Nerve repair by denatured muscle autografts promotes sustained sensory recovery in leprosy.

A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality.

Crystallization and preliminary X-ray diffraction analysis of a eumenine mastoparan toxin: a new class of mast-cell degranulating peptide in the wasp venom.

Mastoparans are tetradecapeptides found to be the major component of vespid venoms. A mastoparan toxin isolated from the venom of Anterhynchium flavomarginatum micado has been crystallized and X-ray diffraction data collected to 2.7 A resolution using a synchrotron-radiation source. Crystals were determined to belong to the space group P6(2)22 (P6(4)22). This is the first mastoparan to be crystallized and will provide further insights into the conformational significance of mastoparan toxins with respect to their potency and activity in G-protein regulation.

Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 2. Recovery of peripheral peptide-containing nerves assessed by quantitative immunohistochemical study.

A marked depletion of neuropeptide-immunoreactive nerves, a consequence of the nerve damage which is commonly found in leprosy, has been reported in peripheral tissues of leprosy patients and of a leprosy animal model. The aim of this study was to investigate peripheral reinnervation following a denatured autologous muscle graft in an animal model of leprosy nerve damage. Possible reinnervation of the foot-pad skin was studied by immunohistochemistry using antisera to the neuronal marker protein gene product 9.5 (PGP), the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and the C-flanking peptide of neuropeptide Y (CPON). The extent of the reinnervation process was assessed by image analysis quantification at different time points. At 8 weeks after muscle grafting, there were small numbers of immunoreactive nerves (p < 0.05). At 12, 16, and 20 weeks postoperatively there was a gradual increase in all immunostaining. At 20 weeks, no significant difference was found for PGP-, CGRP-, and SP-immunoreactive nerves in the epidermal and subepidermal layers compared to control (contralateral) tissue. In experimental tissue the recovery of immunoreactive nerves around sweat glands took longer (up to 12 weeks) than in other skin compartments, but after that time the recovery was rapid and at 20 weeks no difference was measured for VIP-immunoreactive nerves in comparison with controls. Around blood vessels, the recovery of CGRP- and CPON-immunoreactive fibers was slow, and at 20 weeks a difference with control samples (p < 0.01) was noted. In the same area, there was no significant difference for PGP immunoreactivity between controls and tissues at 20 weeks. In contrast, the immunoreactive nerve bundles in the dermis showed a faster recovery than nerves in other skin areas, with amounts similar to controls at 20 weeks. The significant recovery of immunoreactive nerves, in particular of those containing sensory neuropeptide, is consistent with the described functional recovery.

Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 1. A functional and morphometric study.

The effectiveness of denatured autologous muscle grafts for nerve repair in an experimental model of leprosy was assessed. Nerve damage resembling that caused by Mycobacterium leprae in humans was induced by the injection of cobalt-irradiated M. leprae into the tibial nerve of guinea pigs. At the time of maximum functional loss, caused by the formation of a granuloma within the nerve, the area of damage was excised and a denatured autologous muscle graft was used to repair the nerve. Assessment of nerve regeneration through the graft was made using clinical, electrophysiological and microscopic morphometric analysis at intervals up to 20 weeks. The results were compared with regeneration after grafting of a normal nerve. Clinically, some motor and sensory recovery occurred in all of the graft recipients in the normal nerve by 8 weeks, and by 11 weeks in the recipients of grafts in the granulomatous nerve. Full sensory recovery occurred in all but one animal by 20 weeks. Motor function recovered to near normal levels at 14 weeks after repair of the normal nerve but, at 20 weeks, there was variation in motor recovery after repair of the granulomatous nerve. Electrophysiology showed increased conduction velocity of the nerve fibers at each time-point. The conduction velocity at 8 weeks after grafting of the normal nerve was similar to that at 12 weeks after grafting of the granulomatous nerve. Morphometry showed an increasing number of myelinated fibers repopulating the distal nerve up to 20 weeks. Myelin fiber numbers, at this time, were one third of normal after repair of the granulomatous nerve and two thirds after repair of the normal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Regeneration at the predilective damage sites of nerve trunks in treated leprosy.

Superficially located large and medium sized mixed peripheral limb nerves in active leprosy have previously been shown to have well-recognized fusiform swellings. It is generally agreed that these are the sites of predilective nerve involvement where the severest degeneration and fibrosis occur. A semiquantitative histopathological study on one of these sites, the flexor retinaculum region of the posterior tibial nerve, has been carried out on 14 treated leprosy patients who suffered from total sensory loss to the foot for between 2 and 40 years. The following observations were made: (1) large-scale nerve regeneration was present as characterized by numerous Schwann cells and unmyelinated axons which formed regeneration clusters; (2) thick myelinated axons were either absent or present only in very low numbers; (3) the intraneural fibrosis was usually not severe; (4) the presence of active inflammation probably interfered with nerve regeneration; (5) it appeared that this regeneration started shortly after the onset of therapy and persisted for decades; (6) lepromatous cases were characterized by evenly distributed pathology, whereas borderline tuberculoid cases had an unevenly distributed pathology; (7) the massive nerve regeneration observed was functionally ineffective--these findings indicate that the total nerve damage may affect the more peripheral nerve branches.

Comparison of results of repair of digital nerves by denatured muscle grafts and end-to-end sutures.

A further report is made on patients with primary and delayed repair of digital nerves with autogenous denatured muscle grafts. There was evidence of continued improvement in threshold response to tactile stimuli, and discriminative function. These results were superior to those in 24 patients with conventional end-to-end sutures on clinical testing.

Denatured autologous muscle graft in leprosy.

Autologous muscle grafts were used to repair 12 mixed peripheral nerves (9 posterior tibial, 3 median) in 10 patients with leprosy who had total anaesthesia and analgesia of the area supplied by the nerve. Postoperatively, 7 patients reported improved sensation in the foot or hand, with a return of vibration sense and joint position sense in 11 and of perception of a 10 g pin in 5; the ability to sweat in the affected area was also restored in 7.

Mycobacteria in nerve trunks of long-term treated leprosy patients.

Mycobacteria were present in 4 out of 8 mixed peripheral nerve trunks from patients (3 BT and 1 BL) treated with DDS and/or MDT for periods ranging from 21 months to 8 years. Most of the bacilli appeared to be 'whole'. Nerve destruction with areas of granulomatous infiltration appeared more active than expected. Possible reasons for a continued presence of bacilli in treated nerves and its implications in 'relapse' are discussed.

Ten cases of transitional cell carcinoma of bladder causing ureteric obstruction.

A review was carried out on 10 patients with superficial transitional cell carcinoma of the bladder (Ta lesions) that were causing ureteric obstruction. Evidence of upper tract obstruction did not necessarily indicate deep invasion.

Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy.

About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.