Biomedical subjects
Publications and source records attributed to L C Hurst.
A 38-year-old patient, who can give the day of the week of any day this century, is described. He is believed to have been autistic in early childhood. The relationship of the autistic child and the adolescent idiot savant is discussed and brief reference made to the patient's method.
Localization of calcium-activated neutral protease in normal monkey (Cebus apella) skeletal muscle and peripheral nerve was studied by application of the indirect immunofluorescent and peroxidase-antiperoxidase techniques for light and electron microscopy. In muscle, the protease was demonstrated in association with endomysial collagen fibrils, basal lamina, sarcolemma, and Z-bands and also at neuromuscular junctions. In nerve, the enzyme was demonstrated in association with endoneurial collagen fibrils, basal lamina, axolemma, and neurofilaments of both myelinated and unmyelinated axons. Intramuscular injections of the thiol protease inhibitor, leupeptin, abolished Ca-activated neutral protease immunoreactivity in both muscle and peripheral nerve. These data suggest that the protease is localized both intracellularly and extracellularly in normal primate muscle and peripheral nerve. Inhibition of basal lamina associated neutral protease by leupeptin after denervation may hold significance for protecting this structure against degradation and preserving it as a neurotrophic lattice for axon regeneration.
This investigation describes the use of the calcium-activated protease inhibitor, leupeptin, as an adjunctive therapy to the microsurgical repair of median nerves in a primate model. Our results indicate that leupeptin facilitates morphological recovery in denervated thenar muscles and in distal sensory and mixed motor-sensory nerve trunks and functional recovery measured by motor nerve conduction velocity. Toxicological testing of leupeptin showed that, when administered at a dose of 12 mg/kg, intramuscularly, once daily, haematological and clotting profiles were not adversely affected.
Fifteen patients had culture proven Mycobacterium marinum infections of the hand; 11 had injured their hands while fishing in water around Long Island. No patient had type I lesions (verrucal), six patients had type II lesions (subcutaneous granulomas), and nine patients had type III lesions (deep). Histologic examination showed noncaseating granulomas in all cases. A specific defect in the patients' lymphocytes ability to respond to M. marinum antigens was identified. A combination of surgery and tetracycline provided effective treatment. Follow-up averaged 2 1/2 years.
Solitary congenital or infantile (desmoid-type) fibromatosis is a benign, but potentially locally aggressive lesion that is best treated by wide local excision. It has been confused with congenital fibrosarcoma and other soft-tissue malignant tumors. To our knowledge, ossification has not been reported previously in this lesion. A case of ossifying solitary congenital fibromatosis is presented with a discussion of its differential diagnosis and histologic distinction from other soft-tissue lesions, including soft-tissue and parosteal osteosarcoma.
The cellular immune responses of 12 patients with culture-proved Mycobacterium marinum infection involving deep tissues were studied. Of the 12 patients, 11 failed to respond to M. marinum antigens. All of the patients had, however, normal blastogenic responses to concanavalin A, phytohemagglutinin, pokeweed mitogen, and the antigens tetanus toxoid and Candida albicans. In contrast, 9 of 14 healthy fishermen responded to the M. marinum antigens with significant in-vitro blastogenesis. Infection of deep tissues with M. marinum is associated with antigen-specific T-cell anergy to M. marinum antigens.
Biopsy specimens of human and monkey peripheral nerves, when incubated in calcium containing media, showed a loss of neurofilaments and microtubules with replacement by granular debris. Cytoskeletal structures remained intact when incubated in calcium-free media. Disruption of neurofilaments and microtubules in calcium containing media was inhibited by the thiol protease inhibitor, leupeptin. Similar incubations of excised Pacinian corpuscles revealed evidence of early terminal axon degeneration in the presence of calcium. These data substantiate the hypothesis that neural cytoskeletal degradation in primates and in man is calcium-mediated.
The in vitro response of myofibroblasts to prostaglandins F2alpha (a vasoconstrictor) and E2 (a vasodilator) were evaluated in specimens obtained from the Dupuytren's nodules of 12 patients. Fibroblasts from four control samples of palmar fascia were similarly tested. This study demonstrated the ability of prostaglandin F2alpha to induce significant contraction of myofibroblasts. Prostaglandin E2 was noted to cause significant relaxation of myofibroblasts. The contractile/relaxation responses of control fibroblasts to these prostaglandins were minimal.
The physical characteristics of a new tin radiopharmaceutical, 4+Sn-117m diethylenetriamine-pentaacetic acid (DTPA), may make this compound appropriate for orthopedic therapeutic application. The physical and biologic half-lives of this tracer are 14 and 7.8 days, respectively. The decay scheme consists of short-range tissue destroying beta, conversion, and Auger electrons, and a 159-keV gamma ray. Significantly, this compound has a high degree of affinity for newly calcified bone at the site of experimental burr holes in contrast to the adjacent bone marrow. Radioactive skeletal retention was one-half of whole body retention.
In this series of 1,000 cases of carpal tunnel syndrome (888 patients) there is a statistically significant incidence of bilaterality in patients with cervical arthritis. There is also a statistically significant increase in the incidence of diabetes mellitus over the general population. These findings lend further support to Upton's Double Crush hypothesis. Further, the double crush syndrome predisposes to bilateral carpal tunnel syndrome and may be an important prognostic factor. It may also be an explanation for some of the failures following carpal tunnel surgery and lead surgeons to look for other associated systemic diseases or mechanical blocks, when attempting to alleviate recalcitrant symptoms.
The formation of neuroma scar after trauma or neurorrhaphy is believed to be mediated by the response of collagen forming fibroblasts. In this study of twenty human neuromas, myofibroblasts were identified as a component of the scar. These cells occurred singly or as aggregates. There was a qualitative increase of myofibroblasts during the period from two to six months post-injury. From six months to one and one-half years post-injury, numbers and aggregations of myofibroblasts diminished, concurrent with collagen proliferation. Ultrastructural alcian blue staining and biochemical analyses revealed a glucosamine--glycosaminoglycan matrix within neuromas when compared to control nerves. Myofibroblasts appear to play a part in the pathobiology of human neuromas.
Investigations were undertaken on the regeneration of transected rat sciatic nerves. The ability of the protease inhibitor leupeptin to inhibit wallerian degeneration and muscle atrophy was evaluated. After transection of a sciatic nerve and immediate neurorrhaphy, animals were treated with leupeptin for a period of 1 week to 6 months. Our results indicate a significant increase in the numbers of myelinated and unmyelinated neurofibers in the distal segment of treated nerves. Peroxidase tracer, injected intramuscularly, was transported by retrograde axonal flow and was observed to label increased numbers of treated axons both distal and proximal to the repair site. This finding suggests that treated neurofibers are functionally viable. Evaluation of muscle showed that secondary muscular atrophy is also significantly inhibited by leupeptin.
A patient with a soft tissue T cell lymphoma with symptoms of de Quervain's tenosynovitis and a forearm mass in the area of the abductor pollicis longus and extensor pollicis brevis is described. Previously excised soft tissue masses from other locations had presented a diagnostic dilemma in this patient. This report clarifies the histopathology of soft tissue T cell lymphomas of the extremities. After surgical debulking and local radiotherapy, there has been no evidence of recurrence at 1 year.
Histologic, ultrastructural, and horseradish peroxidase tracing studies have shown that the carbon dioxide laser does not, as previously reported, seal transected axons in peripheral nerves that are subsequently repaired. If sealed nerve ends are the desired effect, such as in treatment of painful neuromas, this experimental animal study in rats suggests that the laser may be contraindicated because of the possible retention of proximal nerve regenerative ability. For resections of peripheral neuromas followed by neurorrhaphy, our data indicate that conventional scissor transection of the nerve may be followed by better reinnervation than that of laser transection.
The role of myofibroblasts in the pathogenesis of Dupuytren's contracture was investigated by light and electron microscopic histochemical methods. Dupuytren's myofibroblasts contain an intracellular contractile mechanism that is driven by the dephosphorylation of adenosine triphosphate. Our study of calcium adenosinetriphosphatase (ATPase) activities verifies that the site of this energy system is on the myofilaments of the myofibroblasts. The degree of ATPase activity, as determined by cell counts, appeared to correlate with the residual contracture as predicted by the Legge and McFarlane Outcome Standard Formula. Further, alcian blue staining on the ultrastructural level indicates that the myofibroblasts are associated with each other and with surrounding collagen by a glycosaminoglycan matrix 300 to 1000 A thick. Collagen fibrils are attached by a similar matrix comprised of 100 A thick fibrils. The dynamic cellular architecture of the multiple adjacent myofibroblasts with their connections to surrounding collagen may be partially responsible for the residual clinical deformities seen in this disease.
The treatment of the uncommon symptomatic and neglected Monteggia fracture-dislocation of childhood can pose a significant clinical problem because of pain, decreased range of motion, unstable cubitus valgus, and possible nerve damage. This unusual injury is presented with a detailed description of a modified Bell Tawse annular ligament reconstruction. The modifications of the procedure simplify it and more closely duplicate the anatomy of the annular ligament. This procedure is indicated in the treatment of the symptomatic and neglected Monteggia fracture-dislocation of childhood.
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