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Biomedical subjects

K P Günther

Publications and source records attributed to K P Günther.

At least 19 recordsLinked to original sources

[Obesity and arthritis].

An increasing prevalence and incidence of osteoarthritis especially in aging populations results in different socioeconomic problems. Recent studies have shown an association between osteoarthritis and overweight especially for knee and hip joints. The mechanisms responsible for the destruction of joints are still unknown, however. Obesity and overweight can lead to higher force transmission on joints at least in lower extremities, but mechanical factors hardly explain the association between overweight and hand osteoarthritis shown in different studies. There may be additional metabolic effects responsible for cartilage destruction, but distinct mechanisms have not been demonstrated up to now. They would, however, support preventive measures as well as therapeutic approaches.

Causality↗

Bone morphogenetic protein 2 accelerates osteointegration and remodelling of solvent-dehydrated bone substitutes.

INTRODUCTION: lt was the purpose of this study to investigate how bone morphogenetic protein 2 (BMP-2) influences remodelling and the biomechanics of solvent-dehydrated bone in the long run. Furthermore, the early influence of this growth factor on the substitute was investigated. MATERIALS AND METHODS: Using a weight-bearing animal model, solvent-dehydrated bone was implanted in the tibial head of merino sheep ( n=12) after being loaded with BMP-2 (100 microg/100 microl). At 4 weeks ( n=6) and 9 months ( n=6) after surgery, histomorphological, histomorphometrical and biomechanical investigations were performed. RESULTS: At 9 months after implantation of BMP-2-loaded specimens, the bone per tissue volume was high, with levels above those of physiological cancellous bone. The amount of remaining solvent-dehydrated bone was markedly decreased, and in contrast, the amount of newly formed bone was extremely high. The specimen degradation had already occurred within the first 4 weeks after implantation, showing no further impact throughout the 9-month period. Biomechanical investigations at 9 months after implantation demonstrated a yield strength which achieved levels at least equivalent to physiological cancellous bone. BMP-2 showed no significant impact on the biomechanical properties after 4 weeks, compared to specimens prior to implantation. CONCLUSION: BMP-2 predominantly has an impact on the early implant degradation as well as bone formation, which leads to an almost completed bone remodelling of the solvent-dehydrated specimen within the study period of 9 months.

Animals↗

[Clinical epidemiology of hip and knee joint arthroses: an overview of the results of the "Ulm Osteoarthrosis Study"].

AIM OF STUDY: To summarize the strategy of patient recruitment, applied methods and published results within the Ulm Osteoarthritis Study, a multicenter cross-sectional survey of patients with advanced hip and knee osteoarthritis. METHODS: 420 patients with hip OA and 398 patients with knee OA scheduled for unilateral total joint replacement in four hospitals in the southwestern part of Germany underwent detailed clinical investigations and a standardized interview in addition to radiographic analyses of ipsilateral and contralateral hip or knee joint and both hands. Odds ratios and 95% confidence intervals for the association of different possible risk factors with OA patterns (unilateral, bilateral and generalized OA) were calculated with logistic regression, adjusting for potential confounders. RESULTS: In 41.7% of patients with hip OA and 33.4% of patients with knee OA, an underlying pathological condition allowed a classification as secondary OA. 82.1% of patients with hip and 87.4% of patients with knee OA had bilateral disease. Generalized OA (GOA) was found in 19.3 and 34.9%, respectively (after adjustment for different age and sex distribution in the two patient groups; however, this difference was not any more significant). A positive association could be observed between hypercholesterolemia and GOA in knee OA patients as well as between serum uric acid and GOA in hip OA patients. Obesity and overweight were associated with bilateral knee OA, but not bilateral hip OA nor GOA. DISCUSSION: Our innovative study design allows the non-invasive investigation of patient subgroups with established disease and a testing of relevant hypotheses in an appropriate setting. The data add to the evidence regarding the independent role of different systemic risk factors for OA. In an ongoing study the natural course of the disease of the contralateral, unoperated joint is currently being investigated in all recruited patients.

Adult↗

Histomorphological, histomorphometrical and biomechanical analysis of ceramic bone substitutes in a weight-bearing animal model.

It was the purpose of this investigation to prove the biomechanical properties, the osteoconductive capacity and the degradation rate of alpha tricalcium phosphate (alpha TCP), a neutralized glass ceramics (GB9N) and a composite material (GB9N+copolymers). In a weight-bearing animal model six substitutes each were implanted in the medial tibial head of the right lower leg of adult Merino-sheep in a standardized surgical technique. After nine months the implants were harvested and prepared for histomorphological and histomorphometrical investigations (undecalcified Masson Goldner staining). For additional biomechanical testing of the specimens, non-operated bone blocks from the contralateral tibia as well as native implants served as controls. No significant differences for the maximum fracture load as well as for the yield strength were detected between harvested specimens and bone blocks from the contralateral tibia. However there were marked differences to ceramics that were not implanted. All substitutes showed osteoconduction, leading to a continuous ingrowth of new formed bone. However in the composite material soft tissue could be identified within the scaffold and there were signs of ongoing bone remodeling, nine months after implantation. The bone per tissue volume of alpha-TCP in conjunction to new bone (=percentage of trabecular bone volume plus percentage of residual substitute) was higher than for GB9N and the composite material. Nine months after implantation the percentage of residual alpha-TCP was 48%, it was 32% for GB9N and 28% for the composite. The intention of further studies should be to accelerate the degradation rates of substitutes and to improve biomechanical properties of implants by either modifying the chemical composition or combining materials with agents as, e.g. growth factors.

Journal Article↗

Expression of collagen type I, II, X and Ki-67 in osteochondroma compared to human growth plate cartilage.

In order to characterize the consequences for the process of endochondral ossification we performed an immunohistochemical study and compared the expression of collagen type I, II and X as markers of cartilage differentiation and Ki-67 as a marker of cell proliferation in solitary (7-26 years, n=9) and multiple (11-42 years, n=6) osteochondromas with their expression in human fetal and postnatal growth plates. In fetal and young postnatal controls, we found a thin superficial layer of articular cartilage that stained positive for collagen type I while collagen II was expressed in the rest of the cartilage and collagen type X was restricted to the hypertrophic zone. Osteochondromas from children showed lobular collagen type II-positive areas surrounded by collagen type I. In adults, the separation of collagen type I- and type II-positive areas was more blurred, or the cartilaginous cap was missing. Collagen type X was detected in a pericellular distribution pattern within hypertrophic zones but also deeper between bone trabecula. The proliferative activity of osteochondromas from children younger than 14 years of age was comparable to postnatal growth plates, whereas in cartilage from individuals older than 14 years of age, we could not detect significant proliferative activity.

Adolescent↗

Proliferation and differentiation rates of a human osteoblast-like cell line (SaOS-2) in contact with different bone substitute materials.

The aim of our study was to investigate the influence of four bone substitutes on the growth behavior of a human osteoblast-like cell line (SaOS-2) culture: pure alpha tricalcium phosphate (alpha-TCP = BIOBASE), a bioactive glass (bioglass), a neutralized glass-ceramic (GB9N), and solvent dehydrated bone. We established an in vitro cell culture model with three-dimensional scaffolds (cubes of 0.7 x 0.7 x 1.0 cm) of porous bone substitutes to investigate proliferation and differentiation rates of SaOS-2 cells. The cultures were analyzed for individual cell morphology after 5 days of growing using scanning electron microscopy. Fracture preparations of the cubes showed that cells could infiltrate the porous structures, but the cell shapes varied from individual round-shaped cells to wide spread cells and cell clusters, depending on the material. Also, the differentiation of the seeded cells was dissimilar after a 5-day incubation. The specific alkaline phosphatase (ALP) enzyme activity (ALP/DNA) measured in the supernatants of alpha-TCP-grown cells was nine times higher than the lowest activity, as observed by cells incubated on GB9N. Early (Collagen1, ALP) and late marker (osteocalcin, bone sialoprotein) of osteoblastic differentiation were proofed by reverse transcriptase-polymerase chain reaction analysis. Cells grown on bone substitutes and bioglass seem to be less differentiated than alpha-TCP-grown cells, because of noticeably less amounts of osteocalcin and bone sialoprotein. The cultivation on GB9N seems to dedifferentiate the cells, because even the ALP expression was reduced as well. Our results indicate that distinct bone substitutes influence proliferation and differentiation of osteoblastic cells in different manners. These results might influence the selection of an adequate bone substitute for clinical use as well, part from degradative and biomechanical properties.

Bone Substitutes↗

Solvent dehydrated bone transplants to bridge segmental bone defects: histomorphological and biomechanical investigations in an animal model.

Cancellous bone is routinely used in human surgery to fill skeletal defects. The availabilty of autogenous and allogenous grafts is limited, however. The aim of this in vivo study was therefore to determine the in-growth behaviour and biomechanical properties of solvent dehydrated human bone as an alternative to the use of autografts. In a weight-bearing experimental model, solvent dehydrated bone transplants were implanted subchondrally in the medial proximal tibia of merino sheep. After 9 months, explants as well as controls from the contralateral leg were harvested and prepared for histomorphological, histomorphometrical and biomechanical examination. A smaller, but statistically insignificant difference was found for the yield strength after 9 months for harvested specimens in comparison with untreated controls. Regarding the histomorphological results, we found a homogenous ingrowth of new bone trabeculae throughout the transplants. The degradation of the solvent dehydrated bone was not complete within the study period as shown by persistent bone remodelling. The bone per tissue volume of remaining solvent dehydrated graft particles together with newly formed bone was significantly higher than for controls. Our observation period was not long enough to document complete remodelling, but good osteointegration and reasonable biomechanical properties in this weight-bearing large animal model support the application of solvent dehydrated bone in cancellous defects of clinical relevance.

Animals↗

Determinants of impaired renal function with use of nonsteroidal anti-inflammatory drugs: the importance of half-life and other medications.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with renal function, but little is known about the effects of the half-life of these agents, or the use of other medications, on renal function. SUBJECTS AND METHODS: Medication use was assessed during a standardized interview in a cross-sectional study of 802 patients undergoing total joint replacement because of osteoarthritis. Preoperative blood samples were used to estimate creatinine clearance using a standard formula that takes age, sex, and weight into account. Impaired renal function was defined as an estimated creatinine clearance less than 60 mL/min (fifteenth percentile). Multivariable logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between NSAID use (alone or in combination with diuretics or angiotensin-converting enzyme [ACE] inhibitors) and impaired renal function. RESULTS: NSAID use per se was only marginally associated with impaired renal function (OR = 1.4; 95% CI, 0.9 to 2.2). This association was almost exclusively the result of the use of NSAIDs with a half-life of 4 or more hours (OR = 2.6; 95% CI: 1.2 to 5.7). Patients who used diuretics with NSAIDs (OR = 3.7; 95% CI: 1.7 to 8.3) or without NSAIDs (OR = 3.5; 95% CI: 1.6 to 7.6) had a higher risk of impaired renal function than did patients using NSAIDs alone (OR = 1.6) or none of these drugs (reference). A similar but less pronounced pattern was observed for ACE inhibitors. CONCLUSION: NSAID-associated impaired renal function seems to be mainly the result of compounds with intermediate-long half-life. We found no evidence that the adverse effects of diuretics and ACE inhibitors on renal function were greater in those who also used NSAIDs.

Angiotensin-Converting Enzyme Inhibitors↗

Surgical approaches for osteoarthritis.

Patients with osteoarthritis (OA) often benefit from properly performed surgical procedures. However, the scientific database from studies investigating appropriate timing of surgery, patient morbidity, quality of life before and after the intervention, and cost utility of different procedures is insufficient. In order to allow a fair allocation of resources in future health care systems, randomized controlled trials (RCTs) with defined entry criteria, sufficient number of patients, and valid outcome measures should be performed for different surgical approaches. They should especially include control groups with conservative treatment in order to allow an evidence based comparison between different therapeutic approaches. At present, however, optimal management of OA as a dynamic disease process must include a combination of conservative as well as operative treatment modalities. In case of malalignment, instability and intra-articular causes of mechanical dysfunction, correction of these abnormalities and relief of symptoms can be achieved with properly indicated and performed osteotomies. Debridement by arthroscopy and arthotomy probably does not alter the natural history of OA and true clinical outcomes are difficult to determine, but it can provide transient relief of symptoms. Joint replacement has to be considered for refractory pain associated with disability and radiological deterioration. As the pre-operative functional status seems to influence the outcome not only in joint replacement but also in joint-preserving osteotomies, the indication for these procedures might be expanded in the future.

Adolescent↗

Non-insulin dependent diabetes mellitus (NIDDM) and patterns of osteoarthritis. The Ulm osteoarthritis study.

OBJECTIVES: Despite recent advances regarding the role of diabetes with respect to cartilage metabolism, epidemiologic data to quantify the role of diabetes in the development of osteoarthritis (OA) are sparse. METHODS: OA patterns were studied in 809 patients with knee or hip joint replacement due to OA. NIDDM was defined by a history of physician diagnosed diabetes or use of antihyperglycemics. RESULTS: Patients with NIDDM had more often bilateral OA (adjusted odds ratio (OR)=2.2; 95% confidence interval (CI): 0.8-6.4). No association between NIDDM and generalized OA (adjusted OR= 1.0; 95%CI: 0.5-1.9) was observed. CONCLUSIONS: Our results are consistent with the hypothesis that NIDDM might be a potentially important systemic risk factor for knee and hip OA, but chance cannot be ruled out as an alternative explanation.

Aged↗

Hysterectomy and patterns of osteoarthritis. The Ulm Osteoarthritis Study.

OBJECTIVE: To determine the association between hysterectomy (HE) and patterns of osteoarthritis (OA) METHODS: We performed a large cross-sectional study including 504 female patients admitted for arthroplasty of knee or hip joint. Patients with OA were categorized as having bilateral or generalized OA (GOA) according to the presence of radiographic OA in the contralateral or different finger joints. Odds ratios (OR) and their 95% confidence intervals (CI) for the association between HE and OA patterns were estimated adjusting for potential confounders. RESULTS: Hysterectomy (HE) was reported by 24.9 percent of the patients. Bilateral OA was present in 86.2 percent and GOA was present in 33.3 percent of the patients. HE was not associated with bilateral OA (adjusted OR=0.9; 95% CI: 0.5-1.8) but with a lower prevalence of GOA (adjusted OR=0.6; CI: 0.3-0.99). CONCLUSION: In contrast to earlier studies our results suggest that HE might be a marker for a reduced risk for a generalized pattern of OA.

Age Distribution↗

Gene expression of stromelysin and aggrecan in osteoarthritic cartilage.

OBJECTIVE: To analyze cartilage gene expression of patients with osteoarthritis (OA) in correlation with radiographic and histological findings. MATERIALS AND METHODS: Twenty-one patients with OA of the knee admitted for total knee replacement were analyzed clinically and radiographically by the Kellgren and Lawrence system. During surgery, cartilage samples from the medial and lateral condyles and tibial plateaus were harvested separately. Specimens were analyzed histologically (Mankin score) and total RNA was extracted directly from cartilage tissue. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. RESULTS: Histology of medial and lateral knee compartments corresponded to radiographic changes (Spearman correlation coefficient: r = 0.7 (p < 0.01)). There was a positive correlation between MMP-3 and AGG gene expression (r = 0.4; p < 0.01). We found considerable variation of expression levels of MMP-3 and AGG and no correlation of gene expression with histological or radiographic scoring. CONCLUSION: The positive correlation between AGG and MMP-3 suggests a common regulation of anabolic and catabolic metabolism. There was no simple dependency between gene expression and histological and radiological findings in cartilage.

Aged↗

BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast-like cells.

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells.

Adult↗

Obesity, overweight and patterns of osteoarthritis: the Ulm Osteoarthritis Study.

The objective of this study was to assess the association between obesity and osteoarthritis (OA) of the knee, hip, and hand. OA patterns were studied in 809 patients with knee or hip joint replacement due to OA. Patients with OA were categorized as having bilateral or generalized OA according to the presence of radiographic OA in the contralateral joint or different finger joints, and as normal weight, overweight, or obese according to their body mass index (BMI). Odds ratios (OR) and 95% confidence intervals (CI) for relative weight and OA patterns were estimated with multivariable logistic regression. Eighty-five percent of participants had bilateral OA, 26% had generalized OA, and 31% were obese. Obesity (BMI >/= 30 kg/m(2); OR = 8.1; 95% CI: 2.4-28) and overweight (BMI >/= 25 kg/m(2); OR = 5.9; 95% CI: 2.0-18) were strongly associated with bilateral knee OA. No association between obesity and bilateral hip OA (OR = 0.7; 95% CI: 0.3-1.7) nor generalized OA (OR = 1.1; 95% CI: 0.6-2.1) was observed. Obesity seems to be a mechanical rather than a systemic risk factor for OA with the knee joint being especially susceptible.

Aged↗

[Stimulation of primary osteoblast cultures with rh-TGF-beta, rh-bFGF, rh-BMP 2 and rx-BMP 4 in an in vitro model].

Bone metabolism is influenced by systemic and local acting hormons. Bone morphogenetic proteins (BMPs) as representatives of the latter substances are known to have the ability for ectopic bone formation. Within this study, we investigated the influence of different growth factors on the proliferation- and differentiation rate of osteoblast-like cells. For that purpose, human osteoblast-like cells (HPOC) were incubated in the presence of either recombinant BMP-4 of the genome of xenopus laevis (rxBMP-4), recombinant human BMP 2 (rhBMP-2), transforming growth factor-beta (TGF-beta) or basic fibroblast growth factor (rh-bFGF) in two different concentrations each (10 ng/ml and 50 ng/ml). Cell proliferation was measured within a MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromid] assay, the amount of cell differentiation by the activity of alcaline phosphatase. Rx-BMP-4 induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied at the same concentration, failed to have any influence on cell differentiation. However, rh-bFGF provoked an increase in cell proliferation when compared with unstimulated HPOC, while rhBMP-2 and rxBMP-4 showed no effect on proliferation. TGF-beta influenced bone proliferation as well as differentiation significantly. The equipotent effect of recombinant human BMP-2 and recombinant BMP-4 obtained from Xenopus laevis with regard to differentiation and proliferation of human primary osteoblast-like cells originates either in the fact that target cells have receptors for BMP 2 as well as BMP 4, or that both BMP's link to the same receptor with almost the same affinity.

Adult↗

Serum uric acid and patterns of radiographic osteoarthritis--the Ulm Osteoarthritis Study.

OBJECTIVE: To assess the association between uric acid and patterns of osteoarthritis (OA). METHODS: OA patterns were studied in 809 patients with arthroplasty due to hip or knee OA. Patients with OA were categorized as having bilateral or generalized OA according to the presence of radiographic OA in the contralateral or different finger joints. Odds ratios (OR) and 95% confidence intervals (CI) for thirds of serum uric acid and OA patterns were estimated with multivariable logistic regression. RESULTS: Eighty-five percent of the participants had bilateral OA and 26% generalized OA. A positive association between serum uric acid and generalized OA was observed in patients with hip OA (highest versus lowest tertile OR=3.5; 95% CI: 1.3-9.1), but not among patients with knee OA (corresponding OR = 1.1). Serum uric acid was not associated with bilateral OA. CONCLUSION: Our results suggest a possible role of elevated serum uric acid in the multifactorial etiology of generalized OA.

Aged↗

Allergic reactions to latex in myelodysplasia: a review of the literature.

Current research has identified clinically relevant allergens in natural latex. Children with myelodysplasia are especially considered to be at risk for the development of immunoglobulin E-mediated hypersensitivity, which can lead to life-threatening intraoperative anaphylaxis. A careful medical history is mandatory to identify patients who might be predisposed to anaphylactic reactions. Preventive measures involve primarily the avoidance of latex contact at home and in hospitals for all patients with myelodysplasia. The effectiveness of additional pharmacologic prophylaxis has to be determined further.

Adolescent↗

EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

BACKGROUND: Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. METHODS: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. RESULTS: Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.

Combined Modality Therapy↗