Calcaneogenesis.

We report a case in which Ilizarov distraction osteogenesis was used to lengthen the portion of calcaneum that remained after a radical debridement for osteomyelitis. The patient was able to walk normally in unmodified shoes at the end of his treatment.

Expression of EpCAM is up-regulated during regeneration of renal epithelia.

The human epithelial cell adhesion molecule (hEpCAM) is involved in epithelial morphogenesis and repair of epithelial tissues. We hypothesized that changes in hEpCAM expression in vivo correlate with regeneration of renal epithelia after ischaemia/reperfusion injury (IRi). Unilateral IRi was performed on kidneys of hEpCAM transgenic mice. Changes in hEpCAM expression were investigated by quantitative RT-PCR in renal cortex and medulla dissected by laser dissection microscopy and expression patterns of hEpCAM in regenerating kidneys were assessed by immunohistochemistry. The mechanism of hEpCAM promoter activation was investigated in vitro, by real-time bioluminescent imaging in HK-2 cells and in primary tubular epithelial cells (PTECs) subjected to hypoxia and reoxygenation. In vivo, the transcription of the human epcam gene significantly increased in the renal cortex during tubular re-epithelialization (p < 0.01). Moreover, the number of tubuli that expressed hEpCAM protein more than doubled in the renal cortex during regeneration. De novo expression of hEpCAM was detected in the S1 segments of proximal tubuli. Under hypoxic conditions in vitro, activity of the hEpCAM promoter was up-regulated two-fold in the HK-2 proximal epithelial cell line. Moreover, both in primary proximal epithelial cells and in HK-2 cells, hEpCAM protein expression was increased after hypoxia and reoxygenation. The significant up-regulation of hEpCAM during post-ischaemic renal regeneration in vivo and during in vitro hypoxia indicates that hEpCAM expression is associated with renal regeneration.

A three-dimensional study of calcaneonavicular tarsal coalitions.

The authors studied 37 presumed calcaneonavicular tarsal coalitions from the Hamann-Todd Osteological Collection at the Cleveland Museum of Natural History. The anatomy of the coalitions and the associated subtalar and transverse tarsal joints was quite variable. The coalitions in 8 specimens completely spared the anterior facet of the calcaneus and in 7 specimens it was partially replaced by the navicular portion of the coalition, whereas in 22 specimens the anterior calcaneal facet was completely replaced by the navicular portion of the coalition. The authors suggest that the pathoanatomy of calcaneonavicular coalitions is not uniform and may involve the subtalar and transverse tarsal joints. This may have clinical relevance and contribute to the unsatisfactory results in feet undergoing coalition resection and soft tissue interposition.

The epithelial glycoprotein 2 (EGP-2) promoter-driven epithelial-specific expression of EGP-2 in transgenic mice: a new model to study carcinoma-directed immunotherapy.

The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), a M(r) 38,000 transmembrane antigen also known as 17-1A or Ep-CAM, is commonly used for targeted immunotherapy of carcinomas because it is strongly expressed by most carcinomas. EGP-2 is, however, also expressed in most normal epithelia. To evaluate anti-EGP-2-directed treatment-associated effects on tumors and on EGP-2-positive normal tissue, we generated EGP-2-expressing transgenic mice. A 55-kb DNA fragment consisting of the 14-kb genomic coding sequence of the human EGP-2 gene with approximately 10-kb-upstream and approximately 31-kb-downstream sequences was isolated and used to direct EGP-2 expression in an epithelium-specific manner. In the EGP-2 transgenic mice, EGP-2 appeared to be specifically expressed in all of those epithelial tissues that also express EGP-2 in humans, whereas all of the other tissues were negative. The specific in vivo localization of the i.v. administered anti-EGP-2 monoclonal antibody MOC31 was studied in EGP-2-positive and -negative tumors induced s.c. in this EGP-2 transgenic mouse model. Immunohistochemical analysis showed specific localization of MOC31 in the EGP-2-positive tumors but not in the EGP-2-negative tumors. No anti-EGP-2 monoclonal antibody localization was observed in any of the EGP-2-positive normal mouse tissues, which indicated a limited in vivo accessibility. In conclusion, an EGP-2 transgenic mouse model has been generated that expresses the EGP-2 antigen as in humans and, therefore, can serve as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities in both tumors and normal tissue.

Quality and outcome determination in health care and orthopaedics: evolution and current structure.

Quality health care has many definitions. Among those definitions is "care that consistently contributes to the improvement or maintenance of the quality and/or duration of life." The current evolution in health care has been fueled by three necessities frequently demanded by payers and employers: improvement in access, lowering of cost, and definition and quantification of the quality of care. This evolution has been facilitated by the so-called industrialization of medicine. This concept includes the adoption of industrial economic principles and techniques that facilitate the measurement of processes and outcomes. Quality health care is currently recognized as health care that is characterized by three elements: the use of practice guidelines or standards, the implementation of continuous quality improvement techniques, and the use of outcome determination and management. Practice guidelines demand the adoption of evidence-based principles in evaluation and care, as well as minimization of variations in evaluation and care. Continuous quality improvement seeks to determine why variations in processes of care occur and then to minimize those variations. Outcomes may be measured in terms of both very objective and very subjective variables and also on the basis of cost-efficiency. Most tools currently used to quantify outcomes, especially in orthopaedics, involve measurements of general health and of specific body part or organ system function. This evolution in health care is producing significant alterations in methods of traditional health-care delivery. The accumulating evidence indicates that these changes, although frequently unpopular, are improving the quality of health care.

Tibial shaft fractures with an associated infrapopliteal arterial injury: a survey of vascular surgeons opinions on the need for vascular repair.

OBJECTIVE: To determine current practice for tibial arterial revascularization in trauma patients with tibial shaft fractures associated with infrapopliteal arterial injuries. DESIGN: Nationwide survey of board-certified vascular surgeons, proportionally stratified by geographic region. METHODS: We surveyed a random sample (probability sample stratified by geographic region) of 200 members of the 729 active members of the Society for Clinical Vascular Surgery. We designed a twenty-one-item questionnaire to elicit opinions on the need for vascular repair for a variety of clinical scenarios. RESULTS: Completed questionnaires were returned by fifty-one vascular surgeons. For the eight isolated and combined infra-popliteal arterial injuries we studied, agreement between vascular surgeons as to the need for arterial repair was better for scenarios with clinical evidence of limb ischemia than for those without clinical evidence of limb ischemia. For injuries with clinical evidence of limb ischemia, excellent agreement (90 percent or more of respondents agreeing) was seen for five of the eight injuries, good agreement (80 to 89 percent of respondents agreeing) was seen for two injuries, and poor agreement (less than 70 percent of respondents agreeing) was seen for one injury. For injuries without clinical evidence of limb ischemia, excellent agreement was seen for one injury, good agreement was seen for two injuries, fair agreement (70 to 79 percent of respondents agreeing) was seen for three injuries, and poor agreement was seen for two injuries. CONCLUSIONS: A review of the literature and results of our study suggest that no standardized protocol exists in the current practice of revascularization of infrapopliteal arterial injuries with concomitant tibial shaft fractures; disagreement among vascular surgeons was particularly common for cases where a vessel was known to be injured but there was no clinical evidence of limb ischemia. Our study highlights the need for randomized prospective studies so that standardized protocols can be developed for these serious injuries. Because of the relatively small numbers of this type of injury and the wide variety of injury patterns seen, a study such as this would best be designed as a multi-center study.

Development of a method to analyze orthopaedic practice expenses.

The purpose of the current investigation was to present a standard method by which an orthopaedic practice can analyze its practice expenses. To accomplish this, a five-step process was developed to analyze practice expenses using a modified version of activity-based costing. In this method, general ledger expenses were assigned to 17 activities that encompass all the tasks and processes typically performed in an orthopaedic practice. These 17 activities were identified in a practice expense study conducted for the American Academy of Orthopaedic Surgeons. To calculate the cost of each activity, financial data were used from a group of 19 orthopaedic surgeons in Houston, Texas. The activities that consumed the largest portion of the employee work force (person hours) were service patients in office (25.0% of all person hours), maintain medical records (13.6% of all person hours), and resolve collection disputes and rebill charges (12.3% of all person hours). The activities that comprised the largest portion of the total expenses were maintain facility (21.4%), service patients in office (16.0%), and sustain business by managing and coordinating practice (13.8%). The five-step process of analyzing practice expenses was relatively easy to perform and it may be used reliably by most orthopaedic practices.

Orthopedic medical malpractice: an attorney's perspective.

Orthopedic surgeons are trained to manage problems involving the musculoskeletal system. It would be helpful to identify certain procedures, anatomic areas, or issues related to the physician-patient relationship that could potentially lead to a malpractice lawsuit. Once the problems are identified, steps toward continuing education and physician awareness could be initiated. In this study, we performed a randomized nationwide survey of medical malpractice attorneys to evoke their opinion on these issues. We found that the lumbar spine was the most common anatomic area involved in orthopedic medical malpractice cases, and a physician appearing rushed and uninterested is most likely to be the subject of a lawsuit where a poor physician-patient relationship was a contributing factor. Educational and professional programs are needed to increase the awareness and knowledge of orthopedic malpractice risks, and also to identify potentially preventable problems leading to malpractice litigation.

The ubiquitin-activating enzyme E1-like protein in lung cancer cell lines.

The UBE1L gene isolated from the chromosome 3p21 region has an extremely reduced level of mRNA in lung cancer. Sequence analysis showed a 45% homology to the human ubiquitin-activating enzyme E1 at the amino acid level. To further characterize the protein product, we generated UBE1L protein-specific antibodies. Immunoblot analysis revealed a full-length gene product of approximately 112 kDa. Assessment of the level and distribution pattern of the UBE1L protein in normal and tumor tissue using the generated antibodies showed that the UBE1L protein was present in normal lung cells and non-lung cancer cell lines, but was undetectable in all 14 human lung cancer cell lines analyzed. This difference in expression of the UBE1L protein between normal lung tissue and lung tumor-derived cell lines suggests a possible involvement of an E1-like protein in the origin and/or progression of lung tumors.

Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection.

OBJECTIVE: To investigate the risk of hepatotoxicity after initiation of protease inhibitor-containing highly active antiretroviral therapy (HAART) for HIV-1 infected patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) co-infection. DESIGN: Retrospective study with 394 HIV-1-infected patients initiating HAART at a single university clinic. METHODS: Liver enzyme elevation (LEE) was defined as alanine aminotransferase or aspartate aminotransferase at least five times the upper limit of normal and an absolute increase of > 100 U/l. Relative risks for time to LEE were estimated using Cox proportional hazards models. RESULTS: Of 394 patients 7% were hepatitis B surface antigen (HBsAg)-positive and 14% were anti-HCV-positive. Patients with chronic hepatitis had a higher risk for LEE compared with patients without co-infection: 37% versus 12% respectively. After adjustment for higher baseline transaminases, the presence of HBsAg or anti-HCV remained associated with an increased risk of LEE - relative risk 2.78 (95% confidence interval, 1.50-5.16) and 2.46 (95% confidence interval, 1.43-4.24) respectively. In patients with LEE, transaminases declined whether HAART was continued or modified. Of patients with chronic HBV infection 38% lost HBeAg or developed anti-HBe after initiation of HAART, and one seroconverted from HBsAg-positive to anti-HBs-positive. However, there was no clear relationship with LEE. CONCLUSIONS: HIV-1-infected patients co-infected with HBV or HCV were at considerably higher risk of developing LEE when HAART was initiated compared with patients without co-infection, but it is usually not necessary to modify antiretroviral therapy.

Confidence of graduating family practice residents in their management of musculoskeletal conditions.

A study was undertaken to determine the confidence of graduating family practice residents in the management of musculoskeletal conditions and to determine the level of exposure of graduating family practice residents to fracture care. A 2-page questionnaire consisting of 50 items was sent to 680 graduating family practice residents at 100 randomly selected residency training programs throughout the United States. Family practice residents were questioned about their fracture care experience, including the number of fractures diagnosed, the number of fractures reduced, the number of fractures treated to healing, and the number of casts and splints applied. Residents were also asked about their training experience on an orthopedic surgery service. Residents were asked to rate their confidence on a scale of 1 (least confident) to 10 (most confident) in the physical examination, radiographic evaluation, diagnosis, and treatment of a variety of musculoskeletal conditions, including physical examination of the knee, lower back, ankle, wrist, cervical spine, shoulder, hand, and foot; radiographic evaluation of the lumbosacral spine, traumatic cervical spine, hand injuries, adult shoulder trauma, osteomyelitis, and pediatric elbow injuries; diagnosis of carpal tunnel syndrome, herniated lumbar disc, knee instability, rotator cuff tear, and shoulder instability; and treatment of ankle sprain, tennis elbow, olecranon bursitis, distal radius fracture (Colles), bimalleolar ankle fracture, hip avascular necrosis, knee dislocation, and pediatric elbow fracture. These results were compared with graduating family practice residents' confidence in the physical examination, radiographic evaluation, diagnosis, and treatment of a variety of nonmusculoskeletal conditions. Completed questionnaires were returned by 351 graduating family practice residents. The overall fracture care experience of graduating family practice residents was minimal. Seventy-nine percent of graduating residents had reduced 5 or fewer fractures during their entire residency training program. Experience with cast and splint application was also relatively limited. Graduating family practice residents reported an average of 5.1 weeks (range, 0-10 wk) of training experience on an orthopedic surgery service during their residency. Graduating family practice residents were significantly more confident in the physical examination, radiographic evaluation, diagnosis, and treatment of nonmusculoskeletal conditions than in those of musculoskeletal conditions (P = .0001). Family practice residents who had rotated on an orthopedic service for 8 weeks or more during their training reported significantly higher confidence for all 4 skills-physical examination (P = .003), radiographic evaluation (P = .003), diagnosis (P = .007), and treatment (P = .009). In conclusion, family practice residents show relatively low confidence in the management of musculoskeletal conditions and receive minimal exposure to all aspects of fracture care. Confidence can be improved with greater exposure to the musculoskeletal sciences--such as a rotation of 8 weeks or more on an orthopedic surgery service.

An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy.

The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5' and 3' distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.

Orthopedic patients' satisfaction with their health care plan: a study performed by the Research and Education Committee of the Texas Orthopaedic Association.

To determine the satisfaction of orthopedic patients in regards to their health care plan, a four-page questionnaire was designed, pilot tested, and sent to 200 orthopedic surgeons randomly selected from members of the American Academy of Orthopaedic Surgeons in Texas. Fifty-seven orthopedic surgeons were not eligible to participate; our eligible cohort was 143 orthopedic surgeons. These surgeons were asked to administer the questionnaire to 20 randomly selected patients. Fifty-six of the 143 orthopedic surgeons participated, and surveys were completed by 939 patients. Patients were asked to rate their satisfaction with their health insurance, access to primary care physicians, and access to orthopedic surgeons. Although satisfaction was generally high, the patients with a gate-keeper (no direct access to specialists) were significantly less satisfied with their access to primary care physicians and orthopedic surgeons than those without a gatekeeper.

Technology evolution: the technology spectrum and its application to orthopedic technologies.

The evolution of clinical technologies presents potential adopters with considerations in planning for clinical program development that include the stage and the rate of a technology's evolution. This paper presents a conceptual framework for these considerations and applies the framework to orthopedic technologies. Eight orthopedic surgeons were asked to assess 14 orthopedic technologies and position each of them along a spectrum of research, clinical, and adopted technologies. The distribution of responses for each technology-year combination is presented, and estimates of central tendency, dispersion, and variances provide measures of the change in the distribution of responses over time for each technology and the change in the degree of rater consensus over time for each technology. While orthopedic trauma was chosen to illustrate the technology spectrum model, the model and assessment methodology is applicable to other medical specialties as well. Adoption of this framework in a hospital setting should enable more systematic and effective clinical program development.

Pseudo-dislocation of the sternoclavicular joint.

Fractures of the medial third of the clavicle are the rarest of all clavicle fractures. We present two cases of medial clavicle fracture nonunions that were initially thought to be chronic anterior sternoclavicular dislocations and describe the entity of pseudo-dislocation of the sternoclavicular joint. Computed tomography should be performed on all patients with suspected or established injuries of the sternoclavicular region to ensure differentiation between fracture and dislocation.

An analysis of sports knee evaluation instruments.

This study examined four commonly used sports knee evaluation instruments to establish normative data. A total of 91 volunteers who had not sought treatment for knee pain or any other knee complaint at any time in the past underwent a detailed medical history and examination of both of their knees. Three numerical systems (Feagin and Blake Knee Score, Lysholm Knee Score, and the Hospital for Special Surgery Knee Disability Assessment) and one nonnumerical system (the International Knee Documentation Committee Quick Knee Profile) were evaluated. A significant difference in the proportion of knees with excellent/normal ratings was seen among the four evaluation systems (P<.0001): Hospital for Special Surgery Knee Disability Assessment, 99.5%; Feagin and Blake Knee Score, 84.6%; Lysholm Knee Score, 84.1%; and the International Knee Documentation Committee Quick Knee Profile, 50.5%. Results showed that three objective component scores for the International Knee Documentation Quick Knee Profile were significantly lower than all other component scores (P<.05). These components included: overall ligament examination, Lachman, and total AP translation. These data may be useful as a baseline by which investigators studying patients following knee reconstructive procedures have a basis for comparison of their results.

Early changes in nutrient artery blood flow following tibial nailing with and without reaming: a preliminary study.

OBJECTIVE: To quantify the changes in nutrient artery blood flow following reamed and unreamed nailing of intact canine tibias. DESIGN: In vivo animal study. INTERVENTION: Eighteen dogs underwent nutrient artery blood flow measurements over a fourteen-day period. The intervention groups consisted of controls (Group I), nailing without reaming (Group II), and nailing with reaming (Group III). MAIN OUTCOME MEASUREMENTS: Nutrient artery blood flow was measured through implantable ultrasonic blood flow probes placed around the nutrient artery of the tibia. RESULTS: Nutrient artery blood flow averaged 1.94 milliliters per minute over the fourteen-day period in Group I (no reaming or nailing performed). Nutrient artery blood flow following nailing without reaming (Group II) decreased to 44 percent of baseline values immediately after the procedure. By postoperative day 1, flow had decreased to 23 percent of baseline; over the fourteen-day period, nutrient artery blood flow recovered toward baseline values. Immediately following nailing with reaming (Group III), nutrient artery blood flow measured zero milliliters per minute. Over the fourteen-day period, nutrient artery blood flow in this group averaged 39 percent of the baseline level (range 19 to 58 percent). Whereas nutrient artery blood flow recovered toward baseline values (99 percent of baseline) by fourteen days in Group II, nutrient artery blood flow measured only 26 percent of the baseline level on postoperative day fourteen in Group III. CONCLUSIONS: The preliminary data suggest that nailing with reaming provides a double insult to the nutrient artery distribution.

Use of Ilizarov external fixation for a periprosthetic supracondylar femur fracture.

Supracondylar femur fractures above a total knee replacement are rare injuries that may be challenging to treat. We present a case of an elderly woman whose supracondylar femur fracture was not deemed amenable to conventional treatment. This patient underwent fixation of her femur fracture above a total knee replacement using an Ilizarov external fixator. The fixator was removed at 10 weeks, at which time the fracture was solidly healed. At the most recent follow-up, the patient is 19 months postinjury. She is fully weight bearing without walking aids and has a knee range of motion of 0 degree to 110 degrees.

[3H]thymidine incorporation into whole liver as an alternative to [3H]thymidine incorporation into DNA as a parameter of cell proliferation in regenerating liver tissue in rats.

OBJECTIVE: To monitor liver regeneration following partial hepatectomy, liver cell proliferation can be measured by assaying in vivo [3H]thymidine incorporation into liver cell DNA. We hypothesized that [3H]thymidine incorporation into whole liver tissue parallels [3H]thymidine incorporation into liver cell DNA, both in high proliferating and low proliferating liver. STUDY DESIGN: Liver cell proliferation in rats after partial hepatectomy or a sham operation was studied by measuring incorporation of [3H]thymidine into various fractions of liver tissue on days 1, 2, 3, 4 and 10 after surgery. RESULTS: [3H]thymidine incorporation into whole liver tissue and in the protein fraction correlated well with DNA-specific [3H]thymidine incorporation into regenerating (r > .80, P < .0001) and nonregenerating liver (r > .69, P < .005). [3H]thymidine incorporation into DNA was < 5% of the total amount of administered [3H]thymidine in both sham-operated and hepatectomized rats. Significant differences in [3H]thymidine incorporation into partially hepatectomized livers as compared to sham-operated rat livers were found on days 1 and 2 (whole liver tissue and protein fraction) or day 1 (DNA) after surgery. CONCLUSION: [3H]thymidine incorporation into whole liver tissue is a simple technique that can be used for the study of liver cell proliferation after partial hepatectomy in rats.

The results of total knee arthroplasty in workers' compensation patients.

Total knee arthroplasty was evaluated in 10 patients with post-traumatic osteoarthrosis secondary to work-related knee injuries (age- and sex-matched with 10 controls who had total knee arthroplasties for nonwork-related osteoarthrosis) to determine if Workers' Compensation status influenced treatment outcome. Using the Hospital for Special Surgery Knee Rating System (maximum possible score: 100), most recent follow-up scores averaged 64.1 for Workers' Compensation patients and 91.9 for controls. Subjective indices (pain, function) were significantly different between groups (p < 0.05), but objective indices (range of motion, strength, deformity, instability) were not. No significant differences were noted between groups on either immediate postoperative or most recent follow-up radiographs (which were assessed for alignment and radiolucencies at implant surfaces, respectively). Suboptimal outcomes can be anticipated in total knee arthroplasties performed on Workers' Compensation patients, particularly in cases where claims have not been settled at the time of surgery.