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Biomedical subjects

E A Morris

Publications and source records attributed to E A Morris.

At least 19 recordsLinked to original sources
PubMed2007

Osteoarthritis severity is sex dependent in a surgical mouse model.

OBJECTIVE: To investigate the role of sex hormones in cartilage degradation and progression of osteoarthritis (OA) in a murine model induced by destabilization of the medial meniscus (DMM). DESIGN: Accelerated OA development in mice was induced by transection of the menisco-tibial ligament, which anchors the medial meniscus to the tibial plateau. Intact male and female, and orchiectomized (ORX) male and ovariectomized (OVX) female mouse knee histology were compared for signs of OA following DMM. The effect of testosterone or estrogen addition in vivo was assessed in ORX males in the surgical OA model. RESULTS: OA severity was markedly higher in males than females after DMM. OVX females developed significantly more severe OA than control females. ORX males developed significantly less severe OA than control males. When ORX male mice were supplemented with exogenous dihydrotestosterone (DHT), the severity of OA was restored to the level experienced by the control male mice. Hip cartilage from mice of both sexes demonstrated similar spontaneous and interleukin-1alpha (IL-1alpha) induced proteoglycan (PG) release in vitro. DHT and 17-beta estradiol (E2) did not significantly alter the PG release pattern when supplemented to cartilage cultures of either sex. CONCLUSION: Sex hormones play a critical role in the progression of OA in the murine DMM surgical model, with males having more severe OA than females. Intact females had more OA than OVX females, indicating that ovarian hormones decrease the severity of OA in the female mice. Male hormones, such as testosterone, exacerbate OA in male mice as demonstrated by the fact that ORX mice experienced less OA than intact males, and that addition of DHT to ORX males was able to counteract the effect of castration and re-establish severe OA.

Animals↗
PubMed2003

Magnetic resonance imaging detects unsuspected disease in patients with invasive lobular cancer.

BACKGROUND: Predicting the extent of disease in the breasts of patients with invasive lobular cancer (ILC) can be difficult because of the limits of physical examination and standard imaging. We determined the utility of magnetic resonance imaging (MRI) in finding otherwise unsuspected cancer in the ipsilateral or contralateral breast of patients with ILC. METHODS: Through database review of all breast MRIs performed between January 1, 1999, and December 30, 2002, we identified patients with newly diagnosed ILC who underwent an MRI for extent-of-disease evaluation or contralateral screening. MRI findings separate from the primary tumor were biopsied and correlated with pathology by using MRI-guided biopsy. RESULTS: Sixty-two patients were identified. In all, 59 ipsilateral and 57 contralateral studies were performed. Suspicious lesions separate from the primary tumor were found by MRI in 38 (61%) of 62 patients. Eight patients were excluded from further analysis (seven elected mastectomy without biopsy; one had an unguided excision). Nineteen of 51 patients with an ipsilateral finding underwent MRI-guided biopsy, which revealed cancer in 11, or 22% of those imaged. Twenty of 53 patients with a contralateral finding underwent MRI-guided biopsy, which revealed cancer in 5, or 9% of those imaged. CONCLUSIONS: MRI of the breast identifies unsuspected multicentric or contralateral cancer in patients with ILC. These findings support the use of MRI in selected patients with ILC, particularly in the ipsilateral breast.

Biopsy↗
PubMed2001

BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.

Bone morphogenetic proteins play important roles in connective tissue morphogenesis. In this study, we used human multipotential mesenchymal cells as a target to analyze the effect of bone morphogenetic proteins on chondrogenesis. We also analyzed the effect of proinflammatory cytokine interleukin-1 on chondrogenic-differentiated cells and the interaction of IL-1beta with bone morphogenetic proteins. Cells placed in a 3-dimensional matrix of alginate beads and cultured in a serum-free media with bone morphogenetic protein-2 and -9 induced expression of type II collagen (Col2A1) mRNA and increased expression of aggrecan and cartilage oligomeric matrix protein suggesting chondrogenic differentiation of the cells. The transcription factor Sox-9 that regulates both Col2A1 and aggrecan gene expression showed increased expression with BMP treatment. Chondrogenic differentiated cells treated with interleukin-1 decreased Sox-9, Col2A1 and aggrecan gene expression. Removal of interleukin-1 and further addition of bone morphogenetic proteins resulted in returned expression of chondrogenic markers. Chondrogenic differentiated cells cultured in the presence of different concentrations of bone morphogenetic proteins and interleukin-1 showed that bone morphogenetic proteins were able to partially block the suppressive effect of interleukin-1. This study shows that bone morphogenetic proteins play an important role in chondrogenesis and may prove to be potential therapeutics in cartilage repair.

Aggrecans↗
PubMed2001

An apparatus for MR-guided breast lesion localization and core biopsy: design and preliminary results.

System design and initial results are presented from a new unilateral MR-guided breast lesion localization and core biopsy system. Over 150 imaging studies, an accuracy study on phantoms with 50 localization wire deployments and 33 core biopsy trials, and 19 clinical procedures are reported. The mean spatial accuracy from the lesion center for a 20-gauge (G) needle (N = 13) was within 1.2 +/- 1.4 mm (SD) and for a 14G biopsy (N = 4) 0.8 +/- 1.1 mm. For sampling using a 16G core through a 14G needle, the mean accuracy was 5.6 mm (N = 2). The needle guide geometry imposed a small, calculable targeting error. For phantom measurements using the 20G device, the mean geometry-induced error was 0.73 +/- 0.43 mm. However, this contribution was, on average, 42% of the mean measured 2.35 +/- 1.65 mm offset. The new device design provided an accurate and simple guidance method for localization or core biopsy of MR-visible breast lesions.

Adult↗
PubMed2001

Illustrated breast MR lexicon.

A group of international breast MRI experts is currently working on a definitive lexicon for breast MRI that will incorporate both morphologic and kinetic features of lesions identified on breast MRI. The work to develop the lexicon is supported currently by the American College of Radiology (ACR). This article is aimed at introducing this material and should not be used as a definitive guide as the breast MRI lexicon is a work in progress. It is hoped that radiologists will use the terms and concepts presented here as a template to which future lexicon terminology can be added.

Algorithms↗
PubMed2001

Performance of standard and reservoir-type Hudson masks in pregnant and non-pregnant subjects.

We have assessed the performance of the Hudson-type mask without reservoir and the Hudson non-rebreathing mask with reservoir bag in 10 pregnant and 10 non-pregnant women at different oxygen flow rates by measuring end-expired oxygen fraction (FEO(2)). The Hudson mask without reservoir behaved similarly in pregnant and non-pregnant women, providing a mean FEO(2) of 0.32 with oxygen flow of 4 L.min(-1) which increased to 0.46 at 15 L.min(-1). The reservoir mask produced a lower FEO(2) in pregnant subjects than in non-pregnant subjects, with a mean FEO(2) of 0.33 and 0.64 at 4 L.min(-1) and 15 L.min(-1) in pregnant subjects compared to 0.44 and 0.72, respectively, in non-pregnant women. Neither mask delivers the expected maximum inspired oxygen fraction quoted by its manufacturer, assuming that inspired oxygen fraction quoted by its manufacturer, assuming that inspired oxygen fraction is 0.06 higher than expired and correcting for humidification of inhaled gases within the respiratory tract. The importance of these findings in the care of the obstetric patient and the treatment of acute fetal hypoxia is discussed.

Journal Article↗
PubMed2001

Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily.

The authors recently reported on the principle of an intrinsic repair strategy for partial-thickness articular cartilage defects, which is based on the introduction of a biocompatible and biodegradable matrix loaded with a free chemotactic and mitogenic agent (transforming growth factor-beta 1, at low concentration) and a liposome-encapsulated chondrogenic factor (transforming growth factor-beta 1 at high concentration). In the current study, the potential of other members of the transforming growth factor-beta superfamily (transforming growth factor-beta 2, transforming growth factor-beta 3, bone morphogenetic protein-2 and bone morphogenetic protein-13), and of insulinlike growth factor-1, epidermal growth factor, transforming growth factor-alpha, and Tenascin-C, to induce chondrogenesis within the authors' adult miniature pig articular cartilage defect model, was evaluated. The degree of chondrogenic tissue differentiation was assessed 6 weeks after surgery, on a semiquantitative basis, histologic assessment of cell morphologic features, and intercellular matrix staining being used as the relevant criteria. All selected members of the transforming growth factor-beta superfamily were efficacious in inducing chondrogenic tissue transformation, whereas the other signaling substances tested were not. When encapsulated at high activity levels, bone morphogenetic proteins were less prone than transforming growth factor-beta 1, transforming growth factor-beta 2, and transforming growth factor-beta 3 to evoke undesired side effects as a result of incidental leakage into the joint cavities and subsynovial connective tissue spaces, and therefore they are potentially more suitable candidates for use in human patients.

Animals↗
PubMed2001

Learning curve for stereotactic breast biopsy: how many cases are enough?

OBJECTIVE: The objective of this study was to evaluate the learning curve for stereotactic breast biopsy. MATERIALS AND METHODS: Retrospective review was performed of 923 consecutive lesions that underwent stereotactic breast biopsy performed by one of six radiologists. Four hundred fourteen lesions had 14-gauge automated core biopsy, and 509 subsequent lesions had vacuum-assisted biopsy (14-gauge in 163 and 11-gauge in 346). Medical records were reviewed to determine the technical success rate and false-negative rate as a function of operator experience. RESULTS: For 14-gauge automated core biopsy, a significantly lower technical success rate was seen for the first five cases of each radiologist than for subsequent cases (25/30 = 83.3% versus 366/384 = 95.3%, p < 0.02) and for the first 20 cases than for subsequent cases (90/100 = 90% versus 284/296 = 95.9%, p < 0.05). For 11-gauge vacuum-assisted biopsy, a significantly lower technical success rate was seen for the first five cases than for subsequent cases (17/20 = 85.0% versus 310/322 = 96.3%, p < 0.05) and for the first 15 cases than for subsequent cases (54/60 = 90.0% versus 273/283 = 96.5%, p = 0.03). The false-negative rate was higher for the first 15 cases compared with subsequent cases both for stereotactic 14-gauge automated core biopsy (4/31 = 12.9% versus 3/115 = 2.6%, p < 0.04) and for stereotactic 11-gauge vacuum-assisted biopsy (2/27 = 7.4% versus 0/85 = 0%, p < 0.06). CONCLUSION: A learning curve exists for stereotactic breast biopsy. Significantly higher technical success rates and lower false-negative rates were observed after the first five to 20 cases for 14-gauge automated core biopsy and after the first five to 15 cases for 11-gauge vacuum-assisted biopsy. Even after a radiologist has experience with stereotactic biopsy, changes in equipment may result in a new learning curve.

Biopsy, Needle↗
PubMed2001

Calcifications highly suggestive of malignancy: comparison of breast biopsy methods.

OBJECTIVE: The purpose of this study was to compare the usefulness of, and cost of diagnosing with, different breast biopsy methods for women with calcifications highly suggestive of malignancy. MATERIALS AND METHODS: One hundred thirty-nine women with calcifications highly suggestive of malignancy underwent diagnostic biopsy. Of these, 89 women had stereotactic biopsy with a 14-gauge automated needle (n = 25), 14-gauge vacuum-assisted probe (n = 17), or 11-gauge vacuum-assisted probe (n = 47); and 50 women had diagnostic surgical biopsy. Medical records were reviewed. Cost savings for stereotactic biopsy were calculated using Medicare data. RESULTS: The median number of operations was one for women who had stereotactic biopsy versus two for women who had diagnostic surgical biopsy. The likelihood of undergoing a single operation was significantly greater for women who had stereotactic rather than surgical biopsy, among all women (61/89 [68.5%] vs. 19/50 [38.0%], p < 0.001) and among women treated for breast cancer (55/77 [71.4%] vs. 6/37 [16.2%], p = 0.0000001). Stereotactic 11-gauge vacuum-assisted biopsy, as compared with 14-gauge automated core or 14-gauge vacuum-assisted biopsy, was significantly more likely to spare a surgical procedure (36/47 [76.6%] vs. 16/42 [38.1%], p = 0.0005). Stereotactic 11-gauge vacuum-assisted biopsy resulted in the greatest cost reduction, yielding savings of $315 per case compared with diagnostic surgical biopsy; for women with solitary lesions, stereotactic 11-gauge biopsy decreased the cost of diagnosis by 22.2% ($334/$1502). CONCLUSION: For women with calcifications highly suggestive of malignancy, the use of stereotactic rather than surgical biopsy decreases the number of operations. Stereotactic 11-gauge vacuum-assisted biopsy, as compared with 14-gauge automated core or 14-gauge vacuum-assisted biopsy, is significantly more likely to spare a surgical procedure and has the highest cost savings.

Adult↗
PubMed2001

Observer variability and applicability of BI-RADS terminology for breast MR imaging: invasive carcinomas as focal masses.

OBJECTIVE: The purpose of this study was to assess whether the descriptive terminology and final assessment categories of the Breast Imaging Reporting and Data System (BI-RADS) lexicon can be used for breast carcinomas detected on MR imaging and to assess the inter- and intraobserver variabilities in the use of the descriptors and final assessment categories. MATERIALS AND METHODS: In 82 patients, 101 masses, including 68 infiltrating carcinomas and 33 benign lesions, were interpreted independently by four radiologists and described by BI-RADS terminology with respect to mass shape and margin and BI-RADS final assessment categories. The enhancement pattern of the mass was also reported. In addition, two radiologists interpreted each case twice to evaluate intraobserver variability. The final case set for analysis was the 68 infiltrating carcinomas. RESULTS: Most of the infiltrating carcinomas were described as irregular, spiculated, and heterogeneously enhancing masses. The final impression of the 68 carcinomas was BI-RADS category 5 (highly suggestive of malignancy) in 41 (61%), category 4 (suspicious abnormality) in 24 (35%), and category 3 (probably benign) in three (4%). Enhancement pattern was heterogeneous in 40 (59%), homogeneous in 14 (21%), and rim in 14 (21%). Interobserver agreement was moderate for mass margin, shape, enhancement, and final assessment category. CONCLUSION: This study suggests that the mammographic BI-RADS lexicon with some modifications may be applied to describe the features of infiltrating carcinoma seen on breast MR imaging.

Adult↗
PubMed2001

Bracketing wires for preoperative breast needle localization.

OBJECTIVE: The purpose of this study was to evaluate the outcomes of bracketing wire placement during preoperative breast needle localization. SUBJECTS AND METHODS: We prospectively examined mammograms of 1057 consecutive lesions that had preoperative needle localization and surgical excision and classified the lesions according to Breast Imaging Reporting and Data System (BI-RADS) final assessment categories. Bracketing wires, defined as multiple wires placed to delineate the boundaries of a single lesion, were used in 103 (9.7%) of 1057 lesions. Medical records, imaging studies, and histologic findings in these 103 lesions were reviewed. RESULTS: Of 103 bracketed lesions, median lesion size was 3.5 cm (range, 1.5-9.5 cm). Ninety-three lesions (90.3%) contained calcifications; 65 lesions (63.1%) were BI-RADS category 5 (highly suggestive of malignancy); and 33 lesions (32.0%) were percutaneously proven cancers. The median number of wires placed was two (range, 2-5). Surgical histologic findings were carcinoma in 75 lesions (72.8%), atypical hyperplasia in eight lesions (7.8%), and benign in 20 lesions (19.4%). Of 42 calcific lesions that were bracketed and had postoperative mammograms available for review, complete removal of suspicious calcifications was accomplished in 34 (81.0%). Of 75 cancers that were bracketed, clear histologic margins of resection were obtained in 33 (44.0%). CONCLUSION: Bracketing wires were used during preoperative needle localization primarily for larger calcific lesions that were proven cancers or were highly suggestive of malignancy (BI-RADS category 5). Bracketing wires may assist the surgeon in achieving complete excision of calcifications, but bracketing wires do not ensure clear histologic margins of resection.

Adult↗
PubMed2001

Cancer staging with breast MR imaging.

Breast MR imaging is a useful tool for staging breast cancer patients, and staging is more accurate with MR imaging than with conventional imaging techniques. MR imaging is the preferred imaging test for the accurate staging of breast cancer before surgery and for assessment of patients with positive axillary adenopathy and negative mammogram and physical examination. There are many important questions regarding the role of MR imaging in breast cancer staging that must be addressed by future research and involvement of MR imaging of the breast in clinical trials.

Breast Neoplasms↗
PubMed2000

Imaging-histologic discordance at percutaneous breast biopsy.

BACKGROUND: The purpose of the current study was to determine the frequency of imaging-histologic discordance at percutaneous breast biopsy and to assess the likelihood of carcinoma in these discordant lesions. METHODS: Percutaneous imaging guided breast biopsy was performed on 1785 consecutive lesions during a 7-year period under stereotactic (n = 1205) or sonographic (n = 580) guidance, using an automated needle (n = 1044) or directional vacuum-assisted probe (n = 741). Lesions were prospectively classified according to the Breast Imaging Reporting and Data System (BI-RADS) as Category 3 (probably benign), Category 4 (suspicious), or Category 5 (highly suggestive of malignancy). Imaging-histologic discordance was considered to have occurred when the percutaneous biopsy histology did not provide a sufficient explanation for the imaging features; in such cases, repeat biopsy was recommended. Medical records, imaging studies, and histologic findings were reviewed. RESULTS: Imaging-histologic discordance was present in 56 of 1785 (3.1%) lesions. The frequency of discordance was significantly higher in our first 2 years of experience with percutaneous biopsy than in later years (18 of 361 = 5.0% vs. 38 of 1424 = 2.7%; P < 0.04) and was significantly higher for lesions that were BI-RADS Category 5 rather than BI-RADS Category 4 (20 of 416 = 4.8% vs. 36 of 1366 = 2. 6%; P < 0.04). The frequency of discordance was significantly lower with the 11-gauge vacuum-assisted probe than other devices for calcifications (7 of 414 = 1.7% vs. 16 of 251 = 6.8%; P = 0.001) but not for masses (6 of 161 = 3.7% vs. 26 of 959 = 2.7%; P = 0.44). Repeat biopsy, performed in 45 discordant lesions revealed carcinoma in 11 (24.4%; 95% confidence intervals, 12.9-39.5%). The frequency of carcinoma was significantly higher among discordant BI-RADS Category 5 than discordant BI-RADS Category 4 lesions (7 of 16 = 43. 8% vs. 4 of 29 = 13.7%; P < 0.04). CONCLUSIONS: Imaging-histologic discordance occurred in 3.1% of lesions that had percutaneous breast biopsy. Imaging-histologic discordance was an indication for surgical excision because of the high (24.4%) prevalence of carcinoma in these lesions.

Biopsy↗
PubMed2000

Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells.

Multipotential bone marrow stromal cells have the ability to differentiate along multiple connective tissue lineages including cartilage. In this study, we developed an efficient and reproducible procedure for the isolation of stromal cells from bone marrow aspirates of normal human donors based on the expression of endoglin, a type III receptor of the transforming growth factor-beta (TGF-beta) receptor family. We demonstrate that these cells have the ability of multiple lineage differentiation. Stromal cells represented 2-3% of the total mononuclear cells of the marrow. The cells displayed a fibroblastic colony formation in monolayer culture and maintained similar morphology with passage. Expression of cell surface molecules by flow cytometry displayed a stable phenotype with culture expansion. When cocultured with hematopoietic CD34(+) progenitor cells, stromal cells were able to maintain their ability to support hematopoiesis in vitro. Culture expanded stromal cells were placed in a 3-dimensional matrix of alginate beads and cultured in serum-free media in the presence of TGFbeta-3 for chondrogenic lineage progression. Increased expression of type II collagen messenger RNA was observed in the TGFbeta3 treated cultures. Immunohistochemistry performed on sections of alginate beads detected the presence of type II collagen protein. This isolation procedure for stromal cells and the establishment of the alginate culture system for chondrogenic progression will contribute to the understanding of chondrogenesis and cartilage repair.

Bone Marrow Cells↗
PubMed2000

Magnetic resonance imaging facilitates breast conservation for occult breast cancer.

INTRODUCTION: Occult primary breast cancer, i.e., isolated axillary adenocarcinoma without detectable tumor in the breast by either physical exam or mammography, represents up to 1% of operable breast cancer. Modified radical mastectomy (MRM) is generally the accepted treatment for this condition although tumor is identified in only two-thirds of mastectomy specimens. Breast magnetic resonance imaging (MRI) can identify occult breast carcinoma and may direct therapy. This study examined the ability of breast MRI to detect occult breast cancer and to facilitate breast conservation therapy. METHODS: Forty women with biopsy-proven metastatic adenocarcinoma to an axillary lymph node and no evidence of primary cancer were studied. All patients had a physical examination, mammography, and MRI of the breast. Using a dedicated breast coil, MRI imaging was performed with and without gadolinium enhancement. Positive MRI scans were compared with histopathologic findings at the time of operation (n = 21). RESULTS: MRI identified the primary breast lesion in 28 of 40 women (70%). Of these 28 patients, 11 had MRM, 11 had lumpectomy/axillary lymph node dissection (ALND)/radiotherapy (XRT), 2 had ALND/XRT alone, and 4 had no local treatment secondary to stage IV disease. Two women initially treated with lumpectomy/ALND subsequently had mastectomy for positive margins. Of the women with positive MRI who had breast surgery, 21 of 22 (95%) had tumor within the surgical specimen. Twelve women had negative MRI of the breast. Five of these 12 underwent MRM, of whom 4 had no tumor in the mastectomy specimen. The remaining 7 patients had ALND and whole breast radiation (ALND/XRT) (n = 5), or were observed (n = 2). Overall, 18 of 34 women surgically treated had MRM, while 16 (47%) preserved their breast. Tumor yield for patients having breast surgery was 81%. CONCLUSIONS: MRI of the breast can identify occult breast cancer in many patients and may facilitate breast conservation in select women. Negative breast MRI predicts low tumor yield at mastectomy.

Adenocarcinoma↗
PubMed2000

Evaluation of pectoralis major muscle in patients with posterior breast tumors on breast MR images: early experience.

PURPOSE: To evaluate the ability to use breast magnetic resonance (MR) imaging to assess disease extent in patients with posterior breast masses who are suspected to have tumor invasion into underlying muscle. MATERIALS AND METHODS: Nineteen patients with posterior breast masses underwent three-dimensional, gradient-echo, 1.5-T MR imaging before and after the administration of gadopentetate dimeglumine. Thirteen had deep palpable masses that were clinically determined to be fixed to the underlying chest wall. Twelve had mammographic findings that caused muscle involvement to be suspected, and seven had normal mammograms. All patients underwent surgery. MR images were reviewed and were correlated with histologic findings. RESULTS: Enhancing masses were identified on MR images in all 19 patients. Five (26%) of the 19 patients had masses that abutted the muscles, with obliteration of the fat plane and muscle enhancement. All five had muscle involvement at surgery. In the remaining 14 (74%) patients, no enhancement of muscle was seen; none of these had invasion of the muscle at surgery. CONCLUSION: Extension of adjacent tumor into underlying musculature was indicated by abnormal enhancement within these structures. Violation of the fat plane between tumor and muscle, without other findings, did not indicate tumor involvement of these deep structures.

Adult↗
PubMed2000

Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2).

BACKGROUND: Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. METHODS: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. RESULTS: One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartilage. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at twenty-four weeks postoperatively. Immunostaining demonstrated significantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. Immunostaining for other matrix components showed no difference among the treatment groups. The mean residence time of rhBMP-2 in the cartilage defects was eight days with an elimination half-life of 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. CONCLUSIONS: The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.

Animals↗