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- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 4. |
- Hamel, Wolfgang, et al.
(författare)
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The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part I. Surgical Technique for Tailoring Individualized Stereotactic Lesions
- 2016
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger AG. - 1011-6125 .- 1423-0372. ; 94:4, s. 240-253
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Tidskriftsartikel (refereegranskat)abstract
- During the 1950s through the 1970s, Hans Orthner and Fritz Roeder, two German neurologists from Gottingen, developed a sophisticated technique to perform functional stereotactic surgery with outstanding accuracy. They introduced direct air ventriculography performed in the same surgical session as the ablative stereotactic procedure. For individualized surgical targeting, Orthner prepared a stereo tactic atlas (>60 brains) with an ingenious brain-slicing device, the Gottinger macrotome. Brains were grouped based on similarity of six different head and ventricle measurements. A brain cluster representing the best match for a patient was selected for stereotactic targeting. Stereotactic lesions were tailored in an individual manner and shaped by stringing together multiple small coagulations following in-traoperative test stimulation. This was achieved from a single probe trajectory by using well-engineered string electrodes with calibrated curving and involved laborious calculations. Only high-frequency thermocoagulation was regarded as appropriate for lesioning. With this meticulous technique, the most advanced stereotactic procedures were performed, including bilateral pallidotomy that ultimately could be restricted to the ansa lenticularis and ventromedial hypothalamotomy, the most delicate stereotactic operation performed to date. Outside Gottingen, this technique has only been used by Prof. Dieter Muller in Hamburg, Germany. This elaborate stereotactic approach is widely unknown and deserves to be discussed in a historical context.
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| 5. |
- Hamel, Wolfgang, et al.
(författare)
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The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part II : Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era
- 2018
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 96:6, s. 353-363
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Forskningsöversikt (refereegranskat)abstract
- Before the advent of levodopa, pallidotomy was initially the most effective treatment for Parkinson disease, but it was soon superseded by thalamotomy. It is widely unknown that, similar to Leksell, 2 neurologists from Gottingen, Orthner and Roeder, perpetuated pallidotomy against the mainstream of their time. Postmortem studies demonstrated that true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. This was due to a unique and individually tailored stereotactic technique even allowing bilateral staged pallidotomies. In 1962, the long-term effects (3-year follow-up on average) of the first 18 out of 36 patients with staged bilateral pallidotomies were reported in great detail. Meticulous descriptions of each case indicate long-term improvements in parkinsonian rigidity and associated pain, as well as posture, gait, and akinesia (e.g., improved repetitive movements and arm swinging). Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement in speech, drooling, or seborrhea was observed. By 1962, the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up: 5 years). They also described alleviation of nonparkinsonian hyperkinetic disorders (e.g., hemiballism and chorea) with pallidotomy. The reported rates for surgical mortality and other complications had been remarkably low, even if compared to those reported after the revival of pallidotomy by Laitinen in the post-levodopa era. This applies also to bilateral pallidotomy performed with a positive risk-benefit ratio that has remained unparalleled to date. The intricate history of pallidotomy for movement disorders is incomplete without an appreciation of the achievements of the Gottingen group.
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