The therapeutic potential of human olfactory-derived stem cells.

Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.

Immunomagnetic separation of adult human olfactory neural progenitors.

Olfactory neuroepithelium (ONe) has lifelong regenerative capacity owing to the presence of mitotically active progenitors. The accessibility of ONe makes it a unique source of progenitors for cell replacement strategies in the CNS. We have established lines of neurosphere forming cells (NSFCs) from adult postmortem ONe and patients undergoing nasal sinus surgery by endoscopic biopsy. These heterogeneous lines are composed primarily of an immature neuronally restricted and a small glial restricted subpopulation. More homogeneous subpopulations of the NSFCs are essential for detailed study of factors influencing their lineage restriction. Immunomagnetic bead separation using an antibody against tyrosine kinase (Trk) receptors (Trk-pan, which recognizes Trk-A, B, C) resulted in viable, enriched positive and negative subpopulations that could be analyzed immunocytochemically. The positive cells remained positive for the first week after which the number of Trk-pan expressing cells decreased. The negative subpopulation began to express Trk-pan immunoreactivity after five days in vitro. Both subpopulations reverted to the heterogeneous composition after two weeks. Furthermore, most NSFCs were positive for Trk-B, a few for Trk-A, while no reactivity was observed for Trk-C. Because NSFCs produce brain derived neurotrophic factor (BDNF) and express Trk B, the specific receptor for BDNF, it is likely that population dynamics are under a paracrine and/or autocrine regulatory mechanism. Lineage restriction analysis demonstrated that the isolated subpopulation had a restriction potential equivalent to the original heterogeneous population. These studies characterize further the NSFCs and support the future potential therapeutic use of ONe-derived progenitors for CNS injury and neurodegenerative disorders.

Clonal analysis of adult human olfactory neurosphere forming cells.

Olfactory neuroepithelium (ONe) is unique because it contains progenitor cells capable of mitotic division that replace damaged or lost neurons throughout life. We isolated populations of ONe progenitors from adult cadavers and patients undergoing nasal sinus surgery that were heterogeneous and consisted of neuronal and glial progenitors. Progenitor lines have been obtained from these cultures that continue to divide and form nestin positive neurospheres. In the present study, we used clonal and population analyses to probe the self-renewal and multipotency of the neurosphere forming cells (NSFCs). NSFCs plated at the single cell level produced additional neurospheres; dissociation of these spheres resulted in mitotically active cells that continued to divide and produce spheres as long as they were subcultured. The mitotic activity of clonal NSFCs was assessed using bromodeoxyuridine (BrdU) incorporation. Lineage restriction of the clonal cultures was determined using a variety of antibodies that were characteristic of different levels of neuronal commitment: ss-tubulin isotype III, neural cell adhesion molecule (NCAM) and microtubule associated protein (MAP2), or glial restriction: astrocytes, glial fibrillary acidic protein (GFAP); and oligodendrocytes, galactocerebroside (GalC). Furthermore, nestin expression, a marker indicative of progenitor nature, decreased in defined medium compared to serum-containing medium. Therefore, adult human ONe-derived neural progenitors retain their capacity for self-renewal, can be clonally expanded, and offer multipotent lineage restriction. Therefore, they are a unique source of progenitors for future cell replacement strategies in the treatment of neurotrauma and neurodegenerative diseases.

Impact of endoscopic sinus surgery on global health perception: an outcomes study.

The Medical Outcome Study Short-Form 36-item Health Survey (SF-36) was used to prospectively assess outcomes after endoscopic sinus surgery. Our study found that chronic rhinosinusitis has a significant adverse impact on patient-perceived functional status and quality of life. Endoscopic sinus surgery resulted in statistically significant improvement in both disease-specific symptoms and patient-perceived global health status at 6 and 12 months of follow-up. The SF-36 is recommended for use as the global health monitor in outcomes evaluation for chronic rhinosinusitis.

Embolization as the definitive treatment of epistaxis in the pediatric patient.

Epistaxis occurs often in children, but these patients are seldom hospitalized. Two cases of intractable epistaxis, which were definitively treated with internal maxillary artery embolization, are presented with an algorithm for management of similar cases.

Computer-based clinical charting and patient case management.

During the past several years, computer systems have become an essential office tool in the day-to-day operation of many businesses, from large corporations to small companies. Like other businesses, home health care agencies are using computer systems to automate various aspects of their operation. Many companies soon discover that their computer system is second in importance only to their telephones in terms of accomplishing daily tasks.

An update on chronic sinusitis.

The management of chronic sinus disease has been revolutionized by the application of computed tomographic (CT) imaging and rigid endoscopes in diagnostic evaluation and surgical treatment. These diagnostic advances have led to a better understanding of sinus pathophysiology and the development of more rational surgical treatment. Obstruction of mucociliary drainage in the anterior ethmoid sinus-middle meatus region (ostiomeatal complex) is now understood to be the cause of chronic symptomatic sinus disease. Involvement of the maxillary or frontal sinus is usually secondary to disease in the ostiomeatal complex. Three cases are presented to illustrate the use of CT scanning and nasal endoscopy in the evaluation of chronic sinusitis. Precise identification and correction of ostiomeatal complex obstruction with endoscopic surgical techniques has proven efficacious and is associated with minimal patient morbidity. Endoscopic sinus surgery is emerging as the treatment of choice for medically unresponsive chronic sinus disease.