The reinnervation and revascularization of wounds is temporarily altered after treatment with interleukin 10

Denervated wounds fail to heal normally, and hypertrophic scars are abnormally innervated. Wounds can be manipulated with cytokines to reduce subsequent scarring. Wounds treated with the antiscarring cytokine interleukin 10 (IL10) were investigated to assess if the treatment alterered patterns of reinnervation and revascularization as the wounds matured into scars. Thirty CD1 mice underwent intradermal injection of 100 μL phosphate‐buffered saline (PBS) containing 125 ng IL10 or placebo at the margins of 1 cm² full thickness dorsal skin excisions at the time of wounding and at 24 hours after wounding. Wounds were not dressed. Six IL10‐treated and six control were harvested days 7, 14, 21, 42 and 84 postoperatively. Sections underwent histological scar assessment along with immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan‐neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co‐localization and quantification of blood vessels. Quantitative analysis was performed on the periphery and center of wounds. Wounds treated with IL10 healed with dermal collagen organized into a pattern more closely resembling normal skin than control wounds. IL10 changed the pattern of CGRP reinnervation during the healing process, but at 84 days, the density levels of all nerve fiber types were similar to controls. Wounds treated with IL10 were more vascular than untreated wounds during healing, but by 84 days, VWF density was that of unwounded skin.     

Clinical study on stab wounds of chest--factors that may influence their mortality

Stab wounds of the chest occupy an important position in penetrating thoracic injuries in Japan. A retrospective review of 117 patients with stab wounds of the chest admitted to our hospital over the past 12 years (from 1975 to 1987) revealed some factors that might influence their mortality. Seven patients died from trans-diaphragmatic injuries of intra-abdominal organs. The management of intra-abdominal injuries was very important in thoracic stab wounds. Many of the patients with stab wounds of the precordial chest (danger zone) had cardiac or major vascular injuries, and the mortality rate of them was high. The mortality rate of the patients with stab wounds of the right lateral thorax was high, because many of them had trans-diaphragmatic liver injuries. We thought that right lateral thorax as well as precordial chest is the danger zone in thoracic stab wounds. Survival rate in the patients whose circulatory condition had been unstable when they admitted was very low. Five DOA (dead on arrival) patients with stab wounds of the chest required emergency room thoracotomy (ERT). One of them survived. Survival rate in the DOA patients with stab wounds of the chest was higher than that in the DOA patients with blunt thoracic injuries. ERT for cardiac insufficiency following stab wounds of the chest was thought an effective procedure for surviving. Survival rate of the patients with cardiac stab wounds was 63.6 per cent.     

Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips

Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs.Patients and methods 40 patients with strictly unilateral OAH were cross-sectionally investigated with DXA at the hips and heels bilaterally as well as body composition of the legs. 3 regions of interest in the proximal femur were measured: femoral neck (FN), trochanter (TR), and total hip (TH). The design of the study allowed us to perform paired t-test between the OAH side and the healthy side.Results BMD was increased by 4.1% in FN, and reduced by 8.3% in TR and 4.1% in TH (p < 0.001 for all comparisons).Interpretation The differences in BMD, with decrease in the trochanter and increase in the femoral neck, may offer an explanation for the pattern of hip fractures seen in osteoarthritis. External rotation of the hip cannot explain the differences in BMD.     

The sensory reinnervation of muscles following immediate and delayed nerve repair in the cat

An experiment has been performed on adult cats to investigate the sensory reinnervation of muscle spindles and tendon organs in peroneus brevis following immediate and delayed repair of the divided muscle nerve. The results demonstrate that delaying nerve repair for up to 6 weeks does not give rise to any significant detrimental effect on such reinnervation.     

Experimental sensory reinnervation of the median nerve by nerve transfer in monkeys.

Anastomosis of the superficial radial nerve, the dorsal cutaneous branch of the ulnar nerve, or both to the distal cut end of a widely resected median nerve in monkeys was followed by successful sensory reinnervation of the thumb, index finger, and long finger within thiry-five to forty weeks. Success was ascertained by the presence of an intact anastomosis as observed grossly without any evidence of spontaneous regeneration of the median nerve. Reinnervation was confirmed by histological and histochemical reactions observed in the Meissner's corpuscles in the skin innervated by the median nerve. The demonstration of nerve fiber and the presence of normal specific and non-specific cholinesterase reactions exhibited by the Meissner's corpuscles in the cholinesterase preparations were considered the histological criteria for successful reinnervation. These histological and histochemical observations may explain the reported functional sensory recovery in clinical cases when similar nerve transfers were done.     

A new composite midface allotransplantation model with sensory and motor reinnervation

In this study, we extended application of face transplantation model in rat by incorporation of vascularized premaxilla, and nose with infraorbital and facial nerves for evaluation of allotransplanted sensory and motor nerve functional recovery. In group I (n = 3) the dissection technique is studied. In group II (n = 5) isotransplantations were performed. In group III (n = 5) allotransplantations were performed under Cyclosporin A monotherapy. Grafts; composed of nose, lower lip, and premaxilla; were dissected. Infraorbital nerve and facial nerve were included into the transplant. A heterotopic transplantation was performed to inguinal region of recipient. Nerve coaptations were performed between infraorbital‐sapheneous nerve and facial‐femoral nerve. CT scan, somatosensory‐evoked potential testing (SSEP), motor‐evoked potential testing (MEP), and microangiography were used for evaluation. All transplants survived indefinitely over 100 days. Microangiography showed preserved vascularization of the graft. Computed tomography revealed vital premaxillary bone segments. SSEP and MEP confirmed recovery of motor and sensory functions and latencies reached 67% of normal infraorbital nerve value and 70% of normal facial nerve value at 100 days post‐transplant. We have introduced new midface transplant model of composite midface allograft with sensory and motor units. In this model, motor and sensory functional recovery was confirmed at 100 days post‐transplant.     

Reliability and accuracy of techniques for surface area measurements of wounds and scars

The applicability of simple methods to measure the size of pathological skin lesions for management and research has been poorly studied to date. The interobserver reliability and accuracy (validity) was established for planimetry by photography and planimetry by tracing on a transparent sheet in this study. Drawings of 25, 50, and 75 cm(2) were created on 3 locations with increasing curvature (back, thigh, and forearm) in 20 healthy volunteers. Three investigators evaluated the drawings by both planimetry techniques. Both techniques showed a good reliability (r >or= 0.82, intraclass correlation) for 25 cm(2) areas. Planimetry by photography was more reliable than planimetry by tracings for the 50 -and 75-cm(2) areas and was more accurate than planimetry by tracing for all areas except for the area with the greatest curvature, the forearm. The study permits the conclusion that planimetry by photography is more suitable for surface area measurements than planimetry by tracing except for extremely curved body parts, where it is likely that effects of distortion supervene.     

Innervation of normal and hypertrophic human scars and experimental wounds in the rat

The present study was designed to investigate the role of nerve elements in normal and aberrant human wounds, and in experimental rat wound healing model. The innervation of normal and hypertrophic human scars was studied using indirect immunofluorescence labeling with antibodies specific for neurofilament protein. Furthermore, ingrowth of axons into experimental rat wounds was assayed. The results demonstrated that, in contrast to normal wounds, hypertrophic scars were traversed by a high number of bundles of axons. Our results also demonstrated that experimental rat granulation tissue which represented early phases of wound healing attracted axonal growth. To conclude, our findings indicate that normal wound healing is accompanied with innervation of the scars, and that hypertrophy of scars is accompanied with hypertrophy of nerves within the scars. Our results also suggest that aberrations in the innervation of scars may either cause aberrant wound healing, or neural hypertrophy may be a result of disturbed interplay in wound healing mechanisms.     

Complex wounds and their management

Complex wounds present a challenge to both the surgeon and patient in operative management, long-term care, cosmetic outcome, and effects on lifestyle, self-image, and general health. Each patient with complex wounds usually manifests multiple risk factors for their development. This article focuses on complex wounds involved with traumatic and orthopedic blunt or penetrating injuries, particularly in the extremities, as well as massive soft tissue infections including necrotizing fasciitis, gas gangrene, and Fournier gangrene. The principles of management of complex wounds involve assessing the patient's clinical status and the wound itself, appropriate timing of intervention, providing antibiotic therapy when necessary, and planning and executing surgical therapy, including the establishment of a clean wound bed and closure/reconstructive strategies.     

Renin and beta-blockade: prorenin and aldosterone may explain the controversy

The role of the renin-aldosterone system in predicting the hypotensive effect of beta-blockade is controversial. We have measured blood pressure, heart rate, plasma active renin, prorenin and aldosterone in 44 hypertensive patients before and after 18 weeks treatment with either nadolol or metoprolol in a double blind randomized study. Prorenin increased and active renin decreased with treatment, total renin and aldosterone remaining unchanged. After beta-blockade the correlation between active renin and prorenin improved from p less than 0.025 to p less than 0.001, and both variables attained a correlation with aldosterone. There was a weak correlation between the reduction in diastolic pressure and both pretreatment active renin and pretreatment prorenin (p less than 0.05). However, using a multiple regression analysis there was a highly significant correlation between the combination of the pretreatment values of active renin, prorenin and aldosterone and the reduction in diastolic pressure with both nadolol (p less than 0.001) and metoprolol (p less than 0.003). This indicates that the combination of active renin with prorenin and aldosterone is a reliable guide to the hypotensive effects of beta-blockade and that the failure to detect this in previous studies is most likely due to errors in the measurement of renin.     

Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection

Wound infection plays an important role in the development of chronicity, delaying wound healing. This study aimed to identify the bacterial pathogens present in infected wounds and characterise their resistance profile to the most common antibiotics used in therapy. Three hundred and twelve wound swab samples were collected from 213 patients and analysed for the identification of microorganisms and for the determination of their antibiotic susceptibility. Patients with diverse type of wounds were included in this retrospective study, carried out from March to September 2012. A total of 28 species were isolated from 217 infected wounds. The most common bacterial species detected was Staphylococcus aureus (37%), followed by Pseudomonas aeruginosa (17%), Proteus mirabilis (10%), Escherichia coli (6%) and Corynebacterium spp. (5%). Polymicrobial infection was found in 59 (27·1%) of the samples and was mainly constituted with two species. The most common association was S. aureus/P. aeruginosa. All Gram‐positives were susceptible to vancomycin and linezolid. Gram‐negatives showed quite high resistance to the majority of antibiotics, being amikacin the most active against these bacteria. This study is mostly oriented to health care practitioners who deal with wound management, making them aware about the importance of wound infection and helping them to choose the adequate treatment options to control microbial infection in wounds.     

The role of altered fatty acid in pathological scars and their dermal fibroblasts

PurposeThe proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation.MethodsHypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (1p < 0.05, 7p < 0.01, 71p < 0.001, 77p < 0.0001).ResultsCompared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (1p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all 1p < 0.05). However, the mRNA levels of SREBP1 (71p = 0.0002) and FASN (71p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both 1p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05).ConclusionFAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.