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Biomedical subjects

M G Ehrlich

Publications and source records attributed to M G Ehrlich.

At least 19 recordsLinked to original sources
PubMed2001

Weight-bearing alters the expression of collagen types I and II, BMP 2/4 and osteocalcin in the early stages of distraction osteogenesis.

This study was performed to investigate the effect of loading on the biology of newly forming bone during limb lengthening. Unilateral 2.0 mm femoral lengthenings were performed in 20 male Sprague Dawley rats. Half (n = 10) of the animals were allowed to bear weight freely, while the other half were prevented from weight-bearing via an ipsilateral through-knee amputation. The animals in each group were sacrificed after one (n = 5) or four (n = 5) days of consolidation (post-operative days seven and 10, respectively). In situ hybridization for osteocalcin and collagen I, and antibody staining for collagen II and BMP 2/4 were used to evaluate the molecular influence of loading. There was more new bone in the distraction gap of the weight-bearing animals than there was in the non-weight-bearing animals. BMP 2/4 expression, and the messages for collagen I and osteocalcin, were more abundant in tissue from the weight-bearing animals; collagen II was higher in the non-weight-bearing animals. This suggests that early regenerate tissue is capable of responding to loading, and that weight-bearing appears to stimulate intramembranous ossification. These findings support the concept of early weight-bearing after limb lengthening.

Animals↗
PubMed1999

RGD-coated titanium implants stimulate increased bone formation in vivo.

Numerous studies have demonstrated that peptide modified surfaces influence short- and long-term cell responses such as attachment, shape and function in vitro. These responses are mediated via cell receptors known as integrins which bind specifically to short peptide sequences from larger proteins. Integrins transduce information to the nucleus through several cytoplasmic signalling pathways. Little is known, however, about the ability of peptide-coated surfaces to influence cell responses in vivo. The present study was designed to evaluate the quality and quantity of the new bone formed in response to titanium rods surface-coated with the peptide sequence Arg-Gly-Asp-Cys (RGDC) using gold-thiol chemistry and implanted in rat femurs. Histomorphometric analysis of cross-sections perpendicular to the implant long axis showed a significantly thicker shell of new bone formed around RGD-modified versus plain implants at 2 weeks (26.2 +/- 1.9 vs. 20.5 +/- 2.9 microm; P < 0.01). A significant increase in bone thickness for RGD implants was also observed at 4 weeks while bone surrounding controls did not change significantly in thickness (32.7 +/- 4.6 vs. 22.6 +/- 4.0 microm; P < 0.02). Mechanical pull-out testing conducted at 4 weeks revealed the average interfacial shear strength of peptide modified rods was 38% greater than control rods although this difference was not statistically significant. These pilot data suggest that an RGDC peptide coating may enhance titanium rod osseointegration in the rat femur. Long-term studies and evaluation of other peptides in larger animal models are warranted.

Animals↗
PubMed1998

Pediatric throwing injuries about the elbow.

Pediatric elbow injuries that result from repetitive throwing-type activities are common. These injuries differ from those seen in adults, because of anatomic differences. The purpose of this paper is twofold: first, to review the anatomy of the elbow and the mechanics of the throwing motion about the elbow, and second, to discuss the diagnosis, treatment, rehabilitation, and prevention of pediatric throwing injuries of the elbow.

Adolescent↗
PubMed1997

Aggregate degradation by growth plate proteases.

For long bone growth to occur, calcification of the matrix must begin in the lower hypertrophic zone of the growth plate. It generally is accepted that physeal proteoglycans help regulate mineralization, and that, at least in vitro, smaller proteoglycan fragments are less inhibitory of mineral formation. It also has been shown that proteoglycan degrading enzymes are concentrated in the hypertrophic zone, where calcification occurs. Thus, one can hypothesize that these enzymes are involved in the calcification process. Proteoglycans appear mainly as the aggregate form in the physis, and this study demonstrates the ability of the naturally occurring physeal enzymes to degrade proteoglycan aggregate, without first disaggregating it. Because the matrix constituents probably limit hypertrophic cell size and shape, this degradation may have some relationship to the rate of growth of the physis.

Animals↗
PubMed1997

Fracture healing in a rat osteopenia model.

Fracture healing is influenced by mechanical and biologic factors. The capacity for fracture repair has been reported to decrease with age, although the risk of fracture increases with age. Fracture healing in an animal model of postmenopausal osteoporosis or osteopenia would provide a useful technique to evaluate and develop new treatment protocols. The authors examined the tensile and bending properties of healing femoral fractures in normal and ovariectomized rats. Mechanical data from tensile and bending tests indicate ovariectomy impairs fracture healing, which was confirmed through histologic study. Bending and tensile data provide useful information concerning the mechanical properties of the healing fracture. Tensile tests were noted to be sensitive indicators of the properties of the healing fracture.

Animals↗
PubMed1995

Effects of a delayed steroid injection on ligament healing using a rabbit medial collateral ligament model.

Corticosteroids are known to inhibit collagen synthesis in vitro as well as having a deleterious effect on ligament healing when applied immediately following injury. An acute injection of betamethasone into a transected rabbit medial collateral ligament significantly impaired the biomechanical and histological properties compared to non-injected transected ligaments. Differences in mechanical, histological and biochemical properties were observed up to 3 months following injury and an acute steroid injection. The present study explored the effects of a corticosteroid (betamethasone) injection 7 days following the initial injury. Biomechanical and histomorphometric analyses were carried determine if the previously observed deleterious effects of a corticosteroid injection immediately following injury can be linked to an interference in the inflammatory phase of healing due to the presence of the corticosteroid.

Analysis of Variance↗
PubMed1995

Incidence of deep vein thrombosis after arthroscopic knee surgery: a prospective study.

Deep vein thrombosis (DVT) with subsequent pulmonary emboli (PE) is the most life-threatening complication of knee arthroscopy. Although the incidence of clinically diagnosed DVT after arthroscopy is low, clinical examination is less sensitive and specific than other diagnostic modalities for the detection of venous clot. This study used compression ultrasound to prospectively evaluate patients before and after arthroscopic surgery for the presence of DVT. Preoperatively, patients were screened for DVT risk factors. Eighty-five patients completed the study. Three asymptomatic "silent" DVTs were identified, for an incidence of 3.5%. There was no statistically significant difference between those with and without risk factors for the development of DVT.

Adolescent↗
PubMed1995

Human osteoblasts in culture metabolize both 1 alpha, 25-dihydroxyvitamin D3 and its precursor 25-hydroxyvitamin D3 into their respective lactones.

1 alpha, 25-Dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3], the hormonal form of vitamin D3, is further metabolized in the kidney and intestine through the carbon 24 (C-24) oxidation pathway initiated by C-24 hydroxylation, and the carbon 23 (C-23) oxidation pathway initiated by C-23 hydroxylation. The C-24 oxidation pathway leading to the formation of calcitroic acid has been previously reported to be present in bone cells, but the C-23 oxidation pathway leading to the formation of 1 alpha, 25-(OH)2D3-26,23-lactone has not been described in bone cells, even though 1 alpha, 25-(OH)2D3-26,23-lactone is noted to have a significant effect on bone formation. Therefore, in the present study, we investigated the production of 1 alpha, 25-(OH)2D3-26,23-lactone in normal human osteoblasts, and our studies revealed that human osteoblasts possess the activity of both 24- and 23-hydroxylases constitutively. Thus, 1 alpha, 24(R),25-(OH)3D3, 1 alpha, 25-(OH)2-24-oxo-D3, 1 alpha, 23(S), 25-(OH)3-24-oxo-D3, 1 alpha, 23-(OH)2-24,25,26,27-tetranor D3, and calcitroic acid formed through the C-24 oxidation pathway and 1 alpha, 23(S),25-(OH)3D3 and 1 alpha, 25-(OH)2D3-26,23-lactone formed through the C-23 oxidation pathway were detected under basal conditions. Also, the synthesis of these metabolites was increased significantly when the cells were treated with 1 alpha, 25-(OH)2D3 (50 nM) for 24 h before incubation with the tracer. As 25-hydroxyvitamin D3 (25OHD3) follows similar side-chain modifications as 1 alpha, 25-(OH)2D3, the metabolism of 25OHD3 in normal human osteoblasts was studied under basal conditions. We found that 25OHD3 was also metabolized through both C-24 and C-23 oxidation pathways, resulting in significant synthesis of 24(R),25-(OH)2D3 along with 25OH-24-oxo-D3, 23(S),25-(OH)2-24-oxo-D3, 23(S),25-(OH)2D3, and 25OHD3-26,23-lactone. Under the same experimental conditions, we looked for 1 alpha, 25-(OH)2D3 synthesis, as earlier studies have shown production of 1 alpha, 25-(OH)2D3 in human bone cells. During a time-course study ranging from 1-24 h, we found that by 2 h, the 24(R), 25-(OH)2D3 concentration rose and accumulated considerably during the following 24 h, but 1 alpha, 25-(OH)2D3 did not accumulate at any time. However, other 1-hydroxylated metabolites, 1 alpha, 23(S),25-(OH)3D3, 1 alpha, 23(S),25-(OH)3-24-oxo-D3, as well as 1 alpha, 25-(OH)2D3-26,23-lactone were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcifediol↗
PubMed1995

Evaluation of treatment modalities for septic arthritis with histological grading and analysis of levels of uronic acid, neutral protease, and interleukin-1.

We compared the effectiveness of antibiotics alone and in combination with arthroscopy, arthroscopy with debridement, arthrotomy, or needle aspiration for the treatment of septic arthritis. Each modality has its proponents, but, to our knowledge, no comparative studies have been conducted in animals. We used biochemical and histological analysis to compare these methods of treatment in an experimental model. The right hind knee of thirty goats was injected with 1 x 10(5) Staphylococcus aureus bacilli. The left hind knee was not inoculated and served as the normal control. Seventy-two hours after inoculation, a two-week course of treatment with intramuscular administration of cefuroxime sodium, either alone or in combination with another mode of treatment, was initiated in each of five groups. The cartilage was evaluated histologically with biochemical, enzymatic, and interleukin-1 analyses. Despite the early therapeutic intervention, on the average, there was a 25 per cent loss of uronic acid (t test, p < 0.001) and a 43 per cent increase in neutral protease activity (signed-rank test, p = 0.003) in the treatment groups. There were no significant intergroup differences with regard to the histochemical-histological rating or the levels of uronic acid, neutral protease, or interleukin-1.

Analysis of Variance↗
PubMed1995

Effects of local injection of corticosteroids on the healing of ligaments. A follow-up report.

One hundred and one skeletally mature New Zealand White rabbits were used to study the long-term effects of a single injection of corticosteroid on the biomechanical, histological, and biochemical properties of ligament-healing. Two steroid doses were studied, as previously described. The injections were made into a fascial pocket immediately after transection of the ligament. The animals were killed forty-two and eighty-four days after the injury. In our previous investigation, in which we examined the early (inflammatory and proliferative) phases of ligament-healing, the specimens that had been injected with a dose of steroids equivalent to that given to humans demonstrated significantly inferior biomechanical properties and histological organization relative to controls that had not received an injection. In the current study, we examined the later (remodeling and maturation) phases of ligament-healing and found that the tensile strength (the ultimate stress) of the specimens that had been injected with the steroids returned to a value that was equal to that of the controls that had not received an injection; however, the peak load of the specimens that had been injected with steroids remained inferior to that of the controls. This was accompanied by a lag in the histological maturation.

Animals↗
PubMed1995

Remodeling of articular step-offs. Is osteoarthrosis dependent on defect size?

One of the major unresolved questions in trauma repair concerns the degree of step-off that can be accepted in a joint surface. In answer to this question, a new rabbit model of femoral step-off was developed. Osteoarthrotic changes in cartilage and bone and the failure of repair responses were seen at 20 weeks in the presence of a 3-mm wide sagittal defect displaced 5 mm from the joint surface and spanning the anteroposterior extent of the medial femoral condyle. This study examined the effects of a similar defect, displaced 2 mm from the joint surface, to determine whether the development of osteoarthrosis is dependent on the size of the step-off. Defects were created in 18 New Zealand white rabbits. In a second group, the medial joint surface was osteotomized, but was not displaced. In contrast to th first study, cartilaginous and bony repair resulted in closure of the surgical defect and restoration of femoral congruity. Histologic and biochemical parameters did not differ significantly between groups. The results indicate that cartilage and bone possess the ability to remodel small articular step-offs and to restore joint congruity. Furthermore, the combined data suggest that the development of osteoarthrosis requires significant articular incongruity.

Analysis of Variance↗
PubMed1994

Radioulnar synostosis.

Radioulnar synostosis is a rare condition that exists in two forms: congenital and post-traumatic. Although both may involve either a bony or a fibrous union between the radius and ulna, they differ considerably in their etiologies, treatment, and prognosis. This article explores both of these conditions.

Humans↗
PubMed1994

Biomechanical and physical properties of lengthened bone in a canine model.

Reports on the mechanical and physical properties of lengthened bone after completion of the lengthening process remain scarce. Varied results of torsional testing of lengthened bone have been reported. Furthermore, torsional testing provides information on the shear properties of the tissue but does not reflect the elastic properties obtained from tensile, compressive, or bending tests. The present study evaluated the mechanical properties of lengthened bone at various time points, using a uniaxial tension test. Physical properties (density and ash weight) were determined as well. Results indicate that the tensile properties of the lengthened bone increase with time after the completion of lengthening, but they remain significantly weaker than controls (50%) even after 12 weeks. Density and ash weight measurements also increased with time, correlating with the increase in the tensile mechanical properties.

Analysis of Variance↗
PubMed1993

An experimental model of femoral condylar defect leading to osteoarthrosis.

The acute treatment of articular step-off injuries is based largely on reduction criteria, because the presence of residual incongruity has been correlated with the development of posttraumatic arthrosis (PTA). However, this association has not been demonstrated on a prospective basis. Using the rabbit femoral condyle, we developed a surgical model of articular condylar defect without sacrificing the axial alignment or inherent stability of the knee joint. Twenty weeks after the creation of 5-mm femoral condylar defects, progressive osteoarthritic changes were confirmed by radiographic, histological, and biochemical parameters. Osteophytes were observed on the medial aspect of operated knee joints in 67% of cases. Femoral and tibial articular cartilage at the site of the condylar defect exhibited fibrillation, hypocellularity, and severe loss of safranin-O staining. Focal areas of cartilage were denuded or replaced by pannus. In no case was femoral congruity restored by cartilage repair. Statistically significant decreases in proteoglycan content were demonstrated for cartilage sampled from the weight-bearing region of the condylar defect and from the tibial surface directly beneath it. These changes resemble those arising from previously reported models of osteoarthrosis. We present the model as a valid tool for the study of articular condylar defect and its role in the development of PTA.

Animals↗
PubMed1992

Treatment of proteoglycan aggregates with physeal enzymes reduces their ability to inhibit hydroxyapatite proliferation in a gelatin gel.

In vitro, cartilage proteoglycans (PGs) are effective inhibitors of hydroxyapatite formation and growth. Their inhibitory ability decreases with decreasing PG size and charge density. It has been suggested that the enzyme-mediated alteration in the size and conformation of PGs in the growth plate may similarly facilitate the calcification process. In this study, a gelatin gel system was used to monitor hydroxyapatite formation and growth in the presence of proteoglycan aggregates, before and after enzyme treatment. To reproduce the physeal degradation cascade, an enzyme preparation was used that contained all of the growth plate enzymes. At a concentration of 500 micrograms/ml, the untreated proteoglycan aggregates reduced the amount of mineral formed by 30%. When the aggregates were treated with the heat-inactivated enzyme, the same extent of inhibition was found. In contrast, treating the aggregates with the crude growth plate enzyme preparation removed all the inhibitory ability, such that 500 micrograms/ml of proteoglycan preparation yielded 10% more mineral than the controls. Treatment of the aggregates with chondroitinase ABC and trypsin, similarly removed all the inhibitory ability. These data, suggest that enzymatic degradation of proteoglycans may contribute to the regulation of growth plate calcification.

Animals↗
PubMed1992

Sports injuries in children and the clumsy child.

The clumsy child may be clumsy for various reasons. The child may have a host of different athletic injuries that, although trivial, may cause him or her to limp or fall. These have to be ruled out and sought out. The unique physiology of children has to be considered in making the diagnosis. One is also obligated to rule out the other causes of clumsiness, rotational deformities, neurologic problems, or muscle diseases. And finally, one should not label the normal child who may not be a great athlete as clumsy or refer the child for unnecessary therapy or treatment.

Accident Proneness↗