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.

Intrasellar neural-adenohypophyseal choristoma. A morphological and immunocytochemical study.

A patient with mild acromegaly had recurrence of symptoms and signs of a chiasmal-area lesion seventeen years after radiation therapy for a presumed pituitary adenoma. A mass was found anterior to the pituitary gland. Abnormal tissue removed from the sphenoid sinus and sella turcica consisted of a predominantly ganglion-cell lesion. A few ganglion cells were immunoreactive for somatostatin. There were some small cysts lined by cells with immunostaining for glial fibrillary acidic protein, growth hormone or prolactin. Some cells with vacuoles and eosinophilic granules showed immunostaining for growth hormone, prolactin, ACTH, and beta-endorphin and, thus, appeared to be of adenohypophyseal origin. Cases of intrasellar ganglion-cell lesions have been reported, most of them associated with pituitary adenomas and acromegaly. The findings in this case are discussed in relation to the hypothesis that displaced, hypothalamic-type ganglion cells may produce a growth hormone-releasing factor that stimulates the development of a growth hormone-secreting pituitary adenoma. An alternative hypothesis is suggested that includes this concept, but also allows for the influence of non-neuronal cells on neuronal differentiation and for the possible influence of adenohypophyseal hormones on the replication of hypothalamic-type neurons in the lesion.

An overview of the retinoids.

The retinoids, a group of compounds consisting of vitamin A and its derivatives, have been the subject of intense investigation over the past 30 years. These molecules have shown beneficial effects in the areas of acne, psoriasis, neoplastic processes and, most recently, reversal of extrinsically aged skin. Additional retinoids are currently under development. Adverse reactions to these drugs include mucocutaneous irritation, hyperlipidemia, and profound teratogenicity. Appropriate patient selection is imperative before beginning therapy with these medications. An overview of retinoid metabolism and the currently available compounds is presented. The newest class of retinoids, the arotinoids, is also discussed.

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.

Clinical efficacy of antimicrobial therapy in Haemophilus ducreyi infections.

Ulcerative genital disease in the United States is commonly due to herpes simplex or syphilis. Until recently, chancroid, an infection caused by the gram-negative streptobacillus Haemophilus ducreyi, was infrequently diagnosed. Continuing immigration, however, has reintroduced the disease into this country, and urban outbreaks have been associated with contact with infected prostitutes. Extensive resistance has made previous antimicrobial agents ineffective. Evaluations of multiple antibiotics and varied dosing schedules have been undertaken in an effort to circumvent this resistance. Clinicians treating patients with genital ulcerations must be aware of this disease and its geographically variable antibiotic sensitivities. Recent evidence demonstrating an association between seropositivity for the human immunodeficiency virus and ulcerative genital disease places additional importance on the timely diagnosis and appropriate treatment of chancroidal ulcers.

Multiple cutaneous granular cell tumors and neurofibromatosis in childhood. A case report and review of the literature.

Multiple cutaneous granular cell tumors have been previously reported in only 26 children or adolescents. An association of these tumors with neurofibromatosis has never been reported previously. We describe a 12-year-old black girl with multiple cutaneous granular cell tumors and neurofibromatosis. Although the histogenesis of these tumors is not completely clear, the findings of ultrastructural and immunohistochemical evaluation of our patient's tumors and the associated neurofibromatosis support a neural crest origin for granular cell tumors.

Laboratory testing in patients with morbilliform viral eruptions.

The explosion of immunologic testing capabilities over the past 20 years has enabled clinicians to accurately diagnose many conditions that previously were very difficult to identify solely on a clinical basis. Among these disorders are the viral exanthems. Infections with some of these viruses are of relatively little import (erythema infectiosum), whereas others have more significant consequences (HIV, cytomegalovirus). Clinical suspicions may be pursued more fully now, sometimes even in an office setting.

Rickettsialpox.

Rickettsialpox is a member of the spotted-fever group of the rickettsioses and results from an infection with Rickettsia akari. This microbe is transmitted by the bite of the house-mouse mite Liponyssoides sanguineus. Patents experience fevers, sweats, headaches, and a vesicular eruption over the trunk and extremities. The palms and soles are spared. An eschar results at the spot of the mite bite. Tetracycline is the treatment of choice.

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.

Pain suppression by peripheral nerve stimulation. Part I. Observations with transcutaneous stimuli.

A systematic, strict appraisal was made of 100 patients, after preliminary clinical trials suggested that some patients with pain could be helped by peripheral nerve stimulation. Transcutaneous stimulation of different nerve trunks was done with a special electrical stimulation device with various selected electrical parameters. More than half of the patients experienced some relief; in many, this effect was obtained by stimulating nerves distant from the area of referred pain. Pain relief lasted for varying periods after stimulation. The maximum benefit was noticed after certain specific parameters were reached for each patient. A few patients had response decay, gain or worsening. Results differ to some degree from previous reports. The results seem encouraging for the treatment of certain forms of intractable pain.

Pain suppression by peripheral nerve stimulation. Part II. Observations with implanted devices.

Twenty-three patients underwent implantation of a stimulator system and were followed for 6-20 months. Twenty patients estimated between 50% and 100% pain relief. The effect was largely consistent and reproducible. Reduced drug intake and improved social performance were associated with subjective improvement. The surgical technique is given, complications are analyzed and parameters are discussed.

A case of pyoderma vegetans and the follicular occlusion triad.

A case of pyoderma vegetans (PYV) and hidradenitis suppurativa (HS) is described. Our patient had a previous history of perifolliculitis capitis abscedens et suffodiens and acne conglobata. Direct immunofluorescence findings ruled out pemphigus vegetans and suggested a potential pathogenic mechanism.

Lichen spinulosus: case report and overview.

Lichen spinulosus is a benign follicular eruption seen primarily in younger persons and is frequently classified among the follicular keratoses. Grouped patches of spinous papules are seen involving the elbows, knees, and buttocks. An atopic background is frequently present in these patients. We describe here a patient treated with multiple modalities over eleven years without appreciable benefit and whose condition showed significant clearing after his first visit to a dermatologist. An overview of this unusual disease process is presented.

Recalcitrant acne vulgaris secondary to a dental abscess.

This case report describes a middle-aged man with acne that was recalcitrant to numerous medications, including three courses of isotretinoin. His condition cleared after an infected tooth was removed and recurred when another tooth became carious. Acne vulgaris is associated with several immunologic responses including the production of antibodies against Propionibacterium acnes, the gram-positive bacteria found in acne lesions. We believe that the presence of our patient's dental infections provoked a follicular inflammatory response resulting in his recalcitrant acne.

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.

Pityriasis rubra pilaris presenting as subacute cutaneous lupus erythematosus.

Diseases of a very different nature may occasionally present in a similar manner. Differentiating among several possible diagnoses may be complicated by confusing and conflicting laboratory data. Our recent evaluation and treatment of a patient confirmed the need for thorough testing, particularly in patients suspected of having a connective tissue disorder.

Perforating elastosis in necrobiosis lipoidica diabeticorum.

A 58-year-old diabetic woman with necrobiosis lipoidica diabeticorum demonstrated lesions with raised, prominent borders. These areas were found on biopsy to have transepidermal elimination of elastic fibers. We present this case as a unique finding and review the characteristics and possible mechanisms of transepidermal elimination.

Recurrent renal cell carcinoma presenting as skin nodules: two case reports and review of the literature.

The skin is a relatively rare site for metastatic carcinoma compared to other organs such as bone, lung, and liver. Once it is discovered, however, the underlying disease has usually become widespread. We describe two patients with recurrent renal cell carcinoma who presented with skin nodules six and ten years, respectively, after their initial cancers were diagnosed. Treatment options and prognostic factors are outlined and dermatologists are urged to consider neoplastic disease when confronted with patients presenting with acute, asymptomatic skin nodules.

Fixed drug eruption to Tylenol: report of two cases and review of the literature.

Fixed drug eruptions due to Tylenol (paracetamol, acetaminophen) are very rare. The authors report two additional cases and review the literature.