Brief communication: neurotraumatological aspects of head injuries resulting from sharp and blunt force in the early medieval period of southwestern Germany

Approximately 10% (33 of 304) of the predominantly male skulls from the 6th through 8th centuries in southwestern Germany exhibit cranial fractures derived from blunt or sharp force trauma. No evidence of fracture healing characterizes 24% (n = 8) of these individuals. All nonhealed fractures were caused by sharp force, and four of these wounds cross the sagittal sinus. The lengths of these straight-edged wounds, produced exclusively by sword blows, measure around 8.0 cm for fatal, and about 5.0 cm for nonfatal wounds. Seventy-six percent (n = 25) of these skulls exhibit some healing, which indicates that these injuries did not lead to immediate death. In this group are all depressed fractures resulting from blunt force blows. Two thirds of the 45 cranial injuries noted on these 33 skulls are located on the left side of these individuals, with a concentration in the frontoparietal region. Bony indications of wound infection occur in four cases (12%). Three crania exhibit circular trepanations in association with fractures. These phenomena are discussed in the context of modern neurotraumatological knowledge.     

Paleoepidemiolgical patterns of trauma in a prehistoric population from central California

Skeletal trauma was investigated in a large collection of human remains from central California (N = 162 aged and sexed adults). Lesions investigated included cranial and long bone fractures, projectile wounds, and dislocation. Long bone fractures were found in 10.5% of individuals; overall, incidence by element was 2.3%. In addition, cranial injuries were found in 4.4% of complete adult crania. Projectile wounds were seen unambiguously in four individuals (with embedded obsidian fragments) and strongly suggested in two other individuals with partially healed lesions. Finally, one case of traumatic hip dislocation was also observed. In both incidence and patterning of injuries, this population is similar to other archeological groups from California. This evidence further supports earlier reports indicating that interpersonal aggression was quite common in prehistoric California.     

Connexins in wound healing; perspectives in diabetic patients

Skin lesions are common events and we have evolved to rapidly heal them in order to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal without issue, but as we get older our bodies become compromised by poor blood circulation and conditions such as diabetes, leading to slower healing. This can result in stalled or hard-to-heal chronic wounds. Currently about 2% of the Western population develop a chronic wound and this figure will rise as the population ages and diabetes becomes more prevalent [1]. Patient morbidity and quality of life are profoundly altered by chronic wounds [2]. Unfortunately a significant proportion of these chronic wounds fail to respond to conventional treatment and can result in amputation of the lower limb. Life quality and expectancy following amputation is severely reduced. These hard to heal wounds also represent a growing economic burden on Western society with published estimates of costs to healthcare services in the region of $25B annually [3]. There exists a growing need for specific and effective therapeutic agents to improve healing in these wounds. In recent years the gap junction protein Cx43 has been shown to play a pivotal role early on in the acute wound healing process at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in wound edge keratinocytes was shown to underlie the poor rate of healing in diabetic rats, and targeting its expression with an antisense gel restored normal healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the poor healing of human chronic wounds and be amenable therapeutic intervention [7]. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.     

Generation of a Three-dimensional Full Thickness Skin Equivalent and Automated Wounding

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models reflect the human wound situation better than animal models. Although two-dimensional models are widely used to investigate processes such as cellular migration and proliferation, models that are more complex are required to gain a deeper knowledge about wound healing. Besides a suitable model system, the generation of precise and reproducible wounds is crucial to ensure comparable results between different test runs. In this study, the generation of a three-dimensional full thickness skin equivalent to study wound healing is shown. The dermal part of the models is comprised of human dermal fibroblast embedded in a rat-tail collagen type I hydrogel. Following the inoculation with human epidermal keratinocytes and consequent culture at the air-liquid interface, a multilayered epidermis is formed on top of the models. To study the wound healing process, we additionally developed an automated wounding device, which generates standardized wounds in a sterile atmosphere.     

Mast cells and wound healing of the skin in the rat

Summary In healing skin wounds of rat skin an initial disappearance of mast cells occurs. This is followed by a reappearance and degranulation of mast cells at the wound margins between the third and seventh post operative day. By fourteen days the mast cell distribution around the scar tissue resembles that of normal skin, and a few mast cells are present in the fibrous tissue.The presence of mast cells exhibiting a pale metachromasia and fewer granules is noted. These cells lay under the stratum germinativum of the epidermis in normal skin, and similar cells are present below areas of epithelial regeneration in the healing wounds.It is suggested that the mast cell is playing an essential part in wound healing, and that the subepithelial forms may be involved in providing a stimulus for cell division.Supported by American Cancer Society Grant No IN-60.     

Effect of sodium diphenylhydantoin on skin wound healing in rats

This study evaluated the effect of phenytoin (sodium diphenylhydantoin) on skin wound healing in a rat model. The study was divided into two parts. In part I, 20 mul of phenytoin (10 mg/ml) was subcutaneously injected into the 3-cm dorsal full-thickness incisional wounds of 14 rats on postoperative days 0, 3, and 6. Twelve rats that received saline injections were used as the controls. The skin samples were harvested and tested for tensile strength and histology. An additional 12 rats with the same incisional wounds were tested for chemokine gene expressions. In part II, 20 mul of phenytoin (10 mg/ml) was applied topically once a day on a 4 x 4 cm area of the open dorsal wounds of 10 rats. Saline was applied to the wounds of the 10 control group rats. The wounds were measured weekly. The results showed that the average tensile strength of the phenytoin-treated wound was 0.49 +/- 0.08 MPa compared with the control group at 0.02 +/- 0.01 MPa (p < 0.05). The density ratio of chemokine monocyte chemotactic protein (MCP-1) to beta-actin in the phenytoin-treated group was also significantly higher than in the control group (p < 0.05). Histologic analysis of the phenytoin group showed a large amount of fibroblast proliferation, collagen synthesis, and neovascularization. Phenytoin-treated wounds were also smaller at 1 to 6 weeks postoperatively than the control group wounds. The authors conclude that the administration of phenytoin can promote wound healing and significantly increase MCP-1 expression. Phenytoin-treated wounds showed significant increase in collagen deposition and neovascularization, which resulted in an increased wound tensile strength and accelerated healing of both open and closed wounds.     

Accelerated healing of full-thickness skin wounds in a wet environment

Full-thickness skin wounds are preferably allowed to heal under controlled hydration dressings such as hydrocolloids. It was hypothesized that a wet (liquid) environment rather than a dry or moist one would accelerate the wound healing process. We compared skin repair by secondary intention in full-thickness skin wounds in wet (saline), moist (hydrocolloid), and dry (gauze) conditions in an established porcine wound healing model. The study included three animals with a total of 70 wounds layered in a standardized fashion on the back of young Yorkshire pigs. Twelve days after wounding, 0 percent of dry, 20 percent of moist, and 86 percent of saline-treated wounds were completely reepithelialized (p values = 0.0046 and 0.027 for saline wounds compared with dry and moist wounds, respectively). The accelerated healing was caused at least in part by faster contraction in wet wounds (p value < 0.005 compared with that of other groups 9 and 12 days after wounding). Development of granulation tissue was faster in moist conditions than it was for dry and wet wounds. The thickness and number of cell layers of the newly formed epidermis were greater in dry and wet wounds than in moist ones. It was concluded that these full-thickness porcine skin wounds healed faster in a wet environment than in a moist one. Dry wounds healed more slowly than moist wounds. The basic mechanisms of skin wound repair were influenced by the treatment modality as demonstrated by the observed differences in granulation tissue formation, reepithelialization, and rate of wound contraction.     

A Three Species Model to Simulate Application of Hyperbaric Oxygen Therapy to Chronic Wounds

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.     

Non-adenine based purines accelerate wound healing

Wound healing is a complex sequence of cellular and molecular processes that involves multiple cell types and biochemical mediators. Several growth factors have been identified that regulate tissue repair, including the neurotrophin nerve growth factor (NGF). As non-adenine based purines (NABPs) are known to promote cell proliferation and the release of growth factors, we investigated whether NABPs had an effect on wound healing. Full-thickness, excisional wound healing in healthy BALB/c mice was significantly accelerated by daily topical application of NABPs such as guanosine (50% closure by days 2.5–2.8). Co-treatment of wounds with guanosine plus anti-NGF reversed the guanosine-promoted acceleration of wound healing, indicating that this effect of guanosine is mediated, at least in part, by NGF. Selective inhibitors of the NGF-inducible serine/threonine protein kinase (protein kinase N), such as 6-methylmercaptopurine riboside abolished the acceleration of wound healing caused by guanosine, confirming that activation of this enzyme is required for this effect of guanosine. Treatment of genetically diabetic BKS.Cg-m+/+lepr db mice, which display impaired wound healing, with guanosine led to accelerated healing of skin wounds (25% closure by days 2.8–3.0). These results provide further confirmation that the NABP-mediated acceleration of cutaneous wound healing is mediated via an NGF-dependent mechanism. Thus, NABPs may offer an alternative and viable approach for the treatment of wounds in a clinical setting.     

Lymphoscintigraphic monitoring of the lower limb lymphatic system response to bone fracture and healing

Closed bone fractures, and torn muscles and tendons are "internal wounds". What kind of reaction do they evoke in the local and systemic immune system? Cellular debris of damaged tissue and extravasated blood cells are removed by scavenger cells. They are transported via lymphatics to the lymph nodes. There elimination of self antigens takes place. Clinically, no enlargement of lymph nodes is observed after closed fractures and soft tissue damage. The question arises whether there is really no enlargement of regional lymph nodes, in other words, no reaction to damaged cell antigens. This question was studied by using lymphoscintigraphy to visualize lymphatics and lymph nodes draining the site of closed bone fracture. The lymphoscintigraphic pictures of two groups of patients, those with a rapid noncomplicated healing of leg fractures, and those with protracted healing and undergoing surgical reconstructions, were evaluated. The surface area of lymphatic pathways and inguinal lymph nodes on the injured and contralateral normal limb were measured. Enlarged superficial lymphatics and inguinal lymph nodes were found in limbs with healed bone fractures, and decreased inguinal lymph nodes and visualization of deep lymphatics and popliteal nodes in the majority of patients with nonhealing fractures. There was a lack of correlation between age of patients, duration of healing, and surgical interventions and the lymphoscintigraphic changes. These findings suggest that the fracture gap tissue is a dominant source of signals to the lymph nodes, releasing cellular and humoral regulatory factors. Taken together, there is a strong immune reaction of lymph node to the fracture, although it cannot be recognized clinically.     

Comparison of Gunshot Entrance Morphologies Caused by .40-Caliber Smith & Wesson, .380-Caliber,and 9-mm Luger Bullets: A Finite Element Analysis Study

Firearms can cause fatal wounds, which can be identified by traces on or around the body. However, there are cases where neither the bullet nor gun is found at the crime scene. Ballistic research involving finite element models can reproduce computational biomechanical conditions, without compromising bioethics, as they involve no direct tests on animals or humans. This study aims to compare the morphologies of gunshot entrance holes caused by.40-caliber Smith & Wesson (S&W), .380-caliber, and 9×19-mm Luger bullets. A fully metal-jacketed.40 S&W projectile, a fully metal-jacketed.380 projectile, and a fully metal-jacketed 9×19-mm Luger projectile were computationally fired at the glabellar region of the finite element model from a distance of 10 cm, at perpendicular incidence. The results show different morphologies in the entrance holes produced by the three bullets, using the same skull at the same shot distance. The results and traits of the entrance holes are discussed. Finite element models allow feasible computational ballistic research, which may be useful to forensic experts when comparing and analyzing data related to gunshot wounds in the forehead.     

A comparison of the effects of temperature on wound healing in a tropical and a temperate teleost

The rate of healing of a surgical wound was studied in two teleost fish, one with a tropical, and the other with a temperate temperature range. Comparisons were made of both the rate and qualitative nature of wound healing within and between species at temperatures of 30,23,10 and 5° C. The rate of wound healing was found to be proportional to temperature and temperature stress had little effect on healing rates. The findings were related to reported rates of wound healing in man. In general the wounds studied healed at a rate comparable to those reported for the healing of superficial skin wounds in man and other mammals despite the fact that the fish wounds were not merely superficial but involved integument and muscle.     

創傷癒合和組織再生的研究——Ⅰ.白鼠皮膚切除創傷癒合過程中創口的收縮

一.引言在高等動物的皮膚創傷癒合過程中,創口的收縮是很顯著的現象,使它所形成的疤痕往往小於當初創傷的部分。因此,創口的收縮作用,對於創傷癒合來說,是具有極大意義的。最早Carrel(1910)在研究狗的皮膚創傷癒合工作中,即已指出這個創口收縮的重要性;並且提出是由於肉芽的收縮作用(granulous retrac-     

Fracture management of civilian gunshot wounds to the hand

Civilian gunshot wounds to the hand are typically caused by low-velocity weapons, which create a localized pattern of soft-tissue and bone injury that usually allows for early definitive treatment. A retrospective chart review of 72 patients treated for 98 gunshot wound fractures at an urban level I trauma center was conducted to evaluate the results of limited debridement and early definitive fracture fixation of urban gunshot wound fractures of the hand. The incidence of hand fractures, means of fracture fixation, number of operations, occurrence of infection, and level of patient compliance were determined. Twenty-nine fractures were managed definitively with reduction and splinting in the emergency department or intensive care unit. Sixty-eight fractures were treated surgically, at a mean of 2 days after injury. Eleven patients required more than one operation. The overall infection rate was 8 percent and was not influenced by the fracture fixation method. All infections were superficial and resolved with antibiotics alone. Thirty-nine percent of patients were lost to follow-up after hospital discharge and 85 percent of patients were lost to follow-up before documented fracture healing. Twenty-six percent of patients were lost to follow-up with a removable fixation device in place. Limited debridement and early definitive fracture fixation are associated with low rates of complications for typical civilian handgun wound fractures. Cases with extensive injury or contamination do require a staged approach to treatment. Poor patient compliance in the urban trauma setting should be expected and may affect the management plan.     

Effects of topical applications of epidermal growth factor on wound healing. Experimental study on rabbit ears

In wounds in rabbit ears, the application every 12 hours of an ointment containing epidermal growth factor appears to produce faster and better healing. The resulting epithelium is thicker and more cellular than in the untreated ear wounds, and more fibroblasts appeared sooner during the healing process. Less wound contracture occurred in the EFG-treated wounds, and wound maturation occurred earlier. The healed wounds that had been treated with EGF more closely resembled the surrounding normal tissue, producing less local deformity than in the controls. It is too early to know whether this will have clinical application, but other experiments are under way to further investigate the effects of EGF on wound healing.     

Acceleration of healing,reduction of fibrotic scar,and normalization of tissue architecture by an angiotensin analogue,NorLeu3-A(1-7)

Angiotensin peptides have been demonstrated to modulate cellular proliferation, angiogenesis, and dermal repair. In this report, the effects of an analogue of the active angiotensin peptide angiotensin(1-7), namely norLeu3-angiotensin(1-7) (NorLeu3-A(1-7)), on the healing of epithelial wounds are presented. Three models were used to evaluate the normal (rats) and delayed (diabetic mice) healing responses of full-thickness excision wounds and the healing responses of full-thickness incision wounds (rats). NorLeu3-A(1-7) was superior to the naturally occurring angiotensin peptide angiotensin(1-7) and to Regranex (Ortho McNeil, Somerville, N.J.) (a formulation of recombinant platelet-derived growth factor used clinically for the treatment of diabetic ulcers) in accelerating tissue repair. By day 9 (normal rats) and day 11 (diabetic mice), the differences in the rates of closure of full-thickness excision wounds between NorLeu3-A(1-7) and Regranex were statistically significant (n = 5 per group). Full healing was observed for 60 percent of the diabetic mice treated topically with NorLeu3-A(1-7) by day 18 after injury, at which time full healing of wounds on placebo-treated or Regranex-treated diabetic mice was not observed. In the rat incision model, accelerated healing and reduced gross appearance of scarification were observed. Administration of NorLeu3-A(1-7) reduced fibrosis and scarring in the healing wounds. This action was more pronounced with longer administration of the peptide after injury. In fact, if systemic administration of the peptide (NorLeu3-A(1-7)) was continued during the remodeling phase, then the formation of new adnexal structures at the center of full-thickness excision wounds was observed, with an increase in the appearance of small immature hair follicles at the sites of the excision wounds. The action of this peptide was blocked by the AT receptor antagonist d-Ala7-angiotensin(1-7), which suggests that this receptor is involved in the healing responses to exogenous NorLeu3-A(1-7). These data suggest that this novel angiotensin peptide has the potential to be of benefit in accelerating wound repair and reducing scar formation.     

Thrombospondin 2 levels are increased in aged mice: consequences for cutaneous wound healing and angiogenesis.

The inhibitor of angiogenesis, thrombospondin 2 (TSP2), belongs to a group of matricellular proteins that are induced in response to injury and modulate the healing of dermal wounds. Thus, TSP-2-null mice display abnormal connective tissue architecture and increased angiogenesis in the dermis, and heal wounds at an accelerated rate. In this study, we report that the content of TSP2 is increased in the uninjured skin of aged mice. Furthermore, in primary dermal fibroblasts, TSP2 expression is increased both as a function of the age of the donor and days in culture. To determine the significance of the increased TSP2 in aged mice (two years or older), we performed full-thickness excisional wounds and compared their healing in aged and young (3-4 months) wild-type and TSP2-null mice. Gross morphological examination of wounds indicated that aged TSP2-null mice healed faster than their aged wild-type counterparts, but healing in aged mice was always sub-optimal in comparison to that in young animals. Surprisingly, despite the increase in TSP2, a potent inhibitor of angiogenesis, in wounds in aged mice, the vascular density of these wounds was not reduced in comparison to that in young animals. However, immunohistochemical analysis of healing wounds revealed a shift in the peak content of TSP2, from day 10 in young mice to day 14 or later in aged mice, and there was a corresponding delay in the expected increase in matrix metalloproteinase (MMP) 2 levels in aged TSP2-null mice. We suggest that the delay in expression of TSP2 and MMP2 in the wounds of aged mice could contribute to their impaired rate of wound healing.     

Immunohistochemical localization of growth factors in fetal wound healing

Fetal wound healing occurs rapidly, in a regenerative fashion, and without scar formation, by contrast with adult wound healing, where tissue repair results in scar formation which limits tissue function and growth. The extracellular matrix deposited in fetal wounds contains essentially the same structural components as that in the adult wound but there are distinct differences in the spatial and temporal distribution of these components. In particular the organization of collagen in the healed fetal wound is indistinguishable from the normal surrounding tissue. Rapidity of healing, lack of an inflammatory response, and an absence of neovascularization also distinguish fetal from adult wound healing. The mechanisms controlling these differing processes are undefined but growth factors may play a critical role. The distribution of growth factors in healing fetal wounds is unknown. We have studied, by immunohistochemistry, the localization of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta), and basic fibroblast growth factor (bFGF), in fetal, neonatal, and adult mouse lip wounds. TGF beta and bFGF were present in neonatal and adult wounds, but were not detected in the fetal wounds, while PDGF was present in fetal, neonatal, and adult wounds. This pattern correlates with the known effects in vitro of these factors, the absence of an inflammatory response and neovascularization in the fetal wound, and the patterns of collagen deposition in both fetal and adult wounds. The results suggest that it may be possible to manipulate the adult wound to produce more fetal-like, scarless, wound healing.     

A reciprocal relationship between cutaneous nerves and repairing skin wounds in the developing chick embryo.

Various studies have suggested that the rate of adult skin healing may be in some way dependent on signals emanating from cutaneous nerves. Further, it appears that adult wounds become hyperinnervated by sensory nerves during the process of healing. In order to investigate this reciprocal relationship further, we have used a simple embryonic model to look at the effect of wounds on nerves, and conversely, the effect of nerves on wounds. We find that wounds made to the dorsum of the chick wing bud, at a stage prior to normal innervation (at E4), or soon after the normal establishment of cutaneous innervation (at E7), subtly alter the pattern of branching by perturbing developmental guidance cues, but do not cause hyperinnervation, whereas wounding at E14 does cause hyperinnervation. By creating chicks with nerveless wings, we show that from E7, wound healing in the absence of nerves is significantly impaired. These observations suggest that, from the earliest stages of skin innervation, the presence of nerves is beneficial to the healing process, but that, in contrast to neonatal and adult tissues, wound healing in the embryo and early foetus does not trigger hyperinnervation.