Rat supraspinatus tendon expresses cartilage markers with overuse.

The goals of this study were to investigate the response of the rat supraspinatus tendon to overuse at the molecular level using transcriptional profiling, and to identify potential markers of tendinopathy. Adult rats were subjected to an overuse protocol that consists of downhill running (10% grade) at 17 m/min for 1 h/day, 5 days/week, for a total of either 1, 2, or 4 weeks. Another group of rats served as nonrunning time 0 controls. Transcriptional profiling was performed on the supraspinatus and patellar tendons using an Affymetrix rat genome array. A gene was considered to be differentially expressed if the p value from an ANOVA test was less than 0.01 and the difference between runners and controls was at least twofold at any time point. The supraspinatus tendon had increased expression of well-known cartilage genes such as col2a1, aggrecan, and sox9. These genes were not regulated in the patellar tendon, an internal comparator. Few genes associated with inflammation, or angiogenesis, were differentially expressed, and no significant change in the regulation of matrix metalloproteinases was detected. The results of this study suggest that by expressing more cartilage genes, the tendon is converting toward a fibrocartilage phenotype as a result of the repetitive loading and repeated compression of the tendon as it passes through the acromial arch.

Fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling genetic disorder of connective tissue. The condition is characterized by congenital malformation of the great toes and by progressive heterotopic ossification of the tendons, ligaments, fasciae, and striated muscles. Fibrodysplasia ossificans progressiva occurs sporadically and is transmitted as a dominant trait with variable expression and complete penetrance. Reproductive fitness is low. There are fewer than 150 known patients with the disorder in the United States. A point prevalence of one affected patient in every 2 million of population has been observed. There is no sexual, racial, or ethnic predilection. The disease presents in early life; its course is unavoidably progressive. Most patients are confined to a wheelchair by the third decade of life and often succumb to pulmonary complications in the 5th/6th decade of life. At present there is no effective prevention or treatment. The recent discovery of overproduction of bone morphogenetic protein-4 in lesional cells and lymphocytic cells of affected patients provides a clue to both the underlying pathophysiology and potential therapy. The FOP gene has recently been mapped to human chromosome 4q 27-31.

Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP).

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic endochondral ossification in predictable anatomical patterns. Although elevated levels of bone morphogenetic protein 4 (BMP4) occur in lymphoblastoid cells and in lesional cells of patients with FOP, mutations have not been identified in the BMP4 gene, suggesting that the mutation in FOP may reside in a BMP4-interacting factor or in another component of the BMP4 pathway. A powerful antagonist of BMP4 is the secreted polypeptide noggin. A recent case report described a heterozygous 42-bp deletion in the protein-coding region of the noggin gene in a patient with FOP. In order to determine if noggin mutations are a widespread finding in FOP, we examined 31 families with 1 or more FOP patients. Linkage analysis with an array of highly polymorphic microsatellite markers closely linked to the noggin gene was performed in four classically-affected multigenerational FOP families and excluded linkage of the noggin locus to FOP (the multipoint lod score was -2 or less throughout the entire range of markers). We sequenced the noggin gene in affected members of all four families, as well as in 18 patients with sporadic FOP, and failed to detect any mutations. Single-strand conformation polymorphism (SSCP) analysis of 4 of these patients plus an additional 9 patients also failed to reveal any mutations. Among the samples analyzed by SSCP and DNA sequencing was an independently obtained DNA sample from the identical FOP patient previously described with the 42-bp noggin deletion; no mutation was detected. Examination of the DNA sequences of 20 cloned noggin PCR products, undertaken to evaluate the possibility of a somatic mutation in the noggin gene which could be carried by a small subset of white blood cells, also failed to detect the presence of the reported 42-bp deletion. We conclude that mutations in the coding region of noggin are not associated with FOP.

New and clarified safe harbors may ease certain provider transactions.

The recent final rule issued by the Office of Inspector General adds eight new safe harbors to the Federal antikickback statute to the 13 currently in force. This final rule also clarifies six of the original 11 safe harbors published in 1991. In general, safe-harbor provisions to the antikickback statute specify payments that will not provide a basis for criminal prosecution or for exclusion from the Medicare or state healthcare programs. While safe harbors are very narrow and transactions must meet each requirement of an applicable safe harbor to be protected, the new final rule should help facilitate certain financial arrangements between provider organizations. It may, however, prohibit other arrangements.

Osteogenic induction in hereditary disorders of heterotopic ossification.

The formation of heterotopic bone within soft connective tissue is a common feature of at least three distinct genetic disorders of osteogenesis in humans: fibrodysplasia ossificans progressiva; progressive osseous heteroplasia; and Albright hereditary osteodystrophy. The pathobiologic characteristics of osteogenic induction, the histopathologic features of osteogenesis, the anatomic distribution of heterotopic lesions, and the developmental patterns of disease progression differ among all three conditions. The molecular and cellular basis of redirecting a mature connective tissue phenotype to form bone is a remarkable biological phenomenon with enormous implications for the control of bone regeneration, fracture healing, and disorders of osteogenesis.

Well-leg compartment pressures during hemilithotomy position for fracture fixation.

OBJECTIVE: To evaluate the relationship between the well-leg compartment pressures and time during hemilithotomy position for fracture fixation. DESIGN: Prospective. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Ten patients who underwent intramedullary nailing of a fractured femur in the hemilithotomy position (with a well-leg holder). INTERVENTION: Continuous pressure monitoring was achieved with in-dwelling slit catheters inserted into the calf compartments of the well leg. Baseline measurements were obtained in the supine position. After the leg was placed in the hemilithotomy position, compartment pressures were monitored throughout surgery. MAIN OUTCOME MEASUREMENTS: Calf compartment pressures at baseline, during hemilithotomy position, and post-hemilithotomy were compared. The association between body mass index and compartment pressure was analyzed. RESULTS: A consistent pattern was observed between compartment pressures and time. The curve was that of a step function in which the pressure increased as soon as the leg was placed in the well-leg holder and remained elevated until the leg was taken down. The pressure jumped from a baseline of 9.2 to 27.3 millimeters of mercury (mm Hg) (p<0.0001). While in the hemilithotomy position, the leg pressure trended slightly upward. Once the leg was taken down, the pressure immediately returned to a near-baseline level of 8.1 mm Hg (p<0.0001). A significant correlation was also found between the body mass index and leg pressure (R2 = 0.713; F = 0.002). CONCLUSIONS: The use of the well-leg holder to maintain hemilithotomy position increases the calf compartment pressures dramatically and significantly. Therefore, we recommend avoiding this position for fracture fixation in at-risk patients.

From primary care physician employment to private practice: easing the transition.

In most cases, the practice acquisition and employment strategy of the 1990s has backfired, with acquired physician practices losing in the range of $50,000 to $100,000 or more per physician annually. There are two alternatives for addressing the operating deficits incurred from practice ownership and physician employment: (1) restructuring through the implementation of network-wide and practice-specific initiatives to improve financial performance; or (2) wholesale (i.e., all practices) or selective practice divestiture, depending on the individual practice financial performance and "fit" with the physician network strategic priorities. Unraveling a decade's worth of physician-health system relationships that are grounded by the notion of acquisition and employment is going to be a complex process for both parties. But given the magnitude of financial losses on acquired practices and the inability of health care providers to sustain future losses, there simply are not options beyond restructuring or divesting these relationships.

Surgical management of calcaneal unicameral bone cysts.

Unicameral bone cysts are not seen commonly in the calcaneus. Little is known about the etiology and natural history of these lesions. Calcaneal cysts often are symptomatic, although some of these lesions are detected as incidental findings. Treatment has been advocated based on the fear of pathologic fracture and collapse. Several published series have been divided in their favor for either open treatment or injection management. These series are small, and the optimal treatment is still in question. The current study compared the efficacy of methylprednisolone acetate injection treatment with curettage and bone grafting in the treatment of unicameral bone cysts of the calcaneus. All patients treated for unicameral bone cysts of the calcaneus during the past 7 years at two institutions were reviewed. Eleven patients met inclusion criteria. All diagnoses were confirmed radiographically or histologically. Demographic information, presenting complaints, diagnostic imaging, treatment modalities, and outcome were analyzed. Long term radiographic and subjective followup was obtained. Eighteen surgical procedures were performed on 11 patients with 12 cysts. Nine injections performed on six patients failed to show healing of the cyst. Nine cysts treated with curettage and bone grafting showed cyst healing. At mean followup of 28 months (range, 12-77 months), all 11 patients had no symptoms; there were no recurrences of the cyst in the nine patients who underwent bone grafting and persistence of the cyst in the two patients who underwent injection therapy. This review reports one of the largest series of cysts in this location. The results indicate that steroid injection treatment, although useful in other locations, may not be the best option for the management of unicameral bone cysts in the calcaneus. Curettage and bone grafting yielded uniformly good results.

Catastrophic falls in patients who have fibrodysplasia ossificans progressiva.

There have been numerous anecdotal reports of catastrophic falls in patients with fibrodysplasia ossificans progressiva. To determine the incidence of serious morbidity and mortality associated with falls in this patient population, the authors surveyed the 135 patient members of the International Fibrodysplasia Ossificans Progressiva Association and an age and gender matched control group. Eighty-one percent of the fibrodysplasia ossificans progressiva population suffered a fall resulting in injury compared with 44% of the controls. Sixty-seven percent of the falls initiated a painful flareup of fibrodysplasia ossificans progressiva leading to permanent loss of movement in almost all patients. Fifty-four percent of all falls suffered by the fibrodysplasia ossificans progressiva group led to permanent disability compared with 4% of all falls in the control group. Although trauma to the head was a common site of injury in both groups, the injury profile in the fibrodysplasia ossificans progressiva group included traumatic brain injuries, intracranial hemorrhage and death whereas the control group suffered mostly minor soft tissue lacerations. Deficiencies in coordinate gait and protective function likely accounted for the severity of injuries especially to the head in the fibrodysplasia ossificans progressiva population. Precautions are recommended that are intended to minimize the risk of injury without compromising a patient's functional level and independence. These recommendations include limitation of high risk activities, protective head gear, safety improvements in living environments, and augmentation of stabilizing and protective functions.

Osteoporosis. Definition and clinical presentation.

Osteoporosis is a skeletal condition characterized by decreased density (mass/volume) of normally mineralized bone. The reduced bone density leads to decreased mechanical strength, thus making the skeleton more likely to fracture. Postmenopausal osteoporosis (Type I) and age-related osteoporosis (Type II) are the most common primary forms of bone loss seen in clinical practice. Secondary causes of osteoporosis include hypercortisolism, hyperthyroidism, hyperparathyroidism, alcohol abuse, and immobilization. In the development of osteoporosis, there is often a long latent period before the appearance of the main clinical manifestation, pathologic fractures. The earliest symptom of osteoporosis is often an episode of acute back pain caused by a pathologic vertebral compression fracture, or an episode of groin or thigh pain caused by a pathologic hip fracture. In the diagnostic process, the extent and severity of bone loss are evaluated and secondary forms of bone loss are excluded. A careful diagnostic work-up that includes clinical history, physical examination, laboratory evaluation, bone densitometry, and radiographic imaging will allow the clinician to determine the cause of osteoporosis and to institute medical interventions that will stabilize and even reverse this frequently preventable condition.

Choosing medical practice acquisition models.

Various models have been used to carry out medical practice acquisitions. Each model results in a different degree of integration between physicians and purchasing organizations, and all involve potentially detrimental legal and business issues to be resolved. This article describes six models of medical practice acquisition and the most common legal and business problems associated with valuing medical practices.

Legal issues in medical practice acquisitions.

As the changing healthcare delivery environment places increased emphasis on primary care, many healthcare organizations are striving to broaden their base of primary care physicians. One method that organizations are using to accomplish this goal is acquisition of medical practices. Practice acquisitions require careful planning to address the complex legal issues involved, including possible violations of antikickback, self-referral, and antitrust laws. This article offers an overview of the acquisition process and a checklist of relevant legal issues.