TKIs against IGF axis thus have a theoretical advantage over MoAbs given the IR cross reactivity (33). OSI-906 is a potent and highly selective inhibitor of IGF-1R, with 14 times greater selectivity for IGF-1R over IR.34 OSI-906 alone did not show significant efficacy in pancreas cancer cell lines and was further evaluated in

other tumor types preclinically (35). IGF-1R pathway has been reported as potential resistance mechanism to EGFR inhibition and it seems logical to expect increased efficacy when an IGF-1R inhibitor is combined with gemcitabine and erolitinib #this website keyword# in pancreas cancer patients. Clinical trials evaluating OSI-906 with gemcitabine and erlotinib combination have yet to be initiated. However, the dosing regimen and toxicity profile of the combination of OSI-906 and erlotinib were reported at 2010 American Society Inhibitors,research,lifescience,medical of Clinical Oncology

Annual Meeting: OSI-906, administered daily at 50mg and 100mg, combined with erlotinib 100mg daily yielded stable disease in 4 out of 7 (57%) patients, including adrenocortical carcinoma, Ewings Inhibitors,research,lifescience,medical sarcoma, chordoma and adenocarcinoma of unknown primary (36). Toxicities included fatigue (31%) gastrointestinal side effects diarrhea (31%) nausea (15%); grade ≥3 hyperglycemia. Hedgehog/smoothened pathway Smoothened (Smo) is a transmembrane receptor with seven domains, and the activity is repressed by Patched (Ptch). The repression is relieved when ligands bind to Ptch or when there is activating mutations in Ptch, leading to increased Inhibitors,research,lifescience,medical transcription and up-regulation of Gli-1 to 3, thereby

modulating cell cycle and adhesion, angiogenesis, and apoptosis. In a comprehensive genomic analysis of pancreas cancers, mutations in at least one Hedgehog (Hh) signaling component has been reported in all samples Inhibitors,research,lifescience,medical analyzed, indicating the importance of Hh pathway in pancreas tumorgenesis (3). In addition, Hh signaling may be an important modulator of tumor-stromal interaction in the disease (37),(38). Preclinically, Olive et al. evaluated IP-926, a Smo inhibitor, with gemcitabine which the combination improved survival of tumor-bearing Idoxuridine mice and reduced metastasis in a transgenic model (39). The anti-cancer effect seems to be related to a decrease in tumor-associated stromal tissue and improve drug delivery by stimulating VEGF-independent angiogenesis. In this study, the tumor-bearing mice eventually adapted to chronic Smo inhibition and became resistant to the treatment, thus raising the importance in identifying potential resistant mechanisms. Hh signaling is also implicated as an important mediator of cancer stem cell (CSC) phenotype in pancreas cancer. Several groups have reported on the cellular markers of CSCs in pancreas cancer and the CSCs may be identified by the co-expression of CS133/CXCR4, or CD44/CD24/ESA.

We found that their density was normal at 1 month of age (10.2 ± 2 boutons/100 μm) although only 39% of these boutons were ChAT positive (Fig. 3). In contrast, the number of large synaptotagmin-positive boutons decreased (5 ± 0.6 boutons/100 μm) by 2 months of age and most of

them were ChAT-positive boutons (82%). These Epacadostat datasheet results indicated that the content of ChAT within large boutons progressively diminished from 1 month of age and the frequency of these cholinergic terminals tended to be reduced in the 2-month SOD1G93A mice. Figure 3 Early reduction of ChAT content precedes loss of large synaptic boutons. (A–C) Representative imunofluorescent microphotographs Inhibitors,research,lifescience,medical showing ChAT (green), synaptotagmin (Syn, red), and merged images (yellow–orange staining in colocalization) … In the postsynaptic Inhibitors,research,lifescience,medical membrane of the MN, beneath some cholinergic presynaptic boutons, there is a subsynaptic cistern. The cistern is thought to be continuous with the rough endoplasmic reticulum (ER) and directly associated with the function of the synapse (Nagy et al. 1993). In these cisterns, the sigma 1 receptor (Sig1-R) is present to buffer Ca2+ entry overload (Mavlyutov et al. 2010). We found Sig-1R immunoreactivity Inhibitors,research,lifescience,medical at close proximity of the synaptic clefts

in a spotty appearance in MNS of WT mice, but it was absent in lumbar MNs from SOD1G93A mice of 1 month of age (Fig. 4). Curiously, it was still present in thoracic MNs of the same animals although in smaller spots than in the WT (Fig. 4). Figure 4 Early loss of Sigma Inhibitors,research,lifescience,medical 1 receptor expression in lumbar MNs from transgenic SOD1G93A mice at 1 month of age. Representative confocal overlayed microphotographs showing Sig1-R (green) localized in the postsynaptic sites within the

MNs, and synaptotagmin staining Inhibitors,research,lifescience,medical … Further evidences of cholinergic alterations were observed in the local circuitry established between MNs and Renshaw interneurons in the ventral horn. We labeled Renshaw cells with anticalbindin and observed the cholinergic boutons onto their surface. The presence of cholinergic terminals along their processes was diminished form the 1-month-old SOD1G93A mice (Fig. 5). Also note the lack of ChAT staining in the processes efferent from MNs. Figure 5 Cholinergic inputs on Renshaw neurons are reduced in transgenic SOD1G93A mice. Representative Farnesyltransferase confocal overlayed microphotographs showing ChAT immunolabeling (green, left panels), calbindin labeling (red, middle panels) to reveal Renshaw interneurons … In conclusion, these data indicate that ChAT activity may be reduced in the synaptic terminals from very early in the presymptomatic stage of the SOD1G93A mice. This abnormality affects both afferences and efferences onto and from MNs, respectively, that participate in the local spinal motor circuitry.

In this regard, the fundamental principle forming the basis of the accelerated fractionated radiotherapy is to shorten the duration of treatment as well as decreasing the regeneration of tumor cells during treatment in order to improve tumor control and to achieve therapeutic gains in terms of reduced NU7026 in vivo tissue injury in the long term. This approach does not require any increase in the dose

applied per fraction and allows for adequate time between the fractions for Inhibitors,research,lifescience,medical tissue repair. This study aimed to assess the efficacy and tolerability of neoadjuvant chemotherapy and hyperfractionated accelerated radiotherapy in patients with esophageal cancer. Methods and materials Patient eligibility An observational study was carried out to evaluate the efficacy and safety of hyperfractionated-accelerated radiotherapy with concomitant chemotherapy followed by surgery in patients admitted with a diagnosis Inhibitors,research,lifescience,medical of esophageal cancer between June 2006 and January 2008 in the

Department of Radiation Oncology, Istanbul Faculty of Medicine, Istanbul University. A Inhibitors,research,lifescience,medical total of 20 eligible patients were included in the study. Patients were considered eligible if they met all of the following criteria: presence of newly diagnosed treatment-naïve esophageal squamous cell cancer (cervical squamous cell cancers and adenocarcinomas of the lower esophagus excluded); disease limited to esophagus and regional lymph nodes; Eastern Cooperative Oncology Group Performance Status (ECOG PS) Inhibitors,research,lifescience,medical 0-1; acceptable blood count and biochemistry values (i.e. hemoglobin >10 g/dL, WBC >4,000/mL,

PLT >100,000/µL, total bilirubin <2 mg/dL, creatinine <1.3 mg/dL, ALT-AST <80 U/L); and willingness to give written informed consent for the treatment of the study protocol. Exclusion criteria were as follows: presence of distant metastases; Inhibitors,research,lifescience,medical known active infection; cardiac failure; myocardial infarction within the last 6 months; inadequately controlled diabetes; severe COPD; pregnancy or lactation; current or past history of substance or alcohol abuse (social drinking was not an exclusion criteria). In addition, patients were excluded if they were deemed uncooperative by the investigator. The study protocol was approved by the local ethics committee and study procedures were conducted in accordance with Declaration of Helsinki Calpain of 1975, as revised in 2000. All patients gave informed consent prior to study entry. Figure 1 shows study diagram. Figure 1 Study diagram Patient assessment before neoadjuvant radiochemotherapy All diagnoses were based on the result of endoscopic biopsy, and after the initial evaluation of medical history, ECOG performance status, and physical examination, the following assessments were performed: histopathological consultation; complete blood count; blood biochemistry; computerized tomography of the thorax and abdomen and/or positron emission tomography (PET-CT). Planning was done using PET CT in 16 patients and computerized tomography in four patients.

In bipolar disorder, there is increased prefrontal glutamatergic metabolism (elevated Glx) perhaps as a trait measure. In major depression, basal ganglia choline is increased, while prefrontal Glx and occipital GABA are reduced and these may represent state abnormalities. Presently, none

of these effects are sufficiently sensitive or specific to have any diagnostic implication. The literature regarding applicability of 1H-MRS to evaluate effects of treatment is, not surprisingly, more limited. In schizophrenia, NAA reductions are not caused, but also not Inhibitors,research,lifescience,medical restored, by antipsychotic agents. However, there is evidence that antipsychotics may reduce elevated glutamatergic indices, especially in the striatum, their primary

site of action. In bipolar disorder, the 1H-MRS correlates of response to lithium and other mood stabilizers have not been elucidated. However, lithium quantification in brain is possible and may have future clinical applications. Regarding depression, it is encouraging that Inhibitors,research,lifescience,medical restoration of reduced glutamate and GABA have been documented with ECT, TMS, and antidepressant medication. Additionally, a small but reliable increase of NAA with medication is consistent with the neurotrophic effects of antidepressant drugs. However, the correlations with symptom improvement for these 1H-MRS /treatment relationships Inhibitors,research,lifescience,medical have been modest at Inhibitors,research,lifescience,medical best and no clinical applications are available. Table I summarizes the strengths and weaknesses of MRS. TABLE I. Strengths and weaknesses of magnetic resonance spectroscopy Future directions In terms of technique development there

is a need for sequences with broader spatial coverage so that true imaging of multiple metabolites is possible, with Inhibitors,research,lifescience,medical enough spatial resolution to allow full integration with other modalities. This would allow, for example, to test whether NAA reductions in white matter in schizophrenia, correspond or not to the well-described reductions in fractional anisotropy (FA), acquired with DTI. Additionally, techniques that reliably block lipid signal contamination, will permit more specific examination of peripheral cortical regions. Improved hardware and shimming techniques may allow measurements in deeper structures, like the amygdala or hippocampus, which are currently accessible mainly for the Navitoclax nmr singlet peaks easier to measure. Editing techniques at higher field strength with improved spectral resolution may allow of measurement of neuroactive metabolites in smaller, more physiologically plausible regions. Experiments in animals using microscopic and functional tools in addition to descriptive MRS measurements, would greatly advance the interpretation of clinical studies. Finally, in terms of clinical design, large samples (in the hundreds, like other modalities) of different clinical populations early in the illness, with long-term longitudinal follow-up, will be necessary.

However, contemporary neuroimaging technologies mentioned above (especially functional and pharmacological MRI, and PET) combined with behavioral approaches, offer a variety of new opportunities for the investigation of the limbic system in the living human brain.134,149,158,159 Thus, recent articles report the exploration of the corticolimbic circuitries in relation to emotion and cognition.158,160,161 Multimodal in vivo imaging studies add new information on the medial prefrontal cortex and amygdala coupling,160 providing an advanced knowledge on the brain mechanism of certain pathophysiological effects of social anxiety disorder.134

As described above, 5-HT neurons send axons and terminals Inhibitors,research,lifescience,medical throughout the entire brain and therefore can potentially interact with almost all the other neuronal systems via the diversity of 5-HT heteroceptors (ie, receptors expressed by neurons that do not synthesize 5HT).100 Recent Inhibitors,research,lifescience,medical investigations in mice indicate that other mechanisms could also contribute to the 5-HT signaling. Inhibitors,research,lifescience,medical Thus, it was demonstrated that local infusion of fluoxetine (a SSRI) in the dorsal raphe nucleus stimulates the secretion of the protein S100-beta by 5-HT neurons projecting to the locus cereuleus. This protein downregulates the microRNA miR-16

in noradrenergic neurons which in turn switch on serotonergic functions.90 Reciprocally, classical neurotransmitters, especially GABAergic, catecholaminergic, glutamatergic, cholinergic, and histaminergic systems, influence the serotonergic neurotransmission at different sites, including the raphe nuclei. It is well

known that the raphe nuclei contain collections of non-5-HT Inhibitors,research,lifescience,medical neuronal elements (eg, GABAergic, glutamatergic, cholinergic, histaminergic, dopaminergic, noradrenergic) interacting with 5-HT cell bodies via their respective receptor subsets.162,163 Moreover, the richness in heteroreceptors Inhibitors,research,lifescience,medical (eg, alpha2-adrenoceptors, glutamatergic, histaminergic receptors) expressed by 5-HT terminals and other local mechanisms (eg, vesicular-filling synergy) mentioned above illustrate the extent of the reciprocal chemocommunication between serotonergic circuitries and other neurotransmitter networks. others Other interactions of clinical INK-128 importance concern the interaction between serotonergic neurotransmission and neuropeptidergic systems. It is well known that 5-HT influences the activity of the hypothalamo-pituitary-adrenal axis at multiple levels, playing a role in stress-related disorders. Thus, 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor agonists enhance CRH and ACTH secretion and, consecutively, cortisol and other hormone levels in the plasma.164,165 In turn, corticosteroids attenuate the activity of 5-HT1 A receptors in the dorsal raphe nucleus, the hippocampal formation and the frontal cortex.

The numbers of consents to donate and actual organ donations have decreased substantially, and the number of organs transplanted was therefore reduced. With respect to kidney donations, the sharp decrease in deceased kidney transplantations was partially balanced by an increase in live donor kidney transplantations. The factors that led to such a devastating outcome were the strict Inhibitors,research,lifescience,medical requirements for confirmatory tests, without mechanisms to provide an alternative pathway in cases where these tests are meaningless or cannot be performed

for medical reasons, and not allowing the professional committees to decide about ancillary tests. Sometimes a delay in the definition of brain death in itself has led to the loss of the Inhibitors,research,lifescience,medical patient

organs, as multi-organ failure occurred before transplantation could be resumed. So, while the law provided a standard definition of death across the country, it also prevented the definition of brain death in a timely manner in a significant number of patients, as well as created a harmful burden on transplantations Inhibitors,research,lifescience,medical in the first year of its effect. We have also observed that the negative approach to organ donation was enhanced in some portions of the public rather than decreased. Another possible explanation for the drastic reduction in donations in the first year after the implementation of the law may be the incomplete organization of the medical community to the new practice of brain death definitions, i.e. proper training to all physicians, availability of ancillary tests, and expert teams in all hospitals, etc. Therefore, a greater efficiency in conducting Inhibitors,research,lifescience,medical ancillary tests in the process of brain death diagnosis in a timely and professional manner may improve the results Inhibitors,research,lifescience,medical over time, but this buy Cabozantinib remains to be seen. It is my understanding, based on the above, that while the strict standard criteria that are now fully imposed by law create more robust standardization among hospitals in Israel, a mechanism for confirming brain

death in those patients where some ancillary tests are inadequate or impossible must be implemented. There are more than a few examples where possible donors, who had expressed their wish to donate organs during their lives by signing a donor card, could found not be diagnosed as brain-dead because of the barrier of the law and ended up dying without fulfilling their request (Table 2). Therefore, it is suggested that the institutional committees for determination of brain death should be allowed to decide whether and when to use ancillary testing. Thus, instead of being mandatory in all cases, these tests should be indicated in circumstances where one or more of the brain stem tests, e.g. apnea test, cannot be performed. Table 2 National data for critical pathway on deceased donation based on data from Donor Action of the National Transplant Center in Israel, 2010.

If one focuses only on the 53 evaluable men who underwent “adequate” HIFU

treatment of primary disease, 62% were treatment failures based on prostate-specific antigen (PSA) recurrence using the Stuttgart definition of biochemical recurrence. As an isolated observation, this high failure rate is disconcerting and warrants an explanation if HIFU is to be considered a legitimate option for primary treatment of clinically localized prostate cancer. Inhibitors,research,lifescience,medical There are many glaring deficiencies in the Ripert study design. First, only 86 HIFU procedures were performed over a 6-year interval by two urologists using the Ablatherm device. Of these 86 procedures, 12 were performed following failed radiation therapy and 9 were retreatment. Only 65 procedures were performed Inhibitors,research,lifescience,medical as initial primary treatment of clinically localized prostate cancer. Therefore, on average, these two urologists performed approximately five procedures per year which, in my opinion, is far too low to gain proficiency with the technology. This will become evident when examining the

poor posttreatment PSA nadir levels achieved by these French urologists, which is why, in my opinion, their poor surgical technique is the primary explanation for their poor outcomes. Twelve additional cases were excluded for various reasons including recognized inadequate treatment, leaving only 53 evaluable primary disease cases. Half of these men had intermediate Inhibitors,research,lifescience,medical risk disease. Although the manufacturers of the Ablatherm PLX4720 device recommend excluding men with prostate volumes > 40 cm3, men with prostate volumes up to 50 cm3 were included in the Ripert study. HIFU is similar to radiation therapy (RT) in that prostate tissue is ultimately destroyed and not surgically removed. Inhibitors,research,lifescience,medical Because it is virtually impossible

to totally Inhibitors,research,lifescience,medical eradicate every PSA-producing cell with radiation without damaging adjacent structures, various definitions have been recommended for biochemical recurrence (BCR) assuming residual viable prostate tissue will contribute to a measureable PSA after radiation therapy. The Phoenix definition (nadir post-radiation therapy PSA + 2 ng/mL), a consensus definition of BCR following RT, has also been applied to ablative technologies. The Stuttgart definition (nadir post-ablation PSA + 1.2 ng/mL) has been suggested as an alternative definition of BCR following HIFU and other MIAT following whole-gland ablation with the intent to cure prostate Dipeptidyl peptidase cancer. Ripert and colleagues provide a summary of BCR rates for other reported clinical experiences using the Ablatherm device. In those studies reporting very favorable BCR rates, the median PSA nadir following HIFU treatment was 0.1 ng/mL, suggesting that HIFU successfully eradicated the overwhelming majority of the prostate gland. In those studies reporting poor outcomes, including the Ripert study, the median posttreatment PSA nadir ranged between 1.0 ng/mL and 1.3 ng/mL.

In fact, the 7.1-month PFS observed in this study with PLD was significantly higher than that expected for this drug in the general population. These results are in accordance with retrospective data published by Adams

and colleagues on Gynecologic Oncology in 2011 confirming the higher activity of PLD in BRCA-mutated ovarian cancer patients. Although all these data are very preliminary, it seems that PLD may have a special role in patients with BRCA mutation or BRCAness profile [90]. In the same direction are the results of a multicentre retrospective study in relapsed Inhibitors,research,lifescience,medical ovarian patients, BRCA mutation carriers, treated with PLD, where Safra et al. showed an improved outcome in terms of median time to treatment failure (15.8 months versus 8.1 months in nonhereditary OC) and overall survival (56.8 months versus 22.6 months) [91]. 5. Conclusions PLD plays an important role in the management

of ovarian cancer. It represents the standard therapy in platinum-resistant recurrence and one of the standard options in platinum-sensitive Inhibitors,research,lifescience,medical patients. Between the combination regimes, due to the results of efficacy achieved in phase-II and -III trials and considering the favorable safety profile, carboplatin/PLD represents a valid alternative in both first-line (in patients that cannot receive paclitaxel) and recurrent ovarian cancer compared Inhibitors,research,lifescience,medical to actual standard options. Combination with nonplatinum agents (trabectedin), and signaling pathway antiangiogenetic drugs (bevacizumab) represents an alternative treatment option in the recurrent setting, associated in certain cases with remarkable toxicity. New target therapy is Inhibitors,research,lifescience,medical under evaluation in combination with PLD. Acknowledgments The authors thank Dr. Valeria Trocino for bibliography assistance and Mrs. Balbina Apice and Antonietta Linardi for the help in editing the paper. This work has been partially supported by the Associazione Italiana per la Ricerca sul Inhibitors,research,lifescience,medical Cancro (AIRC).
Effective cancer treatment generally implies drug delivery to cancer cells after systemic administration

by taking advantage of the leaky tumor vasculature to deposit at the tumor site [17]. Indeed, liposome uptake by tumors relies primarily on the enhanced permeability and retention (EPR) effect [13, 17–19]. EPR is ADAMTS5 dependent on large endothelial fenestrations in the tumor endothelial vasculature coupled with the incomplete pericyte coverage that permits extravasation of large molecules and liposomes of size below 200nm into tumors with an impaired lymphatic drainage that is responsible for their retention [17, 18, 20]. However, after parenteral administration, most liposomes are captured by the mononuclear phagocyte system (MPS) in the liver and spleen [21]. This elimination is due to the recognition by serum proteins (opsonins) and complement components which prime liposomes for macrophage removal from the circulation [21, 22].

Demand for ambulance services in Japan has risen rapidly over the last decade [6].

The increased demand for ambulance services has gradually lengthened the time it takes for an ambulance crew to respond and arrive at the scene. As delayed response time reduces the number of patients who survive from sudden cardiac arrest [7-9], priority dispatch of ambulances to patients in a critical condition has become a matter of importance for Inhibitors,research,lifescience,medical the Japanese prehospital emergency medical services system. On October 1st, 2008, the city of Yokohama, Japan started a new emergency medical service system that was designed to dispatch ample emergency medical service staff to patients in a critical condition. Distinguishing patients in a critical condition from patients with non-critical conditions at the moment of the emergency call is known as call triage. The algorithm for call triage used in the new ambulance Inhibitors,research,lifescience,medical dispatch system is not a simple flowchart but a mathematical model with coefficients and the constant. The probability of patient being in a life-threatening condition (life threat risk) is calculated with a computerized

dispatch system, in which information provided in the call to the emergency service is used to estimate the risk. The present study was conducted to review Inhibitors,research,lifescience,medical the algorithm. Methods Organization of Emergency Medical Services in Japan In Japan, local governments provide prehospital emergency medical services as a public service. Anyone can use an ambulance free of charge by phoning 119. Most local governments staff ambulances with emergency life-saving technicians who are trained for cardiopulmonary resuscitation and pass a national examination. They play an important role as a first responder in the pre-hospital emergency Inhibitors,research,lifescience,medical field. They are allowed to defibrillate, to perform tracheal

intubation and to administer a resuscitative drug, epinephrine, during out-of-hospital cardiopulmonary resuscitation Inhibitors,research,lifescience,medical under online direction from an emergency medicine physician [10,11]. All patients who received advance life support at the scene were transported to hospitals. The Fire and Disaster Selleck Epacadostat Management Agency, Ministry of General Affaires of Japan reported that Oxygenase the national average call-response interval of ambulances was 7.0 minutes in 2007. Study population and setting The data used in the study was collected during the Yokohama New Emergency System from October 1st, 2008 to March 31st, 2009. Yokohama is Japan’s second largest city (population 3.58 million, Census 2005). Yokohama’s prehospital emergency medical service is unified and managed by the Emergency Medical Division of the Yokohama Safety Management Bureau. The number of ambulances dispatched in 2008 was 146,145, and this number had increased constantly up to 2005, after which the rate of increase reduced [12]. In the system, emergency call workers conduct dispatch.

Competing interests The author(s) declare that they have no competing interests. Authors’ contributions DE carried out all statistical analyses and drafted the manuscript. JN led data collection and assisted in study conceptualization. MC participated in data collection and cleaning, and participated in hypothesis generation. PW was involved in all stages from conceptualization to interpretation of data analyses, and contributed significantly Inhibitors,research,lifescience,medical to writing of all sections of the manuscript. KD is the PI of the parent study, served as senior author and

oversaw all steps of manuscript preparation with DE. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this Inhibitors,research,lifescience,medical paper can be accessed here: http://www.biomedcentral.com/1471-227X/12/14/prepub Acknowledgements This work was supported by Grant HL-088117 from the National Institutes of Health, Bethesda, Maryland. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Dr. Edmondson is supported by grant

KM1 CA-156709. The funders had no role in the design, collection, analysis, or Inhibitors,research,lifescience,medical interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript Inhibitors,research,lifescience,medical for publication.
Traumatic brain injuries (TBI) result in almost 17 000 emergency department (ED) visits per year in Sweden and account for more than 1 million ED

visits each year in both the United States of America and the United Kingdom [1-3]. Most of them (up to 95%) are classified as mild head injuries (MHI) [4], commonly defined as a head trauma Inhibitors,research,lifescience,medical with short loss of consciousness (LOC) or amnesia for the accident, Glasgow Coma Scale (GCS) 14–15 and no neurological deficits at the time of TKI258 medical inspection. These patients have been notoriously difficult to manage since they have a low, but not negligible, risk of an intracranial complication, which may be life threatening [5]. Pathological computed tomography (CT) results after MHI are found in 0.5-20% of ever patients (0-8% for significant complications) and the need for neurosurgical intervention is between 0-1% [6]. Scandinavian guidelines for management of minimal, mild and moderate head injuries were presented by the Scandinavian Neurotrauma Committee (SNC) in the year 2000 [1]. For patients with GCS 14–15 and LOC and/or amnesia, these guidelines recommend head CT or, as a secondary option, hospital admission with clinical observation. Similar guidelines have been published from other groups [7-9] and all have the same goal; to stratify patients with MHI into risk groups for intracranial complications.