Publications

INTRODUCTION

Different technologies have been developed for radiofrequency ablation (RFA), which include increasing electrode (tip) size and cooling the tip through irrigation either internally (closed-loop) with D5W or externally (open-loop) with saline. Although these catheters are widely used clinically, the propensity for adverse events and the lesion profiles of each of these catheter technologies have not been directly compared under a wide range of controlled conditions.

METHODS AND RESULTS

Freshly excised canine thigh muscle was placed in a chamber filled with circulating, heparinized blood heated to 37 degrees C. Five different catheters were tested: 4 mm tip, 10 mm tip single thermistor, 10 mm tip multitemperature sensor, 4 mm closed-loop irrigated cooled-tip, and 4 mm open-loop irrigated cooled tip at several different contact and power settings. The catheter and tissue interface was continuously monitored with intracardiac echocardiography (echo) (Acuson). During the RFA, any bubbling generated from the tip and/or popping seen on echo was noted, and after each RFA, the catheter and lesion were examined for the presence of thrombus. For all of the catheters, complications correlated to the electrode tip temperature and power setting. All of the catheters experienced complications at any lesion size except for the open-irrigated catheter, which only had complications at the largest lesions. Overall, the cooled tip catheters experienced an at least sixfold greater odds of popping, bubbling, and impedance rises than the 4 mm, but the majority occurred at power levels greater than 20 W. The open-irrigated catheters created eccentric lesions that extended away from the tissue-catheter interface, in the direction of blood flow. In addition, it produced saline filled blisters at the lesion site in 16.7% of the burns. The 10 mm catheter had an at least twofold greater odds of thrombus, charring, and bubbling, but larger lesions than the 10 mm multitemperature sensor catheter.

CONCLUSIONS

Catheter type, contact conditions, and power settings all play a role in lesion size and in the frequency of complications that occur during an RFA. Cooling the electrode tip, either internally or externally, does not prevent complications from occurring, especially at the higher power control settings. Adding more temperature sensors to the 10 mm seems to reduce the amount of complications that can occur.

ATP-sensitive potassium (K(+)(ATP)) channels regulate cell excitability and are expressed in steroid-responsive brain regions involved in sexual behavior, such as the preoptic area (POA) and medial basal hypothalamus (MBH). We hypothesized that K(+)(ATP) channels serve as a mechanism by which testosterone can control the electrical activity of neurons and consequently elicit male sexual responsiveness. RT-PCR analysis indicated that castration induces, while testosterone inhibits, mRNA expression of the K(+)(ATP) channel subunit Kir6.2 in both the POA and MBH of adult male rats. Intracerebral infusion of the pharmacological K(+)(ATP) channel inhibitor tolbutamide increased the proportion of long-term castrates displaying sexual behavior and restored mount frequency, intromission frequency, and copulatory efficacy to values observed in testes-intact animals. Infusions of tolbutamide, but not vehicle, also decreased latencies to mount and intromit in castrated males. Unilateral tolbutamide infusion directly into the POA significantly reduced mount latency of castrates; however, it did not affect other copulatory measures, suggesting that blockade of K(+)(ATP) channels in additional brain regions may be necessary to recover the full range of sexual behavior. These data indicate that blockade of K(+)(ATP) channels is sufficient to elicit the male sexual response in the absence of testosterone. Our observations are consistent with the hypothesis that testosterone modulates male sexual behavior by regulating K(+)(ATP) channels in the brain. Decreased channel expression or channel blockade may increase the excitability of androgen-target neurons, rendering them more sensitive to the hormonal, chemical, and somatosensory inputs they receive, and potentially increase secretion of neurotransmitters that facilitate sexual behavior.

The oral mucosa is an attractive cell source for autologous transplantation in human patients who require regenerative therapies of various epithelia. However, the time-course of cellular changes in transplanted oral mucosal epithelia at ectopic sites remains poorly understood. By applying a rat model, we analyzed phenotypic changes in oral mucosal epithelial cell sheets after harvest from temperature-responsive culture dishes and subsequent autologous subcutaneous transplantation. We used monoclonal antibodies to identify epithelial-specific cytokeratins 4, 10, 13, and 14, the stem/progenitor cell marker p63, and proliferating cell nuclear antigen, within the regenerated tissues. Transplanted oral mucosal epithelial cell sheets proliferated during the first week after grafting in conjunction with host inflammation, but then began to degenerate afterward with complete disappearance after 3 weeks. Our findings suggest that host subcutaneous tissues support proliferation and differentiation of the oral mucosal epithelial cell sheets, but are unable to promote maintenance of stem and progenitor cells and therefore cannot produce long-term survivability.

Mutations in the Aire gene result in a clinical phenomenon known as Autoimmune Polyglandular Syndrome (APS) Type I, which classically manifests as a triad of adrenal insufficiency, hypoparathyroidism, and chronic mucocutaneous infections. In addition to this triad, a number of other autoimmune diseases have been observed in APS1 patients including Sjögren's syndrome, vitiligo, alopecia, uveitis, and others. Aire-deficient mice, the animal model for APS1, have highlighted the role of the thymus in the disease process and demonstrated a failure in central tolerance in aire-deficient mice. However, autoantibodies have been observed against multiple organs in both mice and humans, making it unclear what the specific role of B and T cells are in the pathogenesis of disease. Using the aire-deficient mouse as a preclinical model for APS1, we have investigated the relative contribution of specific lymphocyte populations, with the goal of identifying the cell populations which may be targeted for rational therapeutic design. In this study, we show that T cells are indispensable to the breakdown of self-tolerance, in contrast to B cells which play a more limited role in autoimmunity. Th1 polarized CD4(+) T cells, in particular, are major contributors to the autoimmune response. With this knowledge, we go on to use therapies targeted at T cells to investigate their ability to modulate disease in vivo. Depletion of CD4(+) T cells using a neutralizing Ab ameliorated the disease process. Thus, therapies targeted specifically at the CD4(+) T cell subset may help control autoimmune disease in patients with APS1.

OBJECTIVE

To evaluate changes over time in owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries and determine whether scores were associated with underlying etiology or with veterinarian-assigned scores for severity of neurologic dysfunction.

DESIGN

Cohort study.

ANIMALS

100 dogs with spinal cord injury.

PROCEDURES

Duration of dysfunction, modified Frankel neurologic injury score, and etiology were recorded. At initial and recheck (4- to 6-week) evaluations, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each area, and provide a weighting for the importance of each area; results were used to construct a weighted quality-of-life score. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS).

RESULTS

At initial and recheck evaluations, weighted quality-of-life scores were higher for ambulatory than for nonambulatory dogs. However, scores did not differ among groups when dogs were grouped on the basis of underlying etiology or duration of injury. Dogs with an increase in Frankel score between the initial and recheck evaluations had a significant increase in weighted quality-of-life score, whereas for dogs that did not have any change in Frankel score, initial and recheck weighted quality-of-life scores were not significantly different.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that owner-assigned, weighted quality-of-life scores for dogs with spinal cord injuries did not vary significantly on the basis of underlying etiology or duration of injury but were higher for ambulatory than for nonambulatory dogs.