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Biomedical subjects

J H Herndon

Publications and source records attributed to J H Herndon.

At least 19 recordsLinked to original sources

A minimally invasive method for the determination of force in the interosseous ligament.

OBJECTIVE: The objective was to develop and utilize a minimally invasive testing system to determine the force in the interosseous ligament under axial compressive loads across the range of motion of the human forearm. DESIGN: Eleven fresh frozen human cadaveric forearms were used (51-72 years). BACKGROUND: Current studies investigating interosseous ligament forces altered the structure of the forearm by implanting load cells into the radius and ulna. This may affect load transfer through the forearm. Little information was available on interosseous ligament function over the entire flexion range of the elbow. METHODS: A robotic joint testing system was used to apply a 100 N compressive load to the forearm and measure the resulting displacement. Each forearm was tested with no disruption of the bones and soft tissues of the forearm. The principle of superposition was used to calculate the forces in the interosseous ligament and was indirectly validated using fluoroscopy. RESULTS: The force in the interosseous ligament ranged from a minimum of 8 N in neutral forearm rotation at full extension to a maximum of 43 N in supination at 30 degrees of flexion. The largest force was found in supination at all flexion angles. CONCLUSIONS: The interosseous ligament is an important structure in the stability of the forearm. The force in the interosseous ligament depends on the elbow flexion angle and forearm rotation. RELEVANCE: This study suggests that radial head fractures are best treated with the forearm in supination, since the interosseous ligament takes the largest load in this position. Complex injuries which have a poor prognosis, may require interosseous ligament reconstruction to improve clinical outcomes.

Aged↗

Integrated health systems: success or failure?

There continues to be an increasing number of healthcare delivery systems as a result of marketplace changes that include declining reimbursement and increasing costs for healthcare. However, the majority of these systems fail. Failures are a consequence of poor management, lack of a common mission and business rationale, individual's interests that outweigh the entity's interests, and the conflict of cultures. Incremental changes will continue, but the healthcare environment will remain unstable for the foreseeable future.

Delivery of Health Care, Integrated↗

Gene therapy for rheumatoid arthritis.

Advances in understanding the biology of rheumatoid arthritis (RA) have opened new therapeutic avenues. One of these, gene therapy, involves the delivery to patients of genes encoding anti-arthritic proteins. This approach has shown efficacy in animal models of RA, and the first human, phase I trial has just been successfully completed. Hand surgery featured prominently in this pioneering study, as a potentially anti-arthritic gene encoding the interleukin-1 receptor antagonist was transferred to the metacarpophalangeal joints of subjects with RA one week before total joint arthroplasty. This study has confirmed that it is possible to transfer genes safely to human joints. It should pave the way for additional application of gene therapy to arthritis and other orthopaedic conditions.

Arthritis, Rheumatoid↗

Implant arthroplasty of the metacarpophalangeal joint of the thumb.

Thumb metacarpophalangeal arthritis may affect overall hand function more than expected because pain and instability compromise pinch and grip strength. Implant arthroplasty represents one option in the treatment of deformity, destruction, and instability at the metacarpophalangeal joint level. Appropriate use of implant arthroplasty requires careful evaluation of the overall deformity and the status of the interphalangeal joint. If the interphalangeal joint is likely to require fusion--either simultaneous with metacarpophalangeal surgery or subsequently--then implant arthroplasty may be the best treatment option for the metacarpophalangeal joint.

Arthritis↗

Adapalene gel 0.1% is effective and well tolerated in acne patients in a dermatology practice setting.

The US Food and Drug Administration has approved adapalene gel 0.1% for use in the treatment of acne vulgaris. The objective of our study was to evaluate the efficacy and tolerability of adapalene gel 0.1% in the treatment of acne vulgaris in a clinical practice. We used a 12-week, multicenter, open-label, noncomparative phase 4 study of adapalene gel 0.1%. The study involved approximately 600 dermatologists in the United States and included 2,545 healthy men and nonpregnant women older than 14 years who had mild or moderate acne vulgaris. Of the patients enrolled, 75% completed the study and most of them (89%) showed an improvement in their acne (clear of acne or marked, definite, or minimal improvement) from baseline. Most patients (69%) were satisfied or very satisfied with adapalene therapy, and most (80%) wished to continue treatment. Only 3.7% of patients enrolled reported treatment-related adverse events (n=94), the most common being skin irritation (2.2%). We conclude from this open-label trial in a dermatology practice setting that adapalene gel 0.1% was effective and well tolerated and had a favorable safety profile. Furthermore, compliance with once-daily application of adapalene was rated as high by 92% of patients who responded to a self-assessment questionnaire.

Acne Vulgaris↗

Basal joint arthroplasty using an allograft tendon interposition versus no interposition: a radiographic, vascular, and histologic study.

To assess the role of a tendon spacer that fills the trapezial void, the trapeziums were excised and anterior oblique ligaments were reconstructed in 25 monkeys. In addition to the ligament reconstruction, 20 of the monkeys had the trapezial void filled with a tendon allograft. The trapezial space was investigated at 0, 3, 6, 15, and 40 weeks using routine histologic staining, arterial perfusion (Spalteholz), and standardized radiographs. There was a statistically greater decline in trapezial height in the animals without tendon interposition allografts. The tendon grafts became progressively neovascularized and populated with fibroblasts. By 40 weeks, the allograft was no longer a folded tendon but a homogeneous mass of collagen, fibroblasts, and capillaries. The specimens without an interpositional tendon graft had loose fibroadipose tissue filling the carpal void. Polarized light microscopy showed fibers crossing the subchondral bone and moving into the adjacent fibrous spacer in the specimens implanted with a tendon graft. The results indicate that filling the trapezial void with an interposition tendon spacer may aid in maintaining normal wrist anatomy.

Animals↗

Role of the forearm interosseous ligament: is it more than just longitudinal load transfer?

The objective of our study was to measure 3-dimensional force vectors (magnitude and direction) acting in the forearm when load is applied to the hand and to measure the actual force in the interosseous ligament (IOL). Fourteen cadaveric forearms were loaded to 136 N of compression while special load cells measured force vectors in the forearm. Computer forearm models were used to display the 3-dimensional force vector directions. The study results showed that the radius bears most of the load at the wrist but load on the radius at the elbow is reduced because the IOL transfers load to the ulna between the wrist and the elbow. In addition to this role in longitudinal load transfer, our measurement of 3-dimensional forces allowed identification of transverse vectors which suggest that the IOL also functions to keep the radius and ulna from splaying apart. Our results imply that the IOL participates not only in longitudinal load transfer but also in the maintenance of transverse stability of the forearm during compressive load transfer from the hand to the elbow.

Aged↗

Comparison of ulnar shortening osteotomy and the wafer resection procedure as treatment for ulnar impaction syndrome.

A retrospective review was performed that compared the results of 2 different surgical treatments for ulnar impaction syndrome in 22 patients over a 6-year period. Ulnar shortening osteotomy and wafer distal ulna resection (wafer resection procedure) were each performed in 11 patients based on the preference of 3 individual hand surgeons. All patients presented with ulnar wrist pain and positive ulnar variance on either neutral rotation or pronated-grip x-rays and each failed conservative management. At a minimum follow-up time of 18 months, 9 patients had good to excellent results following ulnar shortening osteotomy compared with 8 following the wafer resection procedure. This difference was not statistically significant. All patients regained functional wrist motion and 21 of the 22 patients had satisfactory pain relief. There was 1 poor result in the wafer group that required revision to complete resection of the distal ulna. Five secondary procedures were required in the osteotomy group to remove painful hardware and union was delayed in 2 patients. Although ulnar shortening osteotomy provides effective treatment for ulnar impaction syndrome, the wafer resection procedure provides favorable pain relief and restoration of function but without the potential for nonunion or hardware removal. (J Hand Surg 2000; 25A:55-60.

Adolescent↗

Clinical trials in the gene therapy of arthritis.

Gene therapy clinical trials raise important safety issues that complicate their design and require extensive preclinical testing. Human protocols for the treatment of arthritis and most other orthopaedic and rheumatologic indications are complicated additionally by the perception that they are largely acquired, nonlethal conditions. Taking these considerations into account, the first such human study used the local, ex vivo delivery of a gene whose product, the interleukin-1 receptor antagonist, has an outstanding safety profile. This gene was delivered to the metacarpophalangeal joints of postmenopausal women 1 week before these joints were removed during total joint replacement surgery. In addition to providing an additional safety cushion, the surgical removal of the genetically modified joints made available large amounts of tissue to examine for evidence of successful gene transfer and gene expression. This Phase I safety study was approved at the local and federal levels, and its funding was contingent on the establishment of an external monitoring board. This trial now has been completed and a Phase II, efficacy study is being planned. A similar study has begun in Dusseldorf, Germany and results from the first two patients are similar to the results of the American patients. Permission has been given for two additional human trials, one in the United States and one in the Netherlands, in which a gene encoding herpes thymidine kinase will be transferred to the joints of patients with rheumatoid arthritis who then will be administered gancyclovir. This procedure aims to treat the disease by producing a genetic synovectomy. Additional development of human gene therapies for arthritis and other orthopaedic and rheumatic conditions will be aided by the successful completion of these studies.

Animals↗

The Marshall R. Urist Young Investigator Award. Orthopaedic applications of gene therapy. From concept to clinic.

Gene therapy offers new possibilities for the clinical management of orthopaedic conditions that are difficult to treat by traditional surgical or medical means. To bring the potential of this novel technology into the clinic, a research program was initiated that aimed to identify orthopaedically useful genes and develop methods for delivering them to suitable sites under conditions in which gene expression remains at therapeutic levels for the appropriate periods of time; this program is now 10 years old. Rheumatoid arthritis was selected as the lead disease. Preclinical studies evaluating the local and systemic delivery of numerous different genes by in vivo and ex vivo methods in murine and lapin models led to the development of a human gene therapy protocol for arthritis. In this protocol, a gene encoding the human interleukin-1 receptor antagonist protein is transferred to the metacarpophalangeal joints of female patients with rheumatoid arthritis. The first patient was treated this way in July 1996. This is not only the first orthopaedic application of human gene therapy, but also the first use of gene therapy approved for a nonlethal disease. In addition to providing additional therapeutic options for the treatment of rheumatoid arthritis, the experimental data from this study suggest that gene transfer approaches may improve the treatment of osteoarthritis, the repair of cartilage, ligaments, tendons, menisci, intervertebral discs and bone, and the management of disorders such as osteoporosis and osteogenesis imperfecta. They also show promise as a means for developing novel and improved animal models of orthopaedic diseases. If the current rate of progress continues, wide clinical application of gene therapy in various orthopaedic indications should occur within the next 5 to 10 years.

Animals↗

A new methodology to measure load transfer through the forearm using multiple universal force sensors.

Previous approaches to measuring forces in the forearm have made the assumption that forces acting in the radius and ulna are uniaxial near the wrist and elbow. To accurately describe forces in the forearm and the forces in the interosseous ligament, we have developed a new methodology to quantitatively determine the 3-D force vectors acting in forearm structures when a compressive load is applied to the hand. A materials testing machine equipped with a six degree-of-freedom universal force-moment sensor (UFS) was employed to apply a uniaxial compressive force to cadaveric forearms gripped at the hand and humerus. Miniature UFSs were implanted into the distal radius and proximal ulna to measure force vectors there. A 3-D digitizing device was used to measure transformations between UFS coordinate systems, utilized for calculating the force vectors in the distal ulna, proximal radius, and the interosseous ligament (IOL). This method was found to be repeatable to within 3 N, and accurate to within 2 N for force magnitudes. Computer models of the forearm, generated from CT scans, were used to visualize the force vectors in 3-D. Application of this methodology to eight forearm specimens showed that the radius carries most of the load at the wrist while force in the IOL relieves load acting in the radius at the mid-forearm. For a 136 N applied hand force, the force in the IOL was 36 + 21 N. Advantages of this methodology include the determination of 3-D force vectors, especially those in the IOL, as well as computer generated 3-D visualization of results.

Biomechanical Phenomena↗

Failed endoscopic carpal tunnel release. Operative findings and results of open revision surgery.

From 1994 to 1997, 22 patients (24 wrists) underwent open revision carpal tunnel release for persistent carpal tunnel syndrome after a primary endoscopic release. The age range was from 21 to 77 years. At the time of revision surgery, 22 wrists had an incomplete release of the flexor retinaculum and two patients had median nerve transection (one partial and one complete). One patient had release of Guyon's canal and not the carpal tunnel. After the open revision carpal tunnel release, 20 patients returned to work with five patients returning to jobs of lighter duty. In addition, these 20 patients had significant improvement in symptoms. The remaining two patients had sustained a median nerve injury and did not return to work. One of these patients developed a painful neuroma in continuity of the median nerve which required vein wrapping with a saphenous vein graft. This study indicates that endoscopic release of the flexor retinaculum holds the same risks and complications as open release. Based on our study we believe that patients with persistent carpal tunnel syndrome after failed endoscopic flexor retinaculum release can be successfully treated with open release.

Adult↗

Topical metronidazole maintains remissions of rosacea.

BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea. DESIGN: A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers. SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel. INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed. RESULTS: In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%). CONCLUSION: In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.

Administration, Cutaneous↗