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Biomedical subjects

T Turek

Publications and source records attributed to T Turek.

At least 19 recordsLinked to original sources

Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model.

The purpose of the present study was to determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated implants and gap healing around the implants. In the presence of a 3-mm gap between the implant and host bone, porous-coated implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs. In three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in buffer at a dose of 100 microg/implant (n=5), 400 microg/implant (n=6), or 800 microg/implant (n=5) and placed in the left humerus. In these same animals, an internal control implant was treated only with HA/TCP and buffer and placed in the right humerus. These groups were compared with a previously reported external control group of seven animals in which no growth factor was delivered [J. Orthop. Res. 19 (2001) 85]. The BMP treated implants in the two lower dose groups had significantly more bone ingrowth than the external controls with the greatest effect in the 100 g/implant group (a 3.5-fold increase over the external control, p=0.008). All three dose groups had significantly more bone formation in the 3-mm gap surrounding the BMP treated implants than the external controls with the greatest effect in the 800 microg group (2.9-fold increase, p<0.001). Thus, application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth and gap healing. The enhancement of bone formation within the implant (bone ingrowth) was inversely related to dose.

Animals↗

[The effect of small doses of 7.5% NaCl on brain bulk during elective craniotomies].

In 16 patients (ASA I i II) aged 16-76 years (48 +/- 15; mean +/- SD) operated on because of intracranial expanding mass, the effect of hypertonic saline (7.5%--1 ml/kg b.w.) on brain bulk (BB) was evaluated. Patients were anaesthetised with a slight hypocarbia (PaCO2 = 33.3 +/- 3.5 mmHg). BB was scored after opening the dura (T0) and 15 min. (T15) after hypertonic saline (HS) infusion. Five points BB scale was used. Brain bulk reduction (D BB) was calculated as a difference: BB15-BB0. Tomographic signs of intracranial expansion (TSIE) in preoperative CT were scored using the scale from 5 to 15 points assessing (1 to 3 points) the size of mass lesion, the size of perifocal oedema, midline shift, displacement of ventricles and basal cisterns compression. Systolic (SBP), diastolic (DBP) blood pressures and heart rate (HR) were monitored. Serum natrium (SNa), kalium (SK) and osmolarity (Sosm) were measured at T0, T15 and Tp0 (one hour after operation). Student's t-test, Wilcoxon test and Spearman correlation were used for statistical analysis. P < 0.05 was considered as statistically significant. HS caused significant decrease in BB (p = 0.002). In 12 patients with a solid brain tumor a negative correlation between BB and TSIE was found (r = -0.68). A slight but significant decreases in SBP and DBP at Tp0 and T15 as well as decrease in HR due to HS were stated. SNa and Sosm increased at T15 and reminded elevated at Tpo. We can conclude that 7.5% saline in a dose of 1 ml/kg b.w. reduces brain bulk during craniotomy in patients with supratentorial mass lesions. In patients with a solid brain tumor this effect correlates negatively with a size of expanding mass. A slight changes in blood pressure and heart rate due to HS as well as moderate decrease in SK are within limits of clinical acceptance.

Adolescent↗

Our own experience with CT angiography in early diagnosis of cerebral vascular malformations.

Computed tomography (CT) and intraarterial cerebral angiography are essential methods in early diagnosis of cerebral vascular malformations. In recent years however non-invasive or minimally invasive methods like MR angiography and CT angiography (CTA), which could potentially replace angiography, have been developed. The aim of presented study is to demonstrate our own experience in application of CTA in early diagnosis of cerebral vascular malformations. The material consists of 86 CTA examinations performed shortly after non-traumatic intracranial haemorrhage. Angiographic correlation has been available in 23 patients and surgical one--in 31 cases. CTA studies began with serio-CT to select the optimal time between contrast injection and CT scanning. After that 100-120 ml of non-ionic contrast medium was injected intravenously (5 ml per sec.) and spiral CT acqusition was performed with the delay calculated on the basis of the serio-CT. The obtained images were postprocessed on the workstation using always MIP and in many cases also SSD and VRT reconstructions. Vascular malformations have been diagnosed in 44 of 86 CTA studies including 38 patients with aneurysms (total number 51) and 6 patients with AVMs. In 17 cases the diameter of the aneurysm did not exceed 5 mm. In all surgical cases the CTA diagnosis of the aneurysm has been confirmed. There was however one false-negative case. On the other hand in 7 patients CTA revealed the small aneurysm, despite unclear angiographic appearance. In 2 of 6 patients with CTA suspicion of AVM this diagnosis has been excluded either by angiography or surgery. Comparison of CTA and angiography in 22 aneurysms showed in 17 cases superiority of CTA in evaluation of aneurysmal neck and the relationship between aneurysm and adjacent vessels (especially with VRT and SSD reconstructions). In patients with AVMs however the evaluation of supplying and draining vessels was better with angiography. On the base of our material we can conclude that CTA is very efficient in detecting and evaluating the aneurysms. We believe that CTA can replace angiography if it reveals aneurysm in a site corresponding with location of haemorrhage on CT. In patients with suspicion of AVM value of CTA is doubtful and angiography remains the method of choice.

Cerebral Angiography↗

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair.

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.

Animals↗

Use of bone morphogenetic protein-2 in the rabbit ulnar nonunion model.

The ability of the osteoinductive protein and recombinant human bone morphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defect was tested in a rabbit diaphyseal defect model. Two centimeter nonuniting defects were surgically created in the bilateral ulnae of 50 male New Zealand white rabbits. Each defect was then implanted with a pastelike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogenetic protein-2. The forearms were radiographically assessed on a biweekly schedule for 8 weeks. At 8 weeks, all animals were sacrificed and forearms radiographed. Radiographs were then scored by 3 independent observers for bone formation and union rates. United limbs were tested in torsion for mechanical strength using a Burstein torsion tester. All nonunited limbs were analyzed histologically as were 2 united limbs from each dosage group. Radiographic evaluation revealed that there was a dose dependent response in healing of the ulnar defect with a higher bone formation rate in the 2 higher dose limbs than in the lower dose limbs. Union was achieved in 100% of the highest dose limbs, whereas only 50% of the lowest dose limbs achieved bony union. No defects implanted with carrier alone achieved union. Biomechanical studies revealed significantly stiffer bone than age matched controls. Histologic analysis demonstrated normal bone formation with abundant normal appearing osteoid. These dose response data further support the role of recombinant human bone morphogenetic protein-2 as a potent morphogen in bone regeneration.

Animals↗

BMP-2 for intramuscular bone induction: effect in squirrel monkeys is dependent on implantation site.

Demineralized bone matrix (DBM) reproducibly induces extraskeletal bone formation in rodents, but its effects in dogs and primates are negative or uncertain. In previous studies on the squirrel monkey, DBM did not induce bone, although the same implants were effective in rats. DBM implants augmented with recombinant human bone morphogenetic protein-2 (rhBMP-2) induced intramuscular bone formation in squirrel monkeys. However, the amount of induced bone was often minimal and sometimes absent. One explanation of this weak and unpredictable effect could be reactions to cellular components of the allogeneic DBM that was used as carrier. Therefore, we now repeated the experiment, using bovine type 1 collagen as carrier. 48 collagen discs (10 mm diameter), containing 0, 10, 40 or 200 microgram rhBMP-2, were implanted in 6 monkeys and 6 rats. The BMP-2 implants induced dose-dependent amounts of intramuscular bone in rats whereas, in squirrel monkeys, macroscopic bone induction occurred in less than half of the BMP-2 implants. There was no dose-dependency. Whether bone was formed or not was significantly influenced by individual variation among the monkeys, and by implant location within the muscle. Implants close to the muscle aponeurosis more often induced bone than did purely intramuscular ones. In this small series, we could not demonstrate a significant effect of BMP-2, as compared to control implants. Presumably there were too few cells expressing BMP-2 receptors in the only minimally traumatized muscle of these monkeys.

Animals↗

Incidence of analgesic nephropathy among patients undergoing renal replacement therapy in Czech Republic and Slovak Republic. The Group of Czech and Slovak Nephrologists.

BACKGROUND: The occurrence of analgesic nephropathy (AN) among renal replacement therapy patients in former Czechoslovakia is not known. Previous surveys were not based on representative samples and lacked uniform criteria for diagnosing the disease. METHODS: Incidence of AN in former Czechoslovakia was investigated in patients commencing renal replacement therapy in 24 (1/3 of all) dialysis centres from 1 January to 31 December 1992. Patients showing an unclear renal diagnosis (n = 149) were investigated with an interview and renal imaging techniques. The diagnosis of AN was withheld or rejected on the base of recently published diagnostic criteria demonstrating that a decreased renal mass of both kidneys combined with bumpy contours and/or papillary calcifications had a high performance for diagnosing AN (Nephrol Dial Transplant 1992; 7: 479-486). RESULTS: Based on the renal imaging criteria, AN was diagnosed in 30 of 328 registered patients, resulting in an AN incidence of 9.1% while the EDTA data only mentioned an incidence of 4.8% (period 1986-1989). The products most commonly abused were analgesic mixtures containing two analgesic substances combined with caffeine and/or codeine. CONCLUSIONS: AN was found to be a common disease in the Czech and Slovak Republics. The disease was diagnosed using reliable renal imaging criteria.

Adolescent↗

[The value of CT in diagnosis of low back pain syndromes].

The authors discuss results of CT studies in 300 patients with low back pain syndromes. Apart from herniated discs (56.3% of cases) pain could be often explained by degenerative changes of facet joints or bulging disc leading to spinal canal stenosis. In the group of patients operated on due to disc herniation correlation between CT and surgical results has 85.4%. In the authors' opinion CT is an effective, non-invasive diagnostic method in patients with low back pain syndromes.

Adolescent↗

[Use of multiplanar reconstruction of CT images (MPR) in diagnosis of low back pain syndromes].

The authors describe program of multiplanar reconstruction of CT images (MPR) and discuss its usefulness in diagnosing low back pain syndromes. The program was especially useful in differentiation between herniated disc and osteophytes, in spondylolisthesis and in the cases of asymmetric spine. MPR enables also imaging of pathological spinal lesions in the operative view which is helpful for planning of the surgery. In the authors' opinion CT with MPR is not inferior and in some authors aspects even superior to MR imaging.

Diagnosis, Differential↗

Recombinant human bone morphogenetic protein-2 is superior to demineralized bone matrix in repairing craniotomy defects in rats.

The purpose of this study was to measure bone-regenerative effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) in rat calvarial critical-size defects (CSDs). CSDs (8 mm in diameter) were treated with either 1) 2.2 micrograms rhBMP-2 combined with insoluble collagenous bone matrix (ICBM), 2) 6.5 micrograms rhBMP-2 plus ICBM, 3) ICBM alone, or 4) demineralized bone matrix (DBM), for 7, 14, or 21 days. Multiple linear regression showed that rhBMP-2 had a significant time- and dose-dependent effect on bone regeneration (P < .05). After 7 days, new calcifying cartilage and remineralizing ICBM, with an occasional zone of new woven bone, was evident in defects treated with rhBMP-2/ICBM. By 14 days, both doses of rhBMP-2 reconstituted with ICBM had induced more bone formation than ICBM alone or DBM, and 6.5 micrograms was superior to 2.2 micrograms. There was no evidence of adverse cellular response. This study shows for the first time that rhBMP-2 could restore osseous form to a calvarial defect. In addition, osteoregeneration was accelerated by the higher dose of rhBMP-2.

Animals↗

Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2).

In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP-2 restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP-2 yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21-day time point. Although small differences between delivery systems were evident at 0- and 10-micrograms rhBMP-2 doses, all test articles performed essentially equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2 offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials.

Alginates↗

Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to enhance the repair of congenital or acquired bone pathologies when formulated in the appropriate carrier. Poly [D,L-(lactide-co-glycolide)] (PLGA) has been shown to be an effective carrier of rhBMP-2. We investigated several particle sizes PLGA and several doses of rhBMP-2 in a rat orthotopic model. We also investigated the effects of a fibrinolytic inhibitory agent, epsilon aminocaproic acid (EACA), on the healing response. Our data indicate that higher doses of rhBMP-2 resulted in increased failure torque (408 +/- 70 N-mm or 60% of the intact value) and higher incidence of union (100%). The induced bone in femurs treated with the smaller particle size PLGA achieved the greatest torsional stiffness and strength. The presence of rhBMP-2 was necessary for new bone to form, but the presence of EACA did not change these results; the use of the PLGA carrier appeared to increase bone strength and stiffness. In fact, with higher doses of rhBMP-2 in PLGA, the stiffness of the new bone was equal to that of intact controls (64 +/- 20 N-mm/deg [intact femurs] versus 45 +/- 10 N-mm/degree [medium dose in small PLGA], 61 +/- 17 N-mm/degree [high dose in small PLGA], and 36 +/- 11 N-mm/degree [medium dose in large PLGA]; P > .05). In conclusion, PLGA implanted with rhBMP-2 effectively aided in healing large segmental defects in rat femurs.

Animals↗

Controlled release of polypeptides from polyanhydrides.

The effects of both polymer hydrophobicity and addition of stabilizers on the release and integrity of polymer-encapsulated proteins were studied. By using very hydrophobic poly[1,3-bis(p-carboxyhydroxy)hexane anhydride] with sucrose as an excipient, both recombinant bovine somatotropin and zinc insulin were released intact over 3 weeks. The released proteins appeared to maintain their integrity as judged by acidic reverse-phase HPLC, size-exclusion HPLC, radioimmunoassay, and conformation-sensitive immunoassays. Our results also suggest how polymer hydrophobicity can be used to enhance protein stability.

Animals↗

Biotechnology and bone graft substitutes.

Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages. A critical need for improved treatment methods exists today. Biotechnology now provides access to new bone repair concepts via administration of protein growth and morphogenic factors. Implantable device and drug delivery system technologies also have advanced. The converging biopharmaceutical, device, and delivery technologies represent an opportunity to improve the quality of health care for individuals with orthopedic and maxillofacial deficiencies. This report reviews current concepts in fracture healing and bone repair and examines existing treatment modalities. It also addresses novel protein drugs that stimulate osseous regeneration and delivery systems for these drugs.

Amino Acid Sequence↗

Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.

Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.

Analysis of Variance↗