Genetics and molecular biology of ciliary disorders

Contains fulltext : 88535.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 26 januari 2010Promotor : Slobbe-Knoers, V.V.A.M. Co-promotor : Roepman, R.220 p

Medical genetics of ciliopathies.

Item does not contain fulltex

Scrutinizing ciliopathies by unraveling ciliary interaction networks

Research of cilia has gained significant momentum in the last 15 years, as an increasing number of human genetic diseases were found to be caused by disruption of a protein that localizes to cilia. These ciliopathies are as diverse as the functions of the associated proteins, covering a spectrum of overlapping phenotypes that ranges from relatively mild characteristics in isolated tissues with a late onset, to severe defects of multiple tissues with an onset early in embryogenesis that is incompatible with life. As cilia harbour many receptors and components of key signaling cascades, such as Hedgehog, Wnt, Notch and Hippo signaling, disruption of ciliary function has severe consequences. Recent (affinity) proteomics studies have focused on the composition and dynamics of ciliary protein interaction networks. This has unveiled important knowledge about the highly ordered, interconnected but very dynamic nature of the cilium as a molecular machine. Disruption of the members of the same functional modules of this machine leads to similar phenotypes, and detailed analyses of the binding repertoire, the biochemical properties and the biological functions of these modules have yielded new ciliopathy genes as well as new insights into the pathogenic mechanisms underlying ciliopathies

Human volunteer study with PGME: Eye irritation during vapour exposure

The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated measures design. Each subject was exposed for 2.5 h to each of the three exposure conditions that were spaced 7 days apart. The exposure sequences were counterbalanced and the exposure to the test substance and the effect measurements were conducted in a double-blind fashion. During all exposure sessions, 20 ppm diethyl ether was used as a 'masking agent' for vapour exposure. Measurements of pre- and post exposure eye redness, corneal thickness, tear film break-up time, conjunctival epithelial damage, blinking frequency, and subjective ratings on discomfort were used to evaluate the possible irritating effects of PGME. The results indicated no significant treatment effects for any of the objective parameters. Results of the subjective ratings indicated very slight effects on the eyes in the 150 ppm PGME condition only. No significant effects of treatment were found for the remaining questions concerning the perceived intensity of the smell in the room, the (un)pleasantness of the smell, the perceived effects on the skin, effects on the throat, shivering, muscle aching, and intestinal cramps. In conclusion, the results of the present study indicated minimal subjective eye effects at 150 ppm only, and no impact on the objective measures of eye irritation at either of the two exposure levels. It was concluded that the no adverse effect concentration for eye irritation due to PGME vapour was at least 150 ppm. © 2003 Elsevier Science Ireland Ltd. All rights reserved

The KOUNCIL Consortium: From Genetic Defects to Therapeutic Development for Nephronophthisis

Contains fulltext : 191425.pdf (publisher's version ) (Open Access

Evaluation of anesthesia in endoscopic strip craniectomy: A review of 121 patients

OBJECTIVE: The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in endoscopic strip craniectomy in order to improve anesthesiological care. MATERIALS AND METHODS: This is a retrospective patient cohort study of our first 121 patients treated by endoscopic strip craniectomy. Preoperative as well as intra- and postoperative anesthesiological and neurological parameters were analyzed. Furthermore, the need for intensive care unit admission, blood loss, and blood transfusion rate were measured. RESULTS: The mean age of patients was 3.9 months (standard deviation = 1) at a mean weight of 6.3 kg (standard deviation = 1.3). Comorbidity was registered in 13 (11%) patients of which 5 had syndrome-related comorbidities. Mean duration of anesthesia was 131 minutes (standard deviation = 32) . One hundred and sixteen patients were induced by mask induction with sevoflurane and 5 patients were induced intravenously. In 10 patients, mild intraoperative hypothermia (between 35 and 36 degrees Celsius) occurred. The mean estimated blood loss was 35.4 mL (standard deviation = 28.9) and blood transfusion rate was 21.5%. Brief and small intraoperative oxygen saturation drops were common during this study. No indication for venous air embolism was found based on endtidal CO2 . Postoperative temperature above 38 degrees Celsius occurred 16 times and benign deviations in postoperative cardiopulmonary parameters occurred in 17 patients. Postoperative pain management was mainly established by paracetamol and low-dose morphine when necessary. No postoperative neurological symptoms were reported and no deaths occurred. CONCLUSION: These patients had a relatively short intraoperative course with stable vital parameters during surgery. We report a low incidence of significant venous air embolism, a blood transfusion rate of 21% and only minor perioperative disturbances in vital parameters

Intraoperative complications in pediatric neurosurgery: review of 1807 cases

OBJECTIVE Minimal literature exists on the intraoperative complication rate of pediatric neurosurgical procedures with respect to both surgical and anesthesiological complications. The aim of this study, therefore, was to establish intraoperative complication rates to provide patients and parents with information on which to base their informed consent and to establish a baseline for further targeted improvement of pediatric neurosurgical care. METHODS A clinical complication registration database comprising a consecutive cohort of all pediatric neurosurgical procedures carried out in a general neurosurgical department from January 1, 2004, until July 1, 2012, was analyzed. During the study period, 1807 procedures were performed on patients below the age of 17 years. RESULTS Sixty-four intraoperative complications occurred in 62 patients (3.5% of procedures). Intraoperative mortality was 0.17% (n = 3). Seventy-eight percent of the complications (n = 50) were related to the neurosurgical procedures, whereas 22% (n = 14) were due to anesthesiology. The highest intraoperative complication rates were for cerebrovascular surgery (7.7%) and tumor surgery (7.4%). The most frequently occurring complications were cerebrovascular complications (33%). CONCLUSIONS Intraoperative complications are not exceptional during pediatric neurosurgical procedures. Awareness of these complications is the first step in preventing them