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Drug Resistant (drug + resistant)
Selected AbstractsRing chromosome 20 syndrome: A link between epilepsy onset and neuropsychological impairment in three childrenEPILEPSIA, Issue 11 2009Aglaia Vignoli Summary Purpose:, Ring chromosome 20 [r(20)] syndrome is a well-defined chromosomal disorder characterized by epilepsy, mild-to-moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, even if its appearance is not constantly precocious. Seizures are frequently drug resistant. Methods:, We describe three children with [r(20)] syndrome in whom the onset of epilepsy (age at onset range: 4 years and 6 months to 9 years and 4 months) determined a kind of epileptic status (age at onset range: 6 years and 10 months to 9 years and 8 months) with dramatic neuropsychological deterioration. This epileptic status lasted for several months because of refractoriness to most antiepileptic drugs (AEDs), but it was treated successfully with a combination of valproate and lamotrigine in two children. Results:, As soon as seizures stopped, the children showed prompt recovery with partial restoration of the neuropsychological impairment. Conclusion:, This clinical picture can be described as abrupt epileptic encephalopathy. [source] Drug Resistance in Epilepsy: Putative Neurobiologic and Clinical MechanismsEPILEPSIA, Issue 6 2005Dieter Schmidt Summary:, Drug-resistant epilepsy with uncontrolled severe seizures despite state-of-the-art medical treatment continues to be a major clinical problem for up to one in three patients with epilepsy. Although drug resistance may emerge or remit in the course of epilepsy or its treatment, in most patients, drug resistance seems to be continuous and to occur de novo. Unfortunately, current antiepileptic drugs (AEDs) do not seem to prevent or to reverse drug resistance in most patients, but add-on therapy with novel AEDs is able to exert a modest seizure reduction in as many as 50% of patients in short-term clinical trials, and a few become seizure free during the trial. It is not known why and how epilepsy becomes drug resistant, while other patients with seemingly identical seizure types can achieve seizure control with medication. Several putative mechanisms underlying drug resistance in epilepsy have been identified in recent years. Based on experimental and clinical studies, two major neurobiologic theories have been put forward: (a) removal of AEDs from the epileptogenic tissue through excessive expression of multidrug transporters, and (b) reduced drug-target sensitivity in epileptogenic brain tissue. On the clinical side, genetic and clinical features and structural brain lesions have been associated with drug resistance in epilepsy. In this article, we review the laboratory and clinical evidence to date supporting the drug-transport and the drug-target hypotheses and provide directions for future research, to define more clearly the role of these hypotheses in the clinical spectrum of drug-resistant epilepsy. [source] PLAGUE AND POWER RELATIONSGEOGRAFISKA ANNALER SERIES B: HUMAN GEOGRAPHY, Issue 4 2007Rodrick Wallace ABSTRACT Public policy and economic practice, quintessential expressions of institutional cognition, create an opportunity structure constituting a tunable, highly patterned,,non-white noise' in a generalized epidemiological stochastic resonance that can efficiently amplify unhealthy living and working conditions, particularly within highly concentrated, marginalized urban populations, to evoke infectious disease outbreaks. This is especially true for the infections carried by socially generated ,risk behaviours' which are usually adaptations to histories of resource deprivation or marginalization. A number of local epidemics originating in such ecological keystone communities may subsequently undergo a policy and structure-driven phase transition to become a coherent pandemic, a spreading plague which can entrain more affluent populations into the disease ecology of marginalization. We use this approach to contrast the ecological resilience of apartheid and egalitarian social systems, and apply these perspectives to the forthcoming social and geographical diffusion of multiple drug resistant (MDR) HIV from present AIDS epicentres to the rest of the United States. [source] New mechanism of transforming growth factor-, signaling in hepatoma: Dramatic up-regulation of tumor initiating cells and epidermal growth factor receptor expressionHEPATOLOGY RESEARCH, Issue 5 2009Takeshi Nishimura Aim:, Transforming growth factor-, (TGF-,) has dual activity in tumor cells. We studied the effect of TGF-, on tumor-initiating cells (TICs), which are similar in self-renewal and differentiation features to normal adult stem cells. Methods:, We used side population (SP) cells that exclude DNA binding dye Hoechst 33342 to obtain TICs, studied the differences in the kinetics of the SP cell response to TGF-, treatment between hepatic tumor cell lines, and performed gene analysis. Results:, SP cells from all cell lines have higher proliferative ability compared to non-SP cells and they are drug resistant. TGF-, treatment increased the percentage of SP cells (%SP) and the survival rate; chemotherapeutic drug resistance developed only in K-251 SP cells. Gene analysis showed that TGF-, up-regulated epidermal growth factor receptor (EGFR) only in K-251 cells. There were no EGFR mutations in K-251, which had been reported in lung cancer. Knockdown of Smad4 using the small-interfering RNA technique in K-251 cells inhibited EGFR overexpression and significantly decreased the %SP. In contrast, the JNK inhibitor had little effect on EGFR expression or the %SP. Conclusion:, TGF-, treatment of K-251 cells causes tumor progression and the anti-cancer drug resistant phenotype by increasing SP. [source] Problem solving therapy for the depression-executive dysfunction syndrome of late lifeINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2008George S. Alexopoulos Abstract Background The ,depression executive dysfunction syndrome' afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non-pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression. Methods This paper focuses on problem solving therapy (PST) because it targets concrete problems that can be understood by patients with executive dysfunction and trains patients to address them using an easy to comprehend structured approach. Results We suggest that PST is a suitable treatment for patients with the depression-executive dysfunction syndrome because it has been found effective in uncomplicated geriatric major depression and in other psychiatric disorders accompanied by severe executive dysfunction. Furthermore, PST can address specific clinical features of depressed patients with executive dysfunction, especially when modified to address difficulties with affect regulation, initiation and perseveration. Conclusions A preliminary study suggests that appropriately modified PST improves problem solving skills, depression and disability in elderly patients with the depression-executive dysfunction syndrome of late life. If these findings are confirmed, PST may become a therapeutic option for a large group of depressed elderly patients likely to be drug resistant. Copyright © 2008 John Wiley & Sons, Ltd. [source] Epilepsy in Border Collies: Clinical Manifestation, Outcome, and Mode of InheritanceJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010V. Hülsmeyer Background: There is a lack of data on idiopathic epilepsy (IE) in Border Collies (BCs) in the veterinary literature. Hypothesis: Genetic epilepsy occurs in BCs and is frequently characterized by a severe clinical course and poor response to medical treatment. Animals: Forty-nine BCs diagnosed with IE. Methods: Medical records, seizure data, treatment data, and pedigree information of affected dogs were collected. Cases were classified phenotypically as affected or not affected; mild, moderate, or severe clinical course; active epilepsy (AE) or remission; and drug resistant or not drug resistant. Results: Clinical manifestations were classified as having a moderate (33%) or severe clinical course (49%), characterized by a high prevalence of cluster seizures and status epilepticus. Survival time was significantly decreased in dogs <2 years of age at seizure onset, and in dogs with a severe clinical course. Drug resistance was apparent in 71% of 24 dogs treated with ,2 antiepileptic drugs. The epilepsy remission rate was 18%. Median age at onset was significantly higher and initial seizure frequency was significantly lower in dogs with remission compared with dogs with AE. Pedigree analyses indicated a strong genetic founder effect in the appearance of epilepsy, resembling autosomal recessive inheritance. Conclusion and Clinical Importance: The present study confirms the occurrence of genetically mediated epilepsy with a frequent severe clinical course and drug resistance in BCs. The results provide information about the long-term prognosis of IE in BCs for veterinarians and concerned owners, and may benefit breeders as well. [source] Sphenopalatine Endoscopic Ganglion Block: A Revision of a Traditional Technique for Cluster HeadacheTHE LARYNGOSCOPE, Issue 8 2006Giovanni Felisati MD The diagnosis of chronic cluster headache (CH), the most painful form of headache, is based on typical clinical features characterized by strictly unilateral pain with no side shift and ipsilateral oculofacial autonomic phenomena. The attacks occur several times a day for periods of 1 to 2 months in the episodic form of the disease or less frequently on a daily basis in the chronic form. The pathogenesis of CH involves the activation of parasympathetic nerve structures located within the sphenopalatine ganglion (SPG), which explains many of the associated symptoms, whereas the activation of the ipsilateral hypothalamic gray matter may explain its typical circadian and circannual periodicity. A number of surgical approaches have been tried in cases of chronic CH resistant to pharmacologic therapy, of which SPG blockade has been shown to have certain efficacy. We have adopted a new technique based on endoscopic ganglion blockade that approaches the pterigo-palatine fossa by way of the lateral nasal wall and consists of the injection of a mixture of local anesthetics and corticosteroids, which was performed in 20 selected patients with chronic CH, according to the International Headache Society criteria (18 male, 2 female; mean age 40 yr), who were selected for SPG blockade because they were totally drug resistant. The symptoms improved significantly, but always only temporarily, in 11 cases. These results should be considered rather good because, unlike other frequently used techniques, SPG blockade is not invasive and should therefore always be attempted before submitting patients to more invasive surgical approaches. [source] MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanismsTHE PROSTATE, Issue 14 2010Keitaro Kojima Abstract BACKGROUND Patients with hormone-refractory prostate cancer are treated with taxane drugs, but eventually become drug resistant. We aimed to elucidate the molecular mechanisms underlying paclitaxel resistance of hormone-refractory prostate cancer with a special focus on the roles of miR-34a and SIRT1. METHODS Paclitaxel-resistant cells (PC3PR) were generated from hormone-refractory PC3 cells. The expression levels of mRNA and miRNA were determined by reverse transcriptase PCR and those of protein were by Western blot analysis. Transfection of miRNA precursor or siRNA was performed using the liposome-mediated method. RESULTS MiR-34a over-expression and SIRT1 knockdown attenuated paclitaxel resistance of PC3PR cells. MiR-34a expression was reduced in PC3PR cells compared with PC3 cells, while the expression levels of HuR and Bcl2 as well as SIRT1 were elevated in PC3PR cells. Luciferase reporter assays revealed that both SIRT1 3,-UTR and promoter activities were higher in PC3PR cells than in PC3 cells. Introduction of miR-34a precursor into PC3PR cells resulted in decreases in HuR, Bcl2, and SIRT1 expression and inhibition of the SIRT1 3,-UTR activity. HuR knockdown reduced SIRT1 and Bcl2 expression. These results suggest that miR-34a not only directly but also indirectly via regulating HuR expression acts on the 3,-UTR of SIRT1 and Bcl2 mRNAs, thereby controlling their expression. Thus, in PC3PR cells, reduced expression of miR-34a confers paclitaxel resistance via up-regulating SIRT1 and Bcl2 expression. CONCLUSIONS MiR-34a and its downstream targets SIRT1 and Bcl2 play important roles in the development of paclitaxel resistance, all of which can be useful biomarkers and promising therapeutic targets for the drug resistance in hormone-refractory prostate cancer. Prostate 70: 1501,1512, 2010. © 2010 Wiley-Liss, Inc. [source] Coeliac disease, unilateral occipital calcifications, and drug-resistant epilepsy: successful lesionectomyACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005K. O. Nakken Purpose , To draw attention to the triad of coeliac disease (CD), occipital calcifications, and drug-resistant epilepsy, with focus on the outcome of epilepsy surgery. Methods , We describe a male patient who despite a diagnosis of CD from the age of 9 did not comply with the gluten-free diet. At the age of 11 he developed simple and complex partial seizures with visual symptoms, anxiety, and ambulatory automatisms. His epilepsy appeared to be drug resistant, and after having tried nine antiepileptic drugs (AEDs), alone or in combinations, he underwent a presurgical evaluation at the age of 30. Interictal standard electroencephalograms (EEGs) disclosed frequent biparieto-occipital epileptiform discharges. Computed tomography showed cortical,subcortical punctate calcifications in the right parieto-occipital region, where his seizures seemed to start, according to ictal EEG registrations from intracranial strip electrodes. Results , At the age of 31 he underwent epilepsy surgery. A 5 × 6 cm large area of the right parieto-occipital region was resected, including the area with calcifications. Except for a few short-lasting episodes of anxiety (simple partial seizures?) he has now been seizure-free for 12 years. AEDs were withdrawn 5 years ago. Postoperatively he was left with an upper left-sided quadrant anopsia, which is not bothering him. Conclusions , In patients with CD, unilateral occipital calcifications, and drug-resistant epilepsy, epilepsy surgery should be considered, as a lesionectomy might be very successful. [source] | ||||||||||