[7] The aim of this study was to compare radio- and pathological changes and test the adjunct efficacy of sorafenib to yttrium-90 radioembolization (Y90) as a bridge to transplantation in HCC. We tested WHO, EASL, RECIST, mRECIST and apparent diffusion coefficient (ADC) values (DWI parameter) as surrogate markers of complete pathological response after randomization to Yttrium-90 Epigenetics inhibitor radioembolization (Y90) with or without Sorafenib. This is a detailed imaging analysis from a prospective, randomized study of Y90 radioembolization ± sorafenib in HCC patients being bridged to orthotopic liver transplant (OLT). Patients were randomized 1:1 to

Y90 alone (group A) or in combination with sorafenib (group B). The trial was approved by the Northwestern University Institutional Review Board (Chicago, IL), compliant with the Health Insurance Portability and Accountability Act, and has

been registered (NCT00846131). Clinical effects (adverse events, tolerability, and dose reductions) of combining Y90 with sorafenib are beyond the scope of this imaging analysis and are being reported in a separate article focused on clinical outcomes. Inclusion criteria for the study included HCC confirmed selleck products by American Association for the Study of Liver Diseases (AASLD) guidelines, Child-Pugh score ≤B8, and candidates for OLT (up to University of California San Francisco [UCSF] criteria).[2] Patients with performance status >2, metastatic disease, tumor-related portal vein thrombosis (PVT), and/or biological or clinical abnormality contraindicating sorafenib or radioembolization were not study candidates. By protocol, patients receiving >2 Y90 treatments were withdrawn from the analysis. Despite being classified as advanced HCC by Barcelona staging (Barcelona Clinic Liver Cancer; BCLC), patients Quisqualic acid with performance status >0, but with imaging findings of BCLC A, were still considered for transplantation. Between February 2009 and October 2012, 23 patients

(group A: N = 12; group B: N = 11) were enrolled in the study (study flow chart; Fig. 1). Two did not receive therapy: One patient from group A did not have confirmed angiographic hypervascularity at angiography (despite meeting diagnostic criteria), with a subsequent biopsy being negative for malignancy, and 1 from group B died before treatment (ruptured HCC). One patient from group A withdrew consent; that patient was treated off-study with Y90, followed by OLT. The 20 remaining patients comprise the intention-to-treat patient sample (group A: N = 10; group B: N = 10). The study was officially closed on February 7, 2013, when the last remaining patient in group A died of cardiac causes while awaiting transplantation.

Pointing out the potential pitfalls of butalbital withdrawal, Loder and Biondi correctly pointed out Fulvestrant chemical structure that in the context of erroneous intake reported by the patient (either under- or overreporting), significant risk occurs. In the case of overreporting, patients can become intoxicated as they are tapered off the medication. In those who underreport, withdrawal seizures can occur. The authors devised a safe formula for phenobarbital loading and subsequent titration, the problems being both the lack of verifiable history of dosage intake and that phenobarbital remains a pregnancy category D medication, albeit an effective one to prevent seizures.[6] Also, if a pregnant woman goes into

medication overuse headache, not only does the clinician have to create a safe wean, but also must have a plan for treatment to get the patient back to episodic migraine, an extremely difficult task during pregnancy. Because of the many deviltries associated with butalbital compounds, including the problems with half-life, habituation, high risk of rebound, and risk of withdrawal seizures if quantities SRT1720 spiral out of control, this medication should not be

prescribed to anyone, much less to a pregnant woman. The authors of this article recognize this, and pragmatically point out that nonetheless it is prescribed; therefore, the potential risk of birth defects needs to be studied. While they have selected a very large case-control cohort, the power of their study suffered from the lack of pregnant women using butalbital. They did find, however, that there appeared to be a risk of congenital heart defects with butalbital use, sufficient to recommend caution in its use by pregnant women, and they recommended the need for future study should this drug continue to be used. It would be ideal if there were no need

Amobarbital for such analysis and future study. Unfortunately, I agree with their pragmatic approach, that evaluating the possible teratogenic properties of butalbital remains useful. An even better outcome would be for the FDA to recommend withdrawal of butalbital compounds from the market, given their danger up to and including lethality, and the absence of strong studies of efficacy or need. “
“Headache is one of the most common problems in children and particularly in adolescents in both the inpatient and outpatient settings. Unique challenges to making a diagnosis include the fact that young children may have difficulty describing and recalling their headache and associated symptoms. Therefore, headache in children is often unrecognized, under diagnosed and under treated. Familiarity with common headache syndromes in children combined with careful history taking from parents, and a thorough examination is crucial to exclude secondary etiologies and making the appropriate diagnosis.

The typical radiological feature is that of multiple liver abscesses but multiple small lesions may be difficult to characterize. Percutaneous aspirates can be diagnostic when they contain “sulphur granules” with gram-positive bacilli. Cultures are positive in some but not all patients. Larger abscesses

can be treated by percutaneous drainage but eradication of the infection usually requires prolonged courses of intravenous penicillin. The evolution of hepatic abscesses caused by actinomycosis is usually more insidious than that associated with pyogenic abscesses. Contributed by “
“The child with a neurodisability is at high risk of gastrointestinal complications, in particular feeding and swallowing difficulties. Children with cerebral palsy have a high rate of feeding difficulties ( > 50%) and in those with quadriplegia this can rise to 85%. Important features selleck chemical from history include length of meal times, recurrent chest infections and choking episodes. Assessing malnutrition can be difficult, but growth charts are available for cerebral palsy and certain other neurodisabilites. Triceps skinfold thickness < 10th centile is suggestive of malnutrition in cerebral palsy.

Examination for nutrition should include limb perfusion and muscle strength, including ability to cough and use accessory muscles of respiration. Gastro-oesophageal reflux should be treated medically before consideration of fundoplication, Tigecycline mouse unless there is significant aspiration due to reflux. With good nutrition medical complications are reduced, with fewer hospital admissions and improved family quality of life. “
“Sullivan et al. generated functional human hepatic endoderm from human induced pluripotent stem cells (iPSCs) with four transcription factors (Oct3/4 [octamer 3/4], Sox2 [sex-determining region these Y box 2], Klf4 [Kruppel-like factor 4], and C-MYC).1 Yet, we also generated human hepatocyte-like cells from human iPSCs according to the methods of Song et al.2 These human hepatocyte-like cells would be useful as research tools for liver diseases. First,

in order to better understand the possibilities of the human hepatocyte-like cells, we investigated changes of the human iPSCs during the process of differentiation induction to the human hepatocyte-like cells. However, we then used human iPSCs while maintaining higher expressions of p21 than p53 in order to avoid tumorigenicity of the human iPSCs and to increase the value of the cells as research tools.3 Second, we compared the expression of alfa-fetoprotein (AFP) and albumin between the p21 knockdown group (p21 small interfering RNA [siRNA] (+)) and the control group (p21 siRNA (−)) by reverse transcription polymerase chain reaction (Fig. 1). As a result, the expression of AFP but not albumin was found in the former in 21 days (Fig. 1).

They also had more chance of

cholecystectomy, whereas normal appendix was often found in case of appendectomy. Overlapping extra-colonic manifestations, e.g. dyspepsia and lower urinary tract symptoms were common. Helicobacter pylori infection and female gender were closely related to the coexisted dyspepsia. Various psychiatric disturbances were also confirmed here. Intestinal transit correlated well with bowel symptoms, e.g. slow in constipation but fast in diarrhea. Diminished cholinergic activity was observed among the C-IBS patients. Various agents including mebeverine, pinaverium, peppermint oil, smectitie and tegarserod did somewhat buy MG-132 improve IBS symptoms. Unfortunately, the IBS knowledge was not well understood among the medical professionals. Conclusions:  IBS is common in Taiwan, its impacts on the https://www.selleckchem.com/products/gdc-0068.html society are similarly observed while female gender often results in severe impacts. Disordered motility and cholinergic nervous system are likely some of its pathogeneses. Current recommended treatments are effectively demonstrated. “
“Steroids improve the outcome in alcoholic hepatitis (AH), but up to 40% of patients fail to

respond adequately. Interleukin-2 (IL-2) exacerbates steroid resistance in vitro. We performed a prospective study to determine if intrinsic steroid sensitivity correlates with response to steroids in individuals with severe AH and if IL-2 receptor blockade can reverse this. Peripheral blood mononuclear cells (PBMCs) were isolated from 20 patients with AH and a Maddrey’s score >32. Patients were treated with oral prednisolone plus full supportive measures. Clinical resistance to oral steroid treatment was defined as a drop in serum bilirubin of <25% within 7 days or death within 6 months. In vitro steroid resistance was measured in PBMC using the dexamethasone suppression of lymphocyte proliferation assay and repeated after the addition of the anti-IL-2 receptor (anti-CD25) monoclonal antibody, basiliximab. Suppression of lymphocyte proliferation

Oxymatrine <60% was considered to indicate steroid resistance. In all, 82% (9/11) of in vitro steroid-resistant patients were dead at 6 months as compared to 21% (2/9) of steroid-sensitive patients (P = 0.03). Similarly, 91% (10/11) of in vitro steroid-resistant patients failed to show a significant fall in bilirubin at day 7 as compared to 44% (4/9) of steroid-sensitive patients (P < 0.05). Basiliximab improved the maximal proliferation count in 91% (10/11) of in vitro steroid-resistant patients (P = 0.003). Conclusion: Clinical outcome of steroid therapy in this patient cohort correlated with in vitro steroid resistance. IL-2 blockade improved in vitro steroid sensitivity. This suggests that intrinsic lack of steroid sensitivity may contribute to poor clinical response to steroids in severe AH. IL-2 receptor blockade represents a possible mechanism to overcome this.

1A). To determine whether Fas may be mediating basal cell death in the absence of β-catenin, we

examined changes in expression of two key receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and the hepatocyte growth factor (HGF) receptor Met, as these signaling pathways are known to prevent Fas-induced liver injury and are also known β-catenin targets.11-14 We found a dramatic reduction in Met and EGFR protein in KO mice (Fig. 1B). Additionally, expression of HGF messenger RNA is up-regulated 9.27-fold in KO mice at baseline (Supporting Table 2). As shown previously, β-catenin is known to complex with Met,15 Trichostatin A which in turn is known to complex with Fas13 in hepatocytes. We also observed a β-catenin/Fas complex via immunoprecipitation studies in WT livers, but not in KO livers (Fig. 1C). It has been shown that β-catenin phosphorylation by HGF/Met at tyrosine (Y) 654 and

670 dissociates it from Met.16 To determine whether mutation of β-catenin tyrosine residues destabilizes the Met/Fas/β-catenin interactions altering susceptibility of hepatoma cells to Fas-mediated apoptosis, we transfected Hepa 1-6 cells with WT, phospho-mimetic Y654/670E RXDX-106 in vitro (glutamic acid), or phospho-null Y654/670F (phenylalanine) β-catenin followed by treatment with Jo-2 antibody. Determination of caspase-3 activity via fluorometric assay measuring cleavage of the caspase-3 peptide substrate DEVD-AFC 12 hours after Jo-2 treatment revealed insignificant differences in apoptosis between three conditions, suggesting that gain or loss of β-catenin from the Met/Fas complex does not alter susceptibility to Fas ligand (Fig. 1D). Next, we challenged WT and KO mice with Jo-2. Insignificant differences in survival between WT and Fludarabine in vivo KO in response to

Jo-2 were evident (Fig. 1E and F). Next, we challenged KO and WT mice with GalN followed 30 minutes later by LPS to activate TNF-α-mediated liver injury.17, 18 As expected, all nine WT mice became lethargic and moribund approximately 6 hours after GalN/LPS administration, but surprisingly, most KO mice (14/15) survived past 6 hours, with some being uncompromised and healthy as late as 12 hours posttreatment (Supporting Table 1). Thus, although stimulation of the TNF-α pathway caused predictable morbidity in WT mice, KO mice showed a significant decrease in morbidity and mortality (Fig. 2A). The KO mice were also refractory to GalN pretreatment followed by intravenous injection of TNF-α, the major mediator of LPS-induced hepatotoxicity (data not shown).19 Livers from WT mice injected with GalN/LPS were harvested when they showed signs of morbidity and KO livers were harvested at comparable and later time points despite lack of any morbidity (Supporting Table 1).

The presence of esophageal and gastric varices was noted and classified according to the Japanese Research Society of Portal Hypertension

(7). During the procedure, 2 gastric biopsy specimens were taken from each patient. One biopsy specimen was taken from the antrum and one from the fundus for histopathological examination. Biopsy specimens were analyzed by the same histopathologist see more during the study period. The gastritis was classified as either chronic active or nonactive. Nonactive gastritis was defined by the presence of mononuclear cell infiltration and active gastritis by the presence of neutrophils and/or erosions. H Pylori infection was reported on the histology. Children with Portal hypertension were subsequently

studied. The underlying liver disease, the duration of evolution of the disease, the medical treatment, the presence of systemic or gastrointestinal symptoms, and the indications for upper https://www.selleckchem.com/products/pembrolizumab.html gastrointestinal endoscopy were recorded for those patients. The patients were divided into 2 groups. Group 1 included 190 patients with Portal hypertension without liver cirrhosis (i.e. Portal Cavernoma,Peri Portal fibrosis due to Schistomaisis and congenital hepatic fibrosis). Group 2 included 60 patients with liver disease progressing toward cirrhosis (infectious hepatitis, Idiopathic cirrhosis, Progressive Familiar Intra hepatic Cholestasis (PFIC), Wilson disease, or other metabolic liver diseases.) The x2 test was used to compare qualitative variables, and the Fisher exact test for comparison between small groups. P < 0.05 was considered significant. The study was approved by Al Nileen University Ethical committee. Results: Among 2000 patients enrolled during the study period, 250 (12.5%) received a diagnosis of Portal hypertension and were therefore included in the study. The median age of the patients at the time of endoscopy was 5 years 9 months (range, 5 months–15 years). The median time between the diagnosis of liver disease and endoscopy was 2 years 3 months (range, 2 months–8 years). Table

1 summarizes the clinical Non-specific serine/threonine protein kinase characteristics of the patients. Portal Hypertensive Gastropathy was found in 150 of 250 patients (60%). Moderate PHG was found in 104 of 250 patients and severe PHG in 41 patients (31 of whom had liver cirrhosis). Esophageal varices were found in 135 of 250 patients (54%) (Grade I, n = 52; grade II, n = 62; and grade III, n = 21). The hemorrhagic aspect of the esophageal mucosa was observed in 21 patients. No patient had gastric varices (8). Gastritis was found in 145 of 250 (58%) patients (antrum, n = 70; fundus, n = 75). No glandular atrophy or intestinal metaplasia was seen in the patients in the study. In the group 2 patients (n = 60), PHG was found in 35 patients with Liver Cirrhosis associated with chronic gastritis (active, n = 25; nonactive, n = 20). Esophageal varices were found in 15 patients.

Other studies looking at patient perception of migraine directionality as a predictor of responsiveness to onabotulinumtoxin treatment have shown similar results.[5, Selleck Stem Cell Compound Library 7, 8] The pathophysiology underlying the difference in these 2 groups is not clear, but it has been suggested that imploding or ocular headache may have an extracranial origin that is mediated by activation of meningeal nerves that infiltrate the periosteum through the calvarial sutures.[4] The best methods to differentiate imploding, ocular, and exploding

headache types in migraine sufferers have not been systematically explored. Clinical observations regarding the difficulty with correct assignment of headache directionality have been discussed in the literature.[6, 10] Clinicians have observed that headache patients often have difficulty consistently MI-503 describing and assigning directionality to their headache pain.[6, 10] Currently, no specific criteria exist for defining headache directionality, nor are there agreed upon descriptors to aid the clinician and patient in assigning

directionality. The purpose of our study was to investigate different methods of determining imploding, exploding, and or ocular headaches in women with migraine, to investigate the concordance between physician assignment and patient self-assignment of pain directionality, to assess interattack and intra-attack variability in headache directionality, and to evaluate the consistency with which patients assigned a direction to their usual headache when queried using different methods. We conducted an institutional review board approved prospective, cross-sectional survey study of 198 consecutive patients seen in an outpatient women’s health practice at our institution from January 2008 to October 2012. Female patients between the ages of 18 and 77 who fulfilled the International Classification of Headache Disorders 2nd edition (ICHD-II) diagnostic criteria for migraine with or without aura[11] were asked to participate in the study. A chief complaint of selleck screening library headache was not required

for participation in the study. Patients with migraine headache were identified through direct questioning or chart review at time of clinic appointment and when patients requested a prescription refill of a migraine specific therapy. If identified through prescription refill request, patients were asked to participate in the study at the time of their next appointment. If no appointment was scheduled, patients were asked to come in to complete a survey. Patients were excluded from the study for headache not fulfilling ICHD-II criteria for migraine, an inability to read English, visual or communication impairment that led to an inability to complete the survey, long-term maintenance opioid therapy for headache or another chronic pain condition, and patient refusal.

Nelson – Advisory Committees or Review Panels: Merck; Grant/Research Support: Abbot, BMS, Beohringer Ingelheim, Gilead, Genentech, Merck, Bayer, Idenix, Vertex, Jansen Pietro Andreone – Advisory Committees or Review Panels: Roche, Janssen-Cilag, Gilead, MSD/Schering-Plough, Abbvie, Boehringer Ingelheim; Grant/Research Support: Roche, Gilead; Speaking and Teaching: Roche, MSD/Schering-Plough, Gilead Massimo Colombo – Advisory Committees or Review Panels: BRISTOL-MEY- ERS-SQUIBB, SCHERING-PLOUGH, ROCHE, GILEAD, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, GILEAD, Janssen Cilag,

Achillion; Grant/ Research Support: BRISTOL-MEYERS-SQUIBB, ROCHE, GILEAD, BRISTOL-MEY-ERS-SQUIBB, Everolimus order ROCHE, GILEAD; Speaking and Teaching: Glaxo Smith-Kline, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH,

ROCHE, NOVARTIS, GILEAD, VERTEX, Glaxo Smith-Kline, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, NOVARTIS, GILEAD, VERTEX, Sanofi Filipe Calinas Roscovitine chemical structure – Advisory Committees or Review Panels: Merck Sharp & Dohme, Roche Pharmaceuticals, Gilead sciences, AbbVie, Janssen; Consulting: Boeh-ringer Ingelheim; Speaking and Teaching: Bristol Myers Squibb, Gilead Sciences, Janssen; Stock Shareholder: Merck Sharpe Antonio Olveira – Speaking and Teaching: Gilead, BMS, MSD Dieter Häussinger – Consulting: Noxxon Pharma; Management Position: Dv^ssel-dorf University Press; Patent Held/Filed: Flicker Diagnostics GbR; Speaking and Teaching: Falk Pharma Simone I. Strasser – Advisory Committees or Review Panels: Janssen, AbbVie, Roche Products Australia, MSD, Bristol-Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Bayer Healthcare, Bristol-Myers Squibb, MSD, Roche Products Australia, Gilead, Janssen Tarik Asselah – Advisory Committees or Review Panels: AbbVie, Boerhinger-Ingelheim, Gilead, BMS, Roche, Janssen Curtis Cooper – Advisory Committees or Review Panels: Vertex, MERCK, Roche; Grant/Research Support: MERCK, Roche; Speaking and Teaching: Roche, MERCK Jerry O. Stern – Employment: Boehringer Ingelheim Wulf O. Boecher

– Employment: Boehringer Ingelheim GmbH George Kukolj – Employment: Boehringer Ingelheim Stella Aslanyan – Employment: Boehringer Ingelheim Pharmaceuticals Inc. Qiqi Deng – Employment: Boehringer Ingelheim Edward Wang – Employment: Boehringer Ingelheim Federico J. Mensa – Employment: Boehringer Ingelheim Atorvastatin The following people have nothing to disclose: Jean Delwaide, Denis Ouzan The purpose of this sub-study was to evaluate the pharmacoki-netics of asunaprevir (A), daclatasvir (D) and raltegravir (RAL), when combined to Peg-interferon/ribavirine (PR), in HIV-HCV co-infected patients receiving a RAL-based antiretroviral therapy. The first twenty patients (pts), previous null responders to PR, who were included in the ANRS HC30 study, participated in this pharmacokinetic sub-study. All pts were on RAL (400mg BID) combined with tenofovir and either emtricitabine (n=18) or abacavir (n=1) or emtricitabine+enfuvirtide (n=1).

Disease outbreaks may be important factors affecting populations of other carnivore species; however, we note that not all authors indicate a breakdown for

disease that would allow comparison – for example, disease and starvation/emaciation are often not distinguished. As a consequence of increased food and water availability in urban habitats, coupled with protection from predators, growth rate, body condition, survival and population densities of carnivores are predicted to be favoured. The presence of abundant, high-energy, non-seasonal food sources in urban areas may have a significant effect on the growth of carnivore species. Yom-Tov (2003) examined MI-503 chemical structure museum specimens collected from Israel over 60 years (from 1945 to 2005), a

time span when human population in the country increased approximately eightfold, resulting in a significant increase in anthropogenic food sources (Yom-Tov, 2003). He recorded that, over this time, species that do not use anthropogenic food (the caracal Caracal caracal and jungle cat Felis chaus) did not significantly change in mass or size; however, wolves, golden jackals Canis aureus and striped hyaenas, which all feed from garbage dumps and make use of livestock carcasses, increased in body mass. The larger species appeared to be more capable https://www.selleckchem.com/products/dabrafenib-gsk2118436.html of exploiting the extra food provided by humans (Yom-Tov, 2003). A similar pattern of size increase in skull measurements was also recorded for badger and red fox populations in Denmark from 1862 to 2000, which again could be related to altered human agriculture and therefore food sources (Yom-Tov, Yom-Tov & Baagøe, 2003). Starvation due to substantial weight loss over winter is a significant cause before of death in skunks,

but urban skunks fare better over winter than their rural counterparts (Rosatte et al., 2010). Similarly, urban raccoons exhibit better physical condition than rural ones, possibly due to anthropogenic food (Rosatte, Power & Macinnes, 1991). Black bears in urbanized Nevada average 30% heavier than bears in rural areas due to a diet heavily supplemented by garbage (Beckmann & Lackey, 2008). Urban kit foxes demonstrate greater body mass compared with non-urban individuals (especially for juveniles) and also demonstrate different haematological characteristics (Cypher, 2010). Urban Eurasian badgers can be heavier than nearby rural badgers, presumably due to the availability of anthropogenic food (Roper 2010 and references therein). More research in this area is needed. Increased survivorship has been recorded for a number of urban carnivore species ( Table 1). Opossums are recognized as bin-raiders par excellence (Clark, 1994), and their reliance on anthropogenic sources of food is such that, in areas where one would expect their range to have been limited by the winter cold and lack of natural food, they are, in fact, well-established (Kanda, 2005).

A standard neuropsychological ATM signaling pathway battery was administered. Switching scores tended to be lower in patients. Patients persisted in selecting risky decks throughout the IGT, whereas controls behaved normally. Performance was correlated with hypoxaemia. Brain regions underlying decision making may be affected by OSA-related hypoxaemia. “
“Although alcohol dependency is a burden to society, data on cognitive performance in therapy-resistant patients after multiple withdrawals are poor. In this study, 22 patients without reported

cognitive deficits and 20 control subjects performed extensive cognitive testing and a motor task assessing short-term memory. Patients displayed subtle deficits (mainly in executive function), while memory functions were relatively unimpaired. Our results suggest that subtle

frontal-executive deficits may contribute to a poor prognosis, but could be missed by routine clinical tests. Alcohol dependency is a major burden on society and a devastating disease for many affected individuals. Despite various therapeutic Palbociclib mw approaches, a proportion of patients do not respond to therapy and suffer relapses shortly after hospitalized detoxification and/or withdrawal. While evidence indicates that mild-to-moderate alcohol consumption has neuroprotective effects on cognitive function (Stampfer, Kang, Chen, Cherry, & Grodstein, 2005), excessive drinking has been linked with structural brain damage and deterioration of cognitive performance (Green et al., 2010). The frontal lobes, cerebellum and limbic system appear more vulnerable to the toxic effects of alcohol than other brain areas (Oscar-Berman & Marinkovic, 2007). In particular, several animal studies examining recurrent withdrawals have demonstrated frontal lobe damage due to glutamate-related excitotoxicity (De Witte, Pinto, Ansseau, & Verbanck, 2003; Loeber et al., 2010;

Stephens & Duka, Fludarabine concentration 2008). Unfortunately, studies investigating the neuropsychological sequelae of multiple withdrawals in humans are scarce and provide inconclusive results (Duka, Townshend, Collier, & Stephens, 2003; Loeber et al., 2009, 2010). Furthermore, no studies have examined severely affected individuals who have experienced at least five relapses. We hypothesized that such therapy-resistant patients would suffer from subtle cognitive deficits, especially in frontal-executive functions. A total of 22 inpatients and 20 healthy control subjects were recruited. All subjects gave informed consent, and the study was approved by the local ethics committee. All patients were diagnosed by a senior psychiatrist as being alcohol-dependent according to the criteria of the International Classification of Diseases (ICD) 10 (F10.2), and were clinically examined by an experienced neurologist. Additional criteria included a history of more than 5 years of drinking, and to have experienced at least five withdrawals in the last 5 years.