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PubMedDate not supplied

Paget's disease of bone: indications for treatment and goals of therapy.

Paget's disease of bone is a common disorder of unknown etiology characterized by increased bone remodeling and abnormal bone architecture. The pathologic process is initiated by an increase in osteoclast-mediated bone resorption, accompanied by a compensatory increase in bone formation. The increased bone remodeling results in a disorganized mosaic of woven and lamellar bone. This bone is highly vascular and gradually becomes enlarged and structurally weakened. Paget's disease is generally diagnosed in patients older than 40 years of age, usually as an incidental finding. The disease may be monostotic or polyostotic. The pelvis, femur, spine, tibia, skull, and humerus are most commonly involved. Most patients with Paget's disease are asymptomatic. Pain is the most common presenting symptom. Complications of the disease include bowing deformity of the long bones, fracture, and a variety of nerve compression syndromes. Malignant degeneration of Paget's disease is a rare complication. As safer, more effective therapies have become available, the indications for treatment and goals of therapy have changed. The difficult issue that clinicians are currently facing is whether to treat patients with asymptomatic disease. The progressive nature of the disease, the severity of its complications, its potential negative impact on quality of life, and the availability of therapy capable of controlling its activity have led many experts in the field to recommend treatment of asymptomatic patients who have active disease at sites where complications are likely to develop. There are, however, no data to prove that complications can be prevented by decreasing the rate of bone remodeling in Paget's disease, nor any data to define who is at risk for complications. Until more information is available, the management of patients with Paget's disease will continue to be based on clinical observation and theoretical considerations. This review examines the present understanding of Paget's disease, the rationale for the proposed indications for treatment and the goals of therapy.

Animals↗
PubMed1998

Motor denervation induces altered muscle fibre type densities and atrophy in a rat model of neuropathic pain.

Loose ligation of a sciatic nerve in rats (chronic constriction injury; CCI) provokes sensory, autonomic, and motor disturbances like those observed in humans with partial peripheral nerve injury. So far, it is unknown whether these motor disturbances result from (mechanical) allodynia or from damage to the motor neuron. These considerations prompted us to assess, in CCI rats, the density of motor axons in both the ligated sciatic nerve and the ipsilateral femoral nerve. To this end, we determined the number of cholinesterase positive fibres. It has been demonstrated previously that muscle fibre type density may be used as a measure of motor denervation and/or hypokinesia. Therefore, the myofibrillar ATPase reaction was employed to assess fibre type density in biopsies obtained from the lateral gastrocnemius muscle (innervated by sciatic nerve) and rectus femoris muscle (innervated by femoral nerve). We observed axonal degeneration of motor fibres within the loosely ligated sciatic nerve, both at an intermediate (day 21) and at a late stage (day 90) after nerve injury. The reduction in the number of motor nerve fibres was more pronounced distal to the site of the ligatures than proximal. A (less pronounced) reduction of motor fibres was observed in the ipsilateral (non-ligated) femoral nerve. In line with these findings, we observed altered fibre type densities in muscle tissue innervated by the ligated sciatic nerve as well as the non-ligated femoral nerve indicative of motor denervation rather than hypokinesia. The findings of this study suggest that the motor disorder induced by partial nerve injury involves degeneration of motor nerve fibres not only within the primarily affected nerve but also within adjacent large peripheral nerves. This spread outside the territory of the primarily affected nerve suggests degeneration of motor neurons at the level of the central nervous system.

Acetylcholinesterase↗
PubMed2002

A mouse model of neuropathic cancer pain.

We developed a mouse model of neuropathic cancer pain by inoculating Meth A sarcoma cells to the immediate proximity of the sciatic nerve in BALB/c mice. The tumor grows predictably with time and gradually compresses the nerve, thereby causing nerve injury. Time courses of thermal hyperalgesia and mechanical sensitivity to von Frey hairs were determined and signs of spontaneous pain were evaluated. We compared this model with the chronic constriction injury (CCI) model, which is a neuropathic pain model widely utilized in the rat. Furthermore, to characterize the difference in nerve injury between the two models, we performed histological examination of the nerve of the two models by light and electron microscopy. Progressive compression of the sciatic nerve by growth of a tumor mass resulted in a gradual development of thermal hyperalgesia and mechanical allodynia in the ipsilateral hind paw. Signs of spontaneous pain, such as lifting of the paw, were also observed. However, further growth of the tumor reversed the mechanical hypersensitivity and produced mechanical hyposensitivity, while thermal hyperalgesia and signs of spontaneous pain still persisted. Histologically, gradual compression by the tumor resulted in a progressive damage to both myelinated and unmyelinated fibers. However, the severity of damage to the myelinated fibers was considerably less compared to that of the CCI mice. In the CCI mice, severe damage to myelinated fibers, especially large fibers, was observed and unmyelinated fibers were damaged to a lesser degree. These results suggest that gradual compression of a nerve by a malignant tumor results in nerve damage with a profile considerably different from that of chronic constriction injury produced by loose ligation of the nerve. Our new tumor model may be useful in studies of neuropathic cancer pain due to nerve compression by malignant tumors.

Animals↗
PubMed1998

Afferent activity from myelinated inferior alveolar nerve fibers in ferrets after constriction or section and regeneration.

To investigate possible peripheral mechanisms for post-injury sensory disorders in the trigeminal system, we have made electrophysiological recordings from myelinated fibres in the inferior alveolar nerve (IAN) which have previously sustained an injury. In earlier experiments we have shown that axons in ligature-induced neuromas of the IAN develop spontaneous activity and mechanical sensitivity. The present study has investigated these responses after two different types of injury. In 24 anaesthetised adult male ferrets the left IAN was either chronically constricted by four loose chromic gut ligatures (12 animals) or sectioned and regeneration permitted (12 animals). After recovery periods of 3 days, 1, 3, 6, 12 or 24 weeks, single unit recordings were made from the nerve proximal to the injury site. The proportion of units which were spontaneously active ranged from 0% to 19% after constriction injury and from 0% to 10% after nerve section and regeneration. Both groups revealed a marked variability between individual animals at similar time periods. Mechanical sensitivity was found in 0-42% of units after constriction and 0-25% of units after nerve section; both groups showed a significant negative correlation between mechanical sensitivity and recovery period. None of the fibres which had regained peripheral receptive fields was either spontaneously active or mechanically sensitive. There was no significant difference between the levels of spontaneous activity or mechanical sensitivity in the two groups or that previously found in ligature-induced neuromas. Thus we conclude that widely differing types of peripheral nerve injury are capable of initiating similar raised levels of afferent activity in myelinated inferior alveolar nerve fibres.

Action Potentials↗
PubMed1997

Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a chronic constriction injury.

We compared the time-course of sympathetic nerve sprouting into the L4-6 dorsal root ganglia (DRG) of adult rats following a chronic constriction injury (CCI) made on the sciatic nerve, or following sciatic nerve transection at the same site. We also tested the rats for changes in threshold for withdrawal from mechanical and thermal stimuli delivered to the hindpaws. We found sympathetic sprouting in DRG by 4 days following CCI, paralleling the decreases in mechanosensory threshold and preceding changes in thermal thresholds. However, with sciatic nerve transection, sympathetic sprouting was not detectable until 14 days after nerve injury. Thus, after CCI, sympathetic sprouting occurs with a sufficiently rapid time-course for it to play a role in the genesis of neuropathic pain. We suggest that the more rapid sprouting seen after CCI than after resection is due to the availability of products of Wallerian degeneration, including nerve growth factor, to both spared and regenerating axons following CCI, but not following resection.

Animals↗
PubMed2000

Hyperalgesia due to nerve injury-role of peroxynitrite.

We carried out a partial ligation of the sciatic nerve in rats to induce nerve injury and neuropathic hyperalgesia. We showed that nitrotyrosine, a marker of peroxynitrite activity, was formed after partial nerve injury. Double-labelling immunohistochemistry showed that nitrotyrosine-immunoreactive cells were mainly macrophages and Schwann cells. Daily treatment with uric acid, a scavenger of peroxynitrite, decreased nitrotyrosine formation in the injured sciatic nerve, and produced concomitant alleviation of thermal hyperalgesia and Wallerian degeneration. These results provide the first evidence that peroxynitrite is formed after partial nerve injury, and contributes to the initiation of thermal hyperalgesia and Wallerian degeneration. We hypothesize that uric acid alleviates hyperalgesia and Wallerian degeneration by inhibiting oxidative damage caused by peroxynitrite and possibly also by decreasing the production of other inflammatory mediators such as prostaglandins.

Animals↗
PubMed1986

Histopathology of compression of the superficial radial nerve in the forearm.

A histologic assessment of the radial sensory nerve from a patient with nerve compression is reported. Histologic changes were confined to the region of the nerve compression. Connective tissue changes consisted of an increased thickness of the epineurium and perineurium. Nerve fiber changes consisted of Schwann cell pathology with marked thinning of the myelin noted in the myelinated fibers and evidence of degeneration and regeneration noted in the unmyelinated fiber population. Nerve fiber pathology was not uniform but varied from fascicle to fascicle in the compressed area.

Forearm↗
PubMed1987

An experimental study on the "double crush" hypothesis.

An experimental study investigated the vulnerability of peripheral nerves in the "double crush" situation. Canine sciatic nerves were studied by means of electrophysiologic and histologic examination. Compression was applied by the KEIO compression clamp, with compression force of 15 g (approximately, 27.6 mm Hg). An incomplete conduction block and mild axonal degeneration were induced by a single compression. However, a complete conduction block and severe axonal degeneration could be induced in half of the cases by the double compression. In these cases, the loss of nerve function after a double lesion was greater than the sum of the deficits after each separate lesion. A good therapeutic effect was obtained by removing all compression, but the effect was incomplete when either compression was retained. It is concluded that proximal compression of a nerve could lessen its ability to withstand further compression more distally.

Action Potentials↗
PubMed1997

Questions of the handsurgeon to the radiologist--a survey on the most common lesions in the hand and the implications of diagnostic tools on their therapy.

By the rapid development of imaging techniques, a significant gap developed between the knowledge of the radiologists and that of the hand surgeons on specific indications of the different technical possibilities. The problems to be solved by both specialties together are analyzed. Examples of the most common lesions in the hand like trauma, reflex sympathetic dystrophy, congenital malformation, infection, tumour, rheumatoid and other degenerative processes, nerve compression syndromes etc., are given, and the implications of diagnostic tools on their therapy are discussed.

Hand↗
PubMed1997

[Ulnar nerve fascicle transfer onto to the biceps muscle nerve in C5-C6 or C5-C6-C7 avulsions of the brachial plexus. Eighteen cases].

The authors report 18 cases of transfer of several ulnar nerve fascicles onto the biceps muscle nerve, performed between 1990 and 1997. The patients were between the ages of 17 and 41 years, and presented C5-C6 paralysis in 8 cases and C5-C6-C7 paralysis in 10 cases. The operation was tempted between 4 months and 6 years (m = 17 months) after the initial accident. In the 8 cases of C5-C6 paralysis reviewed, 7 patients recovered elbow flexion and only one required an additional Steindler transfer. In the 9 cases of C5-C6-C7 paralysis reviewed, 4 patients recovered elbow flexion after nerve surgery alone, while 4 patients only obtained elbow flexion after a complementary Steindler transfer. Two of these 4 patients were operated very late (27 and 75 months). Finally, a single 40-year-old patient, operated 28 months after the accident, was considered to be a complete failure. Overall, ulnar biceps nerve transfer appears to be indicated in C5-C6 avulsion, during the months following the initial accident. Flexion against gravity is then regularly obtained in less than 6 months, without any objective or subjective sequelae of the hand.

Adolescent↗
PubMed2002

Arthrodesis as salvage for calcaneal malunions.

Even with greater emphasis on anatomic reduction, outcomes after calcaneal fractures continue to be unsatisfactory in many patients. Lateral wall impingement, subtalar arthrosis with pain and stiffness, nerve compression syndromes, and hindfoot malalignment all can cause disabling symptoms. If conservative treatment fails to relieve symptoms, subtalar arthrodesis can provide a painless, stable hindfoot in most patients. For severe deformity with anterior ankle impingement and loss of the talar angle of declination, distraction bone block arthrodesis through a posterior approach is preferred.

Arthrodesis↗
PubMed2000

Tumour progression and angiogenesis in bone metastasis from breast cancer: new approaches to an old problem.

Breast cancer metastasizes frequently to the skeleton and causes considerable morbidity and deterioration of the quality of life. The clinical consequences of skeletal metastases are bone pain, pathological fractures, hypercalcaemia and nerve compression syndromes. From the moment breast cancer cells are located in the bone microenvironment, they may release factors which stimulate bone resorption and angiogenesis leading to growth of skeletal metastases and a subsequent selective increase in the attraction of new cancer cells to bone. In this review, emerging new concepts of breast cancer-bone interactions, in particular the involvement of angiogenesis, proteolysis and the role of cancer-induced bone resorption in skeletal metastasis are discussed. Better understanding of the processes involved in the metastasis of cancer cells to bone, local tumour growth and subsequent destruction of skeletal architecture can lead to optimal methods for the prevention and treatment of metastatic bone disease.

Animals↗
PubMed2001

Flexor digitorum superficialis nerve transfer to restore pronation: two case reports and anatomic study.

Loss of pronation affects most activities of daily living. We report 2 cases of traumatic loss of pronator teres function and successful reconstruction by transfer of a redundant motor branch to the flexor digitorum superficialis to the pronator teres branch(es). Follow-up period was 2 years and pronation strength was restored to +4/5 and 5/5 in the 2 patients. The anatomy of the median nerve in the proximal forearm was examined by dissecting 31 cadaver specimens. A branching scheme was formulated. The histomorphometric properties of the individual muscular branches were studied in 15 fresh specimens to evaluate their suitability and size match for nerve transfer.

Accidents, Traffic↗