Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

PubMed

Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability

PubMed Central

Singh, Sourabh Moti; Haddad, Peter M.; Husain, Nusrat; Heaney, Eamonn; Tomenson, Barbara; Chaudhry, Imran B.

2016-01-01

Objectives: The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). Method: A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. Results: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Conclusions: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including medication tolerability; assessment of side effects, efficacy and quality of life made by blinded raters; and additional objective side-effect data including changes in weight and key blood parameters. PMID:27354904

A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

PubMed

Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

2013-01-01

Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

A phase I study of human natural interferon-beta in cancer patients.

PubMed

Liberati, A M; Biscottini, B; Fizzotti, M; Schippa, M; De Angelis, V; Senatore, M; Vittori, O; Teggia, L; Natali, R; Palmisano, L

1989-06-01

In this phase I study 15 patients with metastatic tumors were given interferon (IFN)-beta by i.v. bolus injections. Twelve individual doses of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 35, and 46 x 10(6) IU were administered every other day. The single maximal tolerated dose ranged from 9 to 46 x 10(6) IU. Eight patients tolerated the dose of 46 x 10(6) IU without side effects. Disturbances of cardiac rhythm were observed, but were closely related temporally to severe chills and appeared to be the consequence of adrenergic stimulation associated with this side-effect. In addition, no significant variations in the left ventricular function as assessed by nuclear stethoscope were observed. Neurotoxicity was not a major side-effect. The toxicity of IFN-beta given as scheduled in this study was significant, but acceptable.

14-Alkoxy- and 14-acyloxypyridomorphinans: μ agonist/δ antagonist opioid analgesics with diminished tolerance and dependence side effects.

PubMed

Ananthan, Subramaniam; Saini, Surendra K; Dersch, Christina M; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J; Rothman, Richard B

2012-10-11

In the search for opioid ligands with mixed functional activity, a series of 5'-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h, its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects upon prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine upon repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence, and related side effects.

14-Alkoxy- and 14-Acyloxypyridomorphinans: Mu Agonist/Delta Antagonist Opioid Analgesics with Diminished Tolerance and Dependence Side Effects

PubMed Central

Ananthan, Subramaniam; Saini, Surendra K.; Dersch, Christina M.; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J.; Rothman, Richard B.

2012-01-01

In the search for opioid ligands with mixed functional activity, a series of 5′-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects on prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine on repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence and related side effects. PMID:23016952

Opioid receptor desensitization: mechanisms and its link to tolerance

PubMed Central

Allouche, Stéphane; Noble, Florence; Marie, Nicolas

2014-01-01

Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor. PMID:25566076

Levetiracetam in adult patients with and without learning disability: focus on behavioral adverse effects.

PubMed

Brodtkorb, Eylert; Klees, Theresa M; Nakken, Karl O; Lossius, Rasmus; Johannessen, Svein I

2004-04-01

Optimal antiepileptic drug treatment in patients with learning disability (LD) represents a particular challenge. These patients are often unable to report toxicity, and side effects may manifest as behavioral problems. The aim of this open study was to compare efficacy and tolerability of levetiracetam (LEV) in patients with LD and those without LD. One hundred eighty-four consecutive adult patients who received LEV were followed for an average of 8.1 months. Fifty-six patients (30%) had LD. Thirty-nine percent of patients with refractory epilepsy (37% with and 40% without LD) had > 50% seizure reduction. Significantly more behavioral side effects (23% vs 10%) and a tendency toward less reported somatic central nervous side effects were found in the LD group. We conclude that LEV is equally effective and well tolerated in both patients with LD and patients without LD. However, behavioral problems are more frequent in patients with LD, whereas the tendency toward seizure increase is not enhanced.

Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species.

PubMed

Xu, Hongguo; Liu, Guojie; Liu, Guotian; Yan, Bofang; Duan, Wei; Wang, Lijun; Li, Shaohua

2014-06-05

In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed. In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O₂ evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated. The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance.

Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species

PubMed Central

2014-01-01

Background In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed. Results In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O2 evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated. Conclusions The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance. PMID:24898786

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

Use and tolerability of a side pole static ankle foot orthosis in children with neurological disorders.

PubMed

Delvert, Céline; Rippert, Pascal; Margirier, Françoise; Vadot, Jean-Pierre; Bérard, Carole; Poirot, Isabelle; Vuillerot, Carole

2017-04-01

Transverse-plane foot deformities are a frequently encountered issue in children with neurological disorders. They are the source of many symptoms, such as pain and walking difficulties, making their prevention very important. We aim to describe the use and tolerability of a side pole static ankle foot orthosis used to prevent transverse-plane foot deformities in children with neurologic disorders. Monocentric, retrospective, observational study. Medical data were collected from 103 children with transverse-plane foot deformities in one or both feet caused by a neurological impairment. All children were braced between 2001 and 2010. Unilateral orthosis was prescribed for 32 children and bilateral orthosis for 71. Transverse-plane foot deformities were varus in 66% of the cases and an equinus was associated in 59.2% of the cases. Mean age for the first prescription was 8.6 years. For the 23 patients present at the 4-year visit, 84.8% still wore the orthosis daily, and 64.7% wore the orthosis more than 6 h per day. The rate of permanent discontinuation of wearing the orthosis was 14.7%. The side pole static ankle foot orthosis is well tolerated with very few side effects, which promotes regular wearing and observance. Clinical relevance Side pole static ankle foot orthoses are well tolerated and can be safely used for children with foot abnormalities in the frontal plane that have a neurological pathology origin.

Antiepileptic drug therapy: clinical laboratory significance.

PubMed

Naradzay, J F; Olshaker, J S

1996-01-01

When evaluating a patient who is taking an antiepileptic medication, it is important for the emergency physician to correlate the clinical presentation with the antiepileptic drug level. Therapeutic ranges have been suggested for most antiepileptic medications, but these must be interpreted in light of clinical efficacy and patient tolerance. When considering the efficacy of anti-epileptic medications, it is necessary to consider the patient's unique metabolism, side-effect tolerance, and overall response to therapy. Suggested therapeutic ranges should be the first reference for the emergency physician. The purpose of this report is to discuss the laboratory values of commonly prescribed antiepileptic medications. Therapeutic ranges, side-effects, and common medication interactions are discussed concerning phenytoin, phenobarbital, carbamezapine, and valproic acid.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal.

PubMed

Deng, Liting; Guindon, Josée; Cornett, Benjamin L; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G

2015-03-01

Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. We evaluated antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2 knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the prototypic classic cannabinoid Δ(9)-THC. We also explored the site and possible mechanism of action of AM1710. Paclitaxel-induced mechanical and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ(9)-THC suppressed established paclitaxel-induced allodynia in WT mice. In contrast to Δ(9)-THC, chronic administration of AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel-induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis factor-α and monocyte chemoattractant protein 1 in lumbar spinal cord of paclitaxel-treated WT mice. Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Misperceptions About β-Blockers and Diuretics

PubMed Central

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-01-01

BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that β-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and β-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of β-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines. PMID:14687255

Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians.

PubMed

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-12-01

Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P <.001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P <.001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines.

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

PubMed

Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

2015-11-01

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena.

PubMed

Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

2009-09-01

The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes.

Predictors and Diagnostic Significance of the Adenosine Related Side Effects on Myocardial Perfusion SPECT/CT Imaging

PubMed Central

Yıldırım Poyraz, Nilüfer; Özdemir, Elif; Poyraz, Barış Mustafa; Kandemir, Zuhal; Keskin, Mutlay; Türkölmez, Şeyda

2014-01-01

Objective: The aim of this study was to investigate the relationship between patient characteristics and adenosine-related side-effects during stress myocard perfusion imaging (MPI). The effect of presence of adenosine-related side-effects on the diagnostic value of MPI with integrated SPECT/CT system for coronary artery disease (CAD), was also assessed in this study. Methods: Total of 281 patients (109 M, 172 F; mean age:62.6±10) who underwent standard adenosine stress protocol for MPI, were included in this study. All symptoms during adenosine infusion were scored according to the severity and duration. For the estimation of diagnostic value of adenosine MPI with integrated SPECT/CT system, coronary angiography (CAG) or clinical follow-up were used as gold standard. Results: Total of 173 patients (61.6%) experienced adenosine-related side-effects (group 1); flushing, dyspnea, and chest pain were the most common. Other 108 patients completed pharmacologic stress (PS) test without any side-effects (group 2). Test tolerability were similar in the patients with cardiovascular or airway disease to others, however dyspnea were observed significantly more common in patients with mild airway disease. Body mass index (BMI) ≥30 kg/m2 and age ≤45 years were independent predictors of side-effects. The diagnostic value of MPI was similar in both groups. Sensitivity of adenosine MPI SPECT/CT was calculated to be 86%, specificity was 94% and diagnostic accuracy was 92% for diagnosis of CAD. Conclusion: Adenosine MPI is a feasible and well tolerated method in patients who are not suitable for exercise stress test as well as patients with cardiopulmonary disease. However age ≤45 years and BMI ≥30 kg/m2 are the positive predictors of adenosine-related side-effects, the diagnostic value of adenosine MPI SPECT/CT is not affected by the presence of adenosine related side-effects. PMID:25541932

How do stroke survivors and their carers use practitioners' advice on secondary prevention medications? Qualitative study of an online forum.

PubMed

Izuka, Nkeonye J; Alexander, Matthew A W; Balasooriya-Smeekens, Chantal; Mant, Jonathan; De Simoni, Anna

2017-09-01

Secondary prevention medications reduce risk of stroke recurrence, yet many people do not receive recommended treatment, nor take medications optimally. Exploring how patients report making use of practitioners' advice on secondary prevention medicines on an online forum and what feedback was received from other participants. Thematic analysis of the archive of Talkstroke (2004-2011), UK. Posts including any secondary prevention medication terms, General Practitioner (GP) and their replies were identified. Fifity participants talked about practitioners' advice on secondary prevention medications in 43 discussion threads. Patients consulted practitioners for reassurance and dealing with side effects. Practitioners' advice varied from altering to maintaining current treatment. Three main themes emerged from the use of practitioners' advice: patients following advice (reassured, happy when side effects made tolerable, or still retaining anxiety about treatment); patients not following advice (admitting adherence on-off or stopping medications as side effects still not tolerable); asking other participants for feedback on advice received. Practitioners' advice was disregarded mainly when related to dealing with statin side effects, after one or two consultations. Themes for feedback involved sharing experience, directing back to practitioners, or to external evidence. Side effects of secondary prevention medications and statins in particular, cause anxiety and resentment in some patients, and their concerns are not always addressed by practitioners. Practitioners could consider more proactive strategies to manage such side effects. Forum feedback was appropriate and supportive of the practitioners' advice received. Our findings from peer-to-peer online conversations confirm and widen previous research. © The Author 2017. Published by Oxford University Press.

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

Laterality of pain: modulation by placebo and participants' paranormal belief.

PubMed

Klemenz, Caroline; Regard, Marianne; Brugger, Peter; Emch, Oliver

2009-09-01

To investigate the effects of placebo and paranormal belief on the laterality of pain perception. The right hemisphere is dominantly involved in both the mediation of pain sensation and the belief in paranormal phenomena. We set out to assess a possible influence of long-term belief systems on placebo analgesia in response to unilateral nociceptive stimuli. Forty healthy participants (20 high and 20 low believers as indexed by the Magical Ideation Scale) underwent a placebo analgesia study measuring stimulus detection, pain threshold, and pain tolerance by electrostimulation on the right and left hand. Placebo treatment consisted of the application of a sham cream on the hands. Placebo had a positive influence on pain perception in the 3 variables. Enhanced pain sensitivity for the left side was only found for the disbelievers. Placebo treatment resulted in a double dissociation: in believers, it increased tolerance exclusively on the left side, in disbelievers on the right side. Our results confirm laterality effects in pain perception. However, only disbelievers conformed to the expected higher left-sided sensitivity. Placebo effects were dissociated between believers and disbelievers suggesting that short-term reactions to a placebo are modulated by a person's long-term belief system.

A study of cycle control, side effects and client's satisfaction of a low dose combined contraceptive containing ethinylestradiol/drospirenone (24/4 regimen).

PubMed

Chaiyasit, Noppadol; Taneepanichskul, Surasak

2010-05-01

To study cycle control, side effects, and satisfaction of low dose 24-day combined contraceptive containing 20 microg of Ethinylestradiol and 3 mg of Drospirenone. This was an open label, non-comparative study. The healthy females from the family planning clinic at King Chulalongkorn Memorial Hospital were assigned to receive six cycles of combined oral contraceptive containing 20 microg of ethinylestradiol and 3 mg of drospirenone administered daily for 24 days followed by 4-day hormone-free interval. Data were collected on cycle control, side effects, and satisfaction. Data were analyzed using descriptive statistics for descriptive data and Paired t test for comparison. One hundred fifty four women were assigned the study medication, including one (0.64%) who did not start medication. In the second reference period, the occurrence of frequent and infrequent bleeding was low (2.1% and 4.9%). Only one woman (0.65%) discontinued medication because of irregular bleeding. There was no pregnancy reported during the present study. Overall, the study medication was well tolerated and five subjects (3.24%) discontinued study because of side effects. No serious side effects related to the study medication were reported. The majority of women (84.2%) were satisfied and very satisfied with the treatment and most (73.3%) would continue the medication if it were available. The low dose combined contraceptive containing Ethinylestradiol/Drospirenone (24/4 regimen) has acceptable cycle control and good tolerability.

A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

PubMed Central

Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

2009-01-01

Background and purpose: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach: Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Key results: Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. Conclusions and implications: The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes. PMID:19563531

Deconstructing Decisions to Initiate, Maintain, or Discontinue Adjuvant Endocrine Therapy in Breast Cancer Survivors: A Mixed-Methods Study

PubMed Central

Bluethmann, Shirley M.; Murphy, Caitlin C.; Tiro, Jasmin A.; Mollica, Michelle A.; Vernon, Sally W.; Bartholomew, Leona Kay

2017-01-01

Purpose/Objectives Adjuvant endocrine therapy (AET) has been shown to improve survival in hormone receptor–positive breast cancer survivors, but as many as half do not complete recommended treatment. Management of medication-related side effects and engagement with providers are two potentially modifiable factors, but their associations with adherence are not well understood. The aims were to build on survey results to qualitatively explore survivors’ experiences with prescribed AET to (a) describe appraisal and management of AET side effects and (b) deconstruct decisions to initiate, discontinue, or maintain AET. Research Approach The authors used a mixed-methods explanatory sequence research design with a qualitative emphasis. Setting Survivors were recruited from a clinical cancer registry maintained at the University of Texas Southwestern Medical Center, which includes the Harold C. Simmons Comprehensive Cancer Center (National Cancer Institute–designated), in Dallas. Participants 452 survivors completed a survey, and 30 took part in telephone interviews. Methodologic Approach Qualitative methods were used in which the authors recorded and transcribed interviews for analysis and used open coding to reduce data into themes. Findings Among adherent survivors, the themes of tolerance of side effects and perseverance were strong. Nonadherent survivors expressed more difficulty managing side effects and perceived fewer benefits when side effects were bothersome. The most common side effects mentioned by all survivors were menopausal symptoms and joint pain; less common side effects were cognitive decline and cardiac distress. Some sought advice from their oncology team. Nonadherent survivors appeared initially motivated to maintain AET but identified a tolerance limit for side effects after which a provider’s recommendation was less influential in their decision to maintain or discontinue AET. Interpretation This study elucidated adherence as a complex continuum of behaviors, appraisals, and decision points. These insights may be particularly useful in counseling survivors taking AET and promoting timely delivery of clinical interventions to enhance adherence. Implications for Nursing Nurses should be involved in the planning and implementation of clinical interventions to manage side effects and other barriers to AET adherence. PMID:28635973

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2016-01-01

Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

PubMed

Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

2017-06-01

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Cancer.gov

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.

PubMed

Arriola Apelo, Sebastian I; Neuman, Joshua C; Baar, Emma L; Syed, Faizan A; Cummings, Nicole E; Brar, Harpreet K; Pumper, Cassidy P; Kimple, Michelle E; Lamming, Dudley W

2016-02-01

Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA-approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The gut-brain interaction in opioid tolerance.

PubMed

Akbarali, Hamid I; Dewey, William L

2017-12-01

The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

The use of subcutaneous glycopyrrolate in the management of sialorrhoea and facilitating the use of non-invasive ventilation in amyotrophic lateral sclerosis.

PubMed

Cooper-Knock, Johnathan; Ahmedzai, Sam H; Shaw, Pamela

2011-11-01

Sialorrhoea is a recognized complication of bulbar amyotrophic lateral sclerosis (ALS) that leads to an increased risk of potentially harmful aspiration and often prevents patients from tolerating non-invasive ventilation (NIV). A case of treatment-resistant sialorrhoea in bulbar ALS is described where subcutaneous glycopyrrolate was effective without significant side-effects. The patient went on to markedly increase the length of time she could tolerate NIV each night.

Oral ketamine for the treatment of pain and treatment-resistant depression†.

PubMed

Schoevers, Robert A; Chaves, Tharcila V; Balukova, Sonya M; Rot, Marije Aan Het; Kortekaas, Rudie

2016-02-01

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. © The Royal College of Psychiatrists 2016.

Issues in hypertension: drug tolerability and special populations.

PubMed

Gavras, H P

2001-07-01

Improvements in the death rate from coronary heart disease and in the control of hypertension have leveled off in recent years, reversing a trend toward steady improvement that began in 1972. Of the roughly 20% of Americans who suffer from hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment and nearly half receive no treatment at all. Poor adherence to therapy doubtless plays a key role in this failure. As a major cause of poor adherence, tolerability becomes an extremely important element in any discussion of effective antihypertensive treatment. Despite their efficacy in treating hypertension, diuretics, beta-blockers, and calcium channel blockers have all been associated with numerous side effects, including increased serum lipid levels, insulin resistance, and edema. With the introduction of the angiotensin converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure goals with fewer side effects. These agents, however, cause an irritating cough in up to 19% of patients. A newer class of drugs, the angiotensin receptor blockers (ARB), have similar effects to the ACE inhibitors, but their highly selective nature produces even fewer side effects. Eprosartan is a structurally unique ARB. Like the other ARB, this promising new agent has a side effect profile similar to placebo, and its response rate rivals or exceeds that of enalapril. Although it remains to be seen whether the ARB can significantly reduce morbidity and mortality from cardiovascular disease, preliminary data from the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.

Experience of dolutegravir in HIV-infected treatment-naive patients from a tertiary care University Hospital in Ireland

PubMed Central

Waqas, Sarmad; O’Connor, Mairead; Levey, Ciara; Mallon, Paddy; Sheehan, Gerard; Patel, Anjali; Avramovic, Gordana; Lambert, John S

2016-01-01

Objective: Dolutegravir, an HIV integrase inhibitor, is a relatively new treatment option. To assess the tolerability, side effects, and time to viral decline to non-detectable in patients newly started on dolutegravir. Methods: Retrospective health care record of 61 consecutive HIV treatment-naive patients started on dolutegravir was reviewed and analysed on SPSS. Results: The mean initial viral load was 160826.05 copies/mL (range, 79–1,126,617 copies/mL). HIV viral load became non-detectable in 63.9% of patients on dolutegravir within 3 months. In all, 60.7% of patients reported no side effects on dolutegravir; 98.4% of the patients claimed full compliance to their antiretrovirals. Conclusion: Dolutegravir was found to be efficacious and well tolerated in HIV-infected treatment-naive patients. PMID:27826447

Review of the Safety of Second-Generation Antipsychotics: Are They Really “Atypically” Safe for Youth and Adults?

PubMed Central

Rosenberg, David R.; Brooks, Beth Ann; Roberts, Mary W.; Diwadkar, Vaibhav A.

2012-01-01

Objective: There is general consensus that second-generation antipsychotics are at least as effective as and more tolerable than first-generation antipsychotics. We address questions of safety and tolerability in both the short-term and long-term use of these medications by reviewing the existing literature in youth and adults. Data Sources: A MEDLINE search was conducted via PubMed using the following keywords (in various combinations): typical antipsychotics, atypical antipsychotics, children, adolescents, side effects, weight gain, diabetes, metformin, metabolic syndrome, and CATIE. Only English-language articles published from 2000–2010 were included. The bibliographies of papers identified through MEDLINE searches were also reviewed. Results: Six adult studies were analyzed in detail. A summary of the data suggests that there may be a lower association of weight gain and diabetes with ziprasidone, aripiprazole, and haloperidol, while olanzapine, clozapine, quetiapine, and risperidone appear to be more highly associated. There may be less difference than originally thought concerning frequency of extrapyramidal side effects among these medications. All of these antipsychotics, including perphenazine, are similarly efficacious in treating psychosis, with the exception of clozapine, which demonstrates significantly more effectiveness. Although the studies on youth tend to be small (few subjects with large age ranges of 4 to 19 years) and short term in comparison to the adult studies, the data reviewed from 5 studies suggest that, in youth, olanzapine may be associated with the greatest weight gain, extrapyramidal side effects and metabolic changes are quite prevalent, and the antipsychotics studied seem to be similarly effective. Conclusions: Considering effectiveness, safety, and tolerability, this literature review suggests that in adults there may be a lower association of weight gain and diabetes with ziprasidone, aripiprazole, and haloperidol as compared with olanzapine, clozapine, quetiapine, and risperidone. Youth may be particularly sensitive to weight gain, especially with olanzapine, as well as extrapyramidal side effects and metabolic changes. The literature suggests similar effectiveness among the antipsychotics, perhaps with the exception of clozapine having greater effectiveness, at least in adults. PMID:23106030

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

PubMed Central

Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

2009-01-01

Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

A retrospective study evaluating the tolerability and effectiveness of adjunctive antihypertensive drugs in patients with inadequate response to initial treatment.

PubMed

Ayyagari, Rajeev; Xie, Jipan; Cheng, David; Wu, Eric Q; Huang, Xing-Yue; Chen, Stephanie

2018-06-01

Real-world tolerability and effectiveness of nebivolol as first add-on therapy were compared with hydrochlorothiazide, metoprolol, and amlodipine. Medical records of hypertensive adults initiating nebivolol, hydrochlorothiazide, metoprolol, or amlodipine as first add-on therapy between December 16, 2010 and July 21, 2011 were retrospectively abstracted (N = 1600; 400/treatment). Outcomes included medication-related side-effect rates and blood pressure (BP) reduction and control. Compared with nebivolol, metoprolol and amlodipine had significantly higher side-effect rates (incidence rate ratio [95% CI]: 1.82 [1.14-2.92] and 2.67 [1.69-4.21]), respectively); the hydrochlorothiazide-nebivolol rate ratio was not significant (1.61 [0.95-2.71]). All treatments reduced BP at 2 months. Metoprolol, amlodipine, and hydrochlorothiazide were associated with significantly lower odds of achieving 2-month BP control than nebivolol (odds ratios [95% CI]: 0.34 [0.23-0.51], 0.51 [0.35-0.75] and 0.66 [0.44-0.99], respectively). In a real-world setting, nebivolol as first add-on therapy was associated with fewer side effects than metoprolol or amlodipine and with a higher BP control rate than hydrochlorothiazide, metoprolol, or amlodipine. © 2018 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.

Oesophagus side effects related to the treatment of oesophageal cancer or radiotherapy of other thoracic malignancies.

PubMed

Adebahr, Sonja; Schimek-Jasch, Tanja; Nestle, Ursula; Brunner, Thomas B

2016-08-01

The oesophagus as a serial organ located in the central chest is frequent subject to "incidental" dose application in radiotherapy for several thoracic malignancies including oesophageal cancer itself. Especially due to the radiosensitive mucosa severe radiotherapy induced sequelae can occur, acute oesophagitis and strictures as late toxicity being the most frequent side-effects. In this review we focus on oesophageal side effects derived from treatment of gastrointestinal cancer and secondly provide an overview on oesophageal toxicity from conventional and stereotactic fractionated radiotherapy to the thoracic area in general. Available data on pathogenesis, frequency, onset, and severity of oesophageal side effects are summarized. Whereas for conventional radiotherapy the associations of applied doses to certain volumes of the oesophagus are well described, the tolerance dose to the mediastinal structures for hypofractionated therapy is unknown. The review provides available attempts to predict the risk of oesophageal side effects from dosimetric parameters of SBRT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical relevance of cannabis tolerance and dependence.

PubMed

Jones, R T; Benowitz, N L; Herning, R I

1981-01-01

Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems.

Cannabidiol monotherapy for treatment-resistant schizophrenia.

PubMed

Zuardi, Antonio Waldo; Hallak, Jaime E C; Dursun, Serdar Murat; Morais, Sílvio L; Sanches, Rafael Faria; Musty, Richard E; Crippa, José Alexandre S

2006-09-01

Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana's typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data (Zuardi et al., 2002). In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS). This was an in-patient study. All patients were given placebo for the initial 5 days, and from the 6th to 35th day (inclusive) they received CBD (initial oral dose of 40 mg reaching 1280 mg/day). On the 36th day, CBD treatment was discontinued and replaced by placebo for 5 days, which was subsequently switched to olanzapine for over 15 days. Efficacy, tolerability and side effects were assessed. One patient showed mild improvement, but two patients didn't show any improvement during CBD monotherapy. All patients tolerated CBD very well and no side effects were reported. These preliminary data suggest that CBD monotherapy may not be effective for TRS.

Regulation of opioid receptor signalling: Implications for the development of analgesic tolerance

PubMed Central

2011-01-01

Opiate drugs are the most effective analgesics available but their clinical use is restricted by severe side effects. Some of these undesired actions appear after repeated administration and are related to adaptive changes directed at counteracting the consequences of sustained opioid receptor activation. Here we will discuss adaptations that contribute to the development of tolerance. The focus of the first part of the review is set on molecular mechanisms involved in the regulation of opioid receptor signalling in heterologous expression systems and neurons. In the second part we assess how adaptations that take place in vivo may contribute to analgesic tolerance developed during repeated opioid administration. PMID:21663702

Molecular targeted therapies for solid tumors: management of side effects.

PubMed

Grünwald, Viktor; Soltau, Jens; Ivanyi, Philipp; Rentschler, Jochen; Reuter, Christoph; Drevs, Joachim

2009-03-01

This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available. Copyright 2009 S. Karger AG, Basel.

Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

PubMed Central

2012-01-01

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

PubMed

Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

2012-09-19

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

The desire to survive: the adaptation process of adult cancer patients undergoing radiotherapy.

PubMed

Chao, Yu Huan; Wang, Shou-Yu; Hsu, Tsui Hua; Wang, Kai Wei K

2015-01-01

Radiotherapy is one of the primary treatment strategies for cancer. However, patients not only deal with the side-effects of radiotherapy, but they must also endure the psychological distress caused by cancer. This study explores how cancer patients adapt to the treatment process when receiving radiotherapy. This study used a grounded theory approach, and eight in-depth interviews were conducted with newly diagnosed cancer patients who received radiotherapy as a primary treatment. The core category that emerged from this study was "the desire to survive". The categories and subcategories that emerged from the data include facing unknown situations (e.g. searching for relevant information and decision-making considerations, and listening to healthcare professionals' suggestions), experiencing the pain of treatment (e.g. tolerating side-effects, tolerating inconvenience during the treatment, accepting support during the treatment, and adjusting lifestyles), and chances to extend life (e.g. accepting fate, determination to undergo the treatment, and adjusting negative emotions). The study results provide a better understanding of the experiences of cancer patients undergoing radiotherapy. Healthcare professionals should provide effective medical management for side-effects and psychological support to cancer patients during the journey of radiotherapy. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

Computer program determines exact two-sided tolerance limits for normal distributions

NASA Technical Reports Server (NTRS)

Friedman, H. A.; Webb, S. R.

1968-01-01

Computer program determines by numerical integration the exact statistical two-sided tolerance limits, when the proportion between the limits is at least a specified number. The program is limited to situations in which the underlying probability distribution for the population sampled is the normal distribution with unknown mean and variance.

Adrenocorticotropic hormone analog use for podocytopathies.

PubMed

Filippone, Edward J; Dopson, Shirley J; Rivers, Denise M; Monk, Rebeca D; Udani, Suneel M; Jafari, Golriz; Huang, Solomon C; Melhem, Arafat; Assioun, Bassim; Schmitz, Paul G

2016-01-01

Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar(®) Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place.

Adrenocorticotropic hormone analog use for podocytopathies

PubMed Central

Filippone, Edward J; Dopson, Shirley J; Rivers, Denise M; Monk, Rebeca D; Udani, Suneel M; Jafari, Golriz; Huang, Solomon C; Melhem, Arafat; Assioun, Bassim; Schmitz, Paul G

2016-01-01

Background Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar® Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Methods Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. Results All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Conclusion Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place. PMID:27418857

Organic nitrates and nitrate tolerance--state of the art and future developments.

PubMed

Daiber, Andreas; Münzel, Thomas; Gori, Tommaso

2010-01-01

The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two "traditional" hypotheses of nitrate tolerance, that is, the one postulating a decreased bioactivation and the concurrent one suggesting a role of oxidative stress. Furthermore, recent animal and human experimental studies suggest that the organic nitrates are not a homogeneous group but demonstrate a broad diversity with regard to induction of vascular dysfunction, oxidative stress, and other side effects. In the past, attempts to avoid nitrate-induced side effects have focused on administration schedules that would allow a "nitrate-free interval"; in the future, the role of co-therapies with antioxidant compounds and of activation of endogeneous protective pathways such as the heme oxygenase 1 (HO-1) will need to be explored. However, the development of new nitrates, for example, tolerance-free aminoalkyl nitrates or combination of nitrate groups with established cardiovascular drugs like ACE inhibitors or AT(1)-receptor blockers (hybrid molecules) may be of great clinical interest. Copyright © 2010 Elsevier Inc. All rights reserved.

Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment.

PubMed

Jones, Isabela T; Guiha, Isabella; Fabi, Sabrina G

2017-11-21

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction. To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability. Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit. Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure. The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability. © 2017 Wiley Periodicals, Inc.

[Efficacy and tolerability of choline alphoscerate (cereton) in patients with Parkinson's disease with cognitive disorders].

PubMed

Levin, O S; Batukaeva, L A; Anikina, M A; Iunishchenko, N A

2009-01-01

An open 10-day study of treatment effect of cereton in comparison to piracetam has been conducted. Cereton was used in 40 patients (main group) in dosage 1000 mg, piracetam - in 20 patients (control group) in dosage 2000 mg. Both drugs were used intravenous in drops in 200 ml of physiologic saline along with antiparkinsonian medications. Patient's state was assessed with a battery of psychometric scales and neuropsychological tests as well as with instruments for measuring intensity of parkinsonian symptoms, side-effects and quality of life. Marked and moderate improvement of cognitive functions was found in patients of the main group compared to the control one (40% and 25%, respectively, p<0,05). Deterioration of cognitive functions was seen less often in the main group than in the control group (5% and 15%, respectively, p<0,05). Cereton was well-tolerated by patients. Side effects (brief and short-term) were found only in 6 (15%) patients.

Achieving stable remission with maintenance electroconvulsive therapy in a patient with treatment-resistant schizophrenia

PubMed Central

Moeller, Sebastian; Kalkwarf, Neele; Lücke, Caroline; Ortiz, Diana; Jahn, Sonja; Först, Christiane; Braun, Niclas; Philipsen, Alexandra; Müller, Helge H.O.

2017-01-01

Abstract Rationale: Up to one third of all schizophrenic patients are classified as having treatment-resistant schizophrenia (TRS). This subgroup faces remarkable medical and psychosocial damages, and pharmacotherapy is often limited due to nonresponse and/or side effects. Maintenance electroconvulsive therapy (M-ECT) might be effective in TRS. Patient concerns: We present a case of a 26-year-old male patient with a TRS. Diagnoses: He received a treatment series of ECT sessions and a course of 24 M-ECTs. Interventions: The entire treatment was tolerated without significant side effects. Outcomes: Moreover, the Psychotic Symptom Rating Scale (PSYRATS) scores for both positive and negative symptoms decreased and remained stable over the course of M-ECT. Lessons: Because of the remarkable improvement in the negative and positive symptom clusters, we propose systematic examinations in the field of M-ECT in TRS patients. These studies should integrate long-term outcome and tolerance measurements, gaining insight into the optimal duration of treatment for this indication. PMID:29310360

Achieving stable remission with maintenance electroconvulsive therapy in a patient with treatment-resistant schizophrenia: A case report.

PubMed

Moeller, Sebastian; Kalkwarf, Neele; Lücke, Caroline; Ortiz, Diana; Jahn, Sonja; Först, Christiane; Braun, Niclas; Philipsen, Alexandra; Müller, Helge H O

2017-12-01

Up to one third of all schizophrenic patients are classified as having treatment-resistant schizophrenia (TRS). This subgroup faces remarkable medical and psychosocial damages, and pharmacotherapy is often limited due to nonresponse and/or side effects. Maintenance electroconvulsive therapy (M-ECT) might be effective in TRS. We present a case of a 26-year-old male patient with a TRS. He received a treatment series of ECT sessions and a course of 24 M-ECTs. The entire treatment was tolerated without significant side effects. Moreover, the Psychotic Symptom Rating Scale (PSYRATS) scores for both positive and negative symptoms decreased and remained stable over the course of M-ECT. Because of the remarkable improvement in the negative and positive symptom clusters, we propose systematic examinations in the field of M-ECT in TRS patients. These studies should integrate long-term outcome and tolerance measurements, gaining insight into the optimal duration of treatment for this indication.

A vitamin B12 conjugate of exendin-4 improves glucose tolerance without associated nausea or hypophagia in rodents.

PubMed

Mietlicki-Baase, Elizabeth G; Liberini, Claudia G; Workinger, Jayme L; Bonaccorso, Ron L; Borner, Tito; Reiner, David J; Koch-Laskowski, Kieran; McGrath, Lauren E; Lhamo, Rinzin; Stein, Lauren M; De Jonghe, Bart C; Holz, George G; Roth, Christian L; Doyle, Robert P; Hayes, Matthew R

2018-05-01

While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 (B12) bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice. To evaluate whether differences in the profile of effects of B12-Ex4 vs unconjugated Ex4 are the result of altered CNS penetrance, rats received systemic injections of fluorescein-Ex4 (Flex), Cy5-B12 or Cy5-B12-Ex4 and brain penetrance was evaluated using confocal microscopy. Uptake of systemically administered Cy5-B12-Ex4 in insulin-containing pancreatic beta cells was also examined. B12-Ex4 conjugate improves glucose tolerance, but does not elicit the malaise and anorexia produced by unconjugated Ex4. While Flex robustly penetrates into the brain (dorsal vagal complex, paraventricular hypothalamus), Cy5-B12 and Cy5-B12-Ex4 fluorescence were not observed centrally, supporting an absence of CNS penetrance, in line with observed reduction in CNS-associated Ex4 side effects. Cy5-B12-Ex4 colocalizes with insulin in the pancreas, suggesting direct pancreatic action as a potential mechanism underlying the hypoglycaemic effects of B12-Ex4. These novel findings highlight the potential clinical utility of B12-Ex4 conjugates as possible future T2DM therapeutics with reduced incidence of adverse effects. © 2018 John Wiley & Sons Ltd.

Neck injury tolerance under inertial loads in side impacts.

PubMed

McIntosh, Andrew S; Kallieris, Dimitrios; Frechede, Bertrand

2007-03-01

Neck injury remains a major issue in road safety. Current side impact dummies and side impact crashworthiness assessments do not assess the risk of neck injury. These assessments are limited by biofidelity and knowledge regarding neck injury criteria and tolerance levels in side impacts. Side impact tests with PMHS were performed at the Heidelberg University in the 1980s and 1990s to improve primarily the understanding of trunk dynamics, injury mechanisms and criteria. In order to contribute to the definition of human tolerances at neck level, this study presents an analysis of the head/neck biomechanical parameters that were measured in these tests and their relationship to neck injury severity. Data from 15 impact tests were analysed. Head accelerations, and neck forces and moments were calculated from 9-accelerometer array head data, X-rays and anthropometric data. Statistically significant relationships were observed between resultant head acceleration and neck force and neck injury severity. The average resultant head acceleration for AIS 2 neck injuries was 112 g, while resultant neck force was 4925 N and moment 241 Nm. The data compared well to other test data on cadavers and volunteers. It is hoped that the paper will assist in the understanding of neck injuries and the development of tolerance criteria.

[Bright light therapy in pregnant women depression--3 case studies].

PubMed

Krzystanek, Marek; Krupka-Matuszczyk, Irena

2006-01-01

Bright light therapy (BLT) is a new method of biological treatment in psychiatry. Good tolerance makes it an attractive method used not only in seasonal affective disorder. An episode of depression during pregnancy may be a new indication. The study aimed to describe effects of treatment of depression in 3 pregnant women. The women were out-patients in their 6-th, 7-th and 8-th months of pregnancy and diagnosed with depression according to ICD-10 criteria. The treatment was a morning exposure to 1 hour 5 000 LUX bright light from Monday to Friday. The antidepressant effect was assessed after the 2nd and 4th week of BLT. Side effects of BLT were monitored over the whole BLT treatment period. The mean improvement of depressive symptoms after 2 and 4 weeks of BLT was 33% and 55%, respectively. Side effects were not observed in any of the patients. Morning BLT seems to be an effective and a very well tolerated mode of treatment of pregnant women suffering from non-seasonal depression. The manner and length of BLT maintenance treatment requires further studies.

Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

PubMed

Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

2015-04-01

To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Synthesis, Modeling, and Pharmacological Evaluation of UMB 425, a Mixed μ Agonist/δ Antagonist Opioid Analgesic with Reduced Tolerance Liabilities

PubMed Central

2013-01-01

Opioid narcotics are used for the treatment of moderate-to-severe pain and primarily exert their analgesic effects through μ receptors. Although traditional μ agonists can cause undesired side effects, including tolerance, addition of δ antagonists can attenuate said side effects. Herein, we report 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor synthesized from thebaine. Although UMB 425 lacks δ-specific motifs, conformationally sampled pharmacophore models for μ and δ receptors predict it to have efficacy similar to morphine at μ receptors and similar to naltrexone at δ receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. As predicted, UMB 425 exhibits a mixed μ agonist/δ antagonist profile as determined in receptor binding and [35S]GTPγS functional assays in CHO cells. In vivo studies in mice show that UMB 425 displays potent antinociception in the hot plate and tail-flick assays. The antinociceptive effects of UMB 425 are blocked by naloxone, but not by the κ-selective antagonist norbinaltorphimine. During a 6-day tolerance paradigm, UMB 425 maintains significantly greater antinociception compared to morphine. These studies thus indicate that, even in the absence of δ-specific motifs fused to the C-ring, UMB 425 has mixed μ agonist/δ antagonist properties in vitro that translate to reduced tolerance liabilities in vivo. PMID:23713721

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Cancer.gov

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

PubMed

Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

2013-01-01

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

PubMed

Trcka, Jiri; Seitz, Cornelia S; Bröcker, Eva-B; Gross, Gerd E; Trautmann, Axel

2007-07-01

Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Diuretics in primary hypertension - Reloaded.

PubMed

Mishra, Sundeep

Diuretics have long been cherished as drugs of choice for uncomplicated primary hypertension. Robust mortality and morbidity data is available for diuretics to back this strategy. Off-late the interest for diuretics has waned off perhaps due to availability of more effective drugs but more likely due to perceived lack of tolerance and side-effect profile of high-dose of diuretics required for mortality benefit. Low-dose diuretics particularly thiazide diuretics are safer but lack the mortality benefit shown by high-dose. However, indapamide and low dose chlorthalidone have fewer side-effects but continue to provide mortality benefit. Copyright © 2016. Published by Elsevier B.V.

Beta-blockers in the management of hypertension: focus on nebivolol.

PubMed

Wojciechowski, David; Papademetriou, Vasilios

2008-04-01

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.

Variation in sulfide tolerance of photosystem II in phylogenetically diverse cyanobacteria from sulfidic habitats

NASA Technical Reports Server (NTRS)

Miller, Scott R.; Bebout, Brad M.

2004-01-01

Physiological and molecular phylogenetic approaches were used to investigate variation among 12 cyanobacterial strains in their tolerance of sulfide, an inhibitor of oxygenic photosynthesis. Cyanobacteria from sulfidic habitats were found to be phylogenetically diverse and exhibited an approximately 50-fold variation in photosystem II performance in the presence of sulfide. Whereas the degree of tolerance was positively correlated with sulfide levels in the environment, a strain's phenotype could not be predicted from the tolerance of its closest relatives. These observations suggest that sulfide tolerance is a dynamic trait primarily shaped by environmental variation. Despite differences in absolute tolerance, similarities among strains in the effects of sulfide on chlorophyll fluorescence induction indicated a common mode of toxicity. Based on similarities with treatments known to disrupt the oxygen-evolving complex, it was concluded that sulfide toxicity resulted from inhibition of the donor side of photosystem II.

B cells in operational tolerance.

PubMed

Chesneau, M; Danger, R; Soulillou, J-P; Brouard, S

2018-05-01

Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunosuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal. This review summarizes studies that suggest a role for B cells as biomarkers of operational tolerance and discusses the use of B cells as a predictive tool for immunologic risk. Copyright © 2018. Published by Elsevier Inc.

Effects of granulocyte-colony-stimulating factor on potential normal granulocyte donors.

PubMed

McCullough, J; Clay, M; Herr, G; Smith, J; Stroncek, D

1999-10-01

The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.

Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs.

PubMed

Löscher, Wolfgang; Schmidt, Dieter

2006-08-01

Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists.

Nourkrin: objective and subjective effects and tolerability in persons with hair loss.

PubMed

Thom, E

2006-01-01

This randomized, double-blind, placebo-controlled study was designed to investigate the efficacy and tolerability of Nourkrin, a new natural agent for the treatment of hair loss based on marine proteins, and minerals and vitamins. Fifty-five subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments showed a significant positive effect of treatment on hair growth. Intake of the active preparation for a further 6 months in an open phase indicated a subjective further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. Nourkrin may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenetic alopecia.

Highly methanol-tolerant platinum electrocatalyst derived from poly(vinylpoyrrolidone) coating

NASA Astrophysics Data System (ADS)

Yang, Zehui; Ling, Ying; Zhang, Yunfeng; Yang, Ming

2017-02-01

The design and fabrication of a methanol-tolerant electrocatalyst is still one of the most important issues in direct methanol fuel cells (DMFCs). Here, we focus on the design of a cathodic electrocatalyst in DMFCs and describe a new methanol-tolerant electrocatalyst fabricated from poly(vinylpyrrolidone) (PVP) coating on platinum nanoparticles assisted by hydrogen bonding between PVP and polybenzimidazole (PBI). The PVP layer has a negligible effect on the oxygen reduction reaction (ORR) activity, while the methanol oxidation reaction is retarded by the PVP layer. The PVP-coated electrocatalyst shows higher ORR activity under various methanol concentrations in the electrolyte, suggesting that the PVP-coated electrocatalyst has a higher methanol tolerance. Also, the PVP-coated electrocatalyst loses only 14% of the electrochemical surface area after 5000 potential cycles from 0.6-1.0 V versus the reversible hydrogen electrode, indicating better Pt stability than non-coated (27%) and commercial (38%) electrocatalysts due to the unique sandwich structure formed by the PVP and PBI. The power density of the PVP-coated electrocatalyst is four to five times higher compared to non-coated and commercial electrocatalysts with 12 M methanol feeding to the anode side, respectively. PVP coating is important for the enhancement of Pt stability and methanol tolerance. This study offers a new method for preparing a low-cost and high-methanol-tolerant Pt electrocatalyst, and useful information for real DMFC application to eliminate the methanol crossover problem in the cathode side.

Analgesic tolerance to morphine is regulated by PPARγ

PubMed Central

de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Stopponi, Serena; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2014-01-01

Background and Purpose Opioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice. Experimental Approach We monitored analgesia on alternate days using the tail immersion test. Key Results Daily administration of morphine (30 mg·kg−1, bid) resulted in the rapid development of tolerance to thermal analgesia. Co-administration of pioglitazone (10 and 30 mg·kg−1, bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW-9662 (5 mg·kg−1, bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW-9662 and a lower dose of morphine (15 mg·kg−1, bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild-type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance. Conclusions and Implications Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse. PMID:25048682

Feasibility of transcranial direct current stimulation use in children aged 5 to 12 years.

PubMed

Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Allegro, Juleilda Valéria Brasil Nunes; Neto, Carlos Eduardo Borges Passos; Lucena, Rita de Cássia Saldanha; Fregni, Felipe

2014-10-01

Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. © The Author(s) 2013.

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

PubMed

Osei, Elizabeth; Fonville, Susanne; Zandbergen, Adrienne A M; Brouwers, Paul J A M; Mulder, Laus J M M; Lingsma, Hester F; Dippel, Diederik W J; Koudstaal, Peter J; den Hertog, Heleen M

2015-08-05

Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance. NTR3196 , Date of registration: 15 December 2011.

[Initial experiences with amisulpride, an in Germany novel, atypical neuroleptic drug in treatment of adolescents with psychiatric disorders].

PubMed

Göpel, C; Marcus, A

2001-08-01

In addition to conventional antipsychotic drugs, during the past decade an increasing number of atypical neuroleptics has been introduced in the treatment of juvenile schizophrenic and schizoaffective disorders. In 1999 Germany legalized the benzamide amisulpride for the treatment of acute and chronic schizophrenic symptoms. Preliminary treatment results are reported here. Ten adolescent cases are presented with regard to the efficacy, side effects and dosage of amisulpride. Preliminary results on the use of amisulpride are promising. The rate of side effects is tolerable. Amisulprise seems to constitute a useful alternative in the treatment of juvenile schizophrenia for those who suffer from intolerable side effects of classical or atypical neuroleptics. Controlled studies are warranted to further clarify its efficacy and safety in the treatment of adolescents.

Ovarian cancer survivors' acceptance of treatment side effects evolves as goals of care change over the cancer continuum.

PubMed

Frey, Melissa K; Ellis, Annie E; Koontz, Laura M; Shyne, Savannah; Klingenberg, Bernhard; Fields, Jessica C; Chern, Jing-Yi; Blank, Stephanie V

2017-08-01

Women with ovarian cancer can have long overall survival and goals of treatment change over time from cure to remission to stable disease. We sought to determine whether survivors' acceptance of treatment side effects also changes over the disease continuum. Women with ovarian cancer completed an online survey focusing on survivors' goals and priorities. The survey was distributed through survivor networks and social media. Four hundred and thirty-four women visited the survey website and 328 (76%) completed the survey. Among participants, 141 (43%) identified themselves as having ever recurred, 119 (36%) were undergoing treatment at the time of survey completion and 86 (26%) had received four or more chemotherapy regimens. Respondents' goals of care were cure for 115 women (35%), remission for 156 (48%) and stable disease for 56 (17%). When asked what was most meaningful, 148 women (45%) reported overall survival, 135 (41%) reported quality of life and 40 (12%) reported progression-free survival. >50% of survivors were willing to tolerate the following symptoms for the goal of cure: fatigue (283, 86%), alopecia (281, 86%), diarrhea (232, 71%), constipation (227, 69%), neuropathy (218, 66%), arthralgia (210, 64%), sexual side effects (201, 61%), reflux symptoms (188, 57%), memory loss (180, 55%), nausea/vomiting (180, 55%), hospitalization for treatment side effects (179, 55%) and pain (169, 52%). The rates of tolerance for most symptoms decreased significantly as the goal of treatment changed from cure to remission to stable disease. Women with ovarian cancer willingly accept many treatment side effects when the goal of treatment is cure, however become less accepting when the goal is remission and even less so when the goal is stable disease. Physicians and survivors must carefully consider treatment toxicities and quality of life effects when selecting drugs for patients with incurable disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

PubMed Central

Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

2015-01-01

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps.

PubMed

Reckow, Jaclyn; Rahman-Filipiak, Annalise; Garcia, Sarah; Schlaefflin, Stephen; Calhoun, Oliver; DaSilva, Alexandre F; Bikson, Marom; Hampstead, Benjamin M

2018-05-04

Transcranial direct current stimulation (tDCS) is an in-demand form of neuromodulation generally regarded as safe and well tolerated. However, few studies have examined the safety, tolerability, or blinding of High Definition (HD-) tDCS, especially in older adults and at stimulation intensities of 2 milliamps (mA) or greater. We examined the rates of serious adverse events and common side effects to establish safety and tolerability, respectively, in HD-tDCS. Blinding was evaluated using participants' accuracy in correctly stating their condition (i.e., active or sham). The sample included 101 older adults (M age  = 69.69, SD = 8.33; M educ  = 16.27, SD = 2.42) who participated in our double blind randomized controlled studies or in case studies that used HD-tDCS for 20-30 min at 2 mA (n = 66, 31 active) or 3 mA (n = 35, 20 active). Participants completed a standardized side effect questionnaire and were asked whether they received active or sham stimulation at the end of each session. There were no serious adverse events and no participants withdrew, suggesting that HD-tDCS meets basic safety parameters. Tolerability was comparable between active and sham HD-tDCS regardless of intensity (2 mA and 3 mA) in first session (allp > .09). Tingling was the most commonly endorsed item (59% active; 56% sham) followed by burning sensation (51% active; 50% sham), the majority of which were mild in nature. "Severe" ratings were reported in fewer than 4% of sessions. Blinding appeared adequate since there were no significant group differences between individuals correctly stating their stimulation condition (χ2 = 0.689, p = .679). The above tolerability and blinding findings generally persisted when multiple session data (i.e., 186 total sessions) were considered. HD-tDCS appears well-tolerated and safe with effective sham-control in older adults, even at 3 mA. These data support the use of HD-tDCS in randomized controlled trials and clinical translation efforts. Published by Elsevier Inc.

A comparison of the efficacy and tolerability of oxcarbazepine oral suspension between infants and children with epilepsy: a retrospective chart review at a single medical center in Taiwan.

PubMed

Wei, Shu-Hao; Liu, Cheng-Chao; Fan, Pi-Chuan

2014-02-01

Few clinical studies have assessed the efficacy and safety of oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly in infants. The aim of this study was to investigate and compare the efficacy, tolerability, and side effects of OXC oral suspension in Taiwanese infants and children with various types of epilepsy. A retrospective review of the efficacy, tolerability, and side effects of OXC oral suspension in a tertiary medical center in Taiwan was conducted and included children (1-9 years old) and infants (<1 year old) diagnosed with epilepsy, which was classified into idiopathic partial, symptomatic partial, or multifocal subtypes. The OXC oral suspension (Trileptal(®); Novartis) was given in a gradual dose titration, from an initial 7.5 mg/kg/day to 30 mg/kg/day within 1 month in all cases. A total of 20 infants and 38 children were identified. There were no statistically significant differences between the children and infants in efficacy (75 vs. 82 %, p = 0.734) and adverse effects (30 vs. 21 %, p = 0.525) after OXC oral suspension treatment. The efficacy was significantly correlated with the epilepsy subtype (p < 0.01) and the number of combined antiepileptic drugs (AEDs) before OXC treatment (p < 0.01) in both groups. The patients with idiopathic and symptomatic partial epilepsy responded better to OXC oral suspension than those with multifocal epilepsy. OXC oral suspension is effective and well tolerated in both infants and children with partial epilepsy in Taiwan. Treatment efficacy was related to epilepsy subtype and number of combined AEDs before OXC treatment. Monotherapy had an excellent therapeutic response in partial epilepsy but not in multifocal epilepsy.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

PubMed Central

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. PMID:28721057

Pharmacological Issues for Astronauts

NASA Technical Reports Server (NTRS)

Wotring, Virginia E.

2010-01-01

Medication-induced side effects, called untoward effects by pharmacologists, can be a problem with any medication. Few therapies are perfectly specific for the desired physiological activity; rather they act on multiple biological targets and result in multiple physiological effects. There are several strategies that are employed to prevent, alleviate or counteract medication-induced side effects. The administered dose may be optimized to the lowest possible amount that provides the desired therapeutic effect, with the expectation that untoward effects will be minimized by a lower dose. Empirical trials of different therapies for a particular medical problem may be used in the hopes of finding a drug with minimal side effects for a particular patient, or at least of finding a set of side effects that the patient considers tolerable. If these two strategies have been exhausted, it may be possible to administer another medication to block or ameliorate side effects. A recent search of published scientific literature has revealed that there are medications used in spaceflight that seem to be associated with a significant number of reports of untoward effects. To prevent future medical problems and to improve the well-being and productivity of crew members, it would be best to eliminate (or at least reduce) untoward effects. Reports from the literature will be examined, with the aim of identifying a strategy for reducing untoward effects.

The Precautionary Principle and the Tolerability of Blood Transfusion Risks.

PubMed

Kramer, Koen; Zaaijer, Hans L; Verweij, Marcel F

2017-03-01

Tolerance for blood transfusion risks is very low, as evidenced by the implementation of expensive blood tests and the rejection of gay men as blood donors. Is this low risk tolerance supported by the precautionary principle, as defenders of such policies claim? We discuss three constraints on applying (any version of) the precautionary principle and show that respecting these implies tolerating certain risks. Consistency means that the precautionary principle cannot prescribe precautions that it must simultaneously forbid taking, considering the harms they might cause. Avoiding counterproductivity requires rejecting precautions that cause more harm than they prevent. Proportionality forbids taking precautions that are more harmful than adequate alternatives. When applying these constraints, we argue, attention should not be restricted to harms that are human caused or that affect human health or the environment. Tolerating transfusion risks can be justified if available precautions have serious side effects, such as high social or economic costs.

‘Side effects’ are ‘central effects’ that challenge retention in HIV treatment programmes in six sub-Saharan African countries: a multicountry qualitative study

PubMed Central

McLean, Estelle; Ddaaki, William; Odongo, Fred; Bukenya, Dominic; Wamoyi, Joyce; Bonnington, Oliver; Seeley, Janet; Zaba, Basia; Wringe, Alison

2017-01-01

Objectives To explore the bodily and relational experience of taking antiretroviral therapy (ART) and the subsequent effect on retention in HIV care in six sub-Saharan African countries. Methods In-depth interviews were conducted with 130 people living with HIV (PLHIV) who had initiated ART, 38 PLHIV who were lost to follow-up and 53 healthcare workers (HCWs) in Kenya, Uganda, Tanzania, Malawi, Zimbabwe and South Africa. PLHIV were purposely selected to include a range of HIV treatment histories. Deductive and inductive analysis was guided by aspects of practice theory; retention in HIV care following ART initiation was the practice of interest. Results PLHIV who were engaged in HIV care took ART every day, attended clinic appointments and ate as well as possible. For PLHIV, biomedical markers acted as reassurance for their positive treatment progression. However, many described ART side effects ranging from dizziness to conditions severe enough to prevent them from leaving home or caring for themselves or others. In all settings, the primary concern of HCW was ensuring patients achieved viral suppression, with management of side effects seen as a lower priority. Where PLHIV tolerated side effects, they were deemed the lesser of two evils compared with their pre-ART illnesses. Participants who reported feeling well prior to starting ART were often less able to tolerate side effects, and in many cases these events triggered their disengagement from HIV care. Conclusions Retention in ART care is rarely an outcome of rational decision-making, but the consequence of bodily and relational experiences. Initiatives to improve retention should consider how bodily experiences of PLHIV relate to the rest of their lives and how this can be respected and supported by service providers to subsequently improve retention in care. PMID:28736390

Are Senna based laxatives safe when used as long term treatment for constipation in children?

PubMed

Vilanova-Sanchez, Alejandra; Gasior, Alessandra C; Toocheck, Nicole; Weaver, Laura; Wood, Richard J; Reck, Carlos A; Wagner, Andrea; Hoover, Erin; Gagnon, Renae; Jaggers, Jordon; Maloof, Tassiana; Nash, Onnalisa; Williams, Charae; Levitt, Marc A

2018-04-01

Senna is a stimulant laxative commonly used by pediatricians, pediatric gastroenterologists, and pediatric surgeons. Many clinicians avoid Senna for reasons such as tolerance or side effects but this has little scientific justification. We recently found several patients we were caring for developed perineal blistering during the course of Senna treatment. Because of this we chose to review the literature to identify side effects in children taking this medication as well as to analyze our Center's experience with Senna's secondary effects. We performed a literature review (MEDLINE, PUBMED) using the keywords of Senna, sen, sennosides and children, and pediatric and functional (idiopathic) constipation. We looked for articles with information regarding perineal blisters related to Senna as well as other secondary effects of Senna laxatives in children when used on a long-term basis. We also reviewed the charts of our patients who had previously taken Senna or are currently taking Senna, looking for adverse reactions. Eight articles in the literature reported perineal blisters after administration of Senna laxatives in 28 patients. Of those occurrences, 18 patients (64%) had accidental administration of Senna and 10 (36%) had Senna prescribed as a long term treatment. All of the blistering episodes were related to high dose, night-time accidents, or intense diarrhea with a long period of stool to skin contact. At our institution, from 2014 to 2017, we prescribed Senna and have recorded data to 640 patients. During the study period, 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60mg/day; 60 [12-100] vs. 17.5 [1.7-150] (p<0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact. 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea which resolved once the type of laxatives were changed or enemas were started. The doses of Senna was not significantly different in these patients 15mg/day [4.4-150] vs. 17.5mg/day [1.5-150]. There were no other long-term side effects from Senna found in the pediatric literature for long-term treatment besides abdominal cramping or diarrhea during the first weeks of administration. We found no evidence of tolerance to Senna in our review. There is a paucity of information in the literature regarding side effects of sennosides as a long-term therapy, and to our knowledge, this is the first review of Senna side effects in children. Senna induced dermatitis is rare, but may occur when patients need a higher dose. All of the cases described had a long period of exposure of the skin to stool. Besides the perineal rash with blisters, we could find no other described major side effect with Senna administration in the pediatric population or evidence of the frequently mentioned concern of the development of tolerance to Senna. Pediatric caregivers should advise families of the rare side effect of skin blistering and educate them to change the diaper frequently in children who are not toilet- trained to reduce stool to skin exposure. We can conclude from this review that Senna is a safe treatment option for constipation in children. IV. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy and tolerability of Hairgain in individuals with hair loss: a placebo-controlled, double-blind study.

PubMed

Thom, E

2001-01-01

This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of a new agent for the treatment of hair loss, based on a marine protein, minerals and vitamins. Sixty subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments indicated that the treatment was effective and subjective assessments showed a statistically significant positive effect of treatment. Exposure to the active preparation for a further 6 months in an open phase indicated a further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. The product investigated may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenic alopecia.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Methylphenidate Abuse and Psychiatric Side Effects

PubMed Central

Morton, W. Alexander; Stockton, Gwendolyn G.

2000-01-01

Methylphenidate is a central nervous system stimulant drug that has become the primary drug of choice in treating attention-deficit/hyperactivity disorder in children. Side effects are usually mild and are generally well tolerated by patients. Along with increases in prescribing frequency, the potential for abuse has increased. Intranasal abuse produces effects rapidly that are similar to the effects of cocaine in both onset and type. The clinical picture of stimulant abuse produces a wide array of psychiatric symptoms. There is little in the literature to differentiate methylphenidate from other stimulants when they are abused. The need for education of all involved with the use of methylphenidate is discussed to help prevent an increasing pattern of methylphenidate abuse. PMID:15014637

Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week, noninferiority, randomized, crossover, pilot study.

PubMed

Cilia, Roberto; Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Raspini, Benedetta; Barichella, Michela; Pezzoli, Gianni

2018-04-01

Thousands of individuals with Parkinson's disease (PD) in low-income countries have limited access to marketed levodopa preparations. Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in tropical areas, may be a sustainable alternative therapy for indigent patients. Single-dose intake of MP proved noninferior to marketed levodopa preparations. Fourteen PD patients with motor fluctuations and dyskinesias received MP powder (obtained from roasted seeds) and marketed levodopa/carbidopa (LD/CD) in a randomized order and crossover design over a 16-week period. Efficacy measures were changes in quality of life, motor and non-motor symptoms, and time with good mobility without troublesome dyskinesias. Safety measures included tolerability, frequency of adverse events, changes in laboratory indices and electrocardiogram. Daily intake of MP was associated with a variable clinical response, especially in terms of tolerability. Seven patients (50%) discontinued MP prematurely due to either gastrointestinal side-effects (n = 4) or progressive worsening of motor performance (n = 3), while nobody discontinued during the LD/CD phase. In those who tolerated MP, clinical response to MP was similar to LD/CD on all efficacy outcome measures. Patients who dropped out entered a study extension using MP supernatant water (median[IQR], 16 [7-20] weeks), which was well tolerated. The overall benefit provided by MP on the clinical outcome was limited by tolerability issues, as one could expect by the relatively rapid switch from LD/CD to levodopa alone in advanced PD. Larger parallel-group studies are needed to identify appropriate MP formulation (e.g. supernatant water), titration scheme and maintenance dose to minimize side-effects in the long-term. CLINICAL TRIALS. NCT02680977. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability.

PubMed

Crowley, Rachel Saylor; Riley, Andrew P; Sherwood, Alexander M; Groer, Chad E; Shivaperumal, Nirajmohan; Biscaia, Miguel; Paton, Kelly; Schneider, Sebastian; Provasi, Davide; Kivell, Bronwyn M; Filizola, Marta; Prisinzano, Thomas E

2016-12-22

Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC 50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased activator of MOR-induced G-protein signaling over β-arrestin-2 recruitment. Metadynamics simulations of 5's binding to a MOR crystal structure suggest energetically preferred binding modes that differ from crystallographic ligands. In vivo studies with 5 demonstrate centrally mediated antinociception, significantly reduced rewarding effects, tolerance, and sedation. We propose that this novel MOR agonist may represent a valuable tool in distinguishing the pathways involved in MOR-induced analgesia from its side effects.

Clinical experience with molindone hydrochloride in geriatric patients.

PubMed

Peper, M

1985-08-01

Elderly patients (N = 28) with a variety of psychiatric disorders were treated with molindone in an 8-week open clinical trial. Many patients had concomitant medical illnesses, and many were on other medications in addition to molindone. Molindone appeared to be safe, clinically effective, and well-tolerated. The most common adverse effects were extrapyramidal side effects, but the occurrence of these symptoms was relatively low.

Anti-Emetic Drug Effects on Performance Phase 1: Laboratory Study.

DTIC Science & Technology

1995-12-01

The objectives of this study were to evaluate the effects of two anti-emetic drugs, granisetron ( 2 mg p.o.) and ondansetron ( 8 mg p.o.) on basic...drugs of interest, granisetron and ondansetron, were extremely well tolerated and with no obvious side effects when compared to the placebo condition...evidence of any cognitive, psychomotor or subjective state changes caused by either granisetron or ondansetron.

Opioid adjuvant strategy: improving opioid effectiveness.

PubMed

Bihel, Frédéric

2016-01-01

Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain

PubMed Central

Forst, Thomas; Smith, Terry; Schütte, Klemens; Marcus, Paul; Pfützner, Andreas

2007-01-01

What is already known about this subject Despite encouraging effects of N-methyl-D-aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side-effects. In a recent study in healthy volunteers, CNS 5161, a novel noncompetetive NMDA receptor antagonist, was well tolerated up to a dosage of 2000 µg without psychotropic side-effects. This is the first study to evaluate the maximal tolerated dosage of CNS 5161 and to gain experience about the analgesic effect of CNS 5161 in patients with different pain syndromes. What this study adds In patients with neuropathic pain CNS 5161 is well tolerated up to a dosage of 500 µg with the most common side-effect of increasing blood pressure, mild visual disturbances and headaches. While no therapeutic effect can be observed in a dosage up to 250 µg, treatment with 500 µg CNS 5161 provides some indications of analgesic activity. It appears that this effect occurs predominantly in patients with diabetic neuropathy. Aims The purpose of the current study was to establish the safety and maximal tolerated dose of CNS 5161 HCl. Methods Forty patients with chronic neuropathic pain (23 male, 17 female) were treated with escalating dosages of CNS 5161. All adverse events to study drug, blood pressure, heart rate, ECG, drug level and clinical laboratory values were monitored. Actual pain was measured on a 100-mm visual analogue scale (VAS) and ordinal verbal pain scores. Results The most commonly occurring nervous system disorder was headache, which was found more often during placebo than during CNS 5161 HCl treatment. Visual disturbances were experienced by 16.7% of patients receiving 250 µg and by 33.3% receiving 500 µg CNS 5161 HCl, but not during placebo treatment. An increase in blood pressure was observed in 8.3% of patients receiving 250 µg and in 50% of patients receiving 500 µg CNS 5161 HCl, compared with 15.4% during placebo treatment. The study was abandoned after two patients entered the 750 µg cohort due to a sustained systolic blood pressure response. Although this study was underpowered for the confirmation of efficacy, some indications of greater pain relief after 500 µg CNS 5161 compared with placebo could be observed (change in VAS between baseline and 12 h 10 ± 22 mm vs. 2 ± 19 mm; P = 0.11). Conclusions CNS 5161 HCl was reasonably well tolerated up to 500 µg. The most common adverse events were hypertension, headache and mild visual disorders. PMID:17391323

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

An examination of the damage tolerance enhancement of carbon/epoxy using an outer lamina of spectra (R)

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1991-01-01

Low velocity instrumented impact testing was utilized to examine the effects of an outer lamina of ultra-high molecular weight polyethylene (Spectra) on the damage tolerance of carbon epoxy composites. Four types of 16-ply quasi-isotropic panels (0, +45, 90, -45) were tested. Some panels contained no Spectra, while others had a lamina of Spectra bonded to the top (impacted side), bottom, or both sides of the composite plates. The specimens were impacted with energies up to 8.5 J. Force time plots and maximum force versus impact energy graphs were generated for comparison purposes. Specimens were also subjected to cross-sectional analysis and compression after impact tests. The results show that while the Spectra improved the maximum load that the panels could withstand before fiber breakage, the Spectra seemingly reduced the residual strength of the composites.

Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients.

PubMed

Lee, Sue J; Ter Kuile, Feiko O; Price, Ric N; Luxemburger, Christine; Nosten, François

2017-01-01

Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

PubMed Central

Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.

2011-01-01

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression. PMID:19687192

Clinical trial tests new schedule of radiation therapy for recurring prostate cancer | Center for Cancer Research

Cancer.gov

In order to find the most compressed schedule of radiation that prostate cancer patients can tolerate without strong side effects, Deborah Citrin, M.D., of the Radiation Oncology Branch wants to see if giving higher doses of radiation over 2–4 weeks can be as effective at killing cancer cells. Read more… 

Human tolerance to a single, high dose of D-tagatose.

PubMed

Buemann, B; Toubro, S; Raben, A; Astrup, A

1999-04-01

The addition of 29 g D-tagatose added as a sweetener to a continental breakfast was tested for the appearance of gastrointestinal side effects in a double-blind randomized cross-over study with 29 g sucrose as a control treatment. The subjects reported the side effects during 72 h following the test meal on a questionnaire grading the symptoms on a five-level scale ranging from "none" to "very strong." Although "rumbling in the stomach," "distention," "nausea," "rumbling in the gut," "flatulence, " and "diarrhea" scored significantly higher with D-tagatose, the sugar otherwise was well tolerated in most of the subjects. Two cases of vomiting after D-tagatose were recorded but in one of the cases its relation to the D-tagatose intake was questionable. Only the "distention" score remained higher with D-tagatose for more than 24 h. Nausea, vomiting, and perceived distension may be due to an osmotic effect in the small intestine of unabsorbed D-tagatose. The increased flatus is caused by D-tagatose being fermented in the large intestine. Diarrhea may be explained by osmotic effects in the colon from nondegraded D-tagatose or nonabsorbed short-chain fatty acids produced by the increased fermentation. Copyright 1999 Academic Press.

Picoprep-3 is a superior colonoscopy preparation to Fleet: a randomized, controlled trial comparing the two bowel preparations.

PubMed

Schmidt, Liu-Ming; Williams, Pamela; King, Denis; Perera, Dayashan

2004-02-01

Bowel preparations for colonoscopy have to balance the demand for adequate cleansing action of the bowel and patient acceptability. There has been no study comparing Picoprep-3 (sodium picosulfate), a relatively new product, to Fleet (sodium phosphate), a well-studied and widely used preparation. This study was designed to compare the efficacy and patient tolerance of these two bowel preparations for colonoscopy. A randomized, single-blinded, prospective trial was conducted. A total of 400 consecutive patients presenting for elective colonoscopy at St George Private Hospital during a 20-week period were randomly assigned to receive Picoprep-3 or Fleet. Patients were asked to record the effects of the preparation, noting tolerability, taste, and side effects. Two hundred patients were assigned to the Picoprep-3 group and 200 to the Fleet group. Surgeons were blinded to the preparation used and rated the quality of the bowel preparation on a scale of 1 to 5 (1 being the optimal score). Picoprep-3 was found to be better tolerated (P < 0.0001) and better tasting (P < 0.0001) than Fleet. Patients in the Picoprep-3 group reported significantly less nausea (P < 0.001), vomiting (P < 0.004), dizziness (P < 0.01), abdominal pains (P = 0.0005), and thirst (P < 0.0001) associated with the preparation. There was no significant difference in visualization of the colon between the two groups as judged by the two colonoscopists (P = 0.06). Colonoscopy preparation with Picoprep-3 has similar efficacy but superior taste and tolerability compared with Fleet. Picoprep-3 caused less adverse side effects in the study population.

Intense pulsed light versus photodynamic therapy using liposomal methylene blue gel for the treatment of truncal acne vulgaris: a comparative randomized split body study.

PubMed

Moftah, Nayera Hassan; Ibrahim, Shady Mahmoud; Wahba, Nadine Hassan

2016-05-01

Acne vulgaris is an extremely common skin condition. It often leads to negative psychological consequences. Photodynamic therapy (PDT) using intense pulsed light has been introduced for effective treatment of acne. The objective was to study the effect of PDT in truncal acne vulgaris using liposomal methylene blue (LMB) versus IPL alone. Thirty-five patients with varying degrees of acne were treated with topical 0.1 % LMB hydrogel applied on the randomly selected one side of the back, and after 60 min the entire back was exposed to IPL. The procedure was done once weekly for three sessions and patients were re-evaluated 1 month after the third session by two independent dermatologists. Acne severity was graded using the Burton scale. Patient satisfaction using Cardiff Acne Disability Index (CADI) was recorded before and after treatment. On LMB-pretreated side, inflammatory acne lesion counts were significantly decreased by 56.40 % compared with 34.06 % on IPL alone. Marked improvement was seen on LMB-pretreated side in 11.5 % of patients compared with 2.8 % on IPL alone. There was a correlation between CADI score and overall improvement. Our study concluded that LMB-IPL is more effective than IPL alone, safe with tolerable pain in the treatment of acne vulgaris on the back. LMB-IPL is more effective than IPL alone, safe with tolerable pain in the treatment of acne vulgaris on the back.

Initial study of transdermal oxybutynin for treating hyperhidrosis.

PubMed

Millán-Cayetano, José Francisco; Del Boz, Javier; Toledo-Pastrana, Tomas; Nieto-Guindo, Miriam; García-Montero, Pablo; de Troya-Martín, Magdalena

2017-06-01

Oral oxybutynin for treating hyperhidrosis is effective and safe. Its side-effects are mild but frequent so we consider whether transdermal oxybutynin (considered to have a better side-effect profile) could be an alternative for treating hyperhidrosis. During 2015, a prospective study was conducted. Epidemiological variables, effectiveness (using the Hyperhidrosis Disease Severity Scale) and tolerance to transdermal oxybutynin were compiled concerning two different groups (patients previously treated or untreated with oral oxybutynin), at baseline, and at 3 and 12 months. Seven previously treated and six previously untreated patients were included. Five patients in the first group discontinued the treatment within 3 months. Of the two remaining patients, one reported ineffectiveness and the other obtained an excellent response but discontinued due to local irritation. Among the untreated patients, two showed no response and four experienced improvement (three with "partial response" and one with "excellent response"). All patients discontinued treatment within 12 months. No major adverse effects were observed. The absence of active metabolites after transdermal oxybutynin could result in less effectiveness than oral oxybutynin, although it is usually well tolerated. In conclusion, transdermal oxybutynin could have low effectiveness for the treatment of hyperhidrosis in patients following intolerance to oral oxybutynin but could provide good results in patients who have never tried systemic drugs. © 2017 Japanese Dermatological Association.

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

PubMed

Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M

2015-10-14

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.

Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI).

PubMed

Dunbar, Geoffrey C; Inglis, Fraser; Kuchibhatla, Ramana; Sharma, Tonmoy; Tomlinson, Mark; Wamsley, James

2007-03-01

Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of ispronicline in the range 50-150 mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150 mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50 mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35 ng/ml ispronicline was associated with the most beneficial effect. These early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation.

PubMed

Campistol, Josep M; Cockwell, Paul; Diekmann, Fritz; Donati, Donato; Guirado, Luis; Herlenius, Gustaf; Mousa, Dujanah; Pratschke, Johann; San Millán, Juan Carlos Ruiz

2009-07-01

m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.

Liver immunology and herbal treatment

PubMed Central

Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

2017-01-01

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

The study of CD side to side error in line/space pattern caused by post-exposure bake effect

NASA Astrophysics Data System (ADS)

Huang, Jin; Guo, Eric; Ge, Haiming; Lu, Max; Wu, Yijun; Tian, Mingjing; Yan, Shichuan; Wang, Ran

2016-10-01

In semiconductor manufacturing, as the design rule has decreased, the ITRS roadmap requires crucial tighter critical dimension (CD) control. CD uniformity is one of the necessary parameters to assure good performance and reliable functionality of any integrated circuit (IC) [1] [2], and towards the advanced technology nodes, it is a challenge to control CD uniformity well. The study of corresponding CD Uniformity by tuning Post-Exposure bake (PEB) and develop process has some significant progress[3], but CD side to side error happening to some line/space pattern are still found in practical application, and the error has approached to over the uniformity tolerance. After details analysis, even though use several developer types, the CD side to side error has not been found significant relationship to the developing. In addition, it is impossible to correct the CD side to side error by electron beam correction as such error does not appear in all Line/Space pattern masks. In this paper the root cause of CD side to side error is analyzed and the PEB module process are optimized as a main factor for improvement of CD side to side error.

Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

PubMed

Savic, Jelena; Dilber, Sanda; Milenkovic, Marina; Kotur-Stevuljevic, Jelena; Markovic, Bojan; Vladimirov, Sote; Brboric, Jasmina

2017-01-01

Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Use of methylphenidate in palliative patients with asthenia: a review].

PubMed

Saralegui, A; Palacio, P; Royo, P

2013-09-06

Asthenia (or fatigue) is one of the most common symptoms in palliative patients. Methylphenidate is currently being assessed for treating this condition. A review of related literature published to date was performed, revealing methylphenidate to be a safe drug which could decrease fatigue in palliative patients with a tolerable side-effects profile.

Levetiracetam monotherapy for treatment of structural epilepsy in dogs: 19 cases (2010-2015).

PubMed

Kelly, Darren; Raimondi, Francesca; Shihab, Nadia

2017-10-14

To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client-owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow-up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Alloreactive Regulatory T Cells Allow the Generation of Mixed Chimerism and Transplant Tolerance.

PubMed

Ruiz, Paulina; Maldonado, Paula; Hidalgo, Yessia; Sauma, Daniela; Rosemblatt, Mario; Bono, Maria Rosa

2015-01-01

The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant (NM-BMT) protocol using retinoic acid (RA)-induced alloantigen-specific Tregs, clinically available immunosuppressive drugs, and lower doses of irradiation. We demonstrate that RA-induced alloantigen-specific Tregs in addition to a NM-BMT protocol generates stable mixed chimerism and induces tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

Statistical computation of tolerance limits

NASA Technical Reports Server (NTRS)

Wheeler, J. T.

1993-01-01

Based on a new theory, two computer codes were developed specifically to calculate the exact statistical tolerance limits for normal distributions within unknown means and variances for the one-sided and two-sided cases for the tolerance factor, k. The quantity k is defined equivalently in terms of the noncentral t-distribution by the probability equation. Two of the four mathematical methods employ the theory developed for the numerical simulation. Several algorithms for numerically integrating and iteratively root-solving the working equations are written to augment the program simulation. The program codes generate some tables of k's associated with the varying values of the proportion and sample size for each given probability to show accuracy obtained for small sample sizes.

Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

PubMed

Ubl, Philipp; Gincu, Tatiana; Keilani, Mohammad; Ponhold, Lothar; Crevenna, Richard; Niederle, Bruno; Hacker, Marcus; Li, Shuren

2014-08-01

The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p < 0.05) and dizziness (p < 0.05) were significantly increased in the female patients as compared to male patients by calcium stimulation test. Significant higher incidences of urgency to micturate (p < 0.05) and warmth feeling (p < 0.05) were found by calcium stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p < 0.05) and abdominal cramping (p < 0.05) in male patients were significantly higher by pentagastrin stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

PubMed

Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S

2011-09-01

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial.

PubMed

Nearing, Bruce D; Libbus, Imad; Amurthur, Badri; Kenknight, Bruce H; Verrier, Richard L

2016-09-01

Chronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T-wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat-to-beat heart rate dynamics have not been systematically characterized in humans. We evaluated acute effects of VNS on R-R-interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM-HF trial by quantifying effects during continuous cyclic VNS (14-seconds on-time, 66-seconds off-time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10-week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right-sided stimulation (-2.22 ± 0.13 bpm) than in the 31 patients with left-sided stimulation (-0.60 ± 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R-R interval was stronger among the 28 patients with right-sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left-sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+0.08 ± 0.06 bpm, P < 0.001). Instantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left- and right-sided stimulation. © 2016 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.

Localized periorbital edema induced by Ibuprofen.

PubMed

Palungwachira, Piti; Palungwachira, Pranee; Ogawa, Hideoki

2005-12-01

We documented localized periorbital edema in one patient with ibuprofen sensitivity without underlying chronic urticaria. The reaction developed one hour after ingestion of 200 mg of ibuprofen. No systemic symptoms were observed. No other NSAIDs did not induce symptoms. This patient was able to tolerate doses of ibuprofen after pretreatment with terfenadine. These observations suggest that histamine played a central role in this ibuprofen-induced skin reaction. Treatment with terfenadine enabled the patient to tolerate ibuprofen without experiencing any side effects. To the best of our knowledge, this is the first reported case of periorbital edema induced by ibuprofen.

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

Systematic review and meta-analysis: Sodium picosulphate with magnesium citrate as bowel preparation for colonoscopy

PubMed Central

Munsterman, Isabelle D; Eskes, Anne M; Maaskant, Jolanda M; van der Hulst, René

2016-01-01

Background An effective and tolerable bowel preparation is important to secure quality of colonoscopies. It remains unclear if sodium picosulphate with magnesium citrate (SPMC), which is considered a tolerable bowel preparation agent, is also an effective alternative for polyethylene glycol (PEG) and sodium phosphate (NaP). Aim The aim of this article is to compare effectiveness of SPMC to PEG and NaP through assessment of quality of bowel cleansing measured by validated tools. Methods We searched electronic databases up to January 2015. Only randomised controlled trials (RCTs) were included. Two authors independently performed selection of studies, risk of bias assessment and data extraction. Results Thirteen RCTs were included, with overall good quality, but large heterogeneity. SPMC had slightly better quality of bowel cleansing than PEG (pooled RR 1.06; 95% CI 1.02 to 1.11). In most trials SPMC was significantly better tolerated than PEG. There were no significant differences in effectiveness or tolerability between SPMC and NaP. Side effects were similar between agents, except for dizziness (pooled RR 1.71; 95% CI 1.32 to 2.21 in favour of PEG vs. SPMC) and vomiting (pooled RR 0.35; 95% CI 0.13 to 0.95 in favour of single-dose SPMC vs. split-dose). Conclusions SPMC is equally effective to NaP and little superior to PEG in terms of bowel cleansing. SPMC preparations were better tolerated than PEG preparations. SPMC may be considered as standard bowel preparation for colonoscopy. PMID:29163958

[Therapy of intermediate uveitis].

PubMed

Doycheva, D; Deuter, C; Zierhut, M

2014-12-01

Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.

Immediate hypersensitivity to moxifloxacin with tolerance to ciprofloxacin: report of three cases and review of the literature.

PubMed

Chang, Brenda; Knowles, Sandra R; Weber, Elizabeth

2010-04-01

To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Moxifloxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.

Propranolol in Treatment of Huge and Complicated Infantile Hemangiomas in Egyptian Children

PubMed Central

Hassan, Basheir A.; Shreef, Khalid S.

2014-01-01

Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed. PMID:24899888

Propranolol in treatment of huge and complicated infantile hemangiomas in egyptian children.

PubMed

Hassan, Basheir A; Shreef, Khalid S

2014-01-01

Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed.

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

Comparative study between: Carboxytherapy, platelet-rich plasma, and tripolar radiofrequency, their efficacy and tolerability in striae distensae.

PubMed

Ahmed, Naglaa A; Mostafa, Osama M

2018-06-19

Striae distensae are very common cutaneous disorders that produce great psychological stress for women. measure and compare between efficacy and tolerability of three modalities for treatment of striae distensae. Forty-five female patients with striae distensae were randomly selected from the outpatient dermatology clinics of Al-Zahra university Hospital within 6 months period. Patients divided into three groups according to the therapeutic modalities were used. Group A: treated with carboxytherapy using carbon dioxide (CO2) injection, Group B: where patients were treated with intradermal injection of autologous platelet-rich plasma (PRP), and Group C: where we used tripolar radiofrequency (RF) for treatment. All treated groups showed overall clinical improvement as regards the width, texture, and overall improvement after treatment (P > .05), with no statistically significant differences between the three groups. Patient's satisfaction was statistically significantly better in both group C (93.33%) and group A (80%) while group B (53.33%) was less with minimal side effects such as pain and ecchymosis, which were more frequent in group B than the other two groups; but with no statistically significance differences both groups A and C were effective with no significant differences in both types of striae and in any site of the body but group B is significantly more effective on striae rubra on trunk, with better improvement of lesions texture. The three modalities of treatments proved to be effective clinically and histopathologically in treating both types of striae, which were well tolerated by the patients with minimal, transient side effects and our study results gave us guidelines for their clinical application. © 2018 Wiley Periodicals, Inc.

Toxicities of topical ophthalmic anesthetics.

PubMed

McGee, Hall T; Fraunfelder, F W

2007-11-01

Topical ocular anesthesia has been part of ophthalmology for more than a century. The most commonly used drugs today are proparacaine, tetracaine, benoxinate (oxybuprocaine) cocaine and lidocaine. Although generally well tolerated, all these can be toxic, particularly when abused. The most common toxicities are to the ocular surface, but abuse can cause deep corneal infiltrates, ulceration and even perforation. Fortunately, systemic side effects are rare. Cocaine is unique for its higher incidence of systemic side effects and high abuse potential, both of which impede its clinical use. When used appropriately, all these drugs are remarkably safe. They are generally not prescribed for home use, as prolonged abuse of these drugs can be expected to result in serious complications.

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

PubMed

Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

2017-07-01

To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

What Are the Definitive Procedures and Instruments Used to Incorporate Chemotherapy Orientation and Preparation for Effective Team Membership, During Inservice and Preservice Training of Teachers and Administrators?

ERIC Educational Resources Information Center

Schwenn, John O.

An administrator discusses aspects of drug therapy with which special educators should be familiar. Briefly examined are administration form, factors affecting rate of absorption, dosage, interaction of one drug with another, drug tolerance, time factors, and side effects. The importance of a teacher's monitoring of the drugs is stressed, and…

An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine.

PubMed

Wauters, Robert H; Hernandez, Camellia L; Petersen, Maureen M

2017-09-19

Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

Oxcarbazepine: a new drug in the management of intractable trigeminal neuralgia.

PubMed Central

Zakrzewska, J M; Patsalos, P N

1989-01-01

The efficacy and tolerability of oxcarbazepine, a keto derivative of carbamazepine, has been assessed in six patients (two males, four females; mean age 61 years, range 42-77), with trigeminal neuralgia refractory to carbamazepine therapy, over a period of 6 months. An excellent therapeutic response to oxcarbazepine was seen in all patients with pain control correlating well with serum drug concentrations of oxcarbazepine and its primary active metabolite 10-OH-carbazepine. Onset of the effect was observed within 24 hours in all cases. An overall serum therapeutic concentration range, in the six patients, of 50-110 mumol/l of 10-OH-carbazepine corresponding to a daily effective dose range of 1200-2400 mg (14.6-35.6 mg/kg body weight) oxcarbazepine, was observed. There was a significant correlation between oxcarbazepine dose and serum oxcarbazepine (r = 0.695, p less than 0.05) and 10-OH-carbazepine (r = 0.957, p less than 0.001) concentrations. Oxcarbazepine was well tolerated and no significant side effects were identified, though a mild hyponatraemia was observed during high doses (greater than 28 and greater than 35 mg/kg/day) in two patients. It is concluded that oxcarbazepine has potent antineuralgic properties in the absence of significant side effects and therefore may be useful in the management of intractable trigeminal neuralgia. Images PMID:2738589

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG).

PubMed

Shimada, Akiko; Cairns, Brian E; Vad, Nynne; Ulriksen, Kathrine; Pedersen, Anne Marie Lynge; Svensson, Peter; Baad-Hansen, Lene

2013-01-24

A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

Effects of positioning on respiratory measures in individuals with cerebral palsy and severe scoliosis.

PubMed

Littleton, Sheila Robertson; Heriza, Carolyn B; Mullens, Pamela A; Moerchen, Victoria A; Bjornson, Kristie

2011-01-01

To examine the effect of positioning on respiratory measurements in individuals with cerebral palsy and severe scoliosis. Five individuals aged 17 to 37 years participated in an alternating treatment, single-subject design. Oxygen saturation, respiratory rate, heart rate, and chest wall excursion measurements were obtained in supine, sitting, and sidelying positions. Level of support for hypotheses varied on the basis of the respiratory measurement and participants' status. Respiratory rate appeared to be most sensitive to change in the positions. Severity of respiratory compromise and age may be associated with less tolerance for supine position versus sitting and sidelying positions. The use of therapeutic positioning in sitting and sidelying positions should be considered as a noninvasive intervention for a population with respiratory compromise. Further research with a larger sample is needed to empirically link specific positions with improved respiratory efficiency.

Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

PubMed

Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

2016-08-01

To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies].

PubMed

Petzke, F; Enax-Krumova, E K; Häuser, W

2016-02-01

Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain. A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool. We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2  with nabilone and 1  with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12). Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.

Hormonal contraception and physiology: a research-based theory of discontinuation due to side effects.

PubMed

Vitzthum, Virginia J; Ringheim, Karin

2005-03-01

Side effects influence the acceptability and continuation of hormonal contraceptives. Counseling the client about the management of side effects is a principal approach advocated for increasing continuation. Evidence of a biological basis for variation in women's tolerance of hormonal contraceptives argues, however, that greater attention should be given to altering the product rather than principally attempting to alter a woman's ability to deal with the product. Discontinuation rates for hormonal contraceptives, largely attributable to side effects and health concerns, are high in nearly all less-developed countries for which Demographic and Health Survey data are available. Oral contraceptives appear to be particularly problematic for Latin American women, most notably in Bolivia. Clinical trials suggest substantial variation in the physiological response to exogenous hormones, and new evidence confirms the hypothesis that the normal hormonal profiles of Bolivian women are significantly lower than those of women in the United States. These findings suggest a need for more population-specific physiological research linked to analyses of the possible association between endogenous hormone differences and contraceptive continuation. Appropriately adjusting the level of the steroid delivered may benefit women's health and improve the acceptability and continuation of hormonal contraceptives.

The effect of platelet-rich plasma on the outcome of short-term narrowband-ultraviolet B phototherapy in the treatment of vitiligo: a pilot study.

PubMed

Ibrahim, Zeinab A; El-Ashmawy, Amal A; El-Tatawy, Rania A; Sallam, Fersan A

2016-06-01

Narrowband - ultraviolet B (NB-UVB) is an emerging, effective, and safe therapy for vitiligo, but the treatment course often requires a long duration of time which may carry a potential risk for various side effects and patients' noncompliance. To explore the effect of platelet-rich plasma (PRP) injection on the outcome of short-term NB-UVB therapy for the patients with stable vitiligo. The study included 60 stable vitiligo patients with overall symmetrical lesions. For each patient, the left side of the body was treated with NB-UVB alone (control side) while the right side was treated with NB-UVB therapy in addition to intradermal injection of PRP, every 2 weeks for 4 months. There was statistically highly significant improvement in the repigmentation in the combination group(PRP plus NB-UVB) compared with NB-UVB group. Intradermal PRP injection in combination with NB-UVB could be considered as a simple, safe, tolerable, and cheap technique for treatment of vitiligo. It shortens the duration of NB-UVB therapy and is expected to increase patient compliance. Longer follow-up is needed. © 2015 Wiley Periodicals, Inc.

Plasticity and local adaptation explain lizard cold tolerance.

PubMed

Card, Daren C; Schield, Drew R; Castoe, Todd A

2018-05-01

How does climate variation limit the range of species and what does it take for species to colonize new regions? In this issue of Molecular Ecology, Campbell-Staton et al. () address these broad questions by investigating cold tolerance adaptation in the green anole lizard (Anolis carolinensis) across a latitudinal transect. By integrating physiological data, gene expression data and acclimation experiments, the authors disentangle the mechanisms underlying cold adaptation. They first establish that cold tolerance adaptation in Anolis lizards follows the predictions of the oxygen- and capacity-limited thermal tolerance hypothesis, which states that organisms are limited by temperature thresholds at which oxygen supply cannot meet demand. They then explore the drivers of cold tolerance at a finer scale, finding evidence that northern populations are adapted to cooler thermal regimes and that both phenotypic plasticity and heritable genetic variation contribute to cold tolerance. The integration of physiological and gene expression data further highlights the varied mechanisms that drive cold tolerance adaptation in Anolis lizards, including both supply-side and demand-side adaptations that improve oxygen economy. Altogether, their work provides new insight into the physiological and genetic mechanisms underlying adaptation to new climatic niches and demonstrates that cold tolerance in northern lizard populations is achieved through the synergy of physiological plasticity and local genetic adaptation for thermal performance. © 2018 John Wiley & Sons Ltd.

Bowel cleansing before colonoscopy: Balancing efficacy, safety, cost and patient tolerance

PubMed Central

Harrison, Nicole M; Hjelkrem, Michael C

2016-01-01

Effective colorectal cancer screening relies on reliable colonoscopy findings which are themselves dependent on adequate bowel cleansing. Research has consistently demonstrated that inadequate bowel preparation adversely affects the adenoma detection rate and leads gastroenterologists to recommend earlier follow up than is consistent with published guidelines. Poor preparation affects as many as 30% of colonoscopies and contributes to an increased cost of colonoscopies. Patient tolerability is strongly affected by the preparation chosen and manner in which it is administered. Poor tolerability is, in turn, associated with lower quality bowel preparations. Recently, several new developments in both agents being used for bowel preparation and in the timing of administration have brought endoscopists closer to achieving the goal of effective, reliable, safe, and tolerable regimens. Historically, large volume preparations given in a single dose were administered to patients in order to achieve adequate bowel cleansing. These were poorly tolerated, and the unpleasant taste of and significant side effects produced by these large volume regimens contributed significantly to patients’ inability to reliably complete the preparation and to a reluctance to repeat the procedure. Smaller volumes, including preparations that are administered as tablets to be consumed with water, given as split doses have significantly improved both the patient experience and efficacy, and an appreciation of the importance of the preparation to colonoscopy interval have produced additional cleansing. PMID:26788258

Cyclosporine induced biochemical remission in childhood autoimmune hepatitis.

PubMed

Franulović, Orjena Zaja; Rajacić, Nada; Lesar, Tatjana; Kuna, Andrea Tesija; Morić, Bernardica Valent

2012-09-01

The conventional treatment of autoimmune hepatitis (AIH) in children, which includes prednisone alone or in combination with azathioprine, induces remission in most cases but is often associated with poorly tolerated side effects. To avoid the adverse effects, Alvarez et al. introduced an alternative treatment regimen, using cyclosporine A (CyA) as primary immunosuppression. We carried out a retrospective study to evaluate the efficacy and tolerance of CyA treatment in children and adolescents with AIH treated in our center. During 2000-2010 period, nine children (6 female) aged 5-17.5 years, were diagnosed with AIH according to established international criteria. Following the suggested protocol, CyA was administered orally and when the transaminases tended to normalise, dose was adjusted to lover serum levels. Conversion to low dose of prednisone and azathioprine was started after 6 months, with gradual tapering and discontinuation of CyA. All nine patient had elevated transaminases and gammaglobulin levels, with proven histological changes typical for AIH in 8 patients that underwent liver biopsy (in one patient biopsy was contraindicated due to the prolonged prothrombin time). Serum ANA/SMA autoantibodies were positive in all but one patient, who had positive anti-LKM1. Complete or near complete and persistent normalisation of transaminase activity was observed in 8/9 patients within first 6 to 12 months. In one patient with partial response, an overlap syndrome was established. After ursodeoxycholic acid was added complete remission was observed. All patients had excellent clinical course and histological improvement. During the long-term follow-up (1.5-9 yrs; median 4.5 yrs), biochemical relapse occured in one patient after discontinuation of maintenance corticosteroid dose. Despite registered improvement, none of the patients fulfilled the criteria for therapy discontinuation, so all of them are still receiving maintenance doses of prednisone or azathioprine. The applied protocol allowed for the control of the liver inflammatory disease in all of our patients and protected them from the side effects related to steroid treatment. Side effects of CyA were minimal and were well tolerated.

Use of Hematopoietic Growth Factor in the Management of Hematological Side Effects Associated to Antiviral Treatment for Hcv Hepatitis

PubMed Central

Mancino, Paola; Falasca, Katia; Ucciferri, Claudio; Pizzigallo, Eligio; Vecchiet, Jacopo

2010-01-01

Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection. PMID:21415945

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

PubMed

Mutimer, D; Naoumov, N; Honkoop, P; Marinos, G; Ahmed, M; de Man, R; McPhillips, P; Johnson, M; Williams, R; Elias, E; Schalm, S

1998-06-01

Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Antigen-Conjugated Human IgE Induces Antigen-Specific T Cell Tolerance in a Humanized Mouse Model

PubMed Central

Baravalle, Günther; Greer, Alexandra M.; LaFlam, Taylor N.; Shin, Jeoung-Sook

2015-01-01

Dendritic cells (DCs) play an important role in immune homeostasis through their ability to present Ags at steady state and mediate T cell tolerance. This characteristic renders DCs an attractive therapeutic target for the induction of tolerance against auto-antigens or allergens. Accordingly, Ag-conjugated DC–specific Abs have been proposed to be an excellent vehicle to deliver Ags to DCs for presentation and tolerance induction. However, this approach requires laborious reagent generation procedures and entails unpredictable side effects resulting from Ab-induced crosslinking of DC surface molecules. In this study, we examined whether IgE, a high-affinity, non–cross-linking natural ligand of FcεRI, could be used to target Ags to DCs and to induce Ag-specific T cell tolerance. We found that Ag-conjugated human IgE Fc domain (Fcε) effectively delivered Ags to DCs and enhanced Ag presentation by 1000- to 2500-fold in human FcεRIα-transgenic mice. Importantly, this presentation resulted in a systemic deletion of Ag-specific T cells and prevented these mice from developing delayed-type hypersensitivity, which is critically dependent on Ag-specific T cell immunity. Thus, targeting FcεRI on DCs via Ag-Fcε fusion protein may serve an alternative method to induce Ag-specific T cell tolerance in humans. PMID:24610015

Tolerance in Kidney Transplantation: What Is on the B Side?

PubMed Central

Borràs, Francesc E.

2016-01-01

Regulatory B cells (Breg) are in the spotlight for their role in immune homeostasis maintenance and tolerance achievement as in the last years the correlation with functional and increased Breg numbers in autoimmune diseases and transplantation has been extensively proven. Their study is, however, in its infancy with still little knowledge and consensus on their origin, phenotype, and mechanism of action. All this hampers the pursuit of an effective Breg induction method for therapeutic purposes. In this review we aim to summarize the studies on human Breg and their implication in kidney transplantation and to further discuss the issues surrounding therapeutic applications of this cell subset. PMID:27956762

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Comparison of injectable molindone and haloperidol followed by oral dosage forms in acutely ill schizophrenics.

PubMed

Escobar, J I; Mann, J J; Keller, J; Wilkins, J; Mason, B; Mills, M J

1985-08-01

The comparative efficacy of molindone and haloperidol, given by injection for the first 2-3 days of hospitalization and then continued orally for up to 4 weeks, is reported from an ongoing double-blind study. Efficacy and side effects were assessed by the Brief Psychiatric Rating Scale, Clinical Global Impressions, Treatment Emergent Symptom Scale, and Target Symptom Ratings. Analyses based on the first 35 patients who entered the study indicate that both drugs were effective and well tolerated. There were slight advantages for molindone early during the injectable phase of treatment and for haloperidol late during the oral portion of the study, but these differences were not clinically significant. No significant differences in side effects were found between the two drugs.

Expectancy-induced placebo analgesia in children and the role of magical thinking.

PubMed

Krummenacher, Peter; Kossowsky, Joe; Schwarz, Caroline; Brugger, Peter; Kelley, John M; Meyer, Andrea; Gaab, Jens

2014-12-01

Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned-stratified for MT and gender-to either an analgesia-expectation or a control-expectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearm side: Low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children aged 6 to 9 years (girls > boys). Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Aerobic fitness and orthostatic tolerance: Evidence against an association

NASA Technical Reports Server (NTRS)

Ebert, Thomas J.

1994-01-01

This presentation will focus on only one side of the debate as to whether high levels of aerobic fitness have a deleterious effect on tolerance to gravitational stress. This issue was raised in the early 1970's as a result of two research publications. The first work investigated the carotid sinus baroreflex of humans with an airtight chamber that surrounded the head and neck. The steady-state reflex changes in blood pressure that were recorded 3 minutes after application of the head and neck stimuli, were attenuated in an athletic group compared to a sedentary group of volunteers. A second report in the NASA literature indicated that five endurance-trained runners were less tolerant to LBNP than five nonrunners. These early research findings have stimulated a considerable amount of interest that has lead to a growing number of research efforts seeking an association between aerobic fitness and orthostatic tolerance in humans. I will briefly review some of the more pertinent published research information which suggests that there is no relationship between aerobic fitness and orthostatic tolerance in humans.

Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

PubMed Central

Gómez-Soriano, Julio; Goiriena, Eider; Taylor, Julian

2010-01-01

For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threatening withdrawal syndrome present serious problems for its management. Now, in an experimental model of spinal cord injury spasticity, AMPA receptor blockade with NGX424 (Tezampanel) has been shown to reduce stretch reflex activity alone and during tolerance to intrathecal baclofen therapy. These results stem from the observation that GluA1 receptors are overexpressed on reactive astrocytes following experimental ischaemic spinal cord injury. Although further validation is required, the appropriate choice of AMPA receptor antagonists for treatment of stretch hyperreflexia based on our recent understanding of reactive astrocyte neurobiology following spinal cord injury may lead to the development of a better adjunct clinical therapy for spasticity without the side effects of intrathecal baclofen therapy. LINKED ARTICLE This article is a commentary on Oshiro et al., pp. 976–985 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2010.00954.x PMID:20662840

Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics.

PubMed

Remesic, Michael; Hruby, Victor J; Porreca, Frank; Lee, Yeon Sun

2017-06-21

Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest. It has been shown that allosteric modulators play key roles in influencing receptor function such as its tolerance to a ligand and affect downstream pathways. There has been a high variance of chemical structures that provide allosteric modulation at a given receptor, but recent studies and reviews tend to focus on the altered cellular mechanisms instead of providing a more rigorous description of the allosteric ligand's structure-function relationship. In this review, we aim to explore recent developments in the structural motifs that potentiate orthosteric binding and their influences on cellular pathways in an effort to present novel approaches to opioid therapeutic design.

Photodynamic therapy using chlorophyll-a in the treatment of acne vulgaris: a randomized, single-blind, split-face study.

PubMed

Song, Byong Han; Lee, Dong Hun; Kim, Byung Chul; Ku, Sang Hyeon; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong

2014-10-01

Chlorophyll-a is a novel photosensitizer recently tested for the treatment of acne vulgaris. We sought to evaluate the clinical efficacy and safety of chlorophyll-a photodynamic therapy used for acne treatment. Subjects with acne on both sides of the face were included. Eight treatment sessions were performed over a 4-week duration. Half of the face was irradiated using a blue and red light-emitting diode after topical application of chlorophyll-lipoid complex. The other half underwent only light-emitting diode phototherapy. The lesion counts and acne severity were assessed by a blinded examiner. Sebum secretion, safety, and histologic changes were also evaluated. In total, 24 subjects completed the study. Facial acne improved on both treated sides. On the chlorophyll-a photodynamic therapy-treated side, there were significant reductions in acne lesion counts, acne severity grades, and sebum levels compared with the side treated with light-emitting diode phototherapy alone. The side effects were tolerable in all the cases. All the subjects were of Asian descent with darker skin types, which may limit the generalizability of the study. A chlorophyll-a arm alone is absent, as is a no-treatment arm. We suggest that chlorophyll-a photodynamic therapy for the treatment of acne vulgaris can be effective and safe with minimal side effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Clinical management of elderly patients with epilepsy; the use of lacosamide in a single center setting.

PubMed

Rainesalo, Sirpa; Mäkinen, Jussi; Raitanen, Jani; Peltola, Jukka

2017-10-01

Lacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i.e., LCM administered for at least 2weeks. Lacosamide was initiated for acute seizure disorders (prolonged complex partial seizures, recurrent seizures, or status epilepticus) in 54 patients (81%) and for chronic epilepsy in 13 patients in an outpatient setting. The mean follow-up period for LCM treatment was 14months. The mean daily dose of LCM at the end of follow-up was 368mg (range: 100-600) for those 57 patients that continued treatment. Ten patients (15%) stopped LCM treatment but none because of lack of efficacy and only three patients (4%) because of side effects. The most frequent side effects were dizziness, fatigue, and tremor. Lacosamide was well tolerated even at relatively high doses and in combination therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

[Ketotifen treatment of chronic urticaria. An open study of therapeutically difficult courses].

PubMed

Taube, K M; Wozniak, K D; Lässig, W

1985-12-01

21 patients suffering from chronic urticaria were treated with Ketotifen (2 X 1 mg/d) for 4 weeks. The suppression of weals and pruritus, the side effects in comparison with antihistamines, as well as the effect after finishing therapy have been studied. Ketotifen has a good suppressing effect on weals and pruritus. The general tolerance of the preparation is good, as well. Thus Ketotifen may be regarded as an additional possibility concerning treatment of chronic urticaria.

Hydroxyurea-induced oral ulceration.

PubMed

Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin

2015-12-01

Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of salicylic acid 30% peel and pneumatic broadband light in the treatment of mild to moderately severe facial acne vulgaris.

PubMed

Thuangtong, Rattapon; Tangjaturonrusamee, Chinmanat; Rattanaumpawan, Pinyo; Ditre, Chérie M

2017-07-01

Acne patients experience not only a medical disease but also an aesthetic condition, and this latter complication greatly motivates patients to seek out the best treatment regimen to hasten improvement in their appearance. The available clinical procedures for acne treatment include salicylic acid 30% peel and pneumatic broadband light (PBBL). The objective of this study was to compare the efficacy of salicylic acid 30% peel and PBBL treatments in patients with mild to moderately severe facial acne vulgaris. Twelve patients were recruited for a 12-week prospective, single-blind, randomized, split-face study. Patients were treated with a salicylic acid 30% peel on one side of the face and PBBL treatment was administered on the opposite side of the face for 6 consecutive weeks without other acne treatments. At every visit, treatment evaluations were performed using a modified Global Acne Grading Score (mGAGS), acne quality of life (QOL) questionnaire, Wong-Baker FACES Pain Rating Scale (WBPRS) assessments, and clinical photography. Improvement in acne symptoms was observed for both treatment procedures without significant differences and with minimal side effects. Salicylic acid 30% peel and PBBL were well tolerated in our study, and both clinical procedures were efficacious and well-tolerated by the patients.

Electroconvulsive therapy--efficacy and side-effects.

PubMed

Moksnes, Kjell Martin; Ilner, Stein Opjordsmoen

2010-12-16

Efficacy of electroconvulsive therapy (ECT) and duration of associated side effects is uncertain. We wanted to study indications, efficacy, time to response and side effects. ECT-protocols and medical records (from the period 1960-95) in three psychiatric wards of Dikemark Mental Hospital, Norway were systematically assessed. 141 persons underwent 241 ECT series comprising 1960 treatment sessions. Major depressive disorder was the main diagnosis in most patients 124 [88 %]. Before ECT, 129 (91 %) patients had been treated with at least one antidepressant, 107 (76 %) with at least two and 67 (48 %) with two different classes of antidepressants without sufficient clinical recovery from the incident. 31 (22 %) had received lithium before ECT. Within four weeks after the first ECT, 120 (85 %) patients had recovered. 61 of these achieved remission and were discharged within four weeks. After the first ECT series, 92 patients showed signs of improvement. 71 (77 %) had signs of improvement within 6 days. Side effects were noted after 123 of totally 241 series (51 %). Five patients experienced serious complications. Interpretation. The immediate effect of ECT was good and signs of recovery were observed in most patients during the first week. Depressed psychotic patients and the elderly seemed to respond best. Considering these patients' serious and long-lasting disorders ECT was fairly safe and well tolerated.

B cell receptor inhibition as a target for CLL therapy.

PubMed

Jeyakumar, Deepa; O'Brien, Susan

2016-03-01

Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy. As a class of medications, BCR inhibitors have some unique side effects including redistribution lymphocytosis. Ibrutinib has specific toxicities including increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities consisting of transaminitis, diarrhea and pneumonitis. Ongoing clinical trials are evaluating these agents in combination with antibodies, chemotherapy and other small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

A model for plasma volume changes during short duration spaceflight

NASA Technical Reports Server (NTRS)

Davis, John E.

1989-01-01

It is well established that plasma volume decreases during spaceflight and simulated weightlessness (bedrest). The decrement in plasma volume is thought to contribute to the orthostatic intolerance that has been observed in some crew members following spaceflight. To date, no studies have evaluated the effectiveness of fluid countermeasures of varying osmolality in the restoration of plasma volume and orthostatic tolerance in a controlled study. The overall objectives of this project were to: (1) provide a model that would rapidly and safely produce a fluid loss comparable to that which occurs during short duration spaceflight; and (2) design a study that would determine the optimal drink solution to restore orthostatic tolerance and describe the mechanism(s) whereby orthostatic tolerance is restored. In summary, Lasix can be used as a way of simulating the plasma volume changes that occur during short duration spaceflight. The total loss of plasma is comparable to spaceflight. Lasix is fast acting, and has relatively few side effects. The present design for evaluating the optimal fluid countermeasures will have important implications in restoring orthostatic tolerance and function in the latter stages of spaceflight when it is essential for safe operation of the spacecraft.

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

PubMed Central

2013-01-01

Background A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Methods Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Results Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). Conclusion In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake. PMID:23565943

Modafinil as a potential motion sickness countermeasure.

PubMed

Hoyt, Robert E; Lawson, Benton D; McGee, Heather A; Strompolis, Melissa L; McClellan, Molly A

2009-08-01

Motion sickness adversely affects military air and sea operations. Medications help prevent motion sickness but are frequently associated with side effects. Better medications or combinations of medications are needed. Dextroamphetamine has documented anti-motion sickness effects but also has a potential for abuse. Modafinil is a relatively new central nervous system stimulant that has none of the drawbacks of dextroamphetamine, but has not been evaluated for the treatment of motion sickness. This double-blind, placebo-controlled study evaluated the anti-motion sickness efficacy of modafinil, alone or in combination with oral scopolamine. Moderate nausea was induced via a Coriolis cross-coupling stimulus. There were 60 participants who were assigned randomly to 1 of 3 conditions: 1) 2 placebo pills (DP); 2) modafinil plus placebo (MP); or 3) modafinil plus oral scopolamine (MS). The primary measure of drug efficacy was the number of head tilts tolerated upon reaching moderate nausea for 1 min without abatement. The combination of modafinil and scopolamine (MS) allowed subjects to tolerate significantly more head tilts than placebo, but modafinil alone (MP) failed to differ significantly from placebo (DP). No significant cognitive performance decrements were observed among the three experimental conditions. Modafinil was not found to be more effective than placebo. Further testing is recommended to determine whether the potentially promising combination of modafinil and scopolamine provides better efficacy or fewer side effects than scopolamine administered alone.

Serial Monitoring of Immune Markers Being Represented Regulatory T Cell/T Helper 17 Cell Ratio: Indicating Tolerance for Tapering Immunosuppression after Liver Transplantation

PubMed Central

Jhun, JooYeon; Lee, Seung Hoon; Lee, Soon Kyu; Kim, Hee Yeon; Jung, Eun Sun; Kim, Dong Goo; Choi, JeongWon; Bae, Si Hyun; Yoon, Seung Kew; Chung, Byung Ha; Yang, Chul Woo; Cho, Mi-La; Choi, Jong Young

2018-01-01

Recipients of liver transplantation (LT) require long-term immunosuppressive drug treatment, but lifelong immunosuppressive treatment has severe side effects. It is known that some LT recipients develop immune tolerance, and although the development of such operational tolerance should allow a decrease in the burden of immunosuppressive drug treatment, the factors that indicate operational tolerance are not clear. This study aimed to monitor immunological markers over time in LT recipients to identify those markers indicating the development of operational tolerance. We performed a prospective pilot study measuring immune markers, including the ratio of regulatory T (Treg) and T helper (Th) 17 cells in peripheral blood in the 14 most immunologically stable patients among 70 clinically stable LT recipients. The doses of immunosuppressive drugs given to these 14 LT recipients were tapered over time and they were monitored for immunological markers related to the development of immune tolerance. As the doses of immunosuppressive drugs were reduced, the Treg/Th17, Th1/Th17, and CD8/Th17 ratio in tolerant recipients was significantly increased compared with that of nontolerant recipients. These results suggest that monitoring of changes in the immune makers, including Treg/Th17 ratio during tapering of immunosuppression may allow prediction of the development of tolerance. PMID:29545795

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.

PubMed

Thorkelson, Gregory; Bielefeldt, Klaus; Szigethy, Eva

2016-06-01

The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and noradrenaline reuptake and has moderate efficacy for depression, and some small support for use in fatigue and smoking cessation. Buspirone has an indication for generalized anxiety disorder though studies show only a minimal benefit. It has some growing evidence for use in functional dyspepsia. Most of these agents have physiological effects on the brain, immune system, and gastrointestinal tract (with the exception of bupropion) hence their therapeutic and side effects manifested in these systems. Antidepressant medications are frequently prescribed for depression, anxiety disorders, and chronic pain syndromes, but overall support for their efficacy is modest at best. Psychological interventions have growing support for having much more robust effects without the side effects of antidepressants and should be considered first-line treatment or at least an adjunct to psychotropic medications for these conditions.

Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes

PubMed Central

Ahmadi, Hamed; Daneshmand, Siamak

2014-01-01

Androgen deprivation therapy (ADT) constitutes the first-line treatment for patients with locally advanced tumors, recurrent or metastatic disease. Given its widespread use, clinicians should be familiar with common side effects of this treatment. This review focuses on common side effects of ADT and available treatment options to control the side effects. Also, it briefly compares continuous ADT with other therapeutic approaches for androgen deprivation in prostate cancer patients. Similar to hormonal medications, newer non-hormonal therapeutic options including gabapentin and acupuncture have at best moderate effect in controlling hot flashes in patients on ADT. Supervised and/or home exercise programs significantly improve ADT-related fatigue, metabolic/cardiovascular side effects, and cognitive dysfunction. Denosumab, a human monoclonal antibody against RANK-L, is more effective than bisphosphonates in preventing skeletal-related events in patients with metastatic or castrate-resistant prostate cancer and unlike bisphosphonates, it can also reduce the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Toremifene, a selective estrogen receptor inhibitor, has dual beneficial effects on ADT-related osteoporosis and metabolic dysfunction. Metformin coupled with lifestyle modification is also a well-tolerated treatment for metabolic changes during ADT. While producing similar oncological outcomes, intermittent ADT is associated with higher quality of life in patients under ADT by improving bone health, less metabolic and hematologic complications, and fewer hot flashes and sexual dysfunction events. PMID:25045284

Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

PubMed Central

Akpınar, Esma; Cerit, Cem; Talas, Anıl; Tural, Ümit

2016-01-01

Objective In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline Methods The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. Results The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. Conclusion Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline. PMID:27776387

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

PubMed

Rex, Douglas K; Katz, Philip O; Bertiger, Gerald; Vanner, Stephen; Hookey, Lawrence C; Alderfer, Vivian; Joseph, Raymond E

2013-07-01

New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). Multicenter, assessor-blinded, randomized, noninferiority study. University hospitals, academic medical centers, and private clinics across the United States. Adults preparing for colonoscopy. P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Behavioral methods of alleviating motion sickness: effectiveness of controlled breathing and a music audiotape.

PubMed

Yen Pik Sang, Fleur D; Billar, Jessica P; Golding, John F; Gresty, Michael A

2003-01-01

Behavioral countermeasures for motion sickness would be advantageous because of the side effects of antiemetic drugs, but few alternative treatments are available. The objective of this study was to compare the effectiveness of controlling breathing and listening to a music audiotape designed to reduce motion sickness symptoms, on increasing tolerance to motion-induced nausea. Twenty-four healthy subjects were exposed to nauseogenic Coriolis stimulation on a rotating turntable under three conditions: whilst focusing on controlling breathing; listening to a music audiotape; or without intervention (control). The three conditions were performed by each subject according to a replicated factorial design at 1-week intervals at the same time of day. Ratings of motion sickness were obtained every 30 seconds. Once a level of mild nausea was reached subjects commenced controlling breathing or listened to the music audiotape. Motion was stopped after the onset of moderate nausea. Mean (+/- SD) motion exposure time in minutes tolerated before the onset of moderate nausea was significantly longer (p <.01) for controlling breathing (10.7 +/- 5.6 min) and longer (p <.01) for music (10.4 +/- 5.6 min) compared with control (9.2 +/- 5.9 min). Both controlling breathing and the music audiotape provided significant protection against motion sickness and with similar effectiveness. These nonpharmacologic countermeasures are only half as effective as standard doses of anti-motion sickness drugs, such as oral scopolamine; however, they are easy to implement and free of side effects.

Immunotherapy of allergic contact dermatitis.

PubMed

Spiewak, Radoslaw

2011-08-01

The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.

Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

PubMed

Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

2010-11-01

Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

Comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for Molluscum Contagiosum in children.

PubMed

Rajouria, E A; Amatya, A; Karn, D

2011-01-01

Molluscum contagiosum is one of the commonest cutaneous viral infections in children. All treatment modalities are associated with substantial pain, tissue destruction, and frequent recurrence. To compare the efficacy and side effects of KOH 5% solution with tretinoin 0.05% cream for the treatment of molluscum contagiosum in children. Fifty patients were randomly divided into 2 groups; 25 each for 5% KOH solution and 0.05% tretinoin cream. The given medication was applied at bed time over molluscum lesions. The assessment of response and side effects were performed weekly for 4 weeks. At the end of 4 weeks, the mean lesion count decreased from 9.48 +/- 3.00 SD to 1.67 +/- 0.58 SD and from 8.35 +/- 2.82 SD to 2.00 +/- 1.00 SD in patients treated with 5% KOH solution and 0.05% tretinoin cream respectively. The result of both KOH and tretinoin showed good response, well tolerated by children but between the two, KOH showed fast recovery and most lesions were resolved before 4 week. The side effects could be minimized if applied as stated above. On the other hand, tretinoin showed delayed response and even some of lesion extended beyond 4 week but the side effect were less, and hence can be used in recurrent cases.

Multicenter study of subjective acceptance during magnetic resonance imaging at 7 and 9.4 T.

PubMed

Rauschenberg, Jaane; Nagel, Armin M; Ladd, Susanne C; Theysohn, Jens M; Ladd, Mark E; Möller, Harald E; Trampel, Robert; Turner, Robert; Pohmann, Rolf; Scheffler, Klaus; Brechmann, André; Stadler, Jörg; Felder, Jörg; Shah, N Jon; Semmler, Wolfhard

2014-05-01

The aims of this study were to investigate the subjective discomfort and sensory side effects during ultrahigh field (UHF) magnetic resonance imaging (MRI) examinations in a large-scale study and to evaluate differences between magnetic resonance (MR) sites. Four MR sites with a 7-T MR system and 2 MR sites with a 9.4-T MR system participated in this multicenter study with a total number of 3457 completed questionnaires on causes of discomfort and sensations during the examination. For a pooled retrospective analysis of the results from the partially different questionnaires, all data were adapted to an answer option with a 4-point scale (0 = no discomfort/side effect, 3 = very unpleasant/very strong sensation). To differentiate effects evoked by the low-frequency time-varying magnetic fields due to movement through the static magnetic field, most questionnaires separated the manifestation of sensory side effects during movement on the patient table from manifestation while lying still in the isocenter. In general, a high acceptance of UHF examinations was found, where in 82% of the completed questionnaires, the subjects stated the examination to be at least tolerable. Although in 7.6% of the questionnaires, subjects felt discomfort during the examination, only 0.9% of the image acquisitions had to be terminated prematurely. No adverse events occurred in any of the examinations. Only 1% of the subjects were unwilling to undergo further UHF MRI examinations. Examination duration was the most complained cause of discomfort, followed by acoustic noise and lying still. All magnetic-field-related sensations were more pronounced when moving the patient table versus the isocenter position (19%/2% of the subjects felt unpleasant vertigo during the moving/stationary state). In general, vertigo was the most often stated sensory side effect and was more pronounced at 9.4 T compared with 7 T. However, the results varied substantially among the different sites. The high levels of subjective acceptance found in this study lead to the conclusion that UHF MRI would be tolerated as a diagnostic tool in clinical practice. For more consistent data ascertainment, we propose a standardized questionnaire for subjective perception monitoring.

The Effectiveness and Tolerability of Central Nervous System Stimulants in School-Age Children with Attention-Deficit/Hyperactivity Disorder and Disruptive Mood Dysregulation Disorder Across Home and School.

PubMed

Baweja, Raman; Belin, Peter J; Humphrey, Hugh H; Babocsai, Lysett; Pariseau, Meaghan E; Waschbusch, Daniel A; Hoffman, Martin T; Akinnusi, Opeolowa O; Haak, Jenifer L; Pelham, William E; Waxmonsky, James G

2016-03-01

This study examines the effectiveness and tolerability of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) and disruptive mood dysregulation disorder (DMDD). To be eligible, participants had to meet Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV) criteria for the combined subtype of ADHD and National Institute of Mental Health (NIMH) severe mood dysregulation criteria. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) DMDD criteria were retrospectively assessed after the study was completed. An open-label medication trial lasting up to 6 weeks was completed to optimize the central nervous system (CNS) stimulant dose. Measures of affective symptoms, ADHD symptoms and other disruptive behaviors, impairment, and structured side effect ratings were collected before and after the medication trial. Optimization of stimulant medication was associated with a significant decline in depressive symptoms on the Childhood Depression Rating Score-Revised Scale (p<0.05, Cohen's d=0.61) and Mood Severity Index score (p<0.05, Cohen's d=0.55), but not in manic-like symptoms on the Young Mania Rating Scale. There was a significant reduction in ADHD (p<0.05, Cohen's d=0.95), oppositional defiant disorder (ODD) (p<0.05, Cohen's d=0.5), and conduct disorder (CD) symptoms (p<0.05, Cohen's d=0.65) as rated by parents. There was also a significant reduction in teacher-rated ADHD (p<0.05, Cohen's d=0.33) but not in ODD symptoms. Medications were well tolerated and there was no increase in side effect ratings seen with dose optimization. Significant improvement in functioning was reported by clinicians and parents (all p's<0.05), but youth still manifested appreciable impairment at end-point. CNS simulants were well tolerated by children with ADHD comorbid with a diagnosis of DMDD. CNS stimulants were associated with clinically significant reductions in externalizing symptoms, along with smaller improvements in mood. However, most participants still exhibited significant impairment, suggesting that additional treatments may be needed to optimize functioning.

The Effectiveness and Tolerability of Central Nervous System Stimulants in School-Age Children with Attention-Deficit/Hyperactivity Disorder and Disruptive Mood Dysregulation Disorder Across Home and School

PubMed Central

Belin, Peter J.; Humphrey, Hugh H.; Babocsai, Lysett; Pariseau, Meaghan E.; Waschbusch, Daniel A.; Hoffman, Martin T.; Akinnusi, Opeolowa O.; Haak, Jenifer L.; Pelham, William E.; Waxmonsky, James G.

2016-01-01

Abstract Objective: This study examines the effectiveness and tolerability of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) and disruptive mood dysregulation disorder (DMDD). Methods: To be eligible, participants had to meet Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV) criteria for the combined subtype of ADHD and National Institute of Mental Health (NIMH) severe mood dysregulation criteria. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) DMDD criteria were retrospectively assessed after the study was completed. An open-label medication trial lasting up to 6 weeks was completed to optimize the central nervous system (CNS) stimulant dose. Measures of affective symptoms, ADHD symptoms and other disruptive behaviors, impairment, and structured side effect ratings were collected before and after the medication trial. Results: Optimization of stimulant medication was associated with a significant decline in depressive symptoms on the Childhood Depression Rating Score–Revised Scale (p<0.05, Cohen's d=0.61) and Mood Severity Index score (p<0.05, Cohen's d=0.55), but not in manic-like symptoms on the Young Mania Rating Scale. There was a significant reduction in ADHD (p<0.05, Cohen's d=0.95), oppositional defiant disorder (ODD) (p<0.05, Cohen's d=0.5), and conduct disorder (CD) symptoms (p<0.05, Cohen's d=0.65) as rated by parents. There was also a significant reduction in teacher-rated ADHD (p<0.05, Cohen's d=0.33) but not in ODD symptoms. Medications were well tolerated and there was no increase in side effect ratings seen with dose optimization. Significant improvement in functioning was reported by clinicians and parents (all p's<0.05), but youth still manifested appreciable impairment at end-point. Conclusions: CNS simulants were well tolerated by children with ADHD comorbid with a diagnosis of DMDD. CNS stimulants were associated with clinically significant reductions in externalizing symptoms, along with smaller improvements in mood. However, most participants still exhibited significant impairment, suggesting that additional treatments may be needed to optimize functioning. PMID:26771437

Relationship among side channels, fish assemblages, and environmental gradients in the unimpounded Upper Mississippi River

USGS Publications Warehouse

Barko, V.A.; Herzog, D.P.

2003-01-01

We analyzed fish abundance and environmental data collected over nine years from six side channels of the unimpounded upper Mississippi River between river km 46.7 and 128.7. A partial canonical correspondence analysis revealed differences in fish assemblages and environmental factors correlated with the six side channels. Fishes correlated with open side channels represented large river species tolerant of current and/or turbidity. Fishes correlated with closed side channels represented assemblages preferring either moderate to low turbidity/current or pools.

Experience with rufinamide in a pediatric population: a single center's experience.

PubMed

Vendrame, Martina; Loddenkemper, Tobias; Gooty, Vasu D; Takeoka, Masanori; Rotenberg, Alexander; Bergin, Ann M; Eksioglu, Yaman Z; Poduri, Annapurna; Duffy, Frank H; Libenson, Mark; Bourgeois, Blaise F; Kothare, Sanjeev V

2010-09-01

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes. Copyright 2010 Elsevier Inc. All rights reserved.

Minoxidil for severe hypertension after failure of other hypotensive drugs.

PubMed Central

Devine, B L; Fife, R; Trust, P M

1977-01-01

Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective. PMID:902045

[Supervised exercise training in patients with pulmonary arterial hypertension - analyses of the effectiveness and safety].

PubMed

Saxer, S; Rhyner, M; Treder, U; Speich, R; van Gestel, A J R

2012-02-01

Both in today's scientific research and in clinical practice, there exists a need to address the uncertainty concerning the effectiveness and safety of cardiopulmonary exercise training (CPET) in patients with pulmonary arterial hypertension (PAH). It is commonly believed that CPET may be dangerous for patients with PAH, because increasing pressure on the pulmonary arteries may worsen right-sided heart failure. Recently, the first clinical trials on exercise training in patients with pulmonary hypertension reported promising results. Extension of the walking distance at the 6-minute walk test improved quality of life, endurance capacity and a reduction in symptoms were observed after CPET. Furthermore, CPET was well tolerated by the patients in five clinical trials. In conclusion, it may be postulated that CPET is an effective therapy in patients with PAH and was tendentially well tolerated by the patients.

Herbs and nutrients in the treatment of depression, anxiety, insomnia, migraine, and obesity.

PubMed

Brown, R P; Gerbarg, P L

2001-03-01

Although a multitude of pharmaceutical agents are available for the treatment of mood disorders, anxiety and insomnia, many patients have difficulty tolerating the side effects, do not respond adequately, or eventually lose their response. Many therapeutic herbs and nutrients have far fewer side effects and may provide an alternative treatment or can be used to enhance the effect of prescription medications. In the article, the authors review the quality of the evidence supporting the clinical effects of a number of commonly used types of complementary/alternative medicine (CAM) for mood disorders, anxiety, and insomnia. They review data on the use of St. John's Wort, S-adenosyl-methionine (SAM-e), B vitamins, inositol, omega-3 fatty acids, and choline for mood disorders; data on the use of kava and other herbal agents and fish extract for anxiety and insomnia; and data on valerian and melatonin for insomnia. The authors also discuss the use of CAM to treat migraines, which may be comorbid with mood and anxiety disorders, and obesity, which can occur as a side effect of psychotropic medications. They consider the data on feverfew and butterbur for migraines and on chromium picolinate and the combination of ephedrine and caffeine for obesity. The authors also review issues related to comorbid medical illness, side effects, drug interactions, dosage, and brand selection.

Effect of GaAs Laser at 904 nm in the Pain Threshold in Tibia and Tolerance in Deltoid Evaluated by Pressure Algometry

NASA Astrophysics Data System (ADS)

Soares, Luiz G. P.; Sato, Sidney K.; Silveira, Landulfo; Aimbire, Flávio; Moreira, Leonardo M.; Pinheiro, Antônio L. B.

2011-08-01

The use of LLLT in pain relief is a controversial issue in Physiotherapy, with the efficacy of LLLT associated to pain relief still requiring significant study. Objective. This work focuses on the evaluation of the effect of low power GaAs laser at 904 nm in pressure pain threshold and tolerance in tibia and deltoid muscle, respectively. A total of 17 subjects were divided in two groups: active and sham laser. Measurements were taken before and after laser irradiation in healthy individuals using a pressure algometry, first verifying the viability of algometry to evaluate the pain threshold and tolerance inter individuals and comparing the differences of right and left sides in the same patients, and finally evaluating the pain threshold and tolerance before and after a single laser application. Laser energy density was of 4.0 J/cm2 with power density of 137 mW/cm2. Comparing algometry values of active laser group and the sham group, the pain tolerance in the deltoid muscle did not change among groups after laser irradiation, while it was also encountered a statistically significant difference in the pain threshold in tibia when comparing the laser active and sham laser (p<0.05). It was found that the active laser was effective in maintaining the pain threshold in tibia. The effective laser action in raising the pain threshold in tibia upon healthy individuals can suggest that the laser could be applied not only as curative but also with preventive purpose.

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PubMed

Rodgers, Anthony; Patel, Anushka; Berwanger, Otavio; Bots, Michiel; Grimm, Richard; Grobbee, Diederick E; Jackson, Rod; Neal, Bruce; Neaton, Jim; Poulter, Neil; Rafter, Natasha; Raju, P Krishnam; Reddy, Srinath; Thom, Simon; Vander Hoorn, Stephen; Webster, Ruth

2011-01-01

There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

PubMed

Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

2015-03-01

The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Fixed, low radiant exposure vs. incremental radiant exposure approach for diode laser hair reduction: a randomized, split axilla, comparative single-blinded trial.

PubMed

Pavlović, M D; Adamič, M; Nenadić, D

2015-12-01

Diode lasers are the most commonly used treatment modalities for unwanted hair reduction. Only a few controlled clinical trials but not a single randomized controlled trial (RCT) compared the impact of various laser parameters, especially radiant exposure, onto efficacy, tolerability and safety of laser hair reduction. To compare the safety, tolerability and mid-term efficacy of fixed, low and incremental radiant exposures of diode lasers (800 nm) for axillary hair removal, we conducted an intrapatient, left-to-right, patient- and assessor-blinded and controlled trial. Diode laser (800 nm) treatments were evaluated in 39 study participants (skin type II-III) with unwanted axillary hairs. Randomization and allocation to split axilla treatments were carried out by a web-based randomization tool. Six treatments were performed at 4- to 6-week intervals with study subjects blinded to the type of treatment. Final assessment of hair reduction was conducted 6 months after the last treatment by means of blinded 4-point clinical scale using photographs. The primary endpoint was reduction in hair growth, and secondary endpoints were patient-rated tolerability and satisfaction with the treatment, treatment-related pain and adverse effects. Excellent reduction in axillary hairs (≥ 76%) at 6-month follow-up visit after receiving fixed, low and incremental radiant exposure diode laser treatments was obtained in 59% and 67% of study participants respectively (Z value: 1.342, P = 0.180). Patients reported lower visual analogue scale (VAS) pain score on the fixed (4.26) than on the incremental radiant exposure side (5.64) (P < 0.0003). The only side-effect was mild and transient erythema. Subjects better tolerated the fixed, low radiant exposure protocol (P = 0.03). The majority of the study participants were satisfied with both treatments. Both low and incremental radiant exposures produced similar hair reduction and high and comparable patient satisfaction. However, low radiant exposure diode laser treatments were less painful and better tolerated. © 2015 European Academy of Dermatology and Venereology.

Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation

PubMed Central

Bohne, Felix; Martínez-Llordella, Marc; Lozano, Juan-José; Miquel, Rosa; Benítez, Carlos; Londoño, María-Carlota; Manzia, Tommaso-María; Angelico, Roberta; Swinkels, Dorine W.; Tjalsma, Harold; López, Marta; Abraldes, Juan G.; Bonaccorsi-Riani, Eliano; Jaeckel, Elmar; Taubert, Richard; Pirenne, Jacques; Rimola, Antoni; Tisone, Giuseppe; Sánchez-Fueyo, Alberto

2011-01-01

Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with non-tolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation. PMID:22156196

Markers of tolerance development to food allergens.

PubMed

Ponce, M; Diesner, S C; Szépfalusi, Z; Eiwegger, T

2016-10-01

IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls.

PubMed

Bandla, Aishwarya; Sundar, Raghav; Liao, Lun-De; Sze Hui Tan, Stacey; Lee, Soo-Chin; Thakor, Nitish V; Wilder-Smith, Einar P V

2016-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects. In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25 °C and 20 °C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects. At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 °C were well tolerated continuously over three hours. Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 °C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study may contribute to alleviating chemotherapy dose limitation due to CIPN and increase the likelihood of success of chemotherapy.

The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A alpha2,3 selective agonist, in comparison with lorazepam in healthy volunteers.

PubMed

de Haas, S L; Franson, K L; Schmitt, J A J; Cohen, A F; Fau, J B; Dubruc, C; van Gerven, J M A

2009-08-01

Benzodiazepines are effective short-term treatments for anxiety disorders, but their use is limited by undesirable side effects related to Central Nervous System impairment and tolerance development. SL65.1498 is a new compound that acts in vitro as a full agonist at the gamma-aminobutyric acid(A) 2 and 3 receptor and as a partial agonist at the 1 and 5 receptor subtypes. It is thought that the compound could be anxiolytic by its activation at the alpha2 and alpha3 receptor subtypes, without causing unfavourable side effects, which are believed to be mediated by the alpha1 and alpha5 subtypes. This study was a double-blind, five-way cross-over study to investigate the effects of three doses of SL65.1498 in comparison with placebo and lorazepam 2 mg in healthy volunteers. The objective was to select a dose level (expected to be therapeutically active), free of any significant deleterious effect. Psychomotor and cognitive effects were measured using a validated battery of measurements, including eye movements, body sway, memory tests, reaction-time assessments, and visual analogue scales. The highest dose of SL65.1498 showed slight effects on saccadic peak velocity and smooth pursuit performance, although to a much lesser extent than lorazepam. In contrast to lorazepam, none of the SL65.1498 doses affected body sway, visual analogue scale alertness, attention, or memory tests. This study showed that the three doses of SL65.1498 were well tolerated and induced no impairments on memory, sedation, psychomotor, and cognitive functions.

Comparison of two humidification systems for long-term noninvasive mechanical ventilation.

PubMed

Nava, S; Cirio, S; Fanfulla, F; Carlucci, A; Navarra, A; Negri, A; Ceriana, P

2008-08-01

There is no consensus concerning the best system of humidification during long-term noninvasive mechanical ventilation (NIMV). In a technical pilot randomised crossover 12-month study, 16 patients with stable chronic hypercapnic respiratory failure received either heated humidification or heat and moisture exchanger. Compliance with long-term NIMV, airway symptoms, side-effects and number of severe acute pulmonary exacerbations requiring hospitalisation were recorded. Two patients died. Intention-to-treat statistical analysis was performed on 14 patients. No significant differences were observed in compliance with long-term NIMV, but 10 out of 14 patients decided to continue long-term NIMV with heated humidification at the end of the trial. The incidence of side-effects, except for dry throat (significantly more often present using heat and moisture exchanger), hospitalisations and pneumonia were not significantly different. In the present pilot study, the use heated humidification and heat and moisture exchanger showed similar tolerance and side-effects, but a higher number of patients decided to continue long-term noninvasive mechanical ventilation with heated humidification. Further larger studies are required in order to confirm these findings.

[Effect of tiapride on the side effects of cerebrospinal fluid depletions in spinal puncture, pneumoencephalography and air myelography].

PubMed

Zenglein, J P; Baldauf, E; Wasser, P h

1978-04-01

The authors report their experience of the treatment post-cerebrospinal fluid loss syndrom, following subtraction by lumbar puncture, pneumoencephalography and air myelography. The study of 70 patients, divided in two equal groups, one receiving classic therapy, one receiving tiapride, a new molecule of original conception, lead to emphasize the interest of this drug. Tolerance in general is good, despite the administration of high doses and effects on the syndrom are positive and remarkable in preventive and curative treatment.

Tolerance in liver transplantation: Biomarkers and clinical relevance

PubMed Central

Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio

2016-01-01

Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as “operational tolerance”. However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. PMID:27678350

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis.

PubMed

Walkup, Laura L; Thomen, Robert P; Akinyi, Teckla G; Watters, Erin; Ruppert, Kai; Clancy, John P; Woods, Jason C; Cleveland, Zackary I

2016-11-01

Hyperpolarized 129 Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized 129 Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent 129 Xe MRI, receiving up to three doses of 129 Xe gas prepared by either a commercially available or a homebuilt 129 Xe polarizer. Subject heart rate and SpO 2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of 129 Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO 2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO 2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following 129 Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of 129 Xe MRI has been assessed in a small group of children as young as 6 years. SpO 2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were consistent with the known anesthetic properties of xenon and with previous safety assessments of 129 Xe MRI in adults. Hyperpolarized 129 Xe is a safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in healthy children and in children with cystic fibrosis who have mild to moderate lung disease.

Office hysteroscopic-guided selective tubal chromopertubation: acceptability, feasibility and diagnostic accuracy of this new diagnostic non-invasive technique in infertile women.

PubMed

Carta, Gaspare; Palermo, Patrizia; Pasquale, Chiara; Conte, Valeria; Pulcinella, Ruggero; Necozione, Stefano; Cofini, Vincenza; Patacchiola, Felice

2018-06-01

The aim of this study was to evaluate accuracy, tolerability and side effects of office hysteroscopic-guided chromoperturbations in infertile women without anaesthesia. Forty-nine infertile women underwent the procedure to evaluate tubal patency and the uterine cavity. Women with unilateral or bilateral tubal stenosis at hysteroscopy with chromoperturbation, and women with bilateral tubal patency who did not conceive during the period of six months, underwent laparoscopy with chromoperturbation. The results obtained from hysteroscopy and laparoscopy in the assessment of tubal patency were compared. Sensitivity, specificity, accuracy, positive-predictive value and negative-predictive value were used to describe diagnostic performance. Pain and tolerance were assessed during procedure using a visual analogue scale (VAS). Side effects or late complications and pregnancy rate were also recorded three and six months after the procedure. The specificity was 87.8% (95% CI: 73.80-95.90), sensitivity was 85.7% (95% CI 57.20-98.20), positive and negative predictive values were 70.6% (95% CI: 44.00-89) and 94.7% (95% CI: 82.30-99.40), respectively. Pregnancy rate (PR) within six months after performance of hysteroscopy with chromoperturbation was 27%. Office hysteroscopy-guided selective chromoperturbation in infertile patients is a valid technique to evaluate tubal patency and uterine cavity.

New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients

PubMed Central

Krivan, Gergely; Jolles, Stephen; Granados, Eduardo Lopes; Paolantonacci, Phillipe; Ouaja, Rabye; Cissé, Ousmane Alfa; Bernatowska, Ewa

2017-01-01

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient’s life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient’s compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient’s preference and needs. PMID:29181272

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

PubMed Central

Elhabazi, K; Trigo, JM; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, JJ; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

2012-01-01

BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. PMID:21718302

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

PubMed

Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

2012-01-01

BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Safety and tolerance of a probiotic formula in early infancy comparing two probiotic agents: a pilot study.

PubMed

Weizman, Zvi; Alsheikh, Ahmed

2006-10-01

To compare the safety and tolerance of two formulas, supplemented with different probiotic agents, in early infancy. Prospective randomized placebo-controlled trial. Clinics of a University Medical Center. Full-term healthy infants aged less than 4 months. Infants were randomly assigned for 4 weeks to a standard milk-based formula supplemented with either Bifidobacterium lactis (BB-12), Lactobacillus reuteri (ATCC 55730) or a probiotics-free formula. Growth parameters, daily characteristics of feeding, stooling and behavior, and side effects. Fifty-nine infants, aged 3-65 days, were included. Subjects in all three groups were similar at entry in terms of gestational age, birth weight, sex, growth parameters and breast feeding rate prior to the study. The supplemented formulas were well accepted and did not reveal any adverse effects. A comparison of growth parameters, and variables of feeding, stooling and crying and irritability did not reveal any significant differences between groups. The use of formula supplemented with either Lactobacillus reuteri or Bifidobacterium lactis in early infancy, was safe, well tolerated and did not adversely affect growth, stooling habits or infant behavior.

Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

PubMed

Mercer, Susan L; Coop, Andrew

2011-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

A current perspective on cancer immune therapy: step-by-step approach to constructing the magic bullet.

PubMed

D'Errico, Gabriele; Machado, Heather L; Sainz, Bruno

2017-12-01

Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the "push the accelerator" and "repair the car" metaphors, to explain the current limitations associated with cancer immunotherapy.

Prevention of peripheral side-effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.

PubMed Central

Ziv, I; Versano, D; Ruach, M; Izraeli, S; Almog, S; Alhalel, A; Alkalay, M; Menahem, S; Tochner, Z

1992-01-01

1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti-muscarinic side effects of a transdermal controlled-release formulation of hyoscine, was tested in a double-blind placebo-controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose. PMID:1524963

Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial.

PubMed

Schollhammer, M; Brenaut, E; Menard-Andivot, N; Pillette-Delarue, M; Zagnoli, A; Chassain-Le Lay, M; Sassolas, B; Jouan, N; Le Ru, Y; Abasq-Thomas, C; Greco, M; Penven, K; Roguedas-Contios, A M; Dupré-Goetghebeur, D; Gouedard, C; Misery, L; Le Gal, G

2015-11-01

Hyperhidrosis is a disorder that can impair quality of life. Localized treatments may be cumbersome and ineffective, and no systemic treatments have proven to be significantly beneficial. To evaluate the effectiveness and tolerance of low-dose oxybutynin for hyperhidrosis. We conducted a prospective, randomized, placebo-controlled trial. From June 2013 to January 2014, 62 patients with localized or generalized hyperhidrosis were enrolled. Oxybutynin was started at a dose of 2·5 mg per day and increased gradually to 7·5 mg per day. The primary outcome was defined as improvement of at least one point on the Hyperhidrosis Disease Severity Scale (HDSS). Dermatology Life Quality Index (DLQI) and tolerance were also reported. Most patients (83%) in our study had generalized hyperhidrosis. Oxybutynin was superior to placebo in improving the HDSS: 60% of patients treated with oxybutynin, compared with 27% of patients treated with placebo, improved at least one point on the HDSS (P = 0·009). The mean improvement in quality of life measured by DLQI was significantly better in the oxybutynin arm (6·9) than in the placebo arm (2·3). The most frequent side-effect was dry mouth, which was observed in 43% of the patients in the oxybutynin arm, compared with 11% in the placebo arm. Treatment with low-dose oxybutynin is effective in reducing symptoms of hyperhidrosis in generalized or localized forms. Side-effects were frequent but minor and mainly involved dry mouth. © 2015 British Association of Dermatologists.

Citalopram in the treatment of dysthymic disorder.

PubMed

Hellerstein, David J; Batchelder, Sarai; Miozzo, Ruben; Kreditor, David; Hyler, Steven; Gangure, Dinu; Clark, Joy

2004-05-01

This study aimed to provide preliminary data on the tolerability and effectiveness of citalopram for patients with dysthymic disorder. Twenty-one adult subjects meeting DSM-IV criteria for dysthymic disorder were enrolled in this 12-week open-label study, of whom 15 had pure dysthymia (e.g. no major depression in the past 2 years). Citalopram was initiated at 20 mg/day, and increased to a maximum of 60 mg/day. Response was defined as 50% or greater drop in score on the Hamilton Depression Rating Scale (HDRS) and a Clinical Global Impressions-I score of 1 ('very much improved') or 2 ('much improved'). Of these 15 pure dysthymic disorder subjects, all completed the trial, and 11 (73.3%) were treatment responders. All paired sample t-tests were highly significant, demonstrating significant average improvement on all measures of symptomatology and functioning. Scores on the 24-item HDRS decreased from 22.3+/-4.3 at baseline to 9.1+/-7.8 at week 12 [t(14)=6.1, P<0.001]. In addition, improvement was noted in self-reported measures of temperament and social functioning. The average final dose of citalopram was 39 mg/day. Side-effects were reported by nine of 15 subjects (60%), most frequently gastrointestinal symptoms (n=5), dry mouth (n=5) and sexual side-effects (n=3). These findings suggest the effectiveness and tolerability of citalopram in treating dysthymic disorder. Double-blind prospective studies are needed comparing citalopram both to placebo and to other medications, assessing both initial and sustained response to treatment.

Antidepressant Prescribing by Pediatricians: A Mixed-Methods Analysis.

PubMed

Tulisiak, Anne K; Klein, Jillian A; Harris, Emily; Luft, Marissa J; Schroeder, Heidi K; Mossman, Sarah A; Varney, Sara T; Keeshin, Brooks R; Cotton, Sian; Strawn, Jeffrey R

2017-01-01

Among pediatricians, perceived knowledge of efficacy, tolerability, dosing, and side effects of antidepressants represent significant sources of variability in the use of these medications in youth with depressive and anxiety disorders. Importantly, the qualitative factors that relate to varying levels of comfort with antidepressants and willingness to prescribe are poorly understood. Using a mixed-methods approach, in-depth interviews were conducted with community-based and academic medical center-based pediatricians (N = 14). Interviews were audio recorded and iteratively coded; themes were then generated using inductive thematic analysis. The relationship between demographic factors, knowledge of antidepressants, dosing, and side effects, as well as prescribing likelihood scores for depressive disorders, anxiety disorders or co-morbid anxiety and depressive disorders, were evaluated using mixed models. Pediatricians reported antidepressants to be effective and well-tolerated. However, the likelihood of individual physicians initiating an antidepressant was significantly lower for anxiety disorders relative to depressive disorders with similar functional impairment. Pediatricians considered symptom severity/functional impairment, age and the availability of psychotherapy as they considered prescribing antidepressants to individual patients. Antidepressant choice was related to the physician׳s perceived knowledge and comfort with a particular antidepressant, financial factors, and the disorder-specific evidence base for that particular medication and consultation with mental health practitioners. Pediatricians noted similar efficacy and tolerability profiles for antidepressants in youth with depressive disorders and anxiety disorders, but tended to utilize "therapy first" approaches for anxiety disorders relative to depressive disorders. Parental and family factors that influenced prescribing of antidepressants by pediatricians included parental ambivalence, family-related dysfunction and impairment secondary to the child׳s psychopathology as well as the child׳s psychosocial milieu. Pediatricians consider patient- and family-specific challenges when choosing prescribing antidepressant medications and are, in general, less likely to prescribe antidepressants for youth with anxiety disorders compared to youth with depressive disorders. The lower likelihood of prescribing antidepressants for anxious youth is not related to perception of the efficacy or tolerability, but rather to a perception that anxiety disorders are less impairing and more appropriately managed with psychotherapy. Copyright © 2016 Mosby, Inc. All rights reserved.

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1968-01-01

This report—the first of a series on codeine and its alternates for pain and cough relief—presents a detailed evaluation of experimental and clinical data concerning the analgesic action of codeine (the antitussive action will be assessed separately). The authors discuss the pharmacology of the drug, including side-effects and toxicity; effects on the respiratory, circulatory, digestive and urinary systems; tolerance, dependence and liability to abuse; metabolic effects; and mechanism of action. Though codeine is generally more toxic than morphine to animals on account of its convulsant action, it is less toxic to man, possibly because it produces less respiratory depression. Again, tolerance to its analgesic effects has been demonstrated in several animal species, but dependence in man is observed far less frequently than it is with morphine, and the abstinence syndrome is less intense. From their extensive review of the evidence available, the authors conclude that codeine is a good analgesic and that little risk to public health is likely to arise from its clinical use to relieve pain. PMID:4972938

Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder.

PubMed

Jakubovski, Ewgeni; Varigonda, Anjali L; Freemantle, Nicholas; Taylor, Matthew J; Bloch, Michael H

2016-02-01

Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder. The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder. Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54). Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.

Immediate versus delayed self-reporting of symptoms and side effects during chemotherapy: does timing matter?

PubMed

Coolbrandt, Annemarie; Van den Heede, Koen; Vanhove, Ellen; De Bom, Ann; Milisen, Koen; Wildiers, Hans

2011-04-01

The aim of this study was to examine how patients recall symptoms at a delayed self-report. Accurate insight into toxicity symptoms during chemotherapy is essential so that nurses and doctors can assess therapeutic tolerance and adjust supportive care accordingly. A non-experimental, longitudinal design was employed. Using the Therapy-Related Symptoms Checklist (TRSC), respondents (n = 142) reported their initial symptoms during the first 7 days of the chemotherapy cycle at two different times: (1) each day of the first seven days after the chemotherapy administration (immediate self-report), and (2) at their next hospital visit for chemotherapy (delayed self-report). We compared the number and severity of symptoms and side effects reported in the immediate and delayed self-reports. Respondents reported significantly fewer symptoms and fewer severe symptoms in the delayed self-report. For 22 out of 25 symptoms the delayed-reported grade was significantly lower than the immediate-reported maximum grade. Compared to the immediate-reported median grade, significant differences occurred in only 10 out of the 25 symptoms. In all cases, except fatigue, the delayed-reported grade was significantly higher than the immediate-reported median grade. This study indicates that delayed self-report of chemotherapy side effects is not an appropriate measure of actual symptoms and side effects experienced by patients. Delayed self-report gives a weaker insight into actual symptom burden. Fatigue is at particular risk to be minimized at the delayed self-report. Therefore it is recommended to assess chemotherapy-related symptoms and side effects by means of immediate self-report. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome.

PubMed

Noaiseh, Ghaith; Baker, Joshua F; Vivino, Frederick B

2014-01-01

There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting. Clinical, laboratory and pathological baseline variables were collected. Failure of therapy was defined as the clinician or patient's decision to stop treatment either due to lack of efficacy or side effects. Cevimeline was associated with lower failure rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side effect leading to cessation of therapy and occurred more frequently in pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously failed one secretagogue were less likely to discontinue treatment with the other agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA positivity was associated with failure: [59% vs. 38%] (p=0.03). pSS patients were more likely to continue cevimeline than pilocarpine long-term due to fewer reported side effects with cevimeline. Therapeutic failure of one secretagogue did not predict similar results with the other since second time users were more likely to continue long-term treatment.

Using a graphical risk tool to examine willingness to take migraine prophylactic medications.

PubMed

Turner, Dana P; Golding, Adrienne N; Houle, Timothy T

2016-10-01

Many migraine sufferers use daily prophylactic therapy to reduce the frequency of their headache attacks. The Food and Drug Administration has approved several different medications for migraine prophylaxis, but it is not clear whether sufferers perceive these treatments to provide clinically significant benefits given their side effect profiles. Three hundred headache sufferers were recruited from the community and local headache clinics using print and television advertising. Participants reported experiencing problematic headache attacks with a median (IQR) frequency of 7.0 (4-13) headache days per month. These sufferers participated in a cross-sectional, single-site, study that used a specially designed computer assessment task. Participants were instructed on the probability of experiencing the 3 most commonly experienced side effects for several blinded medication profiles: divalproex sodium, venlafaxine, gabapentin, propranolol, and topiramate. After learning the likelihood of experiencing side effect profiles of each medication, participants were asked whether they would be willing to take the medication for a given headache reduction level, which ranged from 0 to 7 days per month. The side effect profile for divalproex sodium was associated with the smallest willingness to take, with gabapentin, propranolol, and topiramate perceived to be much more agreeable. However, <60% of participants reported willingness to take any of these medications even if they provided a 50% reduction in headache frequency. Several general predictors of willingness to take were observed including high headache-related disability, depressive symptoms, and pain medication concerns including fear of tolerance. These findings suggest that if properly informed of the side effect profiles of these medications, many patients might opt for other treatments.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

PubMed

Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

PubMed

Haefliger, T; Bonsack, C

2006-01-01

Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case-reports describe the occurrence of retrograde ejaculation associated with risperidone but the exact prevalence is unknown. Retrograde ejaculation is thought to be related to the strong adrenolytic activity of risperidone. Alberto refused his medication because the ejaculatory dysfunction was unbearable for him. A switch to haloperidol depot was eventually well tolerated, without any sexual complaints. His case emphasizes the importance of sexual function for self-esteem and how this may amplify the intolerance to side-effects. David is on depot-risperidone in a setting of a legally forced treatment. Though he - reluctantly - accepts his medication, this side effect exacerbates his pre-existing delusions, strongly focused on sexual themes. His case illustrates how intolerance to sexual side-effects may be amplified by nature of delusions. Mireille is a 58 year old psychotic female patient, whose 2 mg risperidone treatment produced a unilateral galactorrhea. This sign became problematic because potentially visible at a time when Mireille started an activity in a sheltered occupation in town. Lowering dosage of antipsychotic allowed disappearance of the problem. Subjective responses to galactorrhea have been reported to be highly individual. Apart being a potentially visible side-effect, it may be misinterpreted as evidence of pregnancy or of a tumoral process. The cases of Ermina and Denise illustrate two contrasted situations in terms of subjective tolerability of reproductive function side-effects. Both were pre-menopausal patients with hyperprolactinemia secondary to risperidone treatment, resulting in amenorrhea. This was unbearable for Ermina. A switch to olanzapine allowed, one month later, the menses to resume. For Denise, on the other hand, the amenorrhea was a positive event, freeing her of unpleasant menses. Amenorrhea occurs in about 30% of pre-menopausal women treated with risperidone. It is a consequence of hyperprolactinemia, which, although often silent, is not devoid of potential negative consequences (ie increased risk of osteoporosis or neoplasia, worsening of psychopathology) (34). When hyperprolactinemia is symptomatic, lowering of the dose of the antipsychotic, or switching to a prolactin-sparing agent (olanzapine, quetiapine, aripiprazole and clozapine) is recommended. Before this, women with amenorrhea secondary to antipsychotic-induced hyperprolactinemia should be advised that menses may resume. Especially after long-standing amenorrhea they may assume being menopaused, hence may believe birth control measures are no longer required. The prevalence of antipsychotic-induced sexual and reproductive function side-effects is high. Clinicians should be aware of them, because they are often badly tolerated, are associated with a low satisfaction and may therefore result in low adherence with treatment. This implies for the clinician to overtly discuss with the patient of his sexuality and the potential negative impact of antipsychotic treatment on it. The recognition of these problems allows the searching together for a solution. The described cases indicate that solving the problem is often possible, provided that individual preferences and subjective impact are taken in account. Antipsychotic treatment is often prescribed for very long periods. A better knowledge of - and attention to - the associated side effects, particularly on the sexual and reproductive functions, is necessary in order to reduce some potentially negative long-term effects and to improve the adherence to treatment of our patients.

[Proton pump inhibitor - side effects and complications of long-term proton pump inhibitor administration].

PubMed

Ueberschaer, Hendrik; Allescher, Hans-Dieter

2017-01-01

Proton Pump Inhibitors are among the most common drugs taken. The indication is for treatment of heartburn, reflux disease, prophylaxis and treatment of peptic ulcers, in combination with NSAIDs and steroids as well as H. pylori-eradication. PPI's are widely used, even with non-specific symptoms. This certainly has to do with good tolerability and a previously considered low side effect profile. At the moment, there is growing evidence that the long-term intake of PPI's may not be as safe as assumed. In addition to interactions with some drugs, including platelet aggregation inhibitors, recent studies have shown an increased risk of myocardial infarction, interstitial nephritis, chronic renal injury, infections, vitamin deficiencies and electrolyte shifts as well developing dementia. © Georg Thieme Verlag KG Stuttgart · New York.

[Drug management for coronary artery disease in the elderly].

PubMed

Meune, C

2006-11-01

The incidence of side effects increases dramatically with age. It is estimated that almost one third of side effects could be avoided by an appropriate prescription. On the other hand, age is the main factor associated to the non-prescription of major pharmacological classes, which have evidenced their efficacy in younger patients with coronary artery disease. The estimation of the benefit/risk ratio is therefore highly important in the old/very old patient. It seems important to integrate the results of studies and registries including old patients, evidencing the efficacy of the majority of pharmacological classes validated in younger patients, especially antiplatelets, beta-blockers and statins. The assessment of the benefit/risk ratio should also take into account the tolerance profile of the drug and the patient. The prescription should be adapted to the "age-related" changes of pharmacokinetics and pharmacodynamics.

[Antiandrogen gynecomastia: an inescapable harm? Radiotherapy: a simple and efficient solution!].

PubMed

Couke, Philippe A; Jichliski, Patrice; Matzinger, Oscar; Ozsahin, Mahmut; Bulling, Shelley M; Zouhair, Abderrahim

2004-01-01

Anti-androgen induced gynecomastia, resulting from a treatment induced imbalance between oestrogens and androgens, is a frequently encountered side effect in the hormonal treatment of patients with prostatic cancer. One might expect to face an increase in the overall incidence of this side effect in the next-coming years as randomized trials clearly point to the evidence of the therapeutic benefit of anti-androgenic treatment for this prostatic cancer. Gynecomastia is often accompanied by mastodynia and does hamper quality of life. Surgery should be considered for established irreversible gynecomastia characterized by hyalinization and extensive fibrosis. However, radiotherapy is the treatment of choice for gynecomastia at it's early stage, or could eventually be considered as a prophylactic treatment in high risk patients. It is a safe and extremely well tolerated treatment resulting in a high degree of therapeutic success with a demonstrated effect on quality of life as reported in randomized trials. To date no medical treatment is proven effective nor devoid from deleterious effects and licenced for this indication.

Molecular Pharmacology of δ-Opioid Receptors

PubMed Central

Gendron, Louis; Cahill, Catherine M.; von Zastrow, Mark; Schiller, Peter W.

2016-01-01

Opioids are among the most effective analgesics available and are the first choice in the treatment of acute severe pain. However, partial efficacy, a tendency to produce tolerance, and a host of ill-tolerated side effects make clinically available opioids less effective in the management of chronic pain syndromes. Given that most therapeutic opioids produce their actions via µ-opioid receptors (MOPrs), other targets are constantly being explored, among which δ-opioid receptors (DOPrs) are being increasingly considered as promising alternatives. This review addresses DOPrs from the perspective of cellular and molecular determinants of their pharmacological diversity. Thus, DOPr ligands are examined in terms of structural and functional variety, DOPrs’ capacity to engage a multiplicity of canonical and noncanonical G protein–dependent responses is surveyed, and evidence supporting ligand-specific signaling and regulation is analyzed. Pharmacological DOPr subtypes are examined in light of the ability of DOPr to organize into multimeric arrays and to adopt multiple active conformations as well as differences in ligand kinetics. Current knowledge on DOPr targeting to the membrane is examined as a means of understanding how these receptors are especially active in chronic pain management. Insight into cellular and molecular mechanisms of pharmacological diversity should guide the rational design of more effective, longer-lasting, and better-tolerated opioid analgesics for chronic pain management. PMID:27343248

[The efficacy and tolerability of pericyazine in the treatment of patients with schizotypal disorder, organic personality disorders and pathocharacterological changes within personality disorders].

PubMed

Danilov, D S

To assess the efficacy and tolerability of pericyazine in the treatment of patients with mental disorders manifesting with psychopathic-like symptoms and correction of pathocharacterological disorders in patients with personality disorders during the short-term admission to the hospital or the long-term outpatient treatment. Sixty-three patients with schizotypal personality disorder and organic personality disorder with psychopathic-like symptoms and pathocharacterological changes within the diagnosis of dissocial personality disorder and borderline personality disorder were examined. Patients received pericyazine during the short-term admission to the hospital (6 weeks) or the long-term outpatient treatment (6 month). Efficacy, tolerability and compliance were assessed in the study. Treatment with pricyazine was effective in all patients. The improvement was seen in patients with organic personality disorders and patients with personality disorders (psychopathy). The maximal effect was observed in inpatients and this effect remained during outpatient treatment. The improvement of mental state of patients with schizotypal personality disorder achieved during inpatient treatment with pericyazine continued during the long-term outpatient treatment. Side-effects were restricted to extrapyramidal symptoms, the frequency of metabolic syndrome was low. During outpatient treatment, the compliance was higher if the patient was managed by the same psychiatrist during inpatient- and outpatient treatment.

The role of pirfenidone in the treatment of idiopathic pulmonary fibrosis

PubMed Central

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease, with a median survival time of 2–5 years. The search for effective treatment has involved numerous clinical trials of investigational agents without significant success. However, in 2011, pirfenidone was the first drug to be approved for the treatment of IPF in Europe. Four key clinical trials supported the efficacy and tolerability of pirfenidone. In the two recently published Phase III CAPACITY trials evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF were treated with pirfenidone or placebo. Study 004 and pooled analysis of primary endpoint data from both studies showed that pirfenidone significantly reduced decline in percent-predicted forced vital capacity (FVC) compared with placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was also observed with regard to several secondary endpoints. Pirfenidone was generally well tolerated, with the most common side effects being gastrointestinal and photosensitivity. Data from the RECAP extension phase of the CAPACITY studies, where patients were treated with pirfenidone for up to three years, further support the manageable tolerability profile of pirfenidone. The efficacy data, coupled with long-term safety data, provide further evidence of a clinically-meaningful treatment effect with pirfenidone in patients with IPF. PMID:23734908

Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices?

PubMed

González, Mónica; Macias-Escalada, Emilio; Cobo, Juan; Fernández Mondragón, Maria Pilar; Gómez-Moreno, Gerardo; Martínez-Martínez, Marian; de Carlos, Felix

2016-12-01

Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p < 0.001). The risk of suffering muscular alterations during oral device treatment is higher in statin patients (odds ratio 6.67, p = 0.002). Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices.

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial.

PubMed

Gálvez, Verònica; Li, Adrienne; Huggins, Christina; Glue, Paul; Martin, Donel; Somogyi, Andrew A; Alonzo, Angelo; Rodgers, Anthony; Mitchell, Philip B; Loo, Colleen K

2018-04-01

Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment. Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups. IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.

Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain

PubMed Central

Hale, David E; Guindon, Josée; Morgan, Daniel J

2017-01-01

The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits. This study assessed the anti-nociceptive effects of a selective cannabinoid 2 receptor agonist (JWH-133) in pathological pain using mice subjected to inflammatory pain using the formalin test. Furthermore, we examined several ways in which JWH-133 may interact with morphine. JWH-133 produces dose-dependent anti-nociception during both the acute and inflammatory phases of the formalin test. This was observed in both male and female mice. However, a maximally efficacious dose of JWH-133 (1 mg/kg) was not associated with somatic withdrawal symptoms, motor impairment, or hypothermia. After eleven once-daily injections of 1 mg/JWH-133, no tolerance was observed in the formalin test. Cross-tolerance for the anti-nociceptive effects of JWH-133 and morphine were assessed to gain insight into physiologically relevant cannabinoid 2 receptor and mu-opioid receptor interaction. Mice made tolerant to the effects of morphine exhibited a lower JWH-133 response in both phases of the formalin test compared to vehicle-treated morphine-naïve animals. However, repeated daily JWH-133 administration did not cause cross-tolerance for morphine, suggesting opioid and cannabinoid 2 receptor cross-tolerance is unidirectional. However, preliminary data suggest co-administration of JWH-133 with morphine modestly attenuates morphine tolerance. Isobolographic analysis revealed that co-administration of JWH-133 and morphine has an additive effect on anti-nociception in the formalin test. Overall these findings show that cannabinoid 2 receptor may functionally interact with mu-opioid receptor to modulate anti-nociception in the formalin test. PMID:28879802

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

PubMed

Davies, Andrew N; Thompson, Jo

2015-10-05

This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

[Axillary hyperhidrosis--efficacy and tolerability of an aluminium chloride antiperspirant. Prospective evaluation on 20 patients with idiopathic axillary hyperhidrosis].

PubMed

Streker, M; Reuther, T; Verst, S; Kerscher, M

2010-02-01

The purpose of this study was to evaluate the efficacy and tolerability of aluminium chloride gel for treatment of axillary hyperhidrosis. A total of 20 patients aged 22-38 (mean age: 26.9+/-4.3) with idiopathic axillary hyperhidrosis were included and treated with an antiperspirant (Sweat-off, Sweat-off GmbH, Hügelsheim). Study duration was 42 days. Treatment efficacy was evaluated clinically, as well as by starch-iodine test, gravimetric analysis and evaluation of the skin surface pH. After treatment there was a significant clinical improvement accompanied by significant qualitative and quantitative reduction of sweat as well as a significant reduction of skin surface pH. Except for slight skin irritation in 6 patients, there were no other side effects. Patient satisfaction improved markedly during the study. Treatment of axillary hyperhidrosis with aluminium chloride is an effective, safe and inexpensive treatment modality.

Recent advancements in drug treatment of obesity.

PubMed

Carter, Rebeca; Mouralidarane, Angelina; Ray, Shuvra; Soeda, Junpei; Oben, Jude

2012-10-01

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

PubMed

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

PubMed Central

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Abstract Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications. PMID:29379674

Leukapheresis treatment in elderly acute leukemia patients with hyperleukocytosis: A single center experience.

PubMed

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Gozukara Bag, Harika; Nizam, Ilknur; Koroglu, Mustafa; Yigit, Ali; Ozgul, Mustafa

2016-02-01

Leukapheresis is an invasive treatment modality used for hyperleukocytosis. Various drugs and fluids are used during the leukapheresis. Aging itself and associated factors such as increased comorbidity, decreased tolerance to drugs, increased drug toxicity give rise to the application of other treatment modalities in elderly patients. Treatment of acute leukemia in the elderly differs from young patients. Consequently, we assumed that outcome, effectiveness, and side effects of leukapheresis treatment used for acute leukemia patients with hyperleukocytosis may be different in elderly compared to younger patients. We retrospectively evaluated a total of 39 patients. Eighteen patients were 65 years and older. Indications for leukapheresis were determined as symptoms of leukostasis and prophylaxis. Acid citrate dextrose-A, calcium gluconate, and plasma were used during the leukapheresis. Age, sex, diagnosis, count, and indications of leukapheresis procedures, leukocyte count, and lactate dehydrogenase level were analyzed at the onset of and after leukapheresis; side effects, causes of death, early and total mortality rates were also analyzed. We compared the two groups with regard to effectiveness, clinical outcomes, and side effects. There were no statistically significant differences between the two groups with respect to sex, diagnosis, initial leukocyte count, lactate dehydrogenase level, number of leukapheresis procedures, rates of side effects, or early and total mortality (P > 0.05). Leukapheresis treatment was effective in both groups (P < 0.05) and no significant difference was found in its effectiveness between two groups (P > 0.05). Leukapheresis is an effective and safe treatment modality in elderly acute leukemia patients with hyperleukocytosis. © 2015 Wiley Periodicals, Inc.

Assessment of the efficacy and tolerance of a new combination of retinoids and depigmenting agents in the treatment of melasma.

PubMed

Truchuelo, Maria Teresa; Jiménez, Natalia; Jaén, Pedro

2014-12-01

Melasma is a dermatosis with significant repercussions on patients' quality of life, and there is currently no standard treatment. Hydroquinone is deemed the treatment of choice, but its safety has been questioned in certain cases. To determine the efficacy and safety of a new combination of retinoids in the improvement of melasma. Prospective, double-blind, vehicle-controlled, and randomized study in 30 patients with melasma. The product was applied on one side of the face and the vehicle on the other, twice daily during 3 months. Standardized photographs were taken using RBX technology on the three visits (basal, at one and a half months and at 3 months). The main variable to determine the efficacy was the improvement of the hemifacial Melasma Area Severity Index (MASI). Other variables were determined such as improvement perceived by the investigator, improvement perceived by the patient, impact on quality of life or side effects. The MASI improvement at 3 months of treatment was significant on the treated side vs. the vehicle side, reaching an improvement of 70%, which is comparable to the percentage of improvement described with hydroquinone. No notable side effects were detected, in spite of a significant percentage of patients included in the study citing a history that could be compatible with sensitive skin. This new combination of retinoids and depigmenting agents proved to be effective and safe in the treatment of melasma. © 2014 Wiley Periodicals, Inc.

Antioxidants in Photosynthesis and Human Nutrition

NASA Astrophysics Data System (ADS)

Demmig-Adams, Barbara; Adams, William W.

2002-12-01

The harnessing of solar energy by photosynthesis depends on a safety valve that effectively eliminates hazardous excess energy and prevents oxidative damage to the plant cells. Many of the compounds that protect plant cells also protect human cells. Improving plant resistance to stress may thus have the beneficial side effect of also improving the nutritional quality of plants in the human diet. The pathways that synthesize these compounds are becoming amenable to genetic manipulation, which may yield benefits as widespread as improved plant stress tolerance and improved human physical and mental health.

[Integration of nutritional care into cancer treatment: need for improvement].

PubMed

Joly, Caroline; Jacqueline-Ravel, Nathalie; Pugliesi-Rinaldi, Angela; Bigler-Perrotin, Lucienne; Chikhi, Marinette; Dietrich, Pierre-Yves; Dulguerov, Pavel; Miralbell, Raymond; Picard-Kossovsky, Michel; Seium, Yodit; Thériault, Michel; Pichard, Claude

2011-11-16

Progresses in cancer treatment transformed cancer into a chronic disease associated with growing nutritional problems. Poor nutritional status of cancer patients worsens morbidity, mortality, overall cost of care and decreases patients' quality of life, oncologic treatments tolerance and efficacy. These adverse effects lead to treatment modifications or interruptions, reducing the chances to control or cure cancer. Implementation of an interdisciplinary and longitudinal integration of nutritional care and nutritional information into cancer treatment (The OncoNut Program) could prevent or treat poor nutritional status and its adversely side effects.

Three day oral course of Augmentin to treat chancroid.

PubMed Central

Ndinya-Achola, J O; Nsanze, H; Karasira, P; Fransen, L; D'Costa, L J; Piot, P; Ronald, A R

1986-01-01

Amoxycillin and clavulanic acid (Augmentin; Beecham Research Laboratories) was used to treat patients with bacteriologically proved chancroid in three different dose regimens. A single dose of Augmentin (amoxycillin 3 g, clavulanic acid 350 mg) was found to be ineffective. A similar dose repeated after 24 hours was equally ineffective, but a dose (amoxycillin 500 mg, clavulanic acid 250 mg) given every 8 hours for three days was found to be effective. The drug was well tolerated and no side effects were noted in any of the patients treated. PMID:3733082

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

This chapter concludes the survey of experimental and clinical data on the analgesic and antitussive properties of codeine and its potential therapeutic alternates. From an evaluation of their effectiveness on the one hand and the side-effects, including tolerance, dependence and abuse liability on the other, it would appear that the therapeutic goals of codeine could be achieved by other substances, except perhaps where analgesia, cough relief, and sedation are required simultaneously. The use of these other substances would, however, result in no particular gain and probably no particular loss. PMID:4898386

F45. THE EFFICACY AND SAFETY OF BLONASERIN AFTER SWITCHING FROM OTHER ATYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIC INPATIENTS: AN OPEN-LABEL, MULTI-CENTER TRIAL

PubMed Central

Yoon, Bo-Hyun; Bahk, Won-Myong; Kwon, Young Joon; Lee, Sang-Yeol; Lee, Kwanghun; Kim, Moon Doo; Park, Sung-Yong; Song, Min-Kyu

2018-01-01

Abstract Background The aim of this study was to investigate the efficacy and safety of blonanserin treatment after switching from other atypical antipsychotics in schizophrenic inpatients who showed inadequate efficacy and poor tolerability. Methods A total of 63 schizophrenic inpatients (inadequate response group=45 and poor tolerability group=18) were included in this study. They were already treated with atypical antipsychotics except blonanserin and not favored due to inadequate responses or intolerable adverse effects. Blonanserin was administered during 12 weeks after switching from their previous antispsychotics. Treatment response was evaluated with Brief Psychiatric Rating Scale (BPRS) and CGI-S, and safety profile were measured with Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Extrapyramidal Side effects Scale (SAR)S and Barnes Akathisia Rating Scale (BARS). Drug Attitude Inventory (DAI-10) and Subjective Well-being Under Neuroleptic Treatment (SWN) were used for subjective estimates. Assessments were done at baseline, 1, 2, 4, 8 and 12 weeks after blonanserin treatment. Repeated measures of ANOVA were done to analyze the group (inadequate vs. intolerable group) and time effects. Results CGI and BPRS were showed significant treatment responses after switching to Blonaserin. Time effects were significant at 2, 4, 8, 12 weeks after switching and group by time effect were also significant at that time. Mean changes of AIMS, SARS and BARS scores were not significant throughout test trial. Although SWN was significantly improved after switching to Blonaserin, it was not found significant group by time effect. Discussion The results suggest that blonanserin may be effective and well tolerable in schizophrenic patients who showed inadequate treatment response or poor tolerability.

SKELETAL MUSCLE ULTRASTRUCTURE AND FUNCTION IN STATIN-TOLERANT INDIVIDUALS

PubMed Central

Rengo, Jason L.; Callahan, Damien M.; Savage, Patrick D.; Ades, Philip A.; Toth, Michael J.

2015-01-01

Skeletal Muscle Ultrastructure and Function in Statin-Tolerant Individuals: Introduction Statins have well-known benefits on cardiovascular mortality, though up to 15% of patients experience side effects. With guidelines from the American Heart Association, American College of Cardiology, and American Diabetics Association expected to double the number of statin users, the overall incidence of myalgia and myopathy will increase. Methods We evaluated skeletal muscle structure and contractile function at the molecular, cellular, and whole tissue levels in 12 statin tolerant and 12 control subjects. Results Myosin isoform expression, fiber type distributions, single fiber maximal Ca2+-activated tension, and whole muscle contractile force were similar between groups. No differences were observed in myosin-actin cross-bridge kinetics in myosin heavy chain (MHC) I or IIA fibers. Discussion We found no evidence for statin-induced changes in muscle morphology at the molecular, cellular, or whole tissue levels. Collectively, our data show that chronic statin therapy in healthy asymptomatic individuals does not promote deleterious myofilament structural or functional adaptations. PMID:26059690

Topical treatment of tinea pedis using 6% coriander oil in unguentum leniens: a randomized, controlled, comparative pilot study.

PubMed

Beikert, F C; Anastasiadou, Z; Fritzen, B; Frank, U; Augustin, M

2013-01-01

The antifungal activity of coriander oil has already been demonstrated in vitro. Evaluation of the efficacy and tolerability of 6% coriander oil in unguentum leniens in the treatment of interdigital tinea pedis. Half-side comparative pilot study on subjects with symmetric, bilateral interdigital tinea pedis. Active drug and placebo control were applied twice daily on the affected areas, and follow-up visits were performed on days 14 and 28. 40 participants (mean age 52.5 years, 60% male) were included in the study. For 6% coriander oil in unguentum leniens, a highly significant improvement of the clinical signs (p < 0.0001) was observed during the entire observation period; the number of positive fungal cultures also tended to decrease (p = 0.0654). The tolerability of the tested substances was good. Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis. Copyright © 2013 S. Karger AG, Basel.

Comparison of the pattern, efficacy, and tolerability of self-medicated drugs in primary dysmenorrhea: a questionnaire based survey.

PubMed

Sugumar, Ramya; Krishnaiah, Vasundara; Channaveera, Gokul Shetty; Mruthyunjaya, Shilpa

2013-01-01

To compare the pattern, efficacy, and tolerability of self-medicated drugs and to assess the adequacy of their dose in primary dysmenorrhea (PD). A survey using a self-developed, validated, objective, and structured questionnaire as a tool was conducted among subjects with PD. Statistical analysis was carried out using Chi-square test and ANOVA with post-hoc Tuckey's test. Out of 641 respondents, 42% were self-medicated. The pattern of drugs used was: Dicyclomine, an unknown drug, mefenamic acid, mefenamic acid + dicyclomine, and metamizole by 35%, 29%, 26%, 9%, and 1% of respondents, respectively. Mefenamic acid + dicyclomine, the combination was the most efficacious in comparison to other drugs in moderate to severe dysmenorrhea. There was better tolerability with mefenamic acid + dicyclomine group compared to other drugs. Sub-therapeutic doses were used by 86% of self-medicating respondents. The prevailing self-medication practices were inappropriate in a substantial proportion of women with inadequate knowledge regarding appropriate drug choice, therapeutic doses, and their associated side effects.

Tolerability of clindamycin/tretinoin gel vs. tretinoin microsphere gel and adapalene gel.

PubMed

Leyden, James; Wortzman, Mitchell; Baldwin, Edward K

2009-04-01

Newer agents and formulations seek to improve the tolerability of topical retinoid therapy. Recently, a gel containing crystalline clindamycin 1.2% and tretinoin 0.025% (CLIN/RA) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of treating mild-to-moderate acne. This single-center, randomized, evaluator-blind phase 1 study compared the tolerability of CLIN/RA to 0.1% tretinoin gel or 0.1% adapalene gel. Forty-five patients applied CLIN/RA once daily to one side of their face every day for 21 days. Patients were randomized to either tretinoin 0.1% (n = 23) or adapalene 0.1% (n = 22) on the contralateral side. A clinical evaluator assessed degree of erythema and scaling; patients provided subjective evaluations of burning, stinging, and itching. CLIN/RA was significantly better tolerated than was 0.1% tretinoin gel, as evidenced by significantly reduced erythema (P < 0.04), scaling (P < 0.03), itching (P < 0.02), burning (P < 0.03) and stinging (P < 0.04). A trend for greater erythema, scaling, and subjective discomfort for 0.1% adapalene gel compared to CLIN/RA was also evident.

[Iron deficiency anemia and pregnancy. Prevention and treatment].

PubMed

Beucher, G; Grossetti, E; Simonet, T; Leporrier, M; Dreyfus, M

2011-05-01

To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy. French and English publications were searched using PubMed and Cochrane library. Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion. Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis

PubMed Central

Geusens, Piet; Lems, Willem

2008-01-01

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver. PMID:18728796

Novel investigational drugs mimicking exercise for the treatment of cachexia.

PubMed

Penna, F; Pin, F; Ballarò, R; Baccino, F M; Costelli, P

2016-01-01

Cachexia is a syndrome characterized by body weight loss, muscle wasting and metabolic abnormalities, that frequently complicates the management of people affected by chronic diseases. No effective therapy is actually available, although several drugs are under clinical evaluation. Altered energy metabolism markedly contributes to the pathogenesis of cachexia; it can be improved by exercise, which is able to both induce anabolism and inhibit catabolism. This review focuses on exercise mimetics and their potential inclusion in combined protocols to treat cachexia. The authors pay with particular reference to the cancer-associated cachexia. Even though exercise improves muscle phenotype, most patients retain sedentary habits which are quite difficult to disrupt. Moreover, they frequently present with chronic fatigue and comorbidities that reduce exercise tolerance. For these reasons, drugs mimicking exercise could be beneficial to those who are unable to comply with the practice of physical activity. Since some exercise mimetics may exert serious side effects, further investigations should focus on treatments which maintain their effectiveness on muscle phenotype while remaining tolerable at the same time.

Psychotropic drug treatment in anorexia nervosa. Search for differences in efficacy/tolerability between adolescent and mixed-age population.

PubMed

Balestrieri, Matteo; Oriani, Maria Ginevra; Simoncini, Annalisa; Bellantuono, Cesario

2013-09-01

During the last 10 years, the use of psychotropic medications in youth with psychiatric disorders, including eating disorders, has significantly increased, but their role in the treatment of adolescent anorexia nervosa is still controversial. This paper aims to review the literature on the use of antidepressants and antipsychotics in adolescents with anorexia nervosa, comparing the efficacy and tolerability in this population with those reported in trials with patients not selected by age. A systematic review of the available literature published so far. Only few studies met the selection criteria. No strong evidence of beneficial effects was found in using antidepressants and antipsychotics neither in adults nor in adolescents. Side effects were more frequently reported in studies including adolescent population. Among psychotropic drugs, the majority of studies focused on olanzapine, which seems to have, in some studies, only positive effects on body mass index, eating disorder symptoms and functional impairment in both age groups. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement.

PubMed

Ramar, Kannan; Rosen, Ilene M; Kirsch, Douglas B; Chervin, Ronald D; Carden, Kelly A; Aurora, R Nisha; Kristo, David A; Malhotra, Raman K; Martin, Jennifer L; Olson, Eric J; Rosen, Carol L; Rowley, James A

2018-04-15

The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA. © 2018 American Academy of Sleep Medicine.

Comparison of tretinoin 0.05% cream and 3% alcohol-based salicylic acid preparation in the treatment of acne vulgaris.

PubMed

Babayeva, L; Akarsu, S; Fetil, E; Güneş, A T

2011-03-01

No single effective topical treatment is available for treating all pathogenic factors causing acne vulgaris (AV). Salicylic acid (SA), tretinoin (all-TRA) and clindamycin phosphate (CDP) are known to to be effective agents depending on their comedolytic and anti-inflammatory properties. To compare the efficacy and tolerability of SA and CDP combination (SA+CDP) with all-TRA and CDP (all-TRA+CDP) in patients with mild to moderate facial AV. Forty-six patients aged between 18 and 35 years were enrolled in a 12-week prospective, single-blind, randomized and comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurement of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts and showed significant global improvement as evaluated by the investigator. At the end of the study, there was no significant difference between the two groups in terms of all lesion counts. In addition, TL counts decreased faster in the all-TRA+CDP group compared with those in the SA+CDP group, with a significant difference between the two groups occurring as early as 2 weeks. Safety evaluations demonstrated that the incidence of mild to moderate side effects generally peaked at week 2 and declined gradually thereafter. Both combinations did not have an effect on stratum corneum hydration, although skin sebum values decreased with SA+CDP treatment. Combination of SA+CDP and all-TRA+CDP was effective in decreasing lesion counts and well tolerated with minimal local cutaneous reactions in patients with mild to moderate AV. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

PubMed Central

Shen, Jie; Wang, Li-Feng; Zou, Zheng-Yun; Kong, Wei-Wei; Yan, Jing; Meng, Fan-Yan; Chen, Fang-Jun; Du, Juan; Shao, Jie; Xu, Qiu-Ping; Ren, Hao-Zhen; Li, Ru-Tian; Wei, Jia; Qian, Xiao-Ping; Liu, Bao-Rui

2017-01-01

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective. PMID:28839440

[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

PubMed

Suzuki, Kei; Sekine, Takao

2014-05-01

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

PubMed Central

Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina

2016-01-01

Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603

Disulfiram for binge eating disorder: an open trail.

PubMed

Farci, Anna Maria Giulia; Piras, Simona; Murgia, Magnolia; Chessa, Alessandra; Restivo, Angelo; Gessa, Gian Luigi; Agabio, Roberta

2015-01-01

To evaluate the efficacy and safety of disulfiram for treatment of binge eating disorder. Two hundred and fifty milligrams per day of disulfiram was administered to 12 patients affected by binge eating disorder for 16 weeks; the number of binge eating episodes per week and the number of participants who reported side effects were evaluated. Nine participants (75.0%) completed the trial, while the other 3 (25.0%) discontinued prematurely. Disulfiram significantly decreased the mean frequency of binge eating episodes per week from 7.9±1.2 to 0.9±0.6 (p<.001). All patients (100.0%) reduced the frequency of binge eating episodes, and 7 participants (58.3%) achieved remission of binge eating. Eleven participants (91.7%) reported side effects [drowsiness (N=9), headache (N=7), dysgeusia (N=3), tachycardia (N=3), dizziness (N=2), and nausea (N=2)]. While disulfiram reduced the frequency of binge eating episodes, side effects were observed in the majority of participants. Longer-term placebo-controlled studies are warranted to exclude the contribution of a placebo response from these results and to evaluate drugs with similar pharmacological activity but improved tolerability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: expert consensus by a panel of Italian and Spanish psychiatrists.

PubMed

Fagiolini, Andrea; Alfonsi, Emilia; Amodeo, Giovanni; Cenci, Mario; Di Lella, Michele; Farinella, Francesco; Ferraiuolo, Fabrizio; Fraguas, David; Loparco, Natale; Gutierrez-Rojas, Luis; Mignone, Maria Laura; Pataracchia, Giuseppe; Pillai, Gianluca; Russo, Felicia; Sanchez-Gistau, Vanessa; Spinogatti, Franco; Toscano, Marco; Villari, Vincenzo; De Filippis, Sergio

2016-01-01

Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process.

Bayesian and Phylogenic Approaches for Studying Relationships among Table Olive Cultivars.

PubMed

Ben Ayed, Rayda; Ennouri, Karim; Ben Amar, Fathi; Moreau, Fabienne; Triki, Mohamed Ali; Rebai, Ahmed

2017-08-01

To enhance table olive tree authentication, relationship, and productivity, we consider the analysis of 18 worldwide table olive cultivars (Olea europaea L.) based on morphological, biological, and physicochemical markers analyzed by bioinformatic and biostatistic tools. Accordingly, we assess the relationships between the studied varieties, on the one hand, and the potential productivity-quantitative parameter links on the other hand. The bioinformatic analysis based on the graphical representation of the matrix of Euclidean distances, the principal components analysis, unweighted pair group method with arithmetic mean, and principal coordinate analysis (PCoA) revealed three major clusters which were not correlated with the geographic origin. The statistical analysis based on Kendall's and Spearman correlation coefficients suggests two highly significant associations with both fruit color and pollinization and the productivity character. These results are confirmed by the multiple linear regression prediction models. In fact, based on the coefficient of determination (R 2 ) value, the best model demonstrated the power of the pollinization on the tree productivity (R 2  = 0.846). Moreover, the derived directed acyclic graph showed that only two direct influences are detected: effect of tolerance on fruit and stone symmetry on side and effect of tolerance on stone form and oil content on the other side. This work provides better understanding of the diversity available in worldwide table olive cultivars and supplies an important contribution for olive breeding and authenticity.

[Prophylactic drug treatment of migraine].

PubMed

Massiou, H; Bousser, M-G

2005-07-01

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. Based on the results of published controlled trials, the main prophylactic drugs are some beta-blockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, sodium valproate and topiramate. With these drugs, the frequency of attacks can be reduced by half in 50 percent of patients. Some less evaluated substances such as aspirin, DHE, indoramine, and angiotensin II inhibitors may be useful. The decision to treat with drugs and the choice of a prophylactic drug are made together with the patient. The superiority of one major drug over another has never been demonstrated in a comparative trial, thus the choice of the drug to start with depends on the possible side effects and contraindications, the characteristics of the migraine attacks, and the associated morbidities and possible interactions with abortive medications. Doses should be increased gradually, in order to reach the recommended daily dose, only if tolerance permits. Treatment efficacy has to be assessed after 2 or 3 months, and in case of failure or poor tolerance, another treatment should be started. If the treatment is successful, it should be continued for 6 to 12 months, and then tapered off. The moderate efficacy and the frequency of the side effects observed with prophylactic drugs explain the high rate of withdrawals. Some patients nevertheless dramatically improve, warranting trying several drugs successively in order to find the most appropriate one.

Continuous extraovular administration of prostaglandin F2alpha for midtrimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1974-09-15

Midtrimester abortion was successfully induced in 74 of 76 patients by a continuous extraovular administration of (PGF2alpha) prostaglandin F2alpha via a constant-infusion pump. 2 patients in the 13th-14th weeks of gestation failed to abort despite good uterine activity. The mean abortion time for successful inductions was 16.21 hours. Parous patients aborted somewhat faster than nulliparous patients, but the difference was not statistically significant. All patients were monitored throughout the abortion procedure, and uterine activity was calculated and analyzed. Uterine activity developed within 15 minutes of PGF2alpha instillation and showed the characteristic uterine response to PGs with a sharp rise in intrauterine tonus. The gastrointestinal side effects in this series were much less than those reported for intraamniotic instillation of PG, and there was good patient tolerance of the procedure. The main complication of extraovular administration of PGF2alpha for midtrimester abortion was endometritis, which occurred in 7 patients. The patients who developed endometritis had, as a group, longer abortion times (mean=28 hours). 3 patients with severe preeclampsia and intrauterine death in the third trimester also had successfully induced labor with extraovular administration of PGF2alpha. The method of PGF2alpha administration in the series was found to have a high success rate, good patient tolerance, and fewer side effects than when abortion was induced by intraamniotic instillation of PGF2alpha.

Daylight methyl-aminolevulinate photodynamic therapy versus ingenol mebutate for the treatment of actinic keratoses: an intraindividual comparative analysis.

PubMed

Genovese, Giovanni; Fai, Dario; Fai, Carlotta; Mavilia, Luciano; Mercuri, Santo R

2016-05-01

Daylight-photodynamic therapy (D-PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D-PDT versus IM in the treatment of grade I and II AK. Twenty-seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm(2) target area, D-PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D-PDT and IM (p=0.74). In D-PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D-PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D-PDT in terms of LSR and pain. D-PDT was more cosmetically acceptable. Patients preferred D-PDT to IM in most cases. © 2016 Wiley Periodicals, Inc.

Alumina additions may improve the damage tolerance of soft machined zirconia-based ceramics.

PubMed

Oilo, Marit; Tvinnereim, Helene M; Gjerdet, Nils Roar

2011-01-01

The aim of this study was to evaluate the damage tolerance of different zirconia-based materials. Bars of one hard machined and one soft machined dental zirconia and an experimental 95% zirconia 5% alumina ceramic were subjected to 100,000 stress cycles (n = 10), indented to provoke cracks on the tensile stress side (n = 10), and left untreated as controls (n = 10). The experimental material demonstrated a higher relative damage tolerance, with a 40% reduction compared to 68% for the hard machined zirconia and 84% for the soft machined zirconia.

Side effects as influencers of treatment outcome.

PubMed

Sharif, Zafar

2008-01-01

Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

Was Earth ever infected by martian biota? Clues from radioresistant bacteria.

PubMed

Pavlov, Anatoly K; Kalinin, Vitaly L; Konstantinov, Alexei N; Shelegedin, Vladimir N; Pavlov, Alexander A

2006-12-01

Here we propose that the radioresistance (tolerance to ionizing radiation) observed in several terrestrial bacteria has a martian origin. Multiple inconsistencies with the current view of radioresistance as an accidental side effect of tolerance to desiccation are discussed. Experiments carried out 25 years ago were reproduced to demonstrate that "ordinary" bacteria can develop high radioresistance ability after multiple cycles of exposure to high radiation dosages followed by cycles of recovery of the bacterial population. We argue that "natural" cycles of this kind could have taken place only on the martian surface, and we hypothesize that Mars microorganisms could have developed radioresistance in just several million years' time and, subsequently, have undergone transfer to Earth by way of martian meteorites. Our mechanism implies multiple and frequent exchanges of biota between Mars and Earth.

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Long-term treatment of severe hypertension with minoxidil.

PubMed Central

Nawar, T.; Nolin, L.; Plante, G. E.; Caron, C.; Montambault, P.

1977-01-01

Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure. PMID:603847

Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C.

PubMed

Wu, Jing Yuan J; Shadbolt, Bruce; Teoh, Narci; Blunn, Anne; To, Caroline; Rodriguez-Morales, Ilys; Chitturi, Shivakumar; Kaye, Graham; Rodrigo, Kalyana; Farrell, Geoff

2014-06-01

Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P < 0.05) but did not affect treatment outcome. Twenty-seven patients reported schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

PubMed

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2011-12-01

PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility. Copyright © 2011 Elsevier Inc. All rights reserved.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed,more » in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.« less

A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception.

PubMed

Borckardt, Jeffrey J; Bikson, Marom; Frohman, Heather; Reeves, Scott T; Datta, Abhishek; Bansal, Varun; Madan, Alok; Barth, Kelly; George, Mark S

2012-02-01

Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain. Copyright © 2012. Published by Elsevier Inc.

FUEL EFFECTS ON COMBUSTION WITH EGR DILUTION IN SPARK IGNITED ENGINES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szybist, James P

The use of EGR as a diluent allows operation with an overall stoichiometric charge composition, and the addition of cooled EGR results in well-understood thermodynamic benefits for improved fuel consumption. This study investigates the effect of fuel on the combustion and emission response of EGR dilution in spark ignited engines. A 2.0 L GM Ecotec LNF engine equipped with the production side-mounted direct injection (DI) fueling system is used in this study. Ethanol, isooctane and certified gasoline are investigated with EGR from 0% to the EGR dilution tolerance. Constant BMEP at 2000 rpm was operated with varying CA50 from 8more » CAD to 16 CAD aTDCf. The results show that ethanol gives the largest EGR tolerance at a given combustion phasing, engine load and speed. The improved EGR dilution tolerance with ethanol is attributed to a faster flame speed, which manifests itself as shorter combustion duration. Data shows that the combustion stability limit occurs at a critical combustion duration that is fuel independent. Due to different flame speeds, this critical combustion duration occurs at different EGR levels for the different fuels.« less

The safety of istradefylline for the treatment of Parkinson's disease.

PubMed

Müller, Thomas

2015-05-01

Antagonism of the A2A receptor improves motor behavior in patients with Parkinson's disease (PD), according to results of clinical studies which confirm findings of previous experimental research. The xanthine derivative, istradefylline , has the longest half-life out of the available A2A receptor antagonists. Istradefylline easily crosses the blood-brain barrier and shows a high affinity to the human A2A receptor. This narrative review aims to discuss the safety and tolerability of istradefylline against the background of the currently available drug portfolio for the treatment of PD patients. Istradefylline was safe and well tolerated in clinical trials, which have focused on l-DOPA-treated PD patients. The future of istradefylline as a complementary drug for modulation of the dopaminergic neurotransmission also relies on its potential to act like an l-DOPA plus dopamine agonist sparing future treatment alternative and to reduce the risk of predominant l-DOPA-related onset of motor complications in addition to its direct ameliorating effect on motor symptoms. Dopamine-substituting drugs may dose-dependently produce systemic side effects, particularly onset of hypotension and nausea by peripheral dopamine receptor stimulation. Istradefylline does not interfere with these peripheral receptors and therefore shows a good safety and tolerability profile.

Safety of Oral Tenofovir Disoproxil Fumarate-Based Pre-Exposure Prophylaxis for HIV Prevention

PubMed Central

Mugwanya, Kenneth K.; Baeten, Jared M.

2016-01-01

Introduction Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. Areas covered We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability and side effects, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. Expert opinion TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP’s substantial reduction in the risk of HIV infection. PMID:26634852

Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy.

PubMed

Muramatsu, Kazuhiro; Sawaura, Noriko; Ogata, Tomomi; Makioka, Nishiki; Tomita, Keiko; Motojima, Toshino; Ida, Kuniko; Hazama, Kyoko; Arakawa, Hirokazu

2017-03-01

Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status. Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Opioid Analgesics and P-glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

PubMed Central

Mercer, Susan L.; Coop, Andrew

2012-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation. PMID:21050174

Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial.

PubMed

Emad, Maryam; Omidvari, Shapour; Dastgheib, Ladan; Mortazavi, Afshin; Ghaem, Haleh

2010-01-01

To compare the efficacy and tolerability of surgical excision and radiotherapy with those of cryotherapy and intralesional steroid treatment of keloids. Twenty-six patients with a total of 76 keloids were enrolled in this study. Nineteen patients with 44 keloids underwent surgical excision combined with immediate 12-Gy irradiation (group A) while the remaining 9 patients with 32 keloids received multiple sessions of intralesional steroid treatment after cryotherapy which continued until flattening of lesion(s) occurred (group B). Two patients were included in both treatment groups. All patients were followed up at regular intervals for at least 1 year. In both treatment groups, keloids responded well without any major side effect. While patients of group A were all satisfied, those of group B (with a mean number of treatment sessions of 5.84 +/- 2.51) experienced more side effects, a more prolonged course, a higher recurrence rate and less satisfaction. This study showed that surgery plus immediate postoperative irradiation was an effective and relatively safe choice for treatment of keloids. Although cryotherapy combined with intralesional steroids was associated with more side effects and higher relapse rates, it could be a good choice for small and newly formed keloids. Copyright 2010 S. Karger AG, Basel.

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

PubMed

Brito, B E; Vazquez, E; Taylor, P; Alvarado, Y; Vanegas, H; Millan, A; Tortorici, V

2017-03-01

Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl 2 ), an adjuvant that blocks the NMDA receptor channel. Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl 2 (200 mg/kg), or the combination DIP-MgCl 2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl 2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. These results suggest that DIP-MgCl 2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered. © 2016 European Pain Federation - EFIC®.

Cardiovascular Toxicity of Cyclooxygenase Inhibitors and Promising Natur a l Substitutes.

PubMed

Bahmani, Mahmoud; Sarrafchi, Amir; Shirzad, Hedayatollah; Asgari, Sedigheh; Rafieian-Kopaei, Mahmoud

2017-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are used for a wide variety of diseases including pain and inflammatory conditions such as osteoarthritis, rheumatoid arthritis, musculoskeletal disorders, and other comorbid complications. However, this group of drugs have undesirable effects such as peptic ulcer, bleeding and renal failure. Some of these side effects are associated with or caused by generation of oxidative stress. Following the withdrawal of a cyclo-oxygenase-2 (COX-2) inhibitor drug, rofecoxib (VIOXX®) due to cardiovascular complications, scientists suggested that natural COX-2 inhibitors might provide valuable alternatives to COX inhibitors. Although, most of medicinal plants reduce pain and inflammation in a similar manner to synthetic medications, however, they often have fewer side effects and are better tolerated. The present review other than focusing on cardiovascular and some other complications of NSAIDs, is trying to introduce the natural alternative remedies for these medications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

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

2016-03-01

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

Corticosteroid treatment in Sydenham's chorea.

PubMed

Fusco, C; Spagnoli, C

2018-03-01

Sydenham's chorea (SC) is an immune-mediated hyperkinetic movement disorder, developing after group A Beta-hemolytic streptococcal (GABHS) infection. Aside from conventional symptomatic treatment (carbamazepine, valproate, neuroleptics), the use of steroids has also been advocated, mainly in severe, drug-resistant cases or if clinically disabling side effects develop with first line therapies. Based on the description of 5 cases followed in the Child Neurology Unit of Santa Maria Nuova Hospital in Reggio Emilia and on the available medical literature on this topic, we propose considering the use of corticosteroids therapy in children with SC, with the administration of IV methyl-prednisolone followed by oral deflazacort in severe cases and of oral deflazacort alone in mild and moderate degrees of involvement. In our experience this therapy is effective both in the short and long-term period, in different clinical presentations (chorea paralytica, distal chorea, hemichorea, "classic" chorea, association with mood disorder or dyspraxia) and very well tolerated (no significant side effects were recorded). Copyright © 2017. Published by Elsevier Ltd.

Aripiprazole augmentation in highly treatment-resistant obsessive-compulsive disorder - experience from a specialty clinic in India.

PubMed

Hegde, Aditya; Kalyani, Bangalore G; Arumugham, Shyam Sundar; Narayanaswamy, Janardhanan C; Math, Suresh Bada; Reddy, Y C Janardhan

2017-03-01

To study the effectiveness and tolerability of aripiprazole augmentation in patients with highly treatment-resistant obsessive-compulsive disorder (OCD) in a real-world scenario. We conducted a chart review of patients who were initiated on aripiprazole augmentation at a specialty OCD clinic in India between 2004 and 2014. Primary outcome measure was all-cause discontinuation. 23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive-Compulsive Scale. The study demonstrated, in a real-world setting, that aripiprazole may be a useful augmenting agent in a proportion of patients with highly treatment-resistant OCD. However, side effects may lead to premature discontinuation in many of them.

Drug Holidays From ADHD Medication: International Experience Over the Past Four Decades.

PubMed

Ibrahim, Kinda; Donyai, Parastou

2015-07-01

ADHD is managed by stimulants that are effective but can cause growth retardation. Prescribers should ideally monitor children and trial a "drug holiday" to enable catch-up growth. Our aim was to map the experience of drug holidays from ADHD medication in children and adolescents. A comprehensive search of the literature identified 22 studies published during the period 1972 to 2013. Drug holidays are prevalent in 25% to 70% of families and are more likely to be exercised during school holidays. They test whether medication is still needed and are also considered for managing medication side effects and drug tolerance. The impact of drug holidays was reported in terms of side effects and ADHD symptoms. There was evidence of a positive impact on child growth with longer breaks from medication, and shorter breaks could reduce insomnia and improve appetite. Drug holidays from ADHD medication could be a useful tool with multiple purposes: assessment, management, prevention, and negotiation. © 2014 SAGE Publications.

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

PubMed Central

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Asymptomatic chronic gastritis decreases metformin tolerance in patients with type 2 diabetes.

PubMed

Huang, Y; Sun, J; Wang, X; Tao, X; Wang, H; Tan, W

2015-08-01

Digestive disorders represent the most common metformin side effects for type 2 diabetes. The mechanism of these metformin side effects is unclear. The aim of this study was to assess whether asymptomatic chronic gastritis could influence metformin tolerance in patients with type 2 diabetes. Demographic, anthropometric, ultrasound and laboratory data were obtained from 144 metformin naïve patients with diabetes. The diagnosis of chronic gastritis was based on endoscopic and histopathological examination, and H. pylori infection was assessed based on (13) C urea breath test (UBT). All subjects started metformin at 500 mg/day and increasing progressively to 1500 mg/day over 4 weeks. A score of gastrointestinal side effects (abdominal pain, diarrhoea, nausea, vomiting, bloating and anorexia) was assessed each week, and metformin dose was adjusted as appropriate. Based on endoscopy, 64 patients were categorized as non-gastritis subjects and 80 as chronic gastritis subjects. At baseline, there is no statistical difference in gastrointestinal symptoms between two groups. With metformin, the mean scores for gastrointestinal symptoms in the non-gastritis and gastritis subjects were 1·02 ± 1·71 vs. 2·18 ± 2·05 (P = 0·001), 0·20 ± 0·65 vs. 0·50 ± 0·89 (P = 0·022), 0 vs. 0·06 ± 0·24 (P = 0·024) and 1·08 ± 1·03 vs. 1·71 ± 1·66 (P = 0·028). The mean final metformin dose used by gastritis subjects was 706·24 ± 568·90 mg, significantly less than the mean dose used by non-gastritis subjects (1101·56 ± 578·58 mg, P = 0·001). After adjustment for age and sex, the odds ratio (OR) for a final metformin dose of less than 1500 mg/day was found to be 2·76 (95% CI 1·38-5·53, P = 0·004) for chronic gastritis subjects. The OR for a final metformin dose of less than 1000 mg/day was found to be 3·98 (95% CI 1·91-8·27, P = 0·001) for chronic gastritis subjects. Our data suggest that pre-existing non-symptomatic gastritis was associated with metformin-related gastrointestinal side effects. © 2015 John Wiley & Sons Ltd.

One and three doses of propranolol a day in hypertension.

PubMed

van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

1980-01-01

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

Persistent bone marrow depression following short-term treatment with temozolomide

PubMed Central

Vandraas, Kathrine; Tjønnfjord, Geir Erland; Johannesen, Tom Børge; Brandal, Petter

2016-01-01

Temozolomide (TMZ) is, in combination with radiotherapy (RT), the treatment of choice for glioblastoma multiforme. Although generally well tolerated, haematological side effects are observed in approximately 1–10% of patients receiving TMZ. We report a case of a patient who developed severe bone marrow failure (BMF) after only 3 weeks of concomitant TMZ. The BMF was grave with no signs of improvement for 12 months, resulting in more than 100 transfusions of blood cells. PMID:27130558

[Clinical evaluation of Uro-Vaxom in treatment of recurrent urinary tract infections in girls].

PubMed

Gołabek, B; Nowakowska, K; Słowik, M; Paruszkiewicz, G

1995-12-01

Uro-Vaxom was used in the treatment of recurrent urinary tract infections in 28 girls. Most of them (27/28) tolerated the drug very well, no side effects were observed. We stopped administration of the Uro-Vaxom in one girl during the first month of treatment because of vomiting. Uro-Vaxom efficiency was, therefore, evaluated in 27 girls. Uro-Vaxom was found to be a valuable drug, supplementing antibiotic therapy in recurrent urinary tract infections caused by E. coli.

A rare case of imatinib-induced erythroderma

PubMed Central

Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran; Neema, Shekhar

2013-01-01

Imatinib, a specific tyrosine kinase inhibitor is a newer anticancer agent, which has shown excellent efficacy in managing chronic myeloid leukemia. It is generally well tolerated with few side effects. Most commonly reported adverse events are maculopapular eruptions and periorbital edema. Severe adverse reactions are seen in 5% of patients. Exfoliative dermatitis has been very rarely reported with this drug. We report a case of a 52-year-old male who initially presented with a maculopapular rash and developed erythroderma on continuation of the drug. PMID:24347779

Gluten-Free Diet Indications, Safety, Quality, Labels, and Challenges.

PubMed

Rostami, Kamran; Bold, Justine; Parr, Alison; Johnson, Matt W

2017-08-08

A gluten-free diet (GFD) is the safest treatment modality in patient with coeliac disease (CD) and other gluten-related disorders. Contamination and diet compliance are important factors behind persistent symptoms in patients with gluten related-disorders, in particular CD. How much gluten can be tolerated, how safe are the current gluten-free (GF) products, what are the benefits and side effects of GFD? Recent studies published in Nutrients on gluten-free products' quality, availability, safety, as well as challenges related to a GFD are discussed.

"Diazepam loading": ¿Can a strategy for preventing alcohol withdrawal be used to treat benzodiazepine use disorder?

PubMed

Oliveras, Clara; Fortea, Adriana; Espinosa, Laura; Barrio, Pablo; Lligoña, Anna; Balcells-Olivero, Mercè

2018-04-15

Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are widely used to treat insomnia and anxiety, despite having long-term adverse side effects. (Fortea González, Oriolo, Balcells Oliveró, Sánchez Del Valle & Castellvi, 2017). As with alcohol, continued use can lead to tolerance and dependence phenomena. Discontinuation in such cases can produce abstinence symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y Murnion, 2015).

Special coverage: 9th Conference on Retroviruses. New drugs, new data hold promise for next decade of HIV treatment.

PubMed

2002-05-01

Antiretroviral research presented recently at the 9th Conference on Retroviruses and Opportunistic Infections demonstrates that investigators and pharmaceutical companies continue to strive for the next highly potent and easily tolerated anti-HIV drug. Among the new approaches are entry inhibitor drug and second-generation non-nucleoside reverse transcriptase inhibitors. New studies also looked into potency against multidrug-resistant virus and medication regimens that are simpler to take and have fewer side effects.

Specific oral tolerance induction with raw hen's egg in children with very severe egg allergy: a randomized controlled trial.

PubMed

Dello Iacono, Iride; Tripodi, Salvatore; Calvani, Mauro; Panetta, Valentina; Verga, Maria Carmela; Miceli Sopo, Stefano

2013-02-01

Treatment of severe egg allergy is avoidance of hen's egg (HE) and carrying self-injectable epinephrine. Specific oral tolerance induction (SOTI) seems a promising alternative treatment. However, some aspects of SOTI are still considered experimental. We evaluated the efficacy and safety of an original 6-month SOTI protocol in children with very severe HE allergy using raw HE emulsion. Twenty children (age range: 5-11 yr) were randomized equally into a SOTI treatment group and a control group. The treatment group started SOTI and underwent a second challenge 6 months later. Control children were kept on an egg-free diet for 6 months and then underwent a second challenge. After 6 months, 9/10 children of the SOTI group (90%) achieved partial tolerance (at least 10 ml, but <40 ml of raw HE emulsion, in a single dose) and 1 (10%) was able to tolerate only 5 ml (no tolerance). After 6 months, nine control children tested positive to the second challenge at a dose ≤0.9 ml of raw HE emulsion, and one reacted to 1.8 ml (SOTI vs. control group p<0.0001). All children in the SOTI group had side effects, but no child had a grade 5 reaction according to the Sampson grading. Six months of SOTI with raw HE emulsion resulted in partial tolerance, with regular intake, in a significant percentage of children with severe egg allergy. © 2012 John Wiley & Sons A/S.

Randomized, Observer-blind, Split-face Compatibility Study with Clindamycin Phosphate 1.2%/Benzoyl Peroxide 3.75% gel and Facial Foundation Makeup

PubMed Central

Pillai, Radhakrishnan

2015-01-01

Background: Cosmetic compatibility in the treatment of acne is an important issue significantly impacting quality of life, but often overlooked, as dermatologists commonly recommended avoidance of cosmetic foundations when treating adult female patients. Fixed combinations of clindamycin/benzoyl peroxide are widely used in the treatment of acne, but little is known about the impact of their concomitant use with facial foundation. Objective: To assess the compatibility of clindamycin phosphate 1. 2%/benzoyl peroxide 3. 75% gel with foundation makeup for up to six hours after application. Methods: Twenty-nine female subjects applied makeup to their face after randomly applying clindamycin phosphate 1. 2%/benzoyl peroxide 3. 75% gel to one side of the face. Investigator and subject self- assessment included facial skin attributes, facial tolerability, and cosmetic compatibility post-application and at Hour 6; as well as cutaneous tolerability. Results: No statistical difference was noted between the treated and untreated side of the face in terms of coverage, blotchiness, appearance, skin tone, or visual smoothness. Tolerability was excellent, with no erythema, edema, dryness, and peeling post-makeup application. For both the treated and untreated side, there was a slight lack of improvement in cosmetic appearance six hours post-makeup application. Conclusion: Clindamycin/benzoyl peroxide 3. 75% gel was shown to have excellent cosmetic compatibility with facial foundation. PMID:26430488

Randomized, Observer-blind, Split-face Compatibility Study with Clindamycin Phosphate 1.2%/Benzoyl Peroxide 3.75% gel and Facial Foundation Makeup.

PubMed

Bhatia, Neal; Pillai, Radhakrishnan

2015-09-01

Cosmetic compatibility in the treatment of acne is an important issue significantly impacting quality of life, but often overlooked, as dermatologists commonly recommended avoidance of cosmetic foundations when treating adult female patients. Fixed combinations of clindamycin/benzoyl peroxide are widely used in the treatment of acne, but little is known about the impact of their concomitant use with facial foundation. To assess the compatibility of clindamycin phosphate 1. 2%/benzoyl peroxide 3. 75% gel with foundation makeup for up to six hours after application. Twenty-nine female subjects applied makeup to their face after randomly applying clindamycin phosphate 1. 2%/benzoyl peroxide 3. 75% gel to one side of the face. Investigator and subject self- assessment included facial skin attributes, facial tolerability, and cosmetic compatibility post-application and at Hour 6; as well as cutaneous tolerability. No statistical difference was noted between the treated and untreated side of the face in terms of coverage, blotchiness, appearance, skin tone, or visual smoothness. Tolerability was excellent, with no erythema, edema, dryness, and peeling post-makeup application. For both the treated and untreated side, there was a slight lack of improvement in cosmetic appearance six hours post-makeup application. Clindamycin/benzoyl peroxide 3. 75% gel was shown to have excellent cosmetic compatibility with facial foundation.

Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study.

PubMed

Callenbach, Petra M C; Arts, Willem Frans M; ten Houten, Robert; Augustijn, Paul; Gunning, W Boudewijn; Peeters, Els A J; Weber, Alma M; Stroink, Hans; Geerts, Yvette; Geerts, Ada T; Brouwer, Oebele F

2008-07-01

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

Long-Term Pharmacotherapy of Adults With Attention Deficit Hyperactivity Disorder: A Literature Review and Clinical Study.

PubMed

Fredriksen, Mats; Peleikis, Dawn E

2016-01-01

This MiniReview reports and discusses the main findings of the author's thesis including a literature study of long-term pharmacological treatment of adults with attention deficit hyperactivity disorder (ADHD), and a clinical study of 1-year medication. Electronic databases were systematically reviewed for original studies on pharmacotherapy of the defined duration, 24 weeks or more. Although few trials were found with limitations such as excluding comorbidities, treatment with stimulants and atomoxetine was reported tolerated and effective compared to non-treatment. The clinical study of the thesis was conducted on 250 medication-naïve patients with ADHD referred to a specialized outpatient clinic. Comorbid psychiatric disorders were diagnosed among 75% of the patients. About 56% had not completed secondary school, and 51% had been unable to work the preceding year. Persisting inattentive symptoms and comorbid mental disorders in adulthood were related to long-term work disability. In the prospective observational study of the thesis, patients were treated with methylphenidate as first-line drug and atomoxetine or dexamphetamine as second-line drugs, according to current treatment guidelines. At 12-month follow-up, 232 patients completed evaluation and 70% persisted on medication. About 80% of these used methylphenidate. Sustained improvement of symptoms and functioning was related to continued medication. Comorbid mental disorders and side effects were related to lower effectiveness and adherence, and 12% stopped medication due to side effects. Summing up the MiniReview, treatment with stimulants and atomoxetine of adults with ADHD has long-term beneficial effects and is tolerated but more longitudinal studies should be performed. With stated limitations, the findings of the thesis should contribute to a relevant guidance for clinical practice. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Efficacy and side-effects profile of the ethinylestradiol and etonogestrel contraceptive vaginal ring: a systematic review and meta-analysis.

PubMed

López-Picado, Amanda; Lapuente, Oihane; Lete, Iñaki

2017-04-01

To assess the efficacy and tolerability (side-effects profile), and compliance of the combined contraceptive vaginal ring (CCVR) compared with combined oral hormonal contraceptives (COC). The PubMed, Embase, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, ClinicalTrials.gov, Clinical Trials Registry Platform (ICTRP) and CINAHL databases were searched. Electronic databases were searched for randomised clinical trials comparing the CCVR with COC with a duration of at least 3 months between 01 December and 15 December 2015. The primary outcome was efficacy. The secondary outcomes were compliance, absence of withdrawal bleeding, breakthrough bleeding, nausea and headache. Heterogeneity was assessed using I 2 statistic and Cochran's Q statistic. Results were expressed as odds ratios (OR) with 95% confidence intervals (CIs) using random-effects models or fixed-effects models depending on the heterogeneity. 4368 records were identified, 2844 of which were removed after duplicates and 1524 records were screened. Of these, 1503 were excluded and 21 full text articles were assessed for eligibility. After removing another 7 articles, 14 records were finally included in the qualitative and quantitative analysis. The results show a trend to higher efficacy for the CCVR in preventing pregnancy (Peto OR: 0.52 [95% CI: 0.26-1.04]) and a significantly lower presence of nausea (Peto OR: 0.66 [95% CI: 0.46-0.93]). More cycles were compliant in the CCVR group (Peto OR: 1.22 [95% CI: 1.12-1.32]) and fewer women reported breakthrough bleeding (Peto OR: 0.68 [95% CI: 0.51-0.91]). Our findings demonstrate that the CCVR is as effective and tolerable as the COC but with a better bleeding profile.

Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist ligands.

PubMed

Bender, Aaron M; Clark, Mary J; Agius, Michael P; Traynor, John R; Mosberg, Henry I

2014-01-15

In this letter, we describe a series of 4-substituted piperidine and piperazine compounds based on tetrahydroquinoline 1, a compound that shows balanced, low nanomolar binding affinity for the mu opioid receptor (MOR) and the delta opioid receptor (DOR). We have shown that by changing the length and flexibility profile of the side chain in this position, binding affinity is improved at both receptors by a significant degree. Furthermore, several of the compounds described herein display good efficacy at MOR, while simultaneously displaying DOR antagonism. The MOR agonist/DOR antagonist has shown promise in the reduction of negative side effects displayed by selective MOR agonists, namely the development of dependence and tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study.

PubMed

Pakseresht, Siroos; Boostani, Hatam; Sayyah, Mehdi

2011-10-11

Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition. Many herbs with psychotropic effects exist which can have fewer side effects compared to more conventional medications. Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in the world with an effect on GABA. This plant is reported to be safe on humans. Our objective in this study was to compare the efficacy of the extract of Valeriana Officinalis L. with placebo in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty-one adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (765 mg/day) or placebo (30 mg/day) for 8 weeks. The results showed significant difference between the extract and placebo in the end of treatment (P=0.000). Somnolence was the only significant difference between the two groups in terms of observed side effects (P=0.02). The results suggest that Valeriana Officinalis L. has some antiobsessive and compulsive effects. However, further studies are needed to confirm these findings. Psychiatrists often find that many patients cannot tolerate the side effects of psychiatry medicine Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in world with effect on GABA.The results showed significant difference between the extract and placebo in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

PubMed

Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F

1985-12-01

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

FDA approves efavirenz. Food and Drug Administration.

PubMed

Highleyman, L

1998-10-01

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

[Clinical and monitoring experience of isotretinoin in Italy].

PubMed

Cavicchini, S; Bottoni, A; Caputo, R

1989-01-01

We report the results of a multicentric evaluation on effectiveness and safety of isotretinoin in severe acne, recalcitrant to traditional treatments. 208 patients, suffering especially from cystic acne, have been enrolled in a post-marketing clinical trial in 11 Dermatological Italian Departments. The clinical effectiveness of isotretinoin has been very good in 77% of patients, good in 16% and sufficient in 4%. The tolerability of the drug was considered good in 90% of patients. Finally, isotretinoin might be considered as one of the most effective drugs in the therapy of severe forms of acne, resistant to usual treatment, and often affecting patients on the physical and psychological side.

Labetalol, a new alpha- and beta-adrenoreceptor blocking agent, in hypertension.

PubMed

Hansson, L; Hänel, B

1976-08-01

1Labetalol is a new compound with antagonistic effects at both alpha- and beta-adrenoreceptor sites. 2 When given to 12 hypertensive patients at an average daily dosage of 273 mg for 7 months statistically significant reductions (compared with pretreatment values) in recumbent and standing blood pressure were observed. 3 Treatment has to be withdrawn in one patient because of vivid dreams, and dosage was reduced in one patient because of dizziness. Otherwise no side-effects of importance were noted. 4 It can therefore be concluded that labetalol offers a useful anti-hypertensive effect and that this compound is well tolerated.

Autogenic-feedback training - A treatment for motion and space sickness

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.

1990-01-01

A training method for preventing the occurrence of motion sickness in humans, called autogenic-feedback training (AFT), is described. AFT is based on a combination of biofeedback and autogenic therapy which involves training physiological self-regulation as an alternative to pharmacological management. AFT was used to reliably increase tolerance to motion-sickness-inducing tests in both men and women ranging in age from 18 to 54 years. The effectiveness of AFT is found to be significantly higher than that of protective adaptation training. Data obtained show that there is no apparent effect from AFT on measures of vestibular perception and no side effects.

[Antidepressant and tolerance: Determinants and management of major side effects].

PubMed

David, D J; Gourion, D

2016-12-01

Antidepressant therapy aims to reach remission of depressive symptoms while reducing the complications and risks of relapse. Even though they have proven their efficacy, it takes several weeks for antidepressants to demonstrate full effectiveness, and adverse effects occur more quickly or (quicker) which can be a source of poor compliance. This latest aspect often leads to dose reduction and/or change of molecule that have the effect of delaying remission. This review attempts to present, from the pharmacological properties of the major classes of antidepressants (monoamine oxidase inhibitor [MAOI], tricyclic antidepressants [TCA], selective serotonin reuptake inhibitor [SSRI] and serotonin and noradrenaline reuptake inhibitor [SNRI]), to the pharmacological mechanisms involved in adverse effects by focusing on sexual dysfunction, nausea/vomiting, and weight changes and sleep disruption. If the activation of dopamine D 1/2  or norepinephrine receptors through the autonomic nervous system controls and facilitates sexual desire, increasing serotoninergic transmission through 5-HT 1B/2A/2C receptors activation inhibits this process. The pharmacological properties of drugs inducing nausea/vomiting activate opiate receptors μ, increase dopaminergic and serotoninergic transmission activating the dopamine D 2  and serotonin 5-HT 3  receptors, respectively. Among the causes responsible for weight gain under antidepressant therapy, monoamine neurotransmission still plays an important role. The blockade of serotonin 5-HT 2C or histamine H 1  receptors is directly responsible for weight gain. Finally, the activation of 5-HT 1A/1B/3/7 serotoninergique receptors modulates wakefulness, raid eyes movement or sleep duration. In conclusion, if antidepressant activity of SERT or MAO inhibitors is an indirect consequence of postsynaptic 5-HT, DA, NA receptor activation, it is also responsible for side effects, causes of poor compliance and hence therapeutic failures. Finally, we need to take into account the key role of the nocebo effect in the occurrence of adverse effects. The next generation of antidepressant would aim to have a rapid efficacy in patients unresponsive or resistant to drugs currently available while improving certain effects of tolerance through an optimization of their psychopharmacological properties leading to a reduction of their side effects. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Wetlands Research Program. A Concept and Procedure for Developing and Utilizing Vegetation Flood Tolerance Indices in Wetlands Delineation.

DTIC Science & Technology

1986-02-01

reverse side If necessary md identify by block number) Adaptive mechanisms Evapotranspiration Saturation Comunity FTI numbers Soil permeability Delineation...distribution and the fre- quency and duration of inundation/ soil saturation. The numerical expression (Flood Tolerance Index (FTI) number) of this...inundation, a strong correlation may exist between the distribution of a species and its associated hydrologic and soil -moisture conditions (Bedinger

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

PubMed

Zhai, Mei-Li; Chen, Yi; Liu, Chong; Wang, Jian-Bo; Yu, Yong-Hao

2018-05-23

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.

PubMed

Loven, Keith; Stein, Linda; Furst, Katharine; Levy, Sharon

2002-06-01

A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available. This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK). During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events. Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation. In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent reduction in AK lesions and total clearance of AK lesions; it was more effective than the 5% cream in reducing the absolute number of AK lesions from baseline. Patients preferred the 0.5% cream to the 5% cream.

Nabumetone in the treatment of skin and soft tissue injury.

PubMed

Jenner, P N

1987-10-30

Nabumetone, a new nonsteroidal anti-inflammatory agent, has been evaluated for the treatment of skin and soft tissue injury, including sports injury, in clinical trials involving nearly 1,000 patients. Its efficacy, safety, and tolerance in these patients is reviewed. The efficacy of nabumetone in the treatment of soft tissue injury has been demonstrated to be similar to that of soluble aspirin, ibuprofen, and naproxen. It was not possible in these studies to demonstrate a definite advantage over placebo, and the reasons for this are discussed along with some suggestions for future studies. There were no serious adverse experiences reported, and nabumetone was well tolerated and compared favorably with the other agents used, including placebo. It caused significantly fewer gastrointestinal side effects than soluble aspirin. Nabumetone is an appropriate choice of nonsteroidal anti-inflammatory drug for the treatment of sports injury.

Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

PubMed

Buonpensiero, Paolo; De Gregorio, Fabiola; Sepe, Angela; Di Pasqua, Antonio; Ferri, Pasqualina; Siano, Maria; Terlizzi, Vito; Raia, Valeria

2010-11-01

Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.

Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

PubMed

Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

2014-12-01

How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents - rationale and protocol.

PubMed

Wicklow, Brandy; Wittmeier, Kristy; T' Jong, Geert W; McGavock, Jonathon; Robert, Marni; Duhamel, Todd; Dolinsky, Vernon W

2015-10-01

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

PubMed

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study. Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain. © 2017 by the Society for Academic Emergency Medicine.

A novel two-step kit for topical treatment of tinea pedis--an open study.

PubMed

Shemer, A; Grunwald, M H; Davidovici, B; Nathansohn, N; Amichai, B

2010-09-01

Tinea pedis is a common skin disease affecting most of the population during their lifetime. Topical and systemic treatments give only temporary relief. To evaluate the efficacy and safety of a new topical treatment for moderate-to-severe tinea pedis. Fifty patients suffering from tinea pedis were treated in two stages: the active stage--single use of the novel topical solution for 45 min and novel cream twice weekly for 4 weeks; the preventive stage--cream application once weekly for 10 months. Forty-five patients completed the active stage and achieved 76% cure rate. The medication was well tolerated; one patient dropped from the study because of very mild irritation. No other topical or systemic side effects were noted. Another five patients were lost to follow-up during the preventive stage. The total cure rate after the preventive stage was 70%. This novel treatment was found to be effective, well tolerated and safe in the treatment of moderate and severe tinea pedis during the active and the preventive stages.

Angiotensin receptor blockers for management of hypertension.

PubMed

Catanzaro, Daniel F; Frishman, William H

2010-07-01

The renin-angiotensin-aldosterone system (RAAS) plays a major role in blood pressure regulation and is thus an important therapeutic target in the management of hypertension. Angiotensin receptor blockers (ARBs), which interrupt RAAS overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II, represent a major addition to the clinician's armamentarium for the management of hypertension. A solid body of clinical evidence demonstrates that ARBs are effective in the management of hypertension as monotherapy or in combination with other agents. Although comparable to angiotensin-converting enzyme inhibitors and other major classes of antihypertensive agents in the treatment of hypertension, the favorable tolerability profile of ARBs make them an attractive alternative for many patients. Recent evidence suggests that treatment persistence with ARB therapy during a 12-month period is typically higher than with other antihypertensive classes, a finding perhaps driven by fewer treatment-limiting side effects. The combination of clinical efficacy and tolerability should render ARBs as a major treatment alternative for hypertension.

Treatment of Rheumatoid Arthritis with Fenoprofen: Comparison with Aspirin

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.; Berry, H.; Scott, Jane; Hart, F. Dudley; Balme, H. W.

1974-01-01

Fenoprofen, a compound with analgesic, anti-inflammatory, and antipyretic properties in animals, has been compared with placebo in a double-blind cross-over trial in 60 patients with rheumatoid arthritis. There was a statistically highly significant reduction in pain, duration of morning stiffness, analgesic requirements, and articular index, with increase in grip strength. There was no significant reduction in joint size or temperature. In a subsequent double-blind group-comparative study fenoprofen proved to be as effective as aspirin in relieving the symptoms of rheumatoid arthritis, with strikingly fewer side effects. Almost half of the patients taking aspirin were unable to tolerate the drug in adequate dosage for six months. The remainder were able to take on average only 4 g daily, and at this dose almost half still complained of tinnitus and deafness. Fenoprofen is likely to be useful for patients who cannot tolerate aspirin and other more toxic anti-inflammatory drugs or whose disease is not of sufficient severity to justify their use. PMID:4590669

[Effectiveness of fenspiride in patients with chronic obstructive bronchitis].

PubMed

Shorokhova, T D; Medvedeva, I V; Lapik, S V; Solov'eva, O G; Gracheva, E Iu; Iusupova, R S

2001-01-01

Patients with chronic obstructive pulmonary disease of moderate severity were investigated for two months for assessment of fenspiride activity. Examination of the patients (age 42.6 +/- 5.3) took place before and after fenspiride therapy. In comparison to the control group, fenspiride patients showed improvement of external respiration function: FEV 1, FVC, FEF 50-75, PEF increased. Dienic conjugates, malonic dialdehyde levels decreased, alpha-tocopherol in platelet membranes rose, functional activity of platelets fell. Side effects were rare and not serious. It is concluded that fenspiride has an antiinflammatory effect, reduces bronchoconstriction and depresses platelet aggregation, is well tolerated. Fenspiride is an effective drug for the treatment of moderate chronic obstructive bronchitis.

Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice.

PubMed

Guzmán, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; Giordano, Mirta Nilda; Galletti, Jeremías Gastón

2014-09-04

To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor-κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB-dependent fashion after interaction with T cells. Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Results from a study using misoprostol for management of incomplete abortion in Vietnamese hospitals: implications for task shifting.

PubMed

Ngoc, Nguyen Thi Nhu; Shochet, Tara; Blum, Jennifer; Hai, Pham Thanh; Dung, Duong Lan; Nhan, Tran Thanh; Winikoff, Beverly

2013-05-22

Complications following spontaneous or induced abortion are a major cause of maternal morbidity. To manage these complications, post-abortion care (PAC) services should be readily available and easy to access. Standard PAC treatment includes surgical interventions that are highly effective but require surgical providers and medical centers that have the necessary space and equipment. Misoprostol has been shown to be an effective alternative to surgical evacuation and can be offered by lower level clinicians. This study sought to assess whether 400 mcg sublingual misoprostol could effectively evacuate the uterus after incomplete abortion and to confirm its applicability for use at lower level settings. All women presenting with incomplete abortion at one of three hospitals in Vietnam were enrolled. Providers were not asked to record if the abortion was spontaneous or induced. It is likely that all were spontaneous given the legal status and easy access to abortion services in Vietnam. Participants were given 400 mcg sublingual misoprostol and instructed to hold the pills under their tongue for 30 minutes and then swallow any remaining fragments. They were then asked to return one week later to confirm their clinical status. Study clinicians were instructed to confirm a complete expulsion clinically. All women were asked to complete a questionnaire regarding satisfaction with the treatment. Three hundred and two women were enrolled between September 2009 and May 2010. Almost all participants (96.3%) had successful completions using a single dose of 400 mcg misoprostol. The majority of women (87.2%) found the side effects to be tolerable or easily tolerable. Most women (84.3%) were satisfied or very satisfied with the treatment they received; only one was dissatisfied (0.3%). Nine out of ten women would select this method again and recommend it to a friend (91.0% and 90.0%, respectively). This study confirms that 400 mcg sublingual misoprostol effectively evacuates the uterus for most women experiencing incomplete abortion. The high levels of satisfaction and side effect tolerability also attest to the ease of use of this method. From these data and given the international consensus around the effectiveness of misoprostol for incomplete abortion care, it seems timely that use of the drug for this indication be widely expanded both throughout Vietnam and wherever access to abortion care is limited. ClinicalTrials.gov, NCT00670761.

Comparison of the pattern, efficacy, and tolerability of self-medicated drugs in primary dysmenorrhea: A questionnaire based survey

PubMed Central

Sugumar, Ramya; Krishnaiah, Vasundara; Channaveera, Gokul Shetty; Mruthyunjaya, Shilpa

2013-01-01

Objective: To compare the pattern, efficacy, and tolerability of self-medicated drugs and to assess the adequacy of their dose in primary dysmenorrhea (PD). Materials and Methods: A survey using a self-developed, validated, objective, and structured questionnaire as a tool was conducted among subjects with PD. Statistical analysis was carried out using Chi-square test and ANOVA with post-hoc Tuckey's test. Results: Out of 641 respondents, 42% were self-medicated. The pattern of drugs used was: Dicyclomine, an unknown drug, mefenamic acid, mefenamic acid + dicyclomine, and metamizole by 35%, 29%, 26%, 9%, and 1% of respondents, respectively. Mefenamic acid + dicyclomine, the combination was the most efficacious in comparison to other drugs in moderate to severe dysmenorrhea. There was better tolerability with mefenamic acid + dicyclomine group compared to other drugs. Sub-therapeutic doses were used by 86% of self-medicating respondents. Conclusions: The prevailing self-medication practices were inappropriate in a substantial proportion of women with inadequate knowledge regarding appropriate drug choice, therapeutic doses, and their associated side effects. PMID:23716896

WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW.

PubMed

Moreira-Marconi, Eloá; Sá-Caputo, Danubia C; Dionello, Carla F; Guedes-Aguiar, Eliane O; Sousa-Gonçalves, Cintia R; Morel, Danielle S; Paineiras-Domingos, Laisa L; Souza, Patricia L; Kütter, Cristiane R; Costa-Cavalcanti, Rebeca G; Costa, Glenda; Paiva, Patricia C; Figueiredo, Claudia; Brandão-Sobrinho-Neto, Samuel; Stark, Christina; Unger, Marianne; Bernardo-Filho, Mario

2017-01-01

Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients. Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm. A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation. It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients.

Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.

PubMed

Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory

2017-01-03

Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.

Venlafaxine versus methylphenidate in pediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial.

PubMed

Zarinara, Ali-Reza; Mohammadi, Mohammad-Reza; Hazrati, Nazanin; Tabrizi, Mina; Rezazadeh, Shams-Ali; Rezaie, Farzin; Akhondzadeh, Shahin

2010-11-01

The present report aimed to investigate the efficacy and tolerability of venlafaxine compared to methylphenidate in children and adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). This was a 6-week, parallel group, randomized clinical trial. Thirty-eight patients (27 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive treatment using capsules of venlafaxine at doses of 50-75 mg/day depending on weight (50 mg/day for <30 kg and 75 mg/day for >30 kg (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (group 2) for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention Deficit/Hyperactivity Disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 1.77; p = 0.19 and df = 1; F = 1.64; p = 0.20, respectively). Side effects of headaches and insomnia were observed more frequently in the methylphenidate group. The results suggest that venlafaxine may be useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of venlafaxine in the treatment of ADHD. Copyright © 2010 John Wiley & Sons, Ltd.

Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy: A case report and literature review.

PubMed

Li, Cheng-Ming; Liu, Zhi-Chao; Bao, You-Ting; Sun, Xin-Dong; Wang, Lin-Lin

2017-11-07

Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer (PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage IV, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.

Relaxed Manufacturing Design Tolerance Concepts. Volume 2. Appendices

DTIC Science & Technology

1977-07-01

are typical for such a part. A rough and finish pass is made to web thickness, a rough cut is made in the corners and then the stlf- fener walls...the programmed teed rate a little more on the second side due to having less material behind the web ; however, a designer usually provides for...Typical Survov Data Rocord Recommended Relaxation on Drawing Tolerances for Webs and Stiffcners Web Dimensional Deviation Occurrences vs. Stiffener

A double-blind randomized placebo-controlled trial with short-term beta-glucuronidase therapy in children with chronic rhinoconjunctivitis and/or asthma due to dust mite allergy.

PubMed

Galli, E; Bassi, M S; Mora, E; Martelli, M; Gianni, S; Auricchio, G; Arabito, E; Rossi, P

2006-01-01

Enzyme potentiated desensitization, in which beta-glucuronidase (BG) is administered with low doses of mixed allergens, was proposed in the 1970s for specific immunotherapy. The BG currently commercially available in a purified and standardized preparation devoid of any allergen has been suggested as a regulator in the allergic immune response, acting on the cytokine-network of type 2 helper T cells. A double-blind trial with a single-dose of BG proved effective in preventing symptoms in adult patients with rhinoconjunctivitis due to grass pollens. The aim of this randomized double-blind placebo-controlled trial was to confirm the safety and effectiveness of double-dose intradermal BG immunotherapy in preventing symptoms in children suffering from chronic rhinoconjunctivitis and/or asthma due to dust mite. We randomized 125 children with dust-mite related chronic rhinoconjunctivitis and/or asthma to the BG treated group (67) or the placebo group (58). All patients were screened before treatment (TO), at BG or placebo administration (T1 and T3), and at 3 and 9 months after T1 (T2 and T4). Drug intake and bronchial, nasal and ocular symptoms were recorded in a diary. Patients in both groups completed the study and BG treatment was well tolerated without side effects. Significant differences in symptoms were observed, in particular for conjunctivitis (P= .008). The total drug intake for allergic symptoms was significantly lower in the treated group than in the placebo group (P<. 01). BG immunotherapy is efficacious, safe, and well tolerated in allergic children. Moreover, good compliance with the administration of 2 doses per year and the lack of significant side effects makes the benefit/risk ratio of this treatment particularly favorable.

Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

PubMed

Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

2017-10-02

Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

PubMed

Perez, Victor; Cañas, Fernando; Tafalla, Monica

2008-05-01

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets.

PubMed

Guri, Amir J; Hontecillas, Raquel; Si, Hongwei; Liu, Dongmin; Bassaganya-Riera, Josep

2007-02-01

Despite their efficacy in improving insulin sensitivity, thiazolidinediones (TZDs) are associated with a number of side effects (i.e. weight gain, hepatotoxicity, congestive heart failure) that have limited their use by millions of diabetic patients. We have investigated whether abscisic acid (ABA), a naturally occurring phytochemical with structural similarities to TZDs, could be used as an alternative to TZDs to improve glucose homeostasis. We first examined whether ABA, similar to TZDs, activates PPARgamma in vitro. We next determined the lowest effective dose of dietary ABA (100 mg/kg) and assessed its effect on glucose tolerance, obesity-related inflammation, and mRNA expression of PPARgamma and its responsive genes in white adipose tissue (WAT) of db/db mice fed high-fat diets. We found that ABA induced transactivation of PPARgamma in 3T3-L1 pre-adipocytes in vitro. Dietary ABA-supplementation for 36 days decreased fasting blood glucose concentrations, ameliorated glucose tolerance, and increased mRNA expression of PPARgamma and its responsive genes (i.e., adiponectin, aP2, and CD36) in WAT. We also found that adipocyte hypertrophy, tumor necrosis factor-alpha (TNF-alpha) expression, and macrophage infiltration in WAT were significantly attenuated in ABA-fed mice. These findings suggest that ABA could be used as a nutritional intervention against type II diabetes and obesity-related inflammation.

Chlorambucil plus Rituximab as Front-Line Therapy in Elderly/Unfit Patients Affected by B-Cell Chronic Lymphocytic Leukemia: Results of a Single-Centre Experience

PubMed Central

Laurenti, Luca; Vannata, Barbara; Innocenti, Idanna; Autore, Francesco; Santini, Francesco; Piccirillo, Nicola; Za, Tommaso; Bellesi, Silvia; Marietti, Sara; Sica, Simona; Efremov, Dimitar G.; Leone, Giuseppe

2013-01-01

The current standard first line therapy for fit patients with B-CLL/SLL is based on combination of fludarabine-cyclophosphamide and rituximab. However, elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl) only. However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3–4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3–4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL. PMID:23667729

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sevik, James; Pamminger, Michael; Wallner, Thomas

Interest in natural gas as an alternative fuel source to petroleum fuels for light-duty vehicle applications has increased due to its domestic availability and stable price compared to gasoline. With its higher hydrogen-to-carbon ratio, natural gas has the potential to reduce engine out carbon dioxide emissions, which has shown to be a strong greenhouse gas contributor. For part-load conditions, the lower flame speeds of natural gas can lead to an increased duration in the inflammation process with traditional port-injection. Direct-injection of natural gas can increase in-cylinder turbulence and has the potential to reduce problems typically associated with port-injection of naturalmore » gas, such as lower flame speeds and poor dilution tolerance. A study was designed and executed to investigate the effects of direct-injection of natural gas at part-load conditions. Steady-state tests were performed on a single-cylinder research engine representative of current gasoline direct-injection engines. Tests were performed with direct-injection in the central and side location. The start of injection was varied under stoichiometric conditions in order to study the effects on the mixture formation process. In addition, exhaust gas recirculation was introduced at select conditions in order to investigate the dilution tolerance. Relevant combustion metrics were then analyzed for each scenario. Experimental results suggest that regardless of the injector location, varying the start of injection has a strong impact on the mixture formation process. Delaying the start of injection from 300 to 120°CA BTDC can reduce the early flame development process by nearly 15°CA. While injecting into the cylinder after the intake valves have closed has shown to produce the fastest combustion process, this does not necessarily lead to the highest efficiency, due to increases in pumping and wall heat losses. When comparing the two injection configurations, the side location shows the best performance in terms of combustion metrics and efficiencies. For both systems, part-load dilution tolerance is affected by the injection timing, due to the induced turbulence from the gaseous injection event. CFD simulation results have shown that there is a fundamental difference in how the two injection locations affect the mixture formation process. Delayed injection timing increases the turbulence level in the cylinder at the time of the spark, but reduces the available time for proper mixing. Side injection delivers a gaseous jet that interacts more effectively with the intake induced flow field, and this improves the engine performance in terms of efficiency.« less

The control of acute diarrhea in a large industrial plant.

PubMed

Martins, J K; Roedl, G

1978-04-01

Diarrhea causes considerable absenteeism and loss of working time among employees in the United States. One hundred employees with acute diarrhea at a Ford Motor Company plant were studied for four months to determine if loperamide hydrochloride treatment would control diarrheal symptoms, reduce absenteeism due to the condition, and be well-tolerated. Diarrhea was controlled with a median dosage of three capsules (6 mg total dose) and a range of two to 12 capsules. Ninety-six percent of the subjects were controlled after the first day, 98% by the third day. A statistically significant number were symptom free at their last clinical visits. Side effects were generally minor in nature. Substantially more than 1,000 man-hours of lost time were saved because of the treatment. Known drug dependents did not suffer from CNS effects or "highs". Loperamide acts directly on the intestinal wall to inhibit excessive peristalsis, thereby providing prompt, effective relief, with normal bowel patterns observed in these patients. The simple, individualized dosage is patient-oriented, rather than based on a fixed regimen. Because of its rapid onset of action, effective control of symptoms, low dosage, and being well-tolerated, loperamide meets the criteria for an effective antidiarrheal agent in industry.

Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes

PubMed Central

Hanefeld, Markolf

2007-01-01

Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the α-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum. PMID:17697384

Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study.

PubMed

Huang, Feng; Dong, Jianxun; Kong, Jian; Wang, Hongcai; Meng, Hong; Spaeth, Rosa B; Camhi, Stephanie; Liao, Xing; Li, Xia; Zhai, Xu; Li, Shaoyuan; Zhu, Bing; Rong, Peijing

2014-06-26

Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients receiving taVNS significantly differed in measures of FPG (F(2) = 10.62, p < 0.001), 2hPG F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) over the course of the 12 week treatment period. Our study suggests that taVNS is a promising, simple, and cost-effective treatment for IGT/ pre-diabetes with only slight risk of mild side-effects.

Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia.

PubMed

Komen, Manon M C; Breed, Wim P M; Smorenburg, Carolien H; van der Ploeg, Tjeerd; Goey, S H; van der Hoeven, Jacobus J M; Nortier, Johan W R; van den Hurk, Corina J G

2016-06-01

For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post-infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time. In this prospective, multi-centre randomised study, 134 patients who started treatment with docetaxel 75-100 mg/m(2) in a 3-weekly schedule were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 45 or 20 min. The primary end point was the need for a wig or other head covering as assessed by the patient. A visual analogue scale (VAS) with a range from 0 (not tolerable) to 10 (very tolerable) was used to measure tolerance. Scalp cooling results were similar for 45- and 20-min post-infusion cooling times. Thirty-three out of 45 patients (73 %) treated with 20 min of post-infusion cooling did not need a form of head covering, compared with 41 out of 52 patients (79 %) treated with 45 min of post-infusion cooling (p = 0.5). The procedure was well tolerated (mean visual analogue score 8.3). Six patients stopped due to intolerance during the first treatment cycle. A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel-induced alopecia. Trialregister.nl Identifier, NTR 1856.

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)

PubMed Central

Mathieu, C; Barnett, A H; Brath, H; Conget, I; de Castro, J J; Göke, R; Márquez Rodriguez, E; Nilsson, P M; Pagkalos, E; Penfornis, A; Schaper, NC; Wangnoo, S K; Kothny, W; Bader, G

2013-01-01

Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c < 7% without hypoglycaemia or ≥ 3% increase in body weight. Results In this large group of T2DM patients, a second OAD was added at mean HbA1c of 8.2 ± 1.3%, with no baseline HbA1c difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA1c ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data. Conclusion EDGE demonstrates that in a ‘real-life’ setting, vildagliptin as second OAD can lower HbA1c to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs. PMID:23961850

Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

PubMed

Ghaleiha, Ali; Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Tabrizi, Mina; Hajiaghaee, Reza; Hassanzadeh, Elmira; Akhondzadeh, Shahin

2013-05-01

Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

The Hidden Side of Zero Tolerance Policies: The African American Perspective

PubMed Central

Bell, Charles

2015-01-01

Several papers have documented the disproportionate representation of African Americans in school discipline and incarceration settings as a result of zero tolerance policies. In 2009, a federal study of the Chicago Public School system found African American boys represented 23 percent of the school age population, 44 percent of students who were suspended, and 61 percent of students who were expelled within the 2007 school year. Twenty years after the implementation of the Anti-Drug Abuse Acts of 1986 and 1988, studies show African Americans comprised a startling 74 percent of those incarcerated for drug offenses despite being only 15 percent of America’s drug users. Despite overwhelming evidence that suggests African Americans are adversely affected by zero tolerance policies, African American perceptions of zero tolerance policies remain relatively hidden in the literature. The current review seeks to explore a seemingly bidirectional process that involves how zero tolerance impacts African Americans and how African Americans perceive zero tolerance policies. PMID:25893006

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease.

PubMed

Olaosebikan, Rasaq; Ernest, Kolade; Bojang, Kalifa; Mokuolu, Olugbenga; Rehman, Andrea M; Affara, Muna; Nwakanma, Davis; Kiechel, Jean-René; Ogunkunle, Taofik; Olagunju, Tope; Murtala, Rukayat; Omefe, Peter; Lambe, Tosin; Bello, Surajudeen; Ibrahim, Olayinka; Olorunsola, Benedict; Ojuawo, Ayotade; Greenwood, Brian; Milligan, Paul

2015-08-15

Malaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD. Patients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months. A total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%-84%) for MQAS and 36% (40%-70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil. IPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil. NCT01319448 and ISRCTN46158146. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications

PubMed Central

Chou, Timothy Y; Hong, Bennett Y

2014-01-01

Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy. PMID:25187721

Efficacy and tolerability of oral lacosamide as adjunctive therapy in pediatric patients with pharmacoresistant focal epilepsy.

PubMed

Gavatha, M; Ioannou, I; Papavasiliou, A S

2011-04-01

The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range=3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings. Copyright © 2011 Elsevier Inc. All rights reserved.

PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

PubMed

Nuebling, Georg; Hensler, Mira; Paul, Sabine; Zwergal, Andreas; Crispin, Alexander; Lorenzl, Stefan

2016-08-01

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

Thermal ecotypes of amphi-Atlantic algae. I. Algae of Arctic to cold-temperate distribution ( Chaetomorpha melagonium, Devaleraea ramentacea and Phycodrys rubens)

NASA Astrophysics Data System (ADS)

Novaczek, I.; Lubbers, G. W.; Breeman, A. M.

1990-09-01

Three species of Arctic to cold-temperate amphi-Atlantic algae, all occurring also in the North Pacific, were tested for growth and/or survival at temperatures of -20 to 30°C. When isolates from both western and eastern Atlantic shores were tested side-by-side, it was found that thermal ecotypes may occur in such Arctic algae. Chaetomorpha melagonium was the most eurythermal of the 3 species. Isolates of this alga were alike in temperature tolerance and growth rate but Icelandic plants were more sensitive to the lethal temperature of 25°C than were more southerly isolates from both east and west. With regard to Devaleraea ramentacea, one Canadian isolate grew extraordinarily well at -2 and 0°C, and all tolerated temperatures 2 3°C higher than the lethal limit (18 20°C) of isolates from Europe. Concerning Phycodrys rubens, both eastern and western isolates died at 20°C but European plants tolerated the lethal high temperature longer, were more sensitive to freezing, and attained more rapid growth at optimal temperatures. The intertidal species, C. melagonium and D. ramentacea, both survived freezing at -5 and -20°C, at least for short time periods. C. melagonium was more susceptible than D. ramentacea to desiccation. Patterns of thermal tolerance may provide insight into the evolutionary history of seaweed species.

A randomized controlled trial of a middle meatal silastic stent for reducing adhesions and middle turbinate lateralization following endoscopic sinus surgery.

PubMed

Chan, Chun L; Elmiyeh, Behrad; Woods, Charmaine; Ullah, Shahid; Gunawardena, Indunil; Carney, A Simon; Ooi, Eng H

2015-06-01

Endoscopic sinus surgery (ESS) is indicated for patients with recalcitrant chronic rhinosinusitis symptoms. However, surgical revision can be required because of adhesion formation and middle turbinate lateralization. We investigate the efficacy of a middle meatal silastic stent in reducing these complications after ESS. Thirty-six patients were randomized to receive a silastic stent in the middle meatus unilaterally after ESS. The surgeon was blinded to the side receiving the stent until completion of the ESS. The contralateral side, with no stent, was the control side. Patients completed a 7-day, postoperative, visual analog scale symptom diary and were blinded to the stent side until its removal at the first postoperative visit. Patients were followed up after 2, 8, and 24 weeks. Endoscopic video of the sinus cavities were recorded at all visits and 2 blinded, independent ear/nose/throat (ENT) surgeons assessed the videos using a modified Lund-Kennedy scoring system. Thirty-five of 36 patients completed 6-months' follow-up. Middle turbinate lateralization was observed in 13 sides without a stent vs 1 side with a stent. There was a significant reduction in adhesions at weeks 2 and 8 (p < 0.001) and crusting (p < 0.01) in the stent side compared to control. Video scores at 6 months after surgery for stent and control sides remained unchanged from the 8-week visit. There was no difference between sides for symptom scores, edema, or nasal discharge. Middle meatal silastic stents are well tolerated by patients and effective in reducing middle turbinate lateralization, adhesions, and crusting postoperatively in ESS. © 2015 ARS-AAOA, LLC.

Effect of hexamethonium on the vascular response to noradrenaline in man

PubMed Central

Hodge, R. L.; Whelan, R. F.

1962-01-01

Intra-arterial infusion of hexamethonium into the brachial artery had no potentiating effect on the constrictor response of the vessels of the forearm or hand to noradrenaline given by the same route. The response of the hand vessels to intravenous infusion of noradrenaline was enhanced after intra-arterial hexamethonium, but this was attributed to entry of the blocking agent into the general circulation resulting in blockade of baroreceptor reflexes since the potentiation was seen to an equal degree on both sides. It is concluded that if increased sensitivity to noradrenaline plays a part in the phenomenon of tolerance to hexamethonium this must be a slowly developing effect. PMID:13907950

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

PubMed

Besi, E; Boniface, D R; Cregg, R; Zakrzewska, J M

2015-01-01

Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

Molecular dynamics study of linear and comb-like polyelectrolytes in aqueous solution: effect of Ca2+ ions

NASA Astrophysics Data System (ADS)

Tong, Kefeng; Song, Xingfu; Sun, Shuying; Xu, Yanxia; Yu, Jianguo

2014-08-01

All-atom molecular dynamics simulations were employed to provide microscopic mechanism for the salt tolerance of polyelectrolytes dispersants. The conformational variation of polyelectrolytes and interactions between COO- groups and counterions/water molecules were also studied via radius of gyration and pair correlations functions. Sodium polyacrylate (NaPA) and sodium salts of poly(acrylic acid)-poly(ethylene oxide) (NaPA-PEO) were selected as the representative linear and comb-like polyelectrolyte, respectively. The results show that Ca2+ ions interact with COO- groups much stronger than Na+ ions and can bring ion-bridging interaction between intermolecular COO- groups in the NaPA systems. While in the NaPA-PEO systems, the introduced PEO side chains can prevent backbone chains from ion-bridging interactions and weaken the conformational changes. The present results can help in selecting and designing new-type efficient polyelectrolyte dispersants with good salt tolerance.

Physician attitudes and beliefs about use of morphine for cancer pain.

PubMed

Elliott, T E; Elliott, B A

1992-04-01

The recent literature asserts that mistaken physician beliefs and attitudes are critical barriers to adequate cancer pain relief. To determine the prevalence of 12 proposed myths or misconceptions about morphine use in cancer pain management (CPM), we surveyed all physicians engaged in direct patient care in Duluth, Minnesota (N = 243). A 62% response was obtained. Many physicians misunderstood concepts of morphine tolerance, both to analgesia (51%) and to side effects (39%). Many were unaware of the use of adjuvant analgesics (29%), efficacy of oral morphine (27%), and nonexistent risk of addiction in CPM (20%). Analysis of result by physician age and specialy groups confirmed significant levels of misunderstanding in all subsets. Strategies to change physician attitudes and beliefs regarding morphine in CPM should focus on tolerance concepts, dosing schemes, safety, efficacy, lack of addictive risk, use of drug combinations, and the fact that cancer pain can be relieved.

Influence of exocrine and endocrine pancreatic function on intestinal brush border enaymatic activities.

PubMed Central

Caspary, W F; Winckler, K; Lankisch, P G; Creutzfeldt, W

1975-01-01

Digestive enzymatic activities (disaccharidases, alkaline phosphatase, peptide hydrolases) have been determined in the mucosa of 14 patients with chronic pancreatitis. All had an abnormal secretin-pancreozymin test. Four patients had insulin-dependent diabetes mellitus, four a pathological glucose tolerance test. Nine patients had steatorrhoea. Maltase, sucrase, and alkaline phosphatase activity was significantly elevated in patients with exocrine pancreatic insufficiency, whereas those of lactase, trehalase, and peptide hydrolase were normal. Patients with steatorrhoea had higher maltase and sucrase activity than those without steatorrhoea, whereas decreased glucose tolerance had no effect on brush border enzymatic activity. It is suggested thatdecreased exocrine rather than decreased endocrine pancreatic function is responsible for the increase in intestinal disaccharidase and alkaline phosphatase activity, possible by the influence of pacreatic enzymes on the turnover of brush border enzymes from the luminal side of the mucosal membranes or by direct hormonal stimulation though cholecystokinin. PMID:1092602

Static and fatigue testing of full-scale fuselage panels fabricated using a Therm-X(R) process

NASA Technical Reports Server (NTRS)

Dinicola, Albert J.; Kassapoglou, Christos; Chou, Jack C.

1992-01-01

Large, curved, integrally stiffened composite panels representative of an aircraft fuselage structure were fabricated using a Therm-X process, an alternative concept to conventional two-sided hard tooling and contour vacuum bagging. Panels subsequently were tested under pure shear loading in both static and fatigue regimes to assess the adequacy of the manufacturing process, the effectiveness of damage tolerant design features co-cured with the structure, and the accuracy of finite element and closed-form predictions of postbuckling capability and failure load. Test results indicated the process yielded panels of high quality and increased damage tolerance through suppression of common failure modes such as skin-stiffener separation and frame-stiffener corner failure. Finite element analyses generally produced good predictions of postbuckled shape, and a global-local modelling technique yielded failure load predictions that were within 7% of the experimental mean.

[Usefulness of Uro-Vaxom in complex treatment of recurrent urinary tract infections in girls].

PubMed

Gołabek, Bozena; Nowakowska, Krystyna; Słowik, Małgorzata; Paruszkiewicz, Grzegorz

2002-04-01

Uro-Vaxom was used in the treatment of recurrent urinary tract infections in 35 girls. Most of them (34/35) tolerated the drug very well, no side effect were observed. We stopped administration of the Uro-Vaxom in one girl, during the first month of treatment because of vomiting. This way efficiency of Uro-Vaxom was evaluated in the treatment of recurrent urinary tract infections in 34 girls. Uro-Vaxom was found to be a valuable drug, supporting antibiotic therapy in recurrent urinary tract infections caused by E. coli.

Gluten-Free Diet Indications, Safety, Quality, Labels, and Challenges

PubMed Central

Rostami, Kamran; Bold, Justine; Parr, Alison; Johnson, Matt W.

2017-01-01

A gluten-free diet (GFD) is the safest treatment modality in patient with coeliac disease (CD) and other gluten-related disorders. Contamination and diet compliance are important factors behind persistent symptoms in patients with gluten related-disorders, in particular CD. How much gluten can be tolerated, how safe are the current gluten-free (GF) products, what are the benefits and side effects of GFD? Recent studies published in Nutrients on gluten-free products’ quality, availability, safety, as well as challenges related to a GFD are discussed. PMID:28786929

[High-dosed gestagen therapy of the metastatic mammary carcinoma (author's transl)].

PubMed

Firusian, N; Becher, R

1981-12-01

Thirty patients with histologically proven metastatic mammary carcinoma were treated, after exhaustion of hormonal and cytostatic therapeutic means, with high-dosed medroxyprogesterone acetate (MPA) during a ten-day induction phase with 1000 mg MPAi.m. per day and then with 600 mg oral MPA per day. In eleven patients a complete or partial remission was achieved. The median period of remission comprised ten months. A positive relationship was found between the response to high-dosed MPA therapy and the length of free intervals. Side effects were tolerable.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

PubMed

Fond, G; Hamdani, N; Kapczinski, F; Boukouaci, W; Drancourt, N; Dargel, A; Oliveira, J; Le Guen, E; Marlinge, E; Tamouza, R; Leboyer, M

2014-03-01

To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Beta 1 versus nonselective blockade in therapy of essential tremor.

PubMed

Larsen, T A; Teräväinen, H

1983-01-01

The beta 1-selective blocker metoprolol was compared to propranolol and a placebo in a double-blind crossover trial in 24 patients with essential tremor. Both beta blockers suppressed the essential tremor, but metoprolol, which caused a mean reduction of 32.0% in tremor intensity from the base-line value, was less effective than propranolol, which reduced mean tremor intensity by 41.3%. Subjective benefit for their tremor was found by 15 of the patients taking propranolol and by one taking metoprolol. The tremor frequency was not affected. No serious side effects were observed. Metoprolol may offer an alternative for those essential tremor patients who cannot tolerate propranolol.

[Garlic effectiveness in rheumatoid arthritis].

PubMed

Denisov, L N; Andrianova, I V; Timofeeva, S S

1999-01-01

To perform of clinical trial of alisate--a garlic preparation produced in Russia. An open controlled trial of alisate enrolled 30 patients with rheumatoid arthritis (RA). 15 patients with RA of varying clinical form, stage and activity were given alisate in a dose 300 mg (1 tablet) twice a day for 4-6 weeks. 15 control RA patients received conventional antirheumatic therapy. The alisate group achieved a good and partial response in 86.5% of cases. The drug was well tolerated and had no side effects. In control group, some parameters changed for the worse. Alisate can be recommended for treatment of RA patients in combined and monotherapy.

A Unique Preparation and Delivery Method for Acitretin for Neonatal Harlequin Ichthyosis

PubMed Central

Damodaran, Kriti; Bhutada, Alok

2018-01-01

Harlequin ichthyosis is a rare form of congenital ichthyosis with a distinct phenotypic appearance. We describe a case of a newborn baby with harlequin ichthyosis who was treated with an oral formulation of acitretin. The treatment resulted in a satisfactory improvement in the skin condition of the patient. The tolerance to the drug was good with no side effects in the patient. The aim of this case report is to highlight an extemporaneous preparation of acitretin from the commonly available capsule form, which is effective for use in neonates with harlequin ichthyosis. It also highlights the risk of exposure to health care providers to acitretin. PMID:29720920

Saw palmetto for prostate disorders.

PubMed

Gordon, Andrea E; Shaughnessy, Allen F

2003-03-15

Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement

PubMed Central

Ramar, Kannan; Rosen, Ilene M.; Kirsch, Douglas B.; Chervin, Ronald D.; Carden, Kelly A.; Aurora, R. Nisha; Kristo, David A.; Malhotra, Raman K.; Martin, Jennifer L.; Olson, Eric J.; Rosen, Carol L.; Rowley, James A.

2018-01-01

The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA. Citation: Ramar K, Rosen IM, Kirsch DB, Chervin RD, Carden KA, Aurora RN, Kristo DA, Malhotra RK, Martin JL, Olson EJ, Rosen CL, Rowley JA; American Academy of Sleep Medicine Board of Directors. Medical cannabis and the treatment of obstructive sleep apnea: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2018;14(4):679–681. PMID:29609727

Rescue Pharmacotherapy With Duloxetine for Selective Serotonin Reuptake Inhibitor Nonresponders in Late-Life Depression: Outcome and Tolerability

PubMed Central

Karp, Jordan F.; Whyte, Ellen M.; Lenze, Eric J.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F.

2010-01-01

Background Up to 50% of depressed older adults either do not adequately respond to or are unable to tolerate treatment with a serotonin-specific reuptake inhibitor. On the basis of previous experience with serotonin-norepinephrine reuptake inhibitors, we predicted at least a 50% response rate to open-label treatment with duloxetine in subjects who were resistant to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram. Method Community-dwelling subjects aged 65 years or older with current nonpsychotic major depressive disorder as established by the Structured Clinical Interview for DSM-IV received escitalopram under protocolized conditions between April 2004 and September 2006. Subjects who failed to meet response criteria or relapsed after achieving an initial response were subsequently switched to open treatment with duloxetine up to 120 mg/day. Side effects were assessed at every visit. Results Subjects (N = 40) switched to duloxetine had a mean (SD) age of 74.4 (7.0) years and a baseline (before escitalopram) 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of 20.0 (3.5) and were predominantly female (65.0%) and white (82.5%). The mean (SD) maximum dose of duloxetine was 93.0 (27.8) mg/day. Subjects received this maximum dose for a median duration of 6.9 weeks. Fifty percent of subjects (N = 20) met criteria for full response, 17.5% (N = 7) were partial responders, and 32.5% (N = 13) did not respond. The median time to response was 12.0 weeks (95% CI = 8.4 to 14.6). Five of the subjects (12.5%) discontinued duloxetine because of intolerable side effects. Discussion These open-label data suggest that duloxetine at doses up to 120 mg/day is a well-tolerated and potentially effective treatment for older adults who fail to respond to an adequate trial of an SSRI. These results are preliminary, and future controlled studies are required to test the efficacy of rescue pharmacotherapy with duloxetine. Trial Registration clinicaltrials.gov Identifier: NCT00177671 PMID:18251622

[High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure].

PubMed

Tauchert, M; Gildor, A; Lipinski, J

1999-10-01

The efficacy and tolerance of the standardized hawthorn (crataegus) extract WS 1442 were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.d.) over a period of 24 weeks. During and at the end of the observation period a significant improvement in clinical symptoms (reduced performance in the exercise tolerance test, fatigue, palpitation and exercise dyspnea) was observed. Ankle edema and nocturia disappeared by 83%, and by half of the patients respectively manifesting these symptoms before treatment. The improvement and economization of cardiac performance were additionally shown by a reduction in blood pressure, an increased maximal exercise tolerance and a reduction in the difference in the pressure/heart rate product (PHRP). The positive effects of WS 1442 were further demonstrated by an improved ejection fraction and an increased percentile shortening fraction measured using M-mode echocardiography. The stabilizing effect of the hawthorn extract on the heart rate was shown by a slower rest pulse, as well as by an increase in the number of day and night normorhythmic patients, as documented by long-term ECG. The reduction in the number of patients showing ST depressions, arrhythmias and ventricular extrasystoles at the maximum exercise level is regarded as an indication for an improved myocardial perfusion. Fourteen side effects were noted. In two cases (abdominal discomfort and facial pains accompanied by tachycardia) a possible relationship with the hawthorn therapy, was postulated which however was considered unlikely by the treating physicians. Almost 2/3 of the patients felt better or much better following the 24 weeks of treatment. More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. High-dose hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage NYHA II.

Single blind, randomized, controlled trial of a lightening product with and without iontophoresis versus tretinoin and vehicle for hyperpigmentation.

PubMed

Wanner, Molly; Houston, Neil; Javorsky, Emilia; Yuan, Minsheng; Alora-Palli, Maria; Kimball, Alexa B

2015-01-01

Hyperpigmentation is a common concern and has many causes including lentigines and melasma. Currently available topical products for hyperpigmentation are limited by their potential for irritation, lack of demonstrated efficacy or regulatory concerns. To compare the efficacy of a new skin lightening product with and without iontophoresis to a known effective product (tretinoin) and placebo on hyperpigmentation caused by lentigines and/or melasma. Secondary objectives included an assessment of the product's effects on the appearance of rhytides and roughness. Eighty subjects were randomized into one of four treatment groups: proprietary lightening product, proprietary lightening product with iontophoresis, tretinoin 0.05% cream, or vehicle control. Seventy-four subjects completed all study visits. Blinded assessments of subjects were performed at each visit under ambient and Wood's light. The proprietary skin lightening product improved facial hyperpigmentation versus placebo under ambient light (P= 0.05) and Wood's lamp (P= 0.01) examination. Tretinoin also improved facial hyperpigmentation versus placebo under Wood's lamp (P= 0.01). The proprietary product was better tolerated than tretinoin, with fewer subject reported side effects. The investigational product was effective and may be better tolerated than tretinoin cream.

An update on the safety of nutraceuticals and effects on lipid parameters.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2018-03-01

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability in developed countries, whereas a large portion of patients in primary prevention have uncontrolled level of CVD risk factors. Dietary supplementation with bioactive natural compounds with demonstrated lipid-lowering effects is currently supported by the international guidelines for CVD prevention and some international expert panels. Areas covered: This review provides insights on issues concerning the tolerability and safety of the most commonly used nutraceuticals with demonstrated lipid-lowering effect in humans. They will be then divided into three main categories according to their mechanism of action (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) and their pharmacological profile will be discussed. Expert opinion: A growing body of preclinical, epidemiological and clinical evidence has defined the tolerability and safety profile of the most commonly used lipid-lowering nutraceuticals. In the most part of cases, the side effects are mild and reversible. However, detailed knowledge of specific health risks and pharmacological interactions for each individual compound is needed for the management of frail patients, such as children, elderly, patients with liver or renal failure, and patients consuming numerous drugs.

Use of Autoantigen-Loaded Phosphatidylserine-Liposomes to Arrest Autoimmunity in Type 1 Diabetes

PubMed Central

Pujol-Autonell, Irma; Serracant-Prat, Arnau; Cano-Sarabia, Mary; Ampudia, Rosa M.; Rodriguez-Fernandez, Silvia; Sanchez, Alex; Izquierdo, Cristina; Stratmann, Thomas; Puig-Domingo, Manuel; Maspoch, Daniel; Verdaguer, Joan; Vives-Pi, Marta

2015-01-01

Introduction The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes. Objective To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes. Methods A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides. Results We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion. Conclusions We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases. PMID:26039878

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

PubMed

McCracken, J T; Badashova, K K; Posey, D J; Aman, M G; Scahill, L; Tierney, E; Arnold, L E; Vitiello, B; Whelan, F; Chuang, S Z; Davies, M; Shah, B; McDougle, C J; Nurmi, E L

2014-06-01

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.

Combination therapy with retinaldehyde (0.1%) glycolic acid (6%) and efectiose (0.1%) in mild to moderate acne vulgaris during the period of sun exposure--efficacy and skin tolerability.

PubMed

Masini, F; Ricci, F; Fossati, B; Frascione, P; Capizzi, R; De Waure, C; Guerriero, C

2014-08-01

Acne vulgaris is the most common disease of the adolescence age (70-94%). Main topical treatments for acne vulgaris are retinoids, benzoyl peroxide and antibiotics in mono or combination therapy. Topical retinoids, some antibiotics and antiseptics although effective on acne lesions, can due photosensitivity or make the skin more sensitive to the sun. Our study is aimed to evaluate the efficacy and tolerability of a combination therapy with Retinaldheyde (0.1%), Glycolic acid (6%) and Efectiose (0.1%) (RGE) cream in patients affected by acne vulgaris, during the lasting period of sun exposure. We retrospectively observed 30 patients of Central Italy with mild or moderate acne between April and September. All the patients selected underwent only therapy with RGE cream once a day in the evening for 8 weeks, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. The mean GES value showed a statistically significant reduction: 1.83 (SD 0.83) at baseline 1.57 (SD 0.77) and 0.90 (SD 0.76) respectively at 30 and 60 days (p < 0.01). Side effects were very uncommon. Topical treatments with retinoids, antibiotics and antiseptics can be associated with an increased occurrence of facial dryness and erythema restricting their use in sun exposure period. RGE cream has shown a good skin tolerability and efficacy, so it can be considerate an effective maintaining therapy to treat mild to moderate acne during the sun exposure period in which retinoids, antibiotics or antiseptic treatments are not recommended.

Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

PubMed

Pujol-Autonell, Irma; Serracant-Prat, Arnau; Cano-Sarabia, Mary; Ampudia, Rosa M; Rodriguez-Fernandez, Silvia; Sanchez, Alex; Izquierdo, Cristina; Stratmann, Thomas; Puig-Domingo, Manuel; Maspoch, Daniel; Verdaguer, Joan; Vives-Pi, Marta

2015-01-01

The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes. To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes. A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides. We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion. We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases.

The use of rotation to fentanyl in cancer-related pain

PubMed Central

Dima, Delia; Tomuleasa, Ciprian; Frinc, Ioana; Pasca, Sergiu; Magdo, Lorand; Berindan-Neagoe, Ioana; Muresan, Mihai; Lisencu, Cosmin; Irimie, Alexandru; Zdrenghea, Mihnea

2017-01-01

Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. PMID:28223843

Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

PubMed Central

Kishi, Taro; Iwata, Nakao

2015-01-01

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer’s disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=−0.13), activity of daily living scores (standardized mean difference=−0.10), and global assessment scores (standardized mean difference=−0.15). In addition, cognitive function scores (standardized mean difference=−0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer’s disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer’s disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. PMID:25548104

Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis.

PubMed

Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

2014-12-28

We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease. We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. © The Author 2015. Published by Oxford University Press on behalf of CINP.

The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer: Case Report and Review of Literature.

PubMed

Ding, Lin; Li, Qing-Jian; You, Kai-Yun; Jiang, Zhi-Min; Yao, He-Rui

2016-05-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer.The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects.We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle.Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable.Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study.

The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer

PubMed Central

Ding, Lin; Li, Qing-Jian; You, Kai-Yun; Jiang, Zhi-Min; Yao, He-Rui

2016-01-01

Abstract Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer. The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects. We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle. Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable. Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study. PMID:27196461

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

PubMed

Sciurba, Frank C; Criner, Gerard J; Strange, Charlie; Shah, Pallav L; Michaud, Gaetane; Connolly, Timothy A; Deslée, Gaëtan; Tillis, William P; Delage, Antoine; Marquette, Charles-Hugo; Krishna, Ganesh; Kalhan, Ravi; Ferguson, J Scott; Jantz, Michael; Maldonado, Fabien; McKenna, Robert; Majid, Adnan; Rai, Navdeep; Gay, Steven; Dransfield, Mark T; Angel, Luis; Maxfield, Roger; Herth, Felix J F; Wahidi, Momen M; Mehta, Atul; Slebos, Dirk-Jan

Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. To determine the effectiveness and safety of endobronchial coil treatment. Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. clinicaltrials.gov Identifier: NCT01608490.

Utility of Boron in Dermatology.

PubMed

Jackson, David G; Cardwell, Leah A; Oussedik, Elias; Feldman, Steven R

2017-08-09

Boron compounds are being investigated as therapies for dermatologic conditions. Several features of boron chemistry make this element an ideal component in dermatologic treatments. We review the published dermatologically-relevant clinical trials and case studies pertaining to boron compounds. PubMed was utilized to query terms boron, chemistry, drug, development, dermatology, atopic dermatitis, psoriasis, onychomycosis, tavaborole, AN 2690, crisaborole, and AN 2728. Clinical trials, case studies, animal studies and in vitro studies. pertaining to atopic dermatitis, psoriasis and onychomycosis were included. Crisaborole 2% topical solution reduced atopic dermatitis lesions by approximately 60% when compared to pre-treatment baseline. Crisaborole maintains its dose-dependent effect in treatment of psoriasis and significantly reduces psoriatic plaques when compared to controls. Adverse effects were mild, frequency of events varied between studies. Crisaborole was well tolerated when applied to sensitive skin. Topical tavaborole significantly reduced or eliminated onychomycosis with minimal side effects compared to placebo. Tavaborole was effective in treating recalcitrant onychomycosis. Boron-based compounds form stable interactions with enzyme targets and are safe medications for the treatment of atopic dermatitis, psoriasis, and onychomycosis. The mild and rare side effects of topical boron-based compounds may make them ideal treatments for individuals with sensitive skin and pediatric populations.

Role of preemptive tapentadol in reduction of postoperative analgesic requirements after laparoscopic cholecystectomy

PubMed Central

Yadav, Ghanshyam; Jain, Gaurav; Samprathi, Abhishek; Baghel, Annavi; Singh, Dinesh Kumar

2016-01-01

Background and Aims: Poorly managed acute postoperative pain may result in prolonged morbidity. Various pharmacotherapies have targeted this, but research on an ideal preemptive analgesic continues, taking into account drug-related side effects. Considering the better tolerability profile of tapentadol, we assessed its role as a preemptive analgesic in the reduction of postoperative analgesic requirements, after laparoscopic cholecystectomy. Material and Methods: In a prospective-double-blinded fashion, sixty patients posted for above surgery, were randomized to receive tablet tapentadol 75 mg (Group A) or starch tablets (Group B) orally, an hour before induction of general anesthesia. Perioperative analgesic requirement, time to first analgesia, pain, and sedation score were compared for first 24 h during the postoperative period and analyzed by one-way analysis of variance test. A P < 0.05 was considered significant. Results: Sixty patients were analyzed. The perioperative analgesic requirement was significantly lower in Group A. Verbal numerical score was significantly lower in Group A at the time point, immediately after shifting the patient to the postanesthesia care unit. Ramsay sedation scores were similar between the groups. No major side effects were observed except for nausea and vomiting in 26 cases (10 in Group A, 16 in Group B). Conclusion: Single preemptive oral dose of tapentadol (75 mg) is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects. PMID:28096581

Clonidine is effective for the treatment of primary idiopathic hyperhidrosis and hot flushes: a case report.

PubMed

Albadrani, Ahmed

2017-01-17

While primary hyperhidrosis can be seen in men, accompanying hot flushes is rarely seen in men. Primary hyperhidrosis is thought to be related to overactivity of the sympathetic nervous system while hot flushes are believed to be related to altered peripheral vascular reactivity and a narrowed thermoregulatory zone. I report the case of a 29-year-old man of Arab origin who presented to a dermatology clinic with a complaint of generalized sweating, with heavier involvement of his inguinal region, axilla, and lower back. His complaint was associated with a transient hot sensation and erythema over the affected areas. He did not respond to topical antiperspirants containing aluminum chloride, topical aluminum chloride, or to botulinum toxin A injected in both inguinal areas. He was then referred to an endocrinology clinic to rule out secondary causes of hyperhidrosis and hot flushes; a primary diagnosis was confirmed. He did not respond to oral glycopyrrolate and additionally was complaining of its anticholinergic side effects. The glycopyrrolate was then replaced with oral clonidine 0.15 mg twice a day. Clonidine was well tolerated without remarkable side effects and he quickly started to feel marked improvement which was maintained for 2 years. I report an atypical presentation of primary hyperhidrosis and hot flushes that was effectively controlled by clonidine without remarkable side effects. Further research on a large number of patients may be required before recommending clonidine in similar conditions.

Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder.

PubMed

Nikvarz, Nikvarz; Alaghband-Rad, Javad; Tehrani-Doost, Mehdi; Alimadadi, Abbas; Ghaeli, Padideh

2017-01-01

Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Bianco, M.; Wiehagen, J.

This project evaluated the effectiveness and affordability of integrating retrofit insulated panels into a re-siding project. The Partnership for Home Innovation (PHI) teamed with New York State Energy Research and Development Authority (NYSERDA), the Albany Housing Authority (AHA), and the New York State Weatherization Assistance Program (WAP) administered by Albany Community Action Partnership to demonstrate an energy retrofit and siding upgrade on a two-story, seven unit, multifamily building in Albany New York (CZ 5). The project focused on accomplishing three goals - doubling the existing wall thermal resistance (from approximately R-13 to a weighted average of R-27), reduction of buildingmore » air leakage, and completion of the retrofit within a budget where the additional cost for upgrading wall's thermal resistance is equal to the cost of the standard re-siding effort (i.e., the total cost of the energy efficient re-siding scope of work is not more than double the cost of the standard re-siding effort). Lessons learned from the project strongly indicate that the retrofit panel technology can be installed using common installation practices and with minimal training. Other lessons learned include limitation on the use of standard air sealing materials during cold weather installations and the need to develop better installation guidance for trades working with the level of tolerances that may be present in the existing structure. This technology demonstration showed that exterior retrofit panels provide a viable and reasonable option for the siding trades to increase market opportunities and achieve synergistic benefits for aesthetic upgrades to a building's exterior.« less

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease.

PubMed

Oldham, Justin M; Lee, Cathryn; Valenzi, Eleanor; Witt, Leah J; Adegunsoye, Ayodeji; Hsu, Scully; Chen, Lena; Montner, Steven; Chung, Jonathan H; Noth, Imre; Vij, Rekha; Strek, Mary E

2016-12-01

Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown. A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models. Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement. A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement-device-independent quantum coin tossing

NASA Astrophysics Data System (ADS)

Zhao, Liangyuan; Yin, Zhenqiang; Wang, Shuang; Chen, Wei; Chen, Hua; Guo, Guangcan; Han, Zhengfu

2015-12-01

Quantum coin tossing (QCT) is an important primitive of quantum cryptography and has received continuous interest. However, in practical QCT, Bob's detectors can be subjected to detector-side channel attacks launched by dishonest Alice, which will possibly make the protocol completely insecure. Here, we report a simple strategy of a detector-blinding attack based on a recent experiment. To remove all the detector side channels, we present a solution of measurement-device-independent QCT (MDI-QCT). This method is similar to the idea of MDI quantum key distribution (QKD). MDI-QCT is loss tolerant with single-photon sources and has the same bias as the original loss-tolerant QCT under a coherent attack. Moreover, it provides the potential advantage of doubling the secure distance for some special cases. Finally, MDI-QCT can also be modified to fit the weak coherent-state sources. Thus, based on the rapid development of practical MDI-QKD, our proposal can be implemented easily.

[Glucose tolerance and insulinemia in patients with hepatic cirrhosis and portal hypertension treated by portacaval anastomosis].

PubMed

Postiglione, A; Casaretti, B; Masciariello, S; Riccardi, G; Perrotti, N; Lamenza, F; Porcellini, M; Mattioli, P L

1979-02-28

Development of diabetes mellitus is a common complication of side to side porta-caval anastomosis (PCA). Five patients with liver cirrhosis and portal hypertension have been studied with intravehous (IVGTT, 0,5 g/Kg B.W.) and oral (OGTT, 1 g/Kg B.W.) glucose tolerance tests before and three weeks after PCA. Fasting plasma glucose was 84 +/- 7 before and 87 +/- 3 mg/dl after PCA. Fasting IRI increased from 17 +/- 3 to 31 +/- 6 microU/ml. The pattern of plasma glucose and IRI response to IVGTT did not change after PCA. Plasma glucose resonse to OGTT after PCA showed only an earlier rise at 60 instead of 90 minutes, whereas IRI resonse (area under the insulin curve) was significantly enhanced (from 12.4 to 19.8 U/l, p < 0.05). These data suggest a role of gut polipeptides in determining hyperinsulinemia and insulin resistence in PCA patients.

Use of botulinum toxin in individuals with neurogenic detrusor overactivity: State of the art review

PubMed Central

Linsenmeyer, Todd A.

2013-01-01

Background Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox® (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administration, easy learning curve, reproducibility of results on repeated administration, and low incidence of complications. Objective To discuss the structure and function, mechanisms of action, clinical and urodynamic studies, injection technique, potential beneficial and adverse effects, and potential areas of research of BoNT. Methods Literature search focused on botulinum toxin in MEDLINE/PubMed. Search terms included botulinum toxin, neurogenic bladder, NDO, botox bladder, botox spinal cord injury, botox, FDA, botox side effects. All papers identified were English language, full-text papers. In addition, English abstracts of non-English papers were noted. The reference list of identified articles was also searched for further papers. Conclusion Botulinum toxin is an alternative treatment for individuals with NDO who fail to tolerate anticholinergic medications. Its popularity has increased because of the literature, which has supported its effectiveness, safety, easy use and learning curve, reproducibility of results on repeated use, and recent FDA approval of Botox® (onabotulinumtoxinA). PMID:23941788

Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures.

PubMed

Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical practice. Finally, pharmacological properties of BRV are summarized with a description of its pharmacokinetics, safety, and potential/known drug-drug interactions.

Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

PubMed

Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

2016-07-01

Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. © 2016 Blackwell Verlag GmbH.

Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial.

PubMed

Stengel, Joel Z; Jones, David P

2008-09-01

Proper colonic cleansing prior to colonoscopy is paramount to ensuring complete mucosal visualization and polyp identification. In a double-blind fashion, we compared single-dose lubiprostone (24 microg) versus placebo pretreatment prior to a split-dose polyethylene glycol electrolyte (PEG-E) bowel preparation without dietary restriction to determine the efficacy, safety, and patient tolerability. Two hundred patients referred for outpatient colorectal cancer screening were randomized to receive a single-dose of unlabeled lubiprostone (24 microg) or placebo prior to a split-dose PEG-E bowel preparation without dietary restriction. The patients were surveyed prior to the colonoscopy on the tolerability of the bowel preparation, and any adverse events were recorded. The cleanliness of the colon was graded by the endoscopist during the procedure utilizing the Ottawa bowel preparation scale. One hundred ninety-one patients completed the study (95%). Split-dose PEG-E with lubiprostone pretreatment was found to be more effective at bowel cleansing in each segment of the colon when compared with split-dose PEG-E with placebo (P < 0.001). Patients enrolled in the lubiprostone treatment arm rated the overall experience as more tolerable (P 0.003) and complained of less abdominal bloating (P 0.049). No differences were observed between the groups for treatment-emergent side effects or adverse events (P > 0.05). Single-dose lubiprostone prior to split-dose PEG-E without dietary restriction significantly improves colonic mucosa visualization during colonoscopy and is well tolerated by patients.

Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal.

PubMed

West, K P; Khatry, S K; LeClerq, S C; Adhikari, R; See, L; Katz, J; Shrestha, S R; Pradhan, E K; Pokhrel, R P; Sommer, A

1992-01-01

A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects.

Treatment of scabies with 5% permethrin cream: results of a German multicenter study.

PubMed

Hamm, Henning; Beiteke, Ulrike; Höger, Peter H; Seitz, Cornelia S; Thaci, Diamant; Sunderkötter, Cord

2006-05-01

Until recently, no prescription drug containing permethrin for the therapy of scabies was available on the German market.Therefore, a 5% permethrin cream formulation (InfectoScab 5%) was tested in a single-arm multi-center study including adults and children from 3 months of age with proven scabies. On day 0, patients were treated once with permethrin cream in the study center. Control examinations including dermatoscopy were performed on day 14+/-2 and on day 28+/-3. Patients who were not considered cured or who had contact to individuals with untreated scabies received one further treatment with permethrin cream on day 14+/-2. Itching and local tolerability of the cream were documented in patients' diaries. Side effects were assessed by history, skin inspection and evaluation of patients' notes. 106 patients in 13 centers were enrolled in the study. Their mean age was 29.2 years (range, 141 days to 71.9 years); 34% of them were children or adolescents. 78.3% of patients were either severely (3 body sites) or very severely (4-5 sites) affected. The cure rate on day 28+/-3 was 95.1% (95% confidence interval, 91.0-99.3%). Pruritus declined markedly and continuously. In general, the cream was well tolerated; side effects were almost invariably mild. Our results support the efficacy and safety of 5% permethrin cream in adults, children and infants suffering from scabies. These results have contributed to the approval of InfectoScab 5% in Germany for the treatment of scabies in October 2004.

Low back ache treatment with botulinum neurotoxin type A. Local experience in Kuwait.

PubMed

Nagarajan, Venkatesan; Al-Shubaili, Asmahan; Ayad, Yasser M; Alexander, John; Al-Ramezi, Khadijah

2007-01-01

To investigate the efficacy, safety and tolerability of paraspinal administration of botulinum neurotoxin type A (BoNT-A) in patients with chronic low back ache (LBA). Eight patients with chronic LBA were injected with BoNT-A at three sites on either side of lumbar paraspinal muscles. The patients rated their pain intensity using a visual analogue scale (VAS) from 0 to 10, and our physiotherapist assessed the paraspinal muscle spasm using a functional scale (FS) from 0 to 5. The improvement in both VAS and FS 30, 60 and 90 days after BoNT-A from baseline was analyzed separately using paired t test. The correlation between the muscle spasm (FS) and pain relief (VAS) was analyzed using the Spearman's rank correlation coefficient test. The level of statistical significance was p < 0.05. Five (63%) patients showed a remarkable recovery in VAS and FS, whereas 2 (25%) patients showed improvement only in FS. Statistically significant improvement was achieved in VAS and FS independently 30 days (p < 0.02 and p < 0.02, respectively), 60 days (p < 0.01 and p < 0.001, respectively) and 90 days (p < 0.02 and p < 0.001, respectively) after treatment. Pain relief started early and it was independent of relief of muscle spasm 30 days after treatment (r = 0.685; p > 0.05). With this limited study, we have demonstrated that the paraspinal injection of BoNT-A is effective in relieving chronic LBA without producing side effects. The injection is an easy procedure, well tolerated and did not require anesthesia or imaging technique.

Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia.

PubMed

Le, Tien; Menard, Chantal; Hicks-Boucher, Wendy; Hopkins, Laura; Weberpals, Johanne; Fung-Kee-Fung, Michael

2007-09-01

To investigate the activity of 5% Imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3. Patients with histologically confirmed VIN 2/3 were recruited from regional colposcopy units. A Simon two-stage phase 2 study design was used. Imiquimod cream was applied over the abnormal VIN areas by the patients, using an escalating dose regimen for a total treatment duration of 16 weeks. Colposcopy assessments were performed every 2 weeks to evaluate for response. A historical cohort of VIN 2/3 patients treated with primary surgical ablation was used to compare recurrence patterns. Thirty-nine patients enrolled in the study. Six patients dropped out due to side effects and non-compliance with study protocol. Thirty-six patients (92%) had VIN 3. Therapy was well tolerated with the most common observed side effects being only minor skin irritation at the application site. Histologic complete response was observed in 21 patients with partial response in another nine patients. The overall response rate was 77% using intention to treat principle. No VIN progression or cancer was diagnosed. At a median follow-up of 16 months in the whole study cohort, eight recurrences (20.5%) were observed. In comparison, the recurrence rate for primary surgically treated patients was 53.5% (p=0.013). Imiquimod cream was well tolerated and resulted in the regression in a majority of high-grade VIN lesions. The recurrence rate appeared to be comparable to primary surgical ablation.

Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection

PubMed Central

Azocar, Jose; Diaz, Arley

2013-01-01

AIM: To evaluate the safety and efficacy of Chlorella in 18 patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: Eighteen adults with chronic infection by HCV genotype 1 received daily oral supplementation of Chlorella for 12 wk. Changes in the RNA levels of HCV, as well as those of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated following this treatment period. Paired t tests were conducted to compare the means of the different variables at the beginning and end of the study. Side effects and quality of life aspects were also compared between weeks 0 and 12 of the study period. RESULTS: A majority 84.61% of the patients had a significant decrease in their ALT levels from week 0 to week 12. Evaluation of side effects showed that Chlorella was well tolerated. Quality of life assessment showed that 76.9 of the participants reported an improvement in their energy levels and 46.1% reported an improvement in their perception of general health. Although 69.23% also showed a decrease in their AST levels, this was not statistically significant. Most patients that exhibited an improvement in their ALT and AST levels also showed a tendency toward a decreased HCV viral load. The HCV RNA levels showed a decrease in 69.23% of the patients, which along with changes in AST/ALT ratios from week 0 to week 12, these results were not statistically significant. CONCLUSION: Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels. PMID:23467073

Pharmacokinetics, pharmacodynamics and the pharmacokinetic/ pharmacodynamic relationship of zolpidem in healthy subjects.

PubMed

de Haas, S L; Schoemaker, R C; van Gerven, J M A; Hoever, P; Cohen, A F; Dingemanse, J

2010-11-01

Zolpidem is one of the most frequently prescribed hypnotics, as it is a very short-acting compound with relatively few side effects. Zolpidem's short duration of action is partly related to its short elimination half-life, but the associations between plasma levels and pharmacodynamic (PD) effects are not precisely known. In this study, the concentration-effect relationships for zolpidem were modelled. Zolpidem (10 mg) was administered in a double-blind, randomised, placebo-controlled trial to determine PD and pharmacokinetics (PK) in 14 healthy volunteers. Zolpidem was absorbed and eliminated quickly, with a median T(max) of 0.78 h (range: 0.33-2.50) and t(1/2) of 2.2 h. Zolpidem reduced saccadic peak velocity (SPV), adaptive tracking performance, electroencephalogram (EEG) alpha power and visual analogue scale (VAS) alertness score and increased body sway, EEG beta power and VAS 'feeling high'. Short- and long-term memory was not affected. Central nervous system effects normalised more rapidly than the decrease of plasma concentrations. For most effects, zolpidem's short duration of action could be adequately described by both a sigmoid E(max) model and a transit tolerance model. For SPV and EEG alpha power, the tolerance model seemed less suitable. These PK/PD models have different implications for the mechanism underlying zolpidem's short duration of action. A sigmoid E(max) model (which is based on ligand binding theory) would imply a threshold value for the drug's effective concentrations. A transit tolerance model (in which a hypothetical factor builds up with time that antagonises the effects of the parent compound) is compatible with a rapid reversible desensitisation of GABAergic subunits.

A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

PubMed

Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

2017-07-01

Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

RASopathic Skin Eruptions during Vemurafenib Therapy

PubMed Central

Rinderknecht, Jeannine D.; Goldinger, Simone M.; Rozati, Sima; Kamarashev, Jivko; Kerl, Katrin; French, Lars E.

2013-01-01

Purpose Vemurafenib is a potent inhibitor of V600 mutant BRAF with significant impact on progression-free and overall survival in advanced melanoma. Cutaneous side effects are frequent. This single-center observational study investigates clinical and histological features of these class-specific cutaneous adverse reactions. Patients and Methods Patients were all treated with Vemurafenib 960 mg b.i.d. within local ethic committees approved clinical trials. All skin reactions were collected and documented prospectively. Cutaneous reactions were classified by reaction pattern as phototoxic and inflammatory, hair and nail changes, keratinocytic proliferations and melanocytic disorders. Results Vemurafenib was well tolerated, only in two patients the dose had to be reduced to 720 mg due to arthralgia. 26/28 patients (93%) experienced cutaneous side effects. Observed side effects included UVA dependent photosensitivity (n = 16), maculopapular exanthema (n = 14), pruritus (n = 8), folliculitis (n = 5), burning feet (n = 3), hair thinning (mild alopecia) (n = 8), curly hair (n = 2) and nail changes (n = 2). Keratosis pilaris and acanthopapilloma were common skin reactions (n = 12/n = 13), as well as plantar hyperkeratosis (n = 4), keratoacanthoma (n = 5) and invasive squamous cell carcinoma (n = 4). One patient developed a second primary melanoma after more than 4 months of therapy (BRAF and RAS wild type). Conclusion Vemurafenib has a broad and peculiar cutaneous side effect profile involving epidermis and adnexa overlapping with the cutaneous manifestations of genetic diseases characterized by activating germ line mutations of RAS (RASopathy). They must be distinguished from allergic drug reaction. Regular skin examination and management by experienced dermatologists as well as continuous prophylactic photo protection including an UVA optimized sun screen is mandatory. PMID:23516541

Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta‐analysis

PubMed Central

Tsaousi, Georgia; Apostolidou, Eirini; Karakoulas, Konstantinos; Kouvelas, Dimitrios; Amaniti, Ekaterini

2016-01-01

Aims The aim of this study was to perform an up‐to‐date systematic review and meta‐analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. Method A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. Results The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta‐analysis. The combined results from the meta‐analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03–0.42]: χ2 = 1.76: I2 = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14–2.99]: χ2 = 8.79: I2 = 77%). Conclusions The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results. PMID:26945547

The outweigh of toxicity versus risk of recurrence for adjuvant interferon therapy: a survey in German melanoma patients and their treating physicians.

PubMed

Kähler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Hauschild, Axel; Heinzerling, Lucie; Livingstone, Elisabeth; Loquai, Carmen; Müller-Brenne, Tina; Schadendorf, Dirk; Utikal, Jochen; Wagner, Tobias; Augustin, Matthias

2018-05-25

After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS). We compared physicians' preferences ("utilities") for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1.0 (perfect health). We assessed utilities for health states associated with adjuvant IFN using the standard gamble technique in 108 physicians and 130 melanoma patients. Four IFN toxicity scenarios and three outcome scenarios were given to the participants. Both groups were asked for the 5-year disease free survival (DFS) they would need to accept the described IFN-related side effects. In both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse. Physicians indicated higher utilities for each scenario and needed lower 5-year DFS both in case of mild-to-moderate and severe side effects. Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, while physicians only required a chance of 40% and 50%, respectively. Both physicians and patients rated melanoma recurrence much lower than even severe IFN side effects. In direct comparison, physicians rated cancer-related scenarios more positively and accepted IFN toxicity for an even lower treatment benefit.

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

PubMed

Boggs, Douglas L; Surti, Toral; Gupta, Aarti; Gupta, Swapnil; Niciu, Mark; Pittman, Brian; Schnakenberg Martin, Ashley M; Thurnauer, Halle; Davies, Andrew; D'Souza, Deepak C; Ranganathan, Mohini

2018-07-01

Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. https://clinicaltrials.gov/ct2/show/NCT00588731.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

PubMed

Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

2017-02-01

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Is oral immunotherapy the cure for food allergies?

PubMed

Nowak-Wegrzyn, Anna; Fiocchi, Alessandro

2010-06-01

To review current evidence on food oral immunotherapy (OIT). Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50-75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation. These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.

WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW

PubMed Central

Moreira-Marconi, Eloá; Sá-Caputo, Danubia C; Dionello, Carla F; Guedes-Aguiar, Eliane O; Sousa-Gonçalves, Cintia R; Morel, Danielle S; Paineiras-Domingos, Laisa L; Souza, Patricia L; Kütter, Cristiane R; Costa-Cavalcanti, Rebeca G; Costa, Glenda; Paiva, Patricia C; Figueiredo, Claudia; Brandão-Sobrinho-Neto, Samuel; Stark, Christina; Unger, Marianne; Bernardo-Filho, Mario

2017-01-01

Background: Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients. Materials and Methods: Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm. Results: A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation: Conclusion: It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients. PMID:28740938

Prostate histotripsy for BPH: initial canine results

NASA Astrophysics Data System (ADS)

Roberts, William W.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.

2009-02-01

Histotripsy is an extracorporeal ablative technology that utilizes microsecond pulses of intense ultrasound (< 1% duty cycle) to produce nonthermal, mechanical fractionation of targeted tissue. We have previously demonstrated the feasibility of histotripsy prostate ablation. In this study we sought to assess the chronic tissue response, tolerability and safety of histotripsy in a chronic in vivo canine model. Five acute and thirteen chronic canine subjects were anesthetized and treated with histotripsy targeting the prostate. Pulses consisted of 3 cycle bursts of 750 kHz ultrasound at a repetition rate of 300 Hz delivered transabdominally from a highly focused 15 cm aperture array. Transrectal ultrasound imaging provided accurate targeting and real-time monitoring of histotripsy treatment. Prostates were harvested at 0, 7, 28, or 56 days after treatment. Consistent mechanical tissue fractionation and debulking of prostate tissue was seen acutely and at delayed time points without collateral injury. Urothelialization of the treatment cavity was apparent 28 days after treatment. Canine subjects tolerated histotripsy with minimal hematuria or discomfort. Only mild transient lab abnormalities were noted. Histotripsy is a promising non-invasive therapy for prostate tissue fractionation and debulking that appears safe and well tolerated without systemic side effects in the canine model.

Special Blood Donation Procedures

MedlinePlus

... blood. For example, in the weeks before undergoing elective surgery, a person may donate several units of blood ... rigorous donor screening and testing. In addition, elderly patients may not tolerate donating blood before surgery because they are more likely to have side ...

Improving the therapeutic ratio of craniospinal irradiation in medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maor, M.H.; Fields, R.S.; Hogstrom, K.R.

1985-04-01

Radiation therapy delivered to the entire cerebrospinal axis is indicated for a number of pediatric brain tumors, especially medulloblastoma. Improved radiotherapy techniques have changed the near fatal prognosis for children with medulloblastoma to a 50%, 5-year survival. Nevertheless, the treatment results in substantial acute toxicity, and many survivors have serious sequelae. Refinements in radiotherapy technique, however, can improve the therapeutic ratio of the treatment by lowering its side effects. In the last year children who required craniospinal irradiation at M.D. Anderson Hospital were treated with 6 MV photons to the brain and primary tumor and with 15-17 MeV electrons tomore » the spinal canal. The elective dose to the whole brain was 30 Gy in 17 fractions and 30 Gy in 20 fractions to the spine. The primary tumor received an additional 20-25 Gy. An electron-beam dose distribution was drawn on a computerized tomography (CT) reconstructed sagittal plane. The treatment was well tolerated in the first five patients. It is projected that the current technique will cause fewer late effects and improve the tolerance to chemotherapy.« less

Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma?

PubMed

Tournoy, K G; Hove, C; Grooten, J; Moerloose, K; Brusselle, G G; Joos, G F

2006-01-01

Non-specific anti-inflammatory medication is actually the treatment of choice for controlling the T-helper type 2 (Th-2) cell-driven airway inflammation in asthma. The induction of counterbalancing Th-1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side-effects. This is therefore probably not a valid option for the treatment of asthma. With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen-induced airway disease. The induction of antigen-specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non-atopic individuals and have the potential of becoming an effective means of preventing allergen-induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen-induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.

Female sterilization: update on clinical efficacy, side effects and contraindications.

PubMed

Gizzo, Salvatore; Bertocco, Anna; Saccardi, Carlo; Di Gangi, Stefania; Litta, Pietro Salvatore; D'antona, Donato; Nardelli, Giovanni Battista

2014-10-01

The aim of this review is to compare studies concerning female sterilization in order to define the most suitable approach and device for each patient considering timing, safety, cost-effectiveness, failure rate, complication rate and patient satisfaction. A systematic literature search was conducted in electronic databases MEDLINE-EMBASE-Sciencedirect and Cochrane Library between 2000 and 2012. All original descriptions, case reports, retrospective and review articles on tubal sterilization methods have been considered. Outcome measures were effectiveness, tolerability, procedure complications and female satisfaction. The ideal female sterilization system should be a simple, safe, highly efficient, easily learned, inexpensive, one-time procedure without negative side-effects. Nowadays, the trans-cervical approach is associated with minimal postoperative pain, allowing short hospitalization and fast resumption of daily activities. Laparoscopic and laparotomic approaches are considered second choices, since, particularly in developing countries, the transcervical hysteroscopic methods will increasingly spread within gynaecological clinical practice. Safety issues, hospital stay, costs and surgeons' experience are important factors in decision-making of the method for female sterilization. Hysteroscopic devices should be preferred when possible. The counselling time remains a fundamental step in choice. The decision concerning method depends on the setting, the surgeon's experience, the country's economical development and the woman's preference.

An update on pharmacotherapy of autism spectrum disorder in children and adolescents.

PubMed

Goel, Ritu; Hong, Ji Su; Findling, Robert L; Ji, Na Young

2018-02-01

To date, no medication is proven to be effective in treating core symptoms of autism spectrum disorder (ASD). Psychotropic medications are widely used to target emotional and behavioural symptoms in ASD. This article reviewed evidence for pharmacotherapy, novel therapeutic agents, and Complementary and Alternative Medicine (CAM) in children and adolescents with ASD. Currently, only risperidone and aripiprazole have been approved by the US Food and Drug Administration (FDA) for treatment of irritability associated with ASD in children and adolescents. However, associated metabolic side-effects are concerning. Evidence supports use of methylphenidate and atomoxetine for attention deficit hyperactivity disorder (ADHD) symptoms and clonidine and guanfacine ER appear to be helpful. SSRIs are poorly tolerated and lack evidence in reducing restricted repetitive behaviours (RRB), anxiety, and depression. Buspirone shows promise in the treatment of RRB. The evidence is inconsistent for the effectiveness of anti-epileptic medications. Recent studies of glutamatergic, Gamma-aminobutyric acid (GABA)ergic, and cholinergic agents and oxytocin show inconsistent results. Despite wide use of CAM agents, the evidence is inconclusive. Melatonin can be helpful in reducing sleep problems. Overall, the evidence is limited for pharmacotherapy in children with ASD, and side-effects with long-term use can be burdensome.

[Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies].

PubMed

Gollnick, Harald P M; Graupe, Klaus; Zaumseil, Rolf-Peter

2004-10-01

Topical measures are still the mainstay in the therapy of mild-to-moderate acne vulgaris. Azelaic acid 20% in a cream formulation has been established as an efficacious and safe topical drug for 15 years. A new non-alcoholic hydrogel formulation containing 15% azelaic acid was clinically tested against two standard drugs--5% benzoyl peroxide (BPO) and 1% clindamycin. In two independent, randomized, blinded comparative trials 15% azelaic acid gel was clinically tested against 5% benzoyl peroxide (BPO) gel in 351 patients and against 1% clindamycin gel in 229 patients. The drugs were applied b.i.d. for 4 months. Azelaic acid 15% gel proved to be as effective as BPO and clindamycin with median % reduction of the inflamed lesion (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was well-tolerated, the side effects (local burning and irritation) were distinctly less than with BPO but more pronounced than with clindamycin. Despite these side effects, the treatment was well-accepted by the majority of patients. Azelaic acid gel is an effective topical monotherapy for mild-to-moderate acne vulgaris; its new gel form is an enrichment of acne therapy.

Glycolic acid peels versus salicylic-mandelic acid peels in active acne vulgaris and post-acne scarring and hyperpigmentation: a comparative study.

PubMed

Garg, Vijay Kumar; Sinha, Surabhi; Sarkar, Rashmi

2009-01-01

Many clinicians have used glycolic acid (GA) peels for facial acne, scarring, and hyperpigmentation, mainly in lighter skin types. Salicylic-mandelic acid combination peels (SMPs) are a newer modality, and there have been no well-controlled studies comparing them with other conventional agents. To compare the therapeutic efficacy and tolerability of 35% GA peels and 20% salicylic-10% mandelic acid peels in active acne and post-acne scarring and hyperpigmentation. Forty-four patients with facial acne and post-acne scarring and hyperpigmentation were divided into two groups, with one receiving GA peels and the other SMPs at fortnightly intervals for six sessions. The treating physician performed objective evaluation of treatment outcomes. The patients, the treating physician, and an independent observer made subjective assessments. Side effects of both agents were also noted. Both the agents were effective, but SMPs had a higher efficacy for most active acne lesions (p<.001) and hyperpigmentation (p<.001). Side effects were also lesser with SMPs. Both the agents were effective and safe in Indian patients, with SMPs being better for active acne and post-acne hyperpigmentation.

Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology.

PubMed

Fogel, Alexander L; Hill, Sharleen; Teng, Joyce M C

2015-05-01

Significant developments in the use of mammalian target of rapamycin (mTOR) inhibitors (mTORIs) as immunosuppressant and antiproliferative agents have been made. Recent advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTORIs in many challenging disorders such as tuberous sclerosis complex, pachyonychia congenita, complex vascular anomalies, and inflammatory dermatoses. Systemic mTORI therapy has shown benefits in these areas, but is associated with significant side effects that sometimes necessitate drug holidays. To mitigate the side effects of systemic mTORIs for dermatologic applications, preliminary work to assess the potential of percutaneous therapy has been performed, and the evidence suggests that percutaneous delivery of mTORIs may allow for effective long-term therapy while avoiding systemic toxicities. Additional large placebo-controlled, double-blinded, randomized studies are needed to assess the efficacy, safety, duration, and tolerability of topical treatments. The objective of this review is to provide updated information on the novel use of mTORIs in the management of many cutaneous disorders. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A walk on the wild side: Oryza species as source for rice abiotic stress tolerance.

PubMed

Menguer, Paloma Koprovski; Sperotto, Raul Antonio; Ricachenevsky, Felipe Klein

2017-01-01

Oryza sativa, the common cultivated rice, is one of the most important crops for human consumption, but production is increasingly threatened by abiotic stresses. Although many efforts have resulted in breeding rice cultivars that are relatively tolerant to their local environments, climate changes and population increase are expected to soon call for new, fast generation of stress tolerant rice germplasm, and current within-species rice diversity might not be enough to overcome such needs. The Oryza genus contains other 23 wild species, with only Oryza glaberrima being also domesticated. Rice domestication was performed with a narrow genetic diversity, and the other Oryza species are a virtually untapped genetic resource for rice stress tolerance improvement. Here we review the origin of domesticated Oryza sativa from wild progenitors, the ecological and genomic diversity of the Oryza genus, and the stress tolerance variation observed for wild Oryza species, including the genetic basis underlying the tolerance mechanisms found. The summary provided here is important to indicate how we should move forward to unlock the full potential of these germplasms for rice improvement.

A walk on the wild side: Oryza species as source for rice abiotic stress tolerance

PubMed Central

Menguer, Paloma Koprovski; Sperotto, Raul Antonio; Ricachenevsky, Felipe Klein

2017-01-01

Abstract Oryza sativa, the common cultivated rice, is one of the most important crops for human consumption, but production is increasingly threatened by abiotic stresses. Although many efforts have resulted in breeding rice cultivars that are relatively tolerant to their local environments, climate changes and population increase are expected to soon call for new, fast generation of stress tolerant rice germplasm, and current within-species rice diversity might not be enough to overcome such needs. The Oryza genus contains other 23 wild species, with only Oryza glaberrima being also domesticated. Rice domestication was performed with a narrow genetic diversity, and the other Oryza species are a virtually untapped genetic resource for rice stress tolerance improvement. Here we review the origin of domesticated Oryza sativa from wild progenitors, the ecological and genomic diversity of the Oryza genus, and the stress tolerance variation observed for wild Oryza species, including the genetic basis underlying the tolerance mechanisms found. The summary provided here is important to indicate how we should move forward to unlock the full potential of these germplasms for rice improvement. PMID:28323300

Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia.

PubMed

Potkin, Steven G; Preda, Adrian

2016-01-01

Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia. This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 - 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation. AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.

Management of Hypercholesterolemia, Appropriateness of Therapeutic Approaches and New Drugs in Patients with High Cardiovascular Risk.

PubMed

Agabiti Rosei, Enrico; Salvetti, Massimo

2016-09-01

Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet, in combination with a statin or a statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; alone or in combination with other lipid lowering therapies in patients who are statin-intolerant, or those for whom a statin is contraindicated. Evolocumab is also indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.

Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study.

PubMed

Hashimoto, Naoki; Toyomaki, Atsuhito; Honda, Minoru; Miyano, Satoru; Nitta, Nobuyuki; Sawayama, Hiroyuki; Sugawara, Yasufumi; Uemura, Keiichi; Tsukamoto, Noriko; Koyama, Tsukasa; Kusumi, Ichiro

2015-01-01

While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and two additional subjects dropped out because of somnolence. In this open-label, single-arm study of 29 patients, quetiapine improved both the clinical symptoms and the neurocognitive impairment in chronic schizophrenia patients who failed to respond to prior antipsychotic treatment.

Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

PubMed Central

Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

2010-01-01

Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events. PMID:20725567

[Noninvasive alternatives to CPAP in therapy of obstructive sleep apnea syndrome].

PubMed

Fritsch, K; Bloch, K E

2000-07-01

Non-surgical treatment of the sleep apnea syndrome comprises behavioral modification such as sleep hygiene, weight reduction, and positional training as an adjunct to standard therapy with continuous positive airway pressure (CPAP) applied via a nasal mask. For patients who cannot tolerate or are not willing to use CPAP for psychological or other reasons, removable intraoral appliances that advance the mandible during sleep are a valuable treatment alternative. Randomised controlled trials have confirmed effectiveness of intraoral appliances in relieving symptoms and measured sleep and respiratory disturbances. Side effects including hypersalivation, mucosal dryness, tooth and temporo-mandibular joint discomfort are common but usually mild. To timely detect effects of oral appliances on occlusion and on the temporo-mandibular joint longterm orthodontic monitoring is advisable.

[Efficacy and tolerability of long term topiramate in drug resistant epilepsy in adults].

PubMed

Ribacoba Montero, R; Salas Puig, X

With the objective of evaluating the efficacy and tolerability of topiramate (TPM) in resistant epilepsy, we did a retrospective, open, multicentric analysis of 56 patients aged over 15 years in whom TPM was given as the second, third or fourth drug. All patients had already been on treatment for at least 18 months when topiramate was started. The average follow up was 27.2 months. At the close of the study 16% of the patients were asymptomatic, 23% had a 75% reduction in seizures and 36% a 50% reduction. The drug was withdrawn in 25% of the cases. The adverse effects noted were: nephrolithiasis, asthenia, loss of hair, diarrhoea, weight loss of over 5kg., agitation, aggressiveness, language disorders, ataxia, tremor, somnolence and confusion. The drug had to be suspended when these adverse effects affected the central nervous system moderately or severely, and when there were general effects such as renal calculi in one case and weight loss associated with symptoms which worried the patients in two cases. Thus, TPM is an effective drug in refractory epilepsy and most patients continue on this treatment. The side effects are typical of the drug, and although there is no risk to life, the patient should be warned of them.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2010-04-14

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2009-04-15

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2010-01-20

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

Sertraline versus other antidepressive agents for depression

PubMed Central

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2014-01-01

Background The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. Objectives To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. Authors’ conclusions This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies. PMID:20393946

A review of solifenacin in the treatment of urinary incontinence

PubMed Central

Basra, Ramandeep; Kelleher, Con

2008-01-01

Overactive bladder (OAB) is a prevalent condition which has an adverse effect on quality of life. The presence of urgency incontinence confers significant morbidity above and beyond that of OAB sufferers who are continent. The primary treatment for OAB and urgency incontinence is a combination of behavioral measures and antimuscarinic drug therapy. The ideal antimuscarinic agent should effectively relieve the symptoms of OAB, with the minimum of side effects; it should be available as a once-daily sustained release formulation and in dosage strength that allows easy dose titration for the majority of sufferers. Solifenacin succinate was launched in 2005, and has been shown in both short and long term clinical trials to fulfill these requirements. Solifenacin is a competitive M3 receptor antagonist with a long half-life (45–68 hours). It is available in two dosage strengths namely a 5 or 10 mg once-daily tablet. The efficacy and tolerability of solifenacin for the treatment of all symptoms of OAB has been evaluated in a number of large, placebo controlled, randomized trials. Long-term safety, efficacy, tolerability and persistence with treatment have been established in an open label 40 week continuation study. PMID:18728701

Tanezumab in the treatment of chronic musculoskeletal conditions.

PubMed

Jayabalan, Prakash; Schnitzer, Thomas J

2017-02-01

The management of pain associated with chronic musculoskeletal conditions represents a significant challenge for the clinician. There remains a need for novel medications that have a significant analgesic benefit and are also safe and well tolerated. Both pre-clinical and clinical data have provided evidence of the role of nerve growth factor (NGF) in a multitude of pain eliciting conditions. Therefore, the development of monoclonal antibodies to NGF for chronic painful musculoskeletal conditions has generated interest. Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. In addition, the safety and tolerability profile and development history of tanezumab are also discussed. Expert opinion: Most studies provide strong support for the ability of tanezumab to provide clinically meaningful pain relief in individuals with these conditions, with longer-term studies suggesting durability of effect. The adverse event profile appears favorable, assuming the risk mitigation strategies are effective at reducing the incidence of joint-related side effects. Further data are being collected to define the optimal dose and dosing strategy in both OA and chronic low back pain.

Pharmacological action of Panax ginseng on the behavioral toxicities induced by psychotropic agents.

PubMed

Kim, Hyoung-Chun; Shin, Eun-Joo; Jang, Choon-Gon; Lee, Myung-Koo; Eun, Jae-Soon; Hong, Jin-Tae; Oh, Ki-Wan

2005-09-01

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (mu-receptors) and mouse vas deferens (delta-receptors) are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine A2A/ delta-opioid receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

[Antidepressants in the elderly].

PubMed

Cortajarena García, M C; Ron Martin, S; Miranda Vicario, E; Ruiz de Vergara Eguino, A; Azpiazu Gomez, P J; Lopez Aldana, J

2016-10-01

Depression in the elderly is a changing, difficult and common disorder. At this age, there are more relapses and more long-life treatment is required. The pharmacology approach is a challenge because of concurrent factors that make their treatment more difficult. It is very important to have a basic antidepressant scheme, in order to help treat this disorder with efficiency and success from Primary Care. There are no drugs without side effects, and their characteristics have to be known in order to make the right selection depending on effectiveness, safety and tolerance. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Efficacy and Tolerability of Two Different Kinds of Titration of Paroxetine Hydrocloride Solution: an Observational Study.

PubMed

Ielmini, Marta; Poloni, Nicola; Caselli, Ivano; Bianchi, Lucia; Diurni, Marcello; Vender, Simone; Callegari, Camilla

2018-03-13

Depressive disorders are expected to be the second highest cause of morbidity in the world until few years. Moreover, patients with depression frequently show many side effects and low compliance to therapy. To find a more tolerated and more efficacy therapy is a growing need. This observational study investigates the efficacy, safety and tolerability of paroxetine hydrochloride comparing slow versus standard titration in a population affected by Depressive Disoders (according to DSM 5). 186 outpatients were assessed throught the following scales: Hamilton Depression Rating Scale (HDRS) for depression and World Health Organization Quality of Life Scale Bref for the perceived quality of life (WHOQOL BREF). Treatment-emerged Adverse Events (TEAEs) were recorded throught self-reports. Statystical analysys was performed by GraphPad Prism Version 5.1. The efficacy of paroxetine was confirmed in both titrations by the number of clinical remitters (HDRS ≤ 7 at 12 weeks for 53% of the standard titration group and 58% of the slow titration group), without differences. About safety and tolerability there were more frequent TEAEs among the standard titration group (p < 0.01). Comparing WHOQOL BREF between the two groups at the recruitment and at the twelth week emerged a statistically significant difference (p = 0.003), with highest scores reached in slow titration group. Although the short observation period is an evident limit, this study is consistent to the literature about the efficacy of both titrations of paroxetine to improve depression and shows promising results about the increased tolerability of paroxetine slow titration.

Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

PubMed

Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

2017-07-05

Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

A preliminary report on the effects of paclitaxel-impregnated stents on sheep nasal mucosa.

PubMed

Herrmann, Brian W; Citardi, Martin J; Vogler, George; Gardner, Laura; Smith, Greg; Javer, Amin R; Burt, Helen M; Jackson, John; Kuhn, Frederick A

2004-01-01

Traditional frontal sinus stents serve only as mechanical devices. It has been proposed that stents also may serve as drug-delivery systems for the topical application of drugs that minimize postoperative scarring. Paclitaxel (Taxol), which has recognized antiscarring effects, may be incorporated via a polymeric formulation into standard rubber stents. The impact of topically applied paclitaxel on the morphology of the nasal mucosa is unknown. An adult sheep model was used for this study. A modified rubber T-tube stent (incorporating paclitaxel at varying dosages) was secured to each side of the septum in four animals (eight sides). An unmodified T-tube was placed on each side of one animal, a T-tube with the drug carrier (but no paclitaxel) was placed on each side of the second animal, and T-tubes with varying paclitaxel were placed on each side of the final two animals. After 4 weeks, animals were killed and the nasal mucosa was harvested. The nasal mucosa was sectioned and stained with hematoxylin and eosin. A pathologist then assessed the nasal mucosa for vascular congestion, glandular atrophy, chronic inflammation, mucosal metaplasia, and mucosal ulceration. No consistent histopathological differences were noted in the specimens. All specimens showed varying degrees of vascular congestion, glandular atrophy, chronic inflammation, and mucosal metaplasia; the paclitaxel-impregnated stents were not consistently associated with more severe mucosal injury. Finally, mucosal ulceration was noted to be very rare in all specimens. This preliminary report describes the impact of paclitaxel-impregnated stents on sheep nasal mucosa, which tolerated these stents very well. Because paclitaxel minimizes scarring reactions at very low concentrations, paclitaxel-impregnated stents may prove useful in clinical situations in which frontal sinus stenting is deemed necessary. Additional investigations with animal models, as well as clinical trials, may be warranted.

Tadalafil reversal of sexual dysfunction caused by serotonin enhancing medications in women.

PubMed

Ashton, Adam Keller; Weinstein, Wendy

2006-01-01

Sexual dysfunction is a common side effect of many antidepressants, especially those that increase serotonin. Many strategies have been reported to assist patients in minimizing impairment, with variable degrees of success. One of the newer approaches is to augment with phosphodiesterase type-5 inhibitors. Our report using the most recently released agent in this class, tadalafil is the first demonstrating potential benefit in women. We report here of three women who derived benefit from using 20 mg of tadalafil before anticipated sexual activity to reverse medication-induced sexual dysfunction. Tadalafil utility was maintained over time and was well tolerated.

Surgical treatment of axillary hyperhidrosis by suction-curettage of sweat glands*

PubMed Central

de Rezende, Rebeca Maffra; Luz, Flávio Barbosa

2014-01-01

Suction curettage is a dermatologic surgery technique for the treatment of axillary hyperhidrosis, which is becoming more popular. Objective: The purpose of this study is to describe the current technique of removal of axillary sweat glands, and evaluate its efficacy and safety. Conclusion: Suction-curettage of sweat glands is a minimally invasive surgical technique that is easy to perform, safe, has high rates of success and relatively few side-effects. It is generally well tolerated by patients and requires shorter time away from daily activities, when compared with other surgical modalities. PMID:25387499

Production of MPS VII mouse (Gustm(hE540A·mE536A)Sly) doubly tolerant to human and mouse β-glucuronidase

PubMed Central

Tomatsu, Shunji; Orii, Koji O.; Vogler, Carole; Grubb, Jeffrey H.; Snella, Elizabeth M.; Gutierrez, Monica; Dieter, Tatiana; Holden, Christopher C.; Sukegawa, Kazuko; Orii, Tadao; Kondo, Naomi; Sly, William S.

2006-01-01

Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal recessive lysosomal storage disease caused by β-glucuronidase (GUS) deficiency. A naturally occurring mouse model of that disease has been very useful for studying experimental approaches to therapy. However, immune responses can complicate evaluation of the long-term benefits of enzyme replacement or gene therapy delivered to adult MPS VII mice. To make this model useful for studying the long-term effectiveness and side effects of experimental therapies delivered to adult mice, we developed a new MPS VII mouse model, which is tolerant to both human and murine GUS. To achieve this, we used homologous recombination to introduce simultaneously a human cDNA transgene expressing inactive human GUS into intron 9 of the murine Gus gene and a targeted active site mutation (E536A) into the adjacent exon 10. When the heterozygote products of germline transmission were bred to homozygosity, the homozygous mice expressed no GUS enzyme activity but expressed inactive human GUS protein highly and were tolerant to immune challenge with human enzyme. Expression of the mutant murine Gus gene was reduced to about 10% of normal levels, but the inactive murine GUS enzyme also conferred tolerance to murine GUS. This MPS VII mouse model should be useful to evaluate therapeutic responses in adult mice receiving repetitive doses of enzyme or mice receiving gene therapy as adults. Heterozygotes expressed only 9.5–26% of wild-type levels of murine GUS instead of the expected 50%, indicating a dominant-negative effect of the mutant enzyme monomers on the activity of GUS tetramers in different tissues. Corrective gene therapy in this model should provide high enough levels of expression of normal GUS monomers to overcome the dominant negative effect of mutant monomers on newly synthesized GUS tetramers in most tissues. PMID:12700165

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

PubMed

Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Cavity BPM with Dipole-Mode-Selective Coupler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zenghai; Johnson, Ronald; Smith, Stephen R.

2006-06-21

In this paper, we present a novel position sensitive signal pickup scheme for a cavity BPM. The scheme utilizes the H-plane of the waveguide to couple magnetically to the side of the cavity, which results in a selective coupling to the dipole mode and a total rejection of the monopole mode. This scheme greatly simplifies the BPM geometry and relaxes machining tolerances. We will present detailed numerical studies on such a cavity BPM, analyze its resolution limit and tolerance requirements for a nanometer resolution. Finally present the measurement results of a X-band prototype.

Building America Case Study: Trade-Friendly Retrofit Insulated Panels for Existing Buildings, Albany, New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

This project evaluated the effectiveness and affordability of integrating retrofit insulated panels into a re-siding project. The Partnership for Home Innovation (PHI) teamed with New York State Energy Research and Development Authority (NYSERDA), the Albany Housing Authority (AHA), and the New York State Weatherization Assistance Program (WAP) administered by Albany Community Action Partnership to demonstrate an energy retrofit and siding upgrade on a two-story, seven unit, multifamily building in Albany New York (CZ 5). The project focused on accomplishing three goals - doubling the existing wall thermal resistance (from approximately R-13 to a weighted average of R-27), reduction of buildingmore » air leakage, and completion of the retrofit within a budget where the additional cost for upgrading wall's thermal resistance is equal to the cost of the standard re-siding effort (i.e., the total cost of the energy efficient re-siding scope of work is not more than double the cost of the standard re-siding effort). Lessons learned from the project strongly indicate that the retrofit panel technology can be installed using common installation practices and with minimal training. Other lessons learned include limitation on the use of standard air sealing materials during cold weather installations and the need to develop better installation guidance for trades working with the level of tolerances that may be present in the existing structure. This technology demonstration showed that exterior retrofit panels provide a viable and reasonable option for the siding trades to increase market opportunities and achieve synergistic benefits for aesthetic upgrades to a building's exterior.« less

Stimulant Use in Patients with Sturge-Weber Syndrome: Safety and Efficacy

PubMed Central

Lance, Eboni I.; Lanier, Kira E.; Zabel, T. Andrew; Comi, Anne M.

2015-01-01

BACKGROUND Sturge Weber Syndrome (SWS) is characterized by a facial port-wine birthmark, vascular eye abnormalities, and a leptomeningeal angioma. Attention and behavioral issues are common in SWS; however, literature evidence for stimulant treatment is minimal. This study evaluates stimulant medication safety and efficacy in SWS patients. METHODS The research database of the Hunter Nelson Sturge-Weber Center (n = 210 subjects with SWS brain involvement) was reviewed for stimulant use. Twelve subjects (mean age 10.5 years, age range 4 to 21 years) on stimulants were seen between 2003 and 2012. A retrospective chart review obtained co-morbid diagnoses, stimulant type and dosage, medication side effects, vital signs, and medication efficacy. RESULTS All twelve subjects had brain involvement (unilateral - nine; bilateral – three). Additional co-morbidities included epilepsy (twelve), hemi-paresis (eight), headaches (eight), and vision deficits (seven). Eight subjects reported side effects, primarily appetite suppression (four) and headaches (three). There were no statistically significant changes in weight or blood pressure six months after medication initiation. Medication efficacy was subjectively reported in eleven subjects. Seven patients remained on stimulants at their most recent follow up visit. CONCLUSIONS This study preliminarily evaluates stimulant medication use in a small group of SWS patients. Stimulants were tolerated and effective in most subjects. Side effects were mostly minor and medication did not negatively impact growth or vital signs. Stimulant medication may be a safe and effective intervention for SWS children with attention issues/attention deficit hyperactivity disorder (ADHD). Further studies with larger sample sizes are needed. PMID:25439578

Topical Oxybutynin 10% Gel for the Treatment of Primary Focal Hyperhidrosis: A Randomized Double-blind Placebo-controlled Split Area Study.

PubMed

Artzi, Ofir; Loizides, Christophoros; Zur, Eyal; Sprecher, Eli

2017-10-02

Limited efficacy, costs, side-effects and complications are issues of concern for most current therapeutic modalities for focal hyperhidrosis. This study evaluated the efficacy of topical oxybutynin 10% gel in treating 61 patients with primary focal hyperhidrosis. The gel was applied to the right or left axilla, palms or soles vs. a placebo compound to the contralateral side for 30 days. A blinded visual grading of the change in starch-iodine tests was performed by 2 non-involved physicians. The Hyperhidrosis Disease Severity Scale (HDSS) and Dermatology Life Quality Index (DLQI) questionnaires were administered before and after treatment. The patients rated their satisfaction with treatment. Fifty-three patients completed the 4-week treatment. Sweat reduction in the drug-treated sweating areas was higher than in the control-treated areas. There was a significant mean improvement in pre- and post-treatment HDSS and DQLI (p = 0.001 for both). Thirty-nine subjects (74%) reported moderate-to-high satisfaction. Twice-daily topical application of oxybutynin 10% gel appears to be an effective, safe and well-tolerated treatment for focal primary hyperhidrosis.

Minimization of color shift generated in RGBW quad structure.

NASA Astrophysics Data System (ADS)

Kim, Hong Chul; Yun, Jae Kyeong; Baek, Heume-Il; Kim, Ki Duk; Oh, Eui Yeol; Chung, In Jae

2005-03-01

The purpose of RGBW Quad Structure Technology is to realize higher brightness than that of normal panel (RGB stripe structure) by adding white sub-pixel to existing RGB stripe structure. However, there is side effect called 'color shift' resulted from increasing brightness. This side effect degrades general color characteristics due to change of 'Hue', 'Brightness' and 'Saturation' as compared with existing RGB stripe structure. Especially, skin-tone colors show a tendency to get darker in contrast to normal panel. We"ve tried to minimize 'color shift' through use of LUT (Look Up Table) for linear arithmetic processing of input data, data bit expansion to 12-bit for minimizing arithmetic tolerance and brightness weight of white sub-pixel on each R, G, B pixel. The objective of this study is to minimize and keep Δu'v' value (we commonly use to represent a color difference), quantitative basis of color difference between RGB stripe structure and RGBW quad structure, below 0.01 level (existing 0.02 or higher) using Macbeth colorchecker that is general reference of color characteristics.

Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation.

PubMed

Saad, Richard; Chey, William D

2008-08-01

Lubiprostone, a locally acting highly selective type-2 chloride channel activator, has been US FDA approved since January 2006 for the treatment of adults with chronic idiopathic constipation and FDA approved since April 2008 for the treatment of woman aged 18 years or older suffering from irritable bowel syndrome (IBS) with constipation. Through activation of the type-2 chloride channels located on the luminal side of intestinal epithelial cells, it promotes fluid secretion, increasing the liquid content of stool and accelerating small bowel as well as colonic transit. Lubiprostone has demonstrated efficacy with respect to increasing weekly spontaneous bowel movements and improving stool consistency, straining and constipation severity, both in short- and long-term studies. It has also demonstrated efficacy in the treatment of IBS with constipation, with beneficial effects on global symptoms, abdominal pain, constipation-related symptoms and overall quality of life. There is no evidence of a rebound in constipation or IBS symptoms following cessation of lubiprostone. In general, lubiprostone is well tolerated, with the most common side effects including nausea, headache and diarrhea.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Leg preference associated with protective stepping responses in older adults.

PubMed

Young, Patricia M; Whitall, Jill; Bair, Woei-Nan; Rogers, Mark W

2013-10-01

Asymmetries in dynamic balance stability have been previously observed. The goal of this study was to determine whether leg preference influenced the stepping response to a waist-pull perturbation in older adult fallers and non-fallers. 39 healthy, community-dwelling, older adult (>65 years) volunteers participated. Participants were grouped into non-faller and faller cohorts based on fall history in the 12 months prior to the study. Participants received 60 lateral waist-pull perturbations of varying magnitude towards their preferred and non-preferred sides during quiet standing. Outcome measures included balance tolerance limit, number of recovery steps taken and type of recovery step taken for perturbations to each side. No significant differences in balance tolerance limit (P ≥ 0.102) or number of recovery steps taken (η(2)partial ≤ 0.027; P ≥ 0.442) were observed between perturbations towards the preferred and non-preferred legs. However, non-faller participants more frequently responded with a medial step when pulled towards their non-preferred side and cross-over steps when pulled towards their preferred side (P=0.015). Leg preference may influence the protective stepping response to standing balance perturbations in older adults at risk for falls, particularly with the type of recovery responses used. Such asymmetries in balance stability recovery may represent a contributing factor for falls among older individuals and should be considered for rehabilitation interventions aimed at improving balance stability and reducing fall risk. © 2013.

Leg preference associated with protective stepping responses in older adults

PubMed Central

Young, Patricia M.; Whitall, Jill; Bair, Woei-Nan; Rogers, Mark W.

2014-01-01

Background Asymmetries in dynamic balance stability have been previously observed. The goal of this study was to determine whether leg preference influenced the stepping response to a waist-pull perturbation in older adult fallers and non-fallers. Methods 39 healthy, community-dwelling, older adult (>65 years) volunteers participated. Participants were grouped into non-faller and faller cohorts based on fall history in the 12 months prior to the study. Participants received 60 lateral waist-pull perturbations of varying magnitude towards their preferred and non-preferred sides during quiet standing. Outcome measures included balance tolerance limit, number of recovery steps taken and type of recovery step taken for perturbations to each side. Findings No significant differences in balance tolerance limit (P ≥ 0.102) or number of recovery steps taken (η2partial ≤ 0.027; P ≥ 0.442) were observed between perturbations towards the preferred and non-preferred legs. However, non-faller participants more frequently responded with a medial step when pulled towards their non-preferred side and cross-over steps when pulled towards their preferred side (P = 0.015). Interpretation Leg preference may influence the protective stepping response to standing balance perturbations in older adults at risk for falls, particularly with the type of recovery responses used. Such asymmetries in balance stability recovery may represent a contributing factor for falls among older individuals and should be considered for rehabilitation interventions aimed at improving balance stability and reducing fall risk. PMID:23962655

Repacking the Core of T4 lysozyme by automated design.

PubMed

Mooers, Blaine H M; Datta, Deepshikha; Baase, Walter A; Zollars, Eric S; Mayo, Stephen L; Matthews, Brian W

2003-09-19

Automated protein redesign, as implemented in the program ORBIT, was used to redesign the core of phage T4 lysozyme. A total of 26 buried or partially buried sites in the C-terminal domain were allowed to vary both their sequence and side-chain conformation while the backbone and non-selected side-chains remained fixed. A variant with seven substitutions ("Core-7") was identified as having the most favorable energy. The redesign experiment was repeated with a penalty for the presence of methionine residues. In this case the redesigned protein ("Core-10") had ten amino acid changes. The two designed proteins, as well as the constituent single mutants, and several single-site revertants were over-expressed in Escherichia coli, purified, and subjected to crystallographic and thermal analyses. The thermodynamic and structural data show that some repacking was achieved although neither redesigned protein was more stable than the wild-type protein. The use of the methionine penalty was shown to be effective. Several of the side-chain rotamers in the predicted structure of Core-10 differ from those observed. Rather than changing to new rotamers predicted by the design process, side-chains tend to maintain conformations similar to those seen in the native molecule. In contrast, parts of the backbone change by up to 2.8A relative to both the designed structure and wild-type. Water molecules that are present within the lysozyme molecule were removed during the design process. In the redesigned protein the resultant cavities were, to some degree, re-occupied by side-chain atoms. In the observed structure, however, water molecules were still bound at or near their original sites. This suggests that it may be preferable to leave such water molecules in place during the design procedure. The results emphasize the specificity of the packing that occurs within the core of a typical protein. While point substitutions within the core are tolerated they almost always result in a loss of stability. Likewise, combinations of substitutions may also be tolerated but usually destabilize the protein. Experience with T4 lysozyme suggests that a general core repacking methodology with retention or enhancement of stability may be difficult to achieve without provision for shifts in the backbone.

Effects of coffee consumption on gut recovery after surgery of gynecological cancer patients: a randomized controlled trial.

PubMed

Güngördük, Kemal; Özdemir, İsa Aykut; Güngördük, Özgü; Gülseren, Varol; Gokçü, Mehmet; Sancı, Muzaffer

2017-02-01

Paralytic ileus that develops after elective surgery is a common and uncomfortable complication and is considered inevitable after an intraperitoneal operation. The purpose of this study was to investigate whether coffee consumption accelerates the recovery of bowel function after complete staging surgery of gynecologic cancers. In this randomized controlled trial, 114 patients were allocated preoperatively to either postoperative coffee consumption with 3 times daily (n=58) or routine postoperative care without coffee consumption (n=56). Total abdominal hysterectomy and bilateral salpingo-oophorectomy with systematic pelvic and paraaortic lymphadenectomy were performed on all patients as part of complete staging surgery for endometrial, ovarian, cervical, or tubal cancer. The primary outcome measure was the time to the first passage of flatus after surgery. Secondary outcomes were the time to first defecation, time to first bowel movement, and time to tolerance of a solid diet. The mean time to flatus (30.2±8.0 vs 40.2±12.1 hours; P<.001), mean time to defecation (43.1±9.4 vs 58.5±17.0 hours; P<.001), and mean time to the ability to tolerate food (3.4±1.2 vs 4.7±1.6 days; P<.001) were reduced significantly in patients who consumed coffee compared with control subjects. Mild ileus symptoms were observed in 17 patients (30.4%) in the control group compared with 6 patients (10.3%) in the coffee group (P=.01). Coffee consumption was well-tolerated and well-accepted by patients, and no intervention-related side-effects were observed. Coffee consumption after total abdominal hysterectomy and systematic paraaortic lymphadenectomy expedites the time to bowel motility and the ability to tolerate food. This simple, cheap, and well-tolerated treatment should be added as an adjunct to the postoperative care of gynecologic oncology patients. Copyright © 2016 Elsevier Inc. All rights reserved.

A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

PubMed Central

Black, Kevin J

2013-01-01

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.  Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease. PMID:24627787

The effects of ProAlgaZyme novel algae infusion on metabolic syndrome and markers of cardiovascular health

PubMed Central

Oben, Julius; Enonchong, Ebangha; Kuate, Dieudonne; Mbanya, Dora; Thomas, Tiffany C; Hildreth, DeWall J; Ingolia, Thomas D; Tempesta, Michael S

2007-01-01

Background Metabolic Syndrome, or Syndrome X, is characterized by a set of metabolic and lipid imbalances that greatly increases the risk of developing diabetes and cardiovascular disease. The syndrome is highly prevalent in the United States and worldwide, and treatments are in high demand. ProAlgaZyme, a novel and proprietary freshwater algae infusion in purified water, has been the subject of several animal studies and has demonstrated low toxicity even with chronic administration at elevated doses. The infusion has been used historically for the treatment of several inflammatory and immune disorders in humans and is considered well-tolerated. Here, the infusion is evaluated for its effects on the cardiovascular risk factors present in metabolic syndrome in a randomized double-blind placebo-controlled study involving 60 overweight and obese persons, ages 25–60. All participants received four daily oral doses (1 fl oz) of ProAlgaZyme (N = 22) or water placebo (N = 30) for a total of 10 weeks, and were encouraged to maintain their normal levels of physical activity. Blood sampling and anthropometric measurements were taken at the beginning of the study period and after 4, 8 and 10 weeks of treatment. Eight participants did not complete the study. Results ProAlgaZyme brought about statistically significant (p < 0.001) reductions in the following: weight, body fat, total cholesterol, LDL-cholesterol, triglycerides, C-reactive protein and fasting blood glucose levels, accompanied by a significant (p < 0.001) increase in HDL-cholesterol levels over the 10-week study period. The infusion was well-tolerated and no side effects were noted. Conclusion ProAlgaZyme (4 fl oz daily) consumption resulted in significant reductions in weight and blood glucose levels, while significantly improving serum lipid profiles and reducing markers of inflammation, thus improving cardiovascular risk factors in overweight and obese subjects over a course of 10 weeks with an absence of adverse side effects. Trial Registration US ClinicalTrials.gov NCT00489333 PMID:17803818

Efficacy and tolerability of a topical gel containing 3% hydrogen peroxide, 1.5% salicylic acid and 4% D-panthenol in the treatment of mild-moderate acne.

PubMed

Fabbrocini, Gabriella; Panariello, Luigia

2016-06-01

The aim of this paper was to evaluate efficacy and tolerability of a topical gel (ACNAID TM gel medical device) containing 3% hydrogen peroxide (HPO), 1.5% salicylic acid (SA) and 4% D-panthenol (D-p) in the treatment of mild-moderate acne, comparing it with a previous formulation (ACNAID TM gel Cosmetic) containing 4% HPO, 0.5% SA, 4% D-p. Twenty patients of both sex with mild-moderate acne have been selected. The topical gel was applied twice a day for 60 days. Evaluations included: Global Acne Grading System (GAGS); lesions count; photographic assessment; a questionnaire to assess the tolerability. The results have been compared with those obtained in a previous study conducted with the formulation containing 4% HPO, 0.5% SA, 4% D-p. The GAGS score showed a reduction of 43% from T0 to T1 and of 61% from T0 to T2. Count of lesions: comedones reduction of 62% from T0 to T1 and of 95% from T0 to T2; papules reduction of 49% from T0 to T1 and of 68% from T0 to T2; pustules reduction of 75% from T0 to T1 and of 100% from T0 to T2. Digital images showed a significant reduction of acne lesions. At T2 the tolerability of the topical product was excellent according to 83% of patients and good according to 17% of patients. The topical gel has demonstrated to be effective and safe for treatment of mild to moderate acne. No patients reported side effects. These results are superior to those obtained in the previous study.

[Customization of hemodialysis therapy: dialysis is not a washing machine].

PubMed

Santoro, Antonio

2018-02-01

In recent years, the population of chronic dialysis has grown in number but also in age and frequency of co-morbidies such as cardiac diseases, vascular pathologies, diabetes, etc. The majority of patients on chronic hemodialysis are over 70 years and, given the high number of comorbidities, they often exhibit poor tolerance to dialysis treatments. A non-tolerated dialytic treatment can have side-effects that would require an intensification of the dialysis sessions and many hospitalizations. Consequently, the problematic dialysis treatments, as well as harmful for the patient, become economically more detrimental than other treatments apparently more expensive but more tolerated ones In the current days we have, thanks to the huge developments in dialysis technology, powerful weapons to ensure effective and scarcely symptomatic dialysis treatments to the majority of the HD patients. New, highly biocompatible membranes with defined and modular cut-off and / or absorption capacity may allow us to provide adequate purification. Moreover the monitoring and biofeedback systems such as blood volume tracking, body temperature monitoring (BTM) and blood pressure (BPM) can be very useful in reducing the risk of intra-dialytic hypotension and symptoms. Therefore, the dialytic therapy, as well as all the pharmacological therapies for the chronic patient, must consider the specificity of the patient, basing on his metabolic problems, cardiovascular tolerance, residual renal function and on his dietary and general compliance. The central aim of the nephrologist is to formulate the better prescription for the individual patient, considering the dialysis modalities, the membrane type, the dry weight (ideal post-dialysis body weight), the frequency and the duration of the weekly sessions and the technological tools that can optimize the treatment. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Biomechanical analysis of protective countermeasures in underride motor vehicle accidents - biomed 2009.

PubMed

Kumar, Sri; Enz, Bruce; Ponder, Perry L; Anderson, Bob

2009-01-01

Traffic safety has been significantly improved over the past several decades reducing injury and fatality rates. However, there is a paucity of research effort to address the safety issues in underride accidents, specifically the side underride crashes. It is well known that the compromise of occupant space in the vehicle leads to a higher probability of serious or fatal injuries. A better understanding of occupant protection and mechanism of injuries involved in side underride accidents assists in the advancement of safety measures. The present work evaluates the injury potential to occupants during side underride crashes using the car-to-trailer crash methodology. Four crash tests were conducted into the side of a stationary trailer fitted with the side underride guard system (SURG). The SURG used in these tests is 25% lighter than the previous design. A 5th percentile hybrid III female dummy was placed in the driver seat and restrained with the three-point lap and shoulder harness. The anthropometric dummy was instrumented with a head triaxial accelerometer, a chest triaxal accelerometer, a load cell to measure neck force and moment, and a load cell to measure the femur force. The vehicle acceleration was measured using a traxial accelerometer in the rear center tunnel. High speed, standard video and still photos were taken. In all tests, the intrusion was limited to the front structure of the vehicle without any significant compromise to the occupant space. Results indicate that the resultant head and chest accelerations, head injury criterion (HIC), neck force and moment, and femur force were well below the injury tolerance. The present findings support the hypothesis that the SURG not only limits or eliminates the intrusion into the occupant space but also results in biomechanical injury values well below the tolerance limit in motor vehicle crashes.

Effectiveness of CO2 laser with subcision in patients with acne scars.

PubMed

Anupama, Y G; Wahab, Afthab Jameela

2016-11-01

Post-acne facial scarring has always been a challenge to treat. It requires multiple therapeutic modalities as single modality is not hundred percent effective. Therefore, we have combined CO 2 laser resurfacing with subcision in patients with acne scars for better results. The aim is to study the effectiveness and side effects of CO 2 laser with subcision in patients with atrophic acne scars. Fifty patients were selected for the study. Baseline grading was done with Goodman and Baron grading system. Twenty-five patients were randomly selected for subcision followed by CO 2 laser and the remaining patients were selected for CO 2 laser alone. The treatment was done for four sessions at 4-week interval. Clinical photographs were obtained for evaluation. CO 2 laser with subcision showed excellent response in grade-2 and -3 acne scars. Statistically there is a significant difference between CO 2 laser following subcision and CO 2 laser alone at 5% level (p < 0.05). Both procedures were well tolerated with minimal side effects. The highly versatile CO 2 laser is useful for treating acne scars. Subcision prior to the CO 2 laser procedure showed better improvement when compared to CO 2 laser alone. Thus, in acne scars, multiple therapeutic modalities achieve better results.

Clinical utility of curcumin extract.

PubMed

Asher, Gary N; Spelman, Kevin

2013-01-01

Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.

A New Type of ECT Stimuli: Burst Stimulus ECT.

PubMed

Aksay, S S; Bumb, J M; Janke, C; Kranaster, L; Sartorius, A

2015-11-01

Pulse width in electroconvulsive therapy has significant influence on effectiveness and side effects. While shorter pulses are beneficial for cognitive performance, there is still a debate about a negative impact on ECT efficacy at least for ultra-brief pulse durations. We report a first patient treated with burst stimulus ECT, i. e., with 4 consecutive 250-µs pulses, separated by another 250 µs. Within the same patient we compared 6 classical vs. 6 burst stimulus ECT sessions. In all cases a typical tonic-clonic seizure was observed. Seizure parameters like concordance, coherence and mid-ictal amplitude increased numerically, but not significantly with burst ECT. The time needed to show a reorientation was significantly shortened with burst stimuli (30 min vs. 14 min, p=0.007). In conclusion we present the first case of ECT in a single patient comparing "classical" single stimulus pulses vs. burst stimulus ECT. The new burst stimulus was better tolerated regarding reorientation time after the treatment, while parameters of seizure quality remained basically unchanged. Whether burst stimulus ECT has the potential to improve ECT quality by reducing side effects without losing efficacy has to be investigated in clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

Cryolipolysis for Targeted Fat Reduction and Improved Appearance of the Enlarged Male Breast.

PubMed

Munavalli, Girish S; Panchaprateep, Ratchathorn

2015-09-01

Pseudogynecomastia refers to benign male breast enlargement due to excess subareolar fat. Standard treatment is surgical excision under general anesthesia, liposuction, or a combination of both. The safety and efficacy of cryolipolysis was investigated for nonsurgical treatment of pseudogynecomastia. Enrollment consisted of 21 males with pseudogynecomastia. Subjects received a first treatment consisting of a 60-minute cryolipolysis cycle, followed by a two-minute massage, and a second 60-minute cycle with 50% treatment area overlap. At 60 days of follow-up, subjects received a second 60-minute treatment. Safety was evaluated by monitoring side effects and adverse events. Efficacy was assessed by ultrasound, clinical photographs, and subject surveys. Surveys revealed that 95% of subjects reported improved visual appearance and 89% reported reduced embarrassment associated with pseudogynecomastia. Ultrasound showed mean fat layer reduction of 1.6 ± 1.2 mm. Blinded reviewers correctly identified 82% of baseline photographs. Side effects included mild discomfort during treatment and transient paresthesia and tenderness. One case of paradoxical hyperplasia (PH) occurred but likelihood of PH in the male breast is not believed to be greater than in any other treatment area. This study demonstrated feasibility of cryolipolysis for safe, effective, and well-tolerated nonsurgical treatment of pseudogynecomastia.

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

PubMed

Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

2012-08-01

To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Safety and tolerability of intrathecal liposomal cytarabine as central nervous system prophylaxis in patients with acute lymphoblastic leukemia.

PubMed

Valentin, Angelika; Troppan, Katharina; Pfeilstöcker, Michael; Nösslinger, Thomas; Linkesch, Werner; Neumeister, Peter

2014-08-01

Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated.

Combined cannabinoid therapy via an oromucosal spray.

PubMed

Perez, Jordi

2006-08-01

Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

Use of intravenous acetaminophen (paracetamol) in a pediatric patient at the end of life: case report.

PubMed

Marks, Adam D; Keefer, Patricia; Saul, D'Anna

2013-12-01

For the better part of 100 years, acetaminophen (or paracetamol as it is known outside of the United States) has been a common first-line analgesic in pediatrics and is typically well tolerated with minimal side effects. Its use as an anti-pyretic is also well-documented and thus it is used broadly for symptom control in the general pediatric population. In pediatric palliative care, acetaminophen is also used as an adjuvant to opioid therapy for pain as well as an anti-pyretic. For many pediatric patients near end-of-life, however, the ability to tolerate oral intake is diminished and rectal suppository administration can be distressing or contraindicated as in the setting of neutropenia, thus limiting use of acetaminophen by its usual routes. In Europe and Australia, an intravenous formulation of acetaminophen has been used for many years and has only recently become available in the United States. Here, we describe a case using intravenous acetaminophen in a pediatric patient at the end of life.

Slicing of silicon into sheet material: Silicon sheet growth development for the large area silicon sheet task of the Low Cost Silicon Solar Array project

NASA Technical Reports Server (NTRS)

Fleming, J. R.

1978-01-01

The limits of blade tolerance were defined. The standard blades are T-2 thickness tolerance. Good results were obtained by using a slurry fluid consisting of mineral oil and a lubricity additive. Adjustments of the formulation and fine tuning of the cutting process with the new fluid are necessary. Test results and consultation indicate that the blade breakage encountered with water based slurries is unavoidable. Two full capacity (974 wafer) runs were made on the large prototype saw. Both runs resulted in extremely low yield. However, the reasons for the low yield were lack of proper technique rather than problems with machine function. The test on the effect of amount of material etched off of an as-sawn wafer on solar cell efficiency were completed. The results agree with previous work at JPL in that the minimum material removed per side that gives maximum efficiency is on the order of 10 microns.

Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open-label pilot study for assessing the efficacy, tolerability and impact on quality of life.

PubMed

Maschio, M; Dinapoli, L; Sperati, F; Fabi, A; Pace, A; Vidiri, A; Muti, P

2012-02-01

We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.

HFSRT of the resection cavity in patients with brain metastases.

PubMed

Specht, Hanno M; Kessel, Kerstin A; Oechsner, Markus; Meyer, Bernhard; Zimmer, Claus; Combs, Stephanie E

2016-06-01

Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated. 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm(3) (range 1.44-38.68 cm(3)) and median planning target volume (PTV) was 26.19 cm(3) (range 3.45-63.97 cm(3)). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging. The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria. HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed.

A randomized study comparing the side effects and hormonal status of triptorelin and leuprorelin following conservative laparoscopic surgery for ovarian endometriosis in Chinese women.

PubMed

Li, Zheng; Zhang, Hong Yuan; Zhu, Ying Jun; Hu, Yuan Jing; Qu, Peng Peng

2014-12-01

Different gonadotropin-releasing-hormone agonist (GnRH-a) formulations with different potency and associated side effects, therefore, different compliance and persistence of therapy. This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment. A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study.Subjects were randomized into two groups with use of a random table. Twenty two patients dropped out during the study. Thus 142 patients had three doses of i.m. leuprorelin (group A) and 138 patients had three doses of i.m. triptorelin(group B) at 4 weeks intervals after surgical treatment. Menopausal symptoms were evalutaed using a questionnaire and serum sex hormonal levels were also measured during the follow-up. At week 4 after the treatment, most of the patients in leuprorelin group have no obvious side effects. After 9 weeks, bone pain, hot flashes and sweating, and irregular bleeding were the main side effects and showed no difference between the groups. Anxiety, depression, vaginal dryness, headache, and acne rates were all significantly higher in triptorelin group than in leuprorelin group. A significant difference in FSH (p=0.003), LH (p=0.026) and E2 (p=0.002) levels between the groups were observed after 21 days of the GnRHa treatment. The FSH (p=0.021) and E2 (p=0.033) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment, but the difference of LH(p=0.917) level was no longer discernible. Leuprorelin in down-regulating the pituitary-ovarian function was more moderate, and the hormonal levels decrease progressively and gradually, therefore, with lower rate of menopausal symptoms. Leuprorelin acetate maybe better tolerated than triptorelin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture

PubMed Central

van den Bergh, Joop P. W.; Bouts, Marian E.; van der Veer, Eveline; van der Velde, Robert Y.; Janssen, Marcel J. W.; Geusens, Piet P.; Winkens, Bjorn; Oldenhof, Nico J. J.; van Geel, Tineke A. C. M.

2013-01-01

Introduction An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate. Methods In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models. Results There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95%CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p < 0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95%CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12. Conclusions Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture. Trial Registration Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867 PMID:24205135

Inflammatory response and treatment tolerance of long-term infusion of the anti-GD2 antibody ch14.18/CHO in combination with interleukin-2 in patients with high-risk neuroblastoma.

PubMed

Ceylan, Kiraz; Jahns, Luciana J; Lode, Bjoern N; Ehlert, Karoline; Kietz, Silke; Troschke-Meurer, Sascha; Siebert, Nikolai; Lode, Holger N

2018-06-01

The monoclonal anti-GD 2 antibody ch14.18/CHO in combination with IL-2 is active and effective in high-risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long-term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m 2 ; 24 hr) in combination with subcutaneous (s.c.) IL-2 in a single center program. Fifty-three NB patients received up to six cycles of 100 mg/m 2 ch14.18/CHO (d8-18, where d represents day(s)) as LTI combined with 6 × 10 6 IU/m 2 s.c. IL-2 (d1-5; 8-12) and 160 mg/m 2 oral 13-cis retinoic acid (RA) (d19-32). Side effects of ch14.18/CHO and IL-2 treatment require hospitalization of patients on d8. Treatment tolerance was evaluated daily with clinical parameters (body temperature, vital signs, Lansky performance status, requirement of i.v. concomitant medication) to define an outpatient candidate status. sIL-2-R and C-reactive protein values were determined to assess the inflammatory response. LTI of ch14.18/CHO (d8-18) in combination with s.c.IL-2 (d8-12) showed an acceptable treatment tolerance that allowed all patients to receive part of the treatment as an outpatient (median time point of discharge: d15 for all cycles). The treatment tolerance improved from cycle to cycle and the time to become an outpatient candidate decreased from d15 to d13 in subsequent cycles. Clinical and laboratory parameters indicate a maximum inflammatory response at d11 of each cycle. Interestingly, the soluble IL-2 receptor remained increased at baseline of the next cycle indicating immune activation over the entire treatment period of 6 months. LTI of ch14.18/CHO combined with s.c.IL-2 shows an improved tolerance in subsequent cycles allowing outpatient treatment. © 2018 Wiley Periodicals, Inc.

Five Alzheimer's disease cases with refractory behavioural psychological symptoms of dementia treated with blonanserin.

PubMed

Hamuro, Atsushi; Saito, Satona

2010-12-01

The aim of the present study was to determine the efficacy, side-effects and tolerability of blonanserin for treating refractory behavioural psychological symptoms of dementia (BPSD). The present study was a 12-week, prospective, structured clinical trial of blonanserin for the treatment of BPSD. The degree of cognitive function, activities of daily living score, and the degree of BPSD were determined using the Mini-Mental State Examination (MMSE), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). The severity of extrapyramidal symptoms was assessed using the Drug-Induced Extrapyramidal Symptoms scale (DIEEPS). Five patients were enrolled. These patients met the NINCDS-ADRDA criteria. The patients were prescribed more than two kinds of existing antipsychotic drugs and were considered refractory cases; the drugs were discontinued because they were ineffectual and side-effects appeared. Each drug was prescribed independently for at least 2 weeks. The mean changes (at baseline and at the last week, respectively) in the MMSE (12.25, 9.25), in the DAD (6.5, 6.75), in the RAGE (5.5, 5.3) and in the DIEEPS (0.5, 1.5) were minimal. The mean changes in the NPI were two or fewer points. Some side-effects (one gait abnormality and one pneumonia) were observed. The results of this preliminary study show that blonanserin does not have adequate efficacy for the treatment of refractory BPSD. © 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.

The glaucoma research foundation patient survey: patient understanding of glaucoma and its treatment.

PubMed

Herndon, Leon W; Brunner, Thomas M; Rollins, Jane Neff

2006-01-01

Determine patients' understanding of glaucoma and its treatment, their sources of information about glaucoma, their preferences for treatment, their experience with medication side effects, and their reasons for changing eye doctors. Prospective, nonrandomized patient survey study. A questionnaire was developed and sent to the 22,000 subscribers of the Gleams newsletter who have glaucoma. Questionnaires were returned by 4310 glaucoma patients. Most respondents received glaucoma information from their eye doctor. Only 28% of respondents reported having changed eye doctors for reasons related to their glaucoma. Of those who had, 60% cited poor communication as the reason. When queried about specific side effects associated with their medication, over 85% of responding patients were never or rarely bothered by headaches and eyelid darkening. Most respondents (67% and 55%, respectively) were rarely or never disturbed by red eye or burning and stinging. Most respondents understood the importance of intraocular pressure (IOP) lowering in glaucoma, and of those patients who expressed a preference, 92% reported that they would prefer the medication that lowers IOP the most, even if it caused red eye for a few weeks, over a medication that caused no red eye but did not get IOP as low. Patients who subscribe to Gleams and responded to the survey rely most on their doctors for information about glaucoma and its treatment. Most understand the importance of maintaining low IOP to decrease the risk of vision loss, and most will tolerate temporary ocular side effects to achieve low IOP.

Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a double-blind, randomized, crossover study.

PubMed

Krymchantowski, Abouch Valenty; Peixoto, Patricia; Higashi, Rafael; Silva, Ariovaldo; Schutz, Vivian

2005-12-14

The process of inflammation is crucial in migraine, and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs is limited by side effects as well as incomplete efficacy in some patients. Among the available options, lysine clonixinate (LC) and naproxen sodium (NS) have proved effective in migraine. The aim of this study was to compare the efficacy and tolerability of oral formulations of LC and NS in the treatment of moderate or severe migraine attacks, with a double-blind, crossover design. Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41) with migraine according to the criteria of the International Headache Society were prospectively enrolled. The patients were randomized into 2 groups and each participant treated 2 migraine attacks. Group 1 treated the first attack with LC and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal appearance. Headache intensity, nausea, photophobia, and side effects were evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue drugs were allowed after 2 hours for those who didn't respond, and this was also compared between groups. Sixty patients (54 women, 6 men) completed the study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9% who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to group 1 reported nausea, compared with 33.9% in group 2, and both drugs eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly for those taking LC, but only after 2 hours for those who took NS (P < .0001). Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior to NS in reducing photophobia at 2 hours (P = .027). Ten patients who took LC and 8 who took NS required rescue drugs after 2 hours. Twelve patients who used LC and 16 who took NS reported side effects. Although this study did not include a placebo arm, which impairs any definitive efficacy claims, we found LC and NS to be similarly effective and well tolerated in patients presenting moderate or severe attacks of migraine.

Quantifying the variability in stiffness and damping of an automotive vehicle's trim-structure mounts

NASA Astrophysics Data System (ADS)

Abolfathi, Ali; O'Boy, Dan J.; Walsh, Stephen J.; Dowsett, Amy; Fisher, Stephen A.

2016-09-01

Small plastic clips are used in large numbers in automotive vehicles to connect interior trims to vehicle structures. The variability in their properties can contribute to the overall variability in noise and vibration response of the vehicle. The variability arises due to their material and manufacturing tolerances and more importantly due to the boundary condition. To measure their stiffness and damping, a simple experimental rig is used where a mass is supported by the clip which is modelled as a single degree of freedom system. The rig is designed in a way that it simulates the boundary condition as those of the real vehicle. The variability in clip and also due to the boundary condition at the structure side is first examined which is 7% for stiffness and 8% for damping. To simulate the connection of the trim side, a mount is built using a 3D printer. Rattling occurs in the response of the clips with loose connections, however by preloading the mount the effective stiffness increases and the rattling is eliminated. The variability due to the boundary condition at the trim side was as large as 40% for stiffness and 52% for damping.

How oxygen reacts with oxygen-tolerant respiratory [NiFe]-hydrogenases.

PubMed

Wulff, Philip; Day, Christopher C; Sargent, Frank; Armstrong, Fraser A

2014-05-06

An oxygen-tolerant respiratory [NiFe]-hydrogenase is proven to be a four-electron hydrogen/oxygen oxidoreductase, catalyzing the reaction 2 H2 + O2 = 2 H2O, equivalent to hydrogen combustion, over a sustained period without inactivating. At least 86% of the H2O produced by Escherichia coli hydrogenase-1 exposed to a mixture of 90% H2 and 10% O2 is accounted for by a direct four-electron pathway, whereas up to 14% arises from slower side reactions proceeding via superoxide and hydrogen peroxide. The direct pathway is assigned to O2 reduction at the [NiFe] active site, whereas the side reactions are an unavoidable consequence of the presence of low-potential relay centers that release electrons derived from H2 oxidation. The oxidase activity is too slow to be useful in removing O2 from the bacterial periplasm; instead, the four-electron reduction of molecular oxygen to harmless water ensures that the active site survives to catalyze sustained hydrogen oxidation.

Fast acting multiple element valve

DOEpatents

Yang, Jefferson Y. S.; Wada, James M.

1991-01-01

A plurality of slide valve elements having plural axial-spaced annular parts and an internal slide are inserted into a bulkhead in a fluid conduit from a downstream side of the bulkhead, locked in place by a bayonet coupling and set screw, and project through the bulkhead into the upstream conduit. Pneumatic lines connecting the slide valve element actuator to pilot valves are brought out the throat of the valve element to the downstream side. Pilot valves are radially spaced around the exterior of the valve to permit the pneumatic lines to be made identical, thereby to minimize adverse timing tolerances in operation due to pressure variations. Ring manifolds surround the valve adjacent respective pilot valve arrangements to further reduce adverse timing tolerances due to pressure variations, the manifolds being directly connected to the respective pilot valves. Position sensors are provided the valve element slides to signal the precise time at which a slide reaches or passes through a particular point in its stroke to initiate a calibrated timing function.

How oxygen reacts with oxygen-tolerant respiratory [NiFe]-hydrogenases

PubMed Central

Wulff, Philip; Day, Christopher C.; Sargent, Frank; Armstrong, Fraser A.

2014-01-01

An oxygen-tolerant respiratory [NiFe]-hydrogenase is proven to be a four-electron hydrogen/oxygen oxidoreductase, catalyzing the reaction 2 H2 + O2 = 2 H2O, equivalent to hydrogen combustion, over a sustained period without inactivating. At least 86% of the H2O produced by Escherichia coli hydrogenase-1 exposed to a mixture of 90% H2 and 10% O2 is accounted for by a direct four-electron pathway, whereas up to 14% arises from slower side reactions proceeding via superoxide and hydrogen peroxide. The direct pathway is assigned to O2 reduction at the [NiFe] active site, whereas the side reactions are an unavoidable consequence of the presence of low-potential relay centers that release electrons derived from H2 oxidation. The oxidase activity is too slow to be useful in removing O2 from the bacterial periplasm; instead, the four-electron reduction of molecular oxygen to harmless water ensures that the active site survives to catalyze sustained hydrogen oxidation. PMID:24715724

Randomized trial comparing a chemical peel containing a lipophilic hydroxy acid derivative of salicylic acid with a salicylic acid peel in subjects with comedonal acne.

PubMed

Levesque, Annie; Hamzavi, Iltefat; Seite, Sophie; Rougier, André; Bissonnette, Robert

2011-09-01

Lipohydroxyacid is a lipophilic derivative of salicylic acid with comedolytic properties. To compare lipohydroxyacid and salicylic acid peels in subjects with comedonal acne. In this split face, randomized study, 20 subjects with comedonal acne received lipohydroxyacid peels on one side of the face, while the other side was treated with salicylic acid peels. A total of six peels at 2-week intervals were performed. Efficacy was evaluated by counting noninflammatory and inflammatory lesions and by performing a global change in acne assessment. Safety was assessed by evaluating adverse events, global tolerance, and the presence of erythema, scaling, and dryness. There was a statistically significant decrease of 55.6% and 48.5% from baseline to Day 98 in the mean number of noninflammatory lesions for the sides treated with lipohydroxyacid and salicylic acid peels, respectively (P < 0.001). There was no significant difference in the degree of reduction in noninflammatory lesions between the two peels. There was no significant reduction in the number of inflammatory lesions. Both peels were generally very well tolerated. This study suggests that lipohydroxyacid peels can be beneficial to subjects with comedonal acne. © 2011 Wiley Periodicals, Inc.

[Interferons--its method of administration and adverse effect related to pharmacokinetics ].

PubMed

Furue, H

1984-02-01

The potential role of interferons in the treatment of malignant diseases is currently being evaluated. This paper reviews experimental and clinical findings regarding pharmacokinetics, method of administration, and side reactions of interferons. Interferon in the blood is rapidly cleared from the circulation. Intramuscular injection of alpha-interferon causes low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon is never detected consistently in the blood after intramuscular or subcutaneous administration. The studies with animal models suggest that doses higher than those given in current clinical trials will be necessary to obtain clearly beneficial effects in human. The maximum safely tolerated daily dose is appreciably higher than that used in most previous studies, although even at this level, considerable toxicity may be encountered. Adequate method of administration, route, dose and interval are not yet established at all. Exact mechanism of anticancer activity is not yet well defined. The most frequent side reaction is fever. However, the exact mechanism to cause these side reactions is also not yet clarified. Dose limiting central nervous system toxicities, hypotension, hypocalcaemia etc. are occasionally encountered in some instances. Antibody to interferon is demonstrated in some cases. Purification of interferon does not always causes reduction of side reactions. The treatment of cancer cases with interferon has just started and there are many problems to be solved. However, therapeutic beneficial may be achieved in the treatment of malignant tumors by appropriate combinations of interferon with conventional treatment. More laboratory studies as well as carefully controlled clinical observations are warranted.

Efficacy of the addition of salicylic acid to clindamycin and benzoyl peroxide combination for acne vulgaris.

PubMed

Akarsu, Sevgi; Fetil, Emel; Yücel, Filiz; Gül, Eylem; Güneş, Ali T

2012-05-01

Clindamycin phosphate (CDP), benzoyl peroxide (BPO) and salicylic acid (SA) are known to be effective acne therapy agents depending on their anti-inflammatory and comedolytic properties. The purpose of this study was to investigate the efficacy and tolerability of the addition of SA treatment to CDP and BPO (SA and CDP + BPO) and compare it with CDP + BPO in patients with mild to moderate facial acne vulgaris. Forty-nine patients were enrolled in a 12 week prospective, single-blind, randomized, comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurements of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts. There were statistically significant differences between treatment groups for reductions in NIL counts beyond 2 weeks, IL counts and TL counts throughout the all study weeks, and global improvement scores evaluated by patients and investigator at the end of the study in favor of SA and CDP + BPO treatment when compared to CDP + BPO treatment. Both combinations significantly decreased stratum corneum hydration, although skin sebum values decreased with SA and CDP + BPO treatment. These combinations were also well tolerated except significantly higher frequency of mild to moderate transient dryness in patients applied SA and CDP + BPO. The addition of SA to CDP + BPO treatment demonstrated significantly better and faster results in terms of reductions in acne lesion counts and well tolerated except for higher frequency of mild to moderate transient dryness. © 2011 Japanese Dermatological Association.

Duloxetine, an antidepressant with analgesic properties – a preliminary analysis

PubMed Central

Onuţu, Adela Hilda

2015-01-01

Serotonin and norepinephrine reuptake inhibitors are second-line antidepressants largely used because of their good tolerance and their reduced side effects. Two of these drugs, duloxetine and venlafaxine, are used also in chronic pain management. In this review we present recent data regarding duloxetine’s effects on the central nervous system, linked to acute pain management, and their efficiency in reducing postoperative chronic pain. The drug’s efficacy results from its modulating effect on the descending inhibitory pain pathways and the inhibition of the nociceptive input. There are already several studies in favor of the analgesic properties of duloxetine. However, further and larger randomized studies are necessary in order to clarify duloxetine efficiency in acute postoperative settings, and thereafter on persistent chronic postoperative pain. PMID:28913467

Safety and Patient Acceptability of Stellate Ganglion Blockade as a Treatment Adjunct for Combat-Related Post-Traumatic Stress Disorder: A Quality Assurance Initiative.

PubMed

McLean, Brian

2015-09-10

 To perform a quality assurance and performance improvement project through review of our single center data on the safety and patient acceptability of the stellate ganglion blockade (SGB) procedure for the relief of symptoms related to chronic post-traumatic stress disorder.  Our interventional pain management service has been offering trials of SGB therapy to assist with the management of the sympathetically mediated anxiety and hyperarousal symptoms of severe and treatment-refractory combat-related PTSD. There have been multiple case series in the literature describing the potential impact of this procedure for PTSD symptom management as well as the safety of image-guided procedures. We wished to ensure that we were performing this procedure safely and that patients were tolerating and accepting of this adjunctive treatment option.  We conducted a review of our quality assurance and performance improvement data over the past 18 months during which we performed 250 stellate ganglion blocks for the management of PTSD symptoms to detect any potential complications or unanticipated side effects.  We also analyzed responses from an anonymous patient de-identified survey collected regarding the comfort and satisfaction associated with the procedure.  We did not identify any immediate post-procedural complications or delayed complications from any of the 250 procedures performed from November 2013 to April 2015. Of the 110 surveys that were returned and tabulated, 100% of the patients surveyed were overall satisfied with our process and with the procedure, 100% said they would recommend the procedure to a friend, and 95% stated that they would be willing to undergo as many repeat procedures as necessary based on little discomfort and tolerable side effects.  Our quality assurance assessment suggests that in our center the SGB procedure for PTSD is a safe, well-tolerated, and acceptable treatment adjunct in the management of severe symptoms associated with chronic treatment-refractory PTSD. Patient satisfaction responses are strongly suggestive of high therapeutic value, and further studies are indicated to determine the effectiveness, duration of action, and optimal treatment regimen.

Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

PubMed

Bujalska-Zadrożny, Magdalena; Tatarkiewicz, Jan; Kulik, Kamila; Filip, Małgorzata; Naruszewicz, Marek

2017-03-01

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg 2+ ), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.

PubMed

Müller, Thomas

2013-08-01

Recent experimental and clinical research has shown that A2A adenosine receptor antagonism can bring about an improvement in the motor behavior of patients with Parkinson's disease. Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity. In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline. Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential. A2A adenosine receptor antagonists are efficacious in combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects. Future research on A2A adenosine receptor antagonism should consider compounds like istradefylline as l-dopa and/or dopamine agonist-sparing treatment alternatives, since their clinical handling, safety and side-effect profile are superior to l-dopa and/or dopamine agonists. The current focus to demonstrate a specific dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in clinical trials is risky, since the presentation of dyskinesia varies on a day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. The demonstration of an antidyskinetic effect may convince authorities, but this is far less relevant in clinical practice as patients generally better tolerate dyskinesia than other phenomena and dopaminergic side effects.

Manipulation for the control of back pain and curve progression in patients with skeletally mature idiopathic scoliosis: two cases.

PubMed

Tarola, G A

1994-05-01

This report of two cases illustrates the potential effect of chiropractic manipulative therapy on back pain and curve progression in the at-risk, skeletally mature patient with adolescent idiopathic scoliosis. Two patients suffering from lumbar scoliosis and chronic back pain. Both had scoliosis that had progressed after skeletal maturity. Diversified type chiropractic manipulative therapy was used palliatively for back pain relief in one case, and routinely 1-2 times per month in the other case. The manipulation was applied manually, with the patients in the prone and side-posture positions. Vertebral levels manipulated were identified as fixated/dysfunctional segments based on static and/or motion palpation. They were generally applied to areas above and/or below the curve apex. When applied at the apex, cavitation was more easily achieved when the direction of thrust was into the concave side. This was also tolerated better by the patient. No attempt was made to "straighten the curve" by thrusting into the convex side. Gentle manual intersegmental mobilization, stretching and muscle massage techniques were also applied. The case treated palliatively had curve progression consistent with the literature over an 8-yr period. The case treated routinely did not. The procedure was effective in both cases for subjective relief of back pain. Diversified-type CMT has a favorable effect on acute back pain when used palliatively. The procedure may also have a favorable long term effect of preventing recurrence of back pain and on retarding curve progression when used routinely 1-2 times per month.

Underestimation of the efficacy, effectiveness, tolerability, and safety of weekly low-dose methotrexate in information presented to physicians and patients.

PubMed

Pincus, T; Furer, V; Sokka, T

2010-01-01

Ten specific examples of the underestimation of the efficacy, effectiveness and tolerability, and overestimation of adverse events of weekly, low-dose methotrexate, administered with folic acid, in treatment of rheumatic diseases are summarised. These examples include: 1) meta-analyses of clinical trials suggest that methotrexate has an efficacy similar to other disease-modifying anti-rheumatic drugs (DMARDs); 2) information in textbooks and websites may overstate adverse events and drug interactions associated with weekly low-dose methotrexate; 3) information presented to patients when filling a prescription for methotrexate understates 'side effects' of RA and overstates those of methotrexate; 4) an admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary; 5) frequent blood testing in patients who take methotrexate may be overused; 6) eligibility of only a small minority of patients for clinical trials to compare biologic agents and methotrexate; 7) Step-up design in most comparisons of biologic agents with methotrexate includes only patients who had experienced an incomplete response to methotrexate; 8) in parallel design trials, the efficacy of biologic agents is not substantially greater than that of methotrexate; 9) low, inflexible dosage schedules of methotrexate and requirement for withdrawal with minimal liver function abnormalities in many clinical trials may underestimate efficacy, effectiveness, tolerability and safety; 10) interpretation of clinical trial results may overstate the clinical significance of lower radiographic progression in patients treated with biologic agents versus patients treated with methotrexate. More accurate interpretation of information for physicians and other health professionals, as well as patients, concerning use of weekly low-dose methotrexate in contemporary care could improve care and outcomes for patients with RA and other rheumatic diseases.

Biomechanics of side impact: injury criteria, aging occupants, and airbag technology.

PubMed

Yoganandan, Narayan; Pintar, Frank A; Stemper, Brian D; Gennarelli, Thomas A; Weigelt, John A

2007-01-01

This paper presents a survey of side impact trauma-related biomedical investigations with specific reference to certain aspects of epidemiology relating to the growing elderly population, improvements in technology such as side airbags geared toward occupant safety, and development of injury criteria. The first part is devoted to the involvement of the elderly by identifying variables contributing to injury including impact severity, human factors, and national and international field data. This is followed by a survey of various experimental models used in the development of injury criteria and tolerance limits. The effects of fragility of the elderly coupled with physiological changes (e.g., visual, musculoskeletal) that may lead to an abnormal seating position (termed out-of-position) especially for the driving population are discussed. Fundamental biomechanical parameters such as thoracic, abdominal and pelvic forces; upper and lower spinal and sacrum accelerations; and upper, middle and lower chest deflections under various initial impacting conditions are evaluated. Secondary variables such as the thoracic trauma index and pelvic acceleration (currently adopted in the United States Federal Motor Vehicle Safety Standards), peak chest deflection, and viscous criteria are also included in the survey. The importance of performing research studies with specific focus on out-of-position scenarios of the elderly and using the most commonly available torso side airbag as the initial contacting condition in lateral impacts for occupant injury assessment is emphasized.

Biomechanics of side impact: Injury criteria, aging occupants, and airbag technology

PubMed Central

Yoganandan, Narayan; Pintar, Frank A.; Stemper, Brian D.; Gennarelli, Thomas A.; Weigelt, John A.

2007-01-01

This paper presents a survey of side impact trauma-related biomedical investigations with specific reference to certain aspects of epidemiology relating to the growing elderly population, improvements in technology such as side airbags geared toward occupant safety, and development of injury criteria. The first part is devoted to the involvement of the elderly by identifying variables contributing to injury including impact severity, human factors, and national and international field data. This is followed by a survey of various experimental models used in the development of injury criteria and tolerance limits. The effects of fragility of the elderly coupled with physiological changes (e.g., visual, musculoskeletal) that may lead to an abnormal seating position (termed out-of-position) especially for the driving population are discussed. Fundamental biomechanical parameters such as thoracic, abdominal and pelvic forces; upper and lower spinal and sacrum accelerations; and upper, middle and lower chest deflections under various initial impacting conditions are evaluated. Secondary variables such as the thoracic trauma index and pelvic acceleration (currently adopted in the United States Federal Motor Vehicle Safety Standards), peak chest deflection, and viscous criteria are also included in the survey. The importance of performing research studies with specific focus on out-of-position scenarios of the elderly and using the most commonly available torso side airbag as the initial contacting condition in lateral impacts for occupant injury assessment is emphasized. PMID:16527285

[Long-term therapy of idiopathic inflammatory bowel disease].

PubMed

Lukáš, K; Dastych, M; Novotný, A; Prokopová, L; Zbořil, V

2012-01-01

Crohns disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. Both can be treated with medications that induce and maintain remission. The choice of medication is influenced by the balance between drug potency and potential side-effects, previous response to treatment, and the presence of extraintestinal manifestations or complications. After remission has been achieved, the goal of treatment is to maintain the symptom-free status. 5-aminosalicylic acid derivatives have efficacy for maintenance of remission in patients with distal disease. Thiopurines are recommended for the long-term therapy. For the patients who do not have a response to immunosuppressive therapy or cannot tolerate it, anti-TNF-α agents are gradually being adopted. Effective in the remission maintenance are thiopurines, infliximab and adalimumab.

Pramipexole in the treatment of Parkinson's disease: new developments.

PubMed

Möller, J Carsten; Oertel, Wolfgang H

2005-09-01

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

Oral sumatriptan in acute migraine.

PubMed

Goadsby, P J; Zagami, A S; Donnan, G A; Symington, G; Anthony, M; Bladin, P F; Lance, J W

1991-09-28

The efficacy in acute migraine of oral sumatriptan was assessed in a double-blind, randomised, placebo-controlled, crossover study of 61 patients (mean age 39 [SD 10] years). 41 completed treatment of four attacks, two with sumatriptan 100 mg and two with placebo. The response rate (reduction in headache from moderate or severe to mild or absent at 2 h) was 51% (45/89) with sumatriptan and 10% (9/93) with placebo (p less than 0.01); rescue medication was needed at 2 h in 41% and 88%, respectively. Of 28 patients headache-free at 24 h, 11 (39%) had recurrent headache within 24 h. There were no substantial side-effects. Thus, sumatriptan is an effective well-tolerated treatment for acute migraine attacks.

Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

PubMed

Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

1996-08-01

The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

[Improving wound healing after nose surgery by combined administration of xylometazoline and dexpanthenol].

PubMed

Kehrl, W; Sonnemann, U

2000-03-01

The aim of this study was the examination of efficacy and tolerability of an application-form of the new combination of Xylometazoline with Dexpanthenol (Nasic) versus Xylometazoline alone. Randomized verum controlled parallel-group-comparison of two weeks treatment of a nasal-spray. 61 inpatients with the diagnosis Rhinitis following nasal operation were included in this study and 30 patients were treated with verum and placebo each. The assessment of nasal-breathing-resistance according to scores was defined as target-parameter. Confirmatory statistical analysis was carried out according to Wilcoxon-Mann-Whitney-U two-sided at alpha < or = 0.05. The superiority of the combination of Xylometazoline-Dexpanthenol nasal-spray versus Xylometazoline nasal spray could be proven for the target-parameter as clinically relevant and statistically significant. The clinically proven efficacy is emphasized by good tolerability of both treatments. Due to easy handling of the nasal-spray a good compliance was confirmed. Distinct improvement of symptoms in patients following nasal operations underlines the efficacy of both medications. With respect to the tolerability therapy with the combination is more beneficial in comparison to the alternative therapy. The result of this controlled clinical study confirms that the combination Xylometazoline-Dexpanthenol is an enlargement and improvement of effective medicinal treatment of rhinitis following nasal operation in comparison to therapy with Xylometazoline alone.