Original Site Of Injury Research Articles

Successful mechanical thrombectomy for terminal ICA bullet embolism: A case report

Bullet embolism after high velocity penetrating trauma is a rare event that can have devastating and wide-ranging effects distant from the original site of injury. A 29-year-old presented with multiple gunshot wounds to the chest, back, abdomen, and lower extremities but no penetrating head injury. After proper resuscitation, the patient was noted to have left-sided hemiparesis and computed tomography angiography of the head showed a bullet fragment that had traveled to the right M1 segment of the middle cerebral artery resulting in occlusion of the vessel. Mechanical thrombectomy was performed in an attempt to remove the bullet fragment but this was unsuccessful as the fragment was firmly lodged in the blood vessel. Aspiration of clot distal to the fragment was then performed in hopes of preventing a large volume ischemic event which was angiographically successful resulting in TICI 2c revascularization. This case demonstrates that thrombectomy can be safely and successfully performed distal to a lodged foreign body.

Vitamin D in Keloids: An alternative to steroids?

Madam, Keloids are wound healing scars with well-demarcated overgrowth of fibrotic tissue, mainly involving excessive collagen proliferation produced by fibroblasts. They extend beyond the original injury site, and are associated with pain and pruritus (1,2). Few treatments available few for Keloids include occlusive dressings, compression therapy and intralesional corticosteroid injections (1). Triamcinolone acetate, a corticosteroid injection, is considered the first line treatment as it possesses anti-inflammatory and anti-mitotic activities, which reduce scar volume and prevent a recurrence. However, approximately 50percent of keloids are considered to be steroid resistant (3, 4). Moreover, as per literature, the usage of intralesional corticosteroid injections can cause several local and systemic adverse effects such as telangiectasias, skin necrosis, skin and subcutaneous fat atrophy, and Cushing’s syndrome (5) In light of the above, researchers are keen on finding other treatment modalities for treating these lesions, and among them Vitamin D, is being investigated. Vitamin D is a steroid hormone that normally plays a role in regulating serum calcium, inhibiting cellular proliferation and promoting cell differentiation and apoptotic activities. Transforming growth factor-beta (TGF-B), an inflammatory marker, has been implicated in the pathogenesis of keloids. TGF-B is believed to be inhibited with localised Vitamin D. Furthermore, Vitamin D deficiency plays a significant role in keloidogenesis, a process mediated by dysregulation of koebnerisin, an antimicrobial polypeptide (2). A study was conducted recently, where 40 adults, aged 18 to 60 years, were administered intralesional Vitamin D, on keloids sized atleast 5 cm, with sessions carried out every week for a maximum of 3-4 sessions. This study showed a highly significant reduction in the Vancouver Scar Scale, a scarring scoring system (1). However, further trials, specially comparative studies, are needed to effectively weigh in the efficacy of Vitamin D over steroids. Advantages of Vitamin D are evident and promising so far – it’s cost-friendly, and shows mild side effects such as burning, pain, swelling and tenderness that shortly disappears on its own.

Resurgent neuropathic discharge: an obstacle to the therapeutic use of neuroma resection?

Ectopic discharge ("ectopia") in damaged afferent axons is a major contributor to chronic neuropathic pain. Clinical opinion discourages surgical resection of nerves proximal to the original injury site for fear of resurgence of ectopia and exacerbated pain. We tested this concept in a well-established animal neuroma model. Teased-fiber recordings were made of ectopic spontaneous discharge originating in the experimental nerve-end neuroma and associated dorsal root ganglia in rats that underwent either a single transection (with ligation) of the sciatic nerve or 2 consecutive transections separated by 7, 14, 21, or 30 days. Ectopia emerged in afferent A and C fibers after a single cut with kinetics anticipated from previous studies. When resection was performed during the early period of intense A-fiber activity, a brief period of resurgence was observed. However, resection of neuromas of more than 14 days was followed by low levels of activity with no indication of resurgence. This remained the case in trials out to 60 days after the first cut. Similarly, we saw no indication of resurgent ectopia originating in axotomized dorsal root ganglion neuronal somata and no behavioral reflection of resurgence. In summary, we failed to validate the concern that proximal resection of a problematic nerve would lead to intense resurgent ectopic discharge and pain. As the well-entrenched concept of resurgence is based more on case reports and anecdotes than on solid evidence, it may be justified to relax the stricture against resecting neuromas as a therapeutic strategy, at least within the framework of controlled clinical trials.

Scoping Review of Therapeutic Strategies for Keloids and Hypertrophic Scars.

Background:Keloids are an abnormal proliferation of scars that can involve large areas of tissue beyond the original injury site. Hypertrophic scars are similar clinically, but do not exceed the original scar limits. These scarring abnormalities can cause noxious symptoms such as pain, tenderness, itching, and ulcerations. The aim of this review is to discuss current therapies for both types of abnormal scarring, and to determine if guidelines can be provided for excisional treatment with adjuvant therapies versus non-excisional methods.Methods:A systematic literature search was performed through the Web of Science database. The search revolved around keywords such as “keloid,” “hypertrophic scars,” and “treatment.” Articles were reviewed and screened for inclusion and exclusion criteria. The review focuses on an analysis and summarization of randomized control trials regarding keloid or hypertrophic scar treatments.Results:The original searches produced 1161 and 1275 articles for keloid and hypertrophic scars, respectively. In total, 316 duplicates were found. After accounting for 2014–2019 publication time, 655 keloid and 893 hypertrophic scar articles were reviewed. This resulted in 15 articles that pertained to treatment and randomized control trials.Conclusions:Keloids and hypertrophic scars present a clinical challenge. Based on qualitative review of recurrence, neither excision plus adjuvant therapy or nonsurgical treatments can be recommended preferentially at this time. More research is needed to determine if recurrence rate bias exists between the treatment regimens, as excisional treatment plus adjuvant therapy is reserved for refractory scars.

Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain.

Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma-aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.

The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1−/−) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1−/− mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1−/− mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

Repair Method for Complete High Ulnar Nerve Injury Based on Nerve Magnified Regeneration.

PurposeComplete high ulnar nerve injury can cause serious sequelae, including residual sensation and loss of movement and especially dysfunction of the intrinsic muscles of the hand. As a solution to treat complete high ulnar nerve injury, we proposed a new repair method for ulnar nerve injury based on nerve-magnified regeneration.MethodsTwenty-two patients with complete division of the ulnar nerve at a high level who were treated from May 2013 to December 2016 were divided into two groups. The proposed repair method for complete high ulnar nerve injury was performed in group I (11 patients), while the traditional repair method, ie, repair of the original injury site of the ulnar nerve, was used in group II (11 patients).ResultsThe results showed no significant difference in the mean sensory scores assigned by the Highet-Zachary scheme (the Highet Scale) between the two groups. The mean Highet Scale score of muscle strength for the first dorsal interosseus muscle was significantly better in group I than that in group II (p=0.010). In group I, 10 of 11 patients were graded as M4 or M5. Grip strength, pinch strength, and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were significantly better in group I than those in group II (p<0.01).ConclusionTherefore, this method for complete high ulnar nerve injury based on nerve-magnified regeneration can shorten the path of motor nerve regeneration, effectively reduce atrophy of the intrinsic muscles of the hand, and provide better hand function.

Mathematical modelling of blood–brain barrier failure and oedema

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier (BBB) permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic oedema. Although the initial injury may be localized, the resulting oedema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of BBB permeability changes within a region of brain tissue and the onset of vasogenic oedema. We find that such localized changes can indeed result in brain tissue swelling and suggest that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear oedema fluid.

Utility of arteriovenous loops before free tissue transfer for post-traumatic leg defects.

Crush injuries of severe magnitude involving lower limbs require complex bone and soft tissue reconstructions in the form of microvascular free tissue transfers. However, satisfactory recipient vessels are often unavailable in the leg due to their vulnerability to trauma and post traumatic vessel disease (PTVD), which extends well beyond the site of original injury. In such situations, healthy recipient vessels for free flap anastomosis can be made available by constructing temporary arteriovenous loops with saphenous vein grafts, anastomosed to corresponding free flap vessels. Our study included 7 patients with severe crush injuries of leg due to rail and road traffic accidents. Long and short saphenous vein grafts were anastomosed to Femoral artery in the subsartorial canal in 2 cases and to large muscular branches and accompanying veins in rest of the cases. Free flap transfers were performed in the same sitting in 6 cases. One case showed insufficient dilatation of the vein loop and hence free flap transfer was staged. Free Latissimus dorsi, Gracilis and Rectus abdominis flaps were performed. There were two cases of flap necrosis – one in the case of a pathologic vein graft with staged flap transfer which showed vein thrombosis on re exploration. The other case of flap failure was caused by a hematoma underneath the flap. In another patient, secondary haemorrhage occurred on day 18, without any consequence to the flap. All the other cases had complete free flap survival. We consider the use of single stage arteriovenous loops, a valuable tool to increase the applications of free flap, whenever healthy recipient vessels are not available in the periphery of the trauma.

Deep Brain Stimulation of the Subthalamic Nucleus for Peripherally Induced Parkinsonism

RESULTS Trauma to the peripheral nervous system can cause various movement disorders including dystonia, tremor and parkinsonism. Most patients with peripherally-induced parkinsonism develop symptoms that extend beyond the original site of injury, suggesting involvement of the central nervous system, possibly through reorganization in response to altered peripheral input. Most patients with peripherally-induced parkinsonism do not respond to levodopa therapy.

Significance of minor traumatic lesions in focal head injuries

We investigated the significance of minor traumatic lesions associated with focal head injuries. Patients included in the study were admitted between January 2003 and December 2007 and had sustained a head injury with focal injury and undergone MRI examination including T2 ∗-weighted imaging. Patients were divided into two groups: (i) a T2 ∗-positive group – those who had hypointense lesions at sites other than the original injury site as shown by T2 ∗-weighted MRI ( n = 12); and (ii) a control group without hypointense lesions at sites other than the original injury ( n = 25). The median Glasgow Outcome Scale score was significantly lower in the T2 ∗-positive group (median = 4; range = 4–5) than in the control group (median = 5; range = 4–5; p = 0.003). We conclude that patients with a focal head injury and minor traumatic lesions are likely to have a poorer prognosis than patients without additional minor traumatic lesions.

Crossed cerebellar diaschisis on F-18 FDG PET/CT

Diaschisis is the inhibition of function produced by focal disturbances in a portion of the brain at a distance from original site of injury. Many studies using brain SPECT (single-photon emission computed tomography) have demonstrated crossed cerebellar diaschisis (CCD) in patients with cerebral cortical infarct. We report a case of cerebrovascular accident involving the left middle cerebral artery territory. PET/CT performed one month after stroke showed hypometabolism in the left cerebral hemisphere with hypometabolism of the contralateral cerebellum. The finding of diminished glucose metabolism in the contralateral cerebellum represents CCD.

A Complication of Intracorporeal Use of Quikclot for Pelvic Hemorrhage

A 23-year-old Hispanic male sustained a single gun shot wound (GSW) to the left upper buttocks. He arrived to the Emergency Room in hemorrhagic shock with a systolic blood pressure of 73 and heart rate of 120. The patient had a patent airway, good breath sounds with adequate excursion but peripheral pulses were weak. He was able to move all extremities to command but was intermittently obtunded. There was a single GSW just above the left buttocks 5 cm lateral to the midline. The patient had diffuse abdominal tenderness and was in persistent shock. He was taken emergently to the operating room. No adjunct studies were performed in the Emergency Department except for the Focused Abdominal Sonography for Trauma examination that was positive for fluid. Approximately 2 L of blood was evacuated with lap pads at exploration. The bullet was retained in the low anterior abdominal wall on the ipsilateral side of the posterior GSW. There was continued active bleeding from deep within the pelvis. His aortic bifurcation and iliac veins were compressed but this did not arrest his bleeding. Venous bleeding continued from bony and soft tissue destruction. It was not well controlled with pelvic packing, gelfoam packing, foley catheter balloon tamponade, and iliac vein ligation. Bilateral internal iliac artery ligation was performed but the bleeding remained significant from a large bony defect. The patient continued to be hemodynamically unstable despite continued transfusions of red cells (15 units ultimately) and fresh frozen plasma. The decision for damage control laparotomy had been made early in the procedure but the pelvic bleeding eluded attempts at even reasonable surgical control for temporary closure and resuscitation. The left ureter had been identified and was found to be without apparent injury. Because the patient had continued bleeding that was not controlled by conventional means, and the patient’s clinical status was continuing to decline, one pack (1.75 oz.) of QuikClot, Absorbent Hemostatic Agent, was deposited in the large defect and packing was applied. This maneuver resulted in almost instant arrest of significant pelvic bleeding. There was a rapid improvement in hemodynamic parameters; however, the patient remained cold and coagulopathic. The remainder of the pelvis was packed and the uninjured left ureter was placed back in its normal position before the abdomen was temporarily closed and the patient transported to the Surgical Intensive Care Unit. The patient’s coagulopathy was corrected, there was no continued clinical bleeding and the patient’s physiologic parameters were more normal within the first 24 hours postoperatively. He was returned to the Operating Room where his packs were removed. There was only minimal bleeding noted. The remaining QuikClot was removed but there was a moderate amount of material left adherent to the surrounding tissues and deep within the pelvis. Quikclot was adherent to the ureter near the original injury site but it did appear intact. Tissues that were in contact with the material were viable. The patient did well postoperatively. He was transferred to the floor by postoperative day POD 2. He did not have evidence of bleeding and he complained only of left sided back and leg pain which was present preoperatively. He was tolerating a diet and was discharged on postoperative day 7. He was seen in a clinic visit and reported no other problems except for left sided back and leg pain as before. However, approximately 3 weeks postoperatively; he was evaluated and admitted for abdominal pain. Computed Tomography (CT) of the abdomen revealed left hydronephrosis and dilated ureter (Fig. 1). No ureteral extravasation was detected on CT. He was subsequently evaluated by urology and diagnosed with a ureteral injury with leak on anterograde cystourethrogram (Fig. 2). A nephrostomy tube was placed. Stent placement was attempted but was unsuccessful because of the size of the defect. Plans were made for elective operative repair. Two weeks later, he was evaluated emergently for abdominal pain and blood per his nephrostomy tube. He was found to have a hemoglobin of 7.2 g/dL (postoperative hemoglobin was 9.4 g/dL). He was found to be only in mild Submitted for publication August 21, 2006. Accepted for publication December 14, 2006. Copyright © 2009 by Lippincott Williams & Wilkins From the Department of Surgery, Division of Trauma/Surgical Critical Care (D.P., P.R.); and Department of Urology (S.C., C.B.), LAC USC Medical Center, Los Angeles, California. Address for reprints: Dr. David Plurad, MD, Department of Surgery, Division of Trauma/Surgical Critical Care, LAC USC Medical Center, 1200 North State Street, Los Angeles, CA; email: dsplurad@aol.com.

Keloids and hypertrophic scars: review and therapeutic modalities

Hypertrophic scars and Keloids are exuberant fibrous repair tissues following cutaneous injury. A hypetrophic scar remains confined to the site of original injury, keloids however extend beyond this site often with a claw-like extensions. This review is focusing in details on keloids and hypertrophic scars, the pathophysiology, epidemiology, aetiology, clinical features, complications and the management options. Keywords : Hypertrophic scar, Keloid Sudanese Journal of Dermatology Vol. 5 (2) 2008: pp. 43-50

Influence of Prior Hamstring Strain Injury on Sprinting Kinematics and Isokinetic Strength Profile

After straining a hamstring, an athlete's risk of repeat injury remains elevated even after a symptom-free return to sport. Scar tissue may limit the extensibility of the muscle-tendon unit, causing it to operate at shorter lengths. Altered length during activities involving lengthening (eccentric) contractions, such as sprinting, may predispose a previously injured muscle to recurrent injury. PURPOSE: Determine whether subjects with a history of unilateral hamstring injury demonstrate reduced peak biceps femoris musculotendon length during sprinting and greater knee flexion angle at peak isokinetic torque production in the previously injured limb compared to the non-injured limb. METHODS: Passive motion capture was used to gather treadmill sprinting kinematic data from nine athletes with a history of unilateral hamstring strains (3-12 months post-injury), with collection at five sprinting speeds (60, 80, 90, 95 and 100 percent of maximum). The musculotendon length of the biceps femoris long head was calculated throughout the gait cycle based on corresponding hip and knee angles. In addition, maximum knee flexion torque and the angle of occurrence were measured at 60 deg/s using an isokinetic dynamometer. MR images were used to evaluate the presence of residual scar tissue at the original injury site. Repeated-measures ANOVAs were used to determine significance of measurements, with inclusion of limb, speed, and trial effects. RESULTS: There were enlarged regions of low intensity signal on the side of prior hamstring injury for six of the nine subjects, suggesting the presence of residual scar tissue. However, the peak length of the biceps femoris during sprinting (p=0.45), as well as its total excursion (p=0.35), were not significantly different between the previously injured and non-injured limbs. Further, the maximum knee flexion torque (p=0.86) and the corresponding knee flexion angle (p=0.81) were consistent between limbs. CONCLUSIONS: These findings suggest that long-term remodeling effects are present in previously injured muscles, but that changes in function at the joint level may not be measurable using motion analysis techniques. Imaging of muscle-tendon dynamics under load may offer greater insight into residual neuromuscular deficits that contribute to re-injury.

Impact of early sepsis on oxygen delivery in the microvasculature

A defining characteristic of sepsis is progressive blood flow dysfunction in the microvasculature of organs remote to the original site of injury. Previous work has established that microvascular oxygen transport is compromised in sepsis due to a loss of perfused capillaries. In a companion study to this project, which investigated the role of leukocyte traffic in sepsis, it was observed that increased transit times of leukocytes passing through the capillary bed not only resulted in the occlusion of some capillaries, but also served to cause some vessels to experience prolonged periods of low flow. The objective of the present study was to examine how the progressive loss of functional capillary density (FCD) impacts oxygen transport and consumption in skeletal muscle during sepsis. Hemodynamic and oxygen saturation data from video recordings are incorporated into an experiment-based mathematical model of oxygen transport in a three-dimensional volume. This modeling helps to further our understanding of the impact that capillary loss has on tissue oxygenation and consumption. Sepsis was induced in rats by cecal ligation and perforation (CLP). Rats received crystalloid fluid resuscitation to maintain blood pressure and hematocrit at baseline levels. Microvascular flow was observed in the extensor digitorum muscle using a dual wavelength intravital video microscopy set-up. The same field of view was recorded at 30 min intervals between 2 and 5 hours post CLP to follow the progression of capillary dysfunction. Individual capillaries were analyzed for oxygen saturations and hemodynamics. As sepsis progresses we observed that capillaries' hemodynamic profiles transiently change between normal, stopped and fast flow states. Although it has previously been assumed that once a capillary becomes occluded flow is not easily re-established, we observed that capillaries could suddenly become reperfused after being occluded for up to 1 hour or more. The occlusion of capillaries was found to decrease oxygen saturations in nearby vessels by as much as 20%. Subsequent recruitment of previously unperfused capillaries was shown to increase saturations in adjacent vessels by as much as 50%. Changes in perfusion of adjacent vessels had a greater impact on oxygen saturation than changes in hematocrit or velocity in the vessel itself. At 2, 3 and 4 hours post CLP the percentage of stopped flow vessels was 17%, 28% and 48% in CLP compared with 13%, 13% and 20% in sham. The extent of FCD loss is progressive over the course of the injury. However, it is important to note that while the percentage of occluded capillaries increases, the individual vessels constituting this percentage were variable. Our study suggests that in this early stage where the FCD is in transition, affected tissue experiences dynamic changes in tissue oxygenation. This highlights the importance of understanding the mechanisms responsible for this dynamic change in FCD.

Nitric Oxide Scavenging, Abnormal Vasoregulation and Oxidative Damage in sph/sph Mice with Severe Hereditary Spherocytosis: Possible Consequences of Red Blood Cell Hemolysis.

The membrane skeleton, a multiprotein complex located just beneath the plasma membrane, provides the red blood cell (RBC) with the mechanical strength and deformability required to withstand high shear forces generated in the microcapillaries. Spectrin, a tetramer composed of a- and b- subunits, is the backbone of the erythroid membrane skeleton. Previously, we have shown that sph/sph mice have severe hereditary spherocytosis (HS) due to a spontaneous single-base deletion in the murine erythroid a-spectrin gene, Spna1. HS mice have severe hemolytic anemia, compensatory reticulocytosis, altered RBC morphology and increased fragility. Vascular dysfunction in sph/sph mice likely plays an important role in the mechanism by which these mice develop a high incidence of cardiac thrombosis and stroke between 6 and 12 weeks of age. We hypothesize that serum free hemoglobin released from intravascular hemolysis of sph/sph RBCs and xanthine oxidase, released from ischemic tissues, impairs endothelial cell function by scavenging nitric oxide (NO) and increasing oxidative damage. To test this hypothesis, we used helium electroparamagnetic resonance (EPR), to quantify plasma free Hb and NO scavenging capacity in the plasma of the mice; immunohistochemistry to determine tissue and vascular levels of xanthine oxidase and 3-nitrotyrosine; and, facialis arteries to measure changes in acetylcholine, endothelium and eNOS-dependent vasodilation. By EPR we found that the plasma free Hb and NO scavenging capacity in the plasma of sph/sph mice is much greater than that of the normal +/+ mice. Immunohistochemistry (IHC) for XO and NTyr revealed XO staining was decreased in livers of sph/sph mice as compared to livers from normal +/+ mice. XO staining was increased in local patches on the endothelium of lungs isolated from sph/sph mice compared to lungs from +/+ mice. NTyr, a marker of peroxynitrite formation was also increased in a focal manner in lungs of sph/sph mice compared to lungs of +/+ mice. Acetylcholine-induced and eNOS-dependent vasodilation in sph/sph mice was significantly impaired compared to vasodilation in normal +/+ mice. Taken together these data suggest the hemoglobin removal system in sph/sph mice is saturated, leading to increased free Hb and nitric oxide scavenging. IHC studies reveal XO is released from liver in sph/sph mice and once released binds the endothelium of lung, quite distal from the original site of injury. Such changes likely contribute to marked increases in NTyr staining and impaired endothelium and eNOS-dependent vasodilation in facialis arteries isolated from sph/sph mice. Taken together, these data indicate that sph/sph mice with severe HS have increased plasma free Hb and NO scavenging capacity as well as increased release of xanthine oxidase and subsequent binding to vascular endothelial cells to locations that are distal the original site of injury. Such plasma and vascular changes in hemoglobin and oxidative enzymes likely play a critical role in the mechanisms contributing to aberrant vasoregulation and initiating the pathways of oxidative damage found in sph/sph mice.

Prior injury accelerates subsequent wound closure in a mouse model of regeneration

Tissue regeneration and scarless healing involves the complete replacement and functional restoration of damaged organs and tissues. In this study of the "scarless healing" MRL mouse model, we demonstrate that 2-mm diameter through-and-through holes made in the cartilaginous part of previously injured MRL mouse ears are closed more efficiently, and that the regenerative repair response is significantly accelerated compared with unprimed MRL and control "nonhealer" strains of mice. Accelerated healing was detected both locally and distally from the original site of injury indicating the involvement of systemic components such as circulating cell types or soluble factors. Histologically, we observed early differences during the wound repair process (before Day 4 post injury) with accelerated formation of blastema-like structures, epidermal downgrowths, and enhanced epithelium thickening in wound border zones in primed MRL mice versus unprimed MRL mice. Although the mechanism of tissue regeneration remains unclear, the results from this study justify the use of the MRL model for further experimentation directed toward the identification of proteins and cell types capable of stimulating scarless tissue regeneration.

Excitatory amino acid inhibitors for traumatic brain injury.

Glutamate is the principal excitatory neurotransmitter in the brain. Injury to the brain can cause an ionic imbalance in cerebral tissue, creating an excitotoxic cascade involving glutamate and other excitatory amino acids, that leads to neuronal death in the tissue surrounding the original injury site. Research has centred around inhibiting this increase in excitatory amino acid during injury either pre- or post-synaptically. Animal studies appeared promising, but as yet, those results have not been repeated in human clinical trials. To assess systematically the efficacy of excitatory amino acid inhibitors on improving patient outcome following traumatic brain injury. Online searches of the databases; CENTRAL, MEDLINE, EMBASE, IDdb3, and Science Citation Index. Online searches of clinical trial registers. General online searches of the Internet. Authors of published works and associated pharmaceutical companies were contacted. Trials were included if they were randomised, double-blind, controlled trials where excitatory amino acid inhibitors were administered to patients with traumatic brain injury, within 24 hours of sustaining that injury, and compared to a control group. Twelve trials, involving eight compounds, were identified that appeared to fit the inclusion criteria. Further investigation excluded three of these trials. Two of the remaining trials are ongoing. Of the seven included studies, one trial did not report GOS data and we were unable to acquire them. Three trials have not been published and the data were not made available to us. One trial is currently being prepared for publication, leaving two trials where data were available. Data were extracted by two independent reviewers. Data were available for two of the seven relevant trials identified, with 760 recruited participants. Mortality is similar between patients who receive excitatory amino acid inhibitors and those that receive placebo: odds ratio (OR) 1.11; 95% confidence interval (CI) 0.78, 1.60. Patients who have a favourable outcome six months after injury are also similar between treatment and placebo groups: OR 0.86; 95% CI 0.64, 1.16. The case for efficacy of excitatory amino acid inhibitor therapy remains unproven. To date, no product has proven to be efficacious (as determined by the criteria applied) for improving the outcomes of brain-injured patients. Early termination, unpublished, and underpowered studies limit a clear appreciation of the merits of this form of intervention. Additional studies, some of which remain in progress, may more clearly define the efficacy and effectiveness issues.

Supratentorial hydatid cyst with cerebellar signs: a rare case of diaschisis

Intracranial hydatid disease has a distinct predominance in the pediatric age group and still causes serious problems in endemic areas. A 7-year-old girl admitted with a 3-month history of illness involving the main symptoms of ataxic gait, apraxia, headache, and tremor and with positive cerebellar signs and papilledema is presented. Cranial computerized tomography and magnetic resonance imaging revealed a right temporoparietal spherical lesion measuring 50 x 60 x 80 mm, which had a significant mass effect. A preoperative diagnosis of intracranial hydatid cyst was confirmed during the surgical procedure, which allowed removal of the cyst intact. The postoperative course was uneventful. The aim of this presentation is to emphasize the necessity for considering diaschisis--inhibition of function produced by a focal disturbance in a portion of the brain at some distance from the original site of injury, but anatomically connected with it through fiber tracts. We believe that this case, with a mass lesion in a temporoparietal location and definite clinical manifestations with plentiful cerebellar signs, is a good example of this rare phenomenon.