Rick M. Odland

Implanted upper airway stimulation device for obstructive sleep apnea

Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success.

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter

OBJECT A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused. METHODS Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle. RESULTS Hollow fiber catheter-mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that catheter-mediated infusion of adenovirus resulted in gene expression that was 10-times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere. CONCLUSIONS The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED.

Diagnosis and treatment of deep neck space abscesses

Objective: To review our experience with deep neck abscesses and identify unique trends in our patient population. Study Design: Case series with chart review. Subjects and Methods: Evaluation of patients with deep neck space abscesses between 2001 and 2006. Peritonsillar abscess, superficial craniocervical infection, and salivary gland infections were excluded from selection of study population. A total of 106 cases were reviewed. Results: Dental infections were the most common cause of deep neck abscesses (49.1%). Comorbidities included substance abuse (53.7%), psychiatric illness (10.4%), hypertension (9.4%), head and neck cancer (6.6%), and diabetes mellitus (5.7%). All patients received systemic antibiotics, eight patients required tracheotomy, 85 patients underwent surgical drainage in the operating room, and 11 had bedside drainage. Median and lower quartile of time in hospital was 2 and 3 days, respectively, whereas upper quartile was 4 days (range, 1 to 27 days). Patients with comorbidities or concurrent illness tended to stay longer (P < 0.05, Mann-Whitney test). There were six complications and no mortality. Conclusion: Substance abuse and poor orodental hygiene are important predisposing factors to deep neck abscesses. Appropriate management continues to favor a combination of early surgical drainage and systemic antibiotics.

Surgical debridement and adjunctive hyperbaric oxygen in cervical necrotizing fasciitis

Objective: To review our management of cervical necrotizing fasciitis (CNF) with the use of adjunctive hyperbaric oxygen therapy (HBO). Study Design: Case series with chart review. Subjects and Methods: Evaluation of ten patients with CNF between 2001 to 2006. Results: There were five male and six female patients. Mean age was 43 ± 11 years. Eight cases resulted from an odontogenic source. Comorbidities included diabetes mellitus, hypertension, and substance abuse. All patients had computed tomography scans performed, received intravenous antibiotics, and underwent surgical debridement. Eight patients underwent surgery within 24 hours. The average number of debridements was 2.2 ± 0.8. Hospitalization was twice as long for diabetic patients (15.5 ± 8.16 days) compared with nondiabetic patients (7.5 ± 1.6 days, P = 0.029). Nine patients had HBO therapy. Combined data revealed a possible decrease in length of hospitalization with HBO therapy (P < 0.001). No mortality was documented. Conclusion: In addition to early and aggressive medical management and surgical debridement, this study suggests that HBO therapy is a beneficial adjunct by potentially decreasing length of hospitalization. Randomized trials are still needed to demonstrate its efficacy.

Use of tissue ultrafiltration for treatment of compartment syndrome: a pilot study using porcine hindlimbs.

Objectives: To demonstrate the efficacy of compartment syndrome ultrafiltration for the treatment of acute compartment syndrome in an animal model. Our hypothesis is the removal of interstitial fluid will result in a reduction of intramuscular pressure compared with untreated controls in a model of bilateral induced compartment syndrome. Design: Controlled experimental model. Setting: Animal research facility. Patients/Participants: Three pairs of porcine hindlimbs. Intervention: Acute compartment syndrome was created in the pig hindlimb by infusion of saline to maintain the intramuscular pressure 30 mm Hg greater than the animals mean arterial pressure for 8 hours. After a 2-hour reperfusion interval, ultrafiltration (removal of fluid through 1 mm diameter porous catheters, connected to −500 mm Hg suction) was commenced in 1 limb only and continued for 9.5 hours. Main Outcome Measures: Intramuscular pressure, ultrafiltrate volume, ultrafiltrate and serum levels of creatine kinase and lactate dehydrogenase, histologic measurement of extracellular and intracellular edema, as well as the degree of cellular necrosis. Results: Intramuscular pressure tended to be lower on the treated side at the end of the treatment period [treated leg: 9.3 ± 4.0 mm Hg (± SE), control leg: 19.3 ± 1.4 mm Hg, P = 0.03]. Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared with serum levels. Creatine kinase levels in serum were measured at 4150 ± 780 U/L, whereas ultrafiltrate levels of creatine kinase were 28,700 ± 17,700 U/L (± SE) (P = 0.1). Lactate dehydrogenase was measured at 1950 ± 180 U/L in serum, but markedly elevated in ultrafiltrate [160,000 ± 88,900 U/L (± SE), P = 0.05]. Quantification of cellular and interstitial dimensions showed no difference in control and experimental limbs. Quantification of the degree of muscle necrosis revealed 6.1 ± 2.7% necrosis in the treated limb compared to 11.3 ± 1.6% necrosis in the control group (P = 0.02, df = 2, 1-tailed paired t test). Conclusion: This pilot study demonstrates the feasibility of tissue ultrafiltration for reduction of intramuscular pressure in this porcine model. Further studies are underway. Compartment syndrome ultrafiltration may be useful prophylactically in patients at risk for acute compartment syndrome. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis and treatment of acute compartment syndrome, whereas the reduction of tissue pressure by compartment syndrome ultrafiltration may prevent acute compartment syndrome from occurring. Additionally, compartment syndrome ultrafiltration will not hinder the ability of clinicians to use the clinical examination and pressure monitoring as the gold standard.

Hyperosmosis of cerebral injury.

Changes in tissue osmolarity or cerebrospinal fluid osmolarity after cerebral injury have received little attention in the literature, but osmosis may be an important cause of early cerebral edema. This paper reviews concepts and terms relating to osmosis, and reviews the few papers in the literature which have studied osmolarity after cerebral injury. In studies of both traumatic brain injury and ischemia, tissue osmolarity is elevated. Osmolarity of cerebrospinal fluid has also been shown to increase with injury. There have been no human studies examining osmolarity of tissue or cerebrospinal fluid after cerebral injury. Theoretical implications of the osmotic gradient are discussed.

Novel In Situ Collection of Tumor Interstitial Fluid from a Head and Neck Squamous Carcinoma Reveals a Unique Proteome with Diagnostic Potential

IntroductionTumors lack normal drainage of secreted fluids and consequently build up tumor interstitial fluid (TIF). Unlike other bodily fluids, TIF likely contains a high proportion of tumor-specific proteins with potential as biomarkers.MethodsHere, we evaluated a novel technique using a unique ultrafiltration catheter for in situ collection of TIF and used it to generate the first catalog of TIF proteins from a head and neck squamous cell carcinoma (HNSCC). To maximize proteomic coverage, TIF was immunodepleted for high abundance proteins and digested with trypsin, and peptides were fractionated in three dimensions prior to mass spectrometry.ResultsWe identified 525 proteins with high confidence. The HNSCC TIF proteome was distinct compared to proteomes of other bodily fluids. It contained a relatively high proportion of proteins annotated by Gene Ontology as “extracellular” compared to other secreted fluid and cellular proteomes, indicating minimal cell lysis from our in situ collection technique. Several proteins identified are putative biomarkers of HNSCC, supporting our catalog’s value as a source of potential biomarkers.ConclusionsIn all, we demonstrate a reliable new technique for in situ TIF collection and provide the first HNSCC TIF protein catalog with value as a guide for others seeking to develop tumor biomarkers.

The effect of capillary ultrafiltration probes on skin flap edema

OBJECTIVE: Edema clearly has deleterious effects on the microcirculation and, consequently, cell viability. Prior work from this laboratory demonstrated that hyperosmolar microdialysis can reduce tissue edema, but this method is technically challenging. A new, simpler technique of microdialysis using capillary ultrafiltration probes (CUPs) has been studied to determine if CUP microdialysis is as effective in reducing tissue edema in the same animal model. METHODS: Twenty-four Sprague-Dawley rats were studied using a modified McFarlane skin flap. Microdialysis was accomplished using a catheter constructed of four 4-cm hollow fibers that were connected to polyethylene tubing. Catheters on the experimental side of the flap were attached to a vacuum manifold for 8 hours. The control side was treated in 2 ways. In group 1, catheters were placed but not applied to suction. In group 2, no catheters are placed on the control side. Tissue water content was determined by a biopsy-drying technique. RESULTS: Tissue water content was significantly reduced (by paired t test) in both groups by a mean of 3.2 mL/100 g of wet tissue. CONCLUSION: CUP microdialysis reduced tissue water content as effectively as did hyperosmolar microdialysis, but in a simpler and therefore more cost-effective method. The technique could be easily adapted for clinical application.

Threshold Model for Extremity Compartment Syndrome in Swine

BACKGROUND Extremity compartment syndrome occurs when swelling develops within a muscle compartment to such an extent that the microvasculature is compressed and tissue perfusion is compromised. Untreated, this condition can result in widespread tissue destruction and loss of the affected limb. METHODS Swine were subjected to diffuse muscle compression injury using a balloon catheter inserted between the anterior muscle compartment of the hind limb and the anterior face of the tibia. Balloons were inflated with saline to produce a sustained intramuscular pressure (IMP) of approximately 30 mmHg greater than mean arterial pressure. Following injury the IMP was monitored for up to 8 h. At the end of the monitoring period, the tibialis anterior muscle was collected and examined for injury. RESULTS One animal receiving 6 h injury dislodged the implanted pressure transducers and was dropped from the data analysis. In all other limbs (n = 8) receiving 6 h injury, significant spontaneous increases in IMP were observed following injury. The tibialis anterior in all of the 6 h injury limbs also showed extensive tissue damage. In the limbs injured for 5 h (n = 10), only three showed a significant increase in IMP. The magnitude and duration of this increase closely resembled that seen following 6 h injury. Tissue damage was reduced in comparison with 6 h injury. CONCLUSIONS The injury technique described here provides a potential useful threshold model for studying extremity compartment syndrome and the influence of related factors on the progression of this condition.

Morbidity and Cost of Odontogenic Infections

Objective Cost analysis of deep neck space infections from odontogenic origin and review of the morbidity of potentially preventable complications. Study Design Case series with chart review. Setting Level 1 trauma center and academic safety net hospital. Subjects and Methods Patients treated for deep neck space infections due to an odontogenic source between 2001 and 2010 were reviewed. Two hundred patients were included in the study. Ninety-eight patients required inpatient admission. Twelve percent of these patients had difficult airways, and 16% had at least 1 day in the intensive care unit. Cost data were available only for the later 3.5 years of the study period. Results The overall cost of treatment for these 71 individuals exceeded