somnogenic substance that progressively

accumulates with prolonged wakefulness, with adenosine being one of the most cited candidates.7 Both homeostatic and circadian mechanisms are thought, to influence the opposite action of neurons promoting wakefulness and neurons promoting sleep. Wake-active neurons are cholinergic (located in the basal forebrain and in the tegmentum) and monoaminergic (noradrenergic in the locus ceruleus, serotonergic in the dorsal raphe, and histaminergic in the tuberomammillary nucleus), whereas sleep-active neurons are GABAergic and located in the preoptic area of the hypothalamus:4 The discovery Inhibitors,research,lifescience,medical of the hypocretin (also called orexin) system has brought, new inroads into understanding Inhibitors,research,lifescience,medical the sleep-regulatory neural circuit.8 Hypocretin neurons are located in the lateral hypothalamus and have dense excitatory projections to all monoaminergic and cholinergic cell groups. Recent studies suggested that monoaminergic

and hypocretin neurons play a different and complementary role in wakefulness maintenance.4 For example, the dual effects of hypocretins on arousal and food intake (orexin from “appetite-stimulating”) suggest, a more important role for hypocretins in Inhibitors,research,lifescience,medical the control of arousal maintenance related to energy homeostasis.8 In the same way, data summarized in the following section suggest, a role for the norepinephrine (NE)-containing neurons of the locus ceruleus (LC) in stress-induced arousal and concomitant anxiety.

Interactions between stress, anxiety, and sleep Anxiety and stress Anxiety is a universal emotion and it, would at. times be maladaptive not. to experience it; it is a necessary part of the response of the organism to a stress, ie, a threat, to the psychological or the physiological integrity Inhibitors,research,lifescience,medical of an individual. Inhibitors,research,lifescience,medical Anxiety may be polarized between a state and a trait. It may supervene at. some point, in the course of life, in which case anxiety is referred as a state. Anxiety trait. is a long-term feature of a person’s experience, present. throughout, life and considered to be a key feature of the avoidant or anxious personality disorder. It. probably reflects a lifetime maladaptive response to stress due to individual differences in biogenetic background, developmental influences, and early life experiences. There is no hard and fast, distinction between anxiety that may be considered as a normal, acceptable accompaniment of stress and the pathological state that warrants classification as a psychiatric Brefeldin_A disorder. In the latter, the nature of the stress is not. always clearly discernible. In other words, pathological anxiety could be characterized by a sense of fear, but. it. is differentiated from fear in that the threat is not immediate or always obvious. Whether normal or pathological, the constituent, features of anxiety always comprise indices of increased arousal or those alertness that, could lead to sleep-wake alterations.

Summary and Conclusions Future applications of contrast ultrasound have expanded the use of microbubbles beyond enhancement of the left ventricular cavity, improvement in the delineation of cardiac structures and systemic Doppler signals, and even myocardial perfusion imaging. As discussed in this review, microbubbles can now be used to define molecular and cellular pathology within the vascular space. The ability to identify inflammation, angiogenic vessels, and early atheroma are only some examples of how this technology can be applied, and are likely to augment the diagnostic utility

of ultrasound not only for cardiac conditions, Inhibitors,research,lifescience,medical but for diseases affecting other organs which can be imaged using ultrasound. Targeted imaging using ultrasound certainly has the potential to enhance the ability to make earlier diagnoses, and to guide therapy. Furthermore, microbubbles may be used for therapeutic purposes, and enhance the delivery of drugs, genes, or other compounds directly

to a site of greatest need. Certainly much more research, validation, and training are needed before these Inhibitors,research,lifescience,medical technologies will be incorporated into clinical Inhibitors,research,lifescience,medical practice – but the future of contrast ultrasound holds great promise and excitement. ​ Fig. 6 Perivascular deposits of fluorescent DNA delivered using microbubbles coupled to plasmid. See text for details. Redrawn from Christiansen et al.40)
Stress-induced cardiomyopathy (also known as takotsubo cardiomyopathy or apical ballooning syndrome) is characterized by acute, reversible and transient left ventricular (LV) systolic dysfunction that resembles acute coronary syndrome but does not show significant stenosis on coronary angiography.1),2) Inhibitors,research,lifescience,medical Emotional and/or physical stressor can be the triggering factor. Excessive release of catecholamines due to stressors has been proposed to be involved in the pathogenesis of stress-induced cardiomyopathy because it causes structural changes of LV and disturbances in Ca2+ homeostasis.3) Inhibitors,research,lifescience,medical The recent body of evidence shows that postmenopausal women (90%) are predominantly affected by this syndrome and that stress-induced cardiomyopathy comprises 0.7-2.5% of cases of myocardial infarction (MI).4-6) Approximately

20% of complications were reported, including cardiogenic shock, heart failure, arrhythmias, intraventricular thrombus formation, LV free wall rupture, and even death.1),3),4) Easy accessibility at the bedside Cilengitide of the hospitalized patient and the ability to use real-time noninvasive hemodynamic evaluation are the distinctive characteristics of echocardiography, particularly in the emergency setting. This review primarily addresses the role of echocardiography and emphasizes its usefulness in the diagnosis and management of this challenging disease. selleck screening library Definition and Diagnosis The criteria for the diagnosis of stress-induced cardiomyopathy have evolved over the years. The most recently available criteria were proposed by the Mayo Clinic in 2008.

This implies that war-related traumatization is not solely attribut able to physical injury, life-threatening events, or the social consequences of displacement or deportation, but that loss of interpersonal trust plays a paramount role as well. Thus, among the many areas that must be addressed when designing therapeutic methods to deal with traumatized individuals, particular emphasis Inhibitors,research,lifescience,medical should be placed on self-processes as a representation of social interactions and the violation/distortion of these self-processes by the experience of a.

traumatic incident. This concept is in strong support of a more Inhibitors,research,lifescience,medical dialectical approach to the treatment of posttraumatic stress disorder (PTSD). Equating self-processes with representations of social interactions implies that distorted interactions, which have been shown to develop in the wake of most traumatic incidents, exert a

dramatic influence on these self-processes. If such is the case, then therapy must deal in priority with interactional experiences. Our treatment approach was originally developed for patients having experienced Inhibitors,research,lifescience,medical a single traumatic event occurring in a civilian setting, Inhibitors,research,lifescience,medical such as an accident or exposure to violence or sexual assault. It was later applied to war traumatization in Bosnia, during the war and in the postwar period. Joint projects were carried out with workers at the University of Sarajevo to study the diagnosis of PTSD, Inhibitors,research,lifescience,medical empirical treatment, and therapeutic processes (for further details, see references 1-7). The social

interaction model Throughout our lives, we develop models based on our experience of the world in which we live and of the other human beings with whom we come into contact. Our expectations about future U0126 ERK experiences and behaviors are largely influenced by these models, which are constantly being revised, as new experiences Anacetrapib add to previous ones to gradually evolve and stabilize into a set of models of reality out of which we somehow “create” our own representations of our selves and of the world. The complexity of these models depends on many factors, including the sophistication of a given individual’s cognitiveprocessing system, as reflected in its selection, memory, and retrieval functions, and probably several other Z-VAD-FMK msds factors as well.

Sleep is entirely disorganized, especially in apnea syndromes. Microarousals due to respiratory efforts may add up to hundreds of episodes during the night. Non-REM sleep is highly fragmented and some patients do not reach SWS. REM sleep is also fragmented. The patient is sleep-deprived and daytime sleepiness

may become extreme. The apneic index, ie, the number of apneas per hour of sleep, has long been used to quantify the Inhibitors,research,lifescience,medical breathing disorder. Treatment of apneic patients has been transformed by the use of continuous positive airway pressure (CPAP) of 5 to 15 cm H20.54 The only disadvantage of such therapy is the constraint to the patient and his or her partner. Apneas are rapidly eradicated and the symptoms of the illness disappear, especially daytime sleepiness. CPAP is also efficient in the upper airway resistance Inhibitors,research,lifescience,medical syndrome, though no other means have been tested extensively to date. Mandibular selleck chemical MEK162 advancement devices may be of value in nonsevere cases of obstructive sleep apnea syndrome. Postural alarm can be used in position-dependent apneics. No specific medications, drugs (eg, ventilation stimulants), or oxygen therapy have been shown to be effective on sleep apneas. In all cases, the patient should be asked to lose weight. promotion surgical treatments55 are Inhibitors,research,lifescience,medical based on the identification of

the site of airway obstruction (nose, soft palate, and/or tongue). The protocols include various forms of reconstruction depending on the needs and the anatomy of the patient. They range from tracheotomy, glossectomy (surgical removal or laser evaporation of a portion of the tongue), radiofrequency shrinkage of Inhibitors,research,lifescience,medical the obstructive tissues of the upper airway (nose, palate, or tongue), or suspension

techniques with sutures of the tongue base, nasal reconstruction, uvulopalatopharyngoplasty, mandibular osteotomy with genioglossus advancement, hyoid myotomy and suspension, and maxillomandibular advancement. Conclusion Excessive daytime sleepiness is a frequent complaint in industrialized societies, and has a significant impact on work and family life. Physicians have several Inhibitors,research,lifescience,medical methods to affirm the existence of daytime somnolence and diagnose between the numerous causes of hypersomnia. They also have access to large array of medications and therapeutic strategies, which are constantly increasing in quantity and quality. Notes Part of the work was supported by Technical Service Agreement T7/83/2 from the World Health Organization and Drug_discovery the Région Rhône-Alpes (thématiques prioritaires santé, 2000-2002, grant No. 01 018675 01). Dr Jérôme Vix, from the Polyclinique de Rïllïeux (France), is acknowledged for his helpful comments on the manuscript.
Humans, like many other mammals, are awake through the daytime hours and sleep during the night. In some people, this normal sleep-wake rhythm, so taken for granted by most of us, can become chronically impaired, leading to a group of disorders called circadian rhythm sleep disorders (CRSDs).

22 The BRAC was considered to be clearly expressed clinically early after birth and then, within weeks or months, to become less evident during daytime and mostly seen during sleep, with the alternation between rapid eye movement (REM) and nonREM sleep. Apart from sleep, several physiological functions have an ultradian periodicity #JQ1 manufacturer randurls[1|1|,|CHEM1|]# of approximately 90 min In man. The period of the BRAC might be species-specific since, for example, Inhibitors,research,lifescience,medical luteinizing hormone (LH) blood concentrations oscillate with periods of 20 minutes to 2 hours in different animal

species.23 In mice, there Is an ultradian rhythm for avoidance behavior that Is of 9 min in young mice, near the Inhibitors,research,lifescience,medical period of REM/nonREM sleep, while in adult mice it is of 20 mln.24 In humans, a mean period of the BRAC of

around 90 mln was found In endocrine studies or In studies on dreaming and sleep.25 For example, the secretory pulses of prolactin Into blood In humans have a mean period of 95 mln and are closely associated with the secretory pulses of LH.26 There Is an ultradian rhythm of nasal permeability, with a shift between nostrils that Inhibitors,research,lifescience,medical correlates with changes In controlateral electroencephalogram (EEG) wave amplitude.27 The BRAC has the hypothetical role of coordinating bodily functions, hormones, sleep phases, and perceptual and cognitive capacities. This hypothesis raises Inhibitors,research,lifescience,medical several questions, few of which have yet been solved. First, there have been subsequent negative findings, for example regarding the absence of ultradian rhythms in the cognitive task

of the sentence -verification test.28 Also, many variables show more than one Inhibitors,research,lifescience,medical ultradian period and have superimposed circadian components. Finally, the existence of groups of neurons that govern ultradian periodicities has been demonstrated for gonadotrophin-releasing hormone (GnRH, also called LHRH, for luteizining hormone-releasing hormone) in the preoptic area of the hypothalamus and for the sleep architecture, but not for other rhythms; selleckchem moreover, a few authors have suggested that evidence for the existence of BRAC might Brefeldin_A result from artifacts in protocols and calculations.28 Ultradian clocks have not yet been as clearly delineated, as is the case for the circadian clock in the SCN Reciprocal influences and conpling between biological clocks Many biological functions show more than one rhythm and have superimposed ultradian and circadian components. Moreover, many tissues express endogenous rhythms.

e., Val 66 Met) was performed using the TaqMan 5′ exonuclease assay C_11592758_10 from Applied Biosystems™ (Foster City, CA). In order to ensure the correct identification of genotypes, 10% of all samples were randomly reanalyzed obtaining a 100% of concordance. As we recently reported (Velazquez-Aragón et al. 2012), a panel of 10 ancestry informative markers that can distinguish between Amerindian and European ancestry in Mexican populations (δ > 0.44) was genotyped in a random group of 200 samples. The STRUCTURE Inhibitors,research,lifescience,medical software was used to test stratification within samples. An admixture model was employed using the following parameters:

1 × 106 of burn-in period, 1 × 106 repetitions, and K = 2. These markers have been validated in previous case–control studies in the Mexican population. Values of α > 1 obtained indicated that there was

no population substructure in Inhibitors,research,lifescience,medical our sample. For the 44 bp SCL64 polymorphism, analyses were initially performed including the three genotypes. A post-hoc analysis combined genotypes L/L and S/L in order to increase statistical power. In the case of BDNF, analyses were performed collapsing Met/Met and Met/Val individuals in a single category (i.e., Met +), as Met homozygous individuals were infrequent (i.e., 2% of the whole sample). Statistical analysis The selection of samples for this study was obtained from the epidemiological database (stored in the SAS/STAT Inhibitors,research,lifescience,medical format), which contains Inhibitors,research,lifescience,medical the clinical algorithms for depression and noncases as described above. For continuous variables (e.g., age) an F statistic was employed as test for statistical significance in a one-way ANOVA, given otherwise comparison of categorical variables (e.g., gender or genotypes) were made using χ2 tests. Hardy–Weinberg equilibrium (HWE) was tested with the online test of deviation of HWE program (Rodriguez et al. 2009). A logistic regression analysis was carried out to examine the effects of main covariates and effect modification (i.e., interaction) for depression as the output variable.

The Inhibitors,research,lifescience,medical putative association of genetic variants and environmental adversities were analyzed with a selleck chemicals llc multinomial logistic regression analysis (SPSS v.20, Chicago, IL). Results Table 1 shows the descriptive statistics of the demographic variables analyzed in the sample: cases and controls were similar, with exception of Drug_discovery a slight but statistical significant increment in average age in those affected individuals. Table 1 Comparison of sociodemographic variables and BDNF and SLC6A4 genotype frequencies in cases and controls. Analysis of BDNF and SLC6A4 with MDD Table 2 also shows the observed genotype frequencies for the SLC6A4 promoter VNTR and the BDNF Val66Met polymorphisms in cases and controls; no deviation from HWE was detected in both cases: SLC6A4, χ2 = 0.4, P > 0.05; BDNF, χ2 = 0.3, P > 0.05. Moreover, no significant genotype or allele differences were observed between groups of comparison.

2006; Joseph et al. 2008; Bora et al. 2009; Kurtz and Gerraty 2009) and, to a lesser extent, major depression (Snyder 2013). These endophenotypes may be

more closely related to genetic variation (Gottesman and Gould 2003) and provide a window into specific vulnerabilities that increase the probability of mood disorder evolution. A growing number of studies have evaluated the relationships between candidate genes and cognitive processes or brain volumes in healthy and mood disordered samples (Bigos et al. 2010; Krug et al. 2010; Thimm et al. 2011; Frodl et al. 2012; Radua et al. 2012). For example, Frodl et al. (2012) identified associations of genes important for glucocorticoid Inhibitors,research,lifescience,medical and immune function with hippocampal volume in patients with major depressive disorder. Previous data from our group has found altered anterior cingulate volumes Inhibitors,research,lifescience,medical in individuals with bipolar disorder who carried the BDNF minor allele (Matsuo et al. 2009). A single nucleotide polymorphism (SNP)

rs1006737 in CACNA1C, implicated in bipolar disorder (Ferreira et al. 2008) and other neuropsychiatric disorders (Gargus 2006, 2009), has been found to increase brain volumes, particularly grey matter volumes (Kempton et al. 2009), and impair appropriate functioning of fronto-temporal circuits (Wang et al. 2011) important for emotional processing (Radua et al. 2012). Inhibitors,research,lifescience,medical Similarly, variations in ANK3 and DGKH, also implicated in bipolar Inhibitors,research,lifescience,medical disorder (Baum et al. 2008) and other neuropsychiatric disorders (Weber et al. 2011), have been associated with altered brain structure and function (Hatzimanolis et al. 2012; Linke et al. 2012; Whalley et al. 2012). Taken together, these data support a model where genes important for ongoing neural plasticity and immune system functioning influence cognitive and structural brain endophenotypes representing key nodes of mood disorder vulnerability. The present study evaluated four strong candidate polymorphisms from genes important for neurotransmission and plasticity – ANK3 (rs10994336), BDNF (protein inhibitor rs6265), CACNA1C (rs1006737), and Inhibitors,research,lifescience,medical DGKH (rs1170191). The functionality

of the intronic variants in ANK3, CACNA1C, and DGKH have not been demonstrated. However, it was reported that CACNA1C rs1006737 AA genotype subjects have greater mRNA expression in the dorsolateral prefrontal Dacomitinib cortex than subjects with GG or GA genotypes (Bigos et al. 2010). Additionally, each of these candidate polymorphisms is believed to have functional relevance to neuropsychiatric disorders, including mood disorder: ANK3 is thought to influence the function of voltage-gated sodium channels, BDNF regulates neuronal growth and participates in plasticity of neurons throughout the currently lifespan, CACNA1C is the alpha 1C subunit of the L-type voltage-gated calcium channel, and DGKH participates in the lithium-sensitive phosphatidyl inositol pathway.

CG symptoms cause a great deal of distress and usually interfere with functioning and with the ability to find meaning and purpose in life. Many people with CG have suicidal thinking, sometimes at a level that is of concern. In our work, we have found the Inventory of Complicated

Grief (Prigerson et al, 1995) to be an excellent screening tool. However, there are Inhibitors,research,lifescience,medical currently no formal diagnostic criteria for this condition. Based on data20 and extensive clinical experience during three large NIMII-funded treatment studies, we proposed a criteria set21 (Table I) that was used in the deliberations by the DSM-5 workgroup. However, others have proposed alternatives22 and the DSM workgroup is proposing criteria be selleck products placed in the appendix (at www.DSM5.com) Inhibitors,research,lifescience,medical Additionally, they suggest that a bereavement disorder be considered a form of adjustment disorder, described by the text in Box 2. TABLE I. Proposed criteria for complicated grief.21 Box 2 At least 12 months following the death of a close relative or friend, the individual experiences intense yearning/longing for the deceased, intense sorrow, and emotional pain, or preoccupation with the deceased or the circumstances of the death. The person may also display difficulty Inhibitors,research,lifescience,medical accepting the death, intense anger over the loss, a diminished sense of self, a feeling that life is empty, or difficulty planning

for the future or engaging in activities or relationships. Mourning shows substantial cultural variation; the bereavement reaction must be out of proportion or http://www.selleckchem.com/products/U0126.html inconsistent with cultural or religious norms. The main Inhibitors,research,lifescience,medical differential diagnostic considerations for CG include normal acute grief and major depression, and, if the death

is violent, PTSD. Differential diagnosis can be challenging because symptoms overlap and comorbidity is common with CG, especially among those Inhibitors,research,lifescience,medical who are help-seeking. The difference between CG and normal grief is related to the heightened intensity and longer persistence of acute grief symptoms and to the presence of complicating processes, as described above. One of the indicators of CG is that the family and friends of the sufferer are eager for them to get help. Often it is a family member or friend who finds the therapist or treatment Cilengitide program. This is a good indication that the grief symptoms are lasting longer than expected in the person’s cultural context. The symptoms of CG have some overlap with those of major depression, just as normal grief has some overlap with depression. CG symptoms are strongly centered on the loss. For example guilt is specifically related to letting the deceased down, whereas guilt in depression is pervasive and multifaceted. A grieving person maintains a sense of self-esteem and self-worth, whereas depressed people have lost faith in themselves.

In general, patients who present with synchronous pulmonary and CLM can undergo either simultaneous or staged resections. Among patients who need an extensive liver resection, a staged approach may be preferable.

In other circumstances where the disease is more limited a simultaneous approach can be performed with low morbidity and perioperative mortality (51). When undertaking a staged approach, outcome appears Trichostatin A HDAC inhibitor comparable regardless of whether the lung or liver resection is undertaken first (51). As such, the approach should be individualized. For patients with metachronous metastasis, a longer time interval between the detection of the lung and liver metastasis has been associated with Inhibitors,research,lifescience,medical a better prognosis (46-50). After pulmonary metastasectomy, 50-75% of patients will recur, both with pulmonary as well as other EHD sites (35). Inhibitors,research,lifescience,medical Local or intra-pulmonary recurrence can be due to an incomplete

resection, lymphangitic spread, or “floating” cancer cells (52,53). Despite the relatively high incidence of recurrence, the overall survival associated with pulmonary metastasectomy ranges Inhibitors,research,lifescience,medical from 48-60% (Figure 3) (37,39-50,54). In a meta-analysis incorporating 14 studies and 1684 patients, most of whom underwent a unilateral wedge resection for limited disease(53%), the overall 5-year survival was 48% (54). Of note, 5-year survival Inhibitors,research,lifescience,medical was only 17% among patients with peri-bronchial/hilar lymph nodes and no patient with mediastinal lymphadenopathy survived to 5 years (38). In contrast, patients who had no nodal disease had a 5-year survival of 60%. The authors noted a median survival of 29 months overall; however, among those patients with a disease-free interval of 3 years or more between the primary tumor treatment Inhibitors,research,lifescience,medical and the diagnosis

of the pulmonary metastasis median overall survival was 49 months (45). Figure 3 Disease-free (A) and overall survival (B) after initial pulmonary metastasectomy for CRC lung metastasis. Used with permission: Shah SA, Haddad R, Al-Sukhni W, et al. Surgical resection of hepatic Entinostat and pulmonary metastases from colorectal carcinoma. Journal … Given the relative high incidence of recurrence following pulmonary metastasectomy, there has been interest in repeat pulmonary resection (Table 3). Park et al. reported a 79.3% 5-year survival after selleck chem inhibitor second metastasectomy and a 5-year survival of 77.8% after a third resection (50). Other studies have shown similar results with 5-year survival ranging from 42-61%, suggesting that second and third resection of recurrences are viable options for patients with recurrent disease and can lead to long-term survival in a subset of patients (53,55,56). Table 3 Survival following pulmonary metastasectomy stratified according to the number of resection. Used with permission: Park JS, Kim HK, Choi YS, et al.

5% dextrose peritoneal dialysis solution for 90 minutes. The coliseum technique was used. For gastrointestinal malignancies, mitomycin C (10-12.5 mg/m2) was

used. For mesothelioma and ovarian malignancies, cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) or mitomycin C (10-12.5 mg/m2) were employed. Early postoperative intraperitoneal chemotherapy was postoperatively administered in accordance with previously MEK162 manufacturer defined guidelines (4). Anaesthesia At our institution, the indication for intraoperative RBC transfusion was a hemoglobin concentration <80 g/L and/or signs of anaemia (sinus tachycardia with a heart rate of >100 per minute, a systolic blood pressure Inhibitors,research,lifescience,medical of <100 mmHg, urine output of <30 mL/hr due to ongoing blood loss). To minimise unnecessary blood loss we have focused on maintaining normothermia and optimimizing acid-base balance. In the operating theatre, forced warm air blankets were applied and the head was covered

with a heat reflecting cap. All fluids and blood Inhibitors,research,lifescience,medical products were infused via fluid warming devices. Acidosis was managed by resuscitation and mechanical ventilation. Our response to fluid resuscitation and coagulopathy Inhibitors,research,lifescience,medical in patients expected to require an extensive procedure because of high volume disease has changed since June, 2006. Previously, we followed the standard resuscitation strategy with an emphasis on nearly crystalloid and RBC administration to improve cardiac output and oxygen delivery. Procoagulant factors (FFP,

cryoprecipitate, platelets) were transfused in response to abnormal coagulation laboratory parameters, hypotension unresponsive to crystalloid administration, transfusion >6 units or obvious Inhibitors,research,lifescience,medical microvascular bleeding. Since June 2006, a protocol driven approach has been adopted which involves the early and aggressive administration of procoagulant factors Inhibitors,research,lifescience,medical (particularly FFP) to prevent rather than treat coagulopathy. In particular it was deemed not necessary to wait for laboratory results before initiating administration of procoagulants. Procoagulant factors were organized to be available from the outset of surgery and were given such that the ratio of FFP:RBC administered exceeded Drug_discovery 1:1, even through the early intraoperative period. Moreover, a fluid restriction strategy was pursued to minimize dilutional coagulopathy. The rationale behind this change in strategy was multifactorial. Firstly, recent data from trauma surgery has shown that current resuscitation strategies severely underestimate the degree of coagulopathy during surgery. Secondly, our own experience showed that waiting for laboratory results before administering procoagulant factors often resulted in marked coagulation defects and significant blood loss, which could be reduced with a pre-emptive strategy.