausen, B

    2016-05-01

    Suicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term "suicidality" seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided. PMID:26952239

  7. Carvedilol in the treatment of chronic heart failure.

    PubMed

    Moe, G

    2001-05-01

    Along with the angiotensin-converting enzyme inhibitors (ACEIs), the beta-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual beta-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other beta-blockers as being a non-selective beta(1)- and beta(2)-receptor blocker with (1)-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its (1)-receptor blockade property. Experimental and clinical studies have confirmed carvedilol's vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other beta-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding

  8. The place of subfascial endoscopic perforator vein surgery (SEPS) in advanced chronic venous insufficiency treatment

    PubMed Central

    Kurpiewski, Waldemar; Kowalczyk, Marek; Szynkarczuk, Rafał; Łuba, Magdalena; Żurada, Anna; Grabysa, Radosław

    2011-01-01

    In spite of medical science development and initiation of new technologies in minimally invasive surgery, treatment of advanced chronic venous insufficiency at the 5th and 6th degree of CEAP classification is still a great clinical challenge. In case of no satisfactory results of non-surgical treatment of recurrent venous ulcers, scientists search for alternative therapeutic methods which could be more effective and lasting. Subfascial endoscopic perforator vein surgery (SEPS) as a method of reducing venous pressure in the superficial venous system could provide healing of the recurrent venous ulcer. In this study we present a review of contemporary opinions about the place and significance of subfascial endoscopic perforator vein surgery as a treatment of advanced chronic venous insufficiency. PMID:23255980

  9. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies.

    PubMed

    Leussink, Verena I; Hartung, Hans-Peter; Kieseier, Bernd C; Stettner, Mark

    2016-07-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  10. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    PubMed Central

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  11. Treatment of chronic hepatitis C in a Canadian Aboriginal population: Results from the PRAIRIE study

    PubMed Central

    Minuk, Gerald Yosel; O’Brien, Meaghan; Hawkins, Kim; Emokpare, Didi; McHattie, James; Harris, Paul; Worobetz, Lawrence; Doucette, Karen; Kaita, Kelly; Wong, Stephen; Pinette, Gilles; Uhanova, Julia

    2013-01-01

    BACKGROUND: The Aboriginal population of Canada is at increased risk of exposure to the hepatitis C virus (HCV). Previous data indicate that spontaneous clearance of HCV occurs more often in Aboriginals than Caucasians. Whether this enhanced response extends to antiviral therapy for chronic HCV remains to be determined. OBJECTIVES: To document and compare the biochemical and virological responses to antiviral therapy in HCV-infected Canadian Aboriginals and Caucasians. METHODS: A total of 101 treatment-naive adult patients (46 Aboriginal, 55 Caucasian) with chronic HCV genotype 1 infections were prospectively treated with pegylated-interferon and ribavirin and followed as per national guidelines. RESULTS: Aboriginals had higher HCV-RNA loads at baseline (6.42log10 versus 5.98log10; P<0.03). Although normalization of serum aminotransferase levels, decreases in viral loads, and rapid, early and end-of-treatment virological responses were similar in the two cohorts, sustained virological responses were significantly lower in Aboriginals (35% versus 55%; P=0.047). Premature discontinuation of treatment and/or loss of patients to follow-up was common (Aboriginals 37%, Caucasians 27%). Treatment-related side effects were similar in the two cohorts. CONCLUSION: Despite higher rates of spontaneous HCV clearance, the response to antiviral therapy was similar, if not lower, in Aboriginals compared with Caucasians with chronic HCV genotype 1 infections. Compliance with treatment is an issue that needs to be addressed in the management of these patients. PMID:24340315

  12. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats

    PubMed Central

    Dardou, David; Chassain, Carine; Durif, Franck

    2015-01-01

    The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating. PMID:25610366

  13. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    PubMed

    Dardou, David; Chassain, Carine; Durif, Franck

    2014-01-01

    The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating. PMID:25610366

  14. Comparison of Local and Systemic Ciprofloxacin Ototoxicity in the Treatment of Chronic Media Otitis

    PubMed Central

    Samarei, R.

    2014-01-01

    Introduction: Chronic media otitis is a common cause of reference to ear, nose and throat clinics and the treatment is one of the health problems among ENT specialists. Ciprofloxacin drop that is of fluoroquinolone drug class due to good treatment effect is now widely used in the treatment of chronic media otitis. Due to the widespread use, it seems proper research on the human population has not been taken to ensure its non-toxicity in the inner ear, therefore comparison of local ciprofloxacin ototoxicity with systemic in chronic media otitis is investigated in this study. Materials and Methods: This study was conducted as a randomized clinical trial. Prospective methods were considered and the number of samples in the study group was 40 patients that were treated with ciprofloxacin drops. And in the control group 32 patients with chronic media otitis who were treated with ciprofloxacin tablets. The collected data was analyzed using SPSS software. Results: Statistical indicators of different frequencies in air conduction (AC) in both groups showed, there was significant improvement in hearing thresholds at frequencies of 250, 8000, 1000 in air conduction for the group receiving drops compared to the group receiving tablet. Based on statistical indicators in different frequencies of bone conduction in the two treated groups, there was significant difference in the two groups receiving tablets and drops only at a frequency of 4000Hz that drop impact improves hearing threshold and in contrast in the group receiving tablet hearing loss was seen in the frequency of 4000. Discussion: Topical ciprofloxacin is a safe and uncomplicated ototoxic drug that is an effective antibiotic used in the treatment of refractory chronic otitis those dregs such as pseudomonas aerogenusa and staphylococci resistant to methicillin are responsible for it, which in the usual doses has not harmful effects on hearing hairy cells. PMID:25363170

  15. Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers

    PubMed Central

    Brantley, Jonathan N.; Verla, Thomas D.

    2015-01-01

    Significance: Chronic diabetic foot ulcers (DFUs) remain a challenge for physicians to treat. High mortality rates for DFU patients have pointed to the low effectiveness of standard care and lack of quality wound care products. The composition (collagen-rich tissue matrix and endogenous growth factors and cells) and functional properties (anti-inflammatory, anti-bacterial, and angiogenic) of placental membranes are uniquely suited to address the needs of chronic wounds. This led to the commercialization of placental membranes, which are now widely available to physicians as a new advanced wound treatment option. Recent Advances: Progress in tissue processing and preservation methods has facilitated the development of placental products for wounds. Currently, a variety of commercial placental products are available to physicians for the treatment of chronic DFUs and other wounds. This review summarizes the key factors that negatively impact DFU healing (including social factors, such as smoking, vascular deficiencies, hyperglycemia, and other metabolic abnormalities), describes the structure and biology of placental membranes, and overviews commercially available placental products for wounds and data from the most recent DFU clinical trials utilizing commercial placental membranes. Critical Issues: Although the effects of diabetes on wound healing are complex and not fully understood, some of the key factors and pathways that interfere with healing have been identified. However, a multidisciplinary approach for the assessment of patients with chronic DFUs and guidelines for selection of appropriate treatment modalities remain to be implemented. Future Directions: The biological properties of placental membranes show benefits for the treatment of chronic DFUs, but scientific and clinical data for commercially available placental products are limited. Therefore, we need (1) more randomized, controlled clinical trials for commercial placental products; (2) studies

  16. Molecular Signatures of Psychosocial Stress and Cognition Are Modulated by Chronic Lithium Treatment.

    PubMed

    Brzózka, Magdalena M; Havemann-Reinecke, Ursula; Wichert, Sven P; Falkai, Peter; Rossner, Moritz J

    2016-07-01

    Chronic psychosocial stress is an important environmental risk factor of psychiatric diseases such as schizophrenia. Social defeat in rodents has been shown to be associated with maladaptive cellular and behavioral consequences including cognitive impairments. Although gene expression changes upon psychosocial stress have been described, a comprehensive transcriptome profiling study at the global level in precisely defined hippocampal subregions which are associated with learning has been lacking. In this study, we exposed adult C57Bl/6N mice for 3 weeks to "resident-intruder" paradigm and combined laser capture microdissection with microarray analyses to identify transcriptomic signatures of chronic psychosocial stress in dentate gyrus and CA3 subregion of the dorsal hippocampus. At the individual transcript level, we detected subregion specific stress responses whereas gene set enrichment analyses (GSEA) identified several common pathways upregulated upon chronic psychosocial stress related to proteasomal function and energy supply. Behavioral profiling revealed stress-associated impairments most prominent in fear memory formation which was prevented by chronic lithium treatment. Thus, we again microdissected the CA3 region and performed global transcriptome analysis to search for molecular signatures altered by lithium treatment in stressed animals. By combining GSEA with unsupervised clustering, we detected pathways that are regulated by stress and lithium in the CA3 region of the hippocampus including proteasomal components, oxidative phosphorylation, and anti-oxidative mechanisms. Our study thus provides insight into hidden molecular phenotypes of chronic psychosocial stress and lithium treatment and proves a beneficial role for lithium treatment as an agent attenuating negative effects of psychosocial stress on cognition. PMID:26714764

  17. Differential desensitization of mu- and delta- opioid receptors in selected neural pathways following chronic morphine treatment.

    PubMed Central

    Noble, F.; Cox, B. M.

    1996-01-01

    1. Morphine produces a plethora of pharmacological effects and its chronic administration induces several side-effects. The cellular mechanisms by which opiates induce these side-effects are not fully understood. Several studies suggest that regulation of adenylyl cyclase activity by opioids and other transmitters plays an important role in the control of neural function. 2. The aim of this study was to evaluate desensitization of mu- and delta- opioid receptors, defined as a reduced ability of opioid agonists to inhibit adenylyl cyclase activity, in four different brain structures known to be involved in opiate drug actions: caudate putamen, nucleus accumbens, thalamus and periaqueductal gray (PAG). Opiate regulation of adenylyl cyclase in these regions has been studied in control and morphine-dependent rats. 3. The chronic morphine treatment used in the present study (subcutaneous administration of 15.4 mg morphine/rat/day for 6 days via osmotic pump) induced significant physical dependence as indicated by naloxone-precipitated withdrawal symptoms. 4. Basal adenylyl cyclase in the four brain regions was not modified by this chronic morphine treatment. In the PAG and the thalamus, a desensitization of mu- and delta-opioid receptors was observed, characterized by a reduced ability of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO; mu), Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE; delta) and [D-Ala2]-deltorphin-II (DT-II; delta) to inhibit adenylyl cyclase, activity following chronic morphine treatment. 5. The opioid receptor desensitization in PAG and thalamus appeared to be heterologous since the metabotropic glutamate receptor agonists, L-AP4 and glutamate, and the 5-hydroxytryptamine (5-HT)1A receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), also showed reduced inhibition of adenylyl cyclase activity following chronic morphine treatment. 6. In the nucleus accumbens and the caudate putamen, desensitization of delta-opioid receptor

  18. Neuroendoscopic treatment of idiopathic occlusion of unilateral foramen of Monro presenting as chronic headache

    PubMed Central

    Shukla, Dhaval

    2016-01-01

    Asymmetric ventriculomegly due to idiopathic occlusion of the foramen of Monro is rare. Such patients present with clinical features of raised intracranial pressure (ICP). Presentation as chronic headache has not been previously described. In the absence of raised ICP, pursuing surgical treatment raises a clinical dilemma as the headache may be a primary headache with no improvement after surgery. A 21-year-old woman presented with chronic headache. She was found to have asymmetric ventriculomegaly due to the occlusion of the foramen of Monro. She underwent endoscopic septostomy and widening of the foramen of Monro. Her headache subsided after surgery. At 15 months of follow-up, she was free from headache without medications. Unilateral occlusion of the foramen of Monro can present with asymmetric ventriculomegaly resulting in chronic headache. Though the symptoms of raised ICP may not be present, still endoscopic relief of ventriculomegaly leads to cure of headache. PMID:26933359

  19. [Vaginal ectopia of urethra as a cause of chronic recurrent cystitis in women: diagnosis and treatment].

    PubMed

    Derevianko, T I

    2009-01-01

    Ectopia of the urethral opening (female hypospadia) often causes chronic recurrent cystitis in women because of a retrograde delivery of urogenital infection from the introitus and vagina to the short wide urethra and urinary bladder. Etiologically, cystitis develops due to pathogenic vaginal microflora: Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma, urealyticum, Gardnerella vaginalis, Candida, E. coli and other gram-negative bacteria. In 64 female patients aged 16-57 years with female hypospadia (FH) the diagnosis was made by O'Donnel-Hirchhorn symptom. Identification of urinary and vaginal microflora was made using polymerase chain reaction. Radical treatment of chronic recurrent cystitis in FH is surgical transposition of the distal urethra and its opening in the typical place with pre- and perioperative anti-inflammatory therapy according to the pathogen or with drugs having combined antimycotic and antiprotosoic properties. One of such drugs safocid demonstrates a rapid therapeutic effect in mixed urogenital infections causing chronic recurrent cystitis in women. PMID:20209864

  20. Chronic ethanol treatment changes the number of beta-receptors in rat brain microvessels

    SciTech Connect

    Lucchi, L.; Cazzaniga, A.; Picotti, G.B.; Covelli, V.; Magnoni, M.S.; Borriero, L.; Spano, P.F.; Trabucchi, M.

    1984-01-01

    The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.