Publications by authors named "Ville Vuorinen"

16 Publications

  • Page 1 of 1

Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors.

Saf Sci 2020 Oct 11;130:104866. Epub 2020 Jun 11.

Department of Bioproducts and Biosystems, Aalto University, FI-00076 AALTO, Finland.

We provide research findings on the physics of aerosol and droplet dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2 during the current pandemic. We utilize physics-based modeling at different levels of complexity, along with previous literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets ( ) allows lingering in the air for ) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes , into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the individuals, who have been tested positive on COVID-19, could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. . By 3D scale-resolving computational fluid dynamics (CFD) simulations, we give various examples on the transport and dilution of aerosols ( ) over distances in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modelling. The developed model takes into account the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, 'exposure time' to virus containing aerosols is proposed to complement the traditional 'safety distance' thinking. We show that the exposure time to inhale aerosols could range from to or even to depending on the situation. The Monte-Carlo simulations, along with the theory, provide clear quantitative insight to the exposure time in different public indoor environments.
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http://dx.doi.org/10.1016/j.ssci.2020.104866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428778PMC
October 2020

Multiple formin proteins participate in glioblastoma migration.

BMC Cancer 2020 Jul 29;20(1):710. Epub 2020 Jul 29.

Laboratory Division, Department of Pathology, Turku University Hospital, Turku, Finland.

Background: The prognosis of glioblastoma remains poor, related to its diffuse spread within the brain. There is an ongoing search for molecular regulators of this particularly invasive behavior. One approach is to look for actin regulating proteins that might be targeted by future anti-cancer therapy. The formin family of proteins orchestrates rearrangement of the actin cytoskeleton in multiple cellular processes. Recently, the formin proteins mDia1 and mDia2 were shown to be expressed in glioblastoma in vitro, and their function could be modified by small molecule agonists. This finding implies that the formins could be future therapeutic targets in glioblastoma.

Methods: In cell studies, we investigated the changes in expression of the 15 human formins in primary glioblastoma cells and commercially available glioblastoma cell lines during differentiation from spheroids to migrating cells using transcriptomic analysis and qRT-PCR. siRNA mediated knockdown of selected formins was performed to investigate whether their expression affects glioblastoma migration. Using immunohistochemistry, we studied the expression of two formins, FHOD1 and INF2, in tissue samples from 93 IDH-wildtype glioblastomas. Associated clinicopathological parameters and follow-up data were utilized to test whether formin expression correlates with survival or has prognostic value.

Results: We found that multiple formins were upregulated during migration. Knockdown of individual formins mDia1, mDia2, FHOD1 and INF2 significantly reduced migration in most studied cell lines. Among the studied formins, knockdown of INF2 generated the greatest reduction in motility in vitro. Using immunohistochemistry, we demonstrated expression of formin proteins FHOD1 and INF2 in glioblastoma tissues. Importantly, we found that moderate/high expression of INF2 was associated with significantly impaired prognosis.

Conclusions: Formins FHOD1 and INF2 participate in glioblastoma cell migration. Moderate/high expression of INF2 in glioblastoma tissue is associated with worse outcome. Taken together, our in vitro and tissue studies suggest a pivotal role for INF2 in glioblastoma. When specific inhibiting compounds become available, INF2 could be a target in the search for novel glioblastoma therapies.
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http://dx.doi.org/10.1186/s12885-020-07211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391617PMC
July 2020

Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome.

Front Neurol 2018 9;9:223. Epub 2018 Apr 9.

Department of Biomaterials Science and Turku Clinical Biomaterials Centre--TCBC, Institute of Dentistry, University of Turku, Turku, Finland.

Background: In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known.

Objective: We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome.

Methods: A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions.

Results: Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% ( = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication ( = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications.

Conclusion: A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.
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http://dx.doi.org/10.3389/fneur.2018.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904383PMC
April 2018

Caring communication - The impact of interpersonal communication between physician and patient. Can smileys measure the quality of communication?

Duodecim 2017;133(8):735-41

The importance of communication in medical practice is widely recognized, but what is good communication in patient encounter? Feedback and surveys based on patient experience or "smileys" provide a narrow and often too insignificant view of communication. In addition to patient experience, communication benefits the information gathering by the physician and the patient, the patient's ability to promote his/her recovery, the physician's coping with workload, and the effectiveness of health care. In order to evaluate communication and improve it, one has to recognize the criteria and objectives of good communication. Medical communication that supports the rehabilitation of patients is reasonably good and responsible communication.
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January 2018

Somatostatin receptor 2A in gliomas: Association with oligodendrogliomas and favourable outcome.

Oncotarget 2017 Jul;8(30):49123-49132

Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.

Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses. SSTR2A staining intensity and its localization in tumor cells was evaluated and correlated with glioma entities and survival. Diagnoses included 101 glioblastomas (93 isocitrate dehydrogenase (IDH) -wildtype, 3 IDH-mutant, 5 not otherwise specified (NOS)), 60 astrocytomas (22 IDH-wildtype, 37 IDH-mutant, 1 NOS), and 23 oligodendrogliomas (19 IDH-mutant and 1p/19q-codeleted, 4 NOS). SSTR2A expression significantly associated with oligodendrogliomas (79% SSTR2A positive) compared to IDH-mutant or IDH-wildtype astrocytomas (27% and 23% SSTR2A positive, respectively), and especially glioblastomas of which only 13% were SSTR2A positive (p < 0.001, Fisher's exact test). The staining pattern in glioblastomas was patchy whereas more homogeneous membranous and cytoplasmic staining was detected in oligodendrogliomas. Positive SSTR2A was related to longer overall survival in grade II and III gliomas (HR 2.7, CI 1.2-5.8, p = 0.013). In conclusion, SSTR2A expression is infrequent in astrocytomas and negative in the majority of glioblastomas where it is of no prognostic significance. In contrast, oligodendrogliomas show intense membranous and cytoplasmic SSTR2A expression, which carries potential diagnostic, prognostic, and therapeutic value.
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http://dx.doi.org/10.18632/oncotarget.17097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564754PMC
July 2017

A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

J Mech Behav Biomed Mater 2015 Mar 7;55:191-200. Epub 2015 Nov 7.

Department of Otorhinolaryngology - Head and Neck Surgery, Division of Surgery and Cancer Diseases, Turku University Hospital, PO Box 52, 20521 Turku, Finland; City of Turku Welfare Division, PO Box 670, 20101 Turku, Finland.

This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial reconstruction with the presented material appears to be a feasible method.
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http://dx.doi.org/10.1016/j.jmbbm.2015.10.030DOI Listing
March 2015

Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival.

J Neurooncol 2015 Sep 2;124(2):237-45. Epub 2015 Jun 2.

Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland.

Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2-29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.
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http://dx.doi.org/10.1007/s11060-015-1829-7DOI Listing
September 2015

Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy.

EJNMMI Res 2015 22;5:25. Epub 2015 Apr 22.

Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521 Turku, Finland.

Background: High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga-DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype 2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and established biomarkers.

Methods: Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman's rank. Immunohistochemically determined SSTR2 status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively.

Results: All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2 expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015).

Conclusions: In HGGs, uptake of (68)Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR2 expression portends favorable outcome along with established biomarkers such as IDH1 mutation.

Trial Registration: ClinicalTrials.gov NCT01460706.
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http://dx.doi.org/10.1186/s13550-015-0106-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420768PMC
May 2015

Outcomes of cranioplasty with synthetic materials and autologous bone grafts.

World Neurosurg 2015 May 11;83(5):708-14. Epub 2015 Feb 11.

Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.

Objective: Using current surgical methods, cranioplasty is associated with a high complication rate. We analyzed if there are preexisting medical conditions associated with complications and compared the effect of different implant materials on the degree of complications.

Methods: A retrospective review of the medical records of all patients who underwent cranioplasty for cranial bone defects during the period 2002-2012 was conducted, and 100 consecutive cranioplasty procedures that met eligibility criteria were identified. Patients were analyzed in 4 groups, which were created based on the cranioplasty material: autograft (n = 20), bioactive fiber-reinforced composite (n = 20), hydroxyapatite (n = 31), and other synthetic materials (n = 29). Survival estimates were constructed with Kaplan-Meier curves, and the differences between categorical variable levels were determined using a log-rank test. Multiple comparisons were adjusted using a Šidák correction.

Results: During a median follow-up time of 14 months (interquartile range 3-39 months), 32 of 100 patients (32.0%) developed at least 1 complication. A minor complication occurred in 13 patients (13.0%), whereas 19 patients (19.0%) developed a major complication, which required reoperation or removal of the implant. In the autograft subgroup, 40.0% of patients required removal of the cranioplasty. The 3-year survival of the autograft subgroup was lower compared with other subgroups of synthetic materials. In hydroxyapatite and bioactive fiber-reinforced composite groups, fewer complications were observed compared with the autograft group.

Conclusions: Based on these results, synthetic materials for cranial bone defect reconstruction exhibit more promising outcomes compared with autograft. There were differences in survival rates among synthetic materials.
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http://dx.doi.org/10.1016/j.wneu.2015.01.014DOI Listing
May 2015

Paediatric cranial defect reconstruction using bioactive fibre-reinforced composite implant: early outcomes.

Acta Neurochir (Wien) 2015 Apr 10;157(4):681-7. Epub 2015 Feb 10.

Division of Surgery and Cancer Diseases, Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Hospital, PO Box 52, 20521, Turku, Finland,

Background: In children, approximately half of cryopreserved allograft bone flaps fail due to infection and resorption. Synthetic materials offer a solution for allograft bone flap resorption. Fibre-reinforced composite with a bioactive glass particulate filling is a new synthetic material for bone reconstruction. Bioactive glass is capable of chemically bonding with bone and is osteoinductive, osteoconductive and bacteriostatic. Fibre-reinforced composite allows for fabricating thin (0.8 mm) margins for implant, which are designed as onlays on the existing bone. Bioactive glass is dissolved over time, whereas the fibre-reinforced composite serves as a biostable part of the implant, and these have been tested in preclinical and adult clinical trials. In this study, we tested the safety and other required properties of this composite material in large skull bone reconstruction with children.

Method: Eight cranioplasties were performed on seven patients, aged 2.5-16 years and having large (>16 cm(2)) skull bone defects. The implant used in this study was a patient-specific, glass-fibre-reinforced composite, which contained a bioactive glass particulate compound, S53P4.

Results: During follow-up (average 35.1 months), one minor complication was observed and three patients needed revision surgery. Two surgical site infections were observed. After treatment of complications, a good functional and cosmetic outcome was observed in all patients. The implants had an onlay design and fitted the defect well. In clinical and imaging examinations, the implants were in the original position with no signs of implant migration, degradation or mechanical breakage.

Conclusions: Here, we found that early cranioplasty outcomes with the fibre-reinforced composite implant were promising. However, a longer follow-up time and a larger group of patients are needed to draw firmer conclusions regarding the long-term benefits of the proposed novel biomaterial and implant design. The glass-fibre-reinforced composite implant incorporated by particles of bioactive glass may offer an original, non-metallic and bioactive alternative for reconstruction of large skull bone defects in a paediatric population.
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http://dx.doi.org/10.1007/s00701-015-2363-2DOI Listing
April 2015

Novel composite implant in craniofacial bone reconstruction.

Eur Arch Otorhinolaryngol 2012 Feb 1;269(2):623-8. Epub 2011 Jun 1.

Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, P.O. BOX 52, 20521, Turku, Finland.

Bioactive glass (BAG) and polymethyl methacrylate (PMMA) have been used in clinical applications. Antimicrobial BAG has the ability to attach chemically to surrounding bone, but it is not possible to bend, drill or shape BAG during the operation. PMMA has advantages in terms of shaping during the operation, but it does not attach chemically to the bone and is an exothermic material. To increase the usefulness of BAG and PMMA in skull bone defect reconstructions, a new composite implant containing BAG and PMMA in craniofacial reconstructions is presented. Three patients had pre-existing large defects in the calvarial and one in the midface area. An additive manufacturing (AM) model was used preoperatively for treatment planning and custom-made implant production. The trunk of the PMMA implant was coated with BAG granules. Clinical and radiological follow-up was performed postoperatively at 1 week, and 3, 6 and 12 months, and thereafter annually up to 5 years. Computer tomography (CT) and positron emission tomography (PET-CT) were performed at 12 and 24 months postoperatively. Uneventful clinical recovery with good esthetic and functional outcome was seen. CT and PET-CT findings supported good clinical outcome. The BAG-PMMA implant seems to be a promising craniofacial reconstruction alternative. However, more clinical experience is needed.
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http://dx.doi.org/10.1007/s00405-011-1607-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259392PMC
February 2012

Uptake of 4-borono-2-[18F]fluoro-L-phenylalanine in sporadic and neurofibromatosis 2-related schwannoma and meningioma studied with PET.

Eur J Nucl Med Mol Imaging 2007 Jan 29;34(1):87-94. Epub 2006 Jul 29.

Turku PET Centre, University of Turku, P.O. Box 52, 20521, Turku, Finland.

Purpose: Meningiomas and schwannomas associated with neurofibromatosis 2 (NF2) are difficult to control by microsurgery and stereotactic radiotherapy alone. Boron neutron capture therapy (BNCT) is a chemically targeted form of radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET with the boron carrier 4-borono-2-[(18)F]fluoro-L-phenylalanine ([(18)F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible.

Methods: We studied dynamic uptake of [(18)F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five sporadic and five NF2 patients. Tracer input function and cerebral blood volume were measured. [(18)F]FBPA uptake in tumour and brain was assessed with a three-compartmental model and graphical analysis. These, together with standardised uptake values (SUVs), were used to define tumour-to-brain [(18)F]FBPA tissue activity gradients.

Results: Model fits with three parameters K (1) (transport), k (2) (reverse transport) and k (3) (intracellular metabolism) were found to best illustrate [(18)F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher in tumour as compared with normal brain and independent of NF2 status. The increased uptake was due to higher transport of [(18)F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [(18)F]FBPA influx constant (K (i) -MTGA) ratios varied between 1.8 and 5.4 in NF2-associated tumours while in sporadic tumours the ratio was 1-1.4.

Conclusion: [(18)F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [(18)F]FBPA, some of these benign neoplasms may be amenable to BNCT.
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http://dx.doi.org/10.1007/s00259-006-0154-yDOI Listing
January 2007

Host-parasite models on graphs.

Phys Rev E Stat Nonlin Soft Matter Phys 2005 Oct 25;72(4 Pt 2):046134. Epub 2005 Oct 25.

Laboratory of Physics, Helsinki University of Technology, P. O. Box 1100, 02015 HUT, Finland.

The behavior of two interacting populations "hosts" and "parasites" is investigated on Cayley trees and scale-free networks. In the former case analytical and numerical arguments elucidate a phase diagram for the susceptible-infected-susceptible model, whose most interesting feature is the absence of a tricritical point as a function of the two independent spreading parameters. For scale-free graphs, the parasite population can be described effectively by its dynamics in a host background. This is shown both by considering the appropriate dynamical equations and by numerical simulations on Barabási-Albert networks with the major implication that in the thermodynamic limit the critical parasite spreading parameter vanishes. Some implications and generalizations are discussed.
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http://dx.doi.org/10.1103/PhysRevE.72.046134DOI Listing
October 2005

The perineurium modifies the effects of phenol and glycerol in rat sciatic nerve.

Acta Neuropathol 2004 Oct 5;108(4):319-31. Epub 2004 Aug 5.

Department of Pathology, Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.

Endoneurial cell response and type of nerve fibre damage were studied after perineural injections of 7% phenol-aqua and pure glycerol. Our previous studies have shown that phenol and glycerol induce different types of nerve fibre degeneration after intraneural injections: phenol dissolves axons and Schwann cells inside the basal lamina tubes but glycerol breaks them down into cellular flakes. The current study investigated whether the difference in type of endoneurial damage also appears after perineural application and how the perineurium affects the effect of these neurolytic agents. Rat sciatic nerves were treated with perineural injections of 7% phenol-aqua or pure glycerol and were followed up to 6 months. The results support the previous findings that perineural phenol injection induces damage that covers almost the whole endoneurium, but glycerol injection results in minor subperineurial damage. An ultrastructural study showed that the endoneurial effects are much milder after perineural injection than after intraneural injections. Phenol-induced nerve fibre dissolving was only rarely seen and the nerve fibre damage appeared similar to that after regular Wallerian degeneration in both groups. Axonal regeneration began within 2 weeks of the injections. Endoneurial macrophages were numerous in the damaged area in many individual nerves even at 3-6 months in both groups, which may indicate impaired phagocytotic activity. Regenerating axonal sprouts were seen first at 1 week post injection and Schwann cells proliferated within 2 weeks in both groups. However, the number of axonal sprouts was higher (P=0.002) and the size of the sprouts appeared larger after glycerol injection at 4 weeks post injection. The present study shows that the effects of extraneurally applied neurolytic agents phenol and glycerol are modified by the perineurium. Phenol readily penetrates the perineurium, but glycerol causes only subperineurial damage. The type of damage is rather similar to regular Wallerian degeneration in both groups and the endoneurial effects differ from those seen after intraneural injections.
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http://dx.doi.org/10.1007/s00401-004-0896-1DOI Listing
October 2004

The effect of combined neurolytic blocking agent 5% phenol-glycerol in rat sciatic nerve.

Acta Neuropathol 2003 Sep 10;106(3):261-70. Epub 2003 Jul 10.

Department of Anaesthesiology, Loimaa District Hospital, 32200 Loimaa, Finland.

Combined 5% phenol-glycerol has been used to treat cancer pain or spasticity and as sympathetic blocks. The major clinical problems have been the unpredictable effects on pain and on the duration of the blocks. Previously we have shown that intraneurally injected phenol induces haemorrhagic necrosis as well as dissolving of the nerve fibres. Glycerol, on the other hand, induces dispersion of nerve fibre debris into the endoneurium. We have now studied the effects of a combination of these two chemically different agents. The endoneurial and epineurial responses of rat peripheral nerve were followed after intraneural and perineural injections. Samples for electron microscopic and immunohistochemical studies were taken at 1-26 weeks after the injection. The intraneural phenol-glycerol injection resulted in gross endoneurial damage with partly or totally dissolved nerve fibres. Totally dissolved nerve fibres showed empty, collapsed basal lamina tubes and partly dissolved nerve fibres showed breaching of remaining degenerative debris into the endoneurial space. Axonal regeneration was delayed and was observed first after 2 weeks and it took 4 months before most of the nerve fibres were myelinated. The perineural injections resulted in partial subperineurial damage of the endoneurium morphologically similar to the results caused by the intraneural injection. An initial high accumulation of epineurial macrophages was noted at 1 and 2 weeks. An invasion of macrophages into the endoneurium occurred within 1 week after the intraneural and perineural injections and the number of endoneurial macrophages remained high for up to 6 months. The present study shows that glycerol added to phenol diminishes the necrotizing effect of phenol after an intraneural injection. Combined phenol-glycerol-induced nerve injury is reversible and the axons regenerate but residual morphological changes can be observed even after 6 months.
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http://dx.doi.org/10.1007/s00401-003-0730-1DOI Listing
September 2003

The endoneurial response to microsurgically removed epi- and perineurium.

J Peripher Nerv Syst 2002 Sep;7(3):155-62

Department of Pathology, University of Turku, Kiinanmyllynkatu, Finland.

The purpose of the study was to examine the response of the endoneurium of the rat sciatic nerve after removal of the epi- and perineurium. For this purpose, segments (4-5 mm long) of the whole epi- and perineurium around the rat sciatic nerve were microsurgically removed (the peel-off area) and the endoneurium was left intact. The post-operative changes were followed up to 5 weeks post-operatively (PO) by histo- and immunohistochemical studies. Additionally, neuromorphometric analyses considering the number of Schwann cells, axons, macrophages and endothelial cells were examined in the peel-off area. The results showed that at the operative area the central part of the endoneurium (65% of the total area of the endoneurium) remained morphologically intact, but the outer part of the endoneurium (35% of the total area) reacted strongly and showed Wallerian type of degeneration. The number of axons and Schwann cells decreased 3 days PO. However, after 2 weeks the number of Schwann cells increased markedly and the highest number was noted 5 weeks PO. A great number of capillaries were observed in the outer part 1 week PO. A rapid invasion of macrophages was noted at the outer part of the endoneurium immediately after the operation. During the regeneration the endoneurial fibroblasts in the peripheral zone started to form minifascicle-like formations, which resulted in a distinct dense outer part of the endoneurium. This dense outer zone was preserved up to 5 weeks PO and participated in the formation of a new perineurium-like structure, but no distinct new perineurium was formed. At the border zone, areas beside the normal epi- and perineurium proliferation of preserved perineurial cells were noted, which fused to the outer part of the dense endoneurium. On focal areas, an attachment of the operated area to the adjoining muscle was observed. This study shows for the first time that despite the microsurgical removal of epi- and perineurium, the inner part of the endoneurium stays intact, but in the outer part of the endoneurium marked reactive changes ensue, probably to protect the injured peripheral nerve.
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http://dx.doi.org/10.1046/j.1529-8027.2002.02015.xDOI Listing
September 2002