Stromal progenitor cell therapy corrects the wound-healing defect in the ischemic rabbit ear model of chronic wound repair

Chronic wounds create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The etiology for wound healing impairment appears to be multifactorial; however, ischemia is a common factor in most types of chronic wounds. Ideal therapy for such wounds would be to correct deficiencies in growth factors and matrix components and provide cellular precursors required for timely wound closure. We hypothesized that stromal progenitor cell (SPC) therapy could correct the ischemic wound-healing defect through both direct and indirect mechanisms. To test this hypothesis, we used the ischemic rabbit ear model of chronic wound healing. We found that treatment of the wounds with SPCs was able to reverse the ischemic wound-healing impairment, with improved granulation tissue formation and reepithelialization compared with vehicle or bone marrow mononuclear cell controls. In vitro, SPCs were found to produce factors involved in angiogenesis and reepithelialization, and extracellular matrix components, providing evidence for both direct and indirect mechanisms for the observed correction of the healing impairment in these wounds. Treatment of ischemic wounds with SPCs can dramatically improve wound healing and provides a rationale for further studies focused on SPCs as a potential cellular therapy in impaired wound healing.     

db/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.     

Cancer Incidence in Kentucky, Pennsylvania, and West Virginia: Disparities in Appalachia

CONTEXT: Composed of all or a portion of 13 states, Appalachia is a heterogeneous, economically disadvantaged region of the eastern United States. While mortality from cancer in Appalachia has previously been reported to be elevated, rates of cancer incidence in Appalachia remain unreported. PURPOSE: To estimate Appalachian cancer incidence by stage and site and to determine if incidence was greater than that in the United States. METHODS: Using 1994--1998 data from the central registries of Kentucky, Pennsylvania, and West Virginia, age-adjusted incidence rates were calculated for the rural and nonrural regions of Appalachia. These state rates were compared to rates from the Surveillance, Epidemiology, and End Results (SEER) program for the same years by calculating the adjusted rate ratio (RR) and a 95% confidence interval (CI). FINDINGS: Both the entire and rural Appalachian regions had an adjusted incidence rate for all cancer sites similar to the SEER rate (RR = 1.00 [95% CI, 1.00-1.01] and RR = 0.99 [95% CI, 0.99-1.00], respectively). However, incidence of cancer of the lung/ bronchus, colon, rectum, and cervix in Appalachia was significantly elevated (RR = 1.22 [95% CI, 1.20-1.23], 1.13 [95% CI, 1.11-1.14], 1.19 [95% CI, 1.16-1.22], and 1.12 [95% CI, 1.07-1.17], respectively). Incidence of cancer of the lung/bronchus and cervix in rural Appalachia was even more elevated (RR = 1.34 [95% CI, 1.31-1.36] and 1.29 [95% CI, 1.21-1.38], respectively). Incidence of unstaged disease for all cancer sites in Appalachia (RR = 1.06 [95% CI, 1.05-1.08]), particularly rural Appalachia (RR = 1.28 [95%CI, 1.25-1.301), was elevated. CONCLUSIONS: Cancer incidence in Appalachia was not found to be elevated. However, incidence of cancer of the lung/bronchus, colon, rectum, and cervix was elevated in Appalachia. The rates of unstaged cancer of every examined site were elevated in rural Appalachia, suggesting a lack of access to cancer health care.     

Comparative wound healing—Are the small animal veterinarian's clinical patients an improved translational model for human wound healing research?

Despite intensive research efforts into understanding the pathophysiology of both chronic wounds and scar formation, and the development of wound care strategies to target both healing extremes, problematic wounds in human health care remain a formidable challenge. Although valuable fundamental information regarding the pathophysiology of problematic wounds can be gained from in vitro investigations and in vivo studies performed in laboratory animal models, the lack of concordance with human pathophysiology has been cited as a major impediment to translational research in human wound care. Therefore, the identification of superior clinical models for both chronic wounds and scarring disorders should be a high priority for scientists who work in the field of human wound healing research. To be successful, translational wound healing research should function as an intellectual ecosystem in which information flows from basic science researchers using in vitro and in vivo models to clinicians and back again from the clinical investigators to the basic scientists. Integral to the efficiency of this process is the incorporation of models which can accurately predict clinical success. The aim of this review is to describe the potential advantages and limitations of using clinical companion animals (primarily dogs and cats) as translational models for cutaneous wound healing research by describing comparative aspects of wound healing in these species, common acute and chronic cutaneous wounds in clinical canine and feline patients, and the infrastructure that currently exists in veterinary medicine which may facilitate translational studies and simultaneously benefit both veterinary and human wound care patients.     

Bedside Ultrasound Is a Practical and Reliable Measurement Tool for Assessing Quadriceps Muscle Layer Thickness

Background: Critically ill patients commonly experience skeletal muscle wasting that may predict clinical outcome. Ultrasound is a noninvasive method that can measure muscle quadriceps muscle layer thickness (QMLT) and subsequently lean body mass (LBM) at the bedside. However, currently the reliability of these measurements are unknown. The objectives of this study were to evaluate the intra‐ and interreliability of measuring QMLT using bedside ultrasound. Methods: Ultrasound measurements of QMLT were conducted at 7 centers on healthy volunteers. Trainers were instructed to perform measurements twice on each patient, and then a second trainee repeated the measurement. Intrarater reliability measured how consistently the same person measured the subject according to intraclass correlation (ICC). Interrater reliability measured how consistently trainer and trainee agreed when measuring the same subject according to the ICC. Results: We collected 42 pairs of within operator measurements with an ICC of .98 and 78 pairs of trainer‐to‐trainee measurements with an ICC of .95. There were no statistically significant differences between the trainer and trainee results (trainer and trainee mean = ?0.028 cm, 95% CI = ?0.067 to ?0.011, P = .1607). Conclusions: Excellent intra‐ and interrater reliability for ultrasound measurements of QMLT in healthy volunteers was observed when performed by a range of providers with no prior ultrasound experience, including dietitians, nurses, physicians, and research assistants. This technique shows promise as a method to evaluate LBM status in ICU or hospital settings and as a method to assess the effects of nutrition and exercise‐based interventions on muscle wasting.     

Diseases of the foot and nails: Humans, cats, and dogs

The human foot, as differentiated from that of arboreal ancestors, has evolved to function in locomotion; however, in dogs and cats, the paws not only function in locomotion, but also aid in defense and food gathering. The plantar foot of dogs and cats, in contrast to that of humans, has a medial longitudinal arch culminating in weight bearing on the metatarsophalangeal joints, as well as a digital arch. Both animal arches have plantar pads. These pads are thickly keratinized. The epidermis of the foot pad of the adult dog is about 1800 μm thick.¹ The foot pads of most dogs are thick and rubbery to the touch, whereas cats have softer, more pliable pads.     

Trophic effects of neurotensin in massive bowel resection in the rat

The trophic effect of the administration of exogenous neurotensin on the intestinal mucosa was studied in rats following an 80% bowel resection. Villus length and mucosal DNA content were assessed in the jejunal and ileal mucosa of the remnant intestine 14 days after resection. The data obtained in an 80% resected control group (80% group) and an experimental group receiving an infusion of neurotensin (300 µg/kg/day) for 14 days subcutaneously (80%+NT group) were compared. The results indicate that the administration of exogenous neurotensin (80%+NT) increases villus length (jejunum: 920±77 vs 861±25 µm and ileum length: 975±23 vs 875±99 µm) to an extent greater than that observed in the 80% resected group not receiving exogenous neurotensin. The levels of mucosal DNA per milligram of protein increased significantly in both groups but was paradoxically less in the 80%+NT group than in the 80% resection group (jejunum: 8±0.56 vs 10.18±0.80; ileum; 8.63±0.43 vs 10.05±0.46). These data suggest that the administration of exogenous neurotensin to the rat potentiates the growth of intestinal villi and accelerates the intestinal trophic response seen following massive bowel resection. The increase in circulating enteroglucagon levels noted after neurotensin administration (80%+NT: 547±48 pg/ml vs 80%: 341±41 pg/ml) suggests that some of the trophic effects of neurotensin may be mediated, at least in part, by enteroglucagon. These data also suggest a potential role for the use of neurotensin in the initial treatment of individuals with short bowel syndrome.