An experimental study was conducted to investigate the effect of time of adenovirus-mediated vascular endothelial growth factor (VEGF) gene therapy on the viability of epigastric skin flaps. Eighty-four male Sprague-Dawley rats were used. Skin flaps measuring 8 x 8 cm were marked on the ventral abdominal wall. The upper border of the flap was 1 cm above the costal margin, and the lower border was at the pubis and the inguinal fold. The lateral borders of the flap corresponded to the location of the distinct conversion of the thin ventral skin to the thick dorsal skin. Seven sites in the predicted area of necrosis on the outlined skin flaps were chosen for subdermal injections. All injections were administered by an individual who was blinded to the different treatment groups. The rats received either saline (control group I, N = 28) or adenovirus encoding green fluorescent protein (Ad-GFP; group II, N = 28) or Ad-VEGF (group III, N = 28). The epigastric island skin flaps based solely on the right inferior epigastric vessels were elevated either on the same day of injection (day 0 = 12 hours after transfection, N = 7) or on day 3 (N = 7), day 7 (N = 7), or day 14 (N = 7) after subdermal gene therapy. Flaps were sutured back to their native configuration. Flap viability was evaluated on day 7 after surgery. Sections of the flaps were examined histologically after undergoing hematoxylin-eosin staining. There was a significant reduction in mean percentage of necrotic flap area by 56%, 67%, 70%, and 54% in flaps transfected with Ad-VEGF, 12 hours, 3 days, 7 days, and 14 days before flap elevation, respectively ( < 0.05). There was no evidence that the mean percentage of skin necrosis in the Ad-GFP group was different than in the control group ( = 0.26). There was evidence of mild inflammation in flaps pretreated with Ad-GFP and Ad-VEGF compared with the control group. The authors demonstrated that adenovirus-mediated gene therapy of the abdominal skin after subdermal injections was technically feasible. This was demonstrated by the visualization of GFP expression in control experiments using a fluorescence microscope. In this study, adenovirus-mediated VEGF gene therapy promoted epigastric flap survival, which was not related to the time of transfection. These findings raise the possibility that pretreatment with VEGF gene therapy using an adenovirus vector may be applicable in patients at risk for plastic surgery.

An experimental study was conducted to investigate the effect of chronic cyclosporine A (CsA) administration with different doses on peripheral nerve regeneration. Forty adult male Lewis rats weighing 150 to 200 g were used. The right sciatic nerve was transected 1 cm distal to the sciatic notch, and a conventional end-to-end nerve coaptation was performed. According to the daily dose of subcutaneous CsA injections, animals were randomized into one control group and four experimental groups of 8 animals each (group I, control with no treatment; group II, 2 mg per kilogram CsA; group III, 4 mg per kilogram CsA; group IV, 8 mg per kilogram CsA; and group V, 16 mg per kilogram CsA). Daily injections of CsA were administered for 12 weeks by an investigator blinded to the different treatment groups. At 3, 6, and 12 weeks after nerve repair, motor recovery was evaluated by the toe spread test, and sensory recovery was measured using the pin-prick test and somatosensory evoked potentials (SEPs). Evaluations were performed by an investigator who was blinded to the treatment groups. At 12 weeks, sciatic nerve samples were harvested for histomorphometric analysis. Motor recovery was retarded regardless of CsA dose at each time point of evaluation. Sensory recovery was only delayed in the 16-mg-per-kilogram CsA treatment group at the 3 week follow-up. SEP results revealed significantly prolonged N2 and P1 latencies in all CsA treatments regardless of dose and time frame of evaluation compared with the control group (p < 0.05). Histomorphometric analysis demonstrated significantly reduced numbers of myelinated axons, reduced myelin sheath thickness, and reduced diameters in all CsA treatment groups compared with the control group (p < 0.05). Based on these findings in this experimental model of sciatic nerve, the authors conclude that CsA overall had direct deleterious effects on peripheral nerve regeneration as demonstrated by SEP, pin-prick test, toe spread test, and histomorphometric nerve analysis. These adverse effects seemed to be dose related for sensory recovery only at 3 and 6 weeks of CsA exposure after nerve repair. Motor recovery was affected negatively by short- and long-term CsA administration regardless of dose.

Background: The self-administered iPad-based Cleveland Clinic Cognitive Battery (C3B) was designed specifically for the efficient screening of cognitive functioning of older adults in a primary care setting. Objective: 1) Generate regression-based norms from healthy participants to enable demographic corrections to facilitate clinical interpretation; 2) estimate test-retest reliability and practice effects; 3) examine ability to discriminate mild cognitive impairment (MCI) from healthy aging; 4) d etermine validity of screening in a distracting clinical environment; and 5) determine completion rates and patient satisfaction in a primary care setting. Methods: Study 1 (S1) recruited a stratified sample of 428 healthy adults, ages 18–89, to generate regression-based equations. S2 assessed 2-week test-retest reliability and practice effects in 30 healthy elders. S3 recruited 30 MCI patients and 30 demographically-matched healthy controls. In S4, 30 healthy elders self-administered the C3B in a distracting environment and in a quiet private room in counterbalanced order. In a demonstration project, 470 consecutive primary care patients were administered the C3B as part of routine clinical care (S5). Results: C3B performance was primarily influenced by age, education, and race (S1), had acceptably high test-retest reliability and minimal practice effects (S2), discriminated MCI from healthy controls (S3), was not negatively impacted by a distracting clinical environment (S4), had high completion rates (>92%) and positive ratings from primary care patients (S5). Conclusion: The C3B is a computerized cognitive screening tool that is reliable, validated, self-administered, and is conducive to integration into a busy primary care clinical workflow for detecting MCI, early Alzheimer’s disease, and other related dementias.