Aseptic Meningitis with Urinary Retention: A Case Report

Introduction. Aseptic meningitis is serious inflammation of the meninges caused by agents including viruses, non-viral pathogens, non-infectious conditions and chemicals. Case Presentation. This study concerns the case of a 16-year-old healthy Greek female with persistent fever, mild headache and acute urinary retention, secondary to aseptic meningitis. Physical examination revealed no distinct signs of meningeal irritation. The urinary bladder was palpable, painless and over-distended. Serology carried out for common viruses was as follows: CMV IgG (−), CMV IgM (−), HSV IgG (−), HSV IgM (+), VZ IgG (+), VZ IgM (−), EBV IgG (−) and EBV IgM (+). During recovery in hospital, three trials of removing a urinary catheter were carried out; during the first two attempts the patient was unable to urinate and had a loss of bladder sensation. On the third attempt the patient had modest bladder perception but she left a post-voiding residual, and was instructed to perform bladder self-catheterization. Seven days after being discharged the patient underwent a full recovery. Conclusion. There are few reports concerning aseptic meningitis together with acute urinary retention. A number of these cases concern so-called “meningitis-retention syndrome,” which implies an underlying CNS mechanism, while others concerned an underlying peripheral nervous system mechanism

On the influence of biochemical coating on implant bone incorporation

Implantat används idag med goda resultat för att ersätta förlorade tänder. Tandimplantat opereras in i käkbenet och agerar som en konstgjord rot för en konstgjord tand eller för att förankra en protes. Implantatens ytor har utvecklas med åren från att vara släta till måttligt råa. De nya råare ytorna har uppvisat högre lyckandefrekvens framför allt vid kliniskt utmanande fall, såsom patienter med sämre benkvalitet eller benmängd. Strålbehandling mot ansiktet och halsen samt medicinering eller sjukdom är bara några exempel på faktorer som försämrar benbildningsförmågan. Ständigt ökade krav på implantatprestation och ständigt utökade behandlingsområden har givit upphov till mångårig forskning som lett till de moderna implantatytorna. Implantatytornas utveckling fortsätter och experiment med nya implantatytor som är laddade med benstimulerande biomolekyler har genomförts. Den aktuella avhandlingen har studerat proteinet laminin-1 som har uppvisat benstimulerande egenskaper i cellodlingar. Därmed har vår hypotes varit att implantat belagda med proteinet laminin-1 skulle kunde öka benbildningen och förbättra implantatens stabilitet. Proteinets förmåga att fästa sig på titandiskar utsatta för olika ytbehandlingar har utvärderats i en lösning som simulerar det initiala benbildningsstadiet. Mängden kalciumfosfat som fälls ut räknas som mått på benstimuleringsförmågan. Resultaten har visat att mängden laminin-1 som fäster sig på de olika ytorna är jämförbar vilket tyder på god fästförmåga av proteinet. Den gruppen titandiskar som fällde ut mest kalciumfosfat var den som hade sänkts i en stark alkalisk lösning och därefter hettats upp. Dessutom observerades att blästrade titandiskar som var belagda med laminin-1 fällde ut mer kalciumfosfat än icke-belagda blästrade diskar. Vår teori utvärderades i djurstudier som innefattade kaniner och råttor. I den första kaninstudien opererades proteinbelagda implantat gjorda av hydroxylapatit in i skenbenet. Implantaten var mycket släta för att undvika att proteineffekten skulle överskuggas av ytråhetens effekt. Efter två och fyra veckor utvärderades benmängden runt implantaten med histologi och datortomografi. Trots att proteinbelagda implantat uppvisade en positiv trend för bentillväxt, kunde inga statistiskt signifikanta skillnader konstateras. I den andra kaninstudien utvärderade vi effekten av laminin-1 på svarvade samt alkali- och värmebehandlade implantat efter två och fyra veckor. Benbildningsförmågan utvärderades med histologi, datortomografi, urvridningsmotstånd och elasticitetstest i kringliggande benet. Histologin visade att svarvade implantat belagda med protein hade högst urvridningsmotstånd samt att mest nytt ben hade bildats i kontakt med dessa implantat efter två veckor. Benet kring dessa implantat var dock inte hårdare. Datortomografin kunde följa trenderna som uppvisades av histologin men ingen statistiskt säkerställd skillnad kunde påvisas. I råttstudien jämfördes proteinbelagda med icke-belagda svarvade implantat med avseende på histologi och uttryck av gener som är aktiva vid benproduktion, bennedbrytning och inflammation. Tidpunkterna för utvärdering var tre, sju och tjugoen dagar. Resultaten visade att laminin-1 stimulerar uttrycket av benbildande gener och sänkte uttrycket av vissa gener som är relaterade till bennedbrytning och inflammation efter sju dagar. Den histologiska utvärderingen kunde dock inte detektera dessa skillnader. Konklusion: Våra resultat tyder på att proteinet laminin-1 kan förbättra benresponsen beroende på den underliggande ytans material och ytråhet. Eftersom proteinbeläggningen verkar vara mest aktiv i början av läkningen, kan valet av metoderna och tidpunkterna påverka utvärderingsresultatet. I fortsättningen kan våra implantat utvärderas i experimentella modeller där djur har fått försämrad benbildningsförmåga på grund av strålning eller ovariektomi. I den kliniska situationen kan det spekuleras att lamininbelagda svarvade implantat kan dels tillföra ökad benbildningskapacitet under den initiala läkningstiden och dels underlätta rengöringsproceduren i händelse av infektion kring implantat dvs. vid peri-implantit.Introduction: Dental implants have been proven to be a reliable long term therapy against edentulism. However, the reported high success figures of implant therapy have been based on implants in-serted using two-stage surgical protocol and conventional loading. The increased demand on implant performance and the broadened treatment indications have led to the development of new mod-erately rough surfaces. Novel implant surface modifications include coating with bone specific biomolecules to enhance bone formation. Interestingly, even non-bone specific molecules have reported to induce bone formation. One non-bone specific biomolecule with osteogenic potential is laminin-1. Aims: The present thesis has aimed to investigate the role of lami-nin-1 as a biochemical implant coating agent and to compare the osteogenic performance of the coating to the performance of other bioactive surfaces. Furthermore, we aimed to compare the results obtained by the different methods. Materials and methods: Titanium discs were subjected for three surface treatments claimed to provide bioactivity (alkali and heat treatment, anodic oxidation and nano-hydroxyapatite coating) and the ability to precipitate laminin-1 and calcium phosphate in a laboratory model which simulates initial bone formation was as-sessed. Blasted surfaces were used as controls. The animal studies included rabbits and rats. Two studies were conducted in a rabbit model. In the first, hydroxyapatite implants were coated with laminin-1 and bone amount around the implants was evaluated in terms of micro computed tomography and histology. In the second study, turned and alkali and heat treated titanium implants were coated with laminin-1 and the formed bone was evaluated with histology, micro computed tomography and biomechanics. In the rat model, turned implants were coated with laminin-1 and their ability to induce bone formation was assessed in terms of histology and gene expression. Results: In the in vitro studies, the tested surface modifications precipitated equivalent amounts of laminin-1. The alkali and heat treated surfaces precipitated the highest amount calcium phosphate at the shorter period of time. Laminin-1 resulted in precipitation of significantly higher amount calcium phosphate on blasted titanium discs as compared to a negative control. In the rabbit studies, laminin-1 coating of hydroxyapatite implants created positive but non-significant trends. On the contrary, after 2 weeks, coated turned implants demonstrated removal torque values equivalent to alkali and heat treated implants and higher amount of newly formed bone as compared to all other implants. The trend was similar for micro computed tomography, but not significant. In the rat study, laminin coating enhanced gene expression of osteogenic markers and for integrin β1. The histological evaluation failed to show any differences. Conclusions: The results of the present thesis show that laminin-1 precipitates equally to titanium surfaces with various surface topo-graphies and has the ability to increase calcium phosphate precipi-tation in a lab model. Depending on the bulk material and the surface topography of the implant, coating with laminin-1 can en-hance bone response as confirmed by means of biomechanics, his-tomorphometry and gene expression. As the coating seems to be active during the initial stages of osseointegration, the choice of the time points and the methods of evaluation may affect the assessment outcome

On the influence of biochemical coating on implant bone incorporation

Implantat används idag med goda resultat för att ersätta förlorade tänder. Tandimplantat opereras in i käkbenet och agerar som en konstgjord rot för en konstgjord tand eller för att förankra en protes. Implantatens ytor har utvecklas med åren från att vara släta till måttligt råa. De nya råare ytorna har uppvisat högre lyckandefrekvens framför allt vid kliniskt utmanande fall, såsom patienter med sämre benkvalitet eller benmängd. Strålbehandling mot ansiktet och halsen samt medicinering eller sjukdom är bara några exempel på faktorer som försämrar benbildningsförmågan. Ständigt ökade krav på implantatprestation och ständigt utökade behandlingsområden har givit upphov till mångårig forskning som lett till de moderna implantatytorna. Implantatytornas utveckling fortsätter och experiment med nya implantatytor som är laddade med benstimulerande biomolekyler har genomförts. Den aktuella avhandlingen har studerat proteinet laminin-1 som har uppvisat benstimulerande egenskaper i cellodlingar. Därmed har vår hypotes varit att implantat belagda med proteinet laminin-1 skulle kunde öka benbildningen och förbättra implantatens stabilitet. Proteinets förmåga att fästa sig på titandiskar utsatta för olika ytbehandlingar har utvärderats i en lösning som simulerar det initiala benbildningsstadiet. Mängden kalciumfosfat som fälls ut räknas som mått på benstimuleringsförmågan. Resultaten har visat att mängden laminin-1 som fäster sig på de olika ytorna är jämförbar vilket tyder på god fästförmåga av proteinet. Den gruppen titandiskar som fällde ut mest kalciumfosfat var den som hade sänkts i en stark alkalisk lösning och därefter hettats upp. Dessutom observerades att blästrade titandiskar som var belagda med laminin-1 fällde ut mer kalciumfosfat än icke-belagda blästrade diskar. Vår teori utvärderades i djurstudier som innefattade kaniner och råttor. I den första kaninstudien opererades proteinbelagda implantat gjorda av hydroxylapatit in i skenbenet. Implantaten var mycket släta för att undvika att proteineffekten skulle överskuggas av ytråhetens effekt. Efter två och fyra veckor utvärderades benmängden runt implantaten med histologi och datortomografi. Trots att proteinbelagda implantat uppvisade en positiv trend för bentillväxt, kunde inga statistiskt signifikanta skillnader konstateras. I den andra kaninstudien utvärderade vi effekten av laminin-1 på svarvade samt alkali- och värmebehandlade implantat efter två och fyra veckor. Benbildningsförmågan utvärderades med histologi, datortomografi, urvridningsmotstånd och elasticitetstest i kringliggande benet. Histologin visade att svarvade implantat belagda med protein hade högst urvridningsmotstånd samt att mest nytt ben hade bildats i kontakt med dessa implantat efter två veckor. Benet kring dessa implantat var dock inte hårdare. Datortomografin kunde följa trenderna som uppvisades av histologin men ingen statistiskt säkerställd skillnad kunde påvisas. I råttstudien jämfördes proteinbelagda med icke-belagda svarvade implantat med avseende på histologi och uttryck av gener som är aktiva vid benproduktion, bennedbrytning och inflammation. Tidpunkterna för utvärdering var tre, sju och tjugoen dagar. Resultaten visade att laminin-1 stimulerar uttrycket av benbildande gener och sänkte uttrycket av vissa gener som är relaterade till bennedbrytning och inflammation efter sju dagar. Den histologiska utvärderingen kunde dock inte detektera dessa skillnader. Konklusion: Våra resultat tyder på att proteinet laminin-1 kan förbättra benresponsen beroende på den underliggande ytans material och ytråhet. Eftersom proteinbeläggningen verkar vara mest aktiv i början av läkningen, kan valet av metoderna och tidpunkterna påverka utvärderingsresultatet. I fortsättningen kan våra implantat utvärderas i experimentella modeller där djur har fått försämrad benbildningsförmåga på grund av strålning eller ovariektomi. I den kliniska situationen kan det spekuleras att lamininbelagda svarvade implantat kan dels tillföra ökad benbildningskapacitet under den initiala läkningstiden och dels underlätta rengöringsproceduren i händelse av infektion kring implantat dvs. vid peri-implantit.Introduction: Dental implants have been proven to be a reliable long term therapy against edentulism. However, the reported high success figures of implant therapy have been based on implants in-serted using two-stage surgical protocol and conventional loading. The increased demand on implant performance and the broadened treatment indications have led to the development of new mod-erately rough surfaces. Novel implant surface modifications include coating with bone specific biomolecules to enhance bone formation. Interestingly, even non-bone specific molecules have reported to induce bone formation. One non-bone specific biomolecule with osteogenic potential is laminin-1. Aims: The present thesis has aimed to investigate the role of lami-nin-1 as a biochemical implant coating agent and to compare the osteogenic performance of the coating to the performance of other bioactive surfaces. Furthermore, we aimed to compare the results obtained by the different methods. Materials and methods: Titanium discs were subjected for three surface treatments claimed to provide bioactivity (alkali and heat treatment, anodic oxidation and nano-hydroxyapatite coating) and the ability to precipitate laminin-1 and calcium phosphate in a laboratory model which simulates initial bone formation was as-sessed. Blasted surfaces were used as controls. The animal studies included rabbits and rats. Two studies were conducted in a rabbit model. In the first, hydroxyapatite implants were coated with laminin-1 and bone amount around the implants was evaluated in terms of micro computed tomography and histology. In the second study, turned and alkali and heat treated titanium implants were coated with laminin-1 and the formed bone was evaluated with histology, micro computed tomography and biomechanics. In the rat model, turned implants were coated with laminin-1 and their ability to induce bone formation was assessed in terms of histology and gene expression. Results: In the in vitro studies, the tested surface modifications precipitated equivalent amounts of laminin-1. The alkali and heat treated surfaces precipitated the highest amount calcium phosphate at the shorter period of time. Laminin-1 resulted in precipitation of significantly higher amount calcium phosphate on blasted titanium discs as compared to a negative control. In the rabbit studies, laminin-1 coating of hydroxyapatite implants created positive but non-significant trends. On the contrary, after 2 weeks, coated turned implants demonstrated removal torque values equivalent to alkali and heat treated implants and higher amount of newly formed bone as compared to all other implants. The trend was similar for micro computed tomography, but not significant. In the rat study, laminin coating enhanced gene expression of osteogenic markers and for integrin β1. The histological evaluation failed to show any differences. Conclusions: The results of the present thesis show that laminin-1 precipitates equally to titanium surfaces with various surface topo-graphies and has the ability to increase calcium phosphate precipi-tation in a lab model. Depending on the bulk material and the surface topography of the implant, coating with laminin-1 can en-hance bone response as confirmed by means of biomechanics, his-tomorphometry and gene expression. As the coating seems to be active during the initial stages of osseointegration, the choice of the time points and the methods of evaluation may affect the assessment outcome

Effects of Porphyromonas gingivalis surface-associated material on osteoclast formation

Porphyromonas gingivalis strongly correlates with periodontitis, but the underlying mechanisms causing dentoalveolar bone resorption are not fully understood. As contradictory effects of P. gingivalis on osteoclastogenesis have been reported, this study investigates the effect of P. gingivalis extract on osteoclast formation. Osteoclast formation in mouse bone marrow (MBM) cell cultures and RAW 264.7 cells was stimulated by nuclear factor-κB ligand (RANKL) or parathyroid hormone (PTH). Cells were cultured with and without P. gingivalis surface-associated material and phenotypic characteristics were examined using microscopy, flow cytometry, and RT-PCR. P. gingivalis significantly decreased osteoclast formation and the expression of osteoclast phenotypic markers in PTH-stimulated MBM cultures. Additionally, P. gingivalis inhibited expression of osteoclast differentiation factors and stimulated expression of the mouse macrophage marker F4/80. The presence of P. gingivalis in RANKL-stimulated MBM cultures and RAW 264.7 cells inhibited osteoclastogenesis. Interestingly, a transient exposure with P. gingivalis before PTH stimulation increased osteoclastogenesis in MBM cultures. Flow cytometric analyses of cells transiently exposed to P. gingivalis demonstrated an increased proportion of potential osteoclast precursor cells. We conclude that a transient exposure of MBM cultures to P. gingivalis increases the number of osteoclast precursors and osteoclast formation, whereas a prolonged exposure completely abolishes osteoclastogenesis

Novel Implant Coating Agent Promotes Gene Expression of Osteogenic Markers in Rats during Early Osseointegration

The aim of this study was to evaluate the early bone response around laminin-1-coated titanium implants. Forty-five rats distributed in three equally sized groups were provided with one control (turned) and one test (laminin-1-coated) implant and were sacrificed after 3, 7, and 21 days. Real-time reverse-transcriptase polymerase chain reaction was performed for osteoblast markers (alkaline phosphatase, runt-related transcription factor 2, osteocalcin, type I collagen, and bone morphogenic protein 2), osteoclast markers (cathepsin K and tartrate-resistant acid phosphatase), inflammation markers (tumor necrosis factor α, interleukin 1β and interleukin 10), and integrin β1. Bone implant contact (BIC) and bone area (BA) were assessed and compared to the gene expression. After 3 days, the expression of bone markers was higher for the control group. After 7 days, the expression of integrin β1 and osteogenic markers was enhanced for the test group, while cathepsin K and inflammation markers were down-regulated. No significant differences in BIC or BA were detected between test and control at any time point. As a conclusion, implant coating with laminin-1 altered gene expression in the bone-implant interface. However, traditional evaluation methods, as histomorphometry, were not adequately sensitive to detect such changes due to the short follow-up time

In vitro Evaluation of Calcium Phosphate Precipitation on Possibly Bioactive Titanium Surfaces in the Presence of Laminin

Objectives: The aim of the present study was to evaluate calcium phosphate precipitation and the amount of precipitated protein on three potentially bioactive surfaces when adding laminin in simulated body fluid.Material and Methods: Blasted titanium discs were prepared by three different techniques claimed to provide bioactivity: alkali and heat treatment (AH), anodic oxidation (AO) or hydroxyapatite coating (HA). A blasted surface incubated in laminin-containing simulated body fuid served as a positive control (B) while a blasted surface incubated in non laminin-containing simulated body fuid served as a negative control (B-). The immersion time was 1 hour, 24 hours, 72 hours and 1 week. Surface topography was investigated by interferometry and morphology by Scanning Electron Microscopy (SEM). Analysis of the precipitated calcium and phosphorous was performed by Energy Dispersive X-ray Spectroscopy (EDX) and the adsorbed laminin was quantified by iodine (125I) labeling.Results: SEM demonstrated that all specimens except for the negative control were totally covered with calcium phosphate (CaP) after 1 week. EDX revealed that B- demonstrated lower sum of Ca and P levels compared to the other groups after 1 week. Iodine labeling demonstrated that laminin precipitated in a similar manner on the possibly bioactive surfaces as on the positive control surface.Conclusions: Our results indicate that laminin precipitates equally on all tested titanium surfaces and may function as a nucleation center thus locally elevating the calcium concentration. Nevertheless further studies are required to clarify the role of laminin in the interaction of biomaterials with the host bone tissue

Laminin Coating Promotes Calcium Phosphate Precipitation on Titanium Discs in vitro.

Objectives: The objective of this study was to investigate the effect of a laminin coating on calcium phosphate precipitation on three potentially bioactive titanium surfaces in simulated body fluid. Material and Methods: Blasted titanium discs were prepared by alkali and heat treatment (AH), anodic oxidation (AO) or hydroxyapatite coating (HA) and subsequently coated with laminin. A laminin coated blasted surface (B) served as a positive control while a blasted non coated (B-) served as a negative control. Surface morphology was examined by Scanning Electron Microscopy (SEM). The analysis of the precipitated calcium and phosphorous was performed by Energy Dispersive X-ray Spectroscopy (EDX). Results: The thickness of the laminin coating was estimated at 26 Å by ellipsometry. Interferometry revealed that the coating process did not affect any of the tested topographical parameters on µm level when comparing B to B-. After 2 weeks of incubation in SBF, the alkali-heat treated discs displayed the highest calcium phosphate deposition and the B group showed higher levels of calcium phosphate than the B- group. Conclusions: Our results suggest that laminin may have the potential to be used as a coating agent in order to enhance the osseoinductive performance of biomaterial surfaces, with the protein molecules possibly functioning as nucleation centres for apatite formation. Nevertheless, in vivo studies are required in order to clarify the longevity of the coating and its performance in the complex biological environment

Bone apposition to laminin-1 coated implants: histologic and 3D evaluation

Laminin-1 has been reported as one of the factors responsible for the nucleation of calcium phosphates and, in vitro, has been reported to selectively recruit osteoprogenitors. This article focused on its in vivo effects, and evaluated the effect of laminin-1 local application on osseointegration. Polished cylindrical hydroxyapatite implants were coated with laminin-1 (test) and the bone responses in the rabbit tibiae after 2 and 4 weeks were evaluated and compared to the non-coated implants (control). Before the samples were processed for histological sectioning, they were three-dimensionally analysed with micro computed tomography (mu CT). Both evaluation methods were analysed with regards to bone area around the implant and bone to implant contact. From the histologic observation, new bone formation around the laminin-1 coated implant at 2 weeks seemed to have increased the amount of supporting bone around the implant, however, at 4 weeks, the two groups presented no notable differences. The two-dimensional and three-dimensional morphometric evaluation revealed that both histologic and three-dimensional analysis showed some tendency in favour of the test group implants, however there was no statistical significance between the test and control group results

The effect of laminin-1-doped nanoroughened implant surfaces : gene expression and morphological evaluation

Aim. This study aimed to observe the morphological and molecular effect of laminin-1 doping to nanostructured implant surfaces in a rabbit model. Materials and Methods. Nanostructured implants were coated with laminin-1 (test; dilution, 100 μg/mL) and inserted into the rabbit tibiae. Noncoated implants were used as controls. After 2 weeks of healing, the implants were removed and subjected to morphological analysis using scanning electron microscopy (SEM) and gene expression analysis using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. SEM revealed bony tissue attachment for both control and test implants. Real-time RT-PCR analysis showed that the expression of osteoblast markers RUNX-2, osteocalcin, alkaline phosphatase, and collagen I was higher (1.62-fold, 1.53-fold, 1.97-fold, and 1.04-fold, resp.) for the implants modified by laminin-1 relative to the control. All osteoclast markers investigated in the study presented higher expression on the test implants than controls as follows: tartrate-resistant acid phosphatase (1.67-fold), calcitonin receptor (1.35-fold), and ATPase (1.25-fold). The test implants demonstrated higher expression of inflammatory markers interleukin-10 (1.53-fold) and tumour necrosis factor-α (1.61-fold) relative to controls. Conclusion. The protein-doped surface showed higher gene expression of typical genes involved in the osseointegration cascade than the control surface