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Dosage Increases (dosage + increase)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Clinical presentation and management of antibody-induced failure of botulinum toxin therapy

MOVEMENT DISORDERS, Issue S8 2004
Dirk Dressler MD
Abstract Therapy with botulinum toxin (BT) can fail due to numerous reasons, including failure due to formation of antibodies against BT (BT-AB, AB-TF). AB-TF is a secondary therapy failure, i.e. it occurs during the course of an ongoing BT therapy. It can be subjective or objective, temporary or permanent, and partial or complete. Complete AB-TF is usually preceded by injection series with partial AB-TF in which the therapeutic effect is reduced in its intensity and duration. AB-TF usually occurs within 2 or 3 years after initiation of BT therapy. After 4 years it is rare. BT-AB are neutralising or blocking by definition, i.e. they are directly interfering with BT's biological mechanism of action. Non-neutralizing or non-blocking antibodies occur. BT-AB can be detected by the mouse diaphragm assay, the mouse protection assay, and by patient-based tests such as the sternocleidomastoid test, the extensor digitorum brevis test, and the frowning test. Enzyme-linked immunosorbent assays (ELISA) have a low specificity and a low sensitivity for detection of BT-AB. BT-AB titres drop spontaneously after cessation of BT therapy but latencies are too long to be compatible with an effective BT therapy. BT dosage increase can be successful to overcome AB-TF when AB-TF is partial and when BT-AB titres are low. Usage of alternative BT type A preparations fail to overcome AB-TF. Alternative BT types, such as BT type B and BT type F, are initially successful in AB-TF, but stimulate formation of antibodies against the alternative BT types after few applications. BT-AB reduction with immunosuppressants and inactivation of BT-AB by intravenous immunoglobuline application has not yet been achieved. Extraction of BT-AB by plasmapheresis and immunoadsorption is possible but is associated with substantial logistic problems. Prevention of BT-AB formation, therefore, is of paramount importance. Identified risk factors for BT-AB formation must be taken into account when BT therapy is planned. The most interesting perspective seems to be the development of new BT preparations with reduced antigenicity. © 2004 Movement Disorder Society [source]

Negligible Analgesic Tolerance Seen with Extended Release Oxymorphone: A Post Hoc Analysis of Open-Label Longitudinal Data

PAIN MEDICINE, Issue 8 2010
R. Norman Harden MD
Abstract Objective., To examine the development of analgesic tolerance in patients on oxymorphone extended-release (OxymER). Design.,Post hoc analysis of data from a previously conducted prospective 1 year multi-center open-label extension study in which patients were able to titrate as needed. Patients., Sample of 153 hip and knee osteoarthritis (OA) subjects on OxymER. Primary analyses were limited to study completers (n = 62) due to the large amount of missing data for the noncompleters (n = 91). Outcome Measures., Main outcome measures included OxymER doses (pill counts) and pain intensity ratings using a visual analog scale at monthly visits. Results., There were significant dose increases from weeks 1 to 2 and 2 to 6 (P < 0.05). Doses stabilized around week 6, suggesting the completion of what we defined as "titration." Both doses and pain ratings were stable when this titration phase was excluded from the analysis (P = 0.751; P = 0.056, respectively). Only 28% of the patients had any dose changes following this titration. While there was a significantly greater dose at week 52 compared with week 10 (P = 0.010), the increase in dose became insignificant after excluding four subjects who required two dose increases (P = 0.103). Conclusions., The results showed that most of the titration/dose stabilization changes occurred within the first 10 weeks. A minority (28%) of subjects required dosage increases after this (defined) titration period. Pain reports stabilized statistically after 2 weeks. The findings of this post hoc analysis suggest a lack of opioid tolerance in the majority (72%) of these OA patients who completed this study following a defined titration period on OxymER. Summary., This post hoc analysis of oxymorphone ER consumption in osteoarthritis pain vs pain report showed that most dose changes occurred during an initial "titration period" as defined. Following this titration few subjects increased dose and analgesia remained stable. These findings suggest a lack of longitudinal opioid tolerance in the majority of those OA subjects who completed the trial. [source]

Practitioner Review: Psychopharmacology in children and adolescents with mental retardation

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2006
Benjamin L. Handen
Background:, The use of psychotropic medication to treat children and adults with mental retardation (MR) has a long and extensive history. There are no identified medications to address specific cognitive deficits among persons with MR. Instead, psychotropic medications are used to treat specific behavioral symptoms and/or psychiatric syndromes. The purpose of this review is to provide an overview of the recent literature regarding the use of psychotropic medications in this population, focusing primarily on children and adolescents. Methods:, The paper is divided into five general drug categories: psychostimulants, antipsychotics, antidepressants, mood stabilizers, and other drugs. Each section offers an overview of the research supporting the use of that class of medications in children and adolescents with MR as well as cautions regarding potential side effects. Finally, specific clinical recommendations are offered. Results:, The majority of studies in MR tend to be open trials, case reports, or controlled studies with small samples. The available data suggests that persons with MR respond to various psychotropic medications in ways similar to the typically developing population. However, rates of response tend to be poorer and the occurrence of side effects tends to be more frequent. Conclusions:, The use of psychotropic medications in children and adolescents with MR requires even greater monitoring and the use of lower doses and slower dosage increases than in the general population. [source]

Fluorescent Detection of Rat Parathyroid Glands via 5-Aminolevulinic Acid,

THE LARYNGOSCOPE, Issue 6 2008
Scott A. Asher BS
Abstract Objective: Anatomic identification of parathyroid glands during surgery is challenging and time consuming. We sought to determine whether 5-aminolevulinic acid (5-ALA) could produce parathyroid gland fluorescence to improve their detection in a preclinical model. Methods: Thirty-two rats were administered 0 to 700 mg/kg of 5-ALA by intraperitoneal injection prior to neck exploration under the illumination of a blue light (380,440 nm). Tissue fluorescence was assessed at 1, 2, or 4 hours postinjection and then removed for histologic confirmation of parathyroid tissue. Results: Rat parathyroid glands could not be visualized under ambient light. At dosages of 300 mg/kg or greater, bilateral parathyroid glands were visualized in 18 of 19 rats using blue light illumination. At dosages less than 300 mg/kg, parathyroid gland fluorescence was detected in only 1 of 13 rats. At 2 hours after 5-ALA administration, the net mean intensity of parathyroid gland fluorescence was optimal with a dose of 500 mg/kg. At both 1 and 4 hours after 5-ALA injection, the net mean intensity of parathyroid gland fluorescence was optimal at the highest dose (700 mg/kg) and positively correlated with dosage increases. Conclusion: 5-ALA can be used to selectively detect parathyroid tissue from surrounding tissue in a preclinical model. Our data support the use of this technique in the clinical setting. [source]