Engineering a multimodal nerve conduit for repair of injured peripheral nerve.

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Early diagnosis and treatment of laryngeal injuries from prolonged intubation in adults.

Prolonged endotracheal intubation can cause injuries to 1 or more regions of the larynx, making safe extubation impossible and leading to tracheostomy in many patients. Unfortunately, a considerable number of these patients do not benefit from early laryngeal evaluation, which may reveal potentially treatable soft, obstructive tissue before it undergoes irreversible fibrosis. Between July 1992 and December 1995, we performed immediate direct telelaryngoscopy on 142 adults who required tracheostomy because of failed extubation. When present, obstructive tissue was removed with microsurgical techniques. One hundred twenty-nine (90%) patients were decannulated within 3 weeks. The 2 main reasons for failure of early decannulation were intractable granulation (in patients with insulin-dependent diabetes) and coexisting tracheal stenosis. Immediate telelaryngoscopy is recommended in all patients who require tracheostomy because of failed extubation. Flexible laryngoscopy is not adequate for thorough assessment of laryngeal damage from prolonged intubation.

Perianal Paget's disease: distinguishing primary and secondary lesions using immunohistochemical studies including gross cystic disease fluid protein-15 and cytokeratin 20 expression.

BACKGROUND: Extramammary Paget's disease most commonly occurs on the female external genitalia and rarely occurs in the perianal region and male external genitalia. We present the clinical and pathologic features of 5 cases of perianal Paget's disease and review the literature. METHODS: Clinical and pathologic data were recorded for 5 cases of perianal Paget's disease. Cases were studied retrospectively with special stains, including periodic acid-Schiff, mucicarmine, Alcian blue, carcinoembryonic antigen, S100 protein, pan-keratin, gross cystic disease fluid protein-15 (GCDFP-15), lysozyme, CD15 (Leu-M1), cytokeratin 7 (CK7), and cytokeratin 20 (CK20). RESULTS: Three (60%) of 5 patients had concurrent rectal adenocarcinomas. All cases reacted positively for pankeratin, although the intensity and distribution of staining varied. Both cases not associated with an underlying carcinoma showed strong GCDFP-15 and CK7 expression and an absence of CK20 expression. The 3 cases associated with an underlying malignancy demonstrated CK7 and CK20 expression and an absence of GCDFP-15 expression. All cases were negative for lysozyme and CD15 (Leu-M1). CONCLUSIONS: The 5 cases reported herein demonstrate that perianal Paget's disease is a heterogeneous entity. The high frequency of associated underlying malignancies and resultant poor clinical outcomes highlight the importance of an aggressive search for a second malignancy. In some cases, perianal Paget's disease merely represents a cutaneous manifestation of an underlying rectal adenocarcinoma and demonstrates a CK7+/CK20+/GCDFP-15-/lysozyme-/Leu-M1- immunophenotype and signet ring Paget's cells. Other cases represent primary adenocarcinomas of the skin, which are associated with a CK7+/CK20-/GCDFP-15+/lysozyme /Leu-M1- immunophenotype and an excellent prognosis if adequately resected. Immunohistochemical studies, particularly CK20 and GCDFP-15, are useful adjuncts in distinguishing primary and secondary perianal Paget's disease.

Glycogen-rich malignant melanomas and glycogen-rich balloon cell malignant melanomas: frequency and pattern of PAS positivity in primary and metastatic melanomas.

OBJECTIVE: After identifying a metastatic glycogen-rich balloon cell malignant melanoma, originally thought to be a benign clear cell tumor of the lung, we investigated the extent of positive reactions, or "positivity," of malignant melanoma to periodic acid-Schiff (PAS) staining. METHODS: Frequency, intensity, and distribution of PAS positivity was studied in 61 excisional biopsy specimens from 58 patients with malignant melanoma. For comparison, 17 benign nevi from 10 patients were examined. RESULTS: Positivity for PAS was seen in all cases. All malignant melanomas and benign nevi were characterized by weak, diffuse, diastase-resistant PAS positivity. Additionally, focal or diffuse, strong diastase-sensitive PAS positivity was observed in 9 of 61 melanomas (15%); 7 were metastatic and 2 were primary invasive melanomas. Strong diastase-sensitive PAS positivity was seen in all lesions with 30% or more balloon cell features and only in advanced primary or metastatic lesions. The presence of glycogen was confirmed by transmission electron microscopy. CONCLUSIONS: Cutaneous malignant melanomas have weak, diastase-resistant PAS positivity. Strong diastase-sensitive PAS positivity, consistent with the presence of intracytoplasmic glycogen, is seen in many primary and metastatic melanomas with balloon cell features. Depending on the content of the balloon cells, these melanomas are best categorized as either glycogen-rich malignant melanomas or glycogen-rich balloon cell malignant melanomas. Because many tumors with clear cell features contain glycogen, such content often is an unreliable differential feature.

Membranous basal cell adenoma of parotid gland, dermal cylindromas, and trichoepitheliomas. Comparative histochemistry and ultrastructure.

A basal cell adenoma of parotid, eccrine dermal cylindromas and trichoepitheliomas occurring in the same patient were examined by light and electron microscopy and histochemistry. The eccrine and parotid adenomas were similar both structurally and histochemically except for the presence of Langerhans cells in the cutaneous adenoma and well differentiated mucinous cells in the parotid tumor. The three different hamartomas found in this individual may represent the effect of a single pleiotropic gene acting on ontogenetically related stem cells.