Complex reconstructions in head and neck cancer surgery: decision making

Defects in head and neck after tumor resection often provide significant functional and cosmetic deformity. The challenge for reconstruction is not only the aesthetic result, but the functional repair. Cancer may involve composite elements and the in sano resection may lead to an extensive tissue defect. No prospective randomized controlled studies for comparison of different free flaps are available. There are many options to cover defects and restore function in the head and neck area, however we conclude from experience that nearly all defects in head and neck can be closed by 5 different free flaps: radial forearm flap, free fibula flap, anterior lateral thigh flap, lateral arm flap and parascapular flap

Effect of apomorphine on cognitive performance and sensorimotor gating in humans

Contains fulltext : 88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201

Pathways in the Drug Development for Alzheimer's Disease (1906-2016): A Bibliometric Study

Investments in drug development for Alzheimer's disease (AD) have not led to the availability of a treatment to cure or halt the progression of the disease. This study aimed to provide insights into the current lack of an effective therapy against AD by exploring the evolution of research paths in the scientific domains corresponding to fundamental, preclinical and clinical research from the identification of the disease in 1906 up to 2016. More specifically, the influence of the amyloid cascade hypothesis and use of animal models in the evolution of drug development for AD were explored. We used bibliometric analysis for the identification of research paths taken over time, including main path analysis, direct citation analysis and co-word analysis. The results show that the amyloid cascade hypothesis has played an important role in the evolution of research paths in the drug development process of AD. The preclinical domain and to a lesser extent the clinical domain, were found to be increasingly involved in the study of interventions modulating amyloid-beta related neurotoxicity over time in line with the fundamental domain predominantly focussing on amyloid-beta as the primary cause of AD. The results open up a discussion about lock-in, i.e. that decreasing options in the fundamental domain results in less room for manoeuvre in the preclinical and clinical domain

Pathways in the Drug Development for Alzheimer's Disease (1906-2016): A Bibliometric Study

Investments in drug development for Alzheimer's disease (AD) have not led to the availability of a treatment to cure or halt the progression of the disease. This study aimed to provide insights into the current lack of an effective therapy against AD by exploring the evolution of research paths in the scientific domains corresponding to fundamental, preclinical and clinical research from the identification of the disease in 1906 up to 2016. More specifically, the influence of the amyloid cascade hypothesis and use of animal models in the evolution of drug development for AD were explored. We used bibliometric analysis for the identification of research paths taken over time, including main path analysis, direct citation analysis and co-word analysis. The results show that the amyloid cascade hypothesis has played an important role in the evolution of research paths in the drug development process of AD. The preclinical domain and to a lesser extent the clinical domain, were found to be increasingly involved in the study of interventions modulating amyloid-beta related neurotoxicity over time in line with the fundamental domain predominantly focussing on amyloid-beta as the primary cause of AD. The results open up a discussion about lock-in, i.e. that decreasing options in the fundamental domain results in less room for manoeuvre in the preclinical and clinical domain