====== Kuopio ======
https://pshyvinvointialue.fi/neurokirurgian-palvelut
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Kuopio [[University Hospital]] (KUH) in [[Finland]] is a leading [[center]] for neurosurgical [[care]], providing both acute and elective services to the Eastern Finland region. The Department of Neurosurgery at KUH is integrated within the KUH NeuroCenter, which combines neurosurgery, neurology, neuroradiology, neurophysiology, and neurointensive care under one roof to ensure comprehensive and personalized treatment for patients with central nervous system disorders.
Key Services and Expertise:
Neurovascular Surgery: Specialists in microvascular neurosurgery and endovascular neuroradiology collaborate daily to evaluate and treat intracranial aneurysms and other vascular malformations.
Spinal Surgery: The department performs approximately 900 surgeries annually for patients suffering from radiating pain or weakness due to spinal nerve root or spinal cord entrapment.
Epilepsy Surgery: KUH is one of the national centers for epilepsy surgery in Finland, offering advanced diagnostics and surgical treatments for severe epilepsy cases.
Neuromodulation: The Pain Neuromodulation Research Group, led by Adjunct Professor Jukka Huttunen, focuses on treating chronic pain through neuromodulation techniques, combining clinical research with biomarker studies and machine learning.
kuopio.neurocenterfinland.fi
Advanced Surgical Facilities: KUH's operating rooms are equipped with modern neurosurgical technologies, including neuroanesthesia, operation microscopes with intraoperative fluorescence diagnostics, neuronavigation systems, and intraoperative neurophysiological monitoring.
Research and Development:
KUH places a strong emphasis on clinical research and quality control. The department has implemented structured interventions to optimize outpatient clinic operations, leading to increased efficiency and improved patient care. A study highlighted the benefits of adding a predictable neurosurgeon slot, resulting in a 7% increase in new patient visits.
Contact Information:
Address: Puijonlaaksontie 2, 70210 Kuopio, Finland
Phone: +358 44 717 6974
Email: finnhealth@pshyvinvointialue.fi
For more information, you can visit the KUH NeuroCenter's neurosurgery page or the FinnHealth neurosurgery section.
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Neurosurgery of NeuroCenter, Kuopio University Hospital, [[Finland]].
Ville E Korhonen
Virve Kärkkäinen
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In a Prospective Observational Case-Control Study Kärkkäinen et al. aimed to identify [[neuroinflammation]]-related [[protein]]s in [[tear fluid]] (TF) as potential [[biomarker]]s for early-stage [[Alzheimer’s disease]] (AD). The novelty lies in using a non-invasive biofluid (TF) and applying high-resolution proteomics.
2. Strengths
Non-invasive approach: Tear fluid collection via Schirmer strips offers a safe, patient-friendly method ideal for elderly populations.
[[Mass spectrometry]]-based [[proteomics]]: The use of label-free quantitative proteomics enhances the detection of subtle changes in protein expression without bias toward known candidates.
Clear [[case-control]] design: The inclusion of well-defined mild AD patients (CDR 0.5–1, MMSE 23.8 ± 2.8) and cognitively healthy controls (MMSE 28.9 ± 1.4) allows for meaningful comparisons.
Focus on [[neuroinflammation]]: Targeting neuroinflammatory pathways aligns with current hypotheses that inflammation plays a central role in early [[Alzheimer’s disease pathogenesis]].
Identified candidate markers: The study reports 14 differentially expressed proteins, several of which (e.g., [[SERPINA3]], [[ORM1]], [[SPARCL1]]) have known links to inflammatory and neurodegenerative processes.
3. Limitations
Small [[sample size]]: With only 19 AD cases and 34 controls, the study is underpowered for broad generalization or robust statistical correction for [[confounding]] variables.
Cross-sectional nature: Being observational and cross-sectional, it does not address causality or longitudinal stability of these [[biomarker]]s.
Lack of [[external validation]]: The findings are not validated in an independent [[cohort]] or in [[cerebrospinal fluid]]/[[plasma]], limiting translational relevance.
Omission of [[confounding]] factors: Factors like dry eye syndrome, medications, systemic inflammation, or comorbidities were not extensively controlled for, which could significantly affect TF protein composition.
[[Overinterpretation]] risk: While the link between neuroinflammation and AD is established, asserting that these TF proteins are early biomarkers of AD is premature without longitudinal or mechanistic validation.
Lack of [[machine learning]] or biomarker signature development: Despite the proteomic data, no predictive models or ROC analyses were reported to evaluate diagnostic utility.
4. Contribution to the Field
This study provides preliminary evidence that tear fluid proteins may reflect neuroinflammatory changes in early AD. It adds to a growing interest in peripheral biomarkers and supports the exploration of eye-brain connections in [[neurodegeneration]].
5. Recommendations for Future Research
Conduct longitudinal studies to assess temporal evolution of TF biomarkers in preclinical and prodromal AD.
Validate the identified proteins in larger, multicentric cohorts.
Correlate TF protein changes with [[CSF]] biomarkers (Aβ, tau) and neuroimaging findings.
Explore multiplex assays or [[ELISA]]-based panels for potential [[clinical translation]].
Include confounder analysis (e.g., ocular surface disease, systemic inflammation).
Conclusion
This study is a promising [[proof-of-concept]] for using tear fluid as a diagnostic window into [[neurodegeneration]], particularly AD. However, the small sample size, lack of [[validation]], and cross-sectional design limit its current [[clinical utility]]. It should be viewed as a hypothesis-generating work that warrants more rigorous, larger-scale follow-up studies
((Kärkkäinen V, Saari T, Rusanen M, Uusitalo H, Leinonen V, Thiede B, Kaarniranta K, Koivisto AM, Utheim TP. [[Neuroinflammation]] [[Marker]]s in [[Tear Fluid]] of Mild [[Alzheimer's Disease]]. J Mol Neurosci. 2025 Jun 5;75(2):73. doi: 10.1007/s12031-025-02368-x. PMID: 40471493.))
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20: Lillemäe K, Luostarinen T, Reinikainen M, Bendel S, Laitio R, Hoppu S, Ala-
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23: Räisänen S, Huttunen J, Huuskonen TJ, von Und Zu Fraunberg M, Koivisto T,
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MKM, Yasuda C, Bonilha L, Gleichgerrcht E, Focke NK, Kreilkamp BAK, Domin M, von
Podewils F, Langner S, Rummel C, Rebsamen M, Wiest R, Martin P, Kotikalapudi R,
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S, Weber B, Depondt C, Absil J, Carr SJA, Abela E, Richardson MP, Devinsky O,
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32: Eskelinen M, Saimanen I, Koskela R, Holopainen A, Selander T, Eskelinen M.
Plasma Concentration of the Lipid Peroxidation (LP) Biomarker 4-Ηydroxynonenal
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Jan;68(1):20-7. doi: 10.1227/NEU.0b013e3181ff33ca. PMID: 21099703.
419: Leinonen V, Koivisto AM, Savolainen S, Rummukainen J, Tamminen JN, Tillgren
T, Vainikka S, Pyykkö OT, Mölsä J, Fraunberg M, Pirttilä T, Jääskeläinen JE,
Soininen H, Rinne J, Alafuzoff I. Amyloid and tau proteins in cortical brain
biopsy and Alzheimer's disease. Ann Neurol. 2010 Oct;68(4):446-53. doi:
10.1002/ana.22100. PMID: 20976765.
420: Lehecka M, Dashti R, Laakso A, van Popta JS, Romani R, Navratil O,
Kivipelto L, Kivisaari R, Foroughi M, Kokuzawa J, Lehto H, Niemelä M, Rinne J,
Ronkainen A, Koivisto T, Jääskelainen JE, Hernesniemi J. Microneurosurgical
management of anterior choroid artery aneurysms. World Neurosurg. 2010
May;73(5):486-99. doi: 10.1016/j.wneu.2010.02.001. PMID: 20920932.
421: Sinikallio S, Lehto SM, Aalto T, Airaksinen O, Kröger H, Viinamäki H.
Depressive symptoms during rehabilitation period predict poor outcome of lumbar
spinal stenosis surgery: a two-year perspective. BMC Musculoskelet Disord. 2010
Jul 6;11:152. doi: 10.1186/1471-2474-11-152. PMID: 20604949; PMCID: PMC2913992.
422: Karamanakos PN, Koivisto T, Vanninen R, Khallaf M, Ronkainen A, Parviainen
I, Manninen H, von und zu Fraunberg M, Morgan MK, Jaaskelainen JE, Hernesniemi
J, Rinne J. The impact of endovascular management on the outcome of aneurysmal
subarachnoid hemorrhage in the elderly in eastern Finland. Acta Neurochir
(Wien). 2010 Sep;152(9):1493-502. doi: 10.1007/s00701-010-0714-6. Epub 2010 Jul
1. PMID: 20593208.
423: Karamanakos PN, Jaaskelainen JE, Alafuzoff I, Pirinen E, Vanninen R,
Silvennoinen S, Sankilampi U, Immonen A. Malignant giant cell tumor in the
posterior fossa of a neonate. J Neurosurg Pediatr. 2010 Mar;5(3):277-82. doi:
10.3171/2009.10.PEDS09453. PMID: 20192645.
424: Huttunen T, von und zu Fraunberg M, Frösen J, Lehecka M, Tromp G, Helin K,
Koivisto T, Rinne J, Ronkainen A, Hernesniemi J, Jääskeläinen JE. Saccular
intracranial aneurysm disease: distribution of site, size, and age suggests
different etiologies for aneurysm formation and rupture in 316 familial and 1454
sporadic eastern Finnish patients. Neurosurgery. 2010 Apr;66(4):631-8;
discussion 638. doi: 10.1227/01.NEU.0000367634.89384.4B. PMID: 20190670.
425: Simula S, Koivisto T, Rinne J, Vanninen R, Jäkälä P. Hemikraniektomia
pahanlaatuisen aivoinfarktin hoidossa [Malignant cerebral infarction and
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426: Celik O, Piippo A, Romani R, Navratil O, Laakso A, Lehecka M, Dashti R,
Niemelä M, Rinne J, Jääskeläinen JE, Hernesniemi J. Management of dural
arteriovenous fistulas - Helsinki and Kuopio experience. Acta Neurochir Suppl.
2010;107:77-82. doi: 10.1007/978-3-211-99373-6_12. PMID: 19953375.
427: Romani R, Laakso A, Niemelä M, Lehecka M, Dashti R, Isarakul P, Celik O,
Navratil O, Lehto H, Kivisaari R, Hernesniemi J. Microsurgical principles for
anterior circulation aneurysms. Acta Neurochir Suppl. 2010;107:3-7. doi:
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428: Bendel P, Koivisto T, Aikiä M, Niskanen E, Könönen M, Hänninen T, Vanninen
R. Atrophic enlargement of CSF volume after subarachnoid hemorrhage: correlation
with neuropsychological outcome. AJNR Am J Neuroradiol. 2010 Feb;31(2):370-6.
doi: 10.3174/ajnr.A1804. Epub 2009 Nov 26. PMID: 19942696; PMCID: PMC7964141.
429: Koivisto T, Jääskeläinen JE. Chronic subdural haematoma--to drain or not to
drain? Lancet. 2009 Sep 26;374(9695):1040-1. doi: 10.1016/S0140-6736(09)61682-2.
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430: Karamanakos PN, Varis J, Ronkainen A, Koivisto T, Rinne J, Jaaskelainen JE.
Chronic subdural haematoma after endoscopic treatment of a supracellar arachnoid
cyst. Acta Neurol Belg. 2009 Jun;109(2):149-51. PMID: 19681449.
431: Kaikkonen MU, Lesch HP, Pikkarainen J, Räty JK, Vuorio T, Huhtala T,
Taavitsainen M, Laitinen T, Tuunanen P, Gröhn O, Närvänen A, Airenne KJ, Ylä-
Herttuala S. (Strept)avidin-displaying lentiviruses as versatile tools for
targeting and dual imaging of gene delivery. Gene Ther. 2009 Jul;16(7):894-904.
doi: 10.1038/gt.2009.47. Epub 2009 May 14. PMID: 19440224.
432: Myllymaa S, Myllymaa K, Korhonen H, Töyräs J, Jääskeläinen JE, Djupsund K,
Tanila H, Lappalainen R. Fabrication and testing of polyimide-based
microelectrode arrays for cortical mapping of evoked potentials. Biosens
Bioelectron. 2009 Jun 15;24(10):3067-72. doi: 10.1016/j.bios.2009.03.028. Epub
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433: Sinikallio S, Aalto T, Koivumaa-Honkanen H, Airaksinen O, Herno A, Kröger
H, Viinamäki H. Life dissatisfaction is associated with a poorer surgery outcome
and depression among lumbar spinal stenosis patients: a 2-year prospective
study. Eur Spine J. 2009 Aug;18(8):1187-93. doi: 10.1007/s00586-009-0955-3. Epub
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434: Lehecka M, Dashti R, Romani R, Celik O, Navratil O, Kivipelto L, Kivisaari
R, Shen H, Ishii K, Karatas A, Lehto H, Kokuzawa J, Niemelä M, Rinne J,
Ronkainen A, Koivisto T, Jääskelainen JE, Hernesniemi J. Microneurosurgical
management of internal carotid artery bifurcation aneurysms. Surg Neurol. 2009
Jun;71(6):649-67. doi: 10.1016/j.surneu.2009.01.028. Epub 2009 Mar 27. PMID:
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435: Purdy M, Nykopp TK, Kainulainen S, Pääkkönen M. Division of the hepatic
branch of the anterior vagus nerve in fundoplication: effects on gallbladder
function. Surg Endosc. 2009 Sep;23(9):2143-6. doi: 10.1007/s00464-008-0242-0.
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436: Hernesniemi J, Romani R, Albayrak BS, Lehto H, Dashti R, Ramsey C 3rd,
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Microsurgical management of pineal region lesions: personal experience with 119
patients. Surg Neurol. 2008 Dec;70(6):576-83. doi: 10.1016/j.surneu.2008.07.019.
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437: Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Någren K,
Tapiola T, Pirttilä T, Rinne J, Jääskeläinen JE, Soininen H, Rinne JO.
Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by
positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch
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438: Danner N, Julkunen P, Könönen M, Säisänen L, Nurkkala J, Karhu J. Navigated
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439: Julkunen P, Jauhiainen AM, Westerén-Punnonen S, Pirinen E, Soininen H,
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440: Lehecka M, Dashti R, Hernesniemi J, Niemelä M, Koivisto T, Ronkainen A,
Rinne J, Jääskeläinen J. Microneurosurgical management of aneurysms at the A2
segment of anterior cerebral artery (proximal pericallosal artery) and its
frontobasal branches. Surg Neurol. 2008 Sep;70(3):232-46; discussion 246. doi:
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441: Lehecka M, Dashti R, Hernesniemi J, Niemelä M, Koivisto T, Ronkainen A,
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442: Lehecka M, Dashti R, Hernesniemi J, Niemelä M, Koivisto T, Ronkainen A,
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2008 Oct;70(4):352-67; discussion 367. doi: 10.1016/j.surneu.2008.03.017. Epub
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443: Hernesniemi J, Dashti R, Lehecka M, Niemelä M, Rinne J, Lehto H, Ronkainen
A, Koivisto T, Jääskeläinen JE. Microneurosurgical management of anterior
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444: Lehecka M, Lehto H, Niemelä M, Juvela S, Dashti R, Koivisto T, Ronkainen A,
Rinne J, Jääskeläinen JE, Hernesniemi JA. Distal anterior cerebral artery
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Mar;62(3):590-601; discussion 590-601. doi: 10.1227/01.neu.0000317307.16332.03.
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445: Mahindu A, Koivisto T, Ronkainen A, Rinne J, Assaad N, Morgan MK.
Similarities and differences in aneurysmal subarachnoid haemorrhage between
eastern Finland and northern Sydney. J Clin Neurosci. 2008 Jun;15(6):617-21.
doi: 10.1016/j.jocn.2007.08.018. Epub 2008 Apr 18. PMID: 18395449.
446: Mustonen T, Koivisto T, Vanninen R, Hänninen T, Vapalahti M, Hernesniemi J,
Kuikka JT, Vanninen E. Heterogeneity of cerebral perfusion 1 week after
haemorrhage is an independent predictor of clinical outcome in patients with
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Oct;79(10):1128-33. doi: 10.1136/jnnp.2007.142851. Epub 2008 Mar 20. PMID:
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447: Hernesniemi J, Romani R, Dashti R, Albayrak BS, Savolainen S, Ramsey C 3rd,
Karatas A, Lehto H, Navratil O, Niemelä M. Microsurgical treatment of third
ventricular colloid cysts by interhemispheric far lateral transcallosal approach
--experience of 134 patients. Surg Neurol. 2008 May;69(5):447-53; discussion
453-6. doi: 10.1016/j.surneu.2007.11.005. Epub 2008 Mar 4. PMID: 18295836.
448: Bendel P, Koivisto T, Könönen M, Hänninen T, Hurskainen H, Saari T,
Vapalahti M, Hernesniemi J, Vanninen R. MR imaging of the brain 1 year after
aneurysmal subarachnoid hemorrhage: randomized study comparing surgical with
endovascular treatment. Radiology. 2008 Feb;246(2):543-52. doi:
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449: Dashti R, Hernesniemi J, Lehto H, Niemelä M, Lehecka M, Rinne J, Porras M,
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management of proximal anterior cerebral artery aneurysms. Surg Neurol. 2007
Oct;68(4):366-77. doi: 10.1016/j.surneu.2007.07.084. PMID: 17905060.
450: Dashti R, Hernesniemi J, Niemelä M, Rinne J, Lehecka M, Shen H, Lehto H,
Albayrak BS, Ronkainen A, Koivisto T, Jääskeläinen JE. Microneurosurgical
management of distal middle cerebral artery aneurysms. Surg Neurol. 2007
Jun;67(6):553-63. doi: 10.1016/j.surneu.2007.03.023. PMID: 17512323.
451: Dashti R, Hernesniemi J, Niemelä M, Rinne J, Porras M, Lehecka M, Shen H,
Albayrak BS, Lehto H, Koroknay-Pál P, de Oliveira RS, Perra G, Ronkainen A,
Koivisto T, Jääskeläinen JE. Microneurosurgical management of middle cerebral
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452: Leinonen V, Airaksinen M, Taimela S, Kankaanpää M, Kukka A, Koivisto T,
Airaksinen O. Low back pain suppresses preparatory and triggered upper-limb
activation after sudden upper-limb loading. Spine (Phila Pa 1976). 2007 Mar
1;32(5):E150-5. doi: 10.1097/01.brs.0000256886.94791.94. PMID: 17334276.
453: Soppi V, Kokki H, Koivisto T, Lehtonen M, Helin-Tanninen M, Lehtola S,
Rinne J. Early-phase pharmacokinetics of enteral and parenteral nimodipine in
patients with acute subarachnoid haemorrhage - a pilot study. Eur J Clin
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454: Dashti R, Rinne J, Hernesniemi J, Niemelä M, Kivipelto L, Lehecka M,
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455: Hernesniemi J, Niemelä M, Dashti R, Karatas A, Kivipelto L, Ishii K, Rinne
J, Ronkainen A, Peláez JG, Koivisto T, Kivisaari R, Shen H, Lehecka M, Frösen J,
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fast surgery. Surg Technol Int. 2006;15:305-10. PMID: 17029189.
456: Ronkainen A, Niskanen M, Auvinen A, Aalto J, Luosujärvi R. Cervical spine
surgery in patients with rheumatoid arthritis: longterm mortality and its
determinants. J Rheumatol. 2006 Mar;33(3):517-22. PMID: 16511921.
457: Hernesniemi J, Niemelä M, Karatas A, Kivipelto L, Ishii K, Rinne J,
Ronkainen A, Koivisto T, Kivisaari R, Shen H, Lehecka M, Frösen J, Piippo A,
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458: Hernesniemi J, Ishii K, Niemelä M, Kivipelto L, Fujiki M, Shen H.
Subtemporal approach to basilar bifurcation aneurysms: advanced technique and
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459: Koskela AK, Sudah M, Berg MH, Kärjä VJ, Mustonen PK, Kataja V, Vanninen RS.
Add-on device for stereotactic core-needle breast biopsy: how many biopsy
specimens are needed for a reliable diagnosis? Radiology. 2005 Sep;236(3):801-9.
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460: Niskanen M, Koivisto T, Rinne J, Ronkainen A, Pirskanen S, Saari T,
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treatment for unruptured intracranial aneurysms. J Neurosurg Anesthesiol. 2005
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461: Luukkonen MT. Medial facetectomy in recurrent lumbar nerve root
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462: Immonen A, Vapalahti M, Tyynelä K, Hurskainen H, Sandmair A, Vanninen R,
Langford G, Murray N, Ylä-Herttuala S. AdvHSV-tk gene therapy with intravenous
ganciclovir improves survival in human malignant glioma: a randomised,
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463: Niskanen M, Koivisto T, Ronkainen A, Rinne J, Ruokonen E. Resource use
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treatment. Neurosurgery. 2004 May;54(5):1081-6; discussion 1086-88. doi:
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464: Immonen A, Jutila L, Kälviäinen R, Mervaala E, Partanen K, Partanen J,
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465: Kokki H, Ylönen P, Heikkinen M, Reinikainen M. Levobupivacaine for
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466: Reinikainen M, Hedman A, Pelkonen O, Ruokonen E. Cardiac arrest after
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467: van Groen T, Liu L, Ikonen S, Kadish I. Diffuse amyloid deposition, but not
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468: Immonen A, Jutila L, Könönen M, Mervaala E, Partanen J, Puranen M, Rinne J,
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469: Leinonen V, Määttä S, Taimela S, Herno A, Kankaanpää M, Partanen J,
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470: Kadish I, Van Groen T. Differences in lesion-induced hippocampal plasticity
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471: Ropponen KM, Kankkunen JP, Ronkainen A, Vihavainen M, Alafuzoff I.
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473: Koivisto T, Vanninen E, Vanninen R, Kuikka J, Hernesniemi J, Vapalahti M.
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474: Savolainen S, Hurskainen H, Paljärvi L, Alafuzoff I, Vapalahti M. Five-year
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475: Kadish I, Pradier L, van Groen T. Transgenic mice expressing the human
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476: Ronkainen A, Niskanen M, Rinne J, Koivisto T, Hernesniemi J, Vapalahti M.
Evidence for excess long-term mortality after treated subarachnoid hemorrhage.
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477: Koivisto T, Vapalahti M, Parviainen I, Takala J. Gastric tonometry after
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478: Savolainen S, Karhu J, Pääkkönen A, Paljärvi L, Partanen J, Alafuzoff I,
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479: Koivisto T, Vanninen R, Hurskainen H, Saari T, Hernesniemi J, Vapalahti M.
Outcomes of early endovascular versus surgical treatment of ruptured cerebral
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480: Simula S, Lakka T, Kuikka J, Laitinen T, Remes J, Kettunen R, Hartikainen
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481: Savolainen S, Laakso MP, Paljärvi L, Alafuzoff I, Hurskainen H, Partanen K,
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483: Puoliväli J, Miettinen R, Pradier L, Riekkinen P Jr. Apolipoprotein
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484: Herno A, Airaksinen O, Saari T, Pitkänen M, Manninen H, Suomalainen O.
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485: Savolainen S, Paljärvi L, Vapalahti M. Prevalence of Alzheimer's disease in
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486: Herno A, Partanen K, Talaslahti T, Kaukanen E, Turunen V, Suomalainen O,
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487: Ronkainen A, Niskanen M, Piironen R, Hernesniemi J. Familial subarachnoid
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