Comparison of gene expression profiles between Peyronie's disease and Dupuytren's contracture.

OBJECTIVES: To compare the gene expression alterations in human Peyronie's disease (PD) and Dupuytren's disease (DD) to determine whether they share a common pathophysiology. Multiple mRNA expression profiles of human PD have previously shown that genes that regulate fibroblast replication, myofibroblast differentiation, collagen metabolism, tissue repair, and ossification are involved. DD, a palmar fascia fibrosis, may be associated with PD. METHODS: Total RNA samples from PD plaques, normal tunica albuginea, Dupuytren's nodules, and normal palmar fascia (nine samples per group) were subjected to differential gene expression profile analysis (Clontech Atlas DNA microarray) comparing PD with tunica albuginea and DD with normal palmar fascia. Changes of more than 2.0 in PD and DD compared with tunica albuginea and normal palmar fascia, respectively, were recorded. Reverse transcriptase-polymerase chain reactions were performed for some genes whose expression was altered in PD. RESULTS: Some of the gene families upregulated in both PD and DD were (a) collagen degradation: matrix metalloproteinase (MMP), with MMP2 and MMP9, and thymosins (MMP activators), with TMbeta10 and TMbeta4; (b) ossification: osteoblast-specific factors (OSFs) OSF-1 and OSF-2 (DD only); and (c) myofibroblast differentiation: RhoGDP dissociation inhibitor 1. The genes upregulated in PD only were decorin (an inhibitor of transforming growth factor-beta1 and a part of fibroblast replication/collagen synthesis) and early growth response protein. Reverse transcriptase-polymerase chain reaction confirmed these changes. CONCLUSIONS: These data demonstrate that the pattern of alterations in the expression of certain gene families in PD and DD is similar, suggesting that they share a common pathophysiology and may be amenable to the same therapeutic regimens.

The innervation of the triangular fibrocartilage complex: nitric acid maceration rediscovered.

Injury to the triangular fibrocartilage complex (TFCC) is frequently implicated in the etiology of ulnar-sided wrist pain. This study examines the nervous anatomy of the TFCC using a nitric acid maceration technique and attempts to correlate this information with known tear patterns. Ten fresh frozen cadaveric specimens were studied in detail. Gross dissection of each upper-extremity specimen included removal of all flexor and extensor tendons. After identification and labeling with permanent color of the ulnar nerve, dorsal sensory branch of the ulnar nerve, posterior interosseous nerve, anterior interosseous nerve, and median nerve, an en bloc excision of the distal radioulnar region was performed. Digestion of the soft tissue was performed with nitric acid at sequential concentrations of 50% and 33% for 9 of 10 specimens. The digestion was halted by immersing the specimen in a mixture of 10% formaldehyde and 1% glycerine. After removal of bone, the specimens were fixed in paraffin, sectioned, and stained with hematoxylin and eosin. Nine of the 10 specimens were studied microscopically to determine the contribution of the grossly identified nerves to each zone of the triangular fibrocartilage complex as defined by Palmer's classification of acute TFCC tears. The anterior interosseous, median, and superficial radial nerves did not contribute to the innervation of the TFCC. The intraarticular course of the peripheral nerves could not be defined in the one specimen that was not digested with nitric acid. Nitric acid maceration is a rediscovered technique for identifying the nervous anatomy of soft tissues. The study showed that the triangular fibrocartilage complex is innervated by branches of the posterior interosseous, ulnar, and dorsal sensory ulnar nerves in a fairly consistent manner. Improved treatment of TFCC tears may result from an enhanced understanding of the supporting structures' innervation and mechanical function.

A vision of hand surgery over the next 25 years.

Predictions for hand surgery advances over the first 25 years of the new millennium are made. Anticipated changes are categorized as societal, technologic, and research with clinical applications. Certainly advances in computer science and molecular biology will affect all aspects of our lives. Within hand surgery, tissue engineering, materials science, and nanotechnology offer great promise.

Intratendinous rupture of a flexor tendon graft many years after staged reconstruction: a report of three cases.

Three cases of rupture of a flexor tendon graft many years after surgery are presented. Two cases occurred 12 years after reconstruction and the third case occurred 21 years after reconstruction. Each rupture was intratendinous, just proximal to the flexor tendon sheath in 2 cases and at the proximal edge of the transverse carpal ligament in the third case. Active digital flexion was restored by transfer of the flexor digitorum superficialis from an adjacent finger to the distal tendon stump or by direct end-to-end repair of the rupture site reinforced with an onlay autogenous patch graft. Patients undergoing tendon grafting should be alerted to the possibility of rupture, even many years later.

The journal club and its role in hand surgery education.

Journal clubs are a time-honored method of teaching literature appraisal skills in many residency programs. A questionnaire was completed by 57 hand surgery fellowship directors and 91 hand fellows to define the role of the journal club in hand fellowship training. We sought to identify definitive characteristics of hand surgery journal clubs and assess their strengths and weaknesses. One hundred forty-eight of 164 (90%) directors and fellows responded, yielding information on 57 of 58 accredited hand fellowships. Forty-nine of 57 (86%) responding fellowships have a journal club. The majority of clubs meet monthly for 1 to 2 hours, usually within the hospital. The primary purpose is to familiarize both fellows and attendings with the current literature. Most often, fellows choose the articles, which are most commonly original research and review articles. Usually, faculty presides, and residents and fellows present. Increased faculty participation was the most frequently suggested improvement. The great majority of those surveyed felt that their journal club was successful and was an important part of the fellowship training. We conclude that journal clubs have a high perceived value by participants, and recommend the journal club to all hand surgery communities, with or without fellowship involvement.

Right versus left symmetry of ulnar variance. A radiographic assessment.

One hundred skeletally mature healthy volunteers underwent standardized bilateral posteroanterior radiographs in unloaded (static) and loaded (dynamic) conditions to determine the symmetry of ulnar variance. The mean age was 32 +/- 9 years (range, 19-61 years), with 58 women and 42 men. Ulnar variance was measured to the closest 0.5 mm using the method of perpendiculars. Three separate measurements were made of each radiograph in a blinded fashion by the same investigator. An intraobserver standard deviation of 0.21 was used to calculate a 95% tolerance interval of 0.7 mm (rounded up to 1 mm) as a measure of significance. The average static ulnar variance was -0.13 +/- 1.5 mm on the left and -0.29 +/- 1.6 mm on the right. The average dynamic ulnar variance was 0.93 +/- 1.5 mm on the left and 0.82 +/- 1.5 mm on the right. When compared individually, there was a greater than or equal to 1 mm side to side difference in 37% of volunteers under static and 38% under dynamic conditions. There were no significant correlations between ulnar variance measurements and patient age, gender, race, or handedness. Use of the normal wrist radiograph as a baseline for static radial length measurements is valid in only 63% of cases.

Russell's sign. Subtle hand changes in patients with bulimia nervosa.

Bulimia nervosa is a common eating disorder, affecting between 1% to 10% of adolescent girls and college aged women. Because excessive weight loss and amenorrhea are not significant features, as they are in anorexia, bulimia is much harder to diagnose. Orthopaedic surgeons have a unique opportunity to detect one of the few physical signs of the disease, which is skin lesions, consisting of abrasions, small lacerations, and callosities on the dorsum of the hand overlying the metacarpophalangeal and interphalangeal joints. These nondescript dorsal lesions are caused by repeated contact of the incisors to the skin of the hand that occur during self induced vomiting. This finding, known as Russell's sign, may be seen by orthopaedic surgeons during examinations for other reasons. Because eating disorders are recognized as a component of the female athlete triad of osteoporosis, amenorrhea, and eating disorders and because orthopaedic surgeons routinely care for female athletes susceptible to these disorders, recognizing this sign and its implications may have profound influence on the patient's musculoskeletal system and general health.

Publication patterns of papers presented at the Annual Meeting of The American Academy of Orthopaedic Surgeons.

Publication in a peer-reviewed journal is the ultimate lasting acknowledgment of an author's research results. Numerous clinical and basic-science papers are presented at the Annual Meeting of The American Academy of Orthopaedic Surgeons, but not all of these presentations culminate in publication in a peer-reviewed journal. In an effort to determine the percentages and patterns of publication, every presentation from the 1990, 1991, and 1992 meetings (a total of 1465 presentations) was reviewed with use of a Melvyl Medline Plus computer search during the summer of 1996. The presentations were classified on the basis of subspecialty. The over-all rate of publication by August 1996 was 46 per cent (668 of 1465), and the rates were similar for the 1990, 1991, and 1992 meetings. The average time to publication was twenty months, and most publications appeared within three years after presentation, with a plateau thereafter. Basic-science presentations had the highest rate of publication: 64 per cent (eighteen of twenty-eight presentations). The rates of publication by clinical subspecialty ranged from 39 per cent (twenty-eight of seventy-two presentations in the hand subspecialty and eighty-two of 210 presentations in the trauma subspecialty) to 53 per cent (110 of 206 presentations in the spine subspecialty). There was no significant difference among these groups (p = 0.611, chi-square test). The American volume of The Journal of Bone and Joint Surgery published the most papers (24 per cent; 161 of the 668 publications), followed by Clinical Orthopaedics and Related Research (16 per cent; 106 of 668). The over-all rate of publication of presentations at the Annual Meeting of The American Academy of Orthopaedic Surgeons is comparable with reported rates in other medical specialties.

A practical guide to surgical loupes.

Loupes are widely used in both surgical and dental procedures to enhance visualization of tissues and to facilitate optimal instrument placement. Most doctors, however, have limited knowledge of fundamental optical principals or of the various types of loupes available. This article reviews basic optical terminology and principles and highlights features of various commercially available loupes.

Publication pattern of papers presented at the American Society for Surgery of the Hand annual meeting.

Publication of research results in peer-reviewed journals represents the consummation of the scientific method. In order to determine the rate of publication of oral presentations at the annual meeting of the American Society for Surgery of the Hand, every presentation (n = 397) from the 1990, 1991, and 1992 annual meetings was subjected to a Medline Plus computer search in January 1995. Meeting abstracts were grouped by program designation to scientific session, research session, and residents and fellows conference categories, and a Kaplan-Meier survivorship curve was formulated for each category. We determined an ultimate publication rate of 52% at 53 months. Subanalysis by year of presentation showed rates of 32%, 48%, and 51% for the respective years 1992, 1991, and 1990, with publication for most research occurring within 3 years of presentation. No statistically significant difference existed between the three categories, although a distinct trend toward higher ultimate publication rate (74%) was found for research abstracts. The ultimate publication rate for hand surgery presentations is comparable to that reported for other disciplines.

Elbow osteoarthritis and a massive forearm cyst. A case report.

Despite exhaustive evaluation, a massive forearm cyst in a 74-year-old man with elbow osteoarthritis could not be diagnosed. The patient had total elbow arthroplasty, and the cyst did not recur postoperatively. Osteoarthritis presumably caused the huge, but noncommunicating, synovial forearm cyst.

Automotive airbag-related upper extremity injuries: a report of three cases.

Automotive airbag technology has reduced the number of injuries and fatalities resulting from motor vehicle crashes. With the increasingly frequent application of this safety feature in automobiles, recent reports of airbag-associated injuries have emerged, including ocular and non-lethal cardiac trauma. We report three cases of airbag-related upper extremity injuries seen at a level-I trauma center over a 6-month period. A heightened awareness of this type of injury in patients injured in motor vehicle crashes with airbag deployment is recommended. The awareness, identification, and management of these high energy injuries will take on added meaning as the airbag technology becomes universally applied.

Intravascular papillary endothelial hyperplasia: a neoplastic "actor" representing an exaggerated attempt at recanalization mediated by basic fibroblast growth factor.

Intravascular papillary endothelial hyperplasia (IPEH), a lesion of the extremities often encountered by hand surgeons, is characterized histologically by a florid endothelial proliferation that is exclusively intravascular in location and suggests an exaggerated attempt at thrombus recanalization. The mechanism behind this exaggerated response is unknown. Prompted by an apparent increase in cases of IPEH noted at our hospital in the past 2 years and the availability of frozen tissue from these cases, we undertook studies of IPEH designed to better elucidate the pathogenesis of this neoplastic "actor." Studies of eight such lesions revealed them to be uniformly diploid by DNA flow cytometric analysis. Further studies of five pooled cases by Northern blot and immunoblot revealed a 5-10-fold increase in basic fibroblast growth factor transcripts (7.0 and 3.7 kb) and a 10-20-fold increase in immunoreactive basic fibroblast growth factor protein compared to that exhibited by non-IPEH organizing thrombi and cavernous hemangiomas. These results suggest that the pathogenesis of IPEH involves an autocrine loop of endothelial basic fibroblast growth factor secretion stimulating endothelial cell proliferation.

The effect of experimental hemarthrosis on joint stiffness and synovial histology in a rabbit model.

The effect of a single injection of unpreserved blood on joint stiffness and on synovial and cartilage histomorphology in the ankle joints of rabbits was determined at ten and 28 days after injection. The same volume of saline was placed in the contralateral ankle for comparison. After ten days, the hemarthrosis ankle was stiffer than the control ankle (p < 0.027), whereas at 28 days there was no statistical difference in stiffness between the hemarthrosis and control ankles, regardless of whether the limbs had been immobilized. Also after ten days, the hemarthrosis ankles had varying amounts of clotted blood, darkened articular cartilage, hypertrophic synovium with reactive blood vessels, and macrophages containing heme. The gross and histologic appearance of the saline ankles was normal. After 28 days, there were no differences in gross or microscopic appearance between the two ankles of the caged or immobilized rabbits. All ankles exhibited retreating inflammatory response in the synovium and mild synovial thickening. Acute hemarthrosis, unassociated with fracture or discernible joint injury, caused only transient changes in joint stiffness and synovial histology. These results indicate that the presence of blood in an otherwise grossly uninjured joint should not lead to ultimate compromise in cartilage integrity or joint function. Therapeutic arthrocentesis for acute posttraumatic hemarthrosis does not appear to be necessary for the prevention of permanent problems.

The effects of diuretics on posttraumatic joint stiffness and limb swelling in a rabbit periarticular fracture model.

Periarticular long bone fractures usually result in soft-tissue swelling because of edema and hemorrhage, as well as progressive, often permanent joint stiffness. The authors evaluated the effects of chlorothiazide, a commonly used diuretic, and acetazolamide, a weaker diuretic with a different mechanism of action, on joint stiffness and swelling using an established rabbit hindlimb model. Bilateral distal tibial fractures were produced in 30 adolescent New Zealand white rabbits. Twelve rabbits served as age-matched controls and received no treatment, 11 were treated with chlorothiazide, and seven were treated with acetazolamide, each for five days at doses adjusted for body weight but equivalent to human dosing. Eleven limbs were excluded from study because of fracture angulation in excess of 10 degrees. The mean stiffness ratios, comparing preoperative stiffness with stiffness at the end of the three-week study period, for diuretic-treated rabbits were significantly less than those in the control rabbits; there was no difference between the two treated groups. The total swelling and time to peak swelling did not differ among the three groups; however, peak swelling was least in the chlorothiazide group, the strong diuretic, when compared with the control and acetazolamide groups. The marked effect of diuretics on joint stiffness and their minimal effect on limb swelling were unexpected results and, taken in conjunction with previous treatment modalities tested in this model, indicate a complex, still poorly understood sequence of events leading to joint stiffness after periarticular injury.

Effects of antihistamines on joint stiffness and bone healing after periarticular fracture.

In an effort to blunt the inflammatory response following injury, we studied the effects of antihistamines on joint stiffness and bone healing after periarticular fracture. The hind limbs of 37 New Zealand white rabbits were instrumented with intramedullary Steinmann pins to allow immobilization after creating a distal tibia fracture. After periarticular ankle fracture, the rabbits were divided into groups to receive chlorpheniramine, low-dose terfenadine, high-dose terfenadine, or no antihistamine. Antihistamine was administered for the first 5 days after fracture. At 3 weeks after fracture, the rabbits treated with antihistamines showed a significant reduction in joint stiffness compared to control animals. To determine if antihistamine also retarded bone healing, an additional 12 New Zealand white rabbits underwent bilateral drilling of the midshaft of the femur with a 2.5 mm Steinmann pin. Six animals received oral terfenadine, and six served as controls. After 5 weeks of cage activity, the animals treated with the antihistamine showed a significant decrease in energy to failure of the femurs on torsional testing. Qualitative microscopic examination revealed less mature callus at the site of the femoral cortical defect in those animals treated with the terfenadine. Antihistamine may have heretofore unconsidered benefits in preventing post-traumatic joint stiffness but may slow healing of associated bony injuries.