Can Animal Models of Disease Reliably Inform Human Studies?

H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials

Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure

Aesthetic outcome in patients after polymethyl-methacrylate (PMMA) cranioplasty - a questionnaire-based single-centre study

OBJECTIVES: Acquired skull deformities are common and most likely treated surgically by cranioplasty. Since data on patient aesthetic outcome after cranioplasty are rare in literature, we aimed to assess patient satisfaction after polymethyl-methacrylate (PMMA) cranioplasty in this study using a questionnaire. METHODS: A patient questionnaire was developed to evaluate the grade of satisfaction after surgery. After approval by the institutional ethical review board, we were allowed to send to all 115 patients, who received a cranioplasty from 2001 to 2008 at the University Hospital of Zurich, our questionnaire once to retrospectively analyze the patient response together with the patient hospital records. RESULTS: Out of 115 patients, 36 patients were lost to follow-up and our questionnaire was sent out once to 79 patients. Sixty-three of 79 patients replied to the questionnaire (79·7%) and 16 did not reply. Seventeen declined to participate in this study and out of the remaining 46 patients (58·2%, 18 women, mean age 54 years, range 20-83 years), who agreed to participate in this study, 22 (47·8%) judged their cranioplasty to be aesthetically 'excellent', 16 (34·8%) 'favorable' and 4 (8·7%) 'poor'. Another four patients (8·7%) were not satisfied, asking for a surgical revision. Patient age and gender was not related to the assessment of the aesthetic result. A higher satisfaction grade was found in patients with primary PMMA cranioplasty compared to PMMA cranioplasty implanted during a second surgery (Fisher's exact test, P = 0·031). A dent was strongly associated with absence of satisfaction (P<0·01, Fisher's exact test). CONCLUSION: Our questionnaire was suitable to assess patient satisfaction after cranioplasty. Localization of cranioplasty showed to be an important factor of aesthetic outcome, especially in the fronto-temporal region where a carefully planned reconstruction should be performed to guarantee an excellent grade of satisfaction after surgery