Summary:Purpow; To determine whether the toxicity that occurs in some patients when laniotrigine (LTG) i s added to carbaniaxpine (CBZ) is the result of either a pharmacokinetic or a p harmncod y nam ic in tel-ac ti on.Mc/liocl.s: Escalating LTG doses were added to ongoing CBZ treatmcnt in 47 patients. All patients had blood sample9 collected lor drug concentration measurement, including the epoxide metabolite of CBZ, before starting LTG treatment and after stnbilising at each dose escalation. Patients also were examined for signs of toxicity.Kcsirits: After LTG was introduced, nine patients demonhrrated clinical signs of CNS toxicity, mainly diplopia and diLy i n e s b . Thei-e was no significant ( p = 0.05) change in the herum concentrations of either CBZ or its epoxide metabolite when LTG was added either to the group as a whole or t~ the nine patients who experienced adverse CNS effects. LTG serum concentrations also were below the level at which the common sign9 of LTG toxicity, such a\ nausea, vomiting, or unsteadiness, are more likely to occur. In seven of the nine patients who exhibited CNS toxicity. CBZ serum concentrations were >8 mg/L on LTG introduction.Coriclu,\ion.s: Toxicity is more likely to occur when LTG is added to CBZ if the initial CBZ level i s high. typically >8 mg/L. This appears to be the result of a pharmacodynamic interaction. A reduction of CBZ dose usually resolves the toxicity, allowing the LTG dose to be escalated to maximal cffect. I t i s not usually necessary to stop either drug. Key Words: Lainotrigine-Carbam~~epine-Carbai~i~i7~pJne-I0,l 1 -epoxide-Phariiiacodynainic interaction.Lmiotrigine (LTG) has become well established a s an important new drug in treating a wide spectrum of seizure types ( I ) . Its primary mode of action is to block sodium channels. It tnay act through the inhibition of abnormal release of excitatory neurotransmitters, in particular, glutamate (2). LTG is metabolised extensively to a qua te r ti ary 2 -N -g I LIC u roni de which i s subsequent 1 y eliminated in thc urine. It does not induce the mixed function oxidase enzymes in the liver, but the clearance of I,TG is altered by concomitant administration of some other antiepileptic drugs (AEDs): valproate (VPA) decrexes the rate o f metabolism and enzyme-inducing drugs increase it (3.4). These effects indicate that there may be substantial differences in LTG dose requirement for patients who arc taking comedication with these interacting drugs.Diplopia and dizziness, the classic signs of carbaniazepine (CBZ) toxicity, have been reported in some patients when LTG is added to CBZ treatment (5,6). Initially. it W;IS unclear whether ( a ) these were clinical signs of LTG toxicity; (b) LTG was affecting the plasma concentrations of CBZ, and/or its pharmacologically active epoxide metabolite: or, (c) there was a pharmacodynamic interaction between the drugs which enhanced the adverse effects.The present study reports on a series of 47 patients who were already taking CBZ, to which LTG was added in escalating d...
Papillary breast lesions encompass a wide spectrum of pathologies ranging from benign lesions, such as solitary intraductal papilloma, to the uncommon papillary carcinoma. These lesions have various clinical presentations and diverse radiological features. Differentiating benign and malignant papillary lesions based on imaging features may often be difficult. Other benign and malignant pathologies can also mimic papillary lesions on imaging, and tissue diagnosis is essential. Imaging plays an important role in lesion identification, assessment of extent, tissue sampling, and follow-up. Surgical excision has been recommended for all papillary lesions due to an increased incidence of high-risk lesions and neoplasia even with percutaneous, biopsy-proven benign papillomas. This review looks at papillary breast lesions from the radiologists' standpoint and discusses the clinical, imaging, and pathological features of these lesions, as well as the role of imaging in their evaluation. P apillary lesions in the breast are uncommon but arise from a wide range of pathologies and have diverse clinical and imaging features. A papillary lesion is characterized by an arborescent structure composed of fibrovascular stalks covered by a layer of epithelial cells with or without an intervening myoepithelial cell layer (1). Overlapping features make differentiation of benign and malignant papillary lesions difficult on imaging, and a tissue diagnosis is essential. Definitive histopathologic diagnosis on core biopsy can occasionally be difficult. Additionally, even those lesions shown by percutaneous biopsy to be benign papillomas are associated with an increased likelihood of high-risk lesions and neoplasia. Due to nonspecific findings on imaging and histopathology, as well as varying malignant potential, papillary lesions present significant diagnostic and management challenges for the radiologists, pathologists, and surgeons. We briefly review the types of papillary lesions, multimodality imaging findings, and the radiologist's role in their evaluation. The types and clinical features of papillary lesionsPapillary lesions can be broadly categorized as benign or malignant. Benign papillary lesions include a solitary intraductal papilloma, multiple intraductal papillomas, and atypical ductal hyperplasia (ADH) within a papilloma. Malignant papillary lesions include ductal carcinoma in situ (DCIS) arising in a papilloma, papillary DCIS, intracystic or encapsulated papillary carcinoma, solid papillary carcinoma, invasive papillary carcinoma arising in an intracystic papillary carcinoma, and invasive papillary carcinoma (1). Intraductal papillomaSolitary papillomas arise from a large central duct, are more common in perimenopausal women, and present with nipple discharge. Multiple papillomas are peripheral lesions arising from the terminal duct lobular unit. These are less common, usually affect a younger age group, and present as a palpable mass. Both can be associated with proliferative and high-risk lesions, such as radial ...
The aim of this study was to determine whether lamotrigine can be re-introduced safely and with a benefit in young people who previously had a mild rash associated with the first introduction of this drug. In the first 150 young people (5-19 years old) treated with lamotrigine in a special centre for epilepsy, seven developed a mild rash soon after starting the drug. In none of these cases was the rash severe, nor was there any mucous membrane involvement. The lamotrigine was stopped immediately when the rash was identified and was subsequently re-introduced, using a special very-low-dose-escalation regime, starting with 0.1 mg /day total daily dose, after periods ranging from 47 to 236 days. It was possible to re-introduce the lamotrigine without recurrence of persistent rash and without any adverse effects in all seven cases. The re-introduction of lamotrigine was associated with improvement in five of the seven cases. It is recommended that lamotrigine is stopped as soon as any rash attributable to the drug develops but it may be possible to re-introduce the drug after mild rash using a very-slow-dose-escalation regime, with a benefit in at least some cases.
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