Murine skin flap survival may not be affected by underlying fat viability.

One problem in the treatment of degloving injuries is the accurate prediction of the survivability of the avulsed tissue. Initial evaluation frequently underestimates the degree of eventual flap loss, and in many cases, there is a progressive necrosis that continues over the ensuing days. The pathophysiology of this phenomenon is unclear. We undertook this study to test the theory that underlying devascularised fat contributes to overlying skin necrosis. A dorsal random skin flap model was used in the rat. Sixty-six rats were divided into three groups: flaps with viable fat and silicone sheeting underneath, flaps with devascularised fat and silicone sheeting underneath and control flaps with only silicone sheeting underneath. Flap necrosis (% area+/-SEM) was evaluated at one week, and found to be 27.1+/-4% in the live fat group, 33.2+/-4% in the dead fat group and 33.6+/-5% in the control group. One-way analysis of variance showed no statistically significant difference between the three groups at a power of 80%. In this study, we have shown that neither live nor dead fat has a significant influence on the survival of an overlying random skin flap in the rat.     

Inhaled nitric oxide (iNO) delivery with high-frequency jet ventilation (HFJV).

OBJECTIVE: To determine if nitric oxide (NO) therapy can be reliably administered during high-frequency jet ventilation (HFJV) using the INOvent delivery system. STUDY DESIGN: NO concentrations were measured just proximal to the endotracheal (ET) tube and at the distal tip of the ET tube during a bench evaluation. Measurements were taken over a wide range of airway pressure settings and NO concentrations with both high- and low- resistance lung models. Percent changes in set versus proximal and proximal versus distal iNO concentrations were tabulated. RESULTS: Differences between proximal and distal NO concentrations were 10% or less. In the therapeutic range of up to 20 p.p.m., differences in concentration were 1 p.p.m. or less. There was no consistent effect on NO concentration when airway resistance was increased by 500%. CONCLUSION: Nitric oxide therapy can be reliably administered during HFJV with the INOvent delivery system when NO is injected exclusively via the HFJV circuit.     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Three-Dimensional Reconstruction of Basal Cell Carcinomas

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer. One of the main problems with BCC is the risk of local recurrence of the tumor after treatment. This is mainly due to its irregular outgrowths, which cannot be detected clinically. OBJECTIVE: To better understand the tumor morphology and growth pattern of BCC, we tried to develop a method that provides a precise three-dimensional model of the tumor. METHODS: Because Mohs surgery provides the best overview of the tumor and the tumor margins (both lateral and in depth), the reconstruction was based on slides from Mohs surgery. After digitization and processing of the slides, the tumor was then surrounded by a Mohs surgeon on a computer screen. These selections (lines) were used for a three-dimensional reconstruction of the tumor using MedSurf3D software. RESULTS: This method allows three-dimensional reconstruction of any given BCC. The MedSurf3D software enables visualization of a three-dimensional model of the tissue, which is removed during the surgical procedure. CONCLUSIONS: Three-dimensional reconstruction is a fascinating tool that might improve our understanding of the behavior, growth pattern, and tumor morphology of BCCs. This technique might also be useful in other fields of cutaneous oncology, such as the calculation of the tumor volume of melanomas.     

Tritium labelling of several potent fluorinated antipsychotic drugs at high specific activity.

Methods are presented to synthesize and characterize [methylene-3H] haloperidol 2 and [N-methyl-3H]trifluoperazine 6.     

Evaluation of BioCorkscrew and Bioknotless RC suture anchor rotator cuff repair fixation: an in vitro biomechanical study

This in vitro biomechanical study used cadaveric specimens to compare the rotator cuff repair fixation provided by BioCorkscrew and Bioknotless RC suture anchors. Three cm wide by 1-cm long full-thickness supraspinatus defects were repaired using either two BioCorkscrew suture anchors with combined vertical and horizontal mattress sutures (n = 7) or three Bioknotless RC suture anchors with simple sutures (n = 7). Therefore, the BioCorkscrew suture anchor group had two sutures per anchor (four total sutures), while the Bioknotless RC suture anchor group had one suture per anchor (three total sutures). Two-phase cyclic (5–100 N, 1,000 cycles and 5–180 N, 2,000 cycles) and load to failure tests (31 mm/s) were performed. Non-parametric statistics were used to compare group differences (P < 0.05). All of the BioCorkscrew group specimens (seven of seven) completed the two phase cyclic test regimen without failure or gapping ≥ 5 mm, compared to only three of seven of the Bioknotless RC group (Fisher’s Exact test = 0.03). Groups did not differ for repair site gapping during the 5–100 N cyclic test phase (Fisher’s Exact test = 0.77), however more of the Bioknotless RC group displayed gapping ≥ 5 mm during the 5–180 N cyclic test phase than the BioCorkscrew group (P = 0.02). The BioCorkscrew group also displayed greater yield load during load to failure testing (492.2 ± 204 N vs. 296.4 ± 155 N, P = 0.03). In this in vitro biomechanical study, the BioCorkscrew group with combined vertical and horizontal mattress sutures displayed greater cyclic test survival, less repair site gapping, and superior yield load compared to the Bioknotless RC group with simple sutures. These results in human cadaveric rotator cuff-humerus specimens suggest better immediate post-operative repair site strength and a reduced need for post-operative restrictions. Clinical studies are needed to determine how these rotator cuff repair modes withstand the forces of early rehabilitation and activities of daily living that potentially influence patient outcomes.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.

Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment.