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Sample records for chronic clozapine treatment

  1. Subjective experiences of clozapine treatment by patients with chronic schizophrenia.

    PubMed

    Waserman, J; Criollo, M

    2000-05-01

    A 37-item survey covering a variety of somatopsychic domains was constructed to explore patients' subjective response to treatment with clozapine. The survey was administered to 130 patients with diagnoses of chronic schizophrenic or schizoaffective disorders who were on a stable clozapine regimen. The majority reported improvement in their level of satisfaction, quality of life, compliance with treatment, thinking, mood, and alertness. Most patients reported worsening in nocturnal salivation, and smaller numbers reported worsening in various gastrointestinal and urinary symptoms and weight gain. This general health survey highlights the patients' positive regard for clozapine, despite adverse bodily experiences. Subjective reports are a useful component of outcome measures of drug treatment.

  2. Leukocytosis after Clozapine Treatment in a Patient with Chronic Schizophrenia

    PubMed Central

    POLAT, Aslıhan; ÇAKIR, Uğur; GÜNDÜZ, Nermin

    2016-01-01

    Clozapine is an atypical antipsychotic drug that is approved by the US Food and Drug Administration (FDA) for the treatment of psychotic disorders. Agranulocytosis is a well-established side effect of clozapine; clozapine has also been associated with other blood dyscrasias like leukocytosis, albeit rarely. In this paper, we aim to report a case of possible clozapine-associated leukocytosis in a 41-year-old woman.

  3. Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat.

    PubMed

    Rupniak, N M; Hall, M D; Mann, S; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

    1985-08-01

    Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function.

  4. [Obsessive-Compulsive Symptoms in a Sample of Patients with Chronic Schizophrenia Under Clozapine Treatment].

    PubMed

    Schreiter, S; Hasan, A; Majic, T; Wullschleger, A; Schouler-Ocak, M; Bermpohl, F; Gutwinski, S

    2016-11-01

    Background: There is a high prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Antipsychotic treatment, especially duration and type of substance, is suspected to increase or even cause OCS. Methods: We examined in a naturalistic cross-sectional study the severity of OCS (Obsessive-Compulsive Inventory - Revised) and the incidence of obsessive-compulsive disorder (OCD) according to ICD-10 criteria in 70 patients with schizophrenia. 26 patients were treated with clozapine and 44 patients were treated with another second-generation antipsychotic (SGA). After group matching, the two groups did not differ significantly in age, gender, duration of illness, treatment duration with the current antipsychotic substance and chlorpromazine-equivalent dosage. Results: Patients treated with Clozapine showed a significantly higher rate of OCD (χ(2) = 7.304, p = 0.007) and a significantly higher severity of OCS (t = 2.216, p = 0.037) compared to patients treated with another SGA. For the whole sample, duration of treatment with the current antipsychotic medication correlated significantly (p = 0.033, r = 0.323) with the severity of OCS, controlled for duration of illness. However, there was no significant correlation between severity of OCS and duration of illness, controlled for duration of treatment with the current antipsychotic substance. Discussion: Our data suggest an interrelation between the development of OCS or OCD and antipsychotic treatment, especially clozapine. Thereby, duration of treatment is correlated with the severity of OCS, irrespective of the duration of illness.

  5. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

    PubMed

    Goudie, Andrew J; Cooper, Gillian D; Cole, Jon C; Sumnall, Harry R

    2007-03-01

    Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

  6. Chronic clozapine treatment in female rats does not induce weight gain or metabolic abnormalities but enhances adiposity: implications for animal models of antipsychotic-induced weight gain.

    PubMed

    Cooper, G D; Harrold, J A; Halford, J C G; Goudie, A J

    2008-02-15

    The ability of clozapine to induce weight gain in female rats was investigated in three studies with progressively lowered doses of clozapine. In an initial preliminary high dose study, clozapine at 6 and 12 mg/kg (i.p., b.i.d.) was found to induce weight loss. In a subsequent intermediate dose study, we obtained no evidence for clozapine-induced weight gain despite using identical procedures and doses of clozapine (1-4 mg/kg, i.p., b.i.d.) with which we have observed olanzapine-induced weight gain, hyperphagia, enhanced adiposity and metabolic changes [Cooper G, Pickavance L, Wilding J, Halford J, Goudie A (2005). A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology; 181: 80-89.]. Instead, clozapine induced weight loss without alteration in food intake and muscle mass or changes in levels of glucose, insulin, leptin and prolactin. However, these intermediate doses of clozapine enhanced visceral adiposity and elevated levels of adiponectin. In a final study, low doses of clozapine (0.25-0.5 mg/kg, i.p, b.i.d.) induced weight loss. These data demonstrate that clozapine-induced weight gain can be much more difficult to observe in female rats than olanzapine-induced weight gain. Moreover, these findings contrast with clinical findings with clozapine, which induces substantial weight gain in humans. Clozapine-induced enhanced adiposity appears to be easier to observe in rats than weight gain. These findings, along with other preclinical studies, suggest that enhanced adiposity can be observed in the absence of antipsychotic-induced weight gain and hyperphagia, possibly reflecting a direct drug effect on adipocyte function independent of drug-induced hyperphagia [e.g. Minet-Ringuet J, Even P, Valet P, Carpene C, Visentin V, Prevot D, Daviaud D, Quignard-Boulange A, Tome D, de Beaurepaire R (2007). Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Molecular Psychiatry; 12: 562

  7. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia.

    PubMed

    Kinoshita, Makoto; Numata, Shusuke; Tajima, Atsushi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Watanabe, Shinya; Umehara, Hidehiro; Shimodera, Shinji; Nakazawa, Takanobu; Kikuchi, Masataka; Nakaya, Akihiro; Hashimoto, Hitoshi; Imoto, Issei; Hashimoto, Ryota; Ohmori, Tetsuro

    2017-03-14

    Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

  8. Clozapine

    MedlinePlus

    ... Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); sleeping pills; terbinafine (Lamisil); and tranquilizers. Your doctor may need to ... double dose to make up for a missed one.If you miss taking clozapine for more than ...

  9. Adjunctive aripiprazole decreased metabolic side effects of clozapine treatment.

    PubMed

    Masopust, Jirí; Tůma, Ivan; Libiger, Jan

    2008-08-01

    Clozapine is an atypical antipsychotic indicated for the treatment of refractory schizophrenia. Clozapine treatment is associated with the metabolic side effects. Weight gain, hyperlipidemia and hyperglycemia are the risk factors for onset of diabetes and cardiovascular disorders. We report a case vignette of a patient in whom the decrease in negative and general psychopathology after adjunctive aripiprazole appeared simultaneously with a reduction of clozapine-induced increase in weight and metabolic measures. Combined application of clozapine and aripiprazole is in accordance with a neurobiological rationale and appears to be a safe and well tolerated.

  10. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

    PubMed Central

    Kinoshita, Makoto; Numata, Shusuke; Tajima, Atsushi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Watanabe, Shinya; Umehara, Hidehiro; Shimodera, Shinji; Nakazawa, Takanobu; Kikuchi, Masataka; Nakaya, Akihiro; Hashimoto, Hitoshi; Imoto, Issei; Hashimoto, Ryota; Ohmori, Tetsuro

    2017-01-01

    Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ. PMID:28335437

  11. 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.

  12. Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats.

    PubMed

    Invernizzi, R; Morali, F; Pozzi, L; Samanin, R

    1990-08-01

    1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus accumbens of rats given clozapine 20 or 60 mg kg-1 chronically, measured one day after the last drug dose, was not significantly different from that of vehicle-treated animals. 3. Challenge doses of 20 or 60 mg kg-1 clozapine produced similar increases in dopamine levels in the striatum and nucleus accumbens of animals which had received vehicle or clozapine 20 or 60 mg kg-1 once daily for 23 days, except that 1 h after administration 60 mg kg-1 clozapine had a greater effect in the nucleus accumbens. 4. In animals treated chronically with clozapine 20 and 60 mg kg-1 or vehicle, DOPAC levels in the striatum and nucleus accumbens were increased to the same extent by challenge doses of clozapine (20 or 60 mg kg-1). In animals treated chronically with clozapine, a challenge dose of 60 mg kg-1 had significantly greater effect on HVA only in the nucleus accumbens. 5. When DOPAC and HVA were measured post mortem in the striatum and nucleus accumbens 2 h after various oral doses of clozapine, it was found that 10 mg kg-1 significantly increased dopamine metabolites only in the nucleus accumbens whereas 100 mg kg-1 had this effect in both regions. Clozapine, 30mgkg-' significantly raised DOPAC levels in both regions but HVA was elevated only in the nucleus accumbens. 6. There appeared to be no appreciable changes in dopamine release and metabolism nor any reduction in the effect of clozapine in the nucleus accumbens after chronic drug treatment. In fact the effect was greater in chronically treated rats, particularly in the nucleus accumbens of animals given 60mgkg' clozapine. 7. It was confirmed that measurement of

  13. Successful treatment of polydipsia, water intoxication, and delusional jealousy in an alcohol dependent patient with clozapine.

    PubMed

    Margetić, Branimir; Aukst-Margetić, Branka; Zarković-Palijan, Tija

    2006-09-30

    The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.

  14. 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…

  15. 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…

  16. Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia.

    PubMed

    Davidson, M; Kahn, R S; Stern, R G; Hirschowitz, J; Apter, S; Knott, P; Davis, K L

    1993-02-01

    Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment-refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug-free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA.

  17. Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression.

    PubMed

    Ranjan, R; Meltzer, H Y

    1996-08-15

    The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.

  18. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    PubMed Central

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2009-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

  19. The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production.

    PubMed

    Danovich, Lena; Veenman, Leo; Leschiner, Svetlana; Lahav, Michal; Shuster, Vered; Weizman, Abraham; Gavish, Moshe

    2008-01-01

    It has been shown that the atypical antipsychotic drug clozapine increases the levels of the neurosteroid allopregnanolone in the rat brain. The 18 kDa translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been demonstrated to be involved in the process of steroid biosynthesis, in peripheral steroidogenic tissues as well as in glia cells in the brain. In the current study, we investigated the influence of chronic treatment with clozapine and other antipsychotics (thioridazine,sulpiride and risperidone) on TSPO binding in cell cultures and rat tissues. Clozapine significantly increased TSPO binding density in C6 rat glioma cells and in MA-10 mouse Leydig tumor cells, while the antipsychotic sulpiride had no effect on TSPO binding density in both cell lines. In addition, clozapine, but not sulpiride, significantly increased progesterone synthesis by MA-10 Leydig tumor cells. In an animal experiment, male Sprague-Dawley rats were treated with clozapine (20 mg/kg), risperidone (0.5 mg/kg), thioridazine (20 mg/kg), or sulpiride (20 mg/kg) for 21 days, followed by 7 days of withdrawal. Clozapine induced significant increases in TSPO binding in brain and peripheral steroidogenic tissues, whereas the other antipsychotics did not show such pronounced effects on TSPO binding. Our results suggest that TSPO may be involved in the modulation of steroidogenesis by clozapine.

  20. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

    PubMed

    Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

    2014-08-01

    Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups

  1. 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

  2. Clozapine Treatment and Cannabis Use in Adolescents with Psychotic Disorders – A Retrospective Cohort Chart Review

    PubMed Central

    Tang, Sephora M.; Ansarian, Aylar; Courtney, Darren B.

    2017-01-01

    Objectives To examine the association between clozapine treatment and frequency of cannabis use in adolescents with co-occurring psychotic and cannabis use disorder in a retrospective cohort chart review. Method We conducted a retrospective cohort chart review of patients diagnosed with a psychotic disorder and concurrent cannabis use disorder admitted to a tertiary care youth inpatient unit from 2010–2012. Longitudinal exposure and outcome data was coded month-by-month. Frequency of cannabis use was measured using a 7-point ordinal scale. Severity of psychosis was measured on a 3-point ordinal scale. Mixed effects regression modeling was used to describe the relationship between exposure and outcome variables. Results Thirteen patients had exposure to clozapine and fourteen had no exposure to clozapine. Cannabis use decreased in patients treated with clozapine, compared to patients treated with other antipsychotics (OR 2.8; 95% CI 0.97–7.9). Compared to no medication, clozapine exposure was associated with significantly less cannabis use (OR 7.1; 95% CI 2.3–22.3). Relative to treatment with other antipsychotics, clozapine exposure was significantly associated with lower severity of psychotic symptoms (OR 3.7; 95% CI 1.2–11.8). Conclusions Clozapine may lead to decreased cannabis use and psychotic symptoms in adolescents with concurrent psychosis and substance use. Clinical trials are warranted. PMID:28331504

  3. Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.

    PubMed

    Nakazawa, Takanobu; Kikuchi, Masataka; Ishikawa, Mitsuru; Yamamori, Hidenaga; Nagayasu, Kazuki; Matsumoto, Takuya; Fujimoto, Michiko; Yasuda, Yuka; Fujiwara, Mikiya; Okada, Shota; Matsumura, Kensuke; Kasai, Atsushi; Hayata-Takano, Atsuko; Shintani, Norihito; Numata, Shusuke; Takuma, Kazuhiro; Akamatsu, Wado; Okano, Hideyuki; Nakaya, Akihiro; Hashimoto, Hitoshi; Hashimoto, Ryota

    2017-03-01

    Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research.

  4. Long-term impacts of adolescent risperidone treatment on behavioral responsiveness to olanzapine and clozapine in adulthood.

    PubMed

    Qiao, Jing; Zhang, Qinglin; Li, Ming

    2014-01-03

    This preclinical study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response to olanzapine and clozapine in adulthood. Antipsychotic effect was indexed by a drug's suppressive effect on avoidance responding in a rat conditioned avoidance response (CAR) model. Male adolescent Sprague-Dawley rats were first treated with risperidone (1.0mg/kg, sc) or sterile water and tested in the CAR model for 5 consecutive days from postnatal days P 40 to 44. After they became adults (~P 80-84), they were switched to olanzapine (0.5mg/kg, sc), clozapine (5.0mg/kg, sc) or vehicle treatment and tested for avoidance for 5days. During the adolescent period, repeated risperidone treatment produced a persistent inhibition of avoidance response. Throughout the 5days of adulthood drug testing, rats previously treated with risperidone in adolescence made significantly fewer avoidance responses than the vehicle ones when they all were switched to olanzapine, indicating a risperidone-induced enhancement of behavioral sensitivity to olanzapine. In contrast, when switched to clozapine, rats previously treated with risperidone made significantly more avoidance responses than the vehicle rats, indicating a risperidone-induced decrease of behavioral sensitivity to clozapine. Performance in the prepulse inhibition of acoustic startle response in adulthood was not altered by adolescent risperidone treatment. Collectively, adolescent risperidone exposure induced a long-term change in behavioral sensitivity to other atypical antipsychotic drugs, with the specific direction of change (i.e., increase or decrease) dependent on the drug to be switched to. These long-lasting changes are likely mediated by drug-induced neuroplastic changes and may also have significant clinical implications for antipsychotic treatment of chronic patients with an early onset of psychotic symptoms.

  5. 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

  6. Neuropeptide Y mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats.

    PubMed

    Huang, X-F; Deng, Chao; Zavitsanou, Katerina

    2006-06-01

    Using quantitative in situ hybridization, this study examined regional changes in rat brain mRNA levels encoding neuropeptide Y (NPY) following olanzapine, clozapine and haloperidol administration (1.2, 1.5 and 2.0 mg/kg, oral) for 36 days. The NPY mRNA expression levels and patterns were examined after the last drug administration at both time points enabling the measurement of immediate effect at 2h and the effects after 48 h of drug administration. It was found that all these drugs had an immediate effect on NPY mRNA expression, while virtually all these changes normalized 48 h after the drug treatments. A similarity in altered NPY mRNA expression patterns was seen between the olanzapine and clozapine groups; however, haloperidol was very different. Olanzapine and clozapine administration decreased NPY mRNA levels in the nucleus accumbens, striatum and anterior cingulate cortex (from -60% to -77%, p<0.05). Haloperidol decreased NPY mRNA expression in the amygdala and hippocampus (-69%, -64%, p<0.05). In the lateral septal nucleus, NPY mRNA levels significantly decreased in the olanzapine group (-66%, p<0.05), a trend toward a decrease was observed in the clozapine group, and no change was found in the haloperidol treated group. These results suggest that the different effects of atypical and typical antipsychotics on NPY systems may reflect the neural chemical mechanisms responsible for the differences between these drugs in their effects in treating positive and negative symptoms of schizophrenia. The immediate decrease of NPY mRNA levels suggests an immediate reduction of NPY biosynthesis in response to these drugs.

  7. Blood Pressure and Heart Rate Changes During Clozapine Treatment.

    PubMed

    Norman, Sarah M; Sullivan, Kelli M; Liu, Fang; DiPaula, Bethany A; Jose, Pedro A; Kitchen, Christopher A; Feldman, Stephanie M; Kelly, Deanna L

    2016-09-27

    People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355  = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.

  8. 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…

  9. [Clozapine for the treatment of psychosis in 3 elderly patients with Parkinson's disease].

    PubMed

    Diraoui, S; van Melick, E J M; Jansen, P A F

    2004-11-27

    Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

  10. Clozapine in a patient with treatment-resistant schizophrenia and hypertrophic cardiomyopathy: a case report

    PubMed Central

    Sanchez, Asiel Yair Adan; Foster, Jessica J.; Plymen, Carla M.; Shergill, Sukhi

    2016-01-01

    Background There is currently limited experience in the initiation and maintenance of clozapine for treatment-resistant psychosis in adults with established structural heart disease. These complex patients require close supervision and liaison between colleagues. Here we present the successful experience of treating one such patient within our service and describe a monitoring plan to ensure that these treatments can be provided both safely and effectively. Case presentation A 36-year-old man with treatment-resistant schizophrenia and known hypertrophic cardiomyopathy (HCM) was admitted to a specialist unit for a trial of clozapine. His psychiatric illness was characterised by multimodal hallucinations and delusions combined with low mood and poor motivation. The diagnosis of HCM was made 3 years previously following a routine electrocardiogram (ECG), and he had remained asymptomatic throughout this time; there were concerns about the risk of initiating clozapine given his pre-existing cardiac condition. Baseline investigations were performed as per local guidelines prior to commencing clozapine; these were within normal limits other than a mildly raised troponin level of 54 ng/L (normal <16 ng/L), which was attributed to the HCM. In addition, baseline transthoracic echocardiography (TTE) was performed which showed no change in the structural heart disease in comparison with previous TTEs. Clozapine was started at 12.5 mg daily and up-titrated to 150 mg twice daily over 14 days as per our institute’s guidelines. The patient was monitored with regular testing of troponins, inflammatory markers and ECG. On day 18, the troponin level increased to 1371 ng/L. Creatine kinase and inflammatory markers remained stable. No changes in ECG or TTE were noted and the patient remained clinically asymptomatic. Cardiology opinion was sought and reported that the finding of an isolated elevated troponin was likely to reflect a ‘troponin leak’ in the context of increased

  11. »Treatment Resistance« Enigma Resolved by Pharmacogenomics 3 A Case Study of Clozapine Therapy in Schizophrenia

    PubMed Central

    Marić, Nadja P.; Nikolić, Slobodanka Pejović; Buzadžić, Ivana; Jovičić, Milica; Andrić, Sanja; Mihaljević, Marina; Pavlović, Zorana

    2015-01-01

    Summary The introduction of antipsychotic medication in the 1950s forever changed the outlook on the treatment of schizophrenia, although there is still a large proportion of patients who do not reach functional recovery. At least 30% of patients do not respond to clozapine, the tricyclic dibenzodiazepine with complex pharmacological actions, which was proven to be more effective than any other antipsychotic in the treatment of schizophrenia. According to most of the therapeutic guidelines for schizophrenia, clozapine is the third line therapy for patients who did not respond to other antipsychotics. Large inter-individual variability exists for clozapine bioavailability and plasma steady-state concentrations and clearance. Clozapine is metabolized by the cytochrome P450 oxidase enzyme family (CYP450). Cytochrome P450 1A2 (CYP1A2), which is polymorphically expressed in humans, is the main enzyme of clozapine metabolism. This case report addresses the influence of CYP1A2*1F genetic polymorphism on clozapine metabolism, explains the primary non-response of a young patient with schizophrenia due to increased gene expression in homozygous genotype *1F/*1F (increased metabolism of clozapine) and underlies the importance of personalizing schizophrenia treatment by means of genetic and other molecular tools, at least in the cases of »treatment resistance«. PMID:28356835

  12. Use of clozapine alongside chemotherapy in a treatment-resistant bipolar disorder patient with ovarian carcinoma: A case report and brief review

    PubMed Central

    Pakhre, Ashish; Krishnan, Aarya; Pattanayak, Raman Deep; Khandelwal, Sudhir K.

    2016-01-01

    Regular monitoring of blood counts ensures the safety of clozapine use; however, certain clinical situations may pose a dilemma for management such as use of clozapine in the presence of myelosuppressive chemotherapy. Further, there is very limited literature to guide such decisions. We report a case of a clozapine-stabilized, treatment-resistant bipolar disorder patient with ovarian carcinoma requiring chemotherapy. The clinical challenges are discussed in light of a brief review of the available reports. PMID:28197007

  13. Clozapine safety, 35 years later.

    PubMed

    Raja, Michele

    2011-07-01

    Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non 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. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.

  14. Chronic Myeloproliferative Neoplasms Treatment

    MedlinePlus

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

  15. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.

    PubMed

    Barbui, Corrado; Accordini, Simone; Nosè, Michela; Stroup, Scott; Purgato, Marianna; Girlanda, Francesca; Esposito, Eleonora; Veronese, Antonio; Tansella, Michele; Cipriani, Andrea

    2011-06-01

    This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

  16. Loxapine and Cyproheptadine Combined Limit Clozapine Rebound Psychosis and May Also Predict Clozapine Response

    PubMed Central

    McCarthy, Richard H.

    2016-01-01

    Clozapine has been consistently shown to be superior to other antipsychotics in the treatment of psychosis. However, clozapine usage has been limited due to required routine blood monitoring and the potential for life threatening side effects. We report a case of a 66-year-old female patient, who developed clozapine-induced agranulocytosis after 10 weeks of clozapine treatment and was subsequently successfully treated with a combination of loxapine and cyproheptadine. The combination is thought to mimic the pharmacological profile of clozapine, rendering it as a possible alternative to traditional clozapine treatment. PMID:27433365

  17. Loxapine and Cyproheptadine Combined Limit Clozapine Rebound Psychosis and May Also Predict Clozapine Response.

    PubMed

    Aboueid, Lila; McCarthy, Richard H

    2016-01-01

    Clozapine has been consistently shown to be superior to other antipsychotics in the treatment of psychosis. However, clozapine usage has been limited due to required routine blood monitoring and the potential for life threatening side effects. We report a case of a 66-year-old female patient, who developed clozapine-induced agranulocytosis after 10 weeks of clozapine treatment and was subsequently successfully treated with a combination of loxapine and cyproheptadine. The combination is thought to mimic the pharmacological profile of clozapine, rendering it as a possible alternative to traditional clozapine treatment.

  18. 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.

  19. Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Fujita, Yuko; Numata, Shusuke; Yasuda, Yuka; Fujimoto, Michiko; Ohi, Kazutaka; Umeda-Yano, Satomi; Ito, Akira; Ohmori, Tetsuro; Hashimoto, Kenji; Takeda, Masatoshi

    2014-10-17

    Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in the pathophysiology of schizophrenia. Many studies have investigated peripheral NMDA receptor-related glutamatergic amino acid levels because of their potential as biological markers. Peripheral d-serine levels and the ratio of d-serine to total serine have been reported to be significantly lower in patients with schizophrenia than in controls. Peripheral d-serine levels and the d-/l-serine ratio have also been reported to significantly increase in patients with schizophrenia as their clinical symptoms improve from the time of admission to the time of discharge. In this study, we examined whether peripheral NMDA receptor-related glutamatergic amino acids levels were altered in patients with treatment-resistant schizophrenia compared to controls and whether these peripheral amino acids levels were altered by clozapine treatment. Twenty-two patients with treatment-resistant schizophrenia and 22 age- and gender-matched healthy controls were enrolled. The plasma levels of d-serine, l-serine, glycine, glutamate, and glutamine were measured before and after clozapine treatment. We found that the plasma levels of d-serine and the d-/l-serine ratio were significantly lower in the patients before clozapine treatment than in the controls. The d-/l-serine ratio was significantly increased by clozapine treatment in patients, and no significant difference was observed in the plasma levels of d-serine and the d-/l-serine ratio between the patients after clozapine treatment and the controls. We also found that plasma glycine levels and the glycine/l-serine ratio were significantly increased following clozapine treatment in the patients, and the glycine/l-serine ratio was significantly higher in the patients after clozapine treatment than in the controls. There was no significant difference in the plasma levels of glutamate and glutamine both between the controls and patients and

  20. Risk of New-Onset Diabetes After Long-Term Treatment With Clozapine in Comparison to Other Antipsychotics in Patients With Schizophrenia.

    PubMed

    Schulte, Peter F J; Bocxe, Johanna T H; Doodeman, Hieronymus J; van Haelst, Ingrid M M; Cohen, Dan

    2016-04-01

    It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking.

  1. 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…

  2. Gabapentin treatment in clozapine-induced restless legs syndrome: two cases and a review of the literature

    PubMed Central

    Kumar, Vijaya; Venkatasubramanian, Ganesan

    2016-01-01

    Restless legs syndrome (RLS) is a neuro-sensorimotor disorder affecting 2–4% of adults. It is characterized by intense urges to move the legs, associated with unpleasant sensory disturbances in the legs occurring at rest and manifests mostly in the evening and night, relieved by movement. Diagnosis is primarily based on clinical presentation and the consensus criteria for the diagnosis have been established. Antipsychotics, the dopamine antagonists, have been reported to induce RLS. Dopamine agonists, the effective first-line treatment of RLS, carry the risk of inducing or worsening psychosis. Many nondopaminergic agents including antiepileptic medications have also been used in the treatment of primary RLS. In this report we describe clozapine-induced RLS in two patients with schizophrenia and its successful treatment with gabapentin, a nondopaminergic agent. In addition, we have reviewed the available literature on clozapine-induced RLS and its management. PMID:28101323

  3. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    PubMed Central

    2009-01-01

    Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated. PMID:20126316

  4. 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.

  5. Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [(18)F]DOPA PET Study.

    PubMed

    Kim, Euitae; Howes, Oliver D; Veronese, Mattia; Beck, Katherine; Seo, Seongho; Park, Jin Woo; Lee, Jae Sung; Lee, Yun-Sang; Kwon, Jun Soo

    2017-03-01

    Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n=12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [(18)F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.

  6. 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

  7. Risks and Benefits of Rapid Clozapine Titration.

    PubMed

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

    2016-05-18

    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.

  8. Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis.

    PubMed

    Lally, John; Tully, John; Robertson, Dene; Stubbs, Brendon; Gaughran, Fiona; MacCabe, James H

    2016-03-01

    The primary aim of this systematic review and meta-analysis was to assess the proportion of patients with Treatment Resistant Schizophrenia (TRS) that respond to ECT augmentation of clozapine (C+ECT). We searched major electronic databases from 1980 to July 2015. We conducted a random effects meta-analysis reporting the proportion of responders to C+ECT in RCTs and open-label trials. Five clinical trials met our eligibility criteria, allowing us to pool data from 71 people with TRS who underwent C+ ECT across 4 open label trials (n=32) and 1 RCT (n=39). The overall pooled proportion of response to C+ECT was 54%, (95% CI: 21.8-83.6%) with some heterogeneity evident (I(2)=69%). With data from retrospective chart reviews, case series and case reports, 192 people treated with C+ECT were included. All studies together demonstrated an overall response to C+ECT of 66% (95% CI: 57.5-74.3%) (83 out of 126 patients responded to C+ECT). The mean number of ECT treatments used to augment clozapine was 11.3. 32% of cases (20 out of 62 patients) with follow up data (range of follow up: 3-468weeks) relapsed following cessation of ECT. Adverse events were reported in 14% of identified cases (24 out of 166 patients). There is a paucity of controlled studies in the literature, with only one single blinded randomised controlled study located, and the predominance of open label trials used in the meta-analysis is a limitation. The data suggests that ECT may be an effective and safe clozapine augmentation strategy in TRS. A higher number of ECT treatments may be required than is standard for other clinical indications. Further research is needed before ECT can be included in standard TRS treatment algorithms.

  9. Capillary compared to venous blood sampling in clozapine treatment: patients׳ and healthcare practitioners׳ experiences with a point-of-care device.

    PubMed

    Bogers, Jan P A M; Bui, Hong; Herruer, Martien; Cohen, Dan

    2015-03-01

    Underuse of the antipsychotic clozapine for schizophrenia is an impediment to improving outcomes for patients. Because of its possible severe side effects, including granulocytopenia or even agranulocytosis, clozapine treatment entails regular WBC monitoring, which can be a major drawback for patients and practitioners. The HemoCue WBC DIFF system is a point-of-care device using capillary blood sampling which provides WBC counts with differentials, including granulocytes. We investigated if capillary sampling instead of conventional venous sampling might diminish the burden for patients and practitioners and motivate them to continue clozapine treatment. A randomized cross-over trial design was used to compare the two sampling methods. Patients׳ subjective experiences of various aspects of blood sampling were rated on a 10-cm visual analogue scale (VAS). Patients and practitioners were also asked if they had any preference for venous or capillary sampling and patients were asked if the sampling method influenced their motivation to continue clozapine treatment. Seventy-three patients were included in this study. Three dropped out before completion. The VAS ratings on all five aspects and the total burden experienced showed a consistent pattern favouring capillary blood sampling (p<0.001). This pattern was more pronounced for inpatients than for outpatients. Patients strongly preferred capillary testing (p<0.001). The method used moderately influenced their motivation for clozapine therapy. In this study patients tolerated capillary blood testing with a point-of-care device better than traditional venous sampling at a laboratory and practitioners also preferred it. Using this method might therefore boost clozapine prescription rates.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.

    PubMed

    Brouwers, E E M; Söhne, M; Kuipers, S; van Gorp, E C M; Schellens, J H M; Koks, C H W; Beijnen, J H; Huitema, A D R

    2009-01-01

    We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.

  15. [Relationship between clozapine plasma levels and withdrawal symptoms].

    PubMed

    Berecz, R; de la Rubia Martínez, A; Norberto Gamero, M J; Gutiérrez Casares, J R; Glaub, T; Degrell, I; Llerena, A

    2002-01-01

    Discontinuation of clozapine and an attempt to change his medication to sertindol has led to serious psychotic and somatic symptoms in an schizophrenic patient treated with clozapine for five years, however after readministration of clozapine these symptoms rapidly disappeared. To further analyse the case we have developed an HPLC method for the measurement of plasma levels of clozapine and its main metabolite N-desmethyl clozapine in order to monitor the plasma levels of clozapine and to correlate with the clinical symptoms. The present results confirmed that after discontinuation of clozapine no measurable amount of drug or its main metabolite were present in the plasma of the patient. The correlation between the plasma levels of clozapine and the changes in the clinical state of the patient confirmed that the patient's severe psychotic and somatic symptoms were the result of discontinuation of clozapine treatment. The clozapine plasma concentration of the patient reported here was low (100 ng/ml) compared to the generally accepted plasma levels for antipsychotic action of clozapine (350 ng/ml), however the somatic and psychotic clozapine withdrawal symptoms rapidly and completely disappeared.

  16. 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.

  17. Severe Relapsing Clozapine-Withdrawal Catatonia

    PubMed Central

    Shahrour, Tarek; Siddiq, Muez; Ghalib, Saad

    2015-01-01

    Catatonia as a clozapine-withdrawal syndrome has only been documented in the medical literature as case reports. We are reporting a case in which a 32-year-old man develops a catatonic state upon withdrawal of clozapine. The state was quite severe and needed ICU admission. The course was chronic and intermittent which we think was caused by the poor adherence to antipsychotics. The importance of identifying such cases early is underlined. PMID:26788394

  18. [Therapeutic drug monitoring of clozapine].

    PubMed

    Djerada, Zoubir; Daviet, Françoise; Llorca, Pierre-Michel; Eschalier, Alain; Saint-Marcoux, Franck; Bentué-Ferrer, Danièle; Libert, Fréderic

    2016-08-24

    Clozapine is a prototypical atypical antipsychotic used to treat severe schizophrenia and for which a therapeutic drug monitoring (TDM) is quite commonly proposed. Clozapine is rapidly absorbed (maximum concentration reached within 1 to 4hours), and is extensively metabolized in the liver by CYP1A2 to an active metabolite (and to a lesser extent, to inactive metabolites via other enzymes). Its half-life is 8 to 16h. A therapeutic range has been proposed for clozapine as some studies have reported both a relationship between low plasmatic concentrations and resistance to treatment (threshold level is likely between 250 and 400μg/L), and a relationship between high plasmatic concentrations and an increase in the occurrence of toxicity (alert level=1000μg/L). Given the data obtained in different studies, the TDM was evaluated for this molecule, to recommended.

  19. [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.

  20. Treatment of Chronic Cough.

    PubMed

    Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

    2017-01-01

    Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

  1. 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

  2. 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.

  3. 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 ...

  4. 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 ...

  5. Acute clozapine overdose: plasma concentration and outcome.

    PubMed

    Broich, K; Heinrich, S; Marneros, A

    1998-07-01

    Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical neuroleptic" drug for treatment of psychotic diseases. A 19-year-old schizophrenic female, treated with 400 mg clozapine per day, was admitted to the emergency department after ingestion of 5000 mg (50 x 100 mg tablets) of clozapine. Clozapine plasma level 2.5 hours after ingestion was 3.8 microg/ml (normal range 0.2-0.7 microg/ml) and very high in gastric lavage. Contrary to reported cases with such high plasma concentrations the patient suffered only from somnolence with intermittent periods of agitation and a mild anticholinergic syndrome with sinus tachycardia and slight hypotension. After detoxication with gastric lavage and short-term administration of pyridostigmine she remained stable, and 24 hours after ingestion she was transferred to the psychiatric unit without further sequelae. To prevent late-onset complications she was carefully monitored for five days. The clozapine plasma level 24 hours after the first measurement was normal. This case and others reported in the literature confirm that signs and symptoms after clozapine intoxication are variable and that high plasma levels are not lethal in every case.

  6. 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…

  7. 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…

  8. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia.

    PubMed

    Foster, Jessica; Lally, John; Bell, Victoria; Shergill, Sukhi

    2017-01-01

    A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service.

  9. 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

  10. Clozapine augments delta, theta, and right frontal EEG alpha power in schizophrenic patients.

    PubMed

    Maccrimmon, D; Brunet, D; Criollo, M; Galin, H; Lawson, J S

    2012-01-01

    Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4-3.6 Hz), theta (4.2-7.8 Hz), alpha (8.2-11.8 Hz), beta1 (12.2-15.8 Hz), beta2 (16.2-19.8 Hz), and beta3 (20.2-23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias.

  11. Clozapine Augments Delta, Theta, and Right Frontal EEG Alpha Power in Schizophrenic Patients

    PubMed Central

    MacCrimmon, D.; Brunet, D.; Criollo, M.; Galin, H.; Lawson, J. S.

    2012-01-01

    Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4–3.6 Hz), theta (4.2–7.8 Hz), alpha (8.2–11.8 Hz), beta1 (12.2–15.8 Hz), beta2 (16.2–19.8 Hz), and beta3 (20.2–23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias. PMID:23738206

  12. 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.

  13. Cytochrome P450 and therapeutic drug monitoring with respect to clozapine.

    PubMed

    Buur-Rasmussen, B; Brøsen, K

    1999-12-01

    Clozapine is an atypical antipsychotic drug that is mainly used for the treatment of refractory schizophrenia. Clozapine is eliminated by oxidation in the liver, predominantly by cytochrome P4501A2 (CYP1A2). Due to the influence of inhibitors, inducers and genetic factors on CYP1A2-activity, several studies have reported a very large interindividual variability in clozapine plasma concentrations at a fixed dose. A number of methods have been published for the measurement of clozapine and metabolites in plasma. Plasma concentrations are most frequently measured by high-performance liquid chromatography. Most methods measure clozapine and the main metabolite, norclozapine, whereas two methods measure clozapine and two metabolites. Several studies suggest that a minimum effective clozapine plasma concentration of >350 microg/l must be achieved in order to ensure acceptable clinical response, whereas the upper limit of the therapeutic interval not yet has been clearly defined. The occurrence of agranulocytosis, the most serious side-effect of clozapine treatment does not seem to be dose-related and it is not possible to predict which patients are at risk of developing agranulocytosis. The risk of central nervous system side-effects seems to increase with concentrations above 1300 microg/l. Monitoring of clozapine plasma concentrations is recommended during concomitant use of other drugs that are known to interact with the oxidation of clozapine, such as carbamazepine (inducer) or fluvoxamine (inhibitor). Overall, it is concluded that therapeutic drug monitoring may be of value in the clinical management of clozapine.

  14. [Blood clozapine level and therapeutic adjustment].

    PubMed

    Préterre, P

    1995-06-01

    We specify first the pharmacokinetic parameters of clozapine and the utilized dosage technique. In forty-four patients, aged 40 (25-66), suffering from schizophrenia developing for 20 years, with 11 years of hospitalisation. Clozapine has been prescribed for at least three months (until 44 months). We base ourselves on the opinion of the clinicians to show that the measurement of the plasma level can improve therapeutic-results. We analyse different situations where the adaptation of the posology is usefully conditioned by clozapinemia, particularly in case of important side effects, of high posology (over 600 mg) and of non response or inadequate response to the treatment.

  15. Impact of clozapine prescription on inpatient resource utilization.

    PubMed

    Sernyak, M J; Rosenheck, R; Desai, R; Stolar, M; Ripper, G

    2001-11-01

    Although clozapine has been demonstrated to be clinically superior to typical neuroleptics in refractory schizophrenia, it is also more expensive. It had been hoped that the increased costs associated with its use would be offset by decreases in the utilization of other expensive resources, especially inpatient care. All patients who had clozapine initiated during an inpatient hospitalization within the VA for schizophrenia over a 4-year period (N = 1415) were matched with a comparison group (N = 2,830) on key service utilization variables and other possible confounding demographic and clinical variables using propensity scoring-an accepted statistical method, although still relatively little used in psychiatry. By using centralized VA databases, subsequent inpatient resource utilization for the 3 years after index discharge was examined. Veterans exposed to clozapine while inpatients recorded 33 (36%) more inpatient days in the subsequent 3 years after discharge than the comparison group (124 +/- 190 days vs. 91 +/- 181 days, p = .0002). When all patients exposed to clozapine were divided according to whether they had received 1 year of clozapine treatment after discharge, those that received less than 1 year's treatment recorded significantly more inpatient days than either those maintained on clozapine or controls. These results suggest that in actual practice clozapine treatment may cost substantially more than treatment with conventional neuroleptics.

  16. Atypical Antipsychotics in the Treatment of Depressive and Psychotic Symptoms in Patients with Chronic Schizophrenia: A Naturalistic Study

    PubMed Central

    Baratta, Stefano; Di Vittorio, Cristina; Lester, David; Girardi, Paolo; Pompili, Maurizio

    2013-01-01

    Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds. PMID:23401771

  17. Atypical antipsychotics in the treatment of depressive and psychotic symptoms in patients with chronic schizophrenia: a naturalistic study.

    PubMed

    Innamorati, Marco; Baratta, Stefano; Di Vittorio, Cristina; Lester, David; Girardi, Paolo; Pompili, Maurizio; Amore, Mario

    2013-01-01

    Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.

  18. Amisulpride Augmentation for Clozapine-Refractory Positive Symptoms: Additional Benefit in Reducing Hypersialorrhea

    PubMed Central

    Bogorni, Fabiani; Moreira, Frederico Fernandes; Pimentel, Eduardo Mylius; Grohs, Géder Evandro Motta; Diaz, Alexandre Paim

    2015-01-01

    One-third to half of patients taking clozapine suffer from refractory symptoms despite adequate treatment. Among other adverse effects, clozapine-induced hypersalivation (CIH) occurs in approximately half of all patients. This is a case of a 30-year-old male with refractory schizophrenia; in this patient, the remission of residual positive symptoms, as well as the reduction of CIH, was achieved by treatment with clozapine augmented with amisulpride. PMID:25838958

  19. Inflammatory response to clozapine in the absence of myocarditis: case report

    PubMed Central

    Gee, Siobhan; Shergill, Sukhi S.

    2016-01-01

    Summary A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent. Clozapine was started and then stopped twice following extensive investigation and with specialist cardiology consultation. Physical symptoms and CRP elevation resolved shortly after clozapine cessation. We believe this constituted an idiosyncratic systemic inflammatory response to clozapine treatment. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703781

  20. 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

  1. 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

  2. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  3. 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

  4. Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement

    PubMed Central

    Kar, Nilamadhab; Barreto, Socorro; Chandavarkar, Rahul

    2016-01-01

    Clozapine is effective in treatment resistant schizophrenia; however, it is underutilised probably because of its side effects. The side effects are also the potential reasons for clozapine discontinuation. A mandatory requirement for its use is regular monitoring of white blood cell count and absolute neutrophil count. However there are many side effects that need monitoring in clinical practice considering their seriousness. This article tries to summarise the clinical concerns surrounding the serious side effects of clozapine some of which are associated with fatalities and presents a comprehensive way to monitor patients on clozapine in clinical practice. It emphasizes the need to broaden the monitoring beyond the mandatory investigations. This may help in improving the safety in clinical practice and increasing clinician confidence for greater and appropriate use of this effective intervention. PMID:27776383

  5. 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…

  6. [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.

  7. Adult response to olanzapine or clozapine treatment is altered by adolescent antipsychotic exposure: A preclinical test in the phencyclidine hyperlocomotion model

    PubMed Central

    Shu, Qing; Hu, Gang; Li, Ming

    2016-01-01

    This study examined how repeated olanzapine (OLZ) or clozapine (CLZ) treatment in adolescence alters sensitivity to the same drug in adulthood in the phencyclidine (PCP) hyperlocomotion model. Male adolescent Sprague-Dawley rats (postnatal day (P) 44–48) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10.0 or 20.0 mg/kg, sc) and tested in the PCP (3.2 mg/kg, sc)-induced hyperlocomotion model for five consecutive days. Then a challenge test with OLZ (0.5 mg/kg) or CLZ (5.0 mg/kg) was administered either during adolescence (~P 51) or after the rats matured into adults (~P 76 and 91). During adolescence, repeated OLZ or CLZ treatment produced a persistent inhibition of PCP-induced hyperlocomotion across the five test days. In the challenge test during adolescence, rats previously treated with OLZ did not show a significantly stronger inhibition of PCP-induced hyperlocomotion than those previously treated with vehicle (VEH). In contrast, those previously treated with CLZ showed a weaker inhibition than the VEH controls. When assessed in adulthood, the enhanced sensitivity to OLZ and the decreased sensitivity to CLZ were detected on ~P 76, even on ~P 91 in the case of OLZ. These findings suggest that adolescent OLZ or CLZ exposure can induce long-term alterations in antipsychotic response that persist into adulthood. PMID:24257809

  8. 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.

  9. CHRONIC URTICARIA AND TREATMENT OPTIONS

    PubMed Central

    Godse, Kiran Vasant

    2009-01-01

    Chronic urticaria has a wide spectrum of clinical presentations and causes. Still, despite our best efforts no cause may be found in the majority of cases. The treatment options are: Primary prevention in the form of avoidance of aggravating factors; counseling; antihistamines; leukotriene receptor antagonists; prednisolone; sulfasalazine and a host of immunosuppressives like methotrexate, cyclosporine, omalizumab etc. PMID:20101328

  10. Chronic constipation: Current treatment options

    PubMed Central

    Liu, Louis Wing Cheong

    2011-01-01

    Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipation-dominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada. PMID:22114754

  11. Increased Impulsivity and Disrupted Attention Induced by Repeated Phencyclidine are not Attenuated by Chronic Quetiapine Treatment

    PubMed Central

    Amitai, Nurith; Markou, Athina

    2009-01-01

    Atypical antipsychotic medications differ in how effectively they attenuate cognitive and other deficits in schizophrenia. The present study aimed to explore whether quetiapine, an atypical antipsychotic medication, would reverse disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity, induced by repeated administration of the psychotomimetic phencyclidine (PCP). In confirmation of previous findings, repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for two consecutive days, followed by a 2-week PCP-free period and then five consecutive days of PCP treatment) increased premature responding (impulsivity), decreased accuracy (attention), and increased response latencies (processing speed) and timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5 or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in performance, while at the highest dose used, quetiapine disrupted 5-CSRTT performance in the absence of PCP treatment and tended to exacerbate the PCP-induced increase in premature responding. Considering that clozapine, another atypical antipsychotic, was shown previously to reverse PCP-induced deficits in the same task (Amitai et al. 2007), the present findings demonstrate differences between clozapine and quetiapine in their effectiveness on schizophrenia-like cognitive deficits and impulsivity that may be attributable to their different receptor affinity profiles. PMID:18809428

  12. 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.

  13. 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…

  14. 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…

  15. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    PubMed Central

    Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease. PMID:28303200

  16. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine.

    PubMed

    Leonardo, Quevedo-Florez; Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  17. Impramine, fluoxetine and clozapine differently affected reactivity to positive and negative stimuli in a model of motivational anhedonia in rats.

    PubMed

    Scheggi, S; Pelliccia, T; Ferrari, A; De Montis, M G; Gambarana, C

    2015-04-16

    Anhedonia is a relevant symptom in depression and schizophrenia. Chronic stress exposure induces in rats escape deficit, disrupts the dopaminergic response to palatable food and the competence to acquire sucrose self-administration (SA), thus configuring a possible model of motivational anhedonia. Repeated lithium administration reverts stress effects and brings back to control values the breaking point (BP) score, a measure of reward motivation. In this study, we tested on this model two antidepressants, imipramine and fluoxetine, and two antipsychotics, haloperidol and clozapine. The dopaminergic response to sucrose consumption was studied in non food-deprived rats in terms of dopamine D1 receptor signaling in the nucleus accumbens shell (NAcS). More specifically, we studied the modifications in dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32) phosphorylation pattern following sucrose consumption. Fluoxetine reverted the escape deficit and showed no effects on dopaminergic response and sucrose SA. Imipramine reverted sucrose SA and dopamine response deficit in half of the rats and the escape deficit in all animals. Haloperidol did not affect stress-induced deficits. Clozapine-treated rats recovered the dopaminergic response to sucrose consumption and the competence to acquire sucrose SA, although they still showed the escape deficit, thus confirming that motivation toward reward may be dissociated from that to punishment escape. These results indicate that imipramine or fluoxetine are not endowed with a rapid onset antianhedonic effect. On the other hand, clozapine treatment showed a motivational antianhedonic activity similar to that observed after lithium treatment.

  18. Switching bipolar disorder patients treated with clozapine to another antipsychotic medication: a mirror image study

    PubMed Central

    Ifteni, Petru; Teodorescu, Andreea; Moga, Marius Alexandru; Pascu, Alina Mihaela; Miclaus, Roxana Steliana

    2017-01-01

    Bipolar disorder (BD) is associated with periodic symptom exacerbations, leading to functional impairment, and increased risk of suicide. Although clozapine has never been approved for the treatment of BD, it is occasionally used in severe mania. The aim of the study is to evaluate the risks and benefits of switching clozapine in remitted BD patients. This is an observational, mirror image study of 62 consecutive remitted BD outpatients treated with clozapine. Twenty-five patients were switched to another antipsychotic following a change in a drug reimbursement rule, while 37 continued on clozapine. The mean time in remission was shorter for the switched group (9.2±4 months vs 13±6 months, P=0.018), and the number of patients who relapsed was larger (n=21 vs n=8, P<0.0001). The results suggest that switching from clozapine to another antipsychotic may increase the risk of relapses in remitted patients with BD. PMID:28182153

  19. 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.

  20. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  1. Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series.

    PubMed

    Takeuchi, Ippei; Suzuki, Tatsuyo; Kishi, Taro; Kanamori, Daisuke; Hanya, Manako; Uno, Junji; Fujita, Kiyoshi; Kamei, Hiroyuki

    2015-04-30

    Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

  2. Effect of clozapine on neutrophil kinetics in rabbits.

    PubMed

    Iverson, Suzanne; Kautiainen, Antti; Ip, Julia; Uetrecht, Jack P

    2010-07-19

    Clozapine is an atypical antipsychotic drug effective in the treatment of refractory schizophrenia; however, its use is limited due to its propensity to cause agranulocytosis in some patients. Little is known about the mechanism of idiosyncratic drug-induced agranulocytosis, in part because of the lack of a valid animal model. Clozapine is oxidized by activated human neutrophils and bone marrow cells to a reactive nitrenium ion by the myeloperoxidase-hydrogen peroxide system of neutrophils. This reactive metabolite has been shown in vitro to induce the apoptosis of neutrophils and bone marrow cells. While in vitro studies demonstrated the toxic potential of clozapine upon oxidation, it is not clear if similar conditions occur in vivo. In response to the difficulties encountered with detecting apoptotic neutrophils in vivo, we conducted a series of studies in rabbits using two fluorescent cell-labeling techniques to study the effect of clozapine treatment on neutrophil kinetics, that is, their rates of production and removal from circulation. The fluorescein dye, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), was used as a general cell label to measure the half-life of neutrophils in blood. In addition, the thymidine analogue, 5-bromo-2-deoxyuridine (BrdU), was used to label dividing cells, thus enabling the measurement of the efflux of neutrophils from the bone marrow. Clozapine, indeed, increased the rate of both the release of neutrophils from the bone marrow and their subsequent disappearance from circulation. Failure of the bone marrow to compensate for a shorter neutrophil half-life could lead to agranulocytosis. Alternatively, the damage to neutrophils caused by clozapine could, in some patients, lead to an immune-mediated response against neutrophils resulting in agranulocytosis.

  3. NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure.

    PubMed

    Halene, Tobias B; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda C; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula L; Giannaris, Eustathia Lela; Hof, Patrick R; Roussos, Panos; Dracheva, Stella; Hemby, Scott E; Akbarian, Schahram

    2016-02-01

    Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.

  4. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia

    PubMed Central

    Foster, Jessica; Bell, Victoria; Shergill, Sukhi

    2017-01-01

    A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28243462

  5. Satisfaction With Chronic Pain Treatment

    PubMed Central

    Islami Parkoohi, Parisa; Amirzadeh, Kimia; Mohabbati, Vahid; Abdollahifard, Gholamreza

    2015-01-01

    Background: The effects of chronic pain (CP) on physical function and emotional and mental health of individuals, families, and community are well established. No adequate research is conducted in this field in Iran. Objectives: The current study aimed to assess the prevalence of CP, types of treatments used for CP and patients’ satisfaction with the CP treatments in an Iranian urban population. Patients and Methods: In the current study, CP was investigated using the international CP questionnaire administered to 1,050 adults living in Shiraz, Iran. The questionnaire consisted of 28 questions used to evaluate the effects of CP on the studied population including the prevalence of CP, pharmacological and non-pharmacological treatments for CP, and participants’ satisfaction with CP treatments. All the statistical analyses were performed using SPSS software, version 18. Results: In the current study, 6.95% of the 1,050 subjects willing to participate in the study had CP for more than six months. According to the results, 54% of the subjects with CP used analgesics, mostly non-steroidal anti-inflammatory drugs (NSAIDs) and narcotic analgesics. Besides, 37% of the subjects used other pain relief methods such as traditional medicine and acupuncture. The results also showed an acceptable rate of satisfaction with treatments. Conclusions: The number of subjects with CP proved it as a prevalent problem in the study population. Furthermore, characteristics and associations of those experiencing CP demonstrated that it might have significant negative health and psychosocial outcomes in this group. The problem was found significant enough to consider special health programs to prevent and manage CP in urban population of Shiraz. PMID:26473099

  6. Chronic diarrhoea: investigation, treatment and nursing care.

    PubMed

    Metcalf, Chris

    Chronic diarrhoea is a distressing symptom of a number of conditions. This article explains the assessment of patients at the initial outpatient visit through the various investigations and finally medical and surgical treatment. Emphasis is placed on the nursing management of chronic diarrhoea, particularly the treatment of physical effects such as dehydration and perianal skin soreness, and the psychological aspects of care.

  7. Surgical Treatment of Chronic Orofacial Pain

    PubMed Central

    Sisk, Allen L.

    1983-01-01

    There are many conditions in which chronic orofacial pain is a major diagnostic and therapeutic problem. It is generally accepted that surgical treatment for these chronic pain problems should be resorted to only when more conservative treatments have been ineffective. Literature concerning selected orofacial pain problems is reviewed and the indications for surgical management are discussed. PMID:6370045

  8. Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (norclozapine) in human serum.

    PubMed

    Rao, L V; Snyder, M L; Vallaro, G M

    2009-01-01

    Clozapine is indicated for the treatment of schizophrenia and related psychotic disorders. Several methods have been developed for monitoring Clozapine levels; however, they possess limited specificity and are often laborious. This study describes a simple liquid chromatography/tandem mass spectrometer (LCMS) method in human serum. The ion transitions monitored were m/z 327, 270, 296 for Clozapine, m/z 313, 192, 227 for Norclozapine and m/z 328, 271 for Loxapine. The assay is linear (25-1000 ng/ml) and showed a good correlation (r=0.98) within the analytical range of 79-1210 ng/ml in human serum. This assay is highly specific and sensitive for the simultaneous measurements of Clozapine and Norclozapine. The simplification of this assay makes it ideal for high throughput analyses of the patient samples in a routine clinical laboratory staffed with general medical technologists.

  9. [Risk minimization evolution of agranulocytosis caused by the administration of pharmaceutical products containing Clozapine in Argentina].

    PubMed

    Bergman, Maximiliano; Bignone, Inés; Bisio, Agustina; Bologna, Viviana; Sabatini, Analía

    2011-01-01

    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. Compared to other drugs, Clozapine has shown remarkable advantages. However, its use entails a serious risk of causing hematologic alterations (including granulocytopenia/agranulocytosis). Such alterations may result in death if they are not detected early. Clozapine was recalled from the worldwide market and it was reintroduced some years later, but a mandatory hematologic monitoring program was implemented. The program was established in Argentina by ANMAT's regulation 935/00. It helped to monitor of the use of the drug. Currently, the incidence of agranulocytosis in our country is lower than the international incidence rates.

  10. 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.

  11. Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

    PubMed Central

    Bilbily, John; McCollum, Betsy

    2017-01-01

    A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1) occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2) had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3) required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA) receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine.

  12. Comparative analysis of the treatment of chronic antipsychotic drugs on epileptic susceptibility in genetically epilepsy-prone rats.

    PubMed

    Citraro, Rita; Leo, Antonio; Aiello, Rossana; Pugliese, Michela; Russo, Emilio; De Sarro, Giovambattista

    2015-01-01

    Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

  13. 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.

  14. 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.

  15. Use of aripiprazole in clozapine induced enuresis: report of two cases.

    PubMed

    Lee, Myung-Ji; Kim, Chul-Eung

    2010-02-01

    This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

  16. 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.

  17. Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

    PubMed Central

    Benedetti, Alessandra; Di Paolo, Antonello; Lastella, Marianna; Casamassima, Francesco; Candiracci, Chiara; Litta, Antonella; Ciofi, Laura; Danesi, Romano; Lattanzi, Lorenzo; Del Tacca, Mario; Cassano, Giovanni Battista

    2010-01-01

    Aim: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. Patients: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1±12.0 and 5.4±0.5, respectively, were treated with clozapine (mean dose 292.9±220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 ± 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. Results: Total scores at BPRS decreased significantly (from 59.1±12.0 to 51.1±15.6, p=0.007) after aripirazole augmentation. In particular, the factors “thought disorder” (from 10.4±4.4 to 9.0±4.5, p=.047) and “anergia” (from 10.0±2.7 to 8.0±2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. Conclusion: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation. PMID:20648219

  18. Clozapine modifies the differentiation program of human adipocytes inducing browning

    PubMed Central

    Kristóf, E; Doan-Xuan, Q-M; Sárvári, A K; Klusóczki, Á; Fischer-Posovszky, P; Wabitsch, M; Bacso, Z; Bai, P; Balajthy, Z; Fésüs, L

    2016-01-01

    Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson–Golabi–Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly upregulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested whether browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors, it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the upregulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine-induced beige cells displayed increased basal and oligomycin-inhibited (proton leak) oxygen consumption, but these cells showed a lower response to cAMP stimulus as compared with control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for the treatment of SGA-induced weight gain. PMID:27898069

  19. [Operative treatment of chronic pleuritis].

    PubMed

    Duzhyĭ, I D; Hres'ko, I Ia; Chumak, S O; Elastal, R Z

    2008-09-01

    Basing on the literature data and own experience, grounded on results of follow-up on 2000 patients, suffering an acute pleuritis and performance of more than 200 operative interventions--pleurectomy, the clinic-radiological classification of chronic pleuritis, mostly answering the practical health care necessities, was proposed by the authors.

  20. Chronic laminitis: current treatment strategies.

    PubMed

    Parks, Andrew; O'Grady, Stephen E

    2003-08-01

    Laminitis is divided into four different phases: developmental, acute, subacute, and chronic. The focus of this article is on treating the laminitic horse after the cessation of therapy for the acute phase, that is, usually 2 to 4 weeks after the onset of clinical signs.

  1. General Approach to Treatment of Chronic Myelomonocytic Leukemia

    MedlinePlus

    ... Leukemia General Approach to Treatment of Chronic Myelomonocytic Leukemia Stem cell transplant (SCT) is the only way ... of Chronic Myelomonocytic Leukemia More In Chronic Myelomonocytic Leukemia About Chronic Myelomonocytic Leukemia Causes, Risk Factors, and ...

  2. Computers in the treatment of chronic aphasia.

    PubMed

    Katz, Richard C

    2010-02-01

    Computers and related technology can increase the amount of treatment received by adults with chronic aphasia. Computers used in treatment, however, are only valuable to the patient if the intervention is efficacious. Real and potential applications of computer technology are discussed in the context of three roles of computerized aphasia treatment for adults with chronic aphasia. Pertinent studies regarding Phases 1 and 2 are briefly described. The only Phase 3 study of efficacy of computerized aphasia treatment is more fully described and its implications discussed.

  3. 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

  4. Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea.

    PubMed

    Rajagopal, Veeramanikandan; Sundaresan, Lakshmikirupa; Rajkumar, Anto P; Chittybabu, Chithra; Kuruvilla, Anju; Srivastava, Alok; Balasubramanian, Poonkuzhali; Jacob, Kuruthukulangara S; Jacob, Molly

    2014-12-01

    The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

  5. 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

  6. The comparative effects of clozapine versus haloperidol on initiation and maintenance of alcohol drinking in male alcohol-preferring P rat.

    PubMed

    Chau, David T; Khokhar, Jibran Y; Dawson, Ree; Ahmed, Jayme; Xie, Haiyi; Green, Alan I

    2013-12-01

    Alcohol use disorder, characterized by modest levels of alcohol use, commonly occurs in patients with schizophrenia and dramatically worsens their course. Recent data indicate that the atypical antipsychotic clozapine, but not the typical antipsychotic haloperidol, decreases alcohol drinking both in patients with schizophrenia and also in the Syrian golden hamster, an animal model of moderate alcohol drinking. The present study was designed to assess the comparative effects of clozapine and haloperidol in the alcohol-preferring (P) rat, an animal model of alcoholism. First, the study investigated the comparative effects of clozapine and haloperidol on initiation of alcohol consumption in P rats, which models the early stage of alcoholism. Second, the study assessed the comparative effects of clozapine and haloperidol on maintenance of chronic alcohol consumption in P rats to provide a clue as to whether either drug may also limit alcohol consumption in alcohol-dependent patients. Clozapine attenuated the initiation of alcohol drinking and development of alcohol preference while haloperidol did not. However, neither clozapine nor haloperidol attenuated maintenance of chronic alcohol drinking. Taken together, the current data suggest that clozapine, but not haloperidol, may be effective at reducing alcohol abuse or non-dependent drinking and the P rat, used within an alcohol initiation paradigm, and may differentiate the effects of clozapine and haloperidol on alcohol drinking.

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

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About 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 ...

  8. Evaluation of a general practitioner-led cardiometabolic clinic: Physical health profile and treatment outcomes for clients on clozapine.

    PubMed

    Coates, Dominiek; Woodford, Patricia; Higgins, Oliver; Grover, Deborah

    2017-02-24

    The present study is a review of a cardiometabolic clinic for consumers taking clozapine. This clinic was recently established and co-located with the clozapine clinic at a regional hospital in New South Wales, Australia, to enhance engagement and improve the physical health outcomes of consumers taking antipsychotic medication. A descriptive analysis of clients' (n = 73) information collected during routine care for the first 6 months of the clinic's operation, from January 2016 to July 2016, was conducted. First-visit data were analysed to establish a client profile, consisting of weight, height, blood pressure, pulse, a range of blood measurements, smoking status, alcohol consumption, and eating and exercise habits. Data collected for clients who had three or more visits with the general practitioner (n = 40) were analysed separately for outcomes. Two case studies are used to depict the service received and client profile. At the first appointment, the majority of clients had metabolic syndrome that was mostly left untreated; many of these clients were commenced on metformin. The outcomes are positive, and show that the majority of clients lost weight (82.5%) and had a reduction in body mass index (84.6%); nearly half (44.4%) had a reduction in waist circumference. The majority of clients self-reported increased physical activity (72.5%, n = 29) and positive dietary changes (77.5%, n = 31) since their first appointment. The model trialled by the cardiometabolic clinic integrated a specialist mental health and primary care service, and demonstrates success in engaging clients with severe mental illness in physical health care. Co-location is conceptualized as critical for positive patient outcomes and high levels of engagement.

  9. 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…

  10. 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

  11. 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

  12. Clozapine--a dangerous drug in a clozapine-naïve subject.

    PubMed

    Stanworth, D; Hunt, N C A; Flanagan, R J

    2012-01-10

    Clozapine is a uniquely effective antipsychotic, but is very toxic in clozapine-naïve subjects. A 34-year-old male patient in a mental health facility, who was not prescribed clozapine, took 350 mg clozapine obtained from another patient at night. He was found dead the next morning. The presence of cardiomegaly related to obesity may have increased the risk of suffering an acute cardiac event after ingestion of clozapine. The medication prescribed to the patient was not thought to have contributed to the fatal outcome. Post mortem femoral blood clozapine and norclozapine concentrations were 0.48 and 0.20mg/L, respectively. By way of comparison, audit of 104,127 plasma samples (26,796 patients) assayed for therapeutic drug monitoring purposes 1993-2007, showed plasma clozapine 0.35 mg/L or more in 57.5% samples (8.4% 1mg/L or more). Those involved in the investigation of clozapine-associated deaths need to be aware that that death in an adult may occur after a single 'therapeutic' dose. A diagnosis of fatal clozapine poisoning cannot be made solely on the basis of a post mortem blood clozapine measurement.

  13. [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.

  14. Treatment of chronic prostatitis/chronic pelvic pain syndrome

    PubMed Central

    Nickel, J. Curtis

    2008-01-01

    Acceptance of the National Institutes of Health definition of Category III Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and the development and validation of the Chronic Prostatitis Symptom Index has stimulated significant research into treatment of this condition. Evidence-based suggestions for treatment include the following. (i) Antimicrobials cannot be recommended for men with longstanding, previously treated CP/CPPS. (ii) Alpha-blockers can be recommended as first-line medical therapy, particularly in alpha-blocker-naïve men with moderately severe symptoms who have relatively recent onset of symptoms. (iii) Alpha-blockers cannot be recommended in men with longstanding CP/CPPS who have tried and failed alpha-blockers in the past. And (iv) anti-inflammatory therapy, finasteride and pentosan polysulfate are not recommended as primary treatment; however, they may have a useful adjunctive role in a multimodal therapeutic regimen. Early data on herbal therapies, particularly quercetin and cernilton, are intriguing, but larger multicentre, randomised, placebo-controlled trials are required before a high level of evidence recommendation can be made on its use. At this time, surgery (including minimally invasive) is recommended only for definitive indications and not generally for CP/CPPS. PMID:17954024

  15. In a randomized placebo-controlled add-on study orlistat significantly reduced clozapine-induced constipation.

    PubMed

    Chukhin, Evgeny; Takala, Pirjo; Hakko, Helinä; Raidma, Mirjam; Putkonen, Hanna; Räsänen, Pirkko; Terevnikov, Viacheslav; Stenberg, Jan-Henry; Eronen, Markku; Joffe, Grigori

    2013-03-01

    Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

  16. Update on the treatment of chronic urticaria.

    PubMed

    Curto-Barredo, L; Silvestre, J F; Giménez-Arnau, A M

    2014-06-01

    Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.

  17. Probiotics in the Treatment of Chronic Rhinoconjunctivitis and Chronic Rhinosinusitis

    PubMed Central

    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

  18. New treatments for chronic prostatitis/chronic pelvic pain syndrome

    PubMed Central

    Strauss, Adam C.; Dimitrakov, Jordan D.

    2010-01-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition among men of a wide age range, with detrimental effects on quality of life. The etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although progress has been made in these domains in recent years. A wide variety of pharmacologic and nonpharmacologic therapies have been studied in clinical trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is increasingly viewed as a condition that involves variable degrees of neuropathic pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic antidepressants are often used in other neuropathic pain conditions and, therefore, are considered potential treatments for CP/CPPS. Few studies of these agents in patients with CP/CPPS have been reported, but future clinical trials should help to determine their utility and to characterize the pathogenetic mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker, genomic, and imaging studies, in addition to epidemiologic and symptom-based assessments, will maximize the ability to probe disease etiology and pathogenesis, as well as identify effective treatment. PMID:20142810

  19. [Latex ligation in treatment of chronic hemorrhoids].

    PubMed

    Ektov, V N; Somov, K A

    2015-01-01

    We analyzed the results of treatment of 432 patients with chronic hemorrhoids using different variants of latex ligation. New technique including ligation of mucosa and submucosa of low-ampullar rectum providing ligation of hemorrhoidalvessels, lifting and recto-anal repair is developed and suggested. This method is advisable to use in case of chronic internal hemorrhoids stages I and II. The authors recommend simultaneous combined ligation of mucosa of low-ampullar rectum and internal hemorrhoids for stages III and IV. Different variants of latex ligation with external hemorrhoids excision were used in 103 patients. Pointed variants of latex ligation preserve important advantages including mini-invasiveness, simplicity and wide availability, low cost. Good remote results were obtained after these procedures in 87.3% of observations. Suggested tactics extends use of latex ligation and increases its effectiveness in treatment of different stages and forms of chronic hemorrhoids.

  20. Lubiprostone: a novel treatment for chronic constipation.

    PubMed

    Lacy, Brian E; Levy, L Campbell

    2008-01-01

    Chronic constipation is highly prevalent, reduces patients' quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription medications are currently Food and Drug Administration (FDA) approved and available for the treatment of chronic constipation in adults. This review will focus on lubiprostone, the newest medication available for the treatment of chronic constipation. Lubiprostone is a bicyclic fatty acid metabolite analogue ofprostaglandin E1. It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation. This article will provide a brief overview on chloride channel function in the gastrointestinal tract, describe the structure, function, and pharmacokinetics of lubiprostone, and discuss the safety and efficacy of this new medication.

  1. Treatment of chronic airways obstruction with indomethacin.

    PubMed

    Hume, M; Eddey, V

    1977-10-01

    The effect of indomethacin is reported in five patients with chronic asthma. There was both subjective and objective improvment and, in three of the patients, a reduction in steroid dosage. The results suggest that the drug may be of value in the treatment of this condition.

  2. 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.

  3. Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia.

    PubMed

    Levin, Edward D; Christopher, N Channelle

    2006-03-01

    Clozapine is an effective atypical antipsychotic drug used to treat schizophrenia. It has the advantage of producing fewer extrapyramidal motor side effects than typical antipsychotic drugs such as haloperidol. Schizophrenia involves more than the hallmark symptom of psychosis. Substantial cognitive impairment is also seen. Effective drug treatments against the cognitive impairment of schizophrenia need to be developed. The current study was conducted to determine the effects of clozapine on working memory in the rat neonatal hippocampal lesion model of schizophrenia, which includes symptoms of cognitive impairment. Infant Sprague-Dawley rats were given ibotenic acid lesions of the hippocampus on day 7 of age (using the day of birth as day 0). Controls were given vehicle infusions. In adulthood, the rats were trained on the 8-arm radial maze using the win-shift procedure. After 6 sessions of training, the lesioned rats and their controls were administered repeated injections of saline or clozapine (2.5 mg/kg) for the next 12 sessions of training. The females had significant radial-arm maze choice accuracy impairments caused by either clozapine or the hippocampal lesion, but the combination of the two treatments had no additive effect. The males showed a different pattern of effects. Intact males did not show a significant clozapine-induced impairment, whereas males with hippocampal lesions did show significant clozapine-induced impairment although hippocampal lesions by themselves did not significantly impair male choice accuracy. These data show that clozapine can cause memory impairment and it potentiates rather than reverses hippocampal lesion-induced deficits. There are critical sex-related differences in these effects.

  4. 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

  5. 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

  6. Pharmacogenetics of Chronic Pain and Its Treatment

    PubMed Central

    Světlík, Svatopluk; Hronová, Karolína; Bakhouche, Hana; Matoušková, Olga; Slanař, Ondřej

    2013-01-01

    This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of analgesics and other drugs used for chronic pain treatment. Several candidate genes have been identified in the literature, while there is usually only limited clinical evidence substantiating for the penetration of the testing for these candidate biomarkers into the clinical practice. Further, the pain-perception regulation and modulation are still not fully understood, and thus more complex knowledge of genetic and epigenetic background for analgesia will be needed prior to the clinical use of the candidate genetic biomarkers. PMID:23766564

  7. 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

  8. 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

  9. Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients.

    PubMed

    Fehsel, Karin; Loeffler, Stefan; Krieger, Klaus; Henning, Uwe; Agelink, Markus; Kolb-Bachofen, Victoria; Klimke, Ansgar

    2005-10-01

    The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P < or = 0.005, n = 10) and significantly elevated expression levels of the proapoptotic genes p53 (P < or = 0.020), bax alpha (P < or = 0.001), and bik (P < or = 0.002) in all tested non-CA patients (n = 19) and CA patients (n = 4). In non-CA patients, the expression of these genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P < or = 0.001). Under G-CSF therapy of CA, the number of apoptotic neutrophils and the expression of the proapoptotic genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients.

  10. The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis.

    PubMed

    Hou, Mei-Ling; Lin, Chi-Hung; Lin, Lie-Chwen; Tsai, Tung-Hu

    2015-10-01

    Clozapine, an atypical antipsychotic agent, is highly effective in treatment-resistant schizophrenia; however, its major side effect is constipation. Instead of laxatives, rhein is a pharmacologically active component found in Rheum palmatum L., a medicinal herbal remedy for constipation. The purpose of this study is to determine whether rhein impacts the pharmacokinetics (PK) and pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine-induced constipation. Here, we have investigated not only the PK of clozapine in blood but also the effects of rhein on the PK of clozapine in blood and in brain extracellular fluid together with the PD effects on neurotransmitters in extracellular fluid. The concentrations of clozapine and norclozapine in biologic samples were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were assayed by high-performance liquid chromatography-electrochemical detection. The results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein for 7 days increased the total blood concentration of clozapine, but significantly reduced the unbound clozapine concentrations in the mPFC by approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic acid) and altered the profile of homovanillic acid, another metabolite of dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease clozapine and norclozapine concentrations in the mPFC dialysate, and this is accompanied by lower concentrations in the neurotransmitters in the same biophase. These findings suggest that a detailed clinical study for drug-drug interactions is recommended.

  11. Ziconotide for treatment of severe chronic pain.

    PubMed

    Schmidtko, Achim; Lötsch, Jörn; Freynhagen, Rainer; Geisslinger, Gerd

    2010-05-01

    Pharmacological management of severe chronic pain is difficult to achieve with currently available analgesic drugs, and remains a large unmet therapeutic need. The synthetic peptide ziconotide has been approved by the US Food and Drug Administration and the European Medicines Agency for intrathecal treatment of patients with severe chronic pain that is refractory to other treatment modalities. Ziconotide is the first member in the new drug class of selective N-type voltage-sensitive calcium-channel blockers. The ziconotide-induced blockade of N-type calcium channels in the spinal cord inhibits release of pain-relevant neurotransmitters from central terminals of primary afferent neurons. By this mechanism, ziconotide can effectively reduce pain. However, ziconotide has a narrow therapeutic window because of substantial CNS side-effects, and thus treatment with ziconotide is appropriate for only a small subset of patients with severe chronic pain. We provide an overview of the benefits and limitations of intrathecal ziconotide treatment and review potential future developments in this new drug class.

  12. Modafinil for Clozapine-Treated Schizophrenia Patients: A Double-Blind, Placebo-Controlled Pilot Trial

    PubMed Central

    Freudenreich, Oliver; Henderson, David C.; Macklin, Eric A.; Evins, A. Eden; Fan, Xiaoduo; Cather, Cori; Walsh, Jared P.; Goff, Donald C.

    2016-01-01

    Background Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. Objectives To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV–diagnosed schizophrenia patients treated with clozapine. Method A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. Results Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. Conclusions Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. Trial Registration clinicaltrials.gov Identifier: NCT00573417 PMID:19689921

  13. [Carboxytherapy - supportive therapy in chronic wound treatment].

    PubMed

    Sinozić, Tamara; Kovacević, Jadranka

    2013-10-01

    Carboxytherapy is a supportive method in chronic wound treatment conducted by cutaneous and subcutaneous injection of medical carbon dioxide (CO2). The primary effect of the injected CO2 is the correction of tissue hypoxia due to the Bohr effect. With its effects on endothelial growth factors, it stimulates neoangiogenesis and fibroblast collagen synthesis consequently leading to better wound healing. Carboxytherapy is used in many areas from chronic wound treatment, peripheral venous and arterial diseases, dermatological diseases, to cosmetic medicine. It is minimally invasive, patients take it well, it is economically acceptable, and it can be conducted in outpatient conditions by properly trained doctors. The application of new technologic innovations in the healing processes, education and teamwork combined with developed holistic individual approach ensure good cooperation and mutual doctor-patient communication, enhance patient care and improve their quality of life.

  14. 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

  15. 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

  16. Indications for treatment in chronic HCV infection.

    PubMed

    Dávalos Moscol, Milagros

    2010-01-01

    HCV Infection is a global burden disease and it is related to the development of progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. At least 80% of the persons that have an acute infection evolve to chronicity. This event affects the patient and their contacts for the risk of acquiring the infection. Once chronic HCV is present some factors accelerate progression: older age, obesity, alcohol consumption, etc. Severity of fibrosis is one of the most important factors to be analyzed before deciding to treat a patient. Pegylated interferon and ribavirin is the .standard of care. for this disease, however, it has many side effects, some of them life threatening. That is the reason why this treatment must be indicated in the right moment in the right patient. A complete medical evaluation must be done previously to initiate treatment. Other concurrent problems must be ruled out or treated. Decompensated cirrhosis, autoimmune diseases or other uncontrolled disease are contraindication to HCV treatment. Previous failure to treatment for HCV must be analyzed to identify the reasons for that event and consider retreatment. Cryoglobulinemia and membranoproliferative glomerulonephritis are indications for treatment independent from the severity of liver disease.

  17. Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects.

    PubMed

    Hahn, Margaret K; Remington, Gary; Bois, Daniel; Cohn, Tony

    2010-12-01

    Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.

  18. Clozapine use by state programs: public mental health systems respond to a new medication.

    PubMed

    Reid, W H; Pham, V A; Rago, W

    1993-08-01

    The authors present data from a national survey of state departments of mental health showing that two years after reaching the U.S. market, clozapine is available to only a small fraction of the patients whom it might benefit. The primary continuing hurdle for the public sector, where most schizophrenic patients get their care, is funding. Several arguments support the use of clozapine in state mental health systems: it is the most effective or only effective medication for many patients, it can decrease the enormous costs of schizophrenia and related disorders, and access to the medication has become an important issue for advocacy groups and other mental health activists. Two years of experience with clozapine in the Texas mental health system have shown that availability of clozapine in the community is a vital factor for successful use of the drug in hospitals. The authors discuss ways to encourage outpatient clozapine programs that are critical to successful treatment in both the hospital and the community.

  19. [New treatments for chronic obstructive pulmonary disease].

    PubMed

    Miravitlles, Marc

    2005-06-11

    Treatment of chronic obstructive pulmonary disease (COPD) has underwent a very important advance in the last five years. It has been developed a new long-lasting anticholynergic drug, tiotrope bromure, which has been found to improve lung function and exercise capacity and to decrease relapses. Also the combined treatment of long lasting beta 2 adrenergics with inhaled steroids (salmeterol/fluticasone and formoterol/budesonide) has proven similar results. However, the response to these new drugs is not the same in all patients. Individual characteristics such as gravity, degree of bronchial hyperresponsiveness, frequency of relapses, comorbidity, etc will determine the response to several agents. Thus, it is necessary to perform a detailed diagnostic study in COPD patients in order to select the best treatment in an individualized form. In the future, new specific antiinflammatories such as phosphodiesterase 4 inhibitors or agents with a potential action in tissue regeneration could lead to new perspectives, as well as to new questions, in COPD treatment.

  20. [Chronic prostatitis: a new paradigm of treatment].

    PubMed

    Bozhedomov, V A

    2016-08-01

    This paper proposes health care recommendations for men with chronic prostatitis (CP) taking into account etiopathogenesis and the clinical presentation of the disease. The proposal is based on the experience of federal and regional clinics of urology and gynecology, respective departments for postgraduate education and on the analysis of scientific literature. It is shown that managing patients with CP requires consideration of factors beyond the traditional practice of urology. The author validates the need to use the modern prostatitis classification UPOINT instead of the traditional NIH NIDDK (1995) to increase the effectiveness of treatment. It is demonstrated that the concurrent use of medications and non-pharmacological treatments aimed at different aspects of the state improve the treatment effectiveness. Indications are refined for medical and non-pharmacological treatments: antibiotics, alpha-blockers, anticholinergic agents, analgesics, antidepressants, herbal remedies, pelvic floor physiotherapy, psychotherapy. The shortcomings and mistakes of existing guidelines/standards are analyzed.

  1. Increased CSF levels of endorphines in chronic psychosis.

    PubMed

    Terenius, L; Wahlström, A; Lindström, L; Widerlöv, E

    1976-10-01

    The levels of two endorphines, endogenously occurring morphinomimetic peptides, were measured in serial samples of CSF from seven psychiatric patients. Four cases with chronic schizophrenia were studied before and after treatment with the antipsychotic agent clozapine (Leponex). Supernormal fraction II levels were found on at least one sampling occasion in each patient. Two patients, who responded well to clozapine treatment, showed a clear-cut drop in fraction II levels, whereas two patients showed increased levels which paralleled a deterioration of the schizophrenic symptoms. Three manic-depressive cases showed abnormally high levels of endorphine fraction I in the manic phase which declined during normal or depressed phases. Levels of fraction II varied in a less consistent manner and appeared to be at maximum during the apparently normal phases. Although preliminary, the data indicate that endorphines may reach supernormal levels in patients with chronic psychoses.

  2. Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject

    PubMed Central

    Tungaraza, Tongeji E.

    2016-01-01

    It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5–50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge – those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use. PMID:27721972

  3. 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

  4. 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

  5. Aripirazole augmentation in clozapine-associated obsessive-compulsive symptoms in schizophrenia

    PubMed Central

    2013-01-01

    Objective Patients with schizophrenia often experience comorbid obsessive-compulsive symptoms. Within these patients, a significant subgroup developed secondary obsessive-compulsive symptoms during treatment with clozapine. Method In this paper, we report on four cases in which adjunctive therapy with aripiprazole was tested to alleviate obsessive-compulsive symptoms in schizophrenia. Results All four patients had a significant improvement in obsessive-compulsive symptoms. The combination of clozapine and aripiprazole was well tolerated. Conclusion This case series demonstrates the clinical efficacy of aripiprazole adjunctive therapy with clozapine in schizophrenic patients with comorbid obsessive-compulsive symptoms. Larger-sampled and controlled studies are required in order to test and confirm these observations. PMID:24330737

  6. Targeted treatment for chronic lymphocytic leukemia

    PubMed Central

    Masood, Aisha; Sher, Taimur; Paulus, Aneel; Miller, Kena C; Chitta, Kasyapa S; Chanan-Khan, Asher

    2011-01-01

    The treatment of chronic lymphocytic leukemia (CLL) has evolved over the last few decades. Recognition has increased of several key components of CLL biology currently manipulated for therapeutics. A milestone in the treatment of CLL was reached with the incorporation of immunotherapy with conventional chemotherapy. The fludarabine/cyclophosphamide/rituximab combination has demonstrated survival advantage for the first time in the treatment of CLL. Several other biological compounds are being explored with the hope of improving responses, impacting survival, and ultimately curing CLL. Important agents being tested are targeted on CLL surface molecules and their ligands, signal transduction protein and oncogenes. This review provides a brief summary of the recent advances made in preclinical and clinical investigation of selected promising therapeutic agents, which lead the target-directed therapeutic approach. PMID:22162923

  7. Augmentative Asenapine in a Recurrent Manic Catatonic Patient with Partial Response to Clozapine

    PubMed Central

    Buoli, Massimiliano; Dobrea, Cristina; Caldiroli, Alice; Cremaschi, Laura; Altamura, A. Carlo

    2013-01-01

    Catatonia is a severe but treatable neuropsychiatric syndrome known since the middle of the nineteenth century. It has been considered for a long time as a subtype of schizophrenia, even though this association occurs only in 10% of cases. In contrast, it is frequently observed in bipolar patients. First-line treatment consists of benzodiazepines, while in case of resistance electroconvulsive therapy (ECT) and clozapine have shown positive results. In addition, recent studies reported the efficacy of some atypical antipsychotics. The present case shows the clinical response to augmentative asenapine in a catatonic manic patient with a partial response to clozapine. PMID:24171130

  8. Omalizumab for the treatment of chronic urticaria.

    PubMed

    Zuberbier, Torsten; Maurer, Marcus

    2015-02-01

    Urticaria is a common and often debilitating dermatological condition defined by the sudden appearance of wheals, angioedema or both. It is further classified into specific subtypes based on duration and specific triggers. Awareness and understanding of urticaria are important to ensure a correct initial diagnosis and initiate appropriate guideline-based treatment outlining a stepwise approach. However, in chronic urticaria, approximately 50% of patients are refractory to the first step, the use of licensed doses of second-generation H1-antihistamines. If the second step, an increase in the dose of the second-generation H1-antihistamines, is also not successful, in the third step omalizumab (Xolair™, Novartis Pharma AG(©)/Genentech, Inc.(©)), an anti-IgE therapy, is recommended as an add-on. Of all alternative treatments mentioned in the guidelines, omalizumab is currently the only licensed treatment for H1-antihistamine-refractory chronic spontaneous urticaria, has a favorable risk/benefit ratio and was well tolerated in clinical studies.

  9. 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.

  10. Pipamperone augmentation of clozapine and sodium valproate in refractory schizophrenia: a case report.

    PubMed

    Paraschakis, Antonios

    2014-01-01

    Refractory schizophrenia poses many therapeutic dilemmas. Clozapine is currently considered as the most effective medication for the treatment of refractory schizophrenia. Unfortunately, it carries serious and often life-threatening adverse effects such as agranulocitosis, hypersalivation, somnolence, weight gain, diabetes, and epileptic seizures. Various combinations of clozapine with typical and other atypical antipsychotics have been suggested to improve its efficacy and reduce its often dose-related adverse effects. We present a case of a 37-year-old patient with refractory schizophrenia who has responded well to the combination of clozapine, sodium valproate, and pipamperone. The improvement was more evident in the following symptoms: auditory hallucinations, delusions, formal thought disorder, anhedonia, and social withdrawal. The combination was well tolerated: No extrapyramidal adverse effects were noted and the patient's full blood count was within normal limits. Pipamperone, a butyrophenone derivative, is a more selective antagonist of dopaminergic D4 receptors compared with D2 receptors and a serotoninergic 5HT-2A receptors antagonist. Thus, it shows "atypicality" and shares common characteristics with clozapine: 5HT-2A antagonism and D4 > D2 blockade selectivity. Therefore, augmentation of clozapine with pipamperone theoretically should have a synergistic effect that may provide several benefits to the patient: better antipsychotic efficacy with low risk for extrapyramidal adverse effects. This combination may also allow a decrease in clozapine dose, limiting its challenging adverse effects. To the author's knowledge, successful treatment of refractory schizophrenia with this drug combination is reported for the first time in the literature and probably merits further research.

  11. Case report: treatment of chronic osteomyelitis.

    PubMed

    Wolfe, Cameron R

    2011-06-01

    Presented is a case of chronic methicillin-resistant Staphylococcus aureus osteomyelitis, which was unsuccessfully treated with multiple courses of debridement and potent antibiotic therapies. Amputation of the patient's lower limb was believed to be the only option remaining. A compassionate access program, with approval from the US Food and Drug Administration and the institutional review board, enabled the patient to undergo a course of treatment with oral fusidic acid (CEM-102). The patient tolerated the drug well, with no significant toxicities noted to date. His infection improved rapidly, his flap healed, he has returned to work part-time, and he continues to take daily suppressive doses of oral CEM-102.

  12. 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.

  13. Optimized Treatment Schedules for Chronic Myeloid Leukemia

    PubMed Central

    He, Qie; Dingli, David; Foo, Jasmine; Leder, Kevin Zox

    2016-01-01

    Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies. However, the design of such combination therapies (timing, sequence, etc.) remains an open challenge. In this work we mathematically model the dynamics of CML response to combination therapy and analyze the impact of combination treatment schedules on treatment efficacy in patients with preexisting resistance. We then propose an optimization problem to find the best schedule of multiple therapies based on the evolution of CML according to our ordinary differential equation model. This resulting optimization problem is nontrivial due to the presence of ordinary different equation constraints and integer variables. Our model also incorporates drug toxicity constraints by tracking the dynamics of patient neutrophil counts in response to therapy. We determine optimal combination strategies that maximize time until treatment failure on hypothetical patients, using parameters estimated from clinical data in the literature. PMID:27764087

  14. Effects of clozapine on perceptual abnormalities and sensory gating: a preliminary cross-sectional study in schizophrenia.

    PubMed

    Micoulaud-Franchi, Jean-Arthur; Aramaki, Mitsuko; Geoffroy, Pierre Alexis; Richieri, Raphaëlle; Cermolacce, Michel; Faget, Catherine; Ystad, Sølvi; Kronland-Martinet, Richard; Lancon, Christophe; Vion-Dury, Jean

    2015-04-01

    The aim of the present study was to investigate the effect of second-generation antipsychotics (clozapine or another second-generation antipsychotic) on perceptual abnormalities related to sensory gating deficit. Although clozapine is known to improve sensory gating assessed neurophysiologically, we hypothesized that patients with schizophrenia treated with clozapine would report less perceptual abnormalities related to sensory gating deficit than patients treated with other second-generation antipsychotics do. Forty patients with a diagnosis of schizophrenia were investigated (10 patients treated with clozapine and 30 patients treated with another second-generation antipsychotic drug). Perceptual abnormalities were assessed with the Sensory Gating Inventory. Sensory gating was assessed through electroencephalogram with the auditory event-related potential method by measuring P50 amplitude changes in a dual click conditioning-testing procedure. Patients treated with clozapine present normal sensory gating and report less perceptual abnormalities related to sensory gating than patients treated with other second-generation antipsychotics do. Although the cross-sectional design of this study is limited because causal inferences cannot be clearly concluded, the present study suggests clinical and neurophysiological advantages of clozapine compared with other second-generation antipsychotics and provides a basis for future investigations on the effect of this treatment on perceptual abnormalities related to sensory gating deficit in patients with schizophrenia.

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

    MedlinePlus

    ... Myeloid Leukemia (CML) About 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 ...

  16. 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

  17. 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…

  18. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats.

    PubMed

    Lobach, Alexandra R; Uetrecht, Jack

    2014-07-21

    Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF). Employing a rat model of clozapine treatment, we set out to determine if the neutrophilia observed at the start of treatment is characteristic of G-CSF-associated bone marrow stimulation. Female Sprague-Dawley rats were treated with 30 mg/kg/day of clozapine for 10 days, and sustained neutrophilia was evident after 1 week of treatment paired with spikes in G-CSF. Within the bone marrow, clozapine was found to induce proliferation of the granulocyte progenitor colonies as measured by a methylcellulose assay. This led to elevated granulopoiesis observed by H&E and myeloperoxidase staining of bone marrow slices. Increased release of neutrophils from the marrow to the circulation was measured through 5-bromo-2'-deoxyuridine labeling in vivo, and these neutrophils appeared to be less mature based on (a) a decrease in the nuclear lobe count and (b) increased expression of surface CD62L. Furthermore, faster transit of the neutrophils through the marrow was suggested by a shift toward elevated numbers of neutrophils in the bone marrow maturation pool and increased CD11b and CD18 staining on the less mature neutrophils residing in the marrow. Taken together, these data indicate that clozapine stimulates the bone marrow to produce more neutrophils in a manner that is characteristic of endogenous G-CSF stimulation, and it is consistent with the inflammatory response observed in patients treated with clozapine.

  19. Treatment of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Kleyman, Inna; Brannagan, Thomas H

    2015-07-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

  20. Successful switch to olanzapine after rhabdomyolysis caused by water intoxication and clozapine use.

    PubMed

    Tényi, T; Vörös, V

    2006-07-01

    We report on a case of rhabdomyolysis induced by the correction of hyponatremia after psychogenic polydipsia and clozapine use, where the switch to a high dose of olanzapine resulted in the non-recurrence of rhabdomyolysis. The 46-year-old patient with the diagnosis of schizophrenia paranoid type, who had been on clozapine treatment for the previous 4 years, was admitted with the symptoms of generalized seizure and vomiting, and as severe hyponatremia was proved, its correction with the parallel use of clozapine treatment was done. CK concentrations increased to 48 120 U/L without any symptom of neuroleptic malignant syndrome. To prevent acute renal insufficiency, high-volume alkaline diuresis was initiated and clozapine was tapered and stopped. On the day 12 of treatment, olanzapine was started and was elevated to 30 mg/day. CK concentration began to fall returning to the normal concentration on day 20. Six months after the switch to olanzapine no recurrence of rhabdomyolysis was detected; clinical and laboratory findings were normal. We suggest that after a benzodiazepine-type antipychotic-induced rhabdomyolysis, a switch to another atypical antipsychotic can be a cautious clinical strategy.

  1. Diagnosis and treatment of chronic insomnia

    PubMed Central

    Saddichha, Sahoo

    2010-01-01

    Insomnia is a disorder characterized by inability to sleep or a total lack of sleep, prevalence of which ranges from 10 to 15% among the general population with increased rates seen among older ages, female gender, White population and presence of medical or psychiatric illness. Yet this condition is still under-recognized, under-diagnosed, and under-treated. This article aims to review the operational definitions and management of chronic insomnia. A computerized search on PubMed carried from 1980 to January 2009 led to the summarization of the results. There are several strategies to manage chronic insomnia. To initiate treatment, it is necessary to define it and differentiate it from other co-morbid psychiatric disorders. Non-pharmacologic strategies such as stimulus control therapy and relaxation and cognitive therapies have the best effect sizes followed by sleep restriction, paradoxical intention and sleep hygiene education which have modest to less than modest effect sizes. Among pharmacotherapeutic agents, non-benzodiazepine hypnotics are the first line of management followed by benzodiazepines, amitryptiline and antihistaminics. However, adequate trials of combined behavior therapy and pharmacotherapy are the best course of management. PMID:20814491

  2. [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

  3. 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

  4. [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.

  5. Switching from clozapine to zotepine in patients with schizophrenia: a 12-week prospective, randomized, rater blind, and parallel study.

    PubMed

    Lin, Chao-Cheng; Chiu, Hsien-Jane; Chen, Jen-Yeu; Liou, Ying-Jay; Wang, Ying-Chieh; Chen, Tzu-Ting; Bai, Ya-Mei

    2013-04-01

    Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many adverse effects are noted. Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis, although empirical studies are very limited. Zotepine, an atypical antipsychotic with a pharmacologic profile similar to clozapine, was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan. This 12-week study is the first prospective, randomized, and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine. Fifty-nine patients with schizophrenia, who had taken clozapine for at least 6 months with a Clinical Global Impression-Severity score of at least 3, were randomly allocated to the zotepine and the clozapine groups. At the end of the study, 52 patients (88%) had completed the trial. The 7 withdrawal cases were all in the zotepine group. The final mean (SD) dose of zotepine and clozapine was 397.1 (75.7) versus 377.1 (62.5) mg/d, respectively. Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [mean (SD), 4.7 (8.7) vs -1.3 (6.3); P = 0.005], more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [mean (SD), 1.74 (3.9) vs -0.2 (2.8); P = 0.039], more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [mean (SD), 1.29 (3.5) vs 0.17 (2.1); P = 0.022], an increased use of propranolol (37.1% vs 0%, P < 0.0001) and anticholinergics (25.7% vs 0%, P = 0.008), and an increased level of prolactin (29.6 vs -3.8 ng/ mL, P < 0.0005), compared with the clozapine group. The results suggested that switching from clozapine to zotepine treatment should be done with caution.

  6. Olanzapine and clozapine differently affect sleep in patients with schizophrenia: results from a double-blind, polysomnographic study and review of the literature.

    PubMed

    Kluge, Michael; Schacht, Alexander; Himmerich, Hubertus; Rummel-Kluge, Christine; Wehmeier, Peter M; Dalal, Mira; Hinze-Selch, Dunja; Kraus, Thomas; Dittmann, Ralf W; Pollmächer, Thomas; Schuld, Andreas

    2014-01-01

    Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

  7. Effects of central activation of serotonin 5-HT2A/2C or dopamine D2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test

    PubMed Central

    Feng, Min; Gao, Jun; Sui, Nan; Li, Ming

    2014-01-01

    Rationale: Acute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect. Objective: The present study investigated the neuroanatomical basis and receptor mechanisms of acute and repeated effects of clozapine treatment in the conditioned avoidance response test in male Sprague-Dawley rats. Methods: DOI (2,5-dimethoxy-4-iodo-amphetamine, a preferential 5-HT2A/2C agonist) or quinpirole (a preferential dopamine D2/3 agonist) was microinjected into the medial prefrontal cortex (mPFC) or nucleus accumbens shell (NAs), and their effects on the acute and long-term avoidance-disruptive effect of clozapine were tested. Results: Intra-mPFC microinjection of quinpirole enhanced the acute avoidance disruptive effect of clozapine (10 mg/kg, sc), while DOI microinjections reduced it marginally. Repeated administration of clozapine (10 mg/kg, sc) daily for 5 days caused a progressive decrease in its inhibition of avoidance responding, indicating tolerance development. Intra-mPFC microinjection of DOI at 25.0 (but not 5.0) μg/side during this period completely abolished the expression of clozapine tolerance. This was indicated by the finding that clozapine-treated rats centrally infused with 25.0 μg/side DOI did not show higher levels of avoidance responses than the vehicle-treated rats in the clozapine challenge test. Microinjection of DOI into the mPFC immediately before the challenge test also decreased the expression of clozapine tolerance. Conclusions: Acute behavioral effect of clozapine can be enhanced by activation of the D2/3 receptors in the mPFC. Clozapine tolerance expression relies on the neuroplasticity initiated by its antagonist action against 5-HT2A/2C receptors in the mPFC. PMID:25288514

  8. Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review

    PubMed Central

    Sommer, Iris E.; Begemann, Marieke J. H.; Temmerman, Anke; Leucht, Stefan

    2012-01-01

    Background. When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder. Methods. Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g). Results. Twenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal. Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies. Conclusions. Evidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo. PMID:21422107

  9. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

    PubMed Central

    Vilela, Eduardo Machado; Bastos, Jessica Amaral; Fernandes, Natalia; Ferreira, Ana Paula; Chaoubah, Alfredo; Bastos, Marcus Gomes

    2011-01-01

    OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656. PMID:21655762

  10. Chronic heart failure part 2: treatment and management.

    PubMed

    Brake, Rebecca; Jones, Ian David

    2017-01-11

    Chronic heart failure is a common and complex clinical syndrome that results from impaired cardiac relaxation or contraction. There have been considerable advances in the management of chronic heart failure; however, the mortality rate remains high. Patients with chronic heart failure may experience multiple debilitating symptoms, such as fatigue, pain, and peripheral oedema. However, breathlessness may be considered the most debilitating symptom. The management of chronic heart failure aims to improve the patient's quality of life by reducing symptoms and supporting the patient to manage their condition. Treatment of patients with chronic heart failure may involve a combination of pharmacological therapy, device implantation and cardiac rehabilitation. This is the second of two articles on chronic heart failure. Part 1 discussed the pathophysiology of chronic heart failure, its causes, assessment, signs and symptoms. Part 2 outlines the treatment and management of patients with the condition, including pharmacological strategies, device implantation, lifestyle modification, cardiac rehabilitation and palliative care.

  11. 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

  12. 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.

  13. Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction

    PubMed Central

    Proctor, George; Cummings, Michael A.; Dardashti, Laura J.; Stahl, Stephen M.

    2016-01-01

    Objective. Clozapine provides a 50%–60% response rate in refractory schizophrenia but has a narrow therapeutic index and is susceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2. Case Report. We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years on clozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orally twice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity. Conclusion. Given the potentially fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levels prior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtained at baseline. PMID:27872784

  14. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  15. 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.

  16. 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

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

    PubMed

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

    2009-01-01

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

  18. Psychological Neuromodulatory Treatments for Young People with Chronic Pain.

    PubMed

    Miró, Jordi; Castarlenas, Elena; de la Vega, Rocío; Roy, Rubén; Solé, Ester; Tomé-Pires, Catarina; Jensen, Mark P

    2016-12-06

    The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments-neurofeedback, meditation and hypnosis-when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function), at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1) providing an empirical basis for better patient-treatment matching; and (2) identifying specific mechanisms that could be targeted with treatment.

  19. 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.

  20. Psychological Neuromodulatory Treatments for Young People with Chronic Pain

    PubMed Central

    Miró, Jordi; Castarlenas, Elena; de la Vega, Rocío; Roy, Rubén; Solé, Ester; Tomé-Pires, Catarina; Jensen, Mark P.

    2016-01-01

    The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments—neurofeedback, meditation and hypnosis—when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function), at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1) providing an empirical basis for better patient-treatment matching; and (2) identifying specific mechanisms that could be targeted with treatment. PMID:27929419

  1. [Chronic venous insufficiency: Update on pathophysiology, diagnosis and treatment].

    PubMed

    Gkogkolou, P; Meyer, V; Goerge, T

    2015-05-01

    Chronic venous insufficiency is very common and has an important socioeconomic impact. It is associated with a high morbidity for the patients and causes high costs for the healthcare systems. In recent years novel treatment modalities have evolved and their efficacy has been evaluated in many studies. Knowledge of pathophysiology, the diagnostic procedures and therapeutic options for chronic venous insufficiency is important for effective treatment of affected patients.

  2. The effect of galantamine added to clozapine on cognition of five patients with schizophrenia.

    PubMed

    Bora, Emre; Veznedaroğlu, Baybars; Kayahan, Bülent

    2005-01-01

    Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials.

  3. Prevalence and treatment of giardiasis in chronic diarrhoea and malnutrition.

    PubMed Central

    Sullivan, P B; Marsh, M N; Phillips, M B; Dewit, O; Neale, G; Cevallos, A M; Yamson, P; Farthing, M J

    1991-01-01

    To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures. PMID:2025005

  4. Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction

    PubMed Central

    Burghardt, Nesha S.; Sigurdsson, Torfi; Gorman, Jack M.; McEwen, Bruce S.; LeDoux, Joseph E.

    2012-01-01

    Background Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction. Methods Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared to those following chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the NMDA receptor in the amygdala was examined after behavioral testing. Results Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the NMDA receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment. Conclusions These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment. PMID:23260230

  5. The effects of clozapine on levels of total cholesterol and related lipids in serum of patients with schizophrenia: a prospective study.

    PubMed Central

    Dursun, S M; Szemis, A; Andrews, H; Reveley, M A

    1999-01-01

    OBJECTIVE: To investigate the effects of 12 weeks of clozapine treatment on levels of cholesterol and related lipids in patients with schizophrenia. DESIGN: Prospective study. SETTING: University department associated with a teaching hospital. PARTICIPANTS: Eight patients (6 women and 2 men) with a clinical diagnosis of schizophrenia consistent with DSM-IV criteria. The patients were classified as treatment-resistant and had not responded to treatment with at least 2 conventional antipsychotics. INTERVENTIONS: Current antipsychotic medications were tapered and treatment with clozapine was initiated. OUTCOME MEASURES: Cholesterol and serum lipid levels, as well as Brief Psychiatric Rating Scale (BPRS) scores were measured before and after 12 weeks of treatment with clozapine. RESULTS: Clozapine treatment significantly improved the BPRS scores but did not significantly alter serum lipid levels, except triglyceride levels, which increased. CONCLUSION: The previously reported lower levels of cholesterol in treatment-resistant patients with schizophrenia cannot be attributed to the effects of clozapine administration. Further research is required to support and clarify the effects of antipsychotic drugs on lipid levels. Images Fig. 1 PMID:10586536

  6. 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.

  7. Treatment of chronic pulmonary blastomycosis with caspofungin.

    PubMed

    Mardini, Joëlle; Nguyen, Bich; Ghannoum, Marc; Couture, Christian; Lavergne, Valéry

    2011-12-01

    Current practice guidelines recommend that pulmonary blastomycosis be treated with antifungal agents such as amphotericin B and itraconazole. Echinocandins are not recommended because of poor in vitro activity against Blastomyces dermatitidis and lack of supporting clinical data. We report a case of chronic pulmonary blastomycosis treated successfully with caspofungin.

  8. Determination of clozapine in serum of patients with schizophrenia as a measurement of medication compliance.

    PubMed

    Mennickent, S; Sobarzo, A; Vega, M; de Diego, M; Godoy, G; Rioseco, P; Saavedra, L

    2010-03-01

    Abstract Although antipsychotic drugs have been effective in reducing symptoms of schizophrenia, issues with adherence to these agents continue to be a barrier to the implementation and delivery of a successful treatment plan. An estimated 25% of patients with schizophrenia are partially adherent or non-adherent within 7-10 days of beginning therapy. There are some ways to evaluate the pharmacotherapy adherence of the patients: evaluation of the disease symptoms and/or the side effects of the drugs, questionnaires to evaluate quality of life, patient attitude toward his (her) drugs and pill counts. Although these methods represent a good option, they are subjective; for example, if the patients lie this leads to false results. Drug monitoring of patients' biological fluids can be a useful tool to evaluate adherence by relating the serum or plasma levels of drugs with pharmacotherapy compliance. The aim of this study was to determine if serum clozapine levels are a suitable method for evaluating patient adherence to clozapine therapy. Clozapine concentration was determined in serum of 26 volunteer patients who were using this drug as pharmacotheraphy for 6 months to 5 years (steady state conditions at 7-10 days of treatment with the drug). The analysis was done for 6 months, with three samples taken for each patient during this time, relating clozapine serum concentration of lower than therapeutic range with pharmacotherapy non-adherence of patients. Moreover, we compared the evaluation of the pharmacotherapy adherence from serum levels of the drug, with the evaluation of the pharmacotherapy adherence from an indirect tool to evaluate symptoms of disease. Twelve patients were found non-adherent by clozapine serum concentration (46.15%), whereas eight patients were found non-adherent using clinician questionnaire (30.76%). After to evaluate some factors (cigarettes, co-medication, inter-individual variability) that could give different results of adherence from

  9. 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.

  10. Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

    PubMed Central

    Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

    2017-01-01

    Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication

  11. Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

    PubMed

    Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna

    2017-03-01

    Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

  12. Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

    PubMed Central

    GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

    2017-01-01

    Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

  13. 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

  14. Chronic Cholangitides: Aetiology, Diagnosis, and Treatment*

    PubMed Central

    Sherlock, Sheila

    1968-01-01

    A number of different chronic diseases affect the intrahepatic bile radicles or cholangioles. They include primary and secondary sclerosing cholangitis, primary biliary cirrhosis, chronic cholestatic drug jaundice, atresia, and carcinoma. Aetiological factors include infection, immunological changes, hormones, and congenital defects. Patients with chronic cholestasis have decreased bile salts in the intestinal contents and suffer from a bile salt deficiency syndrome. Failure to absorb dietary fat is managed by a low-fat diet and by medium-chain trigly-cerides which are absorbed in the absence of intestinal bile salts. Fat-soluble vitamin deficiencies are prevented by parenteral vitamins A, D, and K1. Calcium absorption is defective, and improvement may follow intramuscular vitamin D, medium-chain triglycerides, a low-fat diet, and oral calcium supplements. In partial intestinal bile salt deficiency the anionic bile-salt-chelating resin cholestyramine controls pruritus though steatorrhoea increases. Pruritus associated with total lack of intestinal bile salts is managed by methyl-testosterone or norethandrolone, though the jaundice increases. PMID:4971054

  15. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    PubMed

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  16. 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

  17. 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…

  18. Pharmacological treatment of chronic pelvic ischemia.

    PubMed

    Andersson, Karl-Erik; Nomiya, Masanori; Sawada, Norifumi; Yamaguchi, Osamu

    2014-06-01

    Epidemiological studies have shown that lower urinary tract symptoms, including overactive bladder, commonly occur in both men and women, with an age-related increase in both sexes. Vascular endothelial dysfunction and urological symptoms are common in the metabolic syndrome; they also occur during the human ageing process and are independent risk factors for the development of atherosclerosis and hypertension. Pelvic arterial insufficiency may lead to impaired lower urinary tract perfusion and play an important role in the development of bladder dysfunction such as detrusor overactivity and overactive bladder. It seems reasonable, but has not been definitely established clinically, that chronic ischemia-related bladder dysfunction will progress to bladder underactivity. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension, oxidative stress, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. Several types of drug may be able to prevent some of these changes. Even if the α1-adrenoceptor blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the β3-α1-adrenoceptor agonist, mirabegron, and the free radical scavenger, melatonin, were unable to prevent the development of neointimal hyperplasia and consequent luminal occlusion in animal models, they all exerted a protecting effect on urodynamic parameters, and on the functional and morphological changes of the bladder demonstrable in vitro. The different mechanisms of action of the drugs suggest that many factors are involved in the pathogenesis of chronic ischemia-induced bladder dysfunction and can be targets for intervention. Since several of the agents tested are used clinically and effectively for relieving lower urinary tract symptoms, the results from animal models of chronic bladder ischemia seem to have translational value

  19. Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

    PubMed Central

    Kim, Hye Sung; Kim, Se Hyun; Lee, Nam Young; Youn, Tak; Lee, Jeoung Hyuk; Chung, Seunghyun; Kim, Yong Sik

    2017-01-01

    Objective This retrospective case series study of the effectiveness of electroconvulsive therapy (ECT) augmentation on clozapine-resistant schizophrenia was conducted by EMR review. Methods Clozapine-resistance was defined as persistent psychotic symptoms despite at least 12 weeks of clozapine administration with blood levels over 350 ng/mL in order to rule out pseudo-resistance. Seven in-patients who were taking clozapine and treated with ECT were selected. We analyzed the psychopathology and subscales changed by ECT. Results The average number of ECT sessions was 13.4 (±4.6). Total Positive and Negative Syndrome Scale (PANSS) score was significantly reduced by 17.9 (±12.8) points (p=0.0384) on average, which represented a reduction of 25.5% (±14.3). 71.4% (5/7) of patients were identified as clinical remission, with at least a 20% reduction in PANSS score. PANSS reduction was associated with number of ECT sessions, stimulus level in the final session, and blood clozapine levels before ECT. However, the negative subscale on the PANSS were not reduced by ECT in any patient. We did not observe any persistent adverse cognitive effects. Conclusion This study supports that ECT augmentation on clozapine-resistant schizophrenia reveals clinically effective and safe. Further research should be done involving a larger number of patients to investigate the effectiveness of clozapine/ECT combination therapy. PMID:28096876

  20. 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

  1. [Almitrine bismesylate treatment in chronic respiratory insufficiency].

    PubMed

    González Ruiz, J M; Villamor León, J; García-Satué, J L; Sánchez Agudo, L; Calatrava, J M; Carreras, J

    1994-12-01

    This study was designed to evaluate the gasometric and functional respiratory responses in chronic bronchitic patients with chronic respiratory insufficiency (CRI) under ambulatory oxygen therapy (AOT) with almitrine bismesylate (AB). It was a double-blind, placebo-controlled, randomized, prospective study which lasted three months and with a dosage regime of 50-100 mg/day of AB. Fiftyfour patients completed the study (28 in AB and 24 in the placebo (P) groups, respectively). All patients were males, with a mean age or 65 +/- 6.1 years. In the study of pulmonary function only airway resistance (Raw) was changed, with a significant decrease at the third month in the AB group compared with the P group (0.83 +/- 0.31 vs. 1.07 +/- 0.46 kpa/L.S), with a p value of 0.05 (mean +/- SD) and PaO2 which improved from 8.15 +/- 0.88 to 8.81 +/- 2.3 kpa (61.17 +/- 6.6 to 66.10 +/- 10 mmHg), with a p value of 0.05. AB therapy was well tolerated.

  2. Treatment of chronic plantar fasciopathy with extracorporeal shock waves (review)

    PubMed Central

    2013-01-01

    There is an increasing interest by doctors and patients in extracorporeal shock wave therapy (ESWT) for chronic plantar fasciopathy (PF), particularly in second generation radial extracorporeal shock wave therapy (RSWT). The present review aims at serving this interest by providing a comprehensive overview on physical and medical definitions of shock waves and a detailed assessment of the quality and significance of the randomized clinical trials published on ESWT and RSWT as it is used to treat chronic PF. Both ESWT and RSWT are safe, effective, and technically easy treatments for chronic PF. The main advantages of RSWT over ESWT are the lack of need for any anesthesia during the treatment and the demonstrated long-term treatment success (demonstrated at both 6 and 12 months after the first treatment using RSWT, compared to follow-up intervals of no more than 12 weeks after the first treatment using ESWT). In recent years, a greater understanding of the clinical outcomes in ESWT and RSWT for chronic PF has arisen in relationship not only in the design of studies, but also in procedure, energy level, and shock wave propagation. Either procedure should be considered for patients 18 years of age or older with chronic PF prior to surgical intervention. PMID:24004715

  3. Treatment Options for Chronic Myelogenous Leukemia

    MedlinePlus

    ... a blood vessel in the chest. Donor lymphocyte infusion (DLI) Donor lymphocyte infusion (DLI) is a cancer treatment that may be ... given to the patient through one or more infusions. The lymphocytes see the patient’s cancer cells as ...

  4. Treatment Option Overview (Chronic Myelogenous Leukemia)

    MedlinePlus

    ... a blood vessel in the chest. Donor lymphocyte infusion (DLI) Donor lymphocyte infusion (DLI) is a cancer treatment that may be ... given to the patient through one or more infusions. The lymphocytes see the patient’s cancer cells as ...

  5. Easing Chronic Pain: Better Treatments and Medications

    MedlinePlus

    ... chemicals to interrupt relay of pain messages between the brain and other parts of the body; and enzymes injected into lumbar disks. Physical methods Common treatments include physical therapy, biofeedback, acupuncture, electrical stimulation, R.I.C.E. ( ...

  6. Chronic heart failure: pathophysiology, diagnosis and treatment.

    PubMed

    Nicholson, Christopher

    2014-08-01

    Heart failure has significant prevalence in older people: the mean average age of patients with the condition is 77. It has serious prognostic and quality of life implications for patients, as well as health service costs. Diagnosis requires confirmatory investigations and consideration of causative processes. First-line treatment involves education, lifestyle modification, symptom-controlling and disease-modifying medication. Further treatment may include additional medications, cardiac devices and surgery. End of life planning is part of the care pathway.

  7. 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

  8. Non-pharmacological treatment of chronic widespread musculoskeletal pain.

    PubMed

    Hassett, Afton L; Williams, David A

    2011-04-01

    Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed.

  9. Chronic proctalgia and chronic pelvic pain syndromes: New etiologic insights and treatment options

    PubMed Central

    Chiarioni, Giuseppe; Asteria, Corrado; Whitehead, William E

    2011-01-01

    This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs: chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing: A recently published large randomized, controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders. PMID:22110274

  10. A clozapine-like effect of cyproheptadine on progressive ratio schedule performance.

    PubMed

    Olarte-Sánchez, C M; Valencia Torres, L; Body, S; Cassaday, H J; Bradshaw, C M; Szabadi, E; Goudie, A J

    2012-06-01

    The atypical antipsychotic drug clozapine has multiple pharmacological actions, some of which, including 5-hydroxytryptamine (5-HT₂) and histamine (H₁) receptor antagonist effects, are shared by the non-selective 5-HT receptor antagonist cyproheptadine. Atypical antipsychotics have a characteristic profile of action on operant behaviour maintained by progressive ratio schedules, as revealed by Killeen's (1994) mathematical model of schedule controlled behaviour. These drugs increase the values of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the 'motor capacity' of the organism (δ). This experiment examined the effects of acute treatment with cyproheptadine and clozapine on performance on a progressive ratio schedule of food reinforcement in rats; the effects of a conventional antipsychotic, haloperidol, and two drugs with food intake-enhancing effects, chlordiazepoxide and Δ⁹-tetrahydrocannabinol (THC), were also examined. Cyproheptadine (1, 5 mg kg⁻¹) and clozapine (3.75, 7.5 mg kg⁻¹) increased a and δ. Haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Chlordiazepoxide (3, 10 mg kg⁻¹) increased a but reduced δ. THC (1, 3 mg kg⁻¹) had no effect. Interpretation based on Killeen's (1994) model suggests that cyproheptadine and clozapine enhanced the incentive value of the reinforcer and impaired motor performance. Motor impairment may be due to sedation (possibly reflecting H₁ receptor blockade). Enhancement of incentive value may reflect simultaneous blockade of H₁ and 5-HT₂ receptors, which has been proposed as the mechanism underlying the food intake-enhancing effect of cyproheptadine. In agreement with previous findings, haloperidol impaired motor performance and reduced the incentive value of the reinforcer. Chlordiazepoxide's effect on a is consistent with its food intake-enhancing effect.

  11. Development of a method of clozapine dosage by selective electrode to the iodides.

    PubMed

    Teyeb, Hassen; Douki, Wahiba; Najjar, Mohamed Fadhel

    2012-07-01

    Clozapine (Leponex(®)), the main neuroleptic indicated in the treatment of resistant schizophrenia, requires therapeutic monitoring because of its side effects and the individual variability in metabolism. In addition, several cases of intoxication by this drug were described in the literature. In this work, we studied the indirect dosage of clozapine by selective electrode to the iodides for the optimization of an analytical protocol allowing therapeutic monitoring and the diagnosis of intoxication and/or overdose. Our results showed that the developed method is linear between 0.05 and 12.5 µg/mL (r = 0.980), with a limit of detection of 0.645.10(-3) µg/mL. It presents good precision (coefficient of variation less than 4%) and accuracy (coefficient less than 10%) for all the studied concentrations. With a domain of linearity covering a wide margin of concentrations, this method can be applicable to the dosage of clozapine in tablets and in different biological matrices, such as plasma, urines, and postmortem samples.

  12. [The treatment of chronic myeloleukemia with recombinant alfa-2 interferon].

    PubMed

    Strozha, I; Petukhov, V; Bondare, D; Feldmane, G; Duks, A; Teilane, I; Medne, I; Mauritsas, M; Grinberga, L

    1993-01-01

    A trial has been conducted of recombinant alpha 2-interferon (reaferon) used in 32 patients with Ph'[correction of Rh']-positive chronic myeloid leukemia (CML). A chronic stage was in 3, transient in 3 and blast in 1 patients. 25 CML patients were newly diagnosed. The treatment lasted from 2 months to 3 years. Clinicohematological remission was confirmed conventionally and by the degree of Ph'-positive clone reduction. An attempt is made to clarify the mechanism underlying the resistance to reaferon basing on the immunological data (detection of antireaferon neutralizing antibodies). The authors propose a combined treatment (myelosan plus reaferon) of CML which has obvious advantages over myelosan monotherapy.

  13. Chronic fatigue syndrome and the treatment process.

    PubMed

    Mechanic, D

    1993-01-01

    Fatigue is a common complaint in general practice and is often associated with psychiatric and psychosocial problems and demoralization. Although the Centers for Disease Control definition of chronic fatigue syndrome (CFS) excludes pre-existing psychiatric illness, common psychosocial problems short of a clinical disorder (such as irritability, difficulty in thinking, inability to concentrate, depression and sleep disturbance) overlap with the criteria for CFS. Psychological states can affect the course of CFS or become confused in the patient's and doctor's mind with the course of infection. The core dilemma in practice is how aggressively to pursue a possible basis for CFS when it persists in the absence of an identifiable external cause. Possibilities for exploration are numerous and potentially expensive. In practice, the persistence of doctors depends on the patient's illness behaviour, on financial and organizational factors, and on the culture of medical care and practice styles. It is essential to differentiate the appropriate management of CFS from scientific study where intensive investigation may be warranted. In practice doctors should proceed in a manner that conveys concern, supports function, and avoids dysfunctional illness behaviour and inadvertent legitimization and reinforcement of disability.

  14. [Chronic kidney disease : What is currently available for treatment?

    PubMed

    Fleig, S; Patecki, M; Schmitt, R

    2016-12-01

    Chronic kidney disease is common in the general population with an estimated prevalence of roughly 2 million in Germany. Typically, chronic kidney disease is progressive and in the terminal stage the patients require dialysis or kidney transplantation. In many cases the disease remains silent for a long time but early stages are already associated with increasing morbidity and mortality. Therefore early detection is very important. In recent years several new concepts have been introduced that might help to slow the progression of chronic kidney disease or improve the accompanying risks. Here, we want to provide a nephrologist's perspective on the current guidelines for the treatment and prevention of chronic kidney disease. We summarize which diagnostic approaches are useful for general practitioners and we take a pragmatic look at the existing opportunities for combating renal functional decline. We also shed light on established measures to minimize the risk of comorbidities.

  15. Idelalisib for the Treatment of Chronic Lymphocytic Leukemia

    PubMed Central

    Khan, Maliha

    2014-01-01

    Chronic lymphocytic leukemia is the most common leukemia in the United States. It is a slowly progressive disease, with an 82% five-year survival rate. The treatment strategies are highly individualized with patients in the early and stable stages typically not requiring treatment. However, those with progressive or clinically advanced disease will require treatment. Cytotoxic drugs, such as the alkylating agents, purine nucleoside antagonists, and immunotherapeutic agents, have been the mainstay of chemotherapeutic treatment in CLL. However, given the lack of therapeutic specificity, these medications (especially older ones) have limited tolerability due to side effects. In this paper, we will discuss the data on the use of phosphatidylinositol 3 kinase inhibitor Idelalisib in the management of patients with chronic lymphocytic leukemia. The preclinical and clinical data thus far demonstrate that Idelalisib produces a dramatic and durable response in patients with chronic lymphocytic leukemia and without causing significant toxicity. Moving forward, the ongoing clinical trials will help address the various questions currently being raised regarding the long-term application and safety of Idelalisib. With greater clinical experience following more widespread use of Idelalisib, we will be able to determine the optimal combination therapies in treatment-naïve and relapsed/refractory patients, resulting in more individualized therapeutic strategies for patients with chronic lymphocytic leukemia. PMID:25093123

  16. Diagnosis and treatment of chronic constipation – a European perspective

    PubMed Central

    Tack, J; Müller-Lissner, S; Stanghellini, V; Boeckxstaens, G; Kamm, M A; Simren, M; Galmiche, J-P; Fried, M

    2011-01-01

    Background Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. Purpose We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted. PMID:21605282

  17. Interaction of St John's wort (Hypericum perforatum) with clozapine.

    PubMed

    Van Strater, Annelies C P; Bogers, Jan P A M

    2012-03-01

    St John's wort (Hypericum perforatum) is notorious for its ability to induce the enzymes of the P450 system. Especially, it induces CYP1A2 and CYP3A4, enzymes that are closely involved in the metabolism of clozapine. We present a patient with schizophrenia, who was stable on a fixed dose with stable plasma level of clozapine, and who deteriorated after she started self-medicating with St John's wort. The reduced plasma clozapine level and the psychiatric condition normalized after the withdrawal of St John's wort. It is possible that, beside the induction of P450-enzymes, the induction of P-glycoprotein by St John's wort aggravated psychiatric deterioration of the patient. Physicians should be alert to patients self-medicating with over-the-counter medicines, especially when these medicines can lower clozapine concentrations below the therapeutic range.

  18. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  19. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    PubMed

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  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.

  1. Nutritional support treatment for severe chronic hepatitis and posthepatitic cirrhosis.

    PubMed

    Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D, the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  2. Chronic amantadine treatment enhances the sexual behaviour of male rats.

    PubMed

    Ferraz, Marcia Martins Dias; Fontanella, Julia Cordeiro; Damasceno, Fabio; Silva de Almeida, Olga Maria Martins; Ferraz, Marcos Rochedo

    2007-04-01

    The acute administration of amantadine (AMA), a dopaminomimetic and NMDA glutamatergic receptor antagonist also used as an anti-Parkinsonian agent, stimulates male rat sexual behaviour. However it remains unclear whether long term AMA supplementation might also provoke a similar increase in male rat sexual conduct. In the present study, male rats were administered AMA (5-50 mg/kg/day) or vehicle daily for 21 days and their sexual response was monitored weekly. Chronic treatment with AMA effectively increased the sexual response of male rats, similarly to what had been observed before with acute amantadine treatment. The main effect of chronic AMA treatment occurs in arousal and in ejaculatory response, whilst the excitatory component was not affected. The 21-day treatment with AMA did not lead to tolerance, suggesting that perhaps AMA could be used in male human patients to prevent sexual inhibition caused by anti-depressant and anti-psychotic agents.

  3. 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

  4. Treatment of Chronic Anger Through Cognitive and Relaxation Controls

    ERIC Educational Resources Information Center

    Novaco, Raymond W.

    1976-01-01

    The study examined the extent to which cognitive self-control processes and relaxation techniques could be therapeutically applied to chronic anger problems. The cognitive treatment was implemented by self-instruction procedures. The cognitive coping procedures involved the use of self-statements for the management of anger and cognitive…

  5. [Gentos in the treatment of chronic abacterial prostatitis].

    PubMed

    Loran, O B; Pushkar', D Iu; Tedeev, V V; Nosovitskiĭ, P B

    2003-01-01

    Gentos was given to 46 patients with chronic abacterial prostatitis. The results of the treatment were analysed for 39 of them. Compared to control group, efficacy of gentos was 64.5-71.8% versus 53.6%. It can be used both as monotherapy and in combination with other modalities. Side effects of gentos were not registered.

  6. [Halotherapy in the combined treatment of chronic bronchitis patients].

    PubMed

    Maev, E Z; Vinogradov, N V

    1999-06-01

    Halotherapy proved to be a highly effective method in a complex sanatorium treatment of patients with chronic bronchitis. Its use promotes more rapid liquidation of clinical manifestations of disease, improves indices of vent function of lungs, especially those values that characterize bronchial conduction (volume of forced exhalations per second, index Tiffno), increases tolerance to physical load, normalizes indices of reduced immunity and leads to increasing the effectiveness of patient treatment in sanatorium.

  7. [Non-sedative antihistaminics in the treatment of chronic urticaria].

    PubMed

    Negro, J M; Sarrió, F; Miralles, J C; García Sellés, F J; López Sánchez, J D; Pagán, J a; Hernándéz, J

    1995-01-01

    Antihistamines are the drugs of choice in the symptomatic relief of chronic idiopathic urticaria; however, the usefulness of classic antihistamines has been limited by side effects. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less side effects (eg anticholinergic side effects, daytime sedation, etc). This review analyzes each of the new nonsedating antihistamines commercially available in Spain (astemizole, ebastine, cetirizine, loratadine and terfenadine) and evaluates its clinical efficacy and safety in the treatment of chronic idiopathic urticaria.

  8. Chronic migraine: current pathophysiologic concepts as targets for treatment.

    PubMed

    Vargas, Bert B

    2009-02-01

    Chronic daily headache (CDH) affects approximately 4% of the population and exerts a significant degree of disability on its sufferers. Chronic migraine (CM) is a subset of CDH that represents migraine without aura occurring on 15 or more days per month for at least 3 months. Although numerous risk factors are associated with the development of CM, the pathophysiology governing its genesis is largely unknown. The role of neurotransmitters, such as glutamate, as well as disruptions of antinociceptive systems and structures, are implicated in CM and are supported by the fact that treatments targeting these abnormalities are effective.

  9. Dose-hair concentration relationship and pigmentation effects in patients on low-dose clozapine.

    PubMed

    Kronstrand, R; Roman, M; Hedman, M; Ahlner, J; Dizdar, N

    2007-06-01

    Several hair components have been suggested as possible molecular sites for drug binding and interaction. Of these, keratin and melanin have been investigated in some detail in order to assess the mechanisms by which the binding occurs. Substances that are positively charged at physiological pH may interact by electrostatic forces between their cationic groups and the anionic carboxylic groups on the surface of the melanin polymer. Studies in human subjects with grey hair have shown that various drugs are detectable in both the coloured (melanin rich) and white (melanin free) hair shafts of these individuals. Again this supports the proposition that keratin and hair proteins play an important role in the binding of drugs in hair. However, drugs are often found in significantly higher concentrations in pigmented hair strands than in senile white hair strands. Another interesting question is if the concentration measured in hair reflects the dose taken. Previous reports have both verified and rejected this hypothesis, but most agree that many factors have impact on the incorporation rate, melanin being one. In this study we obtained blood and hair samples from 12 grey haired patients treated with low-dose clozapine as an adjunct medication in their treatment against Parkinson disease. Each patient's hair was divided into a pigmented and a non-pigmented portion and those were analyzed separately. Clozapine and desmethylclozapine were analyzed with LC-MS-MS after extraction of the analytes from hair and plasma. Paired results from the analysis of pigmented and white hair confirmed the preference for binding to pigmented hair for both clozapine and its metabolite. A majority of the incorporated clozapine was found in the pigmented hair but, as drugs could be detected in white hair, binding to hair protein or association with other hair matrix account for a significant part of drug accumulation in hair. High correlations between dose and the measured concentration of

  10. Oculogyric Crisis with Clozapine: A Case Report and Review of Similar Case Reports in the Literature

    PubMed Central

    Nebhinani, Naresh; Avasthi, Ajit; Modi, Manish

    2015-01-01

    Oculogyric crisis (OGC) is a dystonic reaction and commonly caused by typical antipsychotics and rarely occurs with clozapine. Here, we are presenting a case of OGC with clozapine therapy and reviewing the similar cases reported in the literature. PMID:26664086

  11. 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

  12. Clozapine and cocaine effects on dopamine and serotonin release in nucleus accumbens during psychostimulant behavior and withdrawal.

    PubMed

    Broderick, Patricia A; Hope, Omotola; Okonji, Catherine; Rahni, David N; Zhou, Yueping

    2004-01-01

    There is an increasing awareness that a psychosis, similar to that of schizophrenic psychosis, can be derived from cocaine addiction. Thus, the prototypical atypical antipsychotic medication, clozapine, a 5-HT(2)/DA(2) antagonist, was studied for its effects on cocaine-induced dopamine (DA) and serotonin (5-HT) release in nucleus accumbens (NAcc) of behaving male Sprague-Dawley laboratory rats with In Vivo Microvoltammetry, while animals' locomotor (forward ambulations), an A(10) behavior, was monitored at the same time with infrared photobeams. Release mechanisms for monoamines were determined by using a depolarization blocker, gamma-butyrolactone (gammaBL). BRODERICK PROBE microelectrodes selectively detected release of DA and 5-HT within seconds and sequentially in A(10) nerve terminals, NAcc. Acute and subacute studies were performed for each treatment group. Acute studies are defined as single injection of drug(s) after a stable baseline of each monoamine and locomotor behavior has been achieved. Subacute studies are defined as 24-h follow-up studies on each monoamine and locomotor behavior, in the same animal at which time, no further drug was administered. Results showed that (1) acute administration of cocaine (10 mg/kg ip) (n=5) significantly increased both DA and 5-HT release above baseline (P<.001) while locomotion was also significantly increased above baseline (P<.001). In subacute studies, DA release decreased significantly below baseline (P<.001) and significant decreases in 5-HT release occurred at the 15-min mark and at each time point during the second part of the hour (P<.05); the maximum decrease in 5-HT was 40% below baseline. Locomotor behavior, on the other hand, increased significantly above baseline (P<.05). (2) Acute administration of clozapine/cocaine (20 and 10 mg/kg ip, respectively; n=6) produced a significant block of the cocaine-induced increase in DA (P<.001) and 5-HT release (P<.001). Cocaine-induced locomotion was blocked

  13. 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.

  14. 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.

  15. Sulodexide in the treatment of chronic venous disease.

    PubMed

    Andreozzi, Giuseppe Maria

    2012-04-01

    Chronic venous disease encompasses a range of venous disorders, including those involving the lower limbs resulting from venous hypertension. The spectrum of chronic venous disease signs and symptoms shows variable severity, ranging from mild (aching, pain, and varicose veins) to severe (venous ulcers). The pathophysiology of chronic venous disease is characterized by venous hypertension, which triggers endothelial dysfunction and inflammation leading to microcirculatory and tissue damage, and eventually to varicose veins and venous ulcers. Sulodexide is an orally active mixture of glycosaminoglycan (GAG) polysaccharides with established antithrombotic and profibrinolytic activity. The agent is used in the treatment of a number of vascular disorders with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarction. Sulodexide differs from heparin because it is orally bioavailable and has a longer half-life and a smaller effect on systemic clotting and bleeding. An increasing body of preclinical evidence shows that sulodexide also exerts anti-inflammatory, endothelial-protective, and pleiotropic effects, supporting its potential efficacy in the treatment of chronic venous disease. Clinical studies of sulodexide have shown that the agent is associated with significant improvements in the clinical signs and symptoms of venous ulcers, and is therefore a recommended therapy in combination with local wound care and bandages for patients with persistent venous leg ulcers. Preliminary evidence supports the use of sulodexide in the prevention of recurrent deep venous thrombosis. Sulodexide was generally safe and well tolerated in clinical trials, without hemorrhagic complications. Sulodexide therefore appears to be a favorable option for the treatment of all stages of chronic venous disease and for the prevention of disease progression.

  16. Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients.

    PubMed

    Siribamrungwong, Monchai; Yothasamutr, Kasemsuk; Puangpanngam, Kutchaporn

    2014-06-01

    Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis-related data as well as highly sensitive C-reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C-reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P < 0.01, periodontal disease index; r = 0.56, P < 0.01). After completion of periodontal therapy, clinical periodontal indexes were significantly lower and high sensitivity C-reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status improvement. Erythropoietin dosage requirement decreased from 8000 to 6000 units/week while hemoglobin level was stable. Periodontitis is an important source of chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients.

  17. An overview of treatment approaches for chronic pain management.

    PubMed

    Hylands-White, Nicholas; Duarte, Rui V; Raphael, Jon H

    2017-01-01

    Pain which persists after healing is expected to have taken place, or which exists in the absence of tissue damage, is termed chronic pain. By definition chronic pain cannot be treated and cured in the conventional biomedical sense; rather, the patient who is suffering from the pain must be given the tools with which their long-term pain can be managed to an acceptable level. This article will provide an overview of treatment approaches available for the management of persistent non-malignant pain. As well as attempting to provide relief from the physical aspects of pain through the judicious use of analgesics, interventions, stimulations, and irritations, it is important to pay equal attention to the psychosocial complaints which almost always accompany long-term pain. The pain clinic offers a biopsychosocial approach to treatment with the multidisciplinary pain management programme; encouraging patients to take control of their pain problem and lead a fulfilling life in spite of the pain.

  18. Chronic Lymphocytic Leukemia: An Update on Current Treatment Approaches.

    PubMed

    Rozman, C; Montserrat, E

    1997-01-01

    During the last two decades, important progress has been made in the understanding of the biology, natural history, and prognosis of chronic lymphocytic leukemia (CLL). In addition, new and more effective treatment modalities are changing the objectives of treatment in patients with CLL. In this regard, the purine analogues offer great promise and fludarabine is already considered the treatment of choice for patients failing standard therapies. The role of purine analogues either alone or combined with other agents as front-line therapy is being actively investigated. Certain situations (e.g, autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g., corticosteroids, splenectomy). Transplants of hemopoietic progenitor cells are also increasingly performed. As a result of these advances, treatment of subjects with CLL can be decided on the basis of the individual risk of each patient and the possibility of curing some of them may become a realistic objective.

  19. Eliminating sedimentation for the treatment of chronic pelvic pain syndrome

    PubMed Central

    SUN, ZHONGMING; BAO, YANZHONG

    2013-01-01

    The aim of this study was to evaluate the curative effects of eliminating sedimentation inside the prostate via manipulation for the treatment of chronic pelvic pain syndrome (CPPS) using the National Institutes of Health (NIH)-chronic prostatitis symptom index (CPSI) scores. According to the prostatitis classification standard of the NIH, 721 patients with CPPS were divided into groups IIIA and IIIB by prostatic fluid routine examination (EPSRt) and treated using manipulation. The treatment was performed once per 3 days for 3–5 min and 10 treatments were considered to be a period. The EPSRt and NIH-CPSI scores were tested before and at the end of each period following treatment. After 3 treatment periods, the effectiveness and total effectiveness rates of the IIIA group were 72.3 and 15.9%, respectively and those of the IIIB group were 71.8 and 16.3%, respectively. Statistical analysis showed no significant differences between the curative effects in the two groups (P>0.05). The NIH-CPSI scores of the two groups were significantly improved following each treatment period (P<0.01). Eliminating sedimentation using manipulation dispersed the blockage, discharged the turbidity and cleared the gland, leading to the elimination of sedimentation and the relief of sinus hyperemia around the prostate, which significantly improved the clinical symptoms of CPPS and the quality of life of the patients. PMID:23737875

  20. [Magnetic therapy for complex treatment of chronic periodontal disease].

    PubMed

    P'yanzina, A V

    2017-01-01

    The aim of the study was to elaborate the methodology of magnetic therapy for complex treatment of chronic periodontal disease (CPD). The study included 60 patients aged 35 to 65 years with moderate CPD divided in 2 groups. Patients in group 1 (controls) received impulse carbonate irrigation for 12 min №10, group 2 additionally received magnetic therapy for 5 min №10 in maxillary and mandibular areas.

  1. The treatment of chronic pain with psychotropic drugs

    PubMed Central

    Merskey, H.; Hester, R. A.

    1972-01-01

    The treatment is described of thirty patients with chronic nervous system lesion causing intractable pain. Moderately good relief of pain was obtained with a combination of phenothiazines (especially pericyazine), antidepressant drugs and antihistamines. The theoretical implications of this are discussed and it is suggested that the drugs in question act partly by virtue of an effect on the multisynaptic neuronal systems whose activities are related to the experience of pain. PMID:4404064

  2. 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

  3. Studies on Aplysia neurons suggest treatments for chronic human disorders.

    PubMed

    Abrams, Thomas W

    2012-09-11

    For decades, the marine snail Aplysia has proven to be a powerful system for analyzing basic neurobiological mechanisms, particularly cellular and molecular mechanisms of neural plasticity. Three new findings on Aplysia may be relevant for the understanding and treatment of chronic human disorders. This research on this simple molluscan nervous system may lead to new therapeutic approaches for spinal cord injury, Fragile X syndrome, and genetic learning deficits more generally.

  4. [Efficacy of antacids in the treatment of chronic gastritis].

    PubMed

    Maev, I V; Dicheva, D T; Lebedeva, E G

    2010-01-01

    This article presents main principles of chronic gastritis treatment. Therapeutic abilities and possible side-effects due to components of antacids are analyzed. Special attention is paid to antisecretory and cytoprotective activity of Pepsan-R, which contains haiasulen (the main active component of chamomilla) and dimeticon. The authors of the article emphasize opportunity of using Pepsan-R in case of heartburn, gastric pain, abdominal distention during pregnancy and lactation.

  5. Prescribing pattern of clozapine and other antipsychotics for patients with first-episode psychosis: a cross-sectional survey of early intervention teams

    PubMed Central

    Tungaraza, Tongeji E.; Ahmed, Wakil; Chira, Chinonyelum; Turner, Erin; Mayaki, Susan; Nandhra, Harpal Singh; Edwards, Tom; Farooq, Saeed

    2016-01-01

    Objective: To describe the pattern of antipsychotic drug prescribing in patients with first episode psychosis, with more emphasis in the use of clozapine in this group of patients. Method: A cross-sectional survey involving six early intervention service (EIS) teams in the West Midlands was conducted. Data was extracted from case notes and electronic records by clinicians working in each participating team. The pattern of antipsychotic prescribing and the changes that took place after being accepted in EIS, including the use of clozapine, was established. Clinicians involved in the treatment of patients in each team rated the overall clinical response to treatment based on the presence or absence of positive psychotic symptoms. Result: 431 patients with FEP were included in the final analysis. Low antipsychotic discontinuation rate was observed, with the majority (88.2%) still being prescribed antipsychotics. Most (77.3%) were prescribed second-generation antipsychotic drugs, with olanzapine (21.8%) and aripiprazole (19.7%) being the most frequently prescribed antipsychotics. There was low rate use of antipsychotic combinations (7.4%), high dose antipsychotic regime (3.9%), low depot antipsychotic prescribing (9.3%), and clozapine use was low (9.7%). On average, three antipsychotics were tried before clozapine was initiated and it took on average 19.5 months from being accepted into EIS to clozapine being initiated. Conclusion: The majority of patients were prescribed antipsychotics within the guidelines. EIS was associated with an overall low antipsychotic discontinuation. There was also a short waiting time before clozapine was initiated following patients being accepted into EIS. PMID:28348730

  6. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    PubMed Central

    Steiner, Johann; Martins-de-Souza, Daniel; Schiltz, Kolja; Sarnyai, Zoltan; Westphal, Sabine; Isermann, Berend; Dobrowolny, Henrik; Turck, Christoph W.; Bogerts, Bernhard; Bernstein, Hans-Gert; Horvath, Tamas L.; Schild, Lorenz; Keilhoff, Gerburg

    2014-01-01

    Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies. PMID:25477781

  7. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes.

    PubMed

    Steiner, Johann; Martins-de-Souza, Daniel; Schiltz, Kolja; Sarnyai, Zoltan; Westphal, Sabine; Isermann, Berend; Dobrowolny, Henrik; Turck, Christoph W; Bogerts, Bernhard; Bernstein, Hans-Gert; Horvath, Tamas L; Schild, Lorenz; Keilhoff, Gerburg

    2014-01-01

    Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  8. 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.

  9. Severe chronic venous insufficiency: primary treatment with sclerofoam.

    PubMed

    Bergan, John J; Pascarella, Luigi

    2005-03-01

    Venous insufficiency, for practical purposes, can be divided into primary venous insufficiency and chronic venous insufficiency. The latter is characterized by advanced skin changes of hyperpigmentation, edema, ulceration, scarring from healed ulcers or open ulcerations. These are summarized in the CEAP classification as Classes 4, 5 and 6. Pretreatment evaluation is done with a standing ultrasound reflux examination. Thorough mapping of the extremity reflux is desirable. Physiologic tests of venous function, such as plethysmography, are unnecessary. Treatment is directed at closing refluxing axial veins as well as controlling those perforating veins with outward flow. Varicose veins contribute to axial reflux and must be obliterated. Arterial occlusive disease may complicate venous ulceration in as many as 15% of cases. Initial treatment of severe chronic venous insufficiency is usually carried out by controlling the edema with elastic bandaging or nonelastic support, such as the Unna boot or the CircAid dressing. Surgical intervention has been successful but the advent of foam sclerotherapy has proven to be an attractive alternative to surgery and has added a new tool for the treatment of severe chronic venous insufficiency. In this preliminary experience, the results are quite satisfactory and the technique has been shown to be effective, pain-free, inexpensive, with very little morbidity. Guidelines for obtaining sclerosants for use in foam sclerotherapy legally are provided.

  10. Is exercise an alternative treatment for chronic insomnia?

    PubMed Central

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

    2012-01-01

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

  11. Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide-activated N9 cells.

    PubMed

    Hou, Yue; Wu, Chun Fu; Yang, Jing Yu; He, Xiang; Bi, Xiu Li; Yu, Liang; Guo, Tao

    2006-12-30

    Schizophrenia is a devastating illness of unknown etiology and the basis for its treatment rests in the symptomatic response to antipsychotics. It was found that some of the patients with schizophrenia elicited microglia activation. The present study used lipopolysaccharide (LPS)-activated mouse microglial cell line N9 as an in vitro model to mimic microglia activation seen in the patients with schizophrenia. The effects of clozapine, olanzapine and haloperidol on the release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The results showed that olanzapine significantly inhibited NO release by LPS-stimulated N9 cells. Clozapine and haloperidol did not show significant effects on this model. The present study suggested that the inhibiting effect of olanzapine on the NO release by LPS-stimulated microglial cells might be a new mechanism through which olanzapine exhibits its therapeutic effect in the treatment of schizophrenia.

  12. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins.

    PubMed

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

    2015-07-14

    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.

  13. 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

  14. In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3ζ KO mouse model of schizophrenia-like disorders.

    PubMed

    Jaehne, Emily J; Ramshaw, Hayley; Xu, Xiangjun; Saleh, Eiman; Clark, Scott R; Schubert, Klaus Oliver; Lopez, Angel; Schwarz, Quenten; Baune, Bernhard T

    2015-11-01

    Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spine density observed in 14-3-3ζ KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14-3-3ζ molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug.

  15. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia.

    PubMed

    Goff, D C; Leahy, L; Berman, I; Posever, T; Herz, L; Leon, A C; Johnson, S A; Lynch, G

    2001-10-01

    CX516, a positive modulator of the glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other "ampakines" hold promise for the treatment of schizophrenia.

  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. [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.

  18. 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

  19. Hematological clozapine monitoring with a point-of-care device: a randomized cross-over trial.

    PubMed

    Nielsen, Jimmi; Thode, Dorrit; Stenager, Elsebeth; Andersen, Kristian Øllegaard; Sondrup, Ulla; Hansen, Tine N; Munk, Anne Marie; Lykkegaard, Signe; Gosvig, Annette; Petrov, Igor; le Quach, Phuong

    2012-06-01

    Clozapine remains the drug of choice for patients with treatment-resistant schizophrenia, who show a response rate of about 50% despite their unresponsiveness to other antipsychotics. Although treatment with clozapine can lead to considerable savings on bed days, the drug is underutilized for several reasons, perhaps most importantly because of the mandatory hematological monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care device providing counts of white blood cells (WBC) and granulocytes based on a capillary blood sampling. A randomized cross-over trial design was used comparing capillary blood sampling using a point-of-care device with traditional venous blood sampling. Patients were randomized to two sequences starting with either capillary or venous blood sampling followed by a repeated sequence. Primary outcome was measured on a 10-cm visual analog scale. Eighty-five patients were included in the test. Eight (9.4%) dropped out before completion. Patients indicated that they found capillary blood monitoring less painful than venous sampling (VAS ratings: 0.55 cm 25-75 percentiles: 0.1-1.4 cm vs. 1.75 cm 25-75 percentiles: 0.7-2.6, p<0.001). They also felt less inconvenienced by the point-of-care method than the traditional blood sampling, which involved traveling to the laboratory clinical (0.3 cm 25-75 percentiles: 0.05-0.7 vs. 2.3 cm 25-75 percentiles: 0.75-4.5, p<0.001). For hematological monitoring of clozapine patients a point-of-care device based on capillary blood sampling is better tolerated than traditional venous blood sampling.

  20. Clozapine-associated cardiac dysfunction during a gastroenteritis outbreak

    PubMed Central

    Szema, Anthony M.; Marboe, Charles; Fritz, Paul; Nguyen, Tram N.B.

    2016-01-01

    We report that two young adult patients who were initiated with clozapine for severe psychosis during a hospital-wide gastroenteritis outbreak went into severe shock. Neither patient had troponin elevation. Each required left ventricular assist device support for myocarditis. Endomyocardial biopsy revealed lymphocytic myocarditis in one patient and eosinophilic myocarditis in the other. The former patient expired. Polymerase chain reaction testing was negative for Coxsackie virus. These two patients illustrate that myocarditis can occur at usual incipient doses and that there may be an epidemiologic risk associated with gastroenteritis. Although the white blood cell (WBC) count is expected to decrease with clozapine, these patients had persistently elevated WBC counts. In conclusion, physicians should exercise caution when prescribing clozapine, especially for those with diarrhea. PMID:27987278

  1. 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.

  2. Operative treatment and arthroscopic findings in chronic patellar tendinitis.

    PubMed

    Griffiths, G P; Selesnick, F H

    1998-01-01

    Patellar tendinitis is a well-described clinical entity that usually responds well to conservative treatment. However, a subset of patients continue with symptoms despite exhaustive nonoperative means. The objective of the study was to review the treatment course and operative results of seven patients (eight knees) with chronic patellar tendinitis treated surgically. Five (70%) of these patients were either professional or collegiate athletes. The average age was 30 years (range, 20 to 45 years). Duration of symptoms averaged 1.4 years (range, 3 months to 4 years) before surgical correction. Operative treatment included knee arthroscopy and open repair consisting of excision of degenerated tissue and stimulation of a healing response of the patellar tendon pathology. Operative findings and pathology reports consistently showed marked fibrotendinous degeneration. Follow-up averaged 3.6 years (range, 4 months to 8.5 years). Outcomes were measured subjectively with SF36 results and objectively with Biodex testing (Biodex, Shirley, NY) and return to previous level of competition. Overall, 86% of patients achieved an excellent result and 14% had a fair result. We recommend operative intervention in a patient with chronic patellar tendinitis who does not improve with well-supervised, comprehensive conservative treatment.

  3. [Anemia of chronic disorder - pathogenesis, clinical presentation and treatment].

    PubMed

    Demarmels Biasiutti, Franziska

    2010-05-01

    After iron deficiency anemia the anemia of chronic disorder is the second most frequent anemia, and in hospitalized patients and/or patients suffering from chronic disease, especially infection, cancer and autoimmune disorders it is even the most frequent anemia. Morphologically it belongs to the normochromic, normocytic, hyporegeneratoric anemias. Pathogenetically it is induced by the upregulation of hepcidin, a recently detected acute phase protein with most important regulatory function in the iron-household. As a consequence of elevated hepcidin at the same time iron absorption in the bowel as well as iron release from macrophages are reduced, resulting in sequestration of iron in the RES and therefore functional iron deficiency. The other reason is a blunted release of erythropoetin (EPO) with at the same time reduced effectiveness due to down-regulation of EPO-receptors on erythroid cells. Treatment consists first of all in the therapy of the underlying disease and possibly in the combined application of EPO and iron.

  4. 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

  5. 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.

  6. [Treatment of chronic aphthous stomatitis combined with duodenal ulcer].

    PubMed

    Dudchenko, M A; Skrypnikova, T P; Dudchenko, M A

    2014-01-01

    It is currently proved ulcerous stomatitis and duodenal ulcer to have common pathogenetic infectious link (the most studied agent being Helicobacter pylori) by concominant decrease of local and general immunity with hyperoxidation events. Eighty patients (44 female and 36 male aged 15-60) with chronic aphthous stomatitis (AS) combined with duodenal ulcer were included in the study and divided in two equal groups according to treatment received (control group of 40 patients was treated according to conventional scheme, while in 40 patients a new formulation Vipromak was added to treatment protocol). The symptoms of AS tend to resolve faster in vipromak group thus proving its efficiency in treatment of AS and duodenal ulcer.

  7. [Advances in the treatment of chronic lymphocytic leukaemia].

    PubMed

    Mozas, Pablo; Delgado, Julio

    2016-11-18

    Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape.

  8. Dynorphin A analogs for the treatment of chronic neuropathic pain

    PubMed Central

    Hall, Sara M; Lee, Yeon Sun; Hruby, Victor J

    2016-01-01

    Chronic pain is one of the most ubiquitous diseases in the world, but treatment is difficult with conventional methods, due to undesirable side effects of treatments and unknown mechanisms of pathological pain states. The endogenous peptide, dynorphin A has long been established as a target for the treatment of pain. Interestingly, this unique peptide has both inhibitory (opioid in nature) and excitatory activities (nonopioid) in the CNS. Both of these effects have been found to play a role in pain and much work has been done to develop therapeutics to enhance the inhibitory effects. Here we will review the dynorphin A compounds that have been designed for the modulation of pain and will discuss where the field stands today. PMID:26824470

  9. Update on the Pharmacological Treatment of Chronic Migraine.

    PubMed

    Sun-Edelstein, Christina; Rapoport, Alan M

    2016-01-01

    Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

  10. 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

  11. Renal failure occurs in chronic lithium treatment but is uncommon.

    PubMed

    Bendz, Hans; Schön, Staffan; Attman, Per-Ola; Aurell, Mattias

    2010-02-01

    We sought to establish the prevalence of lithium-induced end-stage renal disease in two regions of Sweden with 2.7 million inhabitants corresponding to about 30% of the Swedish population. Eighteen patients with lithium-induced end-stage renal disease were identified among the 3369 patients in the general lithium-treated population, representing a sixfold increase in prevalence compared with the general population for renal replacement therapy. All lithium-treated patients were older than 46 years at end-stage renal disease with a mean lithium treatment time of 23 years with ten patients having discontinued lithium treatment an average of 10 years before the start of renal replacement therapy. The prevalence of chronic kidney disease (defined as plasma creatinine over 150 micromol/l) in the general lithium-treated population was about 1.2% (excluding patients on renal replacement therapy). Compared with lithium-treated patients without renal failure, those with chronic kidney disease were older and most were men but, as groups, their mean serum lithium levels and psychiatric diagnoses did not differ. We found that end-stage renal disease is an uncommon but not rare consequence of long-term lithium treatment and is more prevalent than previously thought. Time on lithium was the only identified risk factor in this study, suggesting that regular monitoring of renal function in these patients is mandatory.

  12. 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.

  13. Bone Density in Chronic Schizophrenia with Long-Term Antipsychotic Treatment: Preliminary Study

    PubMed Central

    Lee, Tae-Young; Chung, Hae-Kyung; Choi, Jin-Hee; Kim, Tae-Yong; So, Hyung-Seok

    2010-01-01

    Objective Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients. Methods The cross-sectional study was carried out with the subjects of 45 male schizophrenic patients who have undertaken the monotherapy with risperidone, olanzapine and clozapine for at least one year. The demographic factors, clinical symtoms, bone mineral density and hematological test were examined for all the subjects. Results No significant relationship was found between hyperprolactinemia and the decreased bone mineral density in the subjects. The negative schizophrenia symptom of the subjects showed a significant effect on the decreased bone mineral density. Conclusion The decreased bone mineral density finding in the male schizophrenic patients may be caused by the negative schizophrenia symptom rather than the hyperprolactinemia due to the antipsychotics. Additional studies are further required regarding other factors that may affect the decreased bone mineral density such as activity, calcium intake and exposure to sunlight. PMID:21253412

  14. [A new treatment: thermal therapy for chronic fatigue syndrome].

    PubMed

    Masuda, Akinori; Munemoto, Takao; Tei, Chuwa

    2007-06-01

    Thermal therapy using far-infrared ray dry sauna was performed for patients with chronic fatigue syndrome (CFS). Symptoms such as fatigue, pain, and low-grade fever were dramatically improved on two patients. And prednisolone administration was discontinued and became socially rehabilitated 6 months after discharge. On other 11 patients with CFS, physical symptoms such as fatigue and pain improved, too. Furthermore, we reported that repeated thermal therapy had relaxation effect and diminishes appetite loss and subjective complaints in mildly depressed patients. These results suggest that repeated thermal therapy may be a promising method for the treatment of CFS.

  15. 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.

  16. Nutritional treatment in chronic kidney disease: the concept of nephroprotection.

    PubMed

    Riccio, Eleonora; Di Nuzzi, Antonella; Pisani, Antonio

    2015-04-01

    Low-protein diets have been advocated for many decades as the cornerstone in the treatment of chronic kidney disease. Initially, the low intake of protein was used to reduce uremic symptoms; thereafter, albeit controversial, evidences suggested that dietary protein restriction can also slow the rate of progression of renal failure and the time until end-stage renal disease. This reviews focuses on the dietary factors and their influence on the loss of renal function and on the evidences in the literature supporting a nephroprotective role of the low-protein diet.

  17. 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.

  18. 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.

  19. My treatment approach to chronic hepatitis C virus.

    PubMed

    Shiffman, Mitchell L; Long, April G; James, Amy; Alexander, Phillip

    2014-07-01

    The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.

  20. Release behaviour of clozapine matrix pellets based on percolation theory.

    PubMed

    Aguilar-de-Leyva, Angela; Sharkawi, Tahmer; Bataille, Bernard; Baylac, Gilles; Caraballo, Isidoro

    2011-02-14

    The release behaviour of clozapine matrix pellets was studied in order to investigate if it is possible to explain it applying the concepts of percolation theory, previously used in the understanding of the release process of inert and hydrophilic matrix tablets. Thirteen batches of pellets with different proportions of clozapine/microcrystalline cellulose (MCC)/hydroxypropylmethyl cellulose (HPMC) and different clozapine particle size fractions were prepared by extrusion-spheronisation and the release profiles were studied. It has been observed that the distance to the excipient (HPMC) percolation threshold is important to control the release rate. Furthermore, the drug percolation threshold has a big influence in these systems. Batches very close to the drug percolation threshold, show a clear effect of the drug particle size in the release rate. However, this effect is much less evident when there is a bigger distance to the drug percolation threshold, so the release behaviour of clozapine matrix pellets is possible to be explained based on the percolation theory.

  1. 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.

  2. Current options for treatment of chronic coronary artery disease

    PubMed Central

    Prapas, Sotirios N.; Tsakiridis, Kosmas; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Sakkas, Antonios; Zarogoulidis, Konstantinos

    2014-01-01

    The primary issues must be discussed regarding the decision making of treating a patient with chronic coronary artery disease (CAD), are the appropriateness of revascularization and the method which will be applied. The criteria will be the symptoms, the evidence of ischemia and the anatomical complexity of the coronary bed. Main indications are persistence of symptoms, despite oral medical treatment and the prognosis of any intervention. The prognosis is based on left ventricular function, on the number of coronary arteries with significant stenosis and the ischemic burden. For patients with symptoms and no evidence of ischemia, there is no benefit from revascularization. If ischemia is proven, revascularization is beneficial. If revascularization is decided, the next important issue must be taken under consideration is the choice of the appropriate method to be applied, surgical or interventional approach. Current treatment options will be presented. PMID:24672695

  3. Chronic Cluster Headache with an Atypical Presentation and Treatment Response

    PubMed Central

    Morais, Hugo

    2016-01-01

    The management of cluster headache (CH) may be challenging. We report a 50-year-old male with recurrent attacks of dull and severe unilateral periorbital pain, lasting 30–45 minutes, twice a day, exclusively during sleep, and accompanied by ipsilateral rhinorrhea and lacrimation. The pain switched sides within every attack. CH treatment was initiated but the patient maintained recurrence rates compatible with chronic CH, even after increasing verapamil to 460 mg/day. Afterwards we decided to add lithium (800 mg/day). With this treatment the severity and recurrence of CH substantially decreased, despite the patient's autonomous decision to take lithium only during the acute phase of the cluster. The exclusively alternating location and the excellent response to short cycles of lithium represent two unique features of CH. PMID:28127484

  4. 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

  5. New developments in endoscopic treatment of chronic pancreatitis.

    PubMed

    Didden, P; Bruno, M; Poley, J W

    2012-12-01

    The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

  6. Ecological system influences in the treatment of pediatric chronic pain

    PubMed Central

    Logan, Deirdre E; Engle, Lisa; Feinstein, Amanda B; Sieberg, Christine B; Sparling, Penny; Cohen, Lindsey L; Conroy, Caitlin; Driesman, Dana; Masuda, Akihiko

    2012-01-01

    Family, school and the peer network each shape the chronic pain experience of the individual child, and each of these contexts also represents a domain of functioning often impaired by chronic pain. The goal of the present article is to summarize what is known about these bidirectional influences between children with pain and the social systems that surround them. Case reports that illustrate these complex, transactional forces and their ultimate impact on the child’s pain-related functioning are included. A case involving siblings participating in an intensive interdisciplinary program for functional restoration and pain rehabilitation highlights how parents change through this treatment approach and how this change is vital to the child’s outcomes. Another case involving a child undergoing intensive interdisciplinary treatment illustrates how school avoidance can be treated in the context of pain rehabilitation, resulting in successful return to the regular school environment. Finally, an acceptance and commitment therapy-focused group intervention for children with sickle cell disease and their parents demonstrates the benefits of peer contact as an element of the therapeutic intervention. PMID:23248814

  7. 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

  8. 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.

  9. Lamivudine treatment in patients with chronic hepatitis B and cirrhosis.

    PubMed

    Haché, Chantal; Villeneuve, Jean-Pierre

    2006-09-01

    Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.

  10. Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats.

    PubMed

    Vasudevan, Harish; McNeill, John H

    2007-04-01

    Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.

  11. [Medical treatment in patients with chronic thromboembolic pulmonary hypertension].

    PubMed

    Subias, Pilar Escribano; Cano, María José Ruiz; Flox, Angela

    2009-06-01

    Pulmonary thromboendarterectomy is the treatment of choice in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, specific medical treatment of pulmonary hypertension (PH) can be an alternative or play a complementary role to surgery. Thus, in patients unsuitable for surgery due to distal thrombotic obstruction, residual or persistent PH after surgery or very severe PH and a high-risk hemodynamic profile, medical treatment may improve their clinical course and the outcome of thromboendarterectomy. Patients with distal obstruction in the pulmonary tree and those with residual PH after surgery show clinical and hemodynamic deterioration due to progression of the pulmonary vascular disease in the smallcaliber arterioles. Conventional treatment with diuretics, anticoagulants and oxygen therapy has been demonstrated to have little effectiveness. In the last decade, numerous drugs have been developed for the treatment of PH: prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors acting principally in vascular remodelling of small-caliber arterioles. Although evidence of the effectiveness of these drugs in PH and the histological similarity of small-vessel vasculopathy in CTEPH to that of other forms of PH provide the main rationale for the use of these drugs in patients with CTEPH, the evidence from clinical trials is still limited.

  12. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    PubMed

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  13. Brain natriuretic peptide as a biomarker of asymptomatic clozapine-related heart dysfunction: a criterion for a more cautious administration.

    PubMed

    Prisco, Vincenzo; Monica, Petrosino; Fiore, Germano; Tridente, Annamaria; La Rocca, Antonietta; Catapano, Francesco; Fabrazzo, Michele

    2016-12-20

    Clozapine-related pericarditis is a rare side effect of the drug. We reported the clinical cases of two women, aged 22 and 28 years, affected by schizophrenia with pericarditis symptoms related to clozapine treatment of 200 mg/day. Clozapine was discontinued in both patients, resulting in normalization of the ECG changes, and echocardiography confirmed the progressive disappearance of the pericardial effusion. Interestingly, while inflammatory indices and pro-brain natriuretic peptide (pro-BNP) plasma levels were high in both patients, only one of them showed tachycardia, subjective chest pain, shortness of breath and dyspnea, with a clinical symptomatology suggesting a cardiac involvement. BNP is a vasoactive peptide synthetized by the ventricular myocardium which splits in two fragments: BNP and the N-terminal (pro-BNP). Both are considered valuable biomarkers in clinical practice for the prediction of disease state and prognosis in patients with suspected heart failure. Pro-BNP acts as a key regulator in the homeostasis of water and salt excretion and in the maintenance of blood pressure, mainly by inhibiting the renin-angiotensin-aldosterone axis and blocking the sympathetic nervous activity. In our cases, pro-BNP plasma levels proved to be a profitable way to identify subjects with asymptomatic cardiac impairment who could benefit from a therapy preventing progression to heart failure.

  14. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.

    PubMed

    Villeneuve, J P; Condreay, L D; Willems, B; Pomier-Layrargues, G; Fenyves, D; Bilodeau, M; Leduc, R; Peltekian, K; Wong, F; Margulies, M; Heathcote, E J

    2000-01-01

    The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P <.05, baseline vs. 9 months), an increase in serum albumin from 27 +/- 1 to 34 +/- 1g/L (P <.05), and a decrease in Child-Pugh score from 10.3 +/- 0.4 to 7.5 +/- 0.5 (P <.05). Three patients developed resistance to lamivudine because of a mutation in the YMDD motif, but liver function did not deteriorate. We conclude that inhibition of viral replication with lamivudine results in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term benefits remain uncertain.

  15. Chronic lymphocytic leukemia: treatment options for patients with refractory disease.

    PubMed

    Motta, Marina; Wierda, William G; Ferrajoli, Alessandra

    2009-09-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL.

  16. 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

  17. Interferon-induced thyroiditis during treatment of chronic hepatitis C.

    PubMed

    Kozielewicz, Dorota; Halota, Waldemar

    2012-01-01

    Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto's disease and Graves' disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2-3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.

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

    PubMed

    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.

  19. [NON-ONCOLOGIC CHRONIC PAIN TREATMENT WITH OPIATES].

    PubMed

    Molas Ferrer, Glòria; Castellà Kastner, Montse; Lombraña Mencia, María

    2014-09-01

    Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs.

  20. 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.

  1. Treatment of chronic venous leg ulcers by platelet gel.

    PubMed

    Ficarelli, Elena; Bernuzzi, Gino; Tognetti, Elena; Bussolati, Ovidio; Zucchi, Alfredo; Adorni, Daniela; De Panfilis, Giuseppe

    2008-07-01

    Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.

  2. Effect of clozapine on the metabolism of serotonin in rat brain.

    PubMed

    Ruch, W; Asper, H; Bürki, H R

    1976-01-01

    Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleep-inducing properties of this drug.

  3. Treatment of hypertension in children with chronic kidney disease.

    PubMed

    Halbach, Susan; Flynn, Joseph

    2015-01-01

    Hypertension (HTN) is increasingly recognized as a common feature of pediatric chronic kidney disease (CKD). A growing body of evidence demonstrates that HTN is both underdiagnosed and undertreated in this population. The consequences of untreated HTN include adverse effects on CKD progression, markers of cardiovascular morbidity, and neurocognitive functioning. Consensus guidelines issued over the past decade have incorporated recent research on the consequences of HTN in recommendations for the diagnosis and treatment of HTN in pediatric CKD and include lower BP targets. Agents which target the renin-angiotensin-aldosterone system (RAAS) should be considered first-line therapy in CKD-associated HTN in children, though multiple medications may be required to achieve sufficient BP control.

  4. 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

  5. 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

  6. Treatment of younger patients with chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra

    2010-01-01

    Younger patients (defined as patients younger than 50-55 years of age) represent a small group of newly diagnosed patients with chronic lymphocytic leukemia, accounting only for 10% to 20% of newly diagnosed cases. However, once these patients become symptomatic and require treatment, their life expectancy is significantly reduced. Therapeutic approaches for younger patients should be directed at improving survival by achieving a complete remission and, where possible, eradicating minimal residual disease. Chemoimmunotherapy combinations carry the highest response rates and are commonly offered to younger patients. Additional strategies that should be considered for younger patients include early referral for stem-cell transplantation and clinical trials of consolidation therapy to eliminate minimal residual disease.

  7. Cachexia in chronic heart failure: endocrine determinants and treatment perspectives.

    PubMed

    Mangner, Norman; Matsuo, Yae; Schuler, Gerhard; Adams, Volker

    2013-04-01

    It is well documented in the current literature that chronic heart failure is often associated with cachexia, defined as involuntary weight loss of 5 % in 12 month or less. Clinical studies unraveled that the presence of cachexia decreases significantly mean survival of the patient. At the molecular level mainly myofibrillar proteins are degraded, although a reduced protein synthesis may also contribute to the loss of muscle mass. Endocrine factors clearly regulate muscle mass and function by influencing the normally precisely controlled balance between protein breakdown and protein synthesis The aim of the present article is to review the knowledge in the field with respect to the role of endocrine factors for the regulation of cachexia in patients with CHF and deduce treatment perspectives.

  8. Effects of chronic amiodarone treatment on rat testis.

    PubMed

    Özkaya, Ahmet Kağan; Dilber, Embiya; Gürgen, Seren Gülşen; Kutlu, Ömer; Cansu, Ali; Gedik, Yusuf

    2016-04-01

    Amiodarone is a potent agent used to treat tachyarrhythmias, which are especially refractory to other medications, in both adults and children. Although widely used as an antiarrhythmic drug, amiodarone causes many serious adverse effects that limit its use. This study investigated the possible morphological and apoptotic effects of amiodarone on rat testes. Amiodarone was administered to male Sprague-Dawley rats at doses of 20 or 200mg/kg/day for 14 days. A histopathological examination of testicular tissue revealed the presence of inflammatory cells in the seminiferous tubule lumen together with swelling and vacuolization in the cytoplasm of some spermatogonia; these effects occured in a dose-dependent manner. Immunohistochemical staining showed evidence of apoptosis, including caspase-3, caspase-9, Bax and increased DNA fragmentation was detected via a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. In conclusion, the results show that chronic amiodarone treatment causes dose-dependent degenerative and apoptotic effects on rat testes.

  9. [Chronic blepharoconjunctivitis during a treatment with acitretin (Soriatane)].

    PubMed

    Denis, P; Nordmann, J P; Saiag, P; Liotet, S; Laroche, L; Saraux, H

    1993-01-01

    We report external ocular side effects after treatment with acitretin, a new synthetic vitamin A analogue and the main metabolite of etretinate. A patient treated with 20-25 mg/day of acitretin for psoriasis suffered from chronic blepharoconjunctivitis. Schirmer tests, tear lysozyme were normal while rose bengal and fluorescein staining disclosed epithelial punctate defects and tear break-up time was shortened. Meibomian glands of the lower lid were photographed with transillumination and appeared atrophic. Conjunctival cytology and biopsy showed snake-like chromatine appearance, keratinized epithelial cells and some lymphocytes infiltrates. Accessory salivary gland histological aspects were nonspecific. There was a clear relationship between restarting the acitretin therapy and recurrence of ocular symptoms. Acitretin, like other retinoids, may induce or exacerbate blepharoconjunctivitis in patients with psoriasis.

  10. Cardiac actomyosin ATPase activity after chronic doxorubicin treatment.

    PubMed

    Bergson, A; Inchiosa, M A

    1985-04-01

    Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.

  11. [Pharmacological treatment of stable chronic obstructive pulmonary disease].

    PubMed

    Allain, Yves-Marie; Giraud, Frédérique; Huchon, Gérard; Roche, Nicolas

    2009-03-01

    The pharmacological treatment of chronic obstructive pulmonary disease (COPD) can significantly improve quality of life by reducing exacerbations, dyspnea and exercise intolerance, thereby limiting the degree of handicap and improving daily activities. Recently, large randomised trials showed that some treatments can alter the decline in FEV1, which was previously only accessible to smoking cessation, and maybe reduce mortality. Bronchodilators are the first-line pharmacological treatment of COPD. Their clinical efficacy cannot be predicted by the inconstant changes in FEV(1.) Their main mechanism of action is the reduction in lung hyperinflation. Theophylline has a lower efficacy/tolerance ratio than inhaled bronchodilators. In symptomatic patients with FEV1 <50/60% predicted and repeated exacerbations despite bronchodilators, inhaled corticosteroids combined with long acting beta-agonists can be used. Several other approaches targeting inflammation and oxidative stress, remodelling and lung regeneration are also being studied. Medications must be associated with non-pharmacological measures (including help towards smoking cessation, education, exercise training...). Systemic manifestations of COPD must also be taken into account.

  12. Effects of Chronic Buspirone Treatment on Cocaine Self-Administration

    PubMed Central

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

    2013-01-01

    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. 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.

  14. Alitretinoin for the treatment of severe chronic hand eczema.

    PubMed

    Paulden, M; Rodgers, M; Griffin, S; Slack, R; Duffy, S; Ingram, J R; Woolacott, N; Sculpher, M

    2010-05-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time

  15. Liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat plasma.

    PubMed

    Zhang, Guodong; Terry, Alvin V; Bartlett, Michael G

    2007-01-01

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for simultaneous quantification of olanzapine, clozapine, ziprasidone, haloperidol, risperidone, and its active metabolite 9-hydroxyrisperidone, in rat plasma using midazolam as internal standard (IS). The analytes were extracted from rat plasma using a single step liquid-liquid extraction technique. The compounds were separated on a Waters Atlantis dC-18 (30 mm x 2.1 mm i.d., 3 microm) column using a mobile phase of acetonitrile/5 mM ammonium formate (pH 6.1 adjusted with formic acid) with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries and stability were determined. LLOQ was 0.1 ng/mL and correlation coefficient (R(2)) values for the linear range of 0.1-100 ng/mL were 0.997 or greater for all the analytes. The intra-day and inter-day precision and accuracy were better than 8.05%. The relative and absolute recovery was above 77% and matrix effects were low for all the analytes except for ziprasidone. This validated method has been successfully used to quantify the plasma concentration of the analytes after chronic treatment with antipsychotic drugs.

  16. Obinutuzumab for the treatment of chronic lymphocytic leukemia.

    PubMed

    Rogers, K A; Jones, J A

    2014-06-01

    Obinutuzumab is a novel therapeutic anti-CD20 monoclonal antibody recently approved by the United States Food and Drug Administration (FDA) for use in combination with chlorambucil as first-line treatment of chronic lymphocytic leukemia (CLL). It is distinguished from other anti-B-lymphocyte antigen CD20 (anti-CD20) therapeutic antibodies in current clinical use by its type II properties and glycoengineered Fc region. In vitro these unique properties translate into higher rates of antibody-dependent cytotoxicity and direct cell death compared to rituximab, and obinutuzumab demonstrates improved efficacy in human lymphoma xenograft models and whole blood lymphocyte depletion assays. FDA approval was based upon results from a randomized phase III trial comparing treatment with single-agent chlorambucil to the combination of chlorambucil and either rituximab or obinutuzu-mab. The obinutuzumab arm resulted in higher rates of complete remission and significant improvements in progression-free survival versus either comparator regimen. The majority of patients in the obinutuzumab and chlorambucil arm finished all six planned treatment cycles, and therapy was well tolerated. Toxicities of obinutuzumab are similar to those of other anti-CD20 antibodies, although infusion-related reactions and neutropenia appear to be more common. This trial establishes chemoimmunotherapy with obinutuzumab and chlorambucil as an attractive treatment option for CLL patients, particularly those with comorbid medical illnesses or advanced age. Obinutuzumab remains under study in combination with both chemotherapy and novel agents for CLL and non-Hodgkin's lymphoma, where it is expected to find additional clinical applications.

  17. Novel agents for the treatment of chronic lymphocytic leukemia.

    PubMed

    Abou-Nassar, Karim; Brown, Jennifer R

    2010-12-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Currently, the most effective treatment for CLL consists of a combination of fludarabine, cyclophosphamide, and rituximab. Although this approach has encouraging results, patients with CLL eventually relapse and require additional therapies. Many of the current therapeutic regimens for CLL are myelotoxic, immunosuppressive, and associated with infectious complications. Targeted therapies can often minimize these complications. The US Food and Drug Administration has recently approved 2 agents, bendamustine and ofatumumab, for the treatment of CLL. Emerging therapies ranging from new monoclonal antibodies to small molecules that interfere with vital pathways in signal transduction and cell cycle regulation are currently being developed. This article will focus on novel agents in earlier development phases for CLL, including the immunomodulator lenalidomide; monoclonal antibodies, such as lumiliximab, GA-101, and small molecule immunopharmaceuticals; BCL-2 inhibitors, such as oblimersen, obatoclax, and ABT-263; and protein kinase inhibitors, such as flavopiridol, spleen tyrosine kinase inhibitors, and phosphatidylinositol 3-kinase inhibitors.

  18. [Is efalizumab a safe treatment for a chronic disease?].

    PubMed

    Daudén, E; Oñate, M J

    2008-01-01

    Psoriasis is a chronic disease that has a very negative impact on the quality of life of those suffering it. Therefore, treatments that make it possible to satisfactorily control the disease in the long term and maintain a good safety profile are needed. Efalizumab fulfills both requirements. In this article, the potential risks involved in treatment with efalizumab, specifically the acute flu-like syndrome, alterations in laboratory data (leukocytosis, lymphocytosis, thrombocytopenia, hemolytic anemia, elevation of alkaline phosphatase and hepatic biochemistry), infections, neoplasms, skin disorders related with psoriasis (localized papular rash, generalized inflammatory rash, changes in the morphology of psoriasis, rebound phenomenon), joint manifestations, acute inflammatory polyradiculoneuropathy and hypersensitivity reactions are reviewed. The contraindications, presence of antiefalizumab antibodies, their drug interactions, use of vaccines and relationship with pregnancy and breast-feeding are also discussed. An adequate selection of the patient, detailed information to the patient on the benefits and risks and correct knowledge of the potential adverse effects by the clinician are essential requirements for satisfactory use of efalizumab in long-term continued therapy.

  19. Endovascular treatment of chronic arterial mesenteric ischemia: a changing perspective?

    PubMed

    Gibbons, C P; Roberts, D E

    2010-03-01

    Endovascular treatment for chronic mesenteric ischemia is growing in popularity because of its lower periprocedural morbidity and mortality than open surgery. It is especially suitable for the high-risk surgical candidate and for those who have a poor nutritional state, although endovascular surgery may not be possible in patients with ostial occlusions or heavily calcified vessels. A positive response to angioplasty is helpful to secure a diagnosis in patients with slightly atypical symptoms. There are little data at present to suggest that primary stenting is better than angioplasty alone, but insertion of a stent may be valuable as a rescue procedure following dissection, vascular recoil, or thrombosis during angioplasty. The superior mesenteric artery is probably the most important vessel to treat but, where this is impossible, celiac or inferior mesenteric artery dilatation may have therapeutic benefit. However, there is some evidence at present favoring multiple, as opposed to single-vessel, angioplasty or stenting. Long-term patency is better after mesenteric bypass, which may be preferred in the younger and fitter patient. Treatment of the celiac artery compression syndrome is primarily surgical, but stent insertion may have a role as a secondary procedure where there is a residual stenosis after median arcuate ligament division.

  20. Lenalidomide in the Treatment of Chronic Lymphocytic Leukemia

    PubMed Central

    Cortelezzi, Agostino; Sciumè, Mariarita; Reda, Gianluigi

    2012-01-01

    The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently been approved for CLL therapy and many novel agents are under clinical investigation. The role of the tumor microenvironment and of immune dysfunction in CLL have allowed to enlarge the therapeutic armamentarium for CLL patients. This article will provide a comprehensive summary regarding mechanism of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical trials using lenalidomide alone or in combinations are discussed. Lenalidomide shows good activity also in relapsed/refractory or treatment-naive CLL patients. Definitive data from ongoing studies are needed to validate overall and progression-free survival. The toxicity profile might limit lenalidomide use because it can result in serious side effects, but largely controlled by gradual dose escalation. Further understanding of the exact mechanism of action in CLL will allow more efficacious use of lenalidomide alone or in combination regimens. PMID:22851972

  1. Effect and Treatment of Chronic Pain in Inflammatory Arthritis

    PubMed Central

    2013-01-01

    Pain is the most common reason patients with inflammatory arthritis see a rheumatologist. Patients consistently rate pain as one of their highest priorities, and pain is the single most important determinant of patient global assessment of disease activity. Although pain is commonly interpreted as a marker of inflammation, the correlation between pain intensity and measures of peripheral inflammation is imperfect. The prevalence of chronic, non-inflammatory pain syndromes such as fibromyalgia is higher among patients with inflammatory arthritis than in the general population. Inflammatory arthritis patients with fibromyalgia have higher measures of disease activity and lower quality of life than inflammatory patients who do not have fibromyalgia. This review article focuses on current literature involving the effects of pain on disease assessment and quality of life for patients with inflammatory arthritis. It also reviews non-pharmacologic and pharmacologic options for treatment of pain for patients with inflammatory arthritis, focusing on the implications of comorbidities and concurrent disease-modifying antirheumatic drug therapy. Although several studies have examined the effects of reducing inflammation for patients with inflammatory arthritis, very few clinical trials have examined the safety and efficacy of treatment directed specifically towards pain pathways. Most studies have been small, have focused on rheumatoid arthritis or mixed populations (e.g., rheumatoid arthritis plus osteoarthritis), and have been at high risk of bias. Larger, longitudinal studies are needed to examine the mechanisms of pain in inflammatory arthritis and to determine the safety and efficacy of analgesic medications in this specific patient population. PMID:23292816

  2. Treatment of chronic graft-versus-host disease with bortezomib

    PubMed Central

    Pai, Chien-Chun Steven; Chen, Mingyi; Mirsoian, Annie; Grossenbacher, Steven K.; Tellez, Joseph; Ames, Erik; Sun, Kai; Jagdeo, Jared; Blazar, Bruce R.; Abedi, Mehrdad

    2014-01-01

    Chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) has emerged as a predominant complication following HSCT and has a distinct etiology. We and others have previously demonstrated that bortezomib, a proteasome inhibitor, can prevent but not treat acute GVHD in mice. To assess the effects of bortezomib on cGVHD, a mouse minor histocompatibility antigen-mismatched strain combination was used to mimic clinical cGVHD sclerodermatous pathogenesis and phenotype. Treatment of ongoing cGVHD with bortezomib ameliorated cutaneous lesions, which were also associated with a reduction in total numbers of germinal center B cells and lower B-cell activating factor gene expression levels in cutaneous tissues. Importantly, lymphoma-bearing mice receiving allogeneic HSCT with bortezomib preserved graft-versus-tumor (GVT) effects. Based on these animal studies, we initiated an intrapatient dose escalation clinical trial in patients with extensive steroid–intolerant, dependent, or resistant cGVHD. Marked clinical improvement was observed in patients, which was also associated with reductions of peripheral B cells and minimal toxicity. These results indicate that bortezomib can be of significant use in the treatment of cGVHD and may also allow for maintenance of GVT. This trial was registered at www.clinicaltrials.gov as #NCT01672229. PMID:25009225

  3. 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

  4. 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.

  5. Therapeutic monitoring of clozapine in Australia: the need for consensus.

    PubMed

    Oo, Thein Z; Wilson, John F; Naidoo, Divania; Chetty, Manoranjenni

    2006-10-01

    In the absence of well-defined guidelines for the monitoring of plasma concentrations of clozapine, this study examined the practices of seven laboratories from four states in Australia. Laboratories analyzed 5 freeze-dried serum samples containing a mixture of clozapine and norclozapine in varying concentrations and the measurement data were analyzed for accuracy and precision. Additional information on laboratory practices was obtained through questionnaire responses. Measurement precision amongst the laboratories was good but there were significant differences in the accuracy of measurements from one laboratory. There were differences in the ranges for which assays had been validated and in suggested therapeutic ranges. These differences could have a significant impact on the interpretation of measured concentrations and patient care, and emphasize the need for consensus in this area. Repeat concentration measurements are recommended in the case of drug concentration measurements that are inconsistent with clinical observations or previous measurements.

  6. Actively Negotiating the Mind-Body Divide: How Clozapine-Treated Schizophrenia Patients Make Health for Themselves.

    PubMed

    Brown, Julia E H; Dennis, Simone

    2017-01-10

    It is well recognised that antipsychotic treatments impact the whole body, not just the target area of the brain. For people with refractory schizophrenia on clozapine, the gold standard antipsychotic treatment in England and Australia, the separation of mental and physical regimes of health is particularly pronounced, resulting in multiple, compartmentalised treatment registers. Clinicians often focus on the mental health aspects of clozapine use, using physical indicators to determine whether treatment can continue. Our observations of 59 participants in England and Australia over 18 months revealed that patients did not observe this hierarchisation of mental treatments and physical outcomes. Patients often actively engaged in the management of their bodily symptoms, leading us to advance the figure of the active, rather than passive, patient. In our paper, we do not take the position that the facility for active management is a special one utilised only by these patients. We seek instead to draw attention to what is currently overlooked as an ordinary capacity to enact some sort of control over life, even under ostensibly confined and confining circumstances. We argue that clozapine-treated schizophrenia patients utilise the clinical dichotomy between mental and physical domains of health to rework what health means to them. This permits patients to actively manage their own phenomenological 'life projects' (Rapport, I am Dynamite: an Alternative Anthropology of Power, Routledge, London 2003), and forces us to reconsider the notion of clinical giveness of what health means. This making of one's own meanings of health may be critical to the maintenance of a sense of self.

  7. Surgical strategies in the treatment of chronic pancreatitis

    PubMed Central

    Zhao, Xin; Cui, Naiqiang; Wang, Ximo; Cui, Yunfeng

    2017-01-01

    Abstract Background: Chronic pancreatitis (CP) is a common and frequently occurring disease. Pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. The Beger and Frey procedures are 2 main duodenum-preserving techniques in duodenum-preserving pancreatic head resection (DPPHR) strategies. We conducted this systematic review and meta-analysis to compare the clinical efficacy of DPPHR versus PD, the Beger procedure versus PD, the Frey procedure versus PD, and the Beger procedure versus the Frey procedure in the treatment of pancreatitis. The optimal surgical option for chronic pancreatitis is still under debate. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of different surgical strategies for chronic pancreatitis. Methods: Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched with the limitations of human subjects and randomized controlled trials (RCTs) text. Data were extracted by 2 of the coauthors independently and analyzed using the RevMan statistical software, version 5.3. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Results: Seven studies involving a total of 385 patients who underwent the surgical treatments were assessed. The methodological quality of the trials ranged from low to moderate and included PD (n = 134) and DPPHR (n = 251 [Beger procedure = 100; Frey procedure = 109; Beger or Frey procedure = 42]). There were no significant differences between DPPHR and PD in post-operation mortality (RR = 2.89, 95% CI = 0.31–26.87, P = 0.36), pain relief (RR = 1.09, 95% CI = 0.94–1.25, P = 0.26), exocrine insufficiency (follow-up time > 60 months

  8. Treatment of chronic constipation with cisapride and placebo.

    PubMed Central

    Müller-Lissner, S A

    1987-01-01

    The effect of cisapride (20 mg bid), a new prokinetic drug, on bowel habits and laxative consumption was studied in patients with idiopathic painless constipation and chronic laxative intake. After a four week base line period, spontaneous defection (frequency without laxative intake) and total defecation (total frequency) were measured. Patients with a spontaneous defecation of less than three stools per week entered the treatment period and were randomly assigned to double blind treatment with either cisapride (n = 64) or placebo (n = 62). After eight weeks of treatment, a four week run out phase on single blind placebo medication was conducted. Cisapride and placebo increased spontaneous stool frequency from 1.1 +/- 0.2 SEM to 3.0 +/- 0.2 per week (p less than 0.001) and from 1.2 +/- 0.1 to 1.5 +/- 0.2 (p greater than 0.05), respectively. Laxative consumption was decreased from 3.6 +/- 0.3 to 1.8 +/- 0.2 doses/week by cisapride (p less than 0.001) and from 3.3 +/- 0.3 to 2.8 +/- 0.3 by placebo (p less than 0.05). Both drugs improved constipation as assessed by the patient by means of a visual analogue scale, but cisapride did so to a larger extent than placebo. The effects of cisapride partly outlasted active medication by at least four weeks. It is concluded that cisapride improves bowel habits in patients with idiopathic constipation and reduces laxative consumption. PMID:3311905

  9. 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

  10. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients.

    PubMed

    Raaska, Kari; Raitasuo, Virpi; Laitila, Jouko; Neuvonen, Pertti J

    2004-01-01

    Clozapine and caffeine are metabolised mainly by the cytochrome P4501A2 (CYP1A2) enzyme. Studies suggest that caffeine in coffee inhibits clozapine metabolism and increases serum clozapine concentrations. Our objective was to study whether coffee in the amounts usually consumed has an effect on steady-state serum clozapine concentrations. A randomised placebo-controlled cross-over design with two phases was used. Twelve hospitalised clozapine-using patients volunteered in the study where, after one-week run-in period, either caffeine-containing or decaffeinated instant coffee was available ad libitum for seven days. Serum concentrations of clozapine, N-desmethylclozapine, clozapine-N-oxide, caffeine, paraxanthine and C-reactive protein were measured after run-in period and on days 4 and 8 of the following study phases. Two patients were excluded from the statistical analysis because of non-compliance based on serum caffeine and paraxanthine determinations. In six fully compliant patients caffeine-containing coffee increased the mean serum trough concentration of clozapine by 26% (non-significant (NS), 95% CI -3% to +54%, P=0.07), N-desmethylclozapine by 6% (95% CI 1% to 12%, P=0.03), and clozapine-N-oxide by 7% (NS, 95% CI -6% to +20%, P=0.22). The ratio of N-desmethylclozapine/clozapine decreased by 13% (NS, 95% CI -1% to +27%, P=0.06) and that of clozapine-N-oxide/clozapine by 7% (NS, 95% CI -5% to +17%, P=0.19). In the analysis of combined data (including day 4 data of the four patients compliant up to that point) serum trough concentration of clozapine was 20% (95% CI 3% to 37% to P=0.03) higher, and that of N-desmethylclozapine 7% (95% CI 2% to 13%, P=0.02) higher during the caffeine phase than during the decaffeinated phase. We conclude that the effect of instant coffee drinking on serum clozapine concentrations is of minor clinical relevance in most of the patients, but some individuals may be more sensitive to this interaction due e.g. to genetic factors

  11. Effects of a smoking ban on clozapine plasma concentrations in a nonsecure psychiatric unit

    PubMed Central

    Gee, Siobhan H.; Taylor, David M.; Shergill, Sukhwinder S.; Flanagan, Robert; MacCabe, James H.

    2016-01-01

    Background: Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected. Methods: The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected. Results: In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed. Conclusions: Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences. PMID:28255437

  12. Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis.

    PubMed

    John, Thomas; Shah, Ami A

    2008-01-01

    We tested the efficacy of azithromycin ophthalmic solution for the treatment of chronic mixed anterior blepharitis. The findings suggest that patients with chronic mixed anterior blepharitis can be more effectively treated with azithromycin ophthalmic solution than erythromycin ophthalmic ointment. Patients treated with azithromycin ophthalmic solution show an extraordinary clinical response with shorter treatment duration.

  13. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    PubMed Central

    Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

    2015-01-01

    Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

  14. Treatment for Chronic Pain in Patients With Advanced Cancer

    ClinicalTrials.gov

    2016-11-25

    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

  15. 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.

  16. [Chronic lymphocytic leukemia. Treatment and genetic risk profile].

    PubMed

    Stilgenbauer, S; Hallek, M

    2013-02-01

    Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Among the biological features underlying this heterogeneity, genetic lesions and the mutational status of the immunoglobulin heavy chain variable genes (IGHV) are of importance. Therapeutic options in CLL have been considerably expanded during recent years. The combination of fludarabine, cyclophosphamide and rituximab (FCR) has become gold standard in the first-line treatment of physically fit patients. Bendamustine plus rituximab (BR) is currently being compared to FCR in studies and chlorambucil is still of relevance for elderly patients with comorbidities. Alemtuzumab is an alternative for high-risk patients (refractory CLL, 17p deletion, TP53 mutation). Allogeneic stem cell transplantation (allo-SCT) offers the only chance of cure but not without substantial mortality. Innovative approaches focus on individualized, targeted therapies. A number of novel agents are in clinical trials and show marked efficacy combined with good tolerability. This review provides an overview of the current therapeutic options and of promising novel approaches.

  17. 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

  18. TRPV1 and TRPM8 in Treatment of Chronic Cough

    PubMed Central

    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

  19. TRPV1 and TRPM8 in Treatment of Chronic Cough.

    PubMed

    Millqvist, Eva

    2016-07-28

    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.

  20. Surgical Treatment of Chronic Thromboembolic Pulmonary Hypertension: Pulmonary Thromboendarterectomy

    PubMed Central

    Madani, Michael M.

    2016-01-01

    Pulmonary thromboendarterectomy (PTE), also referred to as pulmonary endarterectomy, is the definitive treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The true incidence of CTEPH is unknown and difficult to ascertain; however, most experts agree that approximately 4% to 5% of all patients who have an acute episode of pulmonary embolism (PE) will continue to develop CTEPH. Based on an incidence rate of about 0.1% for acute PE, this translates into a CTEPH incidence of approximately 10,000 to 15,000 annually in the United States alone. Furthermore, there are patients with CTEPH who have no history of prior PE or deep vein thrombosis, adding to the estimated number. Despite these facts, the disease remains significantly underdiagnosed, and currently there are only about 300 PTEs performed nationwide, the majority of which are done at the University of California, San Diego (UCSD) Health System. The technical aspects of the procedure can be somewhat challenging and require meticulous and complete dissection of the entire pulmonary vascular tree, with the patient under profound hypothermic circulatory arrest. However, the determination of true CTEPH patients and those who would benefit from surgery can also be challenging and relies heavily on the experience of the CTEPH team. In this article, we will highlight some key points about the disease and describe the surgical techniques of PTE. PMID:28289496

  1. [Treatment of chronic refractory cardiac insufficiency with enalapril].

    PubMed

    Hannachi, N; Mechmèche, R; Ayari, M; Ben Ismail, M

    1989-06-01

    The objective is here to study the long and intermediate term clinical and haemodynamic effects of enalapril during chronic heart failure resistant to the classic digitalis-diuretics treatment. The study involves 16 patients (12 males and 4 females), with a mean age of 50 years. Before being given enalapril, 12 patients were at stage IV and 4 patients at stage II of the NYHA; the mean capillary pressure was quite elevated (30 +/- 6.3 mmHg), the cardiac index has collapsed (2.12 +/- 0.38 l.min.m2) and the stroke fraction (SF) is 0.28 +/- 0.08. At the 1st month control, there is a definite functional and haemodynamic improvement of the pre-charge as well as the post-charge. This improvement is still present at 6 months. The ventricular function is improved (SF = 0.38 +/- 0.13; p less than 0.001). The clinical tolerance of enalapril is excellent and the only adverse reaction is a transient deterioration of the renal function in a patient with diabetic glomerulopathy.

  2. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

    PubMed Central

    Ortiz, Gabriel M.; Wellons, Melissa; Brancato, Jason; Vo, Ha T. T.; Zinn, Rebekah L.; Clarkson, Daniel E.; Van Loon, Katherine; Bonhoeffer, Sebastian; Miralles, G. Diego; Montefiori, David; Bartlett, John A.; Nixon, Douglas F.

    2001-01-01

    The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4+ T cells >400 per μl. CD4+ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-γ-producing HIV-1-specific CD8+ and CD4+ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8+ T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4+ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4+ T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4+ T cell counts, and showed no enhancement of antiviral CD8+ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution. PMID:11687611

  3. Treatment and molecular monitoring update in chronic myeloid leukemia management.

    PubMed

    Sorel, Nathalie; Cayssials, Émilie; Brizard, Françoise; Chomel, Jean-Claude

    2017-04-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the t(9;22)(q34;q11) translocation. It is characterized by the presence of the BCR-ABL1 fusion gene encoding the BCR-ABL oncoprotein characterized by a deregulated tyrosine kinase activity. Targeted therapies using tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib, bosutinib, or ponatinib have profoundly changed the natural history of the disease with a major impact on survival. Indeed, most patients diagnosed today can enjoy a near normal life expectancy. The efficacy of TKI treatment can be accurately evaluated by a molecular monitoring based on the quantification of BCR-ABL1 mRNA transcripts and the detection of resistance mutations in the BCR-ABL kinase domain. International recommendations for an optimal management of CML using biological parameters are regularly published. They were designed to evaluate the response to the treatment and to consider, if necessary, a switch to another TKI. A sustained and deep molecular response is obtained in a significant percentage of patients. Clinical trials of TKI discontinuation were performed in such a population, and half of patients do not relapse. In the remaining patients, a rapid appearance of the malignant clone was observed, undoubtedly the consequence of the persistence of residual leukemic stem cells (LSCs). How to discriminate patients who may safely stop TKI? How to target residual LSCs, and do we have to eradicate all these cells? Additional research investigation and clinical trials are needed to answer these questions in order to consider a potential cure of CML.

  4. A study of the use of clozapine in old age psychiatry.

    PubMed

    Snowdon, John; Halliday, Graeme

    2011-07-01

    The aim of this study was to review the use of clozapine in a Sydney area old age psychiatry service. Data were extracted from case files of all people who were treated in a health area's old age psychiatry units with clozapine during a 15-year period. Additional details were obtained from clinicians who provided ongoing care after discharge from the hospital. Note was made of psychiatric diagnoses, length of time taking clozapine, dosage, side effects and outcome. Sixteen patients aged over 65 years commenced or continued taking clozapine while inpatients of the service. Of the 13 patients who had a history of schizophrenia or schizoaffective disorder, four patients (all female) developed neutropenia and therefore clozapine was stopped. In one case, neutropenia was first diagnosed 6 years after commencing the medication. Two women died; the nine other women, and one of the deceased, stopped taking clozapine, usually because of side effects. The mean daily dose at cessation was 236 mg. All five men were still taking clozapine (mean 260 mg daily) when followed at a mean age of 72 years, having taken it for an average of 10 years. This case review adds to evidence of the risk of neutropenia when older people are prescribed clozapine.

  5. 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…

  6. Antipsychotic clozapine inhibits the function of alpha7-nicotinic acetylcholine receptors.

    PubMed

    Singhal, Sachin K; Zhang, Li; Morales, Marisela; Oz, Murat

    2007-02-01

    The effects of the antipsychotic clozapine on the function of the cloned alpha(7) subunit of the nicotinic acetylcholine (nACh) receptor expressed in Xenopus oocytes was investigated by using the two-electrode voltage-clamp technique. Clozapine reversibly inhibited nicotine (10 microM)-induced currents in a concentration-dependent manner (300 nM to 90 microM), with an IC(50) value of 3.2+/-0.4 microM. The effect of clozapine was not dependent on the membrane potential. Clozapine did not affect the activity of endogenous Ca(2+)-dependent Cl(-) channels since the inhibition by clozapine was unaltered by the intracellularly injected Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing 2mM Ba(2+). Clozapine decreased the maximal nicotine-induced responses without significantly affecting its potency, indicating that it acts as a noncompetitive antagonist on alpha(7)-nACh receptors. In hippocampal slices, the whole-cell recordings from CA1 pyramidal neurons indicated that the increases in the frequency and amplitudes of the GABA-mediated spontaneous inhibitory postsynaptic currents induced by bath application of 2 mM choline, a specific agonist for alpha(7)-nACh receptors, were abolished after 10 min application of 5 microM clozapine. In conclusion, these results demonstrate that clozapine inhibits the function of alpha(7)-nACh receptors expressed in Xenopus oocytes and in hippocampal neurons.

  7. Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.

    PubMed

    Tanaka, Satoshi; Yamada, Misa; Kitahara, Sari; Higuchi, Teruhiko; Honda, Kazuo; Kamijima, Kunitoshi; Yamada, Mitsuhiko

    2006-02-01

    Using expressed sequence tag (EST) analysis, we previously identified certain molecular machinery that mediates antidepressant effects. To date, several partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been isolated as ESTs from rat brain. In the present study, we identified two of the ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated increased neuroserpin mRNA expression in rat frontal cortex after chronic treatment with several classes of antidepressants, including imipramine, fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT), another therapeutic treatment for depression, also increased neuroserpin expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that is implicated in the regulation of synaptic plasticity, neuronal migration, and axogenesis in the central nervous system. In conclusion, our results support the hypothesis that neuroserpin-mediated plastic changes in frontal cortex may underlie the therapeutic action of antidepressants and ECT.

  8. 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.…

  9. Prevention and treatment of osteoporosis in chronically ill children.

    PubMed

    Munns, C F; Cowell, C T

    2005-01-01

    Osteoporosis secondary to chronic disease in children has emerged as a major health issue. As the severity of a child's illness increases, so too does the number of factors affecting their bone health. Determinants of bone health in children include level of mobility, exposure to osteotoxic medication, nutritional status, calcium and vitamin D intake, chronic inflammation and pubertal development.

  10. 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.

  11. Integrated care for chronic migraine patients: epidemiology, burden, diagnosis and treatment options.

    PubMed

    Diener, Hans-Christoph; Solbach, Kasja; Holle, Dagny; Gaul, Charly

    2015-08-01

    Migraine is a common neurological disorder, characterised by severe headaches. Epidemiological studies in the USA and Europe have identified a subgroup of migraine patients with chronic migraine. Chronic migraine is defined as ≥15 headache days per month for ≥3 months, in which ≥8 days of the month meet criteria for migraine with or without aura, or respond to treatment specifically for migraine. Chronic migraine is associated with a higher burden of disease, more severe psychiatric comorbidity, greater use of healthcare resources, and higher overall costs than episodic migraine (<15 headache days per month). There is a strong need to improve diagnosis and therapeutic treatment of chronic migraine. Primary care physicians, as well as hospital-based physicians, are integral to the identification and treatment of these patients. The latest epidemiological data, as well as treatment options for chronic migraine patients, are reviewed here.

  12. 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.

  13. Treatment Options for High-Risk Chronic Lymphocytic Leukaemia

    PubMed Central

    Hewamana, Saman; Dearden, Claire

    2011-01-01

    Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in the Western world. The natural history of CLL is extremely variable with a survival time from initial diagnosis that ranges from 2 to more than 20 years. Understanding the clinical diversity and allowing the subclassification of CLL into various prognostic groups not only assists in predicting future outcome for patients, but also helps to direct treatment decisions. Chlorambucil and fludarabine were the standard therapy for CLL for decades. Randomized studies have reported superior overall response and progression-free survival (PFS) for fludarabine compared with alkylator-based therapy and for the fludarabine-cyclophospamide (FC) combination over fludarabine alone. More recently the addition of rituximab to the FC regimen (R-FC) has shown significant improvement in overall response, PFS and overall survival compared with FC alone. However, there are patients for whom this regimen still provides less satisfactory results. Within the above studies CLL patients who have some of the poorer prognostic markers, such as unmutated IgVH genes and/or high beta-2 microglobulin (B2M), and those who fail to achieve a minimal residual disease (MRD) negative remission are likely to have a shorter PFS compared with those without these features. Various strategies have been explored to improve the outcome for such patients. These include the addition of agents to a frontline R-FC regimen, use of consolidation and consideration of maintenance. The only group that can be clearly identified pretreatment for whom conventional fludarabine-based therapies produce significantly inferior response rates, PFS and overall survival are the patients who harbour a genetic fault; deletion or mutation or a combination of deletion and mutation of tumour protein p53 (TP53). TP53 inactivation is a less common finding at first treatment but becomes much more common in fludarabine-refractory patients. Alemtuzumab and high

  14. 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

  15. Treatment of a case of refractory feline chronic gingivostomatitis with feline recombinant interferon omega.

    PubMed

    Southerden, P; Gorrel, C

    2007-02-01

    Chronic gingivostomatitis is a common debilitating disease in cats, which is often refractory to medical and surgical treatment. An eight-year-old, neutered female domestic shorthair cat with a history of gingivitis was presented with chronic gingivostomatitis. Initial treatment by extraction of all premolars and molars was unsuccessful. However, the condition resolved within six weeks of treatment with feline recombinant interferon omega (Virbagen; Virbac).

  16. Treatment of common deficits associated with chronic ankle instability.

    PubMed

    Holmes, Alison; Delahunt, Eamonn

    2009-01-01

    Lateral ankle sprains are amongst the most common injuries incurred by athletes, with the high rate of reoccurrence after initial injury becoming of great concern. Chronic ankle instability (CAI) refers to the development of repetitive ankle sprains and persistent residual symptoms post-injury. Some of the initial symptoms that occur in acute sprains may persist for at least 6 months post-injury in the absence of recurrent sprains, despite the athlete having returned to full functional activity. CAI is generally thought to be caused by mechanical instability (MI) or functional instability (FI), or both. Although previously discussed as separate entities, recent research has demonstrated that deficits associated with both MI and FI may co-exist to result in CAI. For clinicians, the main deficits associated with CAI include deficits in proprioception, neuromuscular control, strength and postural control. Based on the literature reviewed, it does seem that subjects with CAI have a deficit in frontal plane ankle joint positional sense. Subjects with CAI do not appear to exhibit any increased latency in the peroneal muscles in response to an external perturbation. Preliminary data suggest that feed-forward neuromuscular control may be more important than feed-back neuromuscular control and interventions are now required to address deficits in feed-forward neuromuscular control. Balance training protocols have consistently been shown to improve postural stability in subjects with CAI. Subjects with CAI do not experience decreased peroneus longus strength, but instead may experience strength deficits in the ankle joint invertor muscles. These findings are of great clinical significance in terms of understanding the mechanisms and deficits associated with CAI. An appreciation of these is vital to allow clinicians to develop effective prevention and treatment programmes in relation to CAI.

  17. 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

  18. 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

  19. Chronic pain and the family: theory-driven treatment approaches.

    PubMed

    Lewandowski, Wendy; Morris, Rebecca; Draucker, Claire Burke; Risko, Judy

    2007-09-01

    The chronic pain experience is the product of a complex interaction of many factors including biological, social, psychological, environmental, and familial. The presence of chronic pain can impact the family system with significant, negative consequences; the family may also be responsible, in part, for maintaining and perpetuating pain problems. The need to examine the family dimension of the chronic pain experience and offer family/couple therapy, should it be indicated, is vital to comprehensive pain management. Operant behavioral, cognitive-behavioral, and structural family therapy approaches are advocated for such families, along with a clear need for controlled evaluations of these approaches.

  20. 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.

  1. 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

  2. [New pharmaceuticals in treatment of chronic dust bronchitis].

    PubMed

    Kosarev, V V; Vakurova, N V; Babanov, S A

    2007-01-01

    The study was dedicated to the assessment of the therapeutic possibilities provided by erespal (fenspirid) as a new class of pharmaceuticals inhibiting the inflammatory process, in patients with chronic dust bronchitis.

  3. [Using hepatomaks forte in the treatment of chronic alcoholic hepatitis].

    PubMed

    Linevskiĭ, Iu V; Linevskaia, K Iu; Voronin, K A

    2013-01-01

    Installed significantly more pronounced positive effect on clinical manifestations and laboratory indicators of liver in patients with chronic alcoholic hepatitis who received within 4 weeks of basal therapy in conjunction with Gepatomax Forte in comparison with a group of patients with chronic alcoholic hepatitis who received during the same time only basic therapy. Side adverse effects in the group of patients receiving Gepatomax Forte were not registered.

  4. [The chronic gastritis, the dysbacteriosis and the use of Hylak forte at the treatment].

    PubMed

    Omarov, T R; Omarova, L A; Omarova, V A; Sarsenova, S V

    2014-01-01

    High effectiveness of a preparation Hylak forte is shown in the treatment of intestinal dysbacteriosis of patients with the chronic gastritis. The received data gives the basis to recommend the prolonged use of Hylak forte after eliminating an exacerbation in order to prevent the relapse of the chronic gastritis.

  5. 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…

  6. 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…

  7. Treatment of Chlamydia pneumoniae infection and chronic obstructive pulmonary disease.

    PubMed

    Karnak, Demet; Beder, Sumru

    2002-10-01

    Chronic obstructive lung disease (COPD) is a general term for chronic, irreversible lung disease that combines qualities of emphysema and chronic bronchitis. The standard definition of chronic bronchitis is a productive cough for three months per year (for at least two consecutive years) without an underlying aetiology. Acute exacerbation of chronic bronchitis (AECB) represents a common complaint that leads patients to seek medical attention. COPD and AECB are directly responsible for the overuse of antibiotics in the developed world. Fifty per cent of exacerbations have either viral or non-infectious origin. For this reason, antibiotic use remains controversial. Among other bacteria, Chlamydia pneumoniae is responsible for 4 - 16% of AECB in hospitalised or out-patients, although among smokers and people using steroids, the incidence is 34%. C. pneumoniae may either be the sole causative agent or a co-agent in AECB. This paper reviews the management of COPD/AECB with respect to antibiotic use. Diagnosis and antimicrobial therapy relevant to Chlamydia in the management of AECB are also evaluated in this review.

  8. Culture-directed topical antibiotic treatment for chronic rhinosinusitis

    PubMed Central

    Davis, Greg E.

    2016-01-01

    Background: Topical antibiotics, delivered optimally as high-volume culture-directed sinus irrigations, are being increasingly used for recalcitrant chronic rhinosinusitis (CRS). Their impact on subjective and objective outcome measures, however, is still unclear. Objective: To assess if the use of topical antibiotics in recalcitrant CRS is associated with improved 20-Item Sino-Nasal Outcome Test and Lund-Kennedy endoscopic scores, and to determine the negative posttreatment culture “control” rate. Methods: Patients were included in the study if they met diagnostic criteria for CRS, received high-volume topical antibiotic sinus irrigations twice daily for 1 month, between December 2009 and May 2015, and had undergone endoscopic sinus surgery. The primary outcome was the 20-Item Sino-Nasal Outcome Test score. Secondary outcomes were the Lund-Kennedy endoscopic score and a negative posttreatment culture “control” rate. Paired t-tests were used to compare pre- and posttreatment scores. Patients with cystic fibrosis were analyzed separately. Results: Of the 58 patients included, 47% had nasal polyposis, 57% had asthma, 16% had aspirin sensitivity, and 55% had environmental allergies. The median Lund-Mackay computed tomography score was 11 (interquartile range, 6–16), and the median time to follow-up was 8 weeks (interquartile range, 6–10 weeks). The 20-Item Sino-Nasal Outcome Test scores improved from pre- to posttreatment period, although this was not significant mean 1.5 [confidence interval {CI} 1.3, 1.7] to mean 1.3 [CI 1.1, 1.6]; p = 0.16). Lund-Kennedy endoscopic scores, however, significantly improved from pre- to posttreatment (mean 4.9 [CI 4.3, 5.6] to mean 4.1 [CI 3.5, 4.7]; p = 0.05). Of the 47 patients with complete culture data, 72% had negative posttreatment culture results, defined as “controlled.” Only one patient discontinued treatment, related to discomfort from irrigations. Conclusion: In patients with recalcitrant CRS, the use of

  9. 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.

  10. 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

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

    PubMed

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

    2015-09-23

    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.

  12. Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials.

    PubMed

    Tuunainen, Arja; Wahlbeck, Kristian; Gilbody, Simon

    2002-07-01

    The aim of this study was to evaluate the effectiveness of newer atypical antipsychotic drugs in comparison to clozapine for schizophrenia. Publications in all languages were searched from all relevant databases and all randomized controlled trials comparing clozapine with newer atypical drugs were included. The review and meta-analysis includes eight studies, most of them short in duration. Newer atypical drugs were broadly similar to clozapine when improvement was measured using a psychosis symptom rating scale or a global index. There was a trend for clozapine to be more effective than the others for positive symptoms, and less effective for the negative symptoms. The adverse effect profile of clozapine and newer atypical drugs was dissimilar: while clozapine produced more fatigue, hypersalivation, and orthostatic dizziness, new atypical drugs, with the exception of olanzapine, produced more extrapyramidal symptoms. As these results were obtained from few studies and a relatively small amount of patients, the equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. More trials of sufficient power, with longer duration, and measuring clinically important outcomes are urgently needed.

  13. IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol.

    PubMed

    Küfferle, B; Tauscher, J; Asenbaum, S; Vesely, C; Podreka, I; Brücke, T; Kasper, S

    1997-10-01

    We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

  14. 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.

  15. [Gel Metrogil Denta photopheresis use in comprehensive treatment of patients with chronic generalized parodontitis].

    PubMed

    Prikuls, V F; Gerasimenko, M Iu; Moskovets, O N; Skovorod'ko, S N

    2008-01-01

    115 patients with chronic generalized parodontitis of middle or severe degree were examined and for them special treatment was developed with laser therapy and photophoresis use. The application of mentioned above physical and pharmacological methods in comprehensive treatment let to shorten the course of treatment and prolong the remission time.

  16. 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…

  17. Developing an enforceable "right to treatment" theory for the chronically mentally disabled in the community.

    PubMed

    Nordwind, B L

    1982-01-01

    Historical developments, mental health approaches, and applicable legal authorities are examined in arguing a legal basis for pursuing greater treatment benefits for chronically mentally disabled persons in the community. Mental health lawyers have traditionally been concerned with patients' right to treatment while in the hospital. Lawyers are called on to examine the plight of (and to extend advocacy for) the chronically mentally disabled in the community.

  18. Treatment of chronic recurrent multifocal osteomyelitis with interferon gamma.

    PubMed

    Gallagher, K T; Roberts, R L; MacFarlane, J A; Stiehm, E R

    1997-09-01

    Chronic recurrent multifocal osteomyelitis is characterized by recurrent episodes of painful swollen lesions of the bone and overlying skin with radiographic changes and an elevated sedimentation rate. It resembles infectious osteomyelitis but with negative findings on bacterial culture and no response to antibiotics. We treated a 13-year-old girl with interferon gamma for 3 months. She had 11 episodes of chronic recurrent multifocal osteomyelitis in 2 1/2 years before therapy and has had none in the 15 months since therapy, an outcome suggesting a favorable therapeutic response.

  19. Clozapine Modulates Glucosylceramide, Clears Aggregated Proteins, and Enhances ATG8/LC3 in Caenorhabditis elegans.

    PubMed

    Hao, Limin; Ben-David, Oshrit; Babb, Suzann M; Futerman, Anthony H; Cohen, Bruce M; Buttner, Edgar A

    2017-03-01

    Defining the mechanisms of action of the antipsychotic drug (APD), clozapine, is of great importance, as clozapine is more effective and has therapeutic benefits in a broader range of psychiatric disorders compared with other APDs. Its range of actions have not been fully characterized. Exposure to APDs early in development causes dose-dependent developmental delay and lethality in Caenorhabditis elegans. A previous genome-wide RNAi screen for suppressors of clozapine-induced developmental delay and lethality revealed 40 candidate genes, including sms-1, which encodes a sphingomyelin synthase. One sms-1 isoform is expressed in the C. elegans pharynx, and its transgene rescues the sms-1 mutant phenotype. We examined pharyngeal pumping and observed that clozapine-induced inhibition of pharyngeal pumping requires sms-1, a finding that may explain the role of the gene in mediating clozapine-induced developmental delay/lethality. By analyzing multiple enzymes involved in sphingolipid metabolism, and by observing the effect of addition of various lipids directly to the worms, we suggest that glucosylceramide may be a key mediator of the effects of clozapine. We further observed that clozapine clears protein aggregates, such as α-synuclein, PolyQ protein, and α-1-antitrypsin mutant protein. In addition, it enhances ATG8/LC3. We conclude that clozapine appears to affect the development and induce lethality of worms, in part, through modulating glucosylceramide. We discuss the possible connections among glucosylceramide, protein aggregate clearance, and autophagy. Interactions, including mechanistic pathways involving these elements, may underlie some of the clinical effects of clozapine.

  20. 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

  1. 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

  2. Epidemiology and treatment of depression in patients with chronic medical illness

    PubMed Central

    J. Katon, Wayne.

    2011-01-01

    There is a bidirectional relationship between depression and chronic medical disorders. The adverse health risk behaviors and psychobiological changes associated with depression increase the risk for chronic medical disorders, and biological changes and complications associated with chronic medical disorders may precipitate depressive episodes. Comorbid depression is associated with increased medical symptom burden, functional impairment, medical costs, poor adherence to self-care regimens, and increased risk of morbidity and mortality in patients with chronic medical disorders. Depression may worsen the course of medical disorders because of its effect on proinflammatory factors, hypothalamic-pituitary axis, autonomic nervous system, and metabolic factors, in addition to being associated with a higher risk of obesity, sedentary lifestyle, smoking, and poor adherence to medical regimens. Both evidence-based psychotherapies and antidepressant medication are efficacious treatments for depression. Collaborative depression care has been shown to be an effective way to deliver these treatments to large primary care populations with depression and chronic medical illness. PMID:21485743

  3. Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

    PubMed

    Uzbay, Tayfun; Kayir, Hakan; Celik, Turgay; Yüksel, Nevzat

    2006-05-01

    Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

  4. Wireless electrical stimulation: an innovative powerful tool for the treatment of a complicated chronic ulcer.

    PubMed

    Castana, Ourania; Dimitrouli, Aekaterini; Argyrakos, Theodoros; Theodorakopoulou, Emilia; Stampolidis, Nektarios; Papadopoulos, Emmanouil; Pallantzas, Athanasios; Stasinopoulos, Ioannis; Poulas, Konstantinos

    2013-03-01

    High-voltage electrical stimulation has been long proposed as a method of accelerating the wound healing process. Its beneficial effect has been successfully evaluated in the treatment of a number of chronic ulcers and burns. We present here the implementation of a new wireless electrical stimulation technique for the treatment of a complicated chronic ulcer of the lower limb. The device is transferring charges to the wound, without any contact with it, creating a microcurrent that is able to generate the current of injury. The results suggest that this easy-to-use method is an effective therapeutic option for chronic ulcers.

  5. Attenuation of acute d-amphetamine-induced disruption of conflict resolution by clozapine, but not α-flupenthixol in rats.

    PubMed

    Reichelt, Amy C; Good, Mark A; Killcross, Simon

    2013-11-01

    Previous research demonstrates that disruption of forebrain dopamine systems impairs the use of high-order information to guide goal-directed performance, and that this deficit may be related to impaired use of task-setting cues in patients with schizophrenia. Such deficits can be interrogated through conflict resolution, which has been demonstrated to be sensitive to prefrontal integrity in rodents. We sought to examine the effects of acute systemic d-amphetamine administration on the contextual control of response conflict in rats, and whether deficits were reversed through pre-treatment with clozapine or the D₁/D₂ antagonist α-flupenthixol. Acute d-amphetamine (1.5 mg/kg) disrupted the utilisation of contextual cues; therefore rats were impaired during presentation of stimulus compounds that require conflict resolution. Evidence suggested that this effect was attenuated through pre-treatment with the atypical antipsychotic clozapine (5.0 mg/kg), but not the typical antipsychotic α-flupenthixol (0.25 mg/kg), at doses previously shown to attenuate d-amphetamine-induced cognitive deficits. These studies therefore demonstrate a potentially viable model of disrupted executive function such as that seen in schizophrenia.

  6. Diagnosis and treatment of diabetes mellitus in chronic pancreatitis.

    PubMed

    Ewald, Nils; Hardt, Philip D

    2013-11-14

    Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5%-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

  7. DNA vaccination as a treatment for chronic kidney disease.

    PubMed

    Wang, Yuan Min; Alexander, Stephen I

    2014-01-01

    Chronic kidney disease is one of the major health problems worldwide. DNA vaccination delivers plasmid DNA encoding the target gene to induce both humoral and cellular immune responses. Here, we describe the methods of CD40 DNA vaccine enhanced by dendritic cell (DC) targeting on the development of Heymann nephritis (HN), a rat model of human membranous nephropathy.

  8. 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)

  9. Stability indicating methods for the determination of clozapine.

    PubMed

    Hasan, Nagiba Y; Elkawy, Mohamed A; Elzeany, Badr E; Wagieh, Nour E

    2002-08-22

    Five new selective, precise and accurate methods are described for the determination of clozapine in the presence of its main degradation product. Method A utilizes the second and third derivative spectrophotometry at 315 and 305 nm, respectively. Method B is RSD(1) spectrophotometric method based on the simultaneous use of the first derivative of ratio spectra and measurement at 295 nm. Method C is a pH-induced difference (delta A) spectrophotometry using UV measurement at 325 nm. Method D is a densitometric one, after separation on silica gel plate using methanol: water as mobile phase, and the spot was scanned at 295 nm. Method E is RP-HPLC using acetonitrile: water (40:60 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection was at 295 nm. Regression analysis showed good correlation in the concentration ranges 3-10, 4-10, 10-25 micro g/ml, 200-1000 ng/spot, 5-100 micro g/ml with percentage recoveries of 99.4+/-0.28, 99.8+/-0.20, 100.05+/-0.11, 99.41+/-0.34, 100.11+/-0.07 and 100.07+/-0.05% for methods A, B, C, D and E, respectively. These methods are suitable as stability indicating methods for the determination of clozapine in the presence of its main degradation product either in bulk powder or in pharmaceutical formulations.

  10. Providing Care for Patients with Chronic Migraine: Diagnosis, Treatment, and Management.

    PubMed

    Dougherty, Carrie; Silberstein, Stephen D

    2015-09-01

    Chronic migraine, a subtype of migraine defined as ≥ 15 headache days per month for ≥ 3 months, in which ≥ 8 days per month meet criteria for migraine with or without aura or respond to migraine-specific treatment, is a disabling, underdiagnosed, and undertreated disorder associated with significant disability, poor health-related quality of life, and high economic burden. The keys to caring for chronic migraine patients include: (1) making a proper diagnosis; (2) identifying and eliminating exacerbating factors; (3) assessing for medication overuse (patients with chronic headache often overuse acute medications); and (4) continued management. Communication between patient and physician about treatment goals is important. The patient management guidelines presented in this article should help physicians improve treatment success and proactively address common comorbidities among their patients with chronic migraine.

  11. Chronic social stress during adolescence: interplay of paroxetine treatment and ageing.

    PubMed

    Scharf, Sebastian H; Sterlemann, Vera; Liebl, Claudia; Müller, Marianne B; Schmidt, Mathias V

    2013-09-01

    Exposure to chronic stress during developmental periods is a risk factor for a number of psychiatric disorders. While the direct effects of stress exposure have been studied extensively, little is known about the long-lasting effects and the interaction with ageing. The same holds true for the treatment with selective serotonin reuptake inhibitors (SSRIs), which have been shown to prevent or reverse some stress-induced effects. Here, we studied the direct and long-lasting impact of chronic social stress during adolescence and the impact of chronic treatment with the SSRI paroxetine in adulthood and aged animals. Therefore, male CD1 mice at the age of 28 days were subjected to 7 weeks of chronic social stress. Treatment with paroxetine was performed per os with a dosage of 20 mg/g BW. We were able to reverse most of the effects of chronic social stress in adult mice (4 months old) and to some extend in aged animals (15 months old) with the SSRI treatment. Especially the regulation of the HPA axis seems to be affected in aged mice with a shift to the use of vasopressin. Our results demonstrate that chronic stress exposure and antidepressant treatment at the end of the developmental period can have a significant and long-lasting impact, highly relevant for healthy ageing.

  12. Treatment of chronic mucocutaneous moniliasis by immunologic reconstitution

    PubMed Central

    Kirkpatrick, C. H.; Rich, R. R.; Graw, R. G.; Smith, T. K.; Mickenberg, Irad; Rogentine, G. N.

    1971-01-01

    The immunological defect in a patient with chronic mucocutaneous moniliasis was characterized. While his Candida skin test was negative. exposure of his lymphocytes to candida extracts in vitro produced an increase in thymidine incorporation. Supernatants from cultures of antigen-stimulated lymphocytes did not contain macrophage migration-inhibition factor (MIF) activity. Restoration of the immune system with transfusions of immuno-competent allogeneic lymphocytes was accompanied by conversion of the Candida skin test to positive, and MIF production by his lymphocytes. During the period that his immune system remained intact, there was marked clearing of the moniliasis. Eight months following the transfusions, the moniliasis recurred and when restudied, the patient again had negative skin tests and insignificant MIF production. These observations demonstrate the importance of mediators in the expression of delayed hypersensitivity and provide evidence of a role of cellular immunity in resistance to certain chronic fungal infections. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:4945734

  13. New strategies in chronic lymphocytic leukemia: shifting treatment paradigms.

    PubMed

    Awan, Farrukh T; Byrd, John C

    2014-12-01

    Over the past two decades, slow but deliberate progress has been made in understanding the genetics of chronic lymphocytic leukemia (CLL) and how the surrounding microenvironment influences leukemia cell survival. The complexity of CLL with respect to different chromosomal aberrations, lack of a common aberrant signaling pathway activation, and associated immune suppression of the disease has been seen a major stumbling block for developing a single targeted therapy similar to imatinib used in chronic myeloid leukemia. The upcoming therapeutic era we are entering with the B-cell receptor (BCR) tyrosine kinase inhibitors ibrutinib and idelalisib appears to be overcoming this obstacle. Indeed, for the large majority of patients, it appears that application of BCR kinase inhibitors can promote durable remissions without the need for chemotherapy. Where other very active targeted agents such as ABT-199, therapeutic antibodies, and chimeric antigen receptor-modified T-cells will be used in CLL also represents a major question that future clinical trials will answer.

  14. Endomorphins as agents for the treatment of chronic inflammatory disease.

    PubMed

    Jessop, David S

    2006-01-01

    Endomorphin (EM)-1 and EM-2 are tetrapeptides located within the mammalian central nervous system and immune tissues, with high affinity and specificity for micro-opioid receptors. Most of the literature has focused on the analgesic properties of EM-1 and EM-2 in animal models of neuropathic or neurogenic pain, but there is persuasive evidence emerging that EMs can also exert potent anti-inflammatory effects in both acute and chronic peripheral inflammation. The purpose of this review is to present and evaluate the evidence for anti-inflammatory properties of EM-1 and EM-2 with a view to their potential for use in chronic human inflammatory disease. Distribution of EMs within the immune system and functional roles as immunomodulatory agents are summarized and discussed. Possible milestones to be met revolve around issues of peptide stability, biodegradability problems and optimal route and method of delivery. The potential for delivery of a low-cost drug with both peripheral anti-inflammatory and analgesic properties, effective in low doses, and targeted to the site of inflammation, should focus our attention on further development of EMs as potent therapeutic agents in chronic inflammation.

  15. Delta-9-tetrahydrocannabinol differently affects striatal c-Fos expression following haloperidol or clozapine administration.

    PubMed

    Marchese, Giorgio; Sanna, Angela; Casu, Gianluca; Casti, Paola; Spada, Gabriele Pinna; Ruiu, Stefania; Pani, Luca

    2008-11-19

    It was previously shown that haloperidol, but not clozapine, induced intense rat catalepsy when co-administered with delta-9-tetrahydrocannabinol. The present study investigated whether similar alterations could be observed on striatal c-Fos immunoreactivity after administration of the same drug combinations. Western Blot and immunocytochemistry stereological analyses indicated that delta-9-tetrahydrocannabinol (0.5 mg/kg) increased striatal c-Fos immunoreactivity induced by haloperidol (0.1 mg/kg). Conversely, no significant alterations of striatal c-Fos immunoreactivity were observed after injections of clozapine (10 mg/kg)+vehicle, clozapine+delta-9-tetrahydrocannabinol or vehicle+delta-9-tetrahydrocannabinol. The present results indicate that the behavioral effects induced by delta-9-tetrahydrocannabinol in haloperidol- and clozapine-treated rats are associated with different striatal c-Fos expressions.

  16. 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.

  17. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients.

    PubMed

    Rostami-Hodjegan, Amin; Amin, Ajmal M; Spencer, Edgar P; Lennard, Martin S; Tucker, Geoffrey T; Flanagan, Robert J

    2004-02-01

    The measurement of plasma clozapine concentrations is useful in assessing compliance, optimizing therapy, and minimizing toxicity. We measured plasma clozapine and norclozapine (N-desmethylclozapine) concentrations in samples from 3782 patients (2648 male, 1127 female). No clozapine was detected in 291 samples (227 patients, median prescribed dose 300 mg/d). In 4963 (50.2 %) samples (2222 patients); plasma clozapine concentration ranged from 10 to 350 ng/mL.Step-wise backward multiple regression analysis (37 % of the total samples) of log10 plasma clozapine concentration against log10 clozapine dose (mg/d), age (year), sex (male = 0, female = 1), cigarette smoking habit (nonsmokers = 0; smokers = 1), body weight (kg), and plasma clozapine/norclozapine ratio (clozapine metabolic ratio, MR) showed that these covariates explained 48% of the observed variation in plasma clozapine concentration (C = ng/mL x 10-3) (P < 0.001) according to the following equation: log 10 (C) = 0.811 log 10 (dose) + 0.332 (MR) + 69.42 X 10 (-3) (sex) + 2.263 x 10 (-3) (age) + 1.976 x 10(-3) (weight) - 0.171 (smoking habit) - 3.180. This model and its associated confidence intervals were used to develop nomograms of plasma clozapine concentration versus dose for male and female smokers and nonsmokers. Predicted plasma clozapine changes by +48% in nonsmokers, +17% in females, +/-8 % for every 0.1 change in MR (reference 1.32), +/-4% for every 5 years (reference 40 years), and +/-5 % for every 10 kg body weight (reference 80 kg). The nomograms can be used (i) to individualize dosage to achieve a given target plasma clozapine concentration, and (ii) for quantitative evaluation of adherence by estimating the likelihood of an observed concentration being achieved by a given dosage regimen. The model has been validated against published data.

  18. 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

  19. Pamidronate treatment of chronic noninfectious inflammatory lesions of the mandible in children.

    PubMed

    Compeyrot-Lacassagne, Sandrine; Rosenberg, Alan M; Babyn, Paul; Laxer, Ronald M

    2007-07-01

    Noninfectious inflammatory lesions of the mandible occur in chronic recurrent multifocal osteomyelitis (CRMO). Diffuse sclerosing osteomyelitis of the mandible (DSOM) is a condition thought to be a localized form of CRMO. Recently, bisphosphonate therapy, and particularly intravenous pamidronate, has been proposed as a treatment for patients with both CRMO and DSOM who do not improve with nonsteroidal antiinflammatory drug treatment. We report our experience using pamidronate in 2 children with chronic noninfectious osteomyelitis affecting the mandible. We describe the clinical and radiographic features and the treatment, side effects, and clinical and radiographic responses. Our experience suggests that pamidronate is an effective second-line therapy.

  20. The atypical antipsychotic clozapine selectively inhibits interleukin 8 (IL-8)-induced neutrophil chemotaxis.

    PubMed

    Capannolo, Marta; Fasciani, Irene; Romeo, Stefania; Aloisi, Gabriella; Rossi, Mario; Bellio, Pierangelo; Celenza, Giuseppe; Cinque, Benedetta; Cifone, Maria Grazia; Scarselli, Marco; Maggio, Roberto

    2015-03-01

    Clozapine is the most effective antipsychotic to date, but its benefits are counterbalanced by the risk of severe hematological effects. In this study, we analyzed whether clozapine inhibits polymorphonuclear (PMN) leukocyte chemotaxis. We found that clozapine, within the therapeutic concentration range, potently and selectively inhibits PMN chemotaxis induced by interleukin 8 (IL-8), a chemokine inducing neutrophil migration. The effect was not due to its action at dopamine, serotonin and muscarinic receptors, or to a direct antagonism to IL-8 receptors. Furthermore, clozapine did not inhibit PMN chemotaxis by its presumed toxic mechanism. In fact, after an overnight incubation in cell culture, the drug did not increase the physiological PMN apoptosis. An interference of clozapine with the autocrine release of leukotriene B4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to the primary chemoattractant IL-8, was hypothesized. In agreement with this hypothesis, clozapine attenuated the IL-8-induced release of LTB4 in PMNs. A series of experiments with an antagonist of the LTB4 receptor, U75302, and an inhibitor of LTB4 synthesis, zileuton, provided support to this conjecture. Intriguingly MK-571, an inhibitor of the multi-drug resistance protein MRP4, playing a pivotal role in effluxing LTB4, completely blocked PMN chemotaxis induced by IL-8, but gave conflicting results when tested for its ability to reduce LTB4 release, increasing LTB4 efflux by itself but reducing the release when in combination with IL-8. The reduction of PMN chemotaxis due to clozapine could predispose patients to infections. Whether this effect is a prelude to clozapine agranulocytosis requires further investigation.

  1. 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

  2. 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

  3. 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.

  4. Pulsed radiofrequency treatment of articular branches of femoral and obturator nerves for chronic hip pain

    PubMed Central

    Chye, Cien-Leong; Liang, Cheng-Loong; Lu, Kang; Chen, Ya-Wen; Liliang, Po-Chou

    2015-01-01

    Purpose Chronic hip pain is a common symptom experienced by many people. Often, surgery is not an option for patients with multiple comorbidities, and conventional drugs either have many side effects or are ineffective. Pulsed radiofrequency (PRF) is a new method in the treatment of pain. We attempt to compare the efficacy of PRF relative to conservative management for chronic hip pain. RPatients and methods Between August 2011 and July 2013, 29 patients with chronic hip pain were divided into two groups (PRF and conservative treatment) according to consent or refusal to undergo PRF procedure. Fifteen patients received PRF of the articular branches of the femoral and obturator nerves, and 14 patients received conservative treatment. Visual analog scale (VAS), Oxford hip scores (OHS), and pain medications were used for outcome measurement before treatment and at 1 week, 4 weeks, and 12 weeks after treatment. Results At 1 week, 4 weeks, and 12 weeks after treatment initiation, improvements in VAS were significantly greater with PRF. Improvements in OHS were significantly greater in the PRF group at 1 week, 4 weeks, and 12 weeks. Patients in the PRF group also used less pain medications. Eight subjects in the conservative treatment group switched to the PRF group after 12 weeks, and six of them had >50% improvement. Conclusion When compared with conservative treatment, PRF of the articular branches of the femoral and obturator nerves offers greater pain relief for chronic hip pain and can augment physical functioning. PMID:25834413

  5. 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…

  6. 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.

  7. 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

  8. 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…

  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. [Photophoresis and mesophotophoresis of angioprotectant group preparations for comprehensive treatment of patients with chronic generalized parodontitis].

    PubMed

    Prikuls, V F

    2008-01-01

    Examination of 118 patients with chronic generalized parodontitis of medium and heavy severity was performed and treatment was elaborated with the use of laser therapy and angioprotectants' photophoresis and mesophotophoresis. Use of the mentioned physical and physical-pharmacological methods in comprehensive cure let to shorten the course of treatment and increase remission duration.

  11. Effect of chronic opioid treatment on phagocytosis in Tetrahymena.

    PubMed

    Salaman, A; Roman, M; Renaud, F L; Silva, W I

    1990-07-01

    Opioid inhibition of phagocytosis in the protozoan ciliate Tetrahymena is antagonized by naloxone and this antagonism can be surmounted by increasing agonist concentration, which suggests a receptor-mediated mechanism. Desensitization of the opioid effect is time dependent in addition to concentration dependent. Chronic exposure to opioids results in the development of tolerance to the inhibitory effect of the agonists, and withdrawal of the latter results in a decrease in phagocytic capacity, which suggests that a state akin to dependence has been developed in these cells. Naloxone appears to behave as a partial agonist in tolerant cells, and there seems to exist cross-tolerance to mu and delta agonists.

  12. Adjunct treatment with yoga in chronic severe airways obstruction.

    PubMed Central

    Tandon, M K

    1978-01-01

    Eleven patients with severe chronic airways obstruction were given training in yogic breathing exercises and postures. A matched group of 11 patients were given physiotherapy breathing exercises. Both groups of patients were followed up at monthly intervals for nine months with pulmonary function tests, tests of exercise tolerance, and inquiry into their symptoms. After training in yoga the mean maximum work increased significantly by 60.55 kpm; whereas no such rise occurred after training in physiotherapy. This objective improvement was associated with symptomatic improvement in a significantly higher number of patients given training in yoga. PMID:694807

  13. Local tissue flaps: definitive treatment for chronic blisters after chemical burns.

    PubMed

    Maguina, Pirko; Busse, Brittany

    2011-01-01

    Chronic blistering in grafted burn wounds is an infrequently described but severely debilitating complication that can appear after alkali burns and seems to coincide with a delay in initial treatment. Histological studies have concluded that the pathogenesis of chronic subepidermal blister formation in previously grafted burn wounds is related to abnormalities in the basement membrane. Although several reports have described this problem, none have reported adequate treatment for the chronic blistering in previously grafted alkali burns. The authors describe the case of a 30-year-old man in whom caustic soda burns treated with excision and split-thickness skin grafting resulted in chronic subepidermal blistering that failed to improve over the next 2 years. The problem was resolved with full-thickness skin excision and reconstruction with bipedicled fasciocutaneous flaps.

  14. 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 ...

  15. 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

  16. 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…

  17. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention.

    PubMed

    Lipton, Richard B; Silberstein, Stephen D

    2015-03-01

    Migraine is a common disabling primary headache disorder that affects an estimated 36 million Americans. Migraine headaches often occur over many years or over an individual's lifetime. By definition, episodic migraine is characterized by headaches that occur on fewer than 15 days per month. According to the recent International Classification of Headache Disorders (third revision) beta diagnostic criteria, chronic migraine is defined as "headaches on at least 15 days per month for at least 3 months, with the features of migraine on at least 8 days per month." However, diagnostic criteria distinguishing episodic from chronic migraine continue to evolve. Persons with episodic migraine can remit, not change, or progress to high-frequency episodic or chronic migraine over time. Chronic migraine is associated with a substantially greater personal and societal burden, more frequent comorbidities, and possibly with persistent and progressive brain abnormalities. Many patients are poorly responsive to, or noncompliant with, conventional preventive therapies. The primary goals of migraine treatment include relieving pain, restoring function, and reducing headache frequency; an additional goal may be preventing progression to chronic migraine. Although all migraineurs require abortive treatment, and all patients with chronic migraine require preventive treatment, there are no definitive guidelines delineating which persons with episodic migraine would benefit from preventive therapy. Five US Food and Drug Association strategies are approved for preventing episodic migraine, but only injections with onabotulinumtoxinA are approved for preventing chronic migraine. Identifying persons who require migraine prophylaxis and selecting and initiating the most appropriate treatment strategy may prevent progression from episodic to chronic migraine and alleviate the pain and suffering associated with frequent migraine.

  18. Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

    DTIC Science & Technology

    2014-10-01

    nociceptive stimuli culminates in profound debilitating pain that serves no adaptive purpose for the sufferer. It is now established that spinal...Award Number: W81XWH-11-1-0806 TITLE: Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment...Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain

  19. Treatment of chronic stomatitis of cats by local paramunization with PIND-ORF.

    PubMed

    Mayr, B; Deininger, S; Büttner, M

    1991-02-01

    33 cats, suffering from chronic stomatitis, were treated with orally given paramunity inducer PIND-ORF (local paramunization). As a control 39 cats in the same practice were treated with other conventional methods. The reconvalescence rate (healing without rezidives) of experimental animals was 42%. From control animals only 13% reached this status. Oral paramunization with PIND-ORF is recommended as an alternative treatment for hitherto existing therapeutic measures against chronic stomatitis.

  20. [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.

  1. 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.

  2. Mitochondrial dysfunction and chronic disease: treatment with natural supplements.

    PubMed

    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.

  3. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements.

    PubMed

    Nicolson, Garth L

    2014-08-01

    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.

  4. 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

  5. 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.

  6. 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…

  7. Acupuncture for the treatment or management of chronic pain.

    PubMed

    Coeytaux, Remy R; Garland, Eric

    2013-01-01

    Evidence supports the safety and efficacy of acupuncture compared with no treatment, but it is unclear what role the placebo effect plays in acupuncture's efficacy. In determining whether acupuncture is indicated for a given individual or patient population, clinicians should consider acupuncture's effectiveness compared with no acupuncture--as well as the effectiveness, safety, and cost of alternative types of treatment.

  8. 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

  9. Cyclosporin in the treatment of severe chronic idiopathic uveitis.

    PubMed Central

    de Vries, J; Baarsma, G S; Zaal, M J; Boen-Tan, T N; Rothova, A; Buitenhuis, H J; Schweitzer, C M; de Keizer, R J; Kijlstra, A

    1990-01-01

    In a randomised double-masked study of 27 patients with a severe chronic idiopathic uveitis we evaluated the efficacy, safety, and tolerability of cyclosporin. All received prednisone in a low dose (0.3 mg/kg/day). In 14 patients this was combined with cyclosporin in a single daily dose of 10 mg/kg/day, while 13 patients received a placebo. The dosages were tapered off in accordance with a protocol, and we compared the number of months of successful therapy before the uveitis relapsed. The efficacy results, as expressed in a Kaplan-Meier curve, were in favour of cyclosporin. Owing to the small sample size, however, this difference did not reach statistical significance. The immunosuppressive effect of cyclosporin was not permanent, and in all but one patient the intraocular inflammation relapsed on reduction of dosage. Rather small cumulative doses of cyclosporin proved to be nephrotoxic, but subjective tolerability for cyclosporin was good. PMID:2198928

  10. New Strategies in Chronic Lymphocytic Leukemia: Shifting Treatment Paradigms

    PubMed Central

    Awan, Farrukh T.; Byrd, John C.

    2014-01-01

    Over the past two decades, slow but deliberate progress has been made in understanding the genetics of CLL and how the surrounding microenvironment influences leukemia cell survival. The complexity of CLL with respect to different chromosomal aberrations, lack of a common aberrant signaling pathway activation, and associated immune suppression of the disease has been seen a major stumbling block for developing a single targeted therapy similar to imatinib used in chronic myeloid leukemia (CML). The upcoming therapeutic era we are entering with the B-cell receptor (BCR) tyrosine kinase inhibitors ibrutinib and idelalisib, appear to be overcoming this obstacle. Indeed, for the large majority of patients it appears that application of BCR kinase inhibitors can promote durable remissions without the need for chemotherapy. Where other very active targeted agents such as ABT-199, therapeutic antibodies, and chimeric antigen receptor-modified T-cells will be used in CLL also represents a major question that future clinical trials will answer. PMID:25294898

  11. 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

  12. Treatment of stable chronic obstructive pulmonary disease: the GOLD guidelines.

    PubMed

    Lee, Hobart; Kim, Jeffrey; Tagmazyan, Karine

    2013-11-15

    Chronic obstructive pulmonary disease (COPD) is a common problem in primary care. COPD is diagnosed with spirometry only in clinically stable patients with a postbronchodilator forced expiratory volume in one second/forced vital capacity ratio of less than 0.70. All patients with COPD who smoke should be counseled about smoking cessation. Influenza and pneumococcal vaccinations are recommended for all patients with COPD. The Global Initiative for Chronic Obstructive Lung Disease assigns patients with COPD into four groups based on the degree of airflow restriction, symptom score, and number of exacerbations in one year. Pulmonary rehabilitation is recommended for patients in groups B, C, and D. Those in group A should receive a short-acting anticholinergic or short-acting beta2 agonist for mild intermittent symptoms. For patients in group B, long-acting anticholinergics or long-acting beta2 agonists should be added. Patients in group C or D are at high risk of exacerbations and should receive a long-acting anticholinergic or a combination of an inhaled corticosteroid and a long-acting beta2 agonist. For patients whose symptoms are not controlled with one of these regimens, triple therapy with an inhaled corticosteroid, long-acting beta2 agonist, and anticholinergic should be considered. Prophylactic antibiotics and oral corticosteroids are not recommended for prevention of COPD exacerbations. Continuous oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD. Lung volume reduction surgery can improve survival rates in patients with severe, upper lobe-predominant COPD with heterogeneous emphysema distribution.

  13. Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

    PubMed Central

    Tadokoro, Shigenori; Okamura, Naoe; Sekine, Yoshimoto; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi

    2012-01-01

    Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. PMID:21402722

  14. Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

    PubMed

    Zicha, Josef; Dobesová, Zdenka; Kunes, Jaroslav

    2006-12-01

    Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

  15. A population-based survey of chronic pain and its treatment with prescription drugs.

    PubMed

    Toblin, Robin L; Mack, Karin A; Perveen, Ghazala; Paulozzi, Leonard J

    2011-06-01

    Chronic pain is a common reason for medical visits, but prevalence estimates vary between studies and have rarely included drug treatment data. This study aimed to examine characteristics of chronic pain and its relation to demographic and health factors, and factors associated with treatment of pain with opioid analgesics. A chronic pain module was added to the 2007 Kansas Behavioral Risk Factor Surveillance System (response rate = 61%). Data on prevalence, duration, frequency, and severity of chronic pain, demographics, and health were collected from a representative sample of 4090 adults 18 years and older by telephone. Logistic regression was used to examine the association of both chronic pain and opioid use with demographic and health factors. Chronic pain was reported by 26.0% of the participants and was associated with activity limitations (adjusted odds ratio [AOR] = 3.6, 95% confidence interval [95% CI] 2.8-4.5), arthritis (AOR = 3.3, 95% CI 2.6-4.0), poor mental health (AOR = 2.0, 95% CI 1.4-2.8), poor overall health (AOR = 1.9; 95% CI 1.5-2.5), and obesity (AOR = 1.6; 95% CI 1.2-2.0). Of the 33.4% of people with pain who use prescription pain medication, 45.7% took opioids, including 36.7% of those with mild pain. Chronic pain affects a quarter of adults in Kansas and is associated with poor health. Opioid analgesics are the mainstay of prescribed pharmacotherapy in this group, even among those reporting mild pain. Chronic pain affects 26.0% of adults in the state of Kansas, U.S.A. Overall, 45.7% of people who take prescription drugs for chronic pain reported taking opioid analgesics.

  16. An analysis of individual treatment on a token economy for chronic schizophrenic patients.

    PubMed

    Butler, R J

    1979-09-01

    Fifty-one individually designed treatment programmes carried out over a 22 month period on a token economy ward for 12 female chronic schizophrenic patients were analysed. Level of withdrawal was found to be a critical factor in patients' response, both in terms of the rate and extent of improvement during the treatment stage, and presence or absence of deterioration during 'weaning' and follow up. No difference in response between type of behavioural problem and methods of treatment or weaning were found.

  17. Specialized Rehabilitation Programs for Children and Adolescents with Severe Disabling Chronic Pain: Indications, Treatment and Outcomes

    PubMed Central

    Stahlschmidt, Lorin; Zernikow, Boris; Wager, Julia

    2016-01-01

    Children and adolescents with highly disabling chronic pain of high intensity and frequency are admitted to specialized pain rehabilitation programs. Some barriers to obtaining this specialized care include a lack of availability of treatment centers, a perceived social stigma and individual barriers such as socioeconomic status. Specialized rehabilitation programs for severe disabling chronic pain worldwide have similarities regarding admission criteria, structure and therapeutic orientation. They differ, however, regarding their exclusion criteria and program descriptions. The short- and long-term effectiveness of some rehabilitation programs is well documented. All countries should promote the establishment of future pediatric pain centers to improve the health care of children and adolescents suffering from severe chronic pain. Standardized reporting guidelines should be developed to describe treatments and outcomes to enable comparability across treatment centers. PMID:27879631

  18. 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.

  19. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

    PubMed

    Sehgal, Nalini; Colson, James; Smith, Howard S

    2013-11-01

    Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

  20. Chronic rapamycin treatment causes diabetes in male mice.

    PubMed

    Schindler, Christine E; Partap, Uttara; Patchen, Bonnie K; Swoap, Steven J

    2014-08-15

    Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice. We observed that treatment with rapamycin for 52 wk induced diabetes in male mice, characterized by hyperglycemia, significant urine glucose levels, and severe glucose and pyruvate intolerance. Glucose intolerance occurred in male mice by 4 wk on rapamycin and could be only partially reversed with cessation of rapamycin treatment. Female mice developed moderate glucose intolerance over 1 yr of rapamycin treatment, but not diabetes. The role of sex hormones in the differential development of diabetic symptoms in male and female mice was further explored. HET3 mice treated with rapamycin for 52 wk were gonadectomized and monitored over 10 wk. Castrated male mice remained glucose intolerant, while ovariectomized females developed significant glucose intolerance over the same time period. Subsequent replacement of 17β-estradiol (E2) in ovariectomized females promoted a recovery of glucose tolerance over a 4-wk period, suggesting the protective role of E2 against rapamycin-induced diabetes. These results indicate that 1) oral rapamycin treatment causes diabetes in male mice, 2) the diabetes is partially reversible with cessation of treatment, and 3) E2 plays a protective role against the development of rapamycin-induced diabetes.

  1. Omalizumab for the Treatment of Chronic Idiopathic Urticaria: Systematic Review of the Literature.

    PubMed

    Tonacci, Alessandro; Billeci, Lucia; Pioggia, Giovanni; Navarra, Michele; Gangemi, Sebastiano

    2017-02-22

    Omalizumab is recombinant humanized monoclonal antibody to immunoglobulin E. Guidelines for the treatment of chronic idiopathic urticaria (also known as chronic spontaneous urticaria) recommend the use of omalizumab as third-line therapy in addition to high doses of histamine receptor type 1 (H1 ) antihistamines when they are unsuccessful as first- and second-line therapy. We performed a systematic review of the literature to identify studies that evaluated the efficacy of omalizumab for the treatment of chronic idiopathic urticaria, in both controlled and real-world settings, to assess its potential role as a preferred therapy. The PubMed, ScienceDirect, LILACS (Latin American and Caribbean Health Sciences Literature), and Google Scholar databases were searched between January 1, 2000, and November 21, 2016. The search was limited to articles published in peer-reviewed journals in the English language, and 29 studies were included in this review. Omalizumab 300 mg administered every 4 weeks appears to be the most effective and safe dosage, with a rapid response time, for the treatment of chronic idiopathic urticaria, with few minor adverse effects, and appears to be safe in the offspring of pregnant patients who received the drug. However, as published studies of omalizumab are sparse, future studies are warranted. When findings are confirmed in larger studies, due to its efficacy, safety, and increased benefit/cost ratio, omalizumab could become the preferred method of treatment for chronic idiopathic urticaria in patients unresponsive to H1 antihistamines.

  2. Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

    PubMed

    Touiki, Khalid; Rat, Pascal; Arib, Ouafa; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2008-05-01

    Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

  3. [The possibilities for the treatment of exudative otitis media in the children presenting with chronic adenoiditis].

    PubMed

    Karpova, E P; Karpycheva, I E; Tulupov, D A

    2014-01-01

    The objective of the present study was to improve the effectiveness of medicamental therapy of exudative otitis media in the children with recurrent and chronic adenoiditis. It was shown that the use of fluifort (carbocysteine lysine salt) for the treatment of exudative otitis media in the children presenting with chronic adenoiditis is a more effective approach in comparison with the expectant management. It is concluded that the application of carbocysteine lysine salt in combination with the mometasone furoate nasal spray ensures the rapid elimination of the symptoms of adenoiditis and significantly accelerates the resolution of exudative otitis media compared with the monotherapeutic treatment.

  4. 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

  5. Renal haemodynamics after chronic treatment with labetalol and properanolol

    PubMed Central

    Malini, P. L.; Strocchi, E.; Negroni, S.; Ambrosioni, E.; Magnani, B.

    1982-01-01

    1 Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured in two groups of 12 patients both at rest and during sub-maximal cycloergometer exercise while on placebo and after 3 months of treatment with either labetalol or propranolol. 2 ERPF increased and renal vascular resistance decreased both at rest and during exercise after labetalol treatment, compared with placebo; the opposite was observed after propranolol treatment. 3 GFR increased after labetalol and decreased after propranolol both at rest and during exercise, compared with placebo, but these changes were not statistically significant. 4 Labetalol and propranolol resulted in the same decrease in blood pressure and a comparable incidence of side effects. PMID:7093095

  6. 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

  7. 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.

  8. [Alpha 2-adrenoceptor agonists for the treatment of chronic pain].

    PubMed

    Kulka, P J

    1996-04-25

    The antinociceptive effect of alpha(2)-adrenoceptor agonists is mediated by activation of descending inhibiting noradrenergic systems, which modulates 'wide-dynamic-range' neurones. Furthermore, they inhibit the liberation of substance P and endorphines and activate serotoninergic neurones. Despite this variety of antinociceptive actions, there is still little experience with alpha(2)-adrenoceptor agonists as therapeutic agents for use in chronic pain syndromes. Studies in animals and patients have shown that the transdermal, epidural and intravenous administration of the alpha(2)-adrenoceptor agonist clonidine reduces pain intensity in neuropathic pain syndromes for periods varying from some hours up to 1 month. Patients suffering from lancinating or sharp pain respond best to this therapy. Topically applied clonidine (200-300 microg) relieves hyperalgesia in sympathetically maintained pain. Epidural administration of 300 microg clonidine dissolved in 5 ml NaCl 0.9 % has also been shown to be effective. In patients suffering from cancer pain tolerant to opioids, pain control has proved possible again with combinations of opioids and clonidine. In isolated cases clonidine has been administered epidurally at a dose of 1500 microg/day for almost 5 months without evidence for any histotoxic property of clonidine. Side effects often observed during administration of alpha(2)-adrenoceptor agonists are dry mouth, sedation, hypotension and bradycardia. Therapeutic interventions are usually not required.

  9. Obinutuzumab treatment in the elderly patient with chronic lymphocytic leukemia.

    PubMed

    Seiter, Karen; Mamorska-Dyga, Aleksandra

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Fludarabine-based regimens demonstrate higher response rates in younger patients but have a significant risk of infection and are thus poorly tolerated by older, frail patients. Anti-CD20 monoclonal antibodies have added to the efficacy of chemotherapy in CLL. Obinutuzumab is a potent Type II anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular toxicity and direct cell death compared with rituximab. In Phase I studies, infusion reactions and neutropenia were the predominant toxicities. Phase II studies demonstrated efficacy both as a single agent and in combination with chemotherapy in patients with CLL. The CLL11 trial was a Phase III randomized trial of chlorambucil alone or with either obinutuzumab or rituximab in elderly, unfit patients. Progression-free survival (the primary end point) was 26.7 months for patients receiving obinutuzumab plus chlorambucil versus 16.3 months for those receiving rituximab plus chlorambucil and 11.1 months for those receiving chlorambucil alone (P<0.001). Overall survival was improved for patients receiving obinutuzumab plus chlorambucil versus chlorambucil alone (P=0.002). This trial led to the US Food and Drug Administration (FDA) approval of obinutuzumab in this patient population.

  10. Onabotulinum toxin A (Botox) for chronic migraine treatment: an Italian experience.

    PubMed

    Grazzi, L; Usai, S

    2015-05-01

    Chronic migraine is a common and debilitating headache syndrome. Botulinum neurotoxin, a potent toxin produced by the anaerobic bacterium clostridium botulinum, used largely for treatment of disorders associated with increased muscle tone and hyperhidrosis, is used for patients suffering from chronic migraine. In this study, a group of patients suffering from chronic migraine with medication overuse was treated with onabotulinum toxin A (Botox) to verify its efficacy for chronic migraine. The results confirmed the efficacy of onabotulinum toxin A (Botox) when used at the dosage of 155 UI according to the PREEMPT protocol. Although these results are preliminary, they led to intense efforts to evaluate the analgesic properties of onabotulinum toxin A (Botox) and to assess its use in clinical practice, in particular in migraine field.

  11. Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study

    PubMed Central

    Jain, Preetesh; Kantarjian, Hagop; Jabbour, Elias; Gonzalez, Graciela Nogueras; Borthakur, Gautam; Pemmaraju, Naveen; Daver, Naval; Gachimova, Evguenia; Ferrajoli, Alessandra; Kornblau, Steven; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge

    2015-01-01

    Summary Background Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. Methods We did a single-arm, phase 2 trial at MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24, 2013, we enrolled patients with early (<6 months) chronic-phase CML and treated them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were given a starting dose of 45 mg per day; we lowered this due to tolerability issues and patients enrolled after this date were given a starting dose of 30 mg per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6, 2013, for vascular complications with ponatinib, we started all patients on aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day for all patients. The primary endpoint was the proportion of patients who achieved complete cytogenetic response by 6 months in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01570868. Findings We enrolled 51 patients. Median follow-up was 20.9 months (IQR 14.9–25.2). 43 patients were started on 45 mg ponatinib every day; eight patients were started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete cytogenetic response at 6 months. Most frequent toxicities included skin-related effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events (mainly hypertension) occurred in 25 (49%) patients. Grade 3–4 myelosuppression occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014, at the recommendation of the FDA due to concern about the increased risk of thromboembolism

  12. [Chemotherapy-free treatment of chronic lymphocytic leukemia?].

    PubMed

    Wendtner, C-M

    2013-10-01

    Treatment of CLL patients with conventional cytotoxic agents is often combined with significant toxicity that prevents broad application especially in elderly patients. In addition, relapse frequently occurs after application of conventional chemotherapy in CLL. Recently several new chemo-free treatment options have been introduced within clinical trials. Among them are monoclonal antibodies, most of them targeting the CD20 molecule: besides the licensed drugs rituximab and ofatumumab obinutuzumab, although in combination with chemotherapy, has recently shown high clinical efficacy in front-line treatment of elderly patients with CLL. Lenalidomide as monotherapy has demonstrated clinical efficacy in patients with relapsed disease and first data within clinical trials have been generated in the front-line setting. A promising class of novel agents has been designed to block aberrant signaling from the B-cell receptor. Ibrutinib acts by inhibiting the Bruton's tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform. Another class of drugs with potential impact for chemo-free treatment strategies in CLL are the BH3-mimetic inhibitors of the Bcl-2 family of pro-survival proteins. Other interesting candidate drugs that are currently explored for CLL patients include small modular immunopharmaceutical (SMIP) proteins (e. g. TRU-016), CDK inhibitors (e. g. dinaciclib), HDAC inhibitors and others. Given all these novel agents and targets, chemo-free or at least chemo-reduced concepts may become reality in the near future for our patients suffering from CLL.

  13. Sofa dermatitis presenting as a chronic treatment resistant dermatitis.

    PubMed

    Lynch, M; Collins, P

    2010-04-01

    There is now a well publicised increase in cases of sofa dermatitis since 2007. These have been linked to allergic contact sensitization to dimethlylfumarate, a novel contact allergen. We report on a case associated with a two year history of a treatment resistant dermatitis.

  14. [Unipolar periodic depressive psychosis and chronic tricyclic antidepressive treatment].

    PubMed

    Pascalis, G

    1981-11-01

    Part of unipolar periodic déxpressions may - enjoy an active and comfortable existence, with-out recourse; - during at the less 10 years after beginning of the cure; - under condition of a long-course treatment by tricyclic antidepressors, the patient being trained to module himself the daily doses.

  15. Treatment Outcomes of Patients With Tardive Dyskinesia and Chronic Schizophrenia

    PubMed Central

    Caroff, Stanley N.; Davis, Vicki G.; Miller, Del D.; Davis, Sonia M.; Rosenheck, Robert A.; McEvoy, Joseph P.; Campbell, E. Cabrina; Saltz, Bruce L.; Riggio, Silvana; Chakos, Miranda H.; Swartz, Marvin S.; Keefe, Richard S. E.; Stroup, T. Scott; Lieberman, Jeffrey A.

    2013-01-01

    Objective We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. Method This analysis compared 200 patients with DSM-IV–defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbase-line or showing changes in AIMS scores were evaluated with χ2 tests. Data were collected from January 2001 to December 2004. Results Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ21 =0.11, P = .743). Changes in PANSS scores were not significantly different (F1,974 = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F1,359=6.53, P =.011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F3,151 = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. Conclusions Schizophrenia patients with and without TD were similar in time to discontinuation of

  16. The impact of chronic imipramine treatment on amino acid concentrations in the hippocampus of mice.

    PubMed

    Nagasawa, Mao; Murakami, Tatsuro; Tomonaga, Shozo; Furuse, Mitsuhiro

    2012-09-01

    The relationship between antidepressants and monoamine concentrations in the brain has been well investigated, but few studies have investigated the relationship between antidepressants and amino acid concentrations in the brain. The purpose of the present study was therefore to investigate the effect of the chronic antidepressant imipramine on amino acid and monoamine concentrations in the mouse brain and plasma. Chronic imipramine treatment decreased the concentration of 5-hydroxyindoleaceticacid/5-hydroxytryptamine in the cerebral cortex and increased that of norepinephrine (NE) in the hippocampus. Since these changes were conspicuous effects of the antidepressant, we concluded that imipramine acts on the central nervous system. No change in amino acid concentrations in plasma was induced by chronic imipramine treatment, but several changes were confirmed in the cerebral cortex, the hypothalamus and the hippocampus. Chronic imipramine treatment caused increases in L-methionine, L-tyrosine, and L-lysine in the cerebral cortex, and an increase in L-aspartate in the hypothalamus. Contrary to this, the concentrations of L-aspartate, L-serine, L-asparagine, glycine, L-glutamine, gamma-aminobutyric acid, L-threonine, L-arginine, L-proline, L-valine, and L-methionine in the hippocampus were decreased by chronic imipramine treatment. The present results demonstrate that the metabolism of several amino acids in the brain, but not of those in plasma, was altered by chronic imipramine treatment. The findings in the present study may help to further elucidate the relationship between amino acids and the effects and side effects of antidepressants.

  17. 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

  18. Long-term macrolide treatment of chronic inflammatory airway diseases: risks, benefits and future developments.

    PubMed

    Cameron, E J; McSharry, C; Chaudhuri, R; Farrow, S; Thomson, N C

    2012-09-01

    Macrolide antibiotics were discovered over 50 years ago and following their use as antimicrobials it became apparent that this group of antibiotics also possessed anti-inflammatory properties. Subsequent clinical trials showed benefits of macrolides as long-term adjuncts in the treatment of a spectrum of chronic inflammatory respiratory diseases, particularly diffuse panbronchiolitis, cystic fibrosis, post-transplant bronchiolitis obliterans and more recently chronic obstructive pulmonary disease (COPD). The evidence for efficacy of macrolides in the long-term treatment of chronic asthma and bronchiectasis is less well established. The mechanism(s) of action of macrolides in the treatment of these diseases remains unexplained, but may be due to their antibacterial and/or anti-inflammatory actions, which include reductions in interleukin-8 production, neutrophil migration and/or function. Macrolides have additional potentially beneficial properties including anti-viral actions and an ability to restore corticosteroid sensitivity. The increased prescribing of macrolides for long-term treatment could result in the development of microbial resistance and adverse drug effects. New macrolides have been developed which do not possess any antimicrobial activity and hence lack the ability to produce microbial resistance, but which still retain immunomodulatory effects. Potentially novel macrolides may overcome a significant barrier to the use of this type of drug for the long-term treatment of chronic inflammatory airway diseases.

  19. From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

    PubMed Central

    Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

    2015-01-01

    Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

  20. Factors associated with low adherence to medicine treatment for chronic diseases in Brazil

    PubMed Central

    Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Mengue, Sotero Serrate; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Oliveira, Maria Auxiliadora; Ramos, Luiz Roberto; Farias, Mareni Rocha; Pizzol, Tatiane da Silva Dal

    2016-01-01

    ABSTRACT OBJECTIVE To analyze factors associated with low adherence to drug treatment for chronic diseases in Brazil. METHODS Analysis of data from Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - Brazilian Survey on Access, Use and Promotion of Rational Use of Medicines), a population-based cross-sectional household survey, based on a probabilistic sample of the Brazilian population. We analyzed the association between low adherence to drug treatment measured by the Brief Medication Questionnaire and demographic, socioeconomic, health, care and prescription factors. We used Poisson regression model to estimate crude and adjusted prevalence ratios, their respective 95% confidence interval (95%CI) and p-value (Wald test). RESULTS The prevalence of low adherence to drug treatment for chronic diseases was 30.8% (95%CI 28.8-33.0). The highest prevalence of low adherence was associated with individuals: young adults; no education; resident in the Northeast and Midwest Regions of Brazil; paying part of the treatment; poor self-perceived health; three or more diseases; reported limitations caused by a chronic disease; using five drugs or more. CONCLUSIONS Low adherence to drug treatment for chronic diseases in Brazil is relevant, and regional and demographic differences and those related to patients’ health care and therapy regime require coordinated action between health professionals, researchers, managers and policy makers. PMID:27982378

  1. Clozapine and norclozapine concentrations in serum and plasma samples from schizophrenic patients.

    PubMed

    Hermida, Jesús; Paz, Eduardo; Tutor, J Carlos

    2008-02-01

    At present, the determination of steady-state trough serum/plasma concentrations of clozapine is considered a useful tool for the clinical management of schizophrenic patients treated with this drug. In a previously published study, it was indicated that only plasma should be used to avoid a significant underestimation of clozapine and norclozapine concentrations; however, a formal evaluation of this topic has still not been made, and a consensus on the use of plasma or serum for therapeutic clozapine monitoring may be desirable. Paired samples of serum and plasma (K3EDTA solution contained in Vacutainer tubes) were obtained from 40 schizophrenic patients, and clozapine and norclozapine concentrations were determined by high-performance liquid chromatography. For the parent drug and its metabolite, serum concentrations were higher than in plasma (approximately 7%), although the correction of plasma concentrations in function of hematocrit values reduced this difference to 3%. High correlation coefficients were found between the serum and uncorrected or corrected plasma clozapine concentrations (r = 0.996, P < 0.001), with clinically acceptable differences between the means and standard error of the estimate and consequently with transferability of the results. The clozapine and norclozapine concentrations in five lithium heparin-containing plasma samples (371.9 +/- 226.7 ng/mL and 217.9 +/- 113.1 ng/mL) were analogous to the corresponding hematocrit-corrected EDTA-containing plasma values (374.4 +/- 225.4 ng/mL and 223.5 +/- 115.2 ng/mL), with correlation coefficients of r > or = 0.998 (P < 0.001). Serum or plasma samples may be used for the therapeutic monitoring of clozapine, and no practical advantages have been found with regard to the stability of the drug or imprecision obtained by using either type of biological matrix.

  2. Annual direct medical costs of bronchiectasis treatment: Impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence.

    PubMed

    de la Rosa, David; Martínez-Garcia, Miguel-Angel; Olveira, Casilda; Girón, Rosa; Máiz, Luis; Prados, Concepción

    2016-04-12

    Patients with bronchiectasis (BE) present exacerbations that increase with severity of the disease. We aimed to determine the annual cost of BE treatment according to its severity, determined by FACED score, as well as the parameters associated with higher costs. Multicentre historical cohorts study with patients from six hospitals in Spain. The costs arising during the course of a year from maintenance treatment, exacerbations, emergency visits and hospital admissions were analysed. In total, 456 patients were included (56.4% mild BE, 26.8% moderate BE and 16.9% severe BE). The mean cost was €4671.9 per patient, which increased significantly with severity. In mild BE, most of the costs were due to bronchodilators and inhaled steroids; in severe BE, most were due to exacerbations and inhaled antibiotics. Forced expiratory volume in 1 second (FEV1%), age, colonization byPseudomonas aeruginosaand the number of admissions were independently related to higher costs. The highest costs were found in patients with BE associated with chronic obstructive pulmonary disease, with the most exacerbations and with chronic bronchial colonization byPseudomonas aeruginosa(PA). In conclusion, BE patients gave rise to high annual costs, and these were doubled on each advance in severity on the FACED score. FEV1%, age, colonization by PA and the number of admissions were independently related to higher costs.

  3. 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.

  4. Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature

    PubMed Central

    Warnatz, K; Keskin, A; Uhl, M; Scholz, C; Katzenwadel, A; Vaith, P; Peter, H; Walker, U

    2005-01-01

    Background: Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed "chronic periaortitis". Objective: To determine the optimal therapeutic and diagnostic approaches to IAAA. Methods: The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. Results: The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. Conclusions: Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment. PMID:15897305

  5. [Clinical and immunological assessment of Polyoxidonium and Tantum Verde efficiency by catarrhal gingivitis treatment in children with chronic gastroduodenitis].

    PubMed

    Kazarina, L N; Pursanova, A E

    2014-01-01

    The article presents findings allowing estimating effect of local application of polioxidonium and yantum verde in 101 children aged 12-17 with chronic catarrhal gingivitis and chronic gastroduodenitis. Statistically significant PMA indeх decrease (40.1±2.3% till 1.4±0.6% (р<0,001)) proved the above mentioned therapy scheme to be highly effective for treatment of chronic catarrhal gingivitis in children with chronic gastroduodenitis.

  6. 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

  7. 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

  8. [Methodic approaches to treatment of the chronic generalized parodontitis in elderly and senile patients].

    PubMed

    Iordanishvili, A K; Soldatov, S V; Moskalev, A V; Soldatova, L N; Ryzhak, G A

    2011-01-01

    A comprehensive treatment with Likopid of chronic generalized parodontitis in 114 elderly and senile patients was carried out. The state of mechanisms of innate immunity (phagocytosis mechanisms) as well as the profile of proinflammatory cytokines was assessed. The effect of antibiotic-resistant strains of prior microflora on the combined therapy of patients of different age with chronic generalized parodontitis was studied. It is established that due to presence of various types of opportunistic pathogens in patients of different age with parodontitis using the prophylactic antibiotics for the empirical (to determine the antibiotic resistance), a combination of Metronidazole and Lincomycin with the mandatory appointment of immunomodulatory drugs for activation of monocyte-phagocytic system of the patient elderly is most advisable. Use of the drug , "Likopid" significantly improves the results of treatment the elderly and old patients with chronic generalized parodonthitis.

  9. 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.

  10. 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.

  11. Nicotine improves working memory span capacity in rats following sub-chronic ketamine exposure.

    PubMed

    Rushforth, Samantha L; Steckler, Thomas; Shoaib, Mohammed

    2011-12-01

    Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel mGlu2/3 agonist, LY404039, in restoring OST performance. Male hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025-0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1-10 mg/kg) and LY404039 (0.3-10 mg/kg) failed to reverse ketamine-induced deficits in doses that were observed to impair performance in the control groups. These data suggest that sub-chronic ketamine exposure in the OST presents a valuable method to examine novel treatments to restore cognitive impairments associated with neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a central role for neuronal nicotinic receptors as viable targets for intervention that may be useful adjuncts to the currently prescribed anti-psychotics.

  12. Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats.

    PubMed

    Gomes, Karin M; Inácio, Cecília G; Valvassori, Samira S; Réus, Gislaine Z; Boeck, Carina R; Dal-Pizzol, Felipe; Quevedo, João

    2009-11-06

    The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.

  13. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    PubMed Central

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  14. 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’ w