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Biomedical subjects

M Jelic

Publications and source records attributed to M Jelic.

12 recordsLinked to original sources

Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis.

We randomly assigned 17 patients with scaphoid non-union at the proximal pole to three treatment groups: (1) autologous iliac graft (n=6), (2) autologous iliac graft + osteogenic protein-1 (OP-1; n=6), and (3) allogenic iliac graft + OP-1 (n=5). Radiographic, scintigraphic, and clinical assessments were performed throughout the follow-up period of 24 months. OP-1 improved the performance of both autologous and allogenic bone implants and reduced radiographic healing time to 4 weeks compared with 9 weeks in group 1. Helical CT scans and scintigraphy showed that in OP-1-treated patients sclerotic bone was replaced by well-vascularised bone. The addition of OP-1 to allogenic bone implant equalised the clinical outcome with the autologous graft procedure. Consequently the harvesting of autologous graft can be avoided.

Adolescent↗

Anomalous branch of the left common carotid artery.

A previously unreported anomalous branch of the left common carotid artery (LCCA) was observed during dissection at the Zagreb Medical School. The anomalous branch arose from the anterior surface of the LCCA approximately 2 cm superior to the aortic arch, and subsequently bifurcated into a right and left branch. We describe its anatomic features. Clinical implications are also discussed.

Cadaver↗

Compressed homologous cancellous bone and bone morphogenetic protein (BMP)-7 or bone marrow accelerate healing of long-bone critical defects.

We studied 18 adult male New Zealand rabbits with a critical right-sided ulnar defect of 15 mm. In six animals the defect was grafted with homologous compressed cancellous bone, in six animals with homologous compressed cancellous bone including 300 micro g bone morphogenetic protein (BMP)-7 and in six animals with homologous compressed cancellous bone including 0.5 ml autologous bone marrow. The defect was studied using radiographs every second week for 10 weeks. At the conclusion of the experiment the animals were killed and the defect studied by histology and histomorphometry. In all animals treated with the addition of autologous bone marrow and in five of six animals treated with the addition of BMP-7, the defect healed. There was no union in animals treated with homologous compressed cancellous bone without additive. The histological picture of the regenerated area was similar in the two experimental groups. Woven bone contained small marrow spaces with fibrous tissue and capillaries. The osteoid seams were on average greater in animals that received autologous bone marrow as compared to animals that received BMP-7.

Animals↗

Distraction osteogenesis by Ilizarov and unilateral external fixators in a canine model.

We studied distraction osteogenesis in canine experimental model using two types of external fixators, Ilizarov (n=6) or AO unilateral (n=9) external fixator. Distraction started 1 week after surgery (2 x 0.5 mm/day) and lasted for 3 weeks. Specimens were harvested from weeks 7 through 12. The outcome was assessed by X-ray, histology, histomorphometry and microradiography. Bone regeneration as observed by X-rays was satisfactory and similar in both groups. Both endochondral ossification and intramembranous ossification were found simultaneously in both groups. In both groups, bone formation parameters were significantly higher in the area of consolidating bone. No differences in histomorphometric parameters existed between the groups. In the study period, the bone formation was enhanced and prevailed in the distraction area. This study demonstrated the utility of the canine experimental model for the study of distraction osteogenesis.

Animals↗

Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep.

The efficacy of osteogenic protein-1 (OP-1; BMP-7) in regeneration of articular cartilage was examined by creating knee chondral defects in sheep. With a specially designed instrument in both knees, two 10 mm (diameter) chondral defects were created: one in the trochlea and the other on the femoral condyle. The recombinant BMP was delivered via an extra-articulary positioned mini-osmotic pump, which was fixed to the femoral diaphysis above the knee joint, and connected by a polyethylene tubing to the articular space. Prior to use, the compatibility of OP-1 with mini-osmotic pumps was tested in vitro by measuring aggregation/precipitation and modification of the released protein by size exclusion and reversed phase HPLC. The average amount of aggregation was 15% and about 5% of OP-1 was modified. However, the biological activity of OP-1 released from pumps over a period of 2 weeks at 37 degrees C was equal to ROS cell assay OP-1 standard. Following surgery, a total of 55 microg (low dose) or 170 microg (high dose) OP-1 in acetate buffer (pH 4.5) was slowly released from the pump over a period of 2 weeks. The pumps connected to control knees were filled with acetate buffer as a vehicle. Twelve animals were operated, six of which were treated with the low OP-1 dose, and six with the high OP-1 dose. Three sheep of each group were killed either at 3 or 6 months following surgery, based on arthroscopical evaluation. The chondral defects in the control knees remained empty during the observation period. At 3 months following surgery, defects treated with both OP-1 doses were filled with connective tissue and cartilage. At 6 months following surgery, both doses of OP-1 stimulated regeneration in treated knees. The boundaries between new and old cartilage were well fused and mechanically resisted animals' weight bearing. The regenerated cartilage was rich in proteoglycans and type II collagen, as demonstrated by toluidine blue staining and immunohistochemistry. No signs of endochondral bone formation above the bony tidemark were observed. We suggest that a recombinant bone morphogenctic protein stimulates ingrowth of mesenchymal cells into the chondral defects which then transform into newly formed articular cartilage-like tissue.

Alkaline Phosphatase↗

Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that approximately 1.4 microg OP-1/ml is available in the circulation 1 min after intravenous administration of 250 microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion. Histochemical and molecular analyses demonstrate that OP-1: (a) minimizes infarction and cell necrosis, and decreases the number of plugged tubules; (b) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, and prevents the accumulation and activity of neutrophils; (c) maintains the expression of the vascular smooth muscle cell phenotype in pericellular capillaries; and (d) reduces programmed cell death during the recovery. Collectively, these data suggest that OP-1 prevents the loss of kidney function associated with ischemic injury and may provide a basis for the treatment of acute renal failure.

Acute Kidney Injury↗

Osteogenic protein-1 mRNA in the uterine endometrium.

OP-1, a bone morphogenetic protein (BMP) in the TGF-beta superfamily, is expressed at high levels in the kidney and in the endometrium of the uterus of non-pregnant mice. During pregnancy the OP-1 mRNA in the endometrium rapidly declined at 4 dpc. Thereafter, OP-1 transcripts were detected in the trophoblastic giant cells of the placenta and the fetal tissues. The uterine OP-1 mRNA downregulation could be mimicked by administration of 17 beta-estradiol but not by progesterone to non-pregnant animals. In contrast, OP-1 mRNA expression in kidneys and ovaries was not affected by pregnancy or estrogen treatment. The selective effect of estrogen on OP-1 mRNA in the uterus suggests that OP-1 expression is regulated by tissue specific mechanisms.

Animals↗

Wound infection after median sternotomy during the war in Croatia.

From 1990 to 1994 at Clinical Hospital Center, Zagreb, 1904 median sternotomies were performed for cardiac operations. Patients shared the same intensive care unit (ICU) with the wounded persons, admitted to the hospital from battlefield. Infection developed in 124 patients, an incidence of 6.51%. Methicillin resistant Staphylococcus aureus (MRSA) was isolated from 90, methicillin resistant Staphylococcus epidermidis (MRSE) from 19, and gram negative bacilli (GNB) from 56 patients, Pseudomonas aeruginosa in 2, and Clostridium pneumoniae in 1 case. Ninety-six patients (5.04%) developed superficial localized infection of subcutaneous tissues and they were treated with frequent dressing changes with antibiotic-soaked gauze in combination with systemic antibiotics. Twenty-eight patients (1.47%) developed mediastinitis and sternal dehiscence. They were treated by operative debridement followed by reclosure of the sternum with continuous antibiotic irrigation. We obtained satisfactory results with our method of closure of sternum which is a modification of Robicsek's technique. Nine of them required further operation. In seven cases we performed muscle flaps and in two omentoplasty. One hundred and twenty patients were discharged in satisfactory condition. The uncontrolled mediastinal sepsis caused death in 4 patients. Higher infection rate after median sternotomy during 1991 and 1992 could be possibly explained with the war circumstances in Croatia, and especially with MRSA strain becoming endemic in surgical ICU.

Anti-Bacterial Agents↗