Benign subcutaneous emphysema of the upper extremity.

Benign subcutaneous emphysema is a rare clinical entity, documented by only a small collection of case reports. The presence of crepitus on physical examination and subcutaneous gas on radiographs is concerning for necrotizing fasciitis. Necrotizing fasciitis is a dangerous and deadly infection accounting for 500 to 1000 cases annually in the United States, with mortality rates of up to 76%. Delay in surgical treatment is related to increased morbidity and mortality; therefore, a high clinical suspicion should be maintained in patients with subcutaneous emphysema and/or crepitus. It is critical to recognize that no laboratory result or radiologic finding should delay surgical intervention if a high clinical suspicion for necrotizing fasciitis exists. However, not all subcutaneous emphysema represents a life-threatening infection. This article presents a case of benign subcutaneous emphysema treated with close observation and prophylactic antibiotics. Patients with necrotizing fasciitis typically appear ill and have the triad of swelling, erythema, and disproportionate pain. Patients who are not systemically ill and have minimal pain, no significant inflammatory changes at the site of crepitus, and stable hemodynamic parameters can be treated conservatively, with the caveat that close clinical monitoring is essential to avoid the unnecessary morbidity and mortality that can result from delaying intervention in the case of necrotizing fasciitis.

Failure of cyclosporin a to rescue peripheral nerve allografts in acute rejection.

Prevention and control of graft rejection remain essential in the investigation of peripheral nerve allotransplantation. Although use of cyclosporin A (CsA) has been shown to suppress successfully the rejection of nerve allografts, limited information exists concerning use of this drug to arrest rejection in progress, and thereby effect salvage of these grafts. The aim of this study was to determine the efficacy of CsA in the treatment of ongoing acute rejection of peripheral nerve allografts. Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals and were divided into five groups: group 1 received isografts and no CsA treatment (n = 8), group 2 received allografts with continuous CsA therapy (n = 10), group 3 received allografts with no treatment (n = 7), group 4 received allografts with initiation of CsA therapy delayed until 3 weeks after the procedure (n = 11), and group 5 received allografts with an interrupted course of CsA (n = 15). All grafts were harvested at 10 weeks. Histomorphometric analysis demonstrated comparable nerve regeneration in groups 1 and 2 and good regeneration in group 3 animals, despite cellular infiltrate suggestive of rejection. At 3 weeks after surgery, group 4 animals showed early rejection and significantly less neuroregeneration than positive controls at 10 weeks after delayed initiation of CsA therapy. Finally, group 5 animals showed early regeneration at 3 weeks but significantly lesser regeneration by 10 weeks after interruption of therapy. In this experimental protocol, CsA was ineffective in rescuing histologically proven rejection in progress.

The effects of rapamycin in murine peripheral nerve isografts and allografts.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.

Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice.

OBJECT: The purpose of this study was to combine the immunosuppressive and neuroregenerative effects of tacrolimus (FK506) with cold preservation of peripheral nerve allografts to maximize axonal regeneration across short peripheral nerve gaps. METHODS: Ninety-six male C3H mice were randomized to six groups, which were composed of animals with isografts (Group 1, positive control), allografts (Group 2, negative control), allografts treated with subtherapeutic doses of FK506 without and with cold preservation (Groups 3 and 4), and allografts treated with therapeutic doses of FK506 without and with cold preservation (Groups 5 and 6). Results were determined using walking-track data and histomorphometric measurements. Three weeks postoperatively, animals treated with therapeutic doses of FK506 after receiving cold-preserved allografts demonstrated accelerated functional recovery relative to all other groups. In addition, histomorphometric parameters in these animals (1,257 +/- 847 total axons, 6.7 +/- 3.3% nerve tissue, 11.8 +/- 6.5% neural debris, 8,844 +/- 4,325 fibers/mm2 nerve density, and 2.53 +/- 0.25 microm fiber width) were the same as or better than in all other groups. The parameters of percent nerve tissue (p < 0.016), nerve density (p < 0.038), and percent neural debris (p < 0.01) were statistically significantly better than those in all other groups, including Group 1 (isograft, positive control). CONCLUSIONS: The combination of FK506 treatment with cold preservation of nerve allografts resulted in functional and histomorphometric recovery superior to that with either modality alone.