When feasible, robotic-assisted surgery is an acceptable procedure for resection of both primary and recurrent oropharyngeal tumors. Trial Registration clinicaltrials.gov Identifier: NCT00473564.
Objectives/Hypothesis-To evaluate outcomes of salvage surgery with free flap reconstruction for recurrent squamous cell carcinoma of the oropharynx and oral cavity with increased use of chemoradiotherapy.Study Design-Retrospective patient review.Methods-All patients undergoing salvage surgery with free flap reconstruction for oropharynx (n = 36) and oral cavity (n = 36) squamous cell carcinomas between January 2001 and January 2008 were obtained. Mean follow-up was 14 months. Previous chemoradiotherapy was used in 40% and radiotherapy alone in 60%.Results-Complications were more frequent in oropharynx than oral cavity tumors (36% and 14%, respectively; P = .05) requiring more secondary procedures (15 for oropharynx vs. six for oral cavity). Few patients returned to a normal diet (8%), and a majority retained an enterogastric feeding tube (56%). Median survival overall following salvage surgery was 44.8 months for oral cavity and 53.8 months for oropharynx head and neck squamous cell carcinoma. Overall estimated 1-, 2-, and 5-year observed survivals were 98%, 77.2%, and 43.7%, respectively. Twelve patients had a disease-free interval of <6 months, 92% of whom died of disease. Of 17 patients with disease at the primary site and involved regional lymph nodes, 94% died of disease.Conclusions-Salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal tumors after chemoradiotherapy has acceptable morbidity and similar cure rates as salvage following radiotherapy without chemotherapy. Concurrent nodal recurrence and short disease-free interval are associated with reduced cure rates. A significant proportion will require enterogastric feeding and few will tolerate a normal diet.
Despite its being the most efficacious drug for symptom reversal in Parkinson's disease (PD), there is concern that chronic levodopa (L-DOPA) treatment may be detrimental. In this paper we review the potential for L-DOPA to 1). autoxidize from a catechol to a quinone, and 2). generate other reactive oxygen species (ROS). Overt toxicity and neuroprotective effects of L-DOPA, both in vivo and in vitro, are described in the context of whether L-DOPA may accelerate or delay progression of human Parkinson's disease.
L-Dihydroxyphenylalanine (L: -DOPA), the anti-parkinsonian drug affording the greatest symptomatic relief of parkinsonian symptoms, is still misunderstood in terms of its neurotoxic potential and the mechanism by which generated dopamine (DA) is able to exert an effect despite the absence of DA innervation of target sites in basal ganglia. This review summaries important aspects and new developments on these themes. On the basis of L: -DOPA therapy in animal models of Parkinson's disease, it appears that L: -DOPA is actually neuroprotective, not neurotoxic, as indicated by L: -DOPA's reducing striatal tissue content of the reactive oxygen species, hydroxyl radical (HO(*)), and by leaving unaltered the extraneuronal in vivo microdialysate level of HO(*). In addition, the potential beneficial anti-parkinsonian effect of L: -DOPA is actually increased because of the fact that the basal ganglia are largely DA-denervated. That is, from in vivo microdialysis studies it can be clearly demonstrated that extraneuronal in vivo microdialysate DA levels are actually higher in the DA-denervated vs. the intact striatum of rats - owing to the absence of DA transporter (i.e., uptake sites) on the absent DA nerve terminal fibers in parkinsonian brain. In essence, there are fewer pumps removing DA from the extraneuronal pool. Finally, the undesired motor dyskinesias that commonly accompany long-term L: -DOPA therapy, can be viewed as an outcome of L: -DOPA's sensitizing DA receptors (D(1)-D(5)), an effect easily replicated by repeated DA agonist treatments (especially agonist of the D(2) class) in animals, even if the brain is not DA-denervated. The newest findings demonstrate that L: -DOPA induces BDNF release from corticostriatal fibers, which in-turn enhances the expression of D(3) receptors; and that this effect is associated with motor dyskinesias (and it is blocked by D(3) antagonists). The recent evidence on mechanisms and effects of L: -DOPA increases our understanding of this beneficial anti-parkinsonian drug, and can lead to improvements in L: -DOPA effects while providing avenues for reducing or eliminating L: -DOPA's deleterious effects.
Background/Aims: Minimizing bleeding during transnasal resections of sinonasal tumors is imperative for optimizing visualization and decreasing complications. The purpose of the present study was to determine whether radiofrequency coblation decreases blood loss during endoscopic tumor removal. Methods: Sinonasal/skull base tumors treated in 2008 with endoscopic techniques were reviewed. The data collected included demographics, histopathology, technique, duration, complications and estimated blood loss (EBL). Full operative videoendoscopy was available in all cases and scored by the authors using the 11-point Wormald surgical field grading scale. Results: Twenty-three patients (average age: 46 years) with sinonasal or skull base tumors treated with transnasal endoscopic techniques were identified. Coblation was used in 10 cases. The sinus/skull base tumors included were esthesioneuroblastoma (n = 6), melanoma (n = 3), squamous cell carcinoma (n = 3), inverted papilloma (n = 3), adenocarcinoma (n = 2), intracranial dermoid cyst (n = 2), adenoid cystic carcinoma (n = 1), craniopharyngioma (n = 1), fibromyxosarcoma (n = 1) and undifferentiated carcinoma (n = 1). The use of the coblation device was associated with a significant decrease in all categories including EBL (350 vs. 1,000 ml; p = 0.0001), EBL per operative time (66 vs. 166 ml/h; p = 0.0001) and Wormald grade (3.3 vs. 6.4; p = 0.0001). Conclusion: Radiofrequency coblation significantly decreased blood loss during endoscopic tumor removal and is a useful tool in the armamentarium of the endoscopic skull base surgeon.
The process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of neuronal denervation. Dopamine (DA) RSS (DARSS) similarly occurs after DA denervation, and this process is invoked in neuropsychiatric and neurodegenerative disorders. From studies largely over the past 25 years, much has been learned regarding DARSS. For example, overt D1 DARSS occurs after perinatal destruction of nigrostriatal DA fibers. However, following perinatal destruction of DA innervation, the most-prominent behavioral effects of a D1 agonist are observed after a series of D1 agonist treatments--a process known as priming of D1 DA receptors. Moreover, perinatal lesioning of DA fibers produces prominent serotonin (5-HT) RSS, and in fact 5-HT RSS appears to modulate D1 DA RSS. In rodents, receptor supersensitization by these means appears to be irreversible. In contrast to the observed D1 DARSS, D2 DARSS apparently does not occur after perinatal DA denervation. Also, while repeated D1 agonist treatment of intact rats has no observable effect, repeated D2 agonist treatments, during or after the ontogenetic phase, produces prominent life-long D2 RSS. The process may have an association with substance abuse. Therefore, production of D1 and D2 DARSS occurs by different means and under different circumstances, and in association with perhaps different neuronal phenotypes, and with greater incidence in either intact (D2) or DA-lesioned counterparts (D1). The physiological consequence of RSS are multiple.
For more than 50 years, heavy metal exposure during pre- or post-natal ontogeny has been known to produce long-lived hyperactivity in rodents. Global brain injury produced by neonatal hypoxia also produced hyperactivity, as did (mainly) hippocampal injury produced by ontogenetic exposure to X-rays, and (mainly) cerebellar injury produced by the ontogenetic treatments with the antimitotic agent methylazoxymethanol or with polychlorinated biphenyls (PCBs). More recently, ontogenetic exposure to nicotine has been implicated in childhood hyperactivity. Because attention deficits most often accompany the hyperactivity, all of the above treatments have been used as models of attention deficit hyperactivity disorder (ADHD). However, the causation of childhood hyperactivity remains unknown. Neonatal 6-OHDA-induced dopaminergic denervation of rodent forebrain also produces hyperactivity - and this model, or variations of it, remain the most widely-used animal model of ADHD. In all models, amphetamine (AMPH) and methylphenidate (MPH), standard treatments of childhood ADHD, typically attenuate the hyperactivity and/or attention deficit. On the basis of genetic models and the noted animal models, monoaminergic phenotypes appear to most-closely attend the behavioral dysfunctions, notably dopaminergic, noradrenergic and serotoninergic systems in forebrain (basal ganglia, nucleus accumbens, prefrontal cortex). This paper describes the various pharmacological models of ADHD and attempts to ascribe a neuronal phenotype with specific brain regions that may be associated with ADHD.
RCSN-3 cells are a cloned cell line derived from the substantia nigra of an adult rat. The cell line grows in monolayer and does not require differentiation to express catecholaminergic traits, such as (i) tyrosine hydroxylase; (ii) dopamine release; (iii) dopamine transport; (iv) norepinephrine transport; (v) monoamine oxidase (MAO)-A expression, but not MAO-B; (vi) formation of neuromelanin; (vii) VMAT-2 expression. In addition, this cell line expresses serotonin transporters, divalent metal transporter, DMT1, dopamine receptor 1 mRNA under proliferating conditions, and dopamine receptor 5 mRNA after incubation with dopamine or dicoumarol. Expression of dopamine receptors D(2), D(3) and D(4) mRNA were not detected in proliferating cells or when the cells were treated with dopamine, CuSO(4), dicoumarol or dopamine-copper complex. Angiotensin II receptor mRNA was also found to be expressed, but it underwent down regulation in the presence of aminochrome. Total quinone reductase activity corresponded 94% to DT-diaphorase. The cells also express antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. This cell line is a suitable in vitro model for studies of dopamine metabolism, since under proliferating conditions the cells express all the pertinent markers.
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