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Biomedical subjects

K de Groot

Publications and source records attributed to K de Groot.

At least 55 records · Page 3Linked to original sources
PubMed2002

Incorporation of tobramycin into biomimetic hydroxyapatite coating on titanium.

Calcium phosphate coatings containing an antibiotic were produced on titanium alloy (Ti6Al4V) implants using a biomimetic approach. Thin, amorphous calcium phosphate (ACP) coatings were first deposited onto Ti6Al4V plates by immersion in 5 times concentrated simulated body fluid (SBF), for 24h at 37 degrees C. The ACP-coated implants were then immersed in a supersaturated calcium phosphate (SCP) solution containing 0, 100, 200, 400, 600 or 800 mg/l of tobramycin for 48 h at 37 degrees C. A carbonated hydroxyapatite (CHA) layer, approximately 40 microm thick, was formed. Approximately 3 microg/mg of tobramycin was co-precipitated with the CHA crystals onto titanium alloy plates, using 800mg/l tobramycin in the coating solution. For comparison, plasma-sprayed calcium phosphate coatings were also immersed in solutions containing 100, 200, 400 or 1,000 mg/l of tobramycin for 10, 40 min, or 48 h. A maximum of about 0.3 microg/mg could be adsorbed onto the plasma-sprayed calcium phosphate coating with the comparable concentration of 800 mg/l in solution. The dissolution of coating and release of tobramycin were also measured in vitro using saline solution buffered at pH 5.0 or 7.3 at 37 degrees C. The release rate of tobramycin was faster at pH 7.3 than at pH 5, with 50 and 4 microg/ml/min, respectively. Tobramycin released from the biomimetic-coated plates could inhibit growth of Staphylococcus aureus bacteria. The result of this study, therefore, indicates that the biomimetic CHA coatings containing antibiotics could be used to prevent post-surgical infections in orthopaedic or trauma.

Anti-Bacterial Agents↗
PubMed2002

Bone growth in biomimetic apatite coated porous Polyactive 1000PEGT70PBT30 implants.

We recently, developed a simple one-day one-step incubation method to obtain bone-like apatite coating on flexible and biodegradable Polyactive 1000PEGT70PBT30. The present study reports a preliminary biological evaluation on the coated polymer after implantation in rabbit femurs. The porous cylindrical implants were produced from a block fabricated by injection molding and salt leaching. This technique provided the block necessary mechanical integrity to make small cylinders (diameter 3.5 x 5 mm2) that were suitable for implantation in rabbits. The coating continuously covered the surface of the polymer, preserving the porous architecture of outer contour of the cylinders. Two defects with a diameter of 3.5 or 4 mm were drilled in the proximal and distal part of femur diaphysis. The implants were inserted as press-fit or undersized into the cortex as well as in the marrow cavity. The polymer swelled after implantation due to hydration, leading to a tight contact with the surrounding bone in both defects. The adherence of the coating on the polymer proved to be sufficient to endure a steam sterilization process as well as the 15% swelling of the polymer in vivo. The coated Polyactive 1000PEGT70PBT30 has a good osteoconductive property, as manifested by abundant bone growth into marrow cavity along the implant surface during 4-week implantation. A favorable bioactive effect of the coating with an intimate bone contact and extensive bone bonding with this polymer was qualitatively confirmed. Concerning the bone ingrowth into the porous implant in the defect of 4 mm diameter, only marginal bone formation was observed up to 8 weeks with a maximal penetration depth of about 1 mm. The pore interconnectivity is important not only for producing a coating inside the porous structure but also for bone ingrowth into this biodegradable material. This preliminary study provided promising evidence for a further study using a bigger animal model.

Animals↗
PubMed2002

Biocompatibility and degradation of poly(ether-ester) microspheres: in vitro and in vivo evaluation.

Microspheres of a hydrophobic and a hydrophilic poly(ether-ester) copolymer were evaluated for their in vitro and in vivo biocompatibility and degradation. The microspheres prior to and after sterilization were tested for in vitro cytotoxicity. The in vivo biocompatibility of the poly(ethylene glycol) terephthalate and poly(butylene terephthalate) (PEGT/PBT) microspheres was evaluated subcutaneously and intramuscularly for 24 weeks in rabbits. The in vivo degradation of the microspheres was studied microscopically and compared to the in vitro degradation. The in vitro and in vivo studies showed the biocompatibility of the microspheres of both the hydrophobic and the hydrophilic PEGT/PBT copolymer. Extracts of these microspheres showed no cytotoxic reactivity in the in vitro cytotoxicity test. Sterilization of the microspheres by gamma irradiation did not affect the cytotoxicity. PEGT/PBT microspheres injected subcutaneously and intramuscularly in rabbits showed a mild tissue response in vivo, in terms of the inflammatory response, the foreign body reaction and the granulation tissue response. Although an in vitro degradation experiment showed a decrease in molecular weight due to hydrolysis, the in vivo degradation of the microspheres was slower than previously published.

Animals↗
PubMed2002

Tolerance of mycophenolate mofetil in end-stage renal disease patients with ANCA-associated vasculitis.

BACKGROUND: Mycophenolate mofetil (MMF) has been used successfully in patients with ANCA-associated vasculitis as maintenance therapy. Only transient and moderate side effects have been reported with a daily dose of 2 g. Since all the treated patients who have been reported so far had no or only moderate renal insufficiency when MMF was initiated, no data are available regarding side effects in patients with end-stage renal disease (ESRD). METHODS: Five ESRD patients with ANCA-associated vasculitis and a relapsing course of their disease were treated. All patients had pretreatment with cyclophosphamide for at least 17 months. MMF was initiated as a remission maintenance therapy, and started with a dose of 1 g/d. The aim was to increase the MMF dose to 2 g/d. Blood counts, liver enzymes and gastrointestinal side effects were monitored. RESULTS: Four patients developed severe anemia, 2 requiring blood transfusion with permanent or temporary cessation of MMF treatment. One patient developed leukopenia. Gastrointestinal symptoms led to a dose reduction to 1 g/d (n = 2) or cessation of treatment (n = 1). Three patients remained on longer MMF treatment; however, their daily dose did not exceed 1 g. CONCLUSION: MMF, a promising drug regarding maintenance therapy in ANCA-associated vasculitis, seems to have more side effects in ESRD patients, leading to dose reduction or even cessation of treatment. Therefore, in this patient group a lower dose and closer monitoring for side effects seems to be required compared to patients with no or moderate renal insufficiency.

Adult↗
PubMed2001

Biomimetic coprecipitation of calcium phosphate and bovine serum albumin on titanium alloy.

Titanium alloy implants were precoated biomimetically with a thin and dense layer of calcium phosphate and then incubated either in a supersaturated solution of calcium phosphate or in phosphate-buffered saline, each containing bovine serum albumin (BSA) at various concentrations, under physiological conditions for 48 h. Coated implants then underwent scanning electron microscopy, immunohistochemical evaluation, Fourier transform infrared spectroscopy, and X-ray diffraction. The quantity of BSA taken up by coatings and the kinetics of protein release were monitored colorimetrically. In coatings prepared by the coprecipitation of calcium phosphate and BSA, protein had become incorporated into the mineral crystal latticework. With increasing BSA concentration, matrices decreased in thickness, became more dense, showed lower crystallinity, and underwent a change in crystal geometry. The octacalcium phosphate structure manifested in the absence of protein was gradually transformed into a carbonated apatite form. Preformed mineral coatings became only superficially mantled with a layer of BSA, and the morphology of the mineral matrices themselves remained unchanged. At equivalent protein concentrations, coatings prepared by the coprecipitation of calcium phosphate released only a minute fraction of its protein component under physiological conditions, whereas preformed mineral matrices showed a "burst" release of their associated protein within a single 2-h period. The biomimetic coating can be a carrier for osteoinductive agents.

Alloys↗
PubMed2001

Genotype versus phenotype: conflicting results in mapping a lung tumor susceptibility locus to the G7c recombination interval in the mouse MHC class III region.

Susceptibility to chemically induced lung tumorigenesis has previously been mapped to a genomic interval of 27 kb in the MHC class III region of the mouse using two H2 (a/b) intra- H2 recombinants, B10.A(1R) and B10.A(2R). Three genes are located within this interval, G7e (encoding a viral envelope protein), G7a/ Vars2 (encoding valyl-tRNA synthetase), and G7c (a gene with unknown function). A 70 kb contig, spanning the 27 kb region and extending 20 kb either side, was constructed from lambda phage libraries with genomic inserts derived from mouse strains B10.A(1R) and B10.A(2R). The region was analyzed for single-nucleotide polymorphisms, which would facilitate further fine mapping of the interval. Analysis of the expression levels of the candidate genes did not reveal any difference between B10.A(1R) and B10.A(2R). In addition, no differences were found at the sequence level in the 27 kb interval except for an A to T transition in intron 7 of G7c. A database comparison of the sequence surrounding this polymorphism did not identify any DNA-binding or enhancer consensus sequence. In conclusion, the previously observed phenotype could not be associated with or assigned to any of the candidate genes G7e, G7a/ Vars2, or G7c, nor could any of the other susceptibility loci, which have been reported to map to this region ( Cps1, Acp, Orch1, and Igis1).

Animals↗
PubMed2001

Bone induction by porous glass ceramic made from Bioglass (45S5).

Porous glass ceramic, which was prepared from Bioglass powder (45S5, U.S. Biomaterials) by foaming with diluted H(2)O(2) solution and sintering at 1000 degrees C for 2 h, was implanted as cylinders (5 mm in diameter and 6 mm in length) in thigh muscles of dogs for 3 months. Histological observation was made on thin un-decalcified sections. Bone formation was histologically found in pores of all implants (X16) retrieved from 16 dogs. The bone tissue was also identified with backscattered scanning electron microscopy observation (BSE) and energy dispersive X-ray microanalysis (EDX). This is the first report of bone induction in soft tissues of animals by glass ceramic that has long been recognized as a bioactive (osteoconductive) biomaterial. The present results justify the impetus to investigate the osteoinductivity of calcium phosphate-based biomaterials, to study the mechanism of bone induction (osteoinduction) by calcium phosphate-based biomaterials, to develop osteoinductive calcium phosphate-based biomaterials, and to examine the relation between osteoinduction and osteoconduction.

Animals↗
PubMed2001

Standardized neurologic evaluations of 128 patients with Wegener granulomatosis.

OBJECTIVE: To assess the frequency and type of neurologic involvement in a cohort of patients with generalized Wegener granulomatosis (WG). PATIENTS AND METHODS: In a prospective analysis the clinical, electrophysiologic, radiological, and serologic data of 128 patients have been studied over a median observation period of 19 months (range, 1-60 months). RESULTS: Sixty-four patients (50%) revealed central or peripheral nervous system involvement. Peripheral neuropathy (PN) affected 56 patients, in 9 cases the central nervous system was involved, and in 6 cases the cranial nerves were involved. Thirty-one patients showed a distal symmetrical polyneuropathy, 25 a mononeuritis multiplex. Within the first 2 years of the disease course 47 of the 56 patients had developed their PN, sometimes as the initial symptom of WG. Patients with PN were significantly more often male (34 of 65 patients) than female (22 of 63 patients, P =.04), were significantly older at the onset of WG (median age, 53 vs 44 years; P =.001), had a significantly larger disease extent (P =.001), and had higher classic antineutrophil cytoplasmic antibody titers (P =.002) than neurologically unaffected patients. Response to immunosuppression was moderate concerning peripheral nervous system manifestations. CONCLUSIONS: Peripheral neuropathy is frequent in generalized WG, occurring early in the disease course. As PN can be the first and sole symptom of a beginning systemic vasculitis, it is important that in cases of PN of an unclear origin, interdisciplinary investigations are initiated to detect, treat, and closely follow-up a possible underlying WG, especially as these patients seem to have a more severe disease course.

Adolescent↗
PubMed2001

Osteoclastic resorption of biomimetic calcium phosphate coatings in vitro.

A new biomimetic method for coating metal implants enables the fast formation of dense and homogeneous calcium phosphate coatings. Titanium alloy (Ti6Al4V) disks were coated with a thin, carbonated, amorphous calcium phosphate (ACP) by immersion in a saturated solution of calcium, phosphate, magnesium, and carbonate. The ACP-coated disks then were processed further by incubation in calcium phosphate solutions to produce either crystalline carbonated apatite (CA) or octacalcium phosphate (OCP). The resorption behavior of these three biomimetic coatings was studied using osteoclast-enriched mouse bone-marrow cell cultures for 7 days. Cell-mediated degradation was observed for both carbonated apatite and octacalcium phosphate coatings. Numerous resorption lacunae characteristic of osteoclastic resorption were found on carbonated apatite after cell culture. The results showed that carbonated apatite coatings are resorbed by osteoclasts in a manner consistent with normal osteoclastic resorption. Osteoclasts also degraded the octacalcium phosphate coatings but not by classical pit formation.

Alloys↗
PubMed2001

The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review.

BACKGROUND: The study aimed at studying efficacy and adverse effects of pulse cyclophosphamide (pCyc) treatment and to compare it to continuous cyclophosphamide (cCyc) for induction of remission in ANCA-associated vasculitides from data in the published literature. METHODS: A Medline search identified 14 studies, containing more than five patients. From the 11 non-randomized studies, data on outcome following pCyc treatment were extracted. Results were given as fraction of the number of evaluable patients. A meta-analysis was performed on the three prospective, randomized controlled trials to compare outcomes concerning remission, relapses, infection, leucopenia, death and renal failure in patients treated with pCyc as opposed to cCyc. RESULTS: The 11 non-randomized studies comprised 202 patients receiving pCyc. Cyc pulses of 375-1000 mg/sqm/pulse were applied at weekly to monthly intervals with different concomitant prednisolone regimens and variable adjunctive therapy. Complete remission was achieved in 112/191, partial remission in 23/191 evaluable patients. Relapses occurred in 68/135 patients, 40/115 patients were non-responders. Leucopenia, infections, haemorrhagic cystitis, and deaths were rare. The meta-analysis, comprising 143 patients, showed that pCyc compared with cCyc treatment was significantly less likely to fail to induce remission (OR 0.29; 95% CI 0.12-0.73) and had a significantly lower risk of infection (OR 0.45; 95% CI 0.23-0.89) and leucopenia (OR 0.36; 95% CI 0.17-0.78). Relapses occurred slightly, although not statistically significantly, more often under pCyc treatment (OR 1.79; 95% CI 0.85-3.75). There were no differences in end-stage renal failure or deaths between the two regimens. CONCLUSIONS: The currently available, rather sparse data show that pCyc is less toxic than cCyc therapy and is an at least equally potent inductor of remission, but possibly at the expense of a higher relapse rate. The existing data do not give sufficient information on outcomes as time to remission and relapse, irreversible damage or quality of life without which a treatment regimen cannot satisfactorily be evaluated today. A large prospective randomized controlled trial is needed to address these issues and their relative importance.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Development and validation of a disease extent index for Wegener's granulomatosis.

AIMS: The quantitative assessment of disease extent (staging) and activity (grading) in patients with ANCA-associated vasculitides is one prerequisite for the comparison of outcomes in different patient cohorts. We present a validation study of the Disease Extent Index (DEI). METHODS: 66 patients with Wegener's granulomatosis were examined to assess the validity, reliability and sensitivity to change of the DEI. Correlation coefficients were calculated to estimate associations between DEI and BVAS (Birmingham Vasculitis Activity Score), a previously established activity score, and between DEI and serological markers. RESULTS: Among patients with active disease, DEI correlated significantly with cANCA titer (r = 0.46), leukocyte count (r = 0.38) and platelet count (r = 0.53). Among patients in remission, DEI correlated significantly with cANCA titer (r = 0.61), CRP (r = 0.47) and sIL2R (r = 0.47). Additionally, a high association of DEI and BVAS (r = 0.9) confirmed a rather high convergent validity. The effect size of DEI equals 2.37 standard deviation units and indicates a considerable change from active disease to remission. CONCLUSIONS: The DEI is valid, reliable, easy, quick to perform and highly reproducible. Although it correlates with some surrogate markers of disease activity and the BVAS, the DEI quantifies different domains of the disease than the BVAS and should therefore be used in conjunction with the BVAS.

Female↗
PubMed2000

Formation of calcium phosphate/collagen composites through mineralization of collagen matrix.

Several types of calcium phosphate/collagen composites, including noncrystalline calcium phosphate/collagen, poorly crystalline carbonate-apatite (PCCA)/collagen, and PCCA + tetracalcium phosphate/collagen composites, were prepared through the mineralization of collagen matrix. The type I collagen was presoaked with a PO(3-)(4) containing solution and then immersed in a Ca(2+) containing solution to allow mineral deposition. The solution of 0.56 M sodium dibasic phosphate (Na(2)HPO(4)) with a pH of nearly 14 was metastable and its crystallization produced Na(2)HPO(4) and sodium tripolyphosphate hexahydrate (Na(5)P(3)O(10)). 6H(2)O), leading to a controlled release of orthophosphate ions during the subsequent mineral precipitation. The development of the composites was investigated in detail. The mineral contributed up to 60-70% of the weight of the final composites. The strength and Young's modulus of the composites in tensile tests overlapped the lower range of values reported for bone. When implanted in muscle tissue, the composite showed biodegradability that was partly through a multinucleated giant cell mediated process. In a bone explant culture model it was observed that bone-derived cells deposited mineralizing collagenous matrix on the composite.

Animals↗
PubMed2000

An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients.

OBJECTIVE: To examine the outcome in 155 consecutive patients with Wegener's granulomatosis (WG) followed up for a median of 7 years. METHODS: Treatment was adapted to the activity and extent of disease, with regular evaluation by an interdisciplinary team accompanied by group education about vasculitis. RESULTS: The estimated median survival time was 21.7 years (95% confidence interval [95% CI] 15.60-27.86). Twenty-two patients died; 19 deaths were attributable to WG and/or its treatment. Significant predictors of survival at diagnosis were age >50 years (hazard ratio [HR] 5.45, 95% CI 1.97-15.02), kidney involvement with impaired renal function (HR 5.42, 95% CI 1.76-16.68), and lung involvement (HR 3.75, 95% CI 1.26-11.16). At some stage, 142 patients received prednisone and cyclophosphamide (CYC), usually as daily CYC plus mesna as uroprotection, 50 patients received trimethoprim/sulfamethoxazole, and 45 received methotrexate. Complete remission was achieved in 83 of the 155 patients. One or more relapses occurred in 99 patients after either complete or partial remission. CYC-induced cystitis and myelodysplastic syndrome occurred in 17 and 11 patients, respectively. A cumulative dose of 100 gm or more of CYC resulted in a 2-fold greater risk of CYC-related morbidity than with lower CYC doses. Serious infections occurred in 41 patients. CONCLUSION: An interdisciplinary approach to the care of 155 WG patients resulted in a median survival of >21 years. Kidney or lung involvement at diagnosis was predictive of a >3-fold higher mortality. Although CYC remains essential in the treatment of WG, it was administered as briefly as possible and under close surveillance to avoid permanent CYC-related morbidity, which can lead to serious therapeutic problems in chronic relapsing WG.

Adolescent↗
PubMed2000

Tissue responses of calcium phosphate cement: a study in dogs.

The in vivo properties of a new kind of calcium phosphate cement were investigated in this study. Calcium phosphate cement was implanted as paste into femoral bone and dorsal muscle of dogs for 3 and 6 months, and as prehardened form into thigh muscles of dogs for 1, 2 and 6 months. Histology was performed on thin un-decalcified sections. No foreign body reaction, no inflammation and no necrosis were found both in bony site and in muscles. There was no connective tissue layer between the cement and bone when cement paste was implanted in the bone. A creeping substitution of cement by bone, in which osteoclast-like cells resorbed the cement as if the cement is a part of bone and new bone was formed directly on the resorption line of calcium phosphate cement, was found. Bone formation was found histomorphologically in pores and deep rugged surface of cement samples (both paste and prehardened form) implanted in muscles of dogs. The induced bone was also identified with backscattered scanning electron microscopy (BSE) and by energy-dispersive X-ray micro-analysis (EDX). The results suggest that the calcium phosphate cement used in this study is biocompatible, resorbable in a manner of creeping substitution, osteoconductive and osteoinductive. It seems that an ideal bone substitute can be developed by using this type of calcium phosphate cement.

Absorbable Implants↗
PubMed1999

Three-dimensional nano-HAp/collagen matrix loading with osteogenic cells in organ culture.

Transplantation of osteogenic cells with a suitable matrix is one strategy for engineering bone tissue. Three-dimensional distribution and growth of cells within the porous scaffold are of clinical significance for the repair of large bony defects. A nano-HAp/collagen (nHAC) composite that mimics the natural bone both in composition and microstructure to some extent was employed as a matrix for the tissue engineering of bone. A porous nHAC composite was produced in sheet form and convolved to be a three-dimensional scaffold. Using organ culture techniques and the convolving method, we have developed three-dimensional osteogenic cells/nHAC constructs in vitro. Scanning electron microscopic and histological examination has demonstrated the development of the cells/material complex. Spindle-shaped cells migrating out of bone fragments continuously proliferated and migrated throughout the network of the coil. The porous nHAC scaffold provided a microenvironment resembling that seen in vivo, and cells within the composite eventually acquired a tridimensional polygonal shape. In addition, new bone matrix was synthesized at the interface of bone fragments and the composite.

Animals↗