Clinical selleck chemical global index scale (CGI): 61% of the 29 patients with schizophrenia and 68% of the 13 patients with manic-episode were rated as at least “much improved” and none as worse EAR (1997): 15.5 EAR (1999): 13.0 AvE (1997): 6.8 AvE (1999): 6.6 AvE

(total): 7 (range 1–19) 95% BL (in accordance with advice in the Royal college of psychiatrists handbook, 1995) Equipment evaluated as: All, up to date Cukurova University Psychiatry Service, Turkey (H) Zeren T (Zeren et al. 2003) Study: Retrospective chart review of hospital ECT-treated patients at Cukurova University, Inhibitors,research,lifescience,medical Department of psychiatry. University, Dept. of psychiatry. N= 384 ECT-treated patients Date: 1990–2001 Time span: 12 years Diagnoses: 45% psychotic 49% affective 6% other (including postpartum psychoses, dissociative, personality disorders, obsessive compulsive) Gender: 52% women Age, year groups: 5%, <18 92%, 18–64 3%, >64 Inhibitors,research,lifescience,medical Mean age 33.1 years Education: Average no. of education years: Inhibitors,research,lifescience,medical 8.7. 54% of patients undergoing ECT had high school and higher education iP: 14% AvE: 8 Side effects: 53% for unmodified 41% for modified

(memory impairment, muscle pain, headache, confusion, prolonged Inhibitors,research,lifescience,medical seizure, cardiovascular, ECT induced mania/hypomania, bone fracture) Outcome: 82% moderate to marked improvement Unmodified N= 179 (47%) Modified N= 205 (53%) Since 1996 all ECT performed under anesthesia. Until 1996 use of anesthesia judged according to age (<40 years) or medical condition. Device constant current brief pulse Siemens

Placement: all BL (bitemporal) Frequency: 3 times week View it in a separate window *TPR: Inhibitors,research,lifescience,medical treated person rate = persons ECT treated per 10,000 resident population per year. *EAR: ECT administration rate = no. of ECTs administered per 10,000 resident population. *iP: inpatient prevalence = proportion (percent,%) ECT treated among inpatient population. *AvE: average number of ECTs administered per patient (in a session or course). **C-ECT: continuation-ECT. **A-ECT: ambulatory-ECT. Table C5 Asia N= 15. Country Reference id Reference Study Demographics Other data Tryptophan synthase Rates Technical parameters Land (L) Ref. id First autdor (reference) Study design Diagnoses Side effects TRP* Modified/Unmodified Region (R) N Indication Outcome EAR* Anesthesia City (C) Date Gender Conditions iP* Devices Hospital (H) Time span Age Training AvE* Current type Ethnicity Guidelines Electrode placement Legal regulations C-ECT** Dosage Other A-ECT** (Monitoring) Japan (L) 295 Motohashi N (Motohashi et al.

Accurate planning relies on 3D transesophageal echocardiography and coronary CT-scan with multiplanar, 3D, and 4D reconstructions. Shape, size, and location of the defect must precisely be evaluated, as well as relationships between heart structures and chambers and between the heart itself and the thoracic wall. Intra-operative guidance is performed by both 3D echocardiography and fluoroscopy (Figure 5). Mitral leak closure can be accomplished both through a venous transfemoral Inhibitors,research,lifescience,medical transseptal route and by a transapical access.49 Figure 5 Perivalvular Leak Closure with the

Amplatzer AVPIII Device. MITRAL VALVE IMPLANTATION Although repair is currently the leading method to treat mitral valve regurgitation in surgical practice, replacement is associated with a number of potential advantages, particularly suitable for a transcatheter approach: the procedure can be more reproducible; it can be applied to the majority of patients, and may provide more Inhibitors,research,lifescience,medical predictable results. However, mitral valve anatomy brings unique and complex features that make transcatheter valve implantation much more Inhibitors,research,lifescience,medical challenging than in the aortic position. The mitral annulus is asymmetrical, non-tubular, and frequently not calcified, so that the main selleckchem problem for any kind of mitral prosthesis remains anchoring, since radial force would not be effective and could cause serious complications. Left-ventricle outflow tract obstruction

and aortic valve deformation (that could derive from a large and rigid mitral stent) are also major concerns. Inhibitors,research,lifescience,medical Moreover, leaks in the mitral position would be poorly tolerated, both hemodynamically and in terms of hemolysis because of the elevated pressure gradients. Mitral valve implantation is not yet routinely available in the clinical setting, but several devices are currently under development. The CardiAQ (CardiAQ Valve Technologies, Inc., Winchester, MA, USA) prosthesis has been the first to reach human implantation Inhibitors,research,lifescience,medical in 2012, although only one case has been reported so far (Sondergaard L. Transcatheter Mitral

Valve Implantation: CardiAQ, TCT Meeting, Miami 2012). It is transseptally delivered and self-anchoring without the need of radial force. The first patient showed early good implantation and hemodynamic result, but died after 3 days due to multi-organ failure. Autopsy did not reveal any prosthesis issue. The Lutter prosthesis (Tendyne Medical, Inc., Baltimore, Bumetanide MD, US) has been successfully implanted transapically in numerous porcine models. The latest version of the prosthesis is made of a flat ring (atrial fixation system) connected at a 45° angle to the tubular stent that accommodates a 28-mm trileaflet bovine pericardial valve; between the base of the stent and the apex, neo-chordae act as ventricular fixation system. A waterproof membrane is sutured in the atrial ring and over the ventricular component to guarantee sealing, minimize paravalvular leakage, and allow easier repositioning.

Mean doses were as follows: learn more olanzapine 13.5 mg/d, risperidone 5.4 mg/d, and haloperidol 12.4 mg/d. After 6 months of treatment, improvement in EuroQol-VAS scores was significantly greater in olanzapine and risperidone-treated patients than in those receiving haloperidol. Gureje et al25 conducted a multicenter, 30-week, doubleblind study comparing the efficacy, safety, use of health care resources, level of functioning, and quality of life between olanzapine and risperidone. Sixty-five patients, either inpatients or outpatients, with a diagnosis of schizophrenia or schizophreniform

disorder (DSM-IV criteria42) and scores on the Brief Psychiatric Rating Scale (BPRS) greater than 36 were randomized to receive Inhibitors,research,lifescience,medical olanzapine 10 to 20 mg/day (n=32) or risperidone 4 to 8 mg/day (n=33). Quality of life was assessed using the QLS35 and

the SF-36.45 A total of 29 patients (17 in the olanzapine group and 12 in the risperidone group) completed the study At the end of the 30 weeks, olanzapinetreated patients had statistically significant greater Inhibitors,research,lifescience,medical improvement compared with the risperidone-treated patients in the QLS intrapsychic foundation subscale and in the SF-36 Role Emotional subscale. The olanzapinetreated group reported statistically significant improvement from baseline to end point in QLS total score, in all QLS subscales except the instrumental role, and in all SF36 scales but the role physical. Inhibitors,research,lifescience,medical For the risperidone-treated group statistically significant improvement was only achieved for the SF-36 bodily pain scale. Ritchie et al26 compared the impact on quality of life of a switch from conventional antipsychotics to risperidone or olanzapine in 66 elderly patients with schizophrenia Inhibitors,research,lifescience,medical (mean age 69.6 years). Quality of life was measured using the World Health Organization Quality of Life [Brief] scale (WHOQOL-BREF).49 Olanzapine-treated patients significantly improved from baseline in the WHOQOL-BREF physical, psychological, and health satisfaction domains, whereas Inhibitors,research,lifescience,medical risperidone-treated patients did not

show significant improvements in any quality of life domain. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the WHOQOL-BREF. The impact of switching from conventional to novel antipsychotic drugs on quality of life was also studied by Voruganti et al.27 One hundred and fifty schizophrenic Ketanserin or schizoaffective patients (DSM-IV42) considered suitable for a switch, based on inadequate control of symptoms, subjective reports of side effects, or clinicians’ concerns about the risk for adverse effects, were consecutively switched to risperidone (50 patients), olanzapine (50), and quetiapine (50). Patients were followed up for a period between 2 and 6 years. Quality of life was assessed by means of the QLS35 and the Sickness Impact Profile (SIP)modified version.

The red arrows describe couplings between areas that were more strongly connected in MS participants than controls during the working memory … In the detailed analysis of pair-wise correlations it was revealed that MS participants had stronger couplings between the right substantia nigra and the left thalamus (−10 −12 14, P = 0.003). In Figure ​Figure7A,7A, it is shown that both Inhibitors,research,lifescience,medical anterior medial and lateral aspects of the thalamus were more strongly coupled

to the right substantia nigra in MS participants than in controls. The results also showed that the left PPC was more strongly coupled to anterior parts of the left DLPFC (−20 56 36, P = 0.012, Fig. ​Fig.7B),7B), whereas it was more weakly coupled to the right caudate head (14 22 6, P = 0.037, Fig. ​Fig.7C)7C) in MS Inhibitors,research,lifescience,medical participants this website compared to controls. The couplings with different functional connectivity in MS participants and controls are visualized in the schematic diagram of the thalamo-striato-cortical network in Figure ​Figure6.6. The red arrows show that MS participants had stronger couplings within the cerebral

cortex (PPC DLPFC) and within subcortical regions (Substantia nigra Thalamus) compared to controls. The blue arrow in Figure ​Figure77 shows Inhibitors,research,lifescience,medical that MS participants had weaker couplings between the cerebral cortex and striatum (PPC Caudate). Figure 7 Images of regions of interest (ROIs) with different functional connectivity Inhibitors,research,lifescience,medical to the seed regions in MS participants. (A) The image shows stronger functional connectivity between the right substantia nigra and the left thalamus in MS participants compared … Discussion During performance of the complex working memory task, the MS participants showed increased activation in the bilateral PPC. This finding is in line with previous

studies that also found increased bilateral cortical activation in MS patients, especially in regions that are normally activated by the administered task (Chiaravalloti et al. 2005; Sweet et al. 2006; Morgen et al. 2007). Frequent findings of hyperactivation Inhibitors,research,lifescience,medical in MS patients have been interpreted as a compensatory reorganization in order to maintain normal performance (Lenzi et al. 2008; Genova et al. 2009). However, the hypothesis of compensatory brain Cell press networks in MS patients is challenged by an alternative hypothesis proposed by Hillary et al. (2006) and Hillary (2008). They argue that increased brain activation in MS patients is a response to increased cognitive demand, which in turn is associated with poorer performance. This argument is well in line with the neural efficiency hypothesis, discussed by Neubauer and Fink (2009). The results in this study support the latter theory, because the MS participants performed worse than the controls during the complex working memory task, and still showed higher activation in cortical areas when solving the administered task.

In some cases, both mechanisms were suggested to contribute to the

transport of lipids between vesicles [18] and to the transport of lipophilic drugs from oil-in-water emulsions to cells [19] and from plasma proteins to lipid vesicles [20]. In our preceding experimental work, where we have investigated the kinetics of temoporfin transport from donor to acceptor liposomes [13], we found that above a certain concentration (corresponding to a liposome-to-liposome distance of about 200nm for our specific system) the transfer was dominated by collisions; for smaller concentrations transport through diffusion was prevalent. The objective of the present work is to introduce and discuss a detailed kinetic model for the release properties of poorly water-soluble Inhibitors,research,lifescience,medical drug molecules from liposomal nanocarriers. Despite

a large number of experimental studies about the kinetics of lipid and drug transfer between liposomes and other nanocarriers, there is FK228 chemical structure little theoretical work available that addresses the nature of the transfer kinetics. Our theoretical formalism is based on Inhibitors,research,lifescience,medical a detailed distribution function of drug molecules among the individual liposomes. Kinetic rate equations for that distribution function account for Inhibitors,research,lifescience,medical two transport mechanisms: collisions between liposomes and drug diffusion through the aqueous phase. We specify a set of conditions at which our microscopic model produces an apparent first-order kinetics Inhibitors,research,lifescience,medical with simple exponential behavior, as used in previous work [14, 19]. We point out that our kinetic model can be applied to any kind of small

mobile pharmaceutical nanocarrier, including liposomes, micelles [21], colloids [22], and nanoparticles [23]. In the second part of our work, we discuss conditions that lead to deviations from simple exponential behavior. First, for the diffusion mechanism, high drug loading tends to increase the transfer rate. The kinetics remains exponential only if donor and acceptor liposomes are chemically similar. Second, the presence of attractive interactions between drug molecules within the liposomes (which can result in the formation of aggregates [24]) is expected Inhibitors,research,lifescience,medical to slow down the transfer kinetics. We note that not much molecular detail is presently known about how poorly water-soluble drug molecules inside a lipid bilayer interact. However, modeling studies Terminal deoxynucleotidyl transferase of rigid membrane-embedded inclusions such as transmembrane proteins or peptides suggest a general tendency of the host membrane to mediate attractive interactions between inclusions that may lead to the formation of aggregates [25]. These attractive interactions may be driven by elastic deformations of the host membrane [26], by depletion of the flexible lipid chains from the region in between rigid inclusions [27], and by fluctuations via the Casimir effect [28]. Our analysis for the collision mechanism suggests that aggregate formation can give rise to sigmoidal behavior of the transfer kinetics.

In addition, the corticosterone implants to the central nucleus of the amygdala increased levels of CRH expression in the dorsal lateral BNST99 and administration of the type 1 CRH receptors decreased this fear-related response.100 In other tests, pretreatment with the type-1 receptor CRH antagonist ameliorated fear-inducing events, or reactivity to the events,100 (see also refs 101-103 for the role of the Inhibitors,research,lifescience,medical CRH type-1 receptor; and 104, 105 for the role of the type II receptor). Furthermore, Cook demonstrated that the CRH response in the amygdala of sheep to a natural (dog) and unnatural (footshock) adversity is regulated by glucocorticoids.106 Following

acute exposure to the dog, for example, amygdala CRH had a large increase during exposure to the dog and a second peak corresponding to the increase Inhibitors,research,lifescience,medical in Cortisol. Administration of a glucocorticoid receptor

antagonist blocked the second CRH peak in the amygdala without affecting the first peak. There is a body of evidence suggesting that the BNST may be important for unconditioned fear107 and that perhaps CRH plays an important role.83 Lesions of the BNST do not interfere with conditioned fear-related responses, unlike lesions Inhibitors,research,lifescience,medical of regions of the amygdala which interfere with fear-potentiated startle or conditioned freezing.108,109 However, inactivation of the BNST can interfere with unconditioned startle responses109 and with longer-term CRH effects on behavior.109 High chronic plasma levels of corticosterone in adrenally intact rats facilitated CRH-induced startle responses.110 Perhaps what occurs normally Inhibitors,research,lifescience,medical is that the glucocorticoids, by increasing CRH gene expression, increase the likelihood that something will be perceived as a threat, which results in a startle response. Lesions of the BNST also interfere with unconditioned freezing of rats to a fox odor,111 while amygdala lesions do not.11,112 Inhibitors,research,lifescience,medical Corticosterone can potentiate freezing to predator odor,113 (Rosen et al, unpublished

observations). Perhaps the BNST may be selleckchem linked to CRH-facilitated unconditioned adaptive anxiety and to general anxiety associated with drug abuse and to symptoms associated with pathological generalized anxiety disorder.114-116 Depression, anxiety, CRH, cortisol, brain A genetic predisposition for a hyperactive amygdala has long been thought to result in a vulnerability however to exaggerated fear and perhaps anxiety/depression.11,117 There is a substantial number of findings of increased activity in the amygdala of depressive patients.27,44,118 correlating with negative affect in other medication-free dépressives119 and patients suffering from a number of anxiety disorders.2 In addition, a finding in depressive patients, particularly in those with comorbid anxiety, is hypercortisolemia.

However, as only about 10 out of 50 studies assessed the relationship of symptomatic remission to functional outcome and cognition, the hope of the RSWG that the availability of a validated remission measure would stimulate new studies on cognition and functional outcomes has only partly been fulfilled. This also holds true for studies on the association of symptomatic remission with quality of life. It is further Inhibitors,research,lifescience,medical important to know

that none of the 50 studies to date have assessed the influence of differing clinical services or different type of interventions on the proposed remission criteria. Finally, only one study to date has assessed the congruence between RSWG remission and remission as perceived by patients, relatives, and professionals. This is surprising considering the hope of the RSWG was that the development of remission criteria should facilitate the dialogue on treatment expectations among physicians, patients and carers, health care administrators, and policy makers. Inhibitors,research,lifescience,medical The authors hope that the present article supports future research in this area. Footnotes Declaration

of interest: Professor Martin Lambert has Pomalidomide received educational grants from AstraZeneca Inhibitors,research,lifescience,medical and Eli Lilly Company and has received fees as speaker from AstraZeneca, Bristol Myers Squibb, Eli Lilly Company, Janssen Cilag, Pfizer, and Sanofi Aventis. Associate Professor Anne Karow has received educational grants from Bristol Myers Squibb and has received fees as speaker from AstraZeneca, Bristol Myers Squibb, Eli Lilly Company, Janssen Inhibitors,research,lifescience,medical Cilag, Pfizer, undbeck, and Essex Pharma. Professor Stefan

Leucht has received peaker/consultancy/advisory board honoraria from SanofiAventis, BMS, EliLilly, Essex Pharma, AstraZeneca, GlaxoSmithKline, Jans-sen/Johnson and Johnson, Lundbeck and Pfizer. SanofiAventis, and EliLilly supported Inhibitors,research,lifescience,medical research projects by Stefan Leucht. Professor Benno G. Schimmelmann has received educational grants from AstraZeneca and Novartis and has received speaker/consultancy/advisory board honoraria from AstraZeneca, Novartis, Bristol Myers Squibb, Eli Lilly Company, Janssen Cilag and Sanofi Aventis. Prof Dieter Naber has received speaker/consultancy/advisory board secondly honoraria from AstraZeneca, BMS, Janssen-Cilag, Lilly, Lundbeck, Pfizer, Servier, and Wyeth.
The use of medication in the acute and long-term treatment of schizophrenia remains the cornerstone of disease management. This paper will attempt to review and highlight recent developments and current controversies in the pharmacologic treatment of schizophrenia. In that context, we will highlight areas where gaps in our knowledge continue to exist, and discuss the types of research ideally suited to fill these gaps.

The patient must have appropriate expectations of a procedure or intervention with appropriate informed consent. Appropriate outcome measures #http://www.selleckchem.com/products/Adrucil(Fluorouracil).html randurls[1|1|,|CHEM1|]# must also be considered and these should include measures from several domains that will include a range of pain scores (eg, worst pain, average pain, frequency), emotional measures, behavioral scores, and, where appropriate, more specific questions around sexual activity Inhibitors,research,lifescience,medical and end-organ functional disorders (eg, bowel and urinary dysfunction). This translates into

clinical practice that the patient needs to be treated as a whole and as an individual through an integrated care team approach. Subsequent intervention should be decided in the context of the biopsychosocial model. There is no doubt about the importance of evaluating and treating UCPPS patients as individuals using

a team approach with comprehensive assessments, expectations, and explanations to optimize outcome. [Andrew Paul Baranowski, BSc Hons, MBBS, FRCA, MD, FFPMRCA] Inhibitors,research,lifescience,medical Optimizing Clinical Outcome Clinical outcome for patients suffering from UCPPS and physicians managing it will depend on multiple factors that can best be described by the biopsychosocial rather Inhibitors,research,lifescience,medical than a pure biomedical model of disease. These factors include antecedent premorbid conditions, associated medical conditions, various etiologic mechanisms, and multiple pathogenic

pathways leading to very heterogenous clinical phenotypic presentations. A comprehensive assessment of all these factors, including diagnosis of all possible pain generators (Table 3), allowing a phenotypic classification (UPOINT is recommended; Figure 3) is therefore required prior Inhibitors,research,lifescience,medical to intervention (Table 4 and Figure 3). Patient and physician expectations must be realistic and patient-oriented goals of therapy must be mutually agreed upon. These should include a clinical meaningful amelioration of symptoms, improvement Inhibitors,research,lifescience,medical in QoL and activities, and reduction in the level of disability. This will only be accomplished TCL by proper diagnosis and phenotyping (sources of pain, associated conditions, impacting factors) and appropriate therapy (treat all pain sources, all associated conditions, and all impacting factors). A multidisciplinary team approach with comprehensive assessment and individually directed therapy will ultimately optimize outcome. Figure 3 UPOINT domains and associated therapies. CPPS, chronic pelvic pain syndrome; IC, interstitial cystitis; PBS, painful bladder syndrome. Table 3 Pain Generators That May Be Operative in Chronic Pelvic Pain Table 4 The Five Steps of UCPPS Management Main Points Urologic Chronic Pelvic Pain Syndromes (UCPPS) are one of the most difficult conditions to manage in urologic practice.

50 Even with the categorical diagnosis of prediabetes, an individual’s risk for progression to DM2 over 5 years can vary widely, from 100% (for those with HbA1c 6.0%–6.4% and FPG 116–125 mg/dL) to close to zero (for those with HbA1c < 6% and FPG < 110 mg/dL), based on prospective studies in a Japanese population.51 Thus a more precise personalized estimate of absolute risk for developing DM2 than is provided for by the broad categories of impaired fasting glucose, impaired glucose tolerance, and prediabetes is highly desirable. Personalized

medicine has the potential to improve prediction of DM2 risk. Simple clinical Inhibitors,research,lifescience,medical risk factors (age, weight, family history of DM) and simple laboratory measures (glucose, triglyceride) explain about 80% of the variance Inhibitors,research,lifescience,medical in DM incidence.52 Novel clinical/anthropometric risk factors for DM development continue to be reported.53 To date at least 65 genetic variants contributing to DM2 have been identified,18,22 but these account for less than 10% of cases. Initial

studies with a limited number of DNA markers showed only modest incremental value of adding genetic data to clinical information in selleck screening library predicting risk for DM2,21,54,55 thus the potential for genomics to enhance prediction of DM2 risk remains unrealized. While weight or body mass index (BMI) is consistently a strong determinant of metabolic syndrome and DM2, Inhibitors,research,lifescience,medical individuals with the same weight or BMI may have very different risks of DM2. A personalized assessment of the metabolic impact of obesity needs to take into account the distribution Inhibitors,research,lifescience,medical pattern of the excessive adipose tissue. Intra-abdominal visceral and in particular hepatic fat accumulation is associated with insulin resistance and systemic inflammation, with increased risk for metabolic syndrome, DM2, and cardiovascular disease, while excess subcutaneous fat does not impair insulin sensitivity, leading to the concept of metabolically “benign versus malign” obesity.56 A large number of additional novel risk factors (including Inhibitors,research,lifescience,medical FEV1, adiponectin, leptin,

gamma-glutamyltransferase, ferritin, inter-cellular adhesion molecule 1, complement C3, white blood cell count, albumin, activated partial thromboplastin time, coagulation factor VIII, magnesium, hip circumference, and heart rate) are each independently associated with risk for DM2 but add little or nothing to basic clinical Bumetanide prediction models in predicting incident DM2.57 Sex hormone-binding globulin (SHBG), traditionally considered to be a passive transporter protein for sex steroids, may have a more active role in DM causation. Observational studies identified lower levels of SHBG as a risk factor for insulin resistance and incident DM, and in-vitro studies demonstrated G-protein-linked receptor-mediated effects of SHBG on intracellular processes related to insulin resistance.58 Multiple confounding factors (e.g.

Grade 4 toxicity of any kind required consultation with study chair to determine dose reductions and consideration for withdrawal from study. Supportive medications were allowed at the discretion of the investigator including antiemetics, anti-anxiolytics and anti-diarrheals. Statistical analysis The statistical design for this study is based on the primary endpoint of tumor response (RECIST) within the first 18 weeks of

treatment with this regimen. Patients whose tumors showed complete response (CR) or partial response (PR) were classified as a response to treatment. All patients meeting the eligibility criteria who signed a consent form and began treatment were followed for Inhibitors,research,lifescience,medical one year or Inhibitors,research,lifescience,medical until death. The study used a two-stage Simon-Optimal study design permitting early termination for poor results. The design assumed that 0.05 success rate would be considered as unacceptably low and that a success rate of at least 0.2 would be considered promising. The design (with the null hypothesis that the true success rate is at most 5%) had a one-sided significance level of 5% and 85% power to detect a success probability of 20%. The maximum Inhibitors,research,lifescience,medical sample size was thus 39 [with an additional 4 (~10%) patients accrued to protect against ineligiblilities, cancellations, major violations, etc.]. The first stage enrolled

18 patients and required 2 or more objective responses to continue on to the second stage. Accrual was not suspended after the first 18 patients to evaluate for disease progression. The study was designed to be terminated if there were 0 or 1 responses in the first stage. If >1 response was seen, Stage 2 would enroll 21 additional patients. If there were 4 or less responses of the 39 patients then no further

studies would be selleck chemicals recommended. Inhibitors,research,lifescience,medical Primary endpoint was overall response Inhibitors,research,lifescience,medical rate (ORR). Secondary outcomes included overall survival (OS), progression-free survival (PFS) and toxicity. The survival function for OS was estimated using Kaplan-Meier method. Though not planned in the original protocol, subgroup analysis was performed with respect to prior use of EGFR monoclonal TCL antibody (cetuximab and panitumumab) and k-ras mutational status. Comparison of overall survival between those with and without prior EGFR monoclonal antibody use was performed with the log-rank test. The study was approved by the institutional review board at each institution that participated and conducted with adherence to good clinical practices (GCP). Results Demographics The first patient was enrolled in June 2008, with the last patient enrolled in April 2009, for an average enrollment rate of 2.6 patients per month. The patient population was primarily Caucasian (97%) and 55% male (see Table 1). The majority of patients did not have K-ras mutational analysis done. Most patients (72%) were ECOG PS 1. Twenty patients had prior EGFR monoclonal antibody use.