Small-fiber neuropathy in patients with ALS.

OBJECTIVE: To investigate the involvement of the epidermal small sensory fibers in the neurodegenerative process in amyotrophic lateral sclerosis (ALS). METHODS: In the present study, skin biopsies of 28 patients with ALS were obtained at an average of 34 months after disease onset by history. Protein gene product 9.5 (PGP9.5) immunohistochemistry findings were compared to 17 age-matched controls. The primary endpoint of the study was to evaluate the decrease in the density of small intraepidermal nerve fibers and to compare the prevalence of small-fiber neuropathy in patients with ALS and in controls. RESULTS: We found a significant reduction in epidermal nerve fiber density in the distal calf of patients with ALS (4.8 ± 3.7 fibers/mm vs 12.2 ± 4.6 in age-matched controls, p<0.0001). The extent of fiber loss was age-dependent. Also, the number of subjects with small-fiber neuropathy was significantly higher in the ALS group than in the controls (79% vs 12%). Correspondingly, mild sensory symptoms including diffuse dysesthesias, paresthesias, and hypesthesia were found in 7 patients. In 17 biopsies of patients with ALS, but only in 2 controls, we saw larger (>1.5 µm in diameter) focal swellings of epidermal axons resembling spheroids, suggesting trafficking defects. CONCLUSIONS: These results indicate that small, distal epidermal nerve fibers are involved in this disease, supporting the concept of distal axonopathy in ALS.

Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis.

Weight loss is a common phenomenon and an independent prognostic factor in amyotrophic lateral sclerosis (ALS). Several potential causal mechanisms, including intrinsic hypermetabolism and deficient food intake, have been discussed. We investigated the influence of fasting serum glucose, cholesterol, and triglyceride levels at time of diagnosis on survival in ALS. Serum cholesterol (LDL, HDL, and LDL/HDL ratio), triglycerides, and glucose were investigated in 488 patients (age of onset = 57.6 ± 12.6 years) in relation to survival and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS) data. High serum levels of both fasting cholesterol and triglycerides had a significantly positive effect on survival (p < 0.05). We found a median prolonged life expectancy by 14 months for patients with serum triglyceride levels above the median of 1.47 mmol/l. The results suggest that the lipid metabolism and the nutritional status of ALS patients are important prognostic factors. These parameters should be thoroughly monitored during the clinical management of these patients. In case of progressive loss of body weight, a diet rich in lipids and calories should be considered. However, the final decision whether a lipid-rich diet should be recommended to ALS patients can only be based on a double-blind placebo-controlled interventional trial. Our results further imply that lipid-lowering drugs, e.g., statins, should be applied carefully in ALS patients although individual risk considerations must be made.

[Reconstruction of osteochondral defects with a stem cell-based cartilage-polymer construct in a small animal model]. / Rekonstruktion von osteochondralen Defekten mit einem stammzellbasierten Knorpel-Polymer-Konstrukt im Kleintiermodell.

AIM: Mesenchymal stem cells have a high therapeutic potential for the reconstruction of articular cartilage defects. In this study, a cartilage-polymer construct using mesenchymal stem cells from trabecular bone and a polylactic acid polymer was fabricated with a press-coating technique. We investigated whether cells from human trabecular bone fragments have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow and whether it is possible to reconstruct an osteochondral lesion in the nude rat with the fabricated construct. METHOD: Cells were obtained from the femoral head of patients undergoing total hip arthroplasty. The fabrication of the constructs was performed by centrifugation of 1.5x10(6) cells to a cell pellet which was then placed in a polymer block. The fabricated cell constructs were cultivated for 3 weeks in a serum-free medium, supplemented with transforming growth factor beta1. Every third day, the chondrogenic differentiation was analysed using chondrogenic and osteogenic marker genes. After three weeks the constructs were implanted into 5 mm osteochondral defects of the knee joint of nude rats. After 4 and 12 weeks histochemical and immunohistochemical analyses were performed. RESULTS: At the end of the culture period the constructs showed a proteoglycan-rich extracellular matrix with the expression of collagen types II, IX and X as well as aggrecan und COMP (cartilage oligomeric matrix protein). No osteogenic markers except collagen type I could be detected. The analysis of the in vivo experiment showed a good defect filling with a reconstructed cartilage surface along with increasing resorption of the polymer. CONCLUSION: We have shown that it is possible to fabricate cartilage-polymer constructs from trabecular bone-derived cells, and that the cells have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow. With the fabricated cartilage-polymer construct it is possible to reconstruct an osteochondral defect in the knee joint of the nude rat.

Cementless acetabular reconstruction and structural bone-grafting in dysplastic hips. Surgical technique.

BACKGROUND: Studies of acetabular reconstruction with use of cement and bulk bone graft have demonstrated increasing rates of cup failure in patients with dysplastic hips seven years after total hip arthroplasty. Comparable data on the long-term results of bulk bone-grafting done in conjunction with cementless implants are limited. The aim of this study was to review the clinical and radiographic results of autologous bulk bone-grafting in conjunction with a cementless cup. METHODS: From 1987 to 1992, forty-seven patients (forty women and seven men, with an average age of 50.4 years) who had developmental dysplasia of the hip underwent fifty-six total hip arthroplasties and received a structural graft in combination with a cementless Harris-Galante type-I cup. All patients were followed prospectively. In fifty-five hips, implant migration was measured with single-image radiographic analysis. RESULTS: After an average duration (and standard deviation) of 10.2 +/- 2.9 years, three patients (four hips) had died. In the surviving patients, four implants had been revised and two had radiographic evidence of loosening. With use of revision and loosening as end points, the eleven-year survival rates were 91.6% and 88.9%, respectively. Of the fifty implants that had no loosening, fourteen had measurable cup migration, thirty-five had no migration, and one implant could not be measured. All migrations but one were progressive. With loosening used as the end point, the survival rate at eleven years was 100% for the implants with no migration; however, the survival rate for the cups that had migrated was 69.3% (p = 0.0012). CONCLUSIONS: The eleven-year survival rate for the spherical press-fit cups in combination with bulk bone-grafting is satisfactory, given the complexity of these reconstructions. However, the difference between the survival of the implants that had migrated and those that had not was significant. We expect that the thirteen implants with progressive acetabular migration at the time of the latest follow-up are at risk for loosening, which will increase the revision rate for this series in the coming years.

[A novel questionnaire to assess activity in patients after hip arthroplasties]. / Aktivitätsmessung von Patienten mit Hüfttotalendoprothesen.

BACKGROUND: Until now, the activity of the lower limb could only be exactly measured with expensive electronic pedometers. The aim of this study was to develop a feasible questionnaire to measure the activity of patients after arthroplasty. METHODS: The "Daily Activity Questionnaire" (DAQ) was developed in several steps and the evaluation was carried out in three groups of patients with osteoarthritis of the hip (160 patients and 855 investigated days). The psychometric characteristics were verified. RESULTS: The retest reliability (ICC) of the DAQ is in a range comparable to the electronic pedometer StepWatch. The testing of the criterion validity showed high correlations between the StepWatch and the DAQ (r=0.743). CONCLUSION: Because of its high correlations to the load changes actually performed, the DAQ is especially suited to answer arthroplasty-related questions. In all patient groups, projected load changes between 1.8 and 2.4 million per year were found, which by far exceed the generally accepted test standards for endoprostheses.

Proposal for a histopathological consensus classification of the periprosthetic interface membrane.

AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.

Cementless acetabular reconstruction and structural bone-grafting in dysplastic hips.

BACKGROUND: Studies of acetabular reconstruction with use of cement and bulk bone graft have demonstrated increasing rates of cup failure in patients with dysplastic hips seven years after total hip arthroplasty. Comparable data on the long-term results of bulk bone-grafting done in conjunction with cementless implants are limited. The aim of this study was to review the clinical and radiographic results of autologous bulk bone-grafting in conjunction with a cementless cup. METHODS: From 1987 to 1992, forty-seven patients (forty women and seven men, with an average age of 50.4 years) who had developmental dysplasia of the hip underwent fifty-six total hip arthroplasties and received a structural graft in combination with a cementless Harris-Galante type-I cup. All patients were followed prospectively. In fifty-five hips, implant migration was measured with single-image radiographic analysis. RESULTS: After an average duration (and standard deviation) of 10.2 +/- 2.9 years, three patients (four hips) had died. In the surviving patients, four implants had been revised and two had radiographic evidence of loosening. With use of revision and loosening as end points, the eleven-year survival rates were 91.6% and 88.9%, respectively. Of the fifty implants that had no loosening, fourteen had measurable cup migration, thirty-five had no migration, and one implant could not be measured. All migrations but one were progressive. With loosening used as the end point, the survival rate at eleven years was 100% for the implants with no migration; however, the survival rate for the cups that had migrated was 69.3% (p = 0.0012). CONCLUSIONS: The eleven-year survival rate for the spherical press-fit cups in combination with bulk bone-grafting is satisfactory, given the complexity of these reconstructions. However, the difference between the survival of the implants that had migrated and those that had not was significant. We expect that the thirteen implants with progressive acetabular migration at the time of the latest follow-up are at risk for loosening, which will increase the revision rate for this series in the coming years.

Anterior cruciate ligament constructs fabricated from human mesenchymal stem cells in a collagen type I hydrogel.

BACKGROUND: Disruptions of the anterior cruciate ligament (ACL) of the knee joint are common and are currently treated using ligament or tendon grafts. In this study, we tested the hypothesis that it is possible to fabricate an ACL construct in vitro using mesenchymal stem cells (MSC) in combination with an optimized collagen type I hydrogel, which is in clinical use for autologous chondrocyte transplantation (ACT). METHODS: ACL constructs were molded using a collagen type I hydrogel containing 5 x 10(5) MSC/mL and non-demineralized bone cylinders at each end of the constructs. The constructs were kept in a horizontal position for 10 days to allow the cells and the gel to remodel and attach to the bone cylinders. Thereafter, cyclic stretching with 1 Hz was performed for 14 days (continuously for 8 h/day) in a specially designed bioreactor. RESULTS: Histochemical analysis for H and E, Masson-Goldner and Azan and immunohistochemical analysis for collagen types I and III, fibronectin and elastin showed elongated fibroblast-like cells embedded in a wavy orientated collagenous tissue, together with a ligament-like extracellular matrix in the cyclic stretched constructs. No orientation of collagen fibers and cells, and no formation of a ligament-like matrix, could be seen in the non-stretched control group cultured in a horizontal position without tension. RT-PCR analysis revealed an increased gene expression of collagen types I and III, fibronectin and elastin in the stretched constructs compared with the non-stretched controls. DISCUSSION: In conclusion, ACL-like constructs from a collagen type I hydrogel, optimized for the reconstruction of ligaments, and MSC have been fabricated. As shown by other investigators, who analyzed the influence of cyclic stretching on the differentiation of MSC, our results indicate a ligament-specific increased protein and gene expression and the formation of a ligament-like extracellular matrix. The fabricated constructs are still too weak for animal experiments or clinical application and current investigations are focusing on the development of a construct with an internal augmentation using biodegradable fibers.

[Long-term results of uncemented Parhofer-Mönch screw rings]. / Langzeitergebnisse der zementfreien Parhofer-Mönch Schraubpfanne.

AIM: The aim of this study was an analysis of the long-term behaviour and implant migration of the Parhofer-Mönch-screw cup seen in patients between 1982 and 1991. METHOD: 92 cups (m : f = 53 : 39, mean age 53 +/- 7 years) were included mainly prospectively. After 118 +/- 45 months all patients were examined clinically and radiologically. Digital migration analysis was performed using the single-film X-ray analysis (Einbildröntgenanalyse, EBRA). RESULTS: 5 patients had died. 32 cups were revised, in 7 patients a loosening of the cup was suspected. The 10-year-survival was 71.4 %. In 53 of 81 analysed cups a migration of more than 1 mm was shown, 28 cups did not migrate. In comparison to these stable implants the survival of migrated cups was significantly inferior. CONCLUSION: The 10-year-survival and the high rate of implant migration document the poor results of the PM cup. In spite of an extraordinary primary stability, the failure of secondary osseointegration represents the main cause of loosening in this type of cup.

Fabrication of homogeneously cross-linked, functional alginate microcapsules validated by NMR-, CLSM- and AFM-imaging.

Cross-linked alginate microcapsules of sufficient mechanical strength can immunoisolate cells for the long-term treatment of hormone and other deficiency diseases in human beings. However, gelation of alginate by external Ba(2+) (or other divalent cations) produces non-homogeneous cross-linking of the polymeric mannuronic (M) and guluronic (G) acid chains. The stability of such microcapsules is rather limited. Here, we show that homogeneous cross-linking can be achieved by injecting BaCl(2) crystals into alginate droplets before they come into contact with external BaCl(2). The high effectiveness of this crystal gun method is demonstrated by confocal laser scanning microscopy and by advanced nuclear magnetic resonance imaging. Both techniques gave clear-cut evidence that homogeneous cross-linkage throughout the microcapsule is only obtained with simultaneous internal and external gelation. Atomic force microscopy showed a very smooth surface topography for microcapsules made by the crystal gun method, provided that excess Ba(2+) ions were removed immediately after gelation. In vitro experiments showed greatly suppressed swelling for crystal gun microcapsules. Even alginate extracted from Lessonia nigrescens (highly biocompatible) yielded microcapsules with long-term mechanical stability not hitherto possible. Encapsulation of rat islets, human monoclonal antibodies secreting hybridoma cells and murine mesenchymal stem cells transfected with cDNA encoding for bone morphogenetic protein (BMP-4) revealed that injection of BaCl(2) crystals has no adverse side effects on cell viability and function. However, the release of low-molecular weight factors (such as insulin) may be delayed when using alginate concentrations in the usual range.

Ultrafast dephasing of surface plasmon excitation in silver nanoparticles: influence of particle size, shape, and chemical surrounding.

By combination of two special methods, i.e., persistent spectral hole burning and laser assisted nanoparticle preparation, the dephasing time T2 of surface plasmon excitation in silver nanoparticles was systematically investigated. A strong dependence of T2 on the plasmon energy is found which reflects the relevance of interband damping and makes necessary a precise control of the particle shape when measuring T2. The influence of the reduced dimension on the dephasing dynamics was observed as a decrease of T2 with shrinking particle size. In addition, for silver nanoparticles on quartz substrates, a considerable amount of chemical interface damping was observed.

Formation of cartilage matrix proteins by BMP-transfected murine mesenchymal stem cells encapsulated in a novel class of alginates.

Proliferation and differentiation of wild-type, BMP-2 and BMP-4 transfected cells of C3H10T1/2, a mouse mesenchymal stem cell line that can differentiate into chondrocytes, were studied under monolayer (2D-) and encapsulation (3D-) conditions. Cells were encapsulated in a novel class of alginate. The alginate was of clinical grade (CG) because of complete removal of mitogenic and cytotoxic contaminants by chemical means. Compared to commercial alginates used so far for encapsulation it was characterized by ultra-high viscosity (UHV; viscosity of a 0.1% w/v solution of about 20 cP). In contrast to monolayer cultures, proliferation of cells was prevented when the cells were encapsulated in UHV/CG alginate at the same suspension density. As revealed by immunohistochemistry and quantitative RT-PCR, transfected and wild-type monolayer cells showed synthesis of type I collagen after transfer into differentiation medium, while culture in an alginate scaffold resulted in an upregulation of type II collagen and other hyaline cartilage proteins. BMP-4 transfected cells produced considerably more type II collagen than BMP-2 transfected and wild-type cells. BMP-4 transfected cells were also characterized by type I collagen production up to Day 10 and exhibited transient alkaline phosphatase activity levels that were much higher than the peak values observed for the other two cell lines. The coincidence of the ALP peak values with downregulation of type I collagen in BMP-4 transfected cells suggested that C3H10T1/2 cells differentiate into chondrocytes via a chondroprogenitor-like cell.

[Standardized testing of skeletal implant surfaces with an osteoblast cell culture system. IV. Specific gene expression during differentiation]. / Standardisierte Testung von Skelett-Implantatoberflächen mit einem Osteoblasten-Zellkultursystem. IV. Spezifische Genexpression während der Differenzierung.

Successful osseointegration of an implant depends on the properties of the material of which it is made. A standardized cell culture system for the assessment of the biological effect of material surfaces has already been described. In the present study, this system has been extended to include the quantitative analysis of the material-dependent osteoblast gene expression. Human foetal osteoblasts (hFOB 1.19) were cultured for 3 weeks on titanium surfaces of varying roughness, and on surfaces of chromium-cobalt-molybdenum alloy (CrCoMo). Using a real time RT-PCR technique, expressions of alkaline phosphatase, collagen 1 and osteocalcin were determined as parameters of osteoblast differentiation. In comparison with CrCoMo, differentiation was accelerated on titanium. While the smooth titanium surface leads to earlier cell growth, the rough surface induces more prolonged and stronger cell proliferation. Our results confirm at the molecular level the excellent clinical biocompatibility of titanium surfaces. The real-time RT-PCR provides a new method for the quantitative assessment of material-dependent osteoblastic differentiation.

A novel class of amitogenic alginate microcapsules for long-term immunoisolated transplantation.

In the light of results of clinical trials with immunoisolated human parathyroid tissue Ba2+-alginate capsules were developed that meet the requirements for long-term immunoisolated transplantation of (allogeneic and xenogeneic) cells and tissue fragments. Biocompatibility of the capsules was achieved by subjecting high-M alginate extracted from freshly collected brown algae to a simple purification protocol that removes quantitatively mitogenic and cytotoxic impurities without degradation of the alginate polymers. The final ultra-high-viscosity, clinical-grade (UHV/CG) product did not evoke any (significant) foreign body reaction in BB rats or in baboons. Similarly, the very sensitive pERK assay did not reveal any mitogenic impurities. Encapsulated cells also exhibited excellent secretory properties under in vitro conditions. Despite biocompatible material, pericapsular fibrosis is also induced by imperfect capsule surfaces that can favor cell attachment and migration under the release of material traces. This material can interact with free end monomers of the alginate polymers under formation of mitogenic advanced glycation products. Smooth surfaces, and thus topographical biocompatibility of the capsules (visualized by atomic force microscopy), can be generated by appropriate crosslinking of the UHV/CG-alginate with Ba2+ and simultaneous suppression of capsule swelling by incorporation of proteins and/or perfluorocarbons (i.e., medically approved compounds with high oxygen capacity). Perfluorocarbon-loaded alginate capsules allow long-term non-invasive monitoring of the location and the oxygen supply of the transplants by using 19F-MRI. Transplantation studies in rats demonstrated that these capsules were functional over a period of more than two years.

The influence of pore geometry in cp Ti-implants--a cell culture investigation.

Biocompatibility testing of differently structured titanium implants was performed using an in vitro test system of a newly established human fetal osteoblastic cell line (hFOB 1.19). Cell adhesion of osteoblastic cells on the different porous geometries and the suitability of a copper vapor laser system for surface structuring was tested with the following parameters: cell-number, cell viability, alkaline phosphatase expression. The analysis of the cell culture results demonstrated that 25 microm and 200 microm porous geometries showed similar or even better results than the negative control of polystyrene; there was no sign of toxic effects. However, the 100 microm porous geometry showed an impressive negative influence on the calculated parameters. The reason for this effect is unclear. The series with 50 microm, 300 microm, 400 microm and 500 microm showed a comparable, intermediate effect on the cell culture with respect to the different parameters. However, the results were worse than with the 25 and 200 microm porous geometry. In conclusion, the 25 microm and 200 microm porous geometry seems to have the most positive effect on the human osteoblastic cell line hFOB 1.19.

[5- to 8-year results of total hip endoprosthesis implantation with the Müller straight shaft prosthesis (cemented TiAlNb shaft)]. / 5-bis 8-Jahres-Ergebnisse nach Hüfttotalendoprothese mit der Müller-Geradschaftprothese (zementierter TiAlNb-Schaft).

The aim of this study was to obtain mid-term results after total hip arthroplasty (THA) with cemented titanium stems. In all, 184 patients with a total of 202 THAs (cemented titanium stem) were clinically and radiologically examined after an average follow-up of 6 years (5-8). The recruitment was 86%. The Harris score was determined clinically. Radiologically, the directly postoperative radiographs were compared to the control radiographs according to the recommendations of Gruen et al. and Johnston et al. In 2 cases (1%) septical complications appeared after 2 years, which were treated in two-stage surgery. To date, revisions after loosening have been carried out in 3 cases (1.5%). This is equivalent to a revision rate of 2.5%. Three further cases showed evidence of loosening in more than 5 radiolucent lines (RLL), according to Gruen, making close-meshed controls necessary. Clinically, in all of the 6 cases of aseptic loosening, the Harris score remained above 80 points. In 36 cases, more than one RLL, compared to the postoperative radiographs, was ascertained and mainly found in zones 1, 7, 8, and 14. Substantial subsidence or varus could only be observed in one case. The clinical results in the Harris score were good or excellent in 78% and satisfactory in 20%. With an average of 75 at the time of follow-up, the age of the patients was, according to the indication that only patients above age 60 are to receive cemented-stem prostheses, clearly advanced. The body weight was significantly higher (82 kg; d = 2.4) in those 6 patients having evident RLL, than in patients without RLL. The ratio body weight to surface of the stem was especially different (1.5 kg/cm2 versus 1 kg/cm2; P < 0.005) in the two groups. This did not apply to sex or activity of the patient, size or kind of stem, Harris score, ectopic ossification, or body weight index. The biggest possible stem should be implanted. Not all cemented titanium stem prostheses are necessarily affected with a high rate of loosening at a mid-term follow-up.

[Cytotoxicity study of high gold content Degutan surfaces of various degrees of roughness with fibroblasts (BALB 3T3) and osteoblasts (hFOB 1.19)]. / Zytotoxizitätsuntersuchung von hochgoldhaltigen Degutan-Oberflächen unterschiedlicher Rauhigkeit mit Fibroblasten (BALB 3T3) und Osteoblasten (hFOB 1.19).

The cytotoxicity of Degutan surfaces with different degrees of roughness, and the effect of surface structures on osteoblast proliferation and differentiation, was investigated with standardised cell culture systems. Fibroblast cell lines (BALB/3T3) and osteoblast cell lines (hFOB 1.19) were used. The number and variability of the cells were determined for assessment of proliferation and alkaline phosphatase activity, collagen I and osteocalcin production were used as parameters for differentiation. In the early phase, the largest numbers of cells and greatest proliferation were measured on polished Degutan surfaces. In the late phase, however, larger numbers of cells and a greater degree of proliferation were to be seen on sandblasted and sandblasted/heat-treated Degutan surfaces. No differences were found for collagen I, osteocalcin production or alkaline phosphatase activity. Neither the osteoblasts nor the fibroblasts revealed a toxic effect of Degutan. The results for osteoblast differentiation correlate with recent studies on identical structured titanium surfaces. In view of the immeasurable amount of ion release, Degutan may be considered an ideal model for an inert material surface.

Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation photosensitizer.

Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.