Local delivery of tacrolimus using electrospun poly-ϵ-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts.

Objective.Repair of nerve gap injuries can be achieved through nerve autografting, but this approach is restricted by limited tissue supply and donor site morbidity. The use of living nerve allografts would provide an abundant tissue source, improving outcomes following peripheral nerve injury. Currently this approach is not used due to the requirement for systemic immunosuppression, to prevent donor-derived cells within the transplanted nerve causing an immune response, which is associated with severe adverse effects. The aim of this study was to develop a method for delivering immunosuppression locally, then to test its effectiveness in reducing the immune response to transplanted tissue in a rat model of nerve allograft repair.Approach.A coaxial electrospinning approach was used to produce poly-ϵ-caprolactone fibre sheets loaded with the immunosuppressant tacrolimus. The material was characterised in terms of structure and tacrolimus release, then testedin vivothrough implantation in a rat sciatic nerve allograft model with immunologically mismatched host and donor tissue.Main results.Following successful drug encapsulation, the fibre sheets showed nanofibrous structure and controlled release of tacrolimus over several weeks. Materials containing tacrolimus (and blank material controls) were implanted around the nerve graft at the time of allograft or autograft repair. The fibre sheets were well tolerated by the animals and tacrolimus release resulted in a significant reduction in lymphocyte infiltration at 3 weeks post-transplantation.Significance.These findings demonstrate proof of concept for a novel nanofibrous biomaterial-based targeted drug delivery strategy for immunosuppression in peripheral nerve allografting.

Localized chronic cutaneous lupus erythematosus masquerading as pigmented lesions: a new clinical subset?

Isolated, hyperpigmented lesions arising on the skin of the head and neck in the elderly rarely prompt consideration of connective tissue diseases. Histologic evaluation, however, may reveal changes compatible with chronic cutaneous lupus erythematosus (CCLE). A retrospective review of cutaneous biopsies compatible with CCLE evaluated by the Vanderbilt University Division of Dermatopathology over a five-year period (1998-2002) was undertaken. Cases with isolated lesions arising on the head and neck in patients 40 years or older were selected and the histopathology was confirmed. Patients were interviewed by phone and their charts were reviewed. A total of 11 cases were found, including nine women and two men. These patients averaged 68 years of age and presented with single, hyperpigmented macular lesions. Photosensitivity was rare and no associated stigmata of lupus erythematosus were noted. Response to topical application of corticosteroid preparations was excellent.

Traumatic osmium tetroxide inoculation.

Osmium tetroxide is a highly oxidizing, corrosive compound commonly found in electron microscopy laboratories. Although osmium tetroxide is known to cause rapid damage to organic tissue, its cutaneous effects have not been well studied. We report a case of traumatic inoculation from a broken vial of 4% osmium tetroxide. Electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of osmium in the tissue specimen. The lesion was treated by simple excision.

Histologic features of actinic keratoses in solid organ transplant recipients and healthy controls.

BACKGROUND: Squamoproliferative lesions are common in patients who are immunosuppressed, particularly in recipients of solid organ transplants. Histologic features in such biopsy specimens may differ from those of otherwise healthy patients. Actinic keratoses (AKs) in transplant recipients may possess pathologic characteristics that suggest that they arose in an immunosuppressed host. OBJECTIVE: We evaluated 30 randomly selected AKs from 25 recipients of solid organ transplants and compared their histologic features to those of 50 AKs from 45 patients who were not immunosuppressed. METHODS: Tissue samples were categorized by sex, patient age, and site of biopsy. Sixteen separate histologic criteria were evaluated in a blinded fashion in each specimen. Statistical analysis was performed between the two groups with and without controlling for the age of the patient. RESULTS: The transplant group was significantly younger (54.8 years) than the nontransplant group (70.0) and contained more men (88%) than women (51%). AKs from transplant recipients were statistically more likely to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis, increased mitotic activity, and verrucous changes. After controlling for age only, hyperkeratosis failed to be more prevalent in the transplant group. CONCLUSION: Certain histopathologic features are more common in AKs of immunosuppressed transplant recipients and may be used to distinguish between those removed from otherwise healthy persons.

Colletotrichum species as emerging opportunistic fungal pathogens: a report of 3 cases of phaeohyphomycosis and review.

BACKGROUND: Numerous etiologic agents of subcutaneous phaeohyphomycosis have been reported. Colletotrichum spp, common plant pathogens, have been reported as a cause of ocular keratomycosis, but only one previous case of cutaneous disease (hyalohyphomycosis) has been attributed to this genus. OBJECTIVE: Our purpose was to describe 3 cases of subcutaneous phaeohyphomycosis due to Colletotrichum spp occurring in patients undergoing chemotherapy for hematologic malignancies. METHODS: Three cases of Colletotrichum-induced phaeohyphomycosis are reviewed. The clinical and histologic features of this infection are presented, the antifungal susceptibilities are reported, and treatment options are discussed. RESULTS: We describe the first report in which C coccodes and C gloeosporioides are implicated as etiologic agents of subcutaneous phaeohyphomycosis. Despite treatment, one patient died after the onset of visceral fungal disease. CONCLUSION: Colletotrichum spp may cause life-threatening phaeohyphomycosis in immunosuppressed patients. Prompt recognition and intervention with surgical and antifungal treatment may result in decreased morbidity and mortality associated with these infections.

Noncovalent interactions between tetrazole and an N,N'-diethyl-substituted benzamidine.

Amidines have long been known to form strong noncovalent complexes with carboxylates and phosphates. However, their interaction with tetrazoles, which are acidic heterocycles and important bioisosteric replacements for carboxylic acids in medicinal chemistry, has remained unexplored so far. The binding of a tetrazole to an N,N'-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry. The amidinium group of model complex 3 was found to prefer an E,Z configuration in the crystal. Benzamidinium and tetrazolate groups alternate along an infinite chain of hydrogen bonds and salt bridges between the amidine-NH groups and the two tetrazole-N atoms next to the ring carbon. In solution, a 1:1 complex was evident from Job's method of continuous variation, and an association constant of 4.0 x 10(3) +/- 1.6 x 10(3) M(-)(1) (in CDCl(3)/CD(3)CN, 6:1) could be determined by (1)H NMR dilution experiments. Tetrazolate was not only found to be a weaker ligand than carboxylates but, surprisingly, the binding mode also changed with concentration in neat CDCl(3). At low concentrations, the amidine group in complex 3 adapted an E,E configuration as it does in a related carboxylic acid complex 4. With increasing concentration, the E,Z isomer starts to predominate. A free activation enthalpy DeltaG(298)() of 64 +/- 1 kJ mol(-)(1) for the E,E to E,Z isomerization was determined by line shape analysis at different magnetic fields. Binding strength was further probed in a competition experiment between a bisamidine, a carboxylate, and a tetrazolate by electrospray mass spectrometry.

Middermal elastolysis in two patients with lupus erythematosus.

Despite lupus erythematosus (LE) being considered a "connective tissue disease," little has been written about the elastic fiber changes in the skin of affected patients. We report our histologic findings in two patients with unusual cutaneous lesions. Elastic fiber loss was noted, and scattered giant cells with elastic fiber phagocytosis were prominent in one patient. The findings are similar to those described for middermal elastolysis. Other authors have reported patients with LE and elastic fiber loss resembling anetoderma. We believe that a spectrum of elastic fiber changes can occur in patients with LE and may be induced by infiltrating lymphocytes and/or circulating antibodies.

Metastatic paraganglionoma presenting as a scalp nodule.

Malignant neoplasms with neural differentiation uncommonly present as cutaneous masses. However, a rapidly growing skin lesion in patients with a past history of retroperitoneal soft tissue tumors suggests that dissemination of that lesion may be taking place.

Idiopathic leukonychia totalis and partialis in a 12-year-old patient.

Leukonychia totalis and partialis are uncommon nail findings characterized by the complete or partial whitening of the nail plate. Most cases of true leukonychia are inherited. We present a rare case of a young man with persistent, progressive, acquired leukonychia totalis and partialis.

Dissecting cellulitis in a white male: a case report and review of the literature.

Dissecting cellulitis is an uncommon, chronic, progressive suppurative disease of unknown etiology. It is characterized by painful papules and nodules, interconnecting sinus tracts, purulent drainage, and scarring alopecia. This disease predominately affects young black men, but is rarely reported in white males. The refractory nature of this process makes treatment difficult. We report a case of dissecting cellulitis in a white male, which responded to oral isotretinoin.

The first redox controlled hydrogen bonded three-pole switch.

The first example of a redox controlled hydrogen bonded three-pole switch is described, which exploits both electrochemical oxidation and reduction of the host-guest dyad to modulate the intermolecular recognition properties.

Hemangioblastoma arising in the skin.

Hemangioblastomas are intracranial and intraspinal tumors arising sporadically or in patients with von Hippel-Lindau disease. To date, hemangioblastomas have not been described in the skin. Proliferating clear cells with a variable vascular component are found histologically. These clear cells stain for neuron-specific enolase but not cytokeratin or epithelial membrane antigen, allowing them to be differentiated from metastatic renal cell carcinoma.

Mycosis fungoides d'embleé: CD30-negative cutaneous large T-cell lymphoma.

The d'embleé variant of mycosis fungoides initially described patients with a rapid onset of tumors without progression through patch- and plaque-stage disease. We report a case of a patient with the clinical presentation of mycosis fungoides d'embleé and correlate the histologic and immunophenotypic data with those of a more updated classification scheme.

Mercury exposure and cutaneous disease.

Human contact with mercury has been ongoing for centuries and was previously considered a legitimate means of treating different cutaneous and systemic conditions. Toxicity from this heavy metal may occur from exposure to elemental, inorganic, and organic forms of mercury. This article outlines the signs and symptoms of mercury poisoning and the different clinical conditions with assorted cutaneous findings.

New and emerging therapies for lichenoid dermatoses.

Lichenoid dermatoses comprise a significant proportion of dermatologic conditions. The pathophysiologic mechanisms are unclear for many such dermatoses making treatment difficult. Ongoing research into these mechanisms is allowing more directed intervention possible. This article describes some of the recent experiences in the therapy of lichen planus, lichen nitidus, toxic epidermal necrolysis, and graft versus host disease.