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Biomedical subjects

A Stemberger

Publications and source records attributed to A Stemberger.

At least 19 recordsLinked to original sources
PubMed2005

Systemic versus local application of gentamicin in prophylaxis of implant-related osteomyelitis in a rat model.

Administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. Besides systemic prophylaxis, only few techniques are established for local application of antibiotics to reduce infection related to orthopedic implants. The aim of this study was to evaluate the efficacy of locally versus systemically applied gentamicin in a rat model (n = 60). For local application, the antibiotic was delivered from a biodegradable poly(D,L-lactide) (PDLLA) coating of titanium implants. The efficacy of local prophylaxis was compared to a systemic single shot application of gentamicin as well as a combination of both administrations. Half of the animals received a weight-adopted single shot application of gentamicin 30 min prior to surgery. At surgery, the medullary cavities of the tibiae were contaminated with Staphylococcus aureus (10(2) colony forming units /CFU) and titanium Kirschner wires were implanted into the medullary canals. The implants were either uncoated, PDLLA coated, or coated with PDLLA + 10% w/w gentamicin. The animals were followed up for 42 days. X-ray examinations were performed; body weight, temperature, and the clinical condition were determined. After sacrifice, infection was evaluated by histological and microbiological analysis. All animals treated with uncoated or PDLLA-coated Kirschner wires without systemic application of the antibiotic developed osteomyelitis and all cultures of implants were tested positive on S. aureus. Implant-related osteomyelitis could be prevented by prophylaxis of systemically applied gentamicin in 15% of animals. In contrast, local application of gentamicin delivered from a PDLLA coating was more effective. Onset of infection could be prevented in 90% of animals treated with gentamicin coated Kirschner wires, and in 80% of the animals that were treated with a combination of local and systemic application. The local application from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis.

Animals↗
PubMed2004

Effects of laser-modified versus osteopromotively coated titanium membranes on bone healing: a pilot study in rat mandibular defects.

Regeneration of alveolar bone with membrane techniques has become an integral part of implant dentistry. The aim of the present study was to determine if laser-modified titanium membranes are of value in the regeneration of so-called critical size defects in the rat model compared with titanium membranes that were coated with growth factors. A total of 24 rats were included in the study. Critical size defects were created bilaterally and covered by titanium membranes coated with (1). polylactide, (2). polylactide and clindamycin, (3). polylactide and growth factors, (4). polylactide, clindamycin and growth factors and (5). uncoated but laser-modified titanium membranes. All 18 control defects were covered by titanium membranes without any substrate. Four weeks after treatment the animals were killed. Laser-modified titanium membranes (group 5) showed new bone formation in many areas. Nevertheless, complete bridging was found only in one specimen. In contrast, in groups 3 and 4, most defects showed almost complete bridging of the defects. In particular, clindamycin had no inhibitory effect on bone healing. Furthermore, after 28 days, there was no significant difference between the individual groups (including controls) with respect to the total amount of lamellar bone. Growth-factor-coated membranes can significantly accelerate the healing process of bony defects in the rat mandibular model. Nevertheless, it is not possible to accelerate bone healing with laser-irradiated membranes or to enhance the quality of bone within the time period examined.

Animals↗
PubMed2003

A new model of implant-related osteomyelitis in rats.

Infection related to osteosynthesis often has dramatic consequences for the patient. Prolonged hospitalization with systemic antibiotic therapy, several revision procedures, possible amputation, and even death may occur. To investigate the pathology of infection in orthopedic surgery, a new rat model of implant related osteomyelitis was developed. Three different concentrations (10(6), 10(3), and 10(2) colony-forming units (CFU)/10 microl) of Staphylococcus aureus were inoculated into the tibial medullary cavity with simultaneous insertion of a titanium Kirschner wire. Controls received phosphate-buffered saline (PBS). Each group consisted of 10 animals. Animals were followed for 4 weeks until sacrifice. X-rays of the tibiae were taken weekly, blood counts were analyzed, and body temperature and weight were determined. After sacrifice, infection was evaluated by histological and microbiological investigations. All animals inoculated with Staph. aureus in either concentration developed microbiological, histological, and radiological signs of osteomyelitis in correlation to the amount of inoculated bacteria. X-rays clearly revealed osseous destruction after 14 days with progression of osteomyelitis during the following weeks. CFU/g bone and bone weight after sacrifice showed dependence on the amount of inoculated CFU. The histological results confirmed the radiological findings. No significant changes in blood counts, body weight, and body temperature between the groups could be observed. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with dependence on the amount of inoculated bacteria. No other promoters of infection besides intramedullary insertion of titanium Kirschner wires were used in this model.

Animals↗
PubMed2001

Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors.

Local application of growth factors like insulin like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta1) from a biodegradable thin layer of poly(D,L-lactide) (PDLLA) coated implants could stimulate fracture healing. A new "cold coating technique" for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 microm on titanium and 10.7 microm on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF-I and 48% TGF-beta1 were released within the first 48 h. After 42 days, 76% of IGF-I and 71% of TGF-beta1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days.

Animals↗
PubMed2001

Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats.

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1). However, for therapeutic use in fracture treatment, questions remain with regard to the local application of these proteins. A controlled, local release of growth factors from a biodegradable polylactide coating of osteosynthetic implants may have a stimulating effect on fracture healing. Such implants could stabilize the fracture and their bioactive surface could function simultaneously as a local drug-delivery system. Previous studies have demonstrated the high mechanical stability of an approximately 10-14-microm-thick poly(D,L-lactide) (PDLLA) coating on metallic implants, which can even withstand the process of intramedullary insertion. Following an initial peak, 80% of incorporated growth factors IGF-1 and TGF-beta1 were continuously released within 42 days. The effect of locally applied IGF-1 and TGF-beta1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing was investigated in a rat model. Midshaft fractures of the right tibia of 5-month-old female Sprague-Dawley rats (n = 127) were stabilized with coated vs. uncoated titanium Kirschner wires. X-ray examinations and blood analyses were performed, and body weight and body temperature measurements were taken throughout the experimental period. After 28 and 42 days, respectively, tibiae were dissected for mechanical torsional testing and histomorphometrical analyses. X-rays demonstrated an almost completely consolidated fracture, biomechanical testing showed a significantly higher maximum load and torsional stiffness, and histological and histomorphometric analyses demonstrated progressed remodeling after 28 and 42 days in the group treated with growth factors as compared with controls. Interestingly, the PDLLA coating itself revealed a positive effect on fracture healing even without incorporated growth factors. No systemic changes of serum parameters, including IGF-1 and IGF binding proteins, and no differences in body weight and body temperature were observed within and between groups. These findings suggest that the local application of growth factors from a biodegradable PDLLA coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.

Animals↗
PubMed2001

Hirudin protects from leukocyte/endothelial cell interaction induced by extracorporeal circulation.

BACKGROUND: The clinical complications of Extracorporeal Circulation (ECC) have been linked to disturbances in the microcirculation. In order to prevent these deleterious effects, a biodegradeable agent to coat the extracorporeal circuit was tested. METHODS: Intravital fluorescence microscopy was used on the hamster skinfold chamber model in permanently instrumented, awake animals. ECC was introduced via a micro-roller-pump and a silicon tube shunted between the carotid artery and the jugular vein. The ECC-tube system was coated with PEG-Hirudin-Iloprost, two additional groups received either Iloprost i.v. (0.8 mg/kg/h) or Hirudin i.v. (1 mg/kg b.w.). RESULTS: ECC for 20 minutes resulted in an increase in rolling and adherent leukocytes in postcapillary venules (Roller 9 to 36 [%]; Sticker 24 to 330 [n/mm2]). Use of the coated tube system reduced L/E cell interaction (Roller 9 to 24* [%], Sticker 28 to 194* [n/mm2]; *p<0.05), whereas Hirudin i.v. nearly abolished it. CONCLUSIONS: The protective effects of the coating and of Hirudin i.v are probably a result of an attenuated activation of the coagulation-fibrinolytic system.

Animals↗
PubMed2000

Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and the prostacyclin analogue iloprost.

BACKGROUND: To minimize acute stent thrombosis and development of restenosis, stents coated with biodegradable and nonbiodegradable polymers have been proposed to serve as sustained-release drug carriers. METHODS AND RESULTS: In both a sheep and a pig model, we examined the vascular response to standard and high-pressure implantation of coronary Palmaz-Schatz stents coated with a 10-microm layer of polylactic acid (MW 30 kDa) releasing recombinant polyethylene glycol (r-PEG)-hirudin and the prostacyclin analogue iloprost, both drugs with antithrombotic and potentially antiproliferative effects. Study observation time was 28 days. Between the corresponding stent groups, no differences were observed with regard to preplacement and postplacement implantation parameters. The morphometric analysis demonstrated that the coating was associated with a greater lumen diameter through a reduction in the mean restenosis area by 22.9% (P<0.02) in the standard-pressure model (sheep) and by 24.8% (P<0.02) in the overstretch pig model compared with uncoated control stents without inducing a local inflammatory response. CONCLUSIONS: The results from this study demonstrate beneficial effects of a polymeric stent coating with polylactic acid releasing r-PEG-hirudin and iloprost on the development of restenosis after coronary stent placement at 4 weeks, independent of the extent of vascular injury. Future studies are proposed to investigate the integration of other substances to further enhance the potential of the stent coating on reducing neointimal formation.

Absorbable Implants↗
PubMed2000

[Local liberation of IGF-I and TGF-beta 1 from a biodegradable poly(D,L-lactide) coating of implants accelerates fracture healing].

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors like IGF-I and TGF-beta 1. However, for therapeutic use in fracture treatment, the local application of these bioactive molecules is still an unsolved problem. The controlled release of growth factors from a biodegradable coating of osteosynthetic implants could stimulate fracture healing locally. Coated implants could stabilise the fracture and work as a local drug delivery system. Previous studies demonstrated a high mechanical stability of a thin 10 microns poly(D,L-lactide) (PDLLA) coating on metallic implants that withstands even an intramedullary insertion process. After an initial peak, 80% of incorporated growth factors IGF-I and TGF-beta 1 were continuously released within 42 days. The effect of locally applied IGF-I and TGF-beta 1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing were investigated in a rat model. A fracture of the right tibia of 5-month-old female Sprague-Dawley rats was stabilised with coated versus uncoated titanium K-wires. X-ray examinations and blood analysis were performed, body weight and body temperature monitored throughout the experimental period. After 42 days both tibiae were dissected for mechanical torsional testing and histomorphometric analyses. The results demonstrate a nearly completely consolidated fracture in the X-ray examinations, a significant higher maximum load and torsional stiffness in the biomechanical tests and a progressed remodeling in the histological and histomorphometric analyses after 42 days in the group treated with growth factors compared to the controls. Interestingly, the PDLLA coating itself had a positive effect on fracture healing even without incorporated growth factors. No systemic change of serum parameters including IGF-I and IGF binding proteins and no differences in body weight and body temperature were seen in any group. These findings suggest that the local application of growth factors from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.

Animals↗
PubMed1999

Antithrombogenic coating of stents using a biodegradable drug delivery technology.

To reduce the thrombogenic properties of coronary artery stents, a biodegradable polylactic acid (PLA) stent coating with an incorporated thrombin inhibitor and a platelet aggregation inhibitor has been developed. In an ex vivo human stasis model, its effect on platelets, plasmatic coagulation and its release characteristics were studied using whole blood. Bare steel and bare gold-surface stents were compared to steel and gold-surface stents coated with PLA (30 kDa) containing 5% polyethyleneglycol (PEG)-hirudin and 1% iloprost, with an empty tube as control. Markers of activated coagulation (prothrombin fragment F1-2 and thrombin-antithrombin III complex, TAT), were assayed and the release of drugs from the coating was assessed by aPTT and collagen-induced platelet aggregation. Bare steel and gold stents were completely covered by a blood clot, and high levels of coagulation markers (F1-2 fragment and TAT) were detected. No differences in the thrombogenic properties were found between bare gold or steel stents. Coated stents were free of blood clots and only minor elevations of markers were detected. Release data from in-vitro studies over 90 days showed a gradual release of the drugs with an initial exponential release characteristic for PEG-hirudin, slow release of iloprost and a 10% degradation of the PLA carrier. This drug releasing biodegradable coating effectively reduced thrombus formation independent of the metallic surface.

Antithrombins↗
PubMed1993

Phase I--study with aprosulate, a new synthetic anticoagulant.

This paper describes the first human study with aprosulate, a new chemically synthesized anticoagulant with a defined molecular structure and a molecular weight of 2388. Twelve healthy male volunteers received subcutaneous injections of placebo on the first day followed by ascending doses of aprosulate in the range of 0.25 mg/kg to 2.0 mg/kg body weight on alternate days. Anticoagulant, pharmacokinetic and safety parameters were assessed for 48 hours after each injection. The activated partial thromboplastin time and the Heptest showed a dose-dependent increase for up to ten hours after each application. A trend towards prolongation of the bleeding time was indicated with higher doses. In general, the tolerance was good. Plasma transaminase concentrations were raised in some volunteers but returned spontaneously to normal during or after the study.

Adolescent↗
PubMed1992

[Blood coagulation and fibrinolysis in prostate surgery].

In 23 patients undergoing transurethral resection of the prostate (n = 11) or suprapubic prostatectomy (n = 12), hemostasis and fibrinolysis were studied. In addition to basic coagulation tests, antithrombin III, plasminogen, antiplasmin and fibrin degradation products were determined preoperatively, intra-operatively and postoperatively over a period of 6 days. Evaluation of the results revealed slightly activated blood coagulation and fibrinolysis intraoperatively and postoperatively, with no significant differences being seen between the two groups. Routine use of antifibrinolytic drugs in patients undergoing surgery of the prostate is not recommended.

Aged↗
PubMed1990

[Coagulation changes during aortofemoral bifurcation bypass: is volume and plasma substitution possible with hydroxyethyl starch alone?].

The study explored the possibility of eliminating the need for plasma replacement with expensive human albumin (HA) and fresh frozen plasma (FFP) and instead using hydroxyethyl starch (HES). Patients undergoing infrarenal aortofemoral bifurcation grafting were randomly assigned to one group, which received FFP and HA, or another group, which received HES as volume replacement. Blood specimens were collected at five time intervals: preoperatively, prior to cross-clamping of the aorta, prior to declamping, at the end of the operation, and 6 h postoperatively. Preoperative coagulation values were all within normal limits. The basic coagulation tests were generally affected by the standardized heparin dose of 5000 IU administered during the clamping phase. Euglobulin lysis demonstrated a perioperative climb that was particularly marked within the HES group at the time of clamping. Values returned to initial levels 6 h postoperatively. Plasminogen, fibrinogen, antithrombin III, and antiplasmin concentrations fell significantly in both groups; 10% to 20% lower values were determined within the HES group due to the lack of factor substitution. The reduction in the coagulation factors can be explained as a dilution effect, but there are also signs of a consumption reaction taking place at the onset of the operation involving activation of coagulation and fibrinolysis. Restricting the use of FFP and simultaneously increasing HES administration is justifiable in procedures involving the abdominal aorta with moderate blood loss.

Aged↗
PubMed1988

Dependence of the so-called heparin availability on experimental factors.

The so-called heparin level in the plasma of patients or healthy volunteers should be determined using only those methods which correspond to the test standard used by the producer of the heparin applied or which approach the corresponding test principle. The correlation of the ex vivo findings gained through biochemical and functional methods to the physiological effect is, as far as possible, only then guaranteed when methodical influences can be excluded. The data obtained through these test series do not, however, allow a transference to the physiological effect of the corresponding heparin preparations regarding anticoagulant as well as antithrombotic efficacy.

Biological Availability↗
PubMed1987

Animal experiments on hemostasis with a collagen-fibrin tissue-adhesive sealant in the nephrostomy tract.

After a median laparatomy, nephrostomy was performed on 22 porcine kidneys: puncture, dilatation and introduction of a 26-French operating sheath through the parenchyma into the renal pelvis. At the end of the operation, an 8-French nephrostomy catheter prepared with a collagen-fibrin tissue-adhesive sealant was introduced through the operating sheath and the sheath was afterwards extracted. The hemostasis in the nephrostomy tract was very good in all 22 cases. There were no complications such as wound infection or stone formation during a post-operative period of between one and 95 days. Experimental investigations showed severe bleeding in nontamponade of the nephrostomy tract, in tamponade with an 8-French nephrostomy catheter and in tamponade of the nephrostomy tract with the collagen fleece wrapped around an 8-French nephrostomy catheter but not coated with the fibrin glue.

Animals↗
PubMed1987

Prophylaxis of deep vein thrombosis in high risk patients undergoing total hip replacement with low molecular weight heparin plus dihydroergotamine.

In 160 high risk patients with total hip replacement the antithrombotic efficacy and tolerance of a single daily injection of 1500 aPTT-U (aPTT = activated partial thromboplastin time) low molecular weight heparin plus 0.5 mg dihydroergotamine (HNMD; Embolex NM) was compared with a twice daily application of 5000 IU of the heparin-dihydroergotamine combination Heparin-Dihydergot in a double-blind study. Deep vein thrombosis measured by means of the radiofibrinogen uptake test occurred in 20.5% of patients in both groups. In addition, intra- and postoperative blood loss and the development of hematoma were similar in both groups. Thus, on account of the "once-daily" application HNMD offers some substantial advantages: The stress of the patient in the postoperative convalescence phase can be appreciably lowered and thereby the nursing staff are spared a great deal of work.

Adult↗