PubMed Health⌕ Search

Biomedical subjects

M W Wolfe

Publications and source records attributed to M W Wolfe.

At least 37 records · Page 2Linked to original sources
PubMed1998

Use of an osteoinductive biomaterial (rhOP-1) in healing large segmental bone defects.

OBJECTIVE: To assess the radiographic, histologic, and mechanical characteristics of new bone formation in large segmental bone defects treated with a new osteoconductive material, recombinant human osteogenic protein-1 (rhOP-1). DESIGN: In vivo animal study. INTERVENTION: Sixteen dogs (thirty-two limbs) with an ulna segmental defect (2.5 centimeters) were randomized to three treatment groups: rhOP-1, collagen alone, and no implant. MAIN OUTCOME MEASUREMENTS: Radiographic evidence of defect healing, mechanical testing (torsional strength) as compared with thirty-one control intact dog ulnas, and histologic analysis. RESULTS: At twelve weeks, complete radiographic healing was observed in twenty-five of twenty-eight defects (89 percent) treated with rhOP-1. The mechanical strength of the rhOP-1-treated defects at twelve weeks was 65 percent of that of intact ulnas. Histologic analysis revealed that defects treated with rhOP-1 were bridged with lamellar and woven bone that was in continuity with the host bone. CONCLUSIONS: The results indicate that osteoinductive materials, which have the ability to quickly fill and heal large defects, may have advantages over osteoconductive materials, which are typically used to fill smaller non-load-bearing bone voids.

Animals↗
PubMed1998

Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment.

Osteoid osteoma, a benign bone tumor, has traditionally been treated with operative excision. A recently developed method for percutaneous ablation of the tumor has been proposed as an alternative to operative treatment. The relative outcomes of the two approaches to treatment have not previously been compared, to our knowledge. The rates of recurrence and of persistent symptoms were compared in a consecutive series of eighty-seven patients who were managed with operative excision and thirty-eight patients who were managed with percutaneous ablation with radiofrequency. Patients who had a spinal lesion were excluded. The minimum duration of follow-up was two years. There was a recurrence, defined as the need for subsequent intervention, after operative treatment in six (9 per cent) of sixty-eight patients who had been managed for a primary lesion and in two of nineteen who had been managed for a recurrent lesion. The average length of the hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days for those who had a recurrent lesion. There was a recurrence after percutaneous treatment in four (12 per cent) of thirty-three patients who had been managed for a primary lesion and in none of five who had been managed for a recurrent lesion. The average length of the hospital stay was 0.2 day for these thirty-eight patients. With the numbers available, we could detect no significant difference between the two treatments with regard to the rate of recurrence. The rate of persistent symptoms (that is, symptoms that did not necessitate additional treatment) was greater than the rate of recurrence. According to responses to a questionnaire, eight (30 per cent) of twenty-seven patients had persistent symptoms after operative treatment and six (23 per cent) of twenty-six patients had persistent symptoms after percutaneous treatment with radiofrequency. Two patients had complications after operative excision, necessitating a total of five additional operations. There were no complications associated with the percutaneous method. The results of the present study suggest that percutaneous ablation with radiofrequency is essentially equivalent to operative excision for the treatment of an osteoid osteoma in an extremity. The percutaneous method is preferred for the treatment of extraspinal osteoid osteoma because it generally does not necessitate hospitalization, it has not been associated with complications, and it is associated with a rapid convalescence.

Adult↗
PubMed1997

Characterization of the equine glycoprotein hormone alpha-subunit gene reveals divergence in the mechanism of pituitary and placental expression.

The equine glycoprotein hormone alpha-subunit gene is expressed in both pituitary and placenta, unlike that of all other nonprimate mammals studied, in which expression is limited to pituitary. Previous studies of the 5'-flanking region of the equine alpha-subunit promoter have revealed unique characteristics as well as similarities with the human alpha-subunit promoter, which demonstrates a similar pattern of tissue-specific expression. We have cloned and sequenced the equine alpha-subunit gene and have used tissue culture systems and transgenic mice to characterize its expression. Unlike the human promoter, the cloned equine alpha-subunit promoter failed to direct trophoblast-specific expression in either tissue culture or transgenic mouse models, suggesting an entirely different mechanism for expression. In contrast, the equine alpha-subunit promoter was able to direct gonadotroph expression in both tissue culture and transgenic mouse models. In alphaT3-1 cells, 550 base pair (bp) was sufficient for expression. This expression involves promoter elements identified in other species as playing a role in gonadotroph expression, but mutation of these elements reveals differences in their relative contributions to promoter activity. In mice, 2800 bp of 5'-flanking sequence allowed specific expression in gonadotrophs but not in thyrotrophs or placenta. The pattern of estrogen regulation observed in transgenic mice matched neither the repression that has been observed with human and bovine alpha-subunit promoters in transgenic mice nor the stimulation in mRNA levels reported in mares, suggesting a unique mechanism that is not recapitulated in the transgenic model. Thus the equine alpha-subunit promoter uses a combination of conserved and unique features of gene regulation to direct its pattern of tissue-specific expression.

Animals↗
PubMed1997

Resurfacing of the patella in total knee arthroplasty. A prospective, randomized, double-blind study.

During a two-year period, eighty-nine patients who were scheduled to have a total knee arthroplasty for the treatment of degenerative osteoarthrosis were randomly assigned to one of two groups: resurfacing of the patella or retention of the patella. All patients received the same posterior cruciate-sparing prosthesis, and all operations were performed by, or under the direct supervision of, one of us. Three patients died in the early postoperative period. The remaining eighty-six patients (118 knees; fifty-eight that had had resurfacing of the patella and sixty that had not) formed the study group. They were followed for a mean of thirty months (range, twenty-four to forty-four months). Evaluation was performed with use of the clinical scoring system of The Knee Society, a patient-satisfaction questionnaire, specific questions regarding patellofemoral symptoms and function, and radiographs. All clinical evaluations were performed by the same research nurse, without the involvement of a physician, in a blinded manner (neither the nurse nor the patient had knowledge of whether the patella had been resurfaced). Preoperatively, the mean Knee Society score, on a scale ranging from 0 to 200 points, was 89.7 points (range, 33 to 132 points); postoperatively, this score improved to a mean of 172.7 points (range, 98 to 200 points). With the numbers available for study, we could detect no significant difference between the knees that had had patellar resurfacing and those that had not with regard to the over-all score (p = 0.63), the subscore for pain (p = 0.56), or the subscore for function (p = 0.77). We also could detect no difference between the treatment groups, with the numbers available, with regard to patient satisfaction or the responses to questions involving the function of the patellofemoral joint, including the ability to exit from an automobile, to rise from a chair, and to climb stairs. Thirty-two patients had bilateral total knee replacement with resurfacing of the patella in one knee and retention of the patella in the other. These patients expressed no clear preference for either knee. Eight (13 per cent) of the sixty knees that had not had resurfacing were painful anteriorly compared with four (7 per cent) of the fifty-eight that had; this was not a significant difference (p = 0.38), with the numbers available. The anterior pain that was noted postoperatively was predominantly of new onset; it had not been observed preoperatively in three of the four knees that had had resurfacing or in four of the eight that had not. No additional treatment options were offered to the patients who had anterior pain in the knee after resurfacing. However, six (10 per cent) of the sixty knees that had not had resurfacing had it subsequently, because of anterior pain in the knee, after the twelfth postoperative month (range, fifteen to thirty-nine months). The pain decreased in four of these knees. Thus, total knee arthroplasty with retention of the patella yielded clinical results that were comparable with those after total knee arthroplasty with patellar resurfacing, but it was associated with a 10 per cent prevalence of the need for subsequent resurfacing. The prevalence of anterior pain after total knee arthroplasty was not influenced by whether or not the patella had been resurfaced. The postoperative clinical scores, the postoperative development of anterior pain, and the need for subsequent resurfacing were not predicted by the presence of preoperative anterior pain, obesity, or the grade of chondromalacia observed intraoperatively. Because of the short duration of follow-up, these results should be considered preliminary. Additional follow-up is planned.

Adult↗
PubMed1997

The Coventry Award. The value of preoperative aspiration before total knee revision.

The value of routine aspiration of a symptomatic total knee replacement before reoperation was evaluated. The study group consisted of a consecutive series of 69 knees in 67 patients in which preoperative aspiration was performed. All aspirations were performed on an outpatient basis in a clinic setting. Local anesthetics and saline washings were not used. Twenty knees were determined to be infected and 49 knees were not infected. Preoperative aspiration had an overall sensitivity of 55%, specificity of 96%, accuracy of 84%, positive predictive value of 85%, and negative predictive value of 84%. Sixteen patients were taking antibiotics at the time of referral including 12 of 20 (60%) who had infected knees. Seven of these 12 (58%) had no growth on their initial knee aspiration. Four of these had their knees reaspirated at a later date because of a high index of suspicion for infection and the subsequent aspiration revealed the infecting organism in all four cases. Two of the remaining three patients had signs of sepsis develop and reaspiration was not performed because immediate reoperation was indicated clinically. The initial aspiration on the third patient was performed after antibiotic therapy was discontinued for 4 weeks and a repeat aspiration was not deemed necessary. When the results of the reaspirations are included, the overall aspiration results improved to a sensitivity of 75%, specificity of 96%, and accuracy of 90%. The results of the study support the use of routine preoperative aspiration before total knee revision. Previous antibiotic use increases the risk of a false negative result, and reaspiration at a later date can be expected to significantly improve the value of this test in such cases.

Aged↗
PubMed1996

Analysis and comparison of operator-specific outcomes in interventional cardiology. From a multicenter database of 4860 quality-controlled procedures.

BACKGROUND: Medical consumers are increasingly requesting methods to discriminate among the results of different providers. Standards for appropriate modeling, risk adjustment, and evaluation ("scorecarding") in this setting are not well developed, although such evaluation is being performed by the medical insurance industry and by several states in the United States. Our objectives were to develop and examine clinically meaningful methodology for assessing the operator-specific results for percutaneous coronary revascularization. METHODS AND RESULTS: From a multicenter database of patients treated since January 1, 1990, we used training and validation samples (n = 4860) to develop several models for risk adjustment and applied them to 38 providers performing 25 to 523 procedures in the database. Models were developed using multivariable logistic regression techniques for combinations of the end points of death, myocardial infarction, bypass surgery, and procedural success. Models were evaluated for predictive accuracy by using receiver operating characteristic (ROC) analysis, for the capacity to discriminate between superior and inferior provider outcomes, and for subjectivity and concordance. Major complications occurred in 3.6% of patients. The area under the ROC curve (with perfect discriminatory accuracy, area = 1.0; with no apparent accuracy, area = 0.5) in the validation sample, and frequency of identification of operators with outcomes outside the 95% CI for the outcome in question for the models were for death, 0.85 and 7.9%; for death, Q-wave infarction, and bypass surgery, 0.77 and 13.2%; for death, all infarction, and bypass surgery, 0.66 and 10.5%; and for procedural success, 0.76 and 23.7%. For the models as a group, identification of outliers was inversely related to provider volume (P = .05). Models evaluating non-Q-wave infarction or requiring measurement of percent diameter stenosis were identified as being most susceptible to provider manipulation. CONCLUSIONS: For percutaneous coronary revascularization, modeling to discriminate between provider outcomes is limited by the low incidence of major adverse events, subjectivity or susceptibility to manipulation of more frequently occurring adverse events, the generally modest predictive capacity of the models, and the low volume of individual provider treatments. Modeling will be most useful in the identification of providers with extremely poor outcomes and for discrimination between providers with very large procedural volume. Until improved understanding of the biological and mechanical correlates of major complications allows the development of more predictive models, interpretation of the results of scorecarding, particularly for low-volume providers, should be made with caution.

Female↗
PubMed1995

Length of hospital stay and complications after percutaneous transluminal coronary angioplasty. Clinical and procedural predictors. Heparin Registry Investigators.

BACKGROUND: Although several studies have established that the complications of percutaneous transluminal coronary angioplasty (PTCA) are related to clinical and angiographic variables such as advanced age and lesion complexity, it is uncertain whether the use of hospital resources after PTCA also depends on the same baseline variables. The purpose of this study was to identify the factors responsible for prolonged hospital stay after PTCA. METHODS AND RESULTS: The study cohort included 591 consecutive patients undergoing conventional balloon angioplasty at nine medical centers in North America. Major or minor complications occurred in 91 patients (15.4%) and were observed to be related to several baseline characteristics, including unstable angina, multivessel coronary artery disease, patient age, and lesion complexity. Compared with a median length of hospital stay of 2.0 days after PTCA (25th, 75th percentiles: 2.0, 4.0) for the entire cohort of patients, the length of stay was increased in patients with unstable angina (3.0 days [2.0, 5.0]; P = .002), multivessel coronary artery disease (3.0 [2.0, 5.5]; P = .001), age > 65 years (3.0 [2.0, 5.5]; P = .02), complex lesions (3.0 [2.0, 6.0]; P = .001), and filling defects (6.0 [2.0, 11.0]; P < .001). The length of stay was more strikingly increased, however, in patients who experienced major or minor PTCA complications, such as emergency bypass surgery (9.0 days [8.0, 18.0]; P < .001), Q-wave or non-Q-wave myocardial infarction (8.0 [6.0, 15.5]; P < .001), transfusion unrelated to bypass surgery (8.0 [4.0, 12.0]; P < .001), or abrupt vessel closure (6.0 [3.0, 10.5]; P < .001). On stepwise multiple linear regression, PTCA complications appeared to be the strongest predictors of length of hospital stay (all P < .001) and overwhelmed the weaker relation between length of stay and several individual baseline variables. Inclusion of a composite clinical risk score (reflecting the presence of unstable angina, multivessel disease, advanced age, complex lesions, or filling defects) in the regression model confirmed that patients with several high-risk baseline variables had a significant increase in length of stay after PTCA (P = .003), but PTCA complications remained the strongest predictors of length of stay. CONCLUSIONS: Although PTCA complications were correlated with baseline variables such as unstable angina, multivessel disease, advanced age, complex lesions, and filling defects, excess length of stay after PTCA was most strongly influenced by the development of minor and major PTCA complications. Because patients with several baseline risk factors experienced significantly prolonged hospitalizations, improved selection of patients may contribute to reductions in length of stay after PTCA. A greater reduction in resource use after PTCA, however, would be expected from developing new treatments to decrease PTCA complications rather than limiting the access of patients with unstable angina, advanced age, or complex lesions to PTCA.

Aged↗
PubMed1995

Increasing concentrations of 17 beta-estradiol has differential effects on secretion of luteinizing hormone and follicle-stimulating hormone and amounts of mRNA for gonadotropin subunits during the follicular phase of the bovine estrous cycle.

The hypothesis tested was that 17 beta-estradiol (E2) would increase amounts of mRNA for alpha, LH beta, and FSH beta subunits during the follicular phase of the estrous cycle prior to the preovulatory surge of gonadotropins in cows. On Day 16 (Day 0 = estrus) of the estrous cycle, all cows were treated with prostaglandin F2 alpha (PGF2 alpha). Cows served as intact controls (CONT, n = 4) were ovariectomized (OVX, n = 5), or were ovariectomized and administered E2 (OVXE, n = 6) in increasing doses starting at the time of treatment with PGF2 alpha. Cows were bled for 6 h before and for 40 h after PGF2 alpha treatment to characterize pulsatile secretion of LH and FSH. Forty hours after PGF2 alpha treatment, pituitaries were collected for evaluation of amounts of mRNA for alpha, LH beta, and FSH beta subunits. Amplitude of LH pulses was greater (p < 0.05) in cows from the OVXE than from the CONT group. Concentrations of FSH were greater in cows from both the OVXE and OVX (p < 0.01) groups than from the CONT group. Amounts of mRNA for alpha and FSH beta subunits were greater (p < 0.01) in pituitaries of cows from the OVX than from the CONT or OVXE groups. Amounts of mRNA for LH beta subunit in pituitaries of cows from the OVX group tended to be greater (p < 0.08) than from the CONT group. Cows in the OVXE group tended (p < 0.08) to have greater amounts of mRNA for FSH beta subunit than did CONT cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of 17 beta-estradiol on distribution of pituitary isoforms of luteinizing hormone and follicle-stimulating hormone during the follicular phase of the bovine estrous cycle.

The objective of this study was to examine the influence of 17 beta-estradiol (E2) on distribution of LH and FSH isoforms during the follicular phase of the bovine estrous cycle prior to the preovulatory surges of LH and FSH. On Day 16 of the estrous cycle (Day 0 = estrus), intact controls (CONT; n = 4) were treated with prostaglandin F2 alpha (PGF2 alpha) to induce luteal regression and initiation of the follicular phase. Other cows were also treated with PGF2 alpha and either ovariectomized (OVX; n = 5) or ovariectomized and given E2 implants (OVXE; n = 6) to mimic the pattern of increasing E2 concentrations during the follicular phase of the estrous cycle. Pituitaries were collected 40 h after treatment with PGF 2 alpha or ovariectomy (0 h). Aliquots of pituitary extracts were chromatofocused on pH 10.5-4.0 gradients. The LH resolved into thirteen isoforms (designated A-L and S, beginning with the most basic form) while FSH resolved into nine isoforms (designated I-IX, beginning with the most basic form). The percentage of LH as isoform F (elution pH = 9.32 +/- 0.01) was greater (p < 0.05) in the OVX group (48.5%) than in the OVXE group (45.0%). LH isoforms I (elution pH = 6.98 +/- 0.01) and J (elution pH = 6.48 +/- 0.01) were more abundant (p < 0.05) in cows from the OVXE (2.3 and 5.8%, respectively) than the OVX group (1.4 and 3.7%, respectively). Distribution of LH isoforms in cows from the three groups did not differ (p > 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates.

The effect of recombinant human osteogenic protein-1 on the healing of segmental bone defects was studied in twenty-eight African green monkeys (Cercopithecus aethiops). A 2.0-centimeter osteoperiosteal defect was created in the middle of the ulnar shaft in fourteen animals and in the diaphysis of the tibia in the other fourteen. The ulnar defect was filled with an implant consisting of 1000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of bovine bone-collagen carrier in six animals, with collagen carrier alone in two animals, and with autogenous cancellous bone graft from the contralateral tibia and femur in six animals. The tibial defect was filled with 250, 500 (two tibiae), 1000, or 2000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of collagen carrier in five animals, with collagen carrier alone in one animal, and with autogenous cancellous bone graft in six animals; in the two remaining animals (controls), the tibial defect was left unfilled. The tibial defects were stabilized with an intramedullary Steinmann pin. All animals were killed at twenty weeks postoperatively. Healing of the defects was evaluated with biweekly radiographs, with histological examination, and with mechanical testing. Radiographically, all of the defects that had been treated with recombinant human osteogenic protein-1 exhibited new-bone formation, but they differed in the degree of healing and remodeling. Five of the six ulnae treated with recombinant human osteogenic protein-1 and four of the five tibiae treated with this substance exhibited complete healing at six to eight weeks, with bridging of the defect by new bone first observed at four weeks. The two unhealed defects both exhibited new-bone formation but incomplete union, which precluded mechanical testing. No defect that had been filled with collagen carrier or that had been left unfilled exhibited any signs of healing or major new-bone formation. None of the six ulnae that had been filled with autogenous bone graft exhibited complete healing, compared with five of the six tibiae that had been so treated. Histological evaluation of the defects treated with recombinant human osteogenic protein-1 revealed the formation of new cortices with areas of woven and lamellar bone and normal-appearing marrow elements at twenty weeks postoperatively. The tibial defects that had been treated with autogenous bone graft had a similar appearance. All control ulnar and tibial defects and all ulnar defects that had been treated with autogenous bone graft had fibrous union with little new-bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Posterior fracture-dislocation of the hip in a jogger.

Posterior fracture-dislocation of the hip is an uncommon athletic injury, occasionally seen in contact and high-energy sports. The mechanism of injury in this case highlights the high hip joint forces possible during running. The key treatment principle is early reduction of the hip joint, since the incidence of osteonecrosis of the femoral head and degenerative arthrosis increases with delay. Operative treatment will frequently be required to achieve a stable, congruent reduction of articular surfaces, essential for good long-term results. Partial weight-bearing exercise such as swimming and bicycling may aid rehabilitation. Long-term follow-up, with serial radiographs, is important to detect late complications.

Acetabulum↗
PubMed1995

Chondroblastoma of the patella presenting as knee pain in an adolescent.

We report a case of chondroblastoma of the patella, associated with an aneurysmal bone cyst and pathologic fracture, that presented as knee pain in a 13-year-old girl. This case is the fifth case in the literature that associates patellar chondroblastoma with fracture, which should probably be regarded as a significant feature of this lesion.

Adolescent↗
PubMed1994

Prognostic significance of right ventricular hypokinesis and perfusion lung scan defects in pulmonary embolism.

We studied the relation between right ventricular (RV) hypokinesis on echocardiography and defects on the initial perfusion lung scan among 90 hemodynamically stable patients with pulmonary embolism (PE). Of the 90, 38 had qualitative evidence of RV hypokinesis, with a mean RV end-diastolic area significantly larger than those with normal RV wall motion (40.0 +/- 10.2 cm2 vs 20.1 +/- 6.4 cm2; p < 0.001). The degree of the perfusion defect was greater in those patients with baseline RV hypokinesis (54% +/- 16% of the lung nonperfused) than in those patients with normal RV wall motion at baseline (30% +/- 18% nonperfused lung; p < 0.001). Receiver operating characteristic curve analysis showed that a perfusion lung scan defect score of 0.3 (i.e., 30% of the lung nonperfused) had a 92% sensitivity for predicting RV hypokinesis and carried a relative risk for observing RV hypokinesis of 6.8 times greater than among those patients with a perfusion scan score of < 0.3. Considering that all patients with recurrent symptomatic PE were in the subgroup with RV hypokinesis (13% vs 0% for those with normal RV wall motion; p = 0.01), a strategy of performing echocardiography in those patients with a perfusion scan defect score of > or = 0.3 appears to identify patients at increased risk for recurrent PE.

Chi-Square Distribution↗
PubMed1994

The proximal promoter of the bovine luteinizing hormone beta-subunit gene confers gonadotrope-specific expression and regulation by gonadotropin-releasing hormone, testosterone, and 17 beta-estradiol in transgenic mice.

Transient transfection studies have proven useful in unraveling the molecular mechanisms underlying gonadotrope-specific expression and hormonal regulation of the gene encoding the alpha-subunit of the glycoprotein hormones. In contrast, similar studies performed with the LH beta gene have been less informative. When assayed by transient transfection into alpha T3-1 cells, activity of a 776-basepair bovine LH beta promoter-chloramphenicol acetyltransferase fusion gene (bLH beta CAT) was no greater than that of a promoterless control. To determine whether limited activity in vitro reflected the absence of critical regulatory elements, we examined activity of bovine LH beta fusion genes after stable integration in transgenic mice. In contrast to transient transfection studies, the LH beta promoter targeted high levels of CAT expression specifically to the pituitary. In addition, a bLH beta TK fusion gene was active only in gonadotropes. The bLH beta CAT transgene was also evaluated for responsiveness to gonadal steroids and GnRH. Testosterone and 17 beta-estradiol were capable of suppressing activity 70-80% in castrated males, despite the absence of high affinity binding sites for androgen or estrogen receptors. This suggests that feedback inhibition of LH beta CAT transgene expression by gonadal steroids may occur through an indirect mechanism, possibly at the level of the hypothalamus. To address whether the bLH beta CAT transgene could be regulated by GnRH, we treated ovariectomized females with antide, a GnRH antagonist. Antide suppressed transgene activity by 60%. Thus, the proximal promoter of the bovine LH beta subunit gene directs appropriate patterns of cell-specific expression and retains responsiveness to gonadal steroids and GnRH. In light of the robust activity of the LH beta promoter in transgenic mice, we suggest that this animal model can be exploited further to dissect the complex mechanisms that underlie gonadotrope-specific expression and hormonal regulation of the LH beta gene.

Animals↗
PubMed1994

The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects.

A rabbit ulnar non-union model was used to evaluate the effect of recombinant human osteogenic protein-1 on the healing of a large segmental osteoperiosteal defect. A 1.5-centimeter segmental defect was created in the mid-part of the ulnar shaft of adult rabbits. The defect was filled with an implant containing either recombinant human osteogenic protein-1 or naturally occurring bovine osteogenic protein. The recombinant human osteogenic protein-1 implants consisted of a carrier of 125 milligrams of demineralized, guanidine-extracted, insoluble rabbit bone matrix (the collagen carrier), reconstituted with 3.13, 6.25, 12.5, twenty-five, fifty, 100, 200, 300, or 400 micrograms of recombinant human osteogenic protein-1. Animals that received recombinant human osteogenic protein-1 were compared with animals that received an implant of 250 micrograms of a preparation of naturally occurring bovine osteogenic protein mixed with the collagen carrier. Limbs that served as controls received either the collagen carrier alone or no implant at all. The treated and the untreated defects were examined radiographically and histologically at eight or twelve weeks after implantation. Mechanical testing was performed on six animals. All implants of recombinant human osteogenic protein-1, except for those containing 3.13 micrograms of the substance, induced complete radiographic osseous union within eight weeks. The defects that were treated with an implant of bovine osteogenic protein also healed within this time-period. The bone induced by both types of implants had new cortices with advanced remodeling and marrow elements. Histological evaluation of this new bone at eight weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. The average torsional strength and energy-absorption capacity of the union induced by recombinant human osteogenic protein-1 was comparable with that of intact bone. The control defects that had been implanted with collagen carrier alone and those with no implant showed no bridging of the defect.

Animals↗
PubMed1994

Use of osteoinductive implants in the treatment of bone defects.

Osteogenic proteins (OPs) are a family of bone matrix polypeptides isolated from a variety of mammalian species, including mouse, rat, bovine, monkey, and man. OPs initiate chondroblastic differentiation in pluripotent mesenchymal progenitor cells, followed by the synthesis of new bone by endochondral ossification. OPs have the ability to induce healing of osteoperiosteal defects in several animal models, supporting a possible therapeutic role in the reconstruction of bone defects. OPs are responsible for the osteoinductive capacity of demineralized bone matrix (DBM) implants, which may also prove to be clinically useful. Preliminary studies using purified, naturally occurring human osteogenic proteins in the clinical management of non-unions have reported promising results. A prospective, randomized clinical trial is currently underway, comparing recombinant human osteogenic protein-1 (rhOP-1) to autograft in the treatment of tibial non-unions. The use of osteogenic protein implants to augment or replace autogenous and allogenous bone grafts will reduce morbidity, and circumvent the risk of disease transmission associated with transplantation.

Animals↗
PubMed1994

Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model.

An ulnar segmental defect model was used in adult male dogs to examine the effect of recombinant human bone morphogenetic protein-7 (recombinant human Osteogenic Protein-1 [rhOP-1]; Creative Biomolecules, Hopkinton, Massachusetts) on new bone induction and healing, and to test the mechanical strength of healed 2.5-cm segmental bone defects. The rhOP-1 composites consisted of a carrier of 500 mg of demineralized, guanidine-extracted, insoluble bovine bone matrix (collagen carrier), reconstituted with rhOP-1. Six animals received 1200 micrograms rhOP-1 unilaterally and were killed at 12 weeks for torsional load-to-failure testing using the contralateral side as a control. Two further animals received varying amounts of rhOP-1 bilaterally and were studied histologically. All defect sites receiving rhOP-1 were completely bridged radiographically by eight weeks. A control composite, containing no rhOP-1, failed to induce new bone formation at any time. Histologically, rhOP-1-treated sites examined at 16 weeks had formation of new cortical and cancellous bone, with normal appearing marrow elements in the reconstituted medullary canal. The torsional strength of the rhOP-1-implanted ulnae averaged 72% of control (range, 30-99%). The angular deformation to failure averaged 92% of control (range, 39-122%). The energy absorption to failure averaged 67% of control (range, 27-111%). This study demonstrates the efficacy of rhOP-1 in healing segmental osteoperiosteal defects in a canine model.

Animals↗