The majority of such patients have a history of serious and usual

The majority of such patients have a history of serious and usually violent offences. Almost all of these patients are detained under the Mental Health Act and are commonly subject to restriction orders [Anderson, 2008]. In these patients, changing to oral antipsychotics is often not a viable option because of a history of poor compliance and insight. If patients with a history of violence related to psychosis are going to achieve discharge it is likely to be on depot medication. Hyperprolactinaemia is a commonly seen adverse effect of antipsychotic medication [Petty, 1999] which is caused by D2 receptor Inhibitors,research,lifescience,medical drug binding [Markianos

et al. 2001]. Because all the available depots are potent D2 blockers, raised prolactin levels can be associated with depression, sexual dysfunction, amenorrhoea, galactorrhoea, breast cancer and osteoporosis [Halbreich et al. 2003; Maguire, 2002]. There is evidence to show that patients are more concerned with the sexual side effects than any other side effects [Finn et al. 1990], which is one of the main reasons why patients Inhibitors,research,lifescience,medical stop taking depot medication. In an adolescent forensic secure hospital we have had clinical experience of reducing prolactin levels and restoring sexual function in two young men with hyperprolactinaemia secondary to depot antipsychotic medication. Case 1 An 18-year-old man with a history of severe unprovoked violence directly Inhibitors,research,lifescience,medical related to

psychosis had made a good clinical response to zuclopenthixol decanoate 500 mg taken fortnightly. Prior to the prescription of depot he had been started on orodispersible olanzapine in a youth offender institute. He refused medication on a frequent basis and following transfer Inhibitors,research,lifescience,medical to hospital was prescribed

a test dose of zuclopenthixol. The dose was Hydroxychloroquine concentration titrated up to 500 mg fortnightly over 3 months. He complained of being unable to ejaculate since being on the depot and had a raised prolactin level of 492 mU/ml (normal range in men is 55.4–276). He had mild gynaecomastia. He experienced a worsening of psychotic symptoms when we attempted Inhibitors,research,lifescience,medical a dose reduction. Because of his poor insight and statements he made about wanting to stop medication we did not consider that a nondepot first would be viable. However, we discussed with him the possibility of prescribing aripiprazole in order to try and restore sexual function and he agreed to try this in addition to the zuclopenthixol decanoate injection. The ariprazole was commenced at a dose of 10 mg. His prolactin levels fell to 182 mU/ml over a period of a month and he stated that he was able to get an erection again and ejaculate. Because he refused to have further blood tests it was not possible to continue to monitor his prolactin level. We excluded other potential causes of hyperprolactinaemia. Case 2 The second case was a 17-year-old man with a psychotic illness and a history of serious violence.

26 Decreased range of neck movement is inconsistent in that some

26 Decreased range of neck movement is inconsistent in that some AT13387 cost studies have found it to be predictive and others have not.15 This is not to say that these factors should not be considered in the clinical assessment of inhibitors patients with WAD, but they should not be used to gauge prognosis. Other factors commonly considered to predict outcome, such as those associated with compensation processes and accident-related factors, are not robust prognostic indicators.27 Similarly, demographic or social factors such as age, income and educational levels

demonstrate inconsistent prognostic capacity.2 and 15 Most prognostic studies of WAD have been phase 1 or exploratory studies, with few confirmatory or validation studies having been conducted.28 Validation studies are important in order

to confirm the prognostic capacity of identified GSK J4 manufacturer factors in a new and independent cohort. A recent study undertook validation of a set of prognostic indicators including initial disability, cold hyperalgesia, age and post-traumatic stress symptoms. The results indicated that the set showed good accuracy (area under the curve 0.89, 95% CI 0.84 to 0.94) in discriminating patients with moderate/severe disability from patients with full recovery or residual milder symptoms at 12 months post-injury.16 These results are clinically useful, as physiotherapists usually aim to broadly identify patients likely to report persistent moderate to severe symptoms. Such a validation study is rare in this area of research and goes some way towards providing greater confidence for the use of these measures in the early assessment of whiplash injury. Based on the results of previous cohort studies, a clinical prediction rule to identify both chronic moderate/severe disability and full recovery at 12 months post-injury was recently developed. The results indicated that an initial Neck Disability

Index score of ≥40%, age ≥35 years, and a score of ≥6 on the hyperarousal subscale of the Posttraumatic Stress Diagnostic Scale29 could predict patients with moderate/severe disability at 12 months with fair sensitivity (43%, Calpain 95% CI 31 to 55), good specificity (94%, 95% CI 89 to 96), and a positive predictive value of 71% (95% CI 55 to 84).30 It is also important to predict patients who will recover well as these patients will likely require less intensive intervention. Initial Neck Disability Index scores of ≤32% and age ≤35 years predicted full recovery at 12 months post-injury, with a positive predictive value of 71%.30 A third medium-risk group could either recover or develop chronic pain and disability (>32% on the Neck Disability Index, score >3 on the hyperarousal subscale). The hyperarousal subscale comprises five items that evaluate the frequency of symptoms including: having trouble falling asleep, feelings of irritability, difficulty concentrating, being overly alert, and being easily startled.

2003) Douglas et al hypothesized that CCT findings may predict

2003). Douglas et al. hypothesized that CCT findings may predict the short-term risk of stroke during a follow-up period of 90 days after a TIA. The impact of CCT findings on the early short-term risk of stroke after a TIA has not been previously investigated. However, data on the use of CCT in patients with a TIA are also lacking. The aims of the present study are to determine the frequency of detection of a new infarct

by noncontrast CCT in patients with a TIA who present to hospital within 48 h of symptom onset, to evaluate the independent Tenofovir nmr predictors of infarct detection, and to investigate the association between the presence of a new infarct and the short-term risk of stroke Inhibitors,research,lifescience,medical during hospitalization. Methods Patients and design During a 36-month period (beginning Inhibitors,research,lifescience,medical November 2007), 1533 consecutive patients (mean age, 75.3 ± 11 years; 54% female; mean National Institutes of Health Stroke Scale [NIHSS] score 1.7 ± 2.9; median, 1; interquartile range, 2–5) who were suffering from a TIA and were admitted to the hospital within 48 h of symptom onset and underwent CCT as a diagnostic evaluation of etiology were enrolled in our prospective study as part of a benchmarking project. Of the 15 participating sites, two were university departments of neurology, eight were departments of neurology at nonuniversity hospitals, and five

Inhibitors,research,lifescience,medical were departments of internal medicine at nonuniversity hospitals. A stroke unit was present in 10 of these hospitals. Inhibitors,research,lifescience,medical All patients provided written informed consents for their inclusion in this prospective study. Patients who met the following criteria were included in this study: patients with a TIA (in accordance with the definition that was put forth by the World Health Organization) with symptom lasting less than Inhibitors,research,lifescience,medical 24 h, patients who were admitted to the hospital within the first 48 h of symptom onset. The exclusion criteria were an admission to hospital after 48 h of symptom onset, a possible seizure, a history of migraine, and age less than 18 years. The documentation and data collection procedures followed a uniform study manual. Baseline

characterizations at admission (Table 1)—gender, age, NIHSS score at admission, duration of symptoms, time to assessment, symptoms of TIA, vascular risk factors, and previous history Metalloexopeptidase of stroke—were documented and analyzed. The evidence of a new infarct that was related to the presenting symptoms was abstracted from CCT findings in patients’ radiology reports. The CT scans were read by neuroradiologists who were not involved in the study. Table 1 Baseline characteristics of patients with TIA and factors associated with evidence of a new infarct1 The CCT was part of the routine diagnostic evaluation of etiology of the stroke-related neurological symptoms in patients presenting with symptoms of cerebrovascular disease including TIA.

4 Remarkably, for each of these genes a majority of studies have

4 Remarkably, for each of these genes a majority of studies have reported significant associations with markers and/or marker combinations (haplotypes). However, the associated markers and haplotypes vary across studies for all three genes. LY2109761 manufacturer Caveats to current claims for susceptibility genes for schizophrenia The confidence in these three claims is, however, limited for the following reasons: The fact that the reported at-risk haplotypes in the different

studies/samples are not overlapping, and do not include a common denominator allele or core haplotype for any of the claimed susceptibility genes. Poor reproducibility of Inhibitors,research,lifescience,medical the identical at-risk haplotype in different samples, although for each of the claimed susceptibility genes the vast majority of published inquiries found alleles and haplotypes. Absence of demonstrated function of any of the extracted at-risk haplotypes. No expressed exonic DNA-sequence variants can explain the reported associations,

Inhibitors,research,lifescience,medical ie, neither of these claimed susceptibility genes contains DNA-sequence variants that might: – result in change of the amino-acid sequence in the expressed protein; – account for any of the reported genetic associations with schizophrenia. The failure Inhibitors,research,lifescience,medical to identify one or more susceptibility variants in any of the claimed susceptibility genes directly influencing the etiology of schizophrenia. Thus, there

is a set of consistencies and inconsistencies which are difficult to understand in combination. What is the meaning of Inhibitors,research,lifescience,medical these finding? Given the variation of associated markers/haplotypes across studies and small relative risks, the reported findings might reflect false-positives. This possibility, however, is very unlikely. For example, let us look at NRG1: The proportion of reports with significant, associations in a 300 kb region around the exon 1 is too high to be due to chance (12 out of 14). In addition, the strong association of the originally identified at-risk haplotypes was independently replicated, Inhibitors,research,lifescience,medical and several subsequent studies did not use this marker combination; furthermore, this lack of association either of original haplotypes occurred in Asian populations, due to its very low frequency, whereas more common variants at the same loci were associated with schizophrenia.5 Taking the findings for all the abovementioned genes together, a general pattern can be recognized: Several genes impact on the manifestation of schizophrenia; causal genes can be excluded; the absence of strong linkages to any locus across all genome-wide linkage scans. All susceptibility genes only contribute by a small or, maximally, moderate effect; the relative risks are small in outbred populations (OR 1.5-2.5). The mode of interaction between genes coding for schizophrenia remains obscure.

The purpose of this work is an update of the pharmacological trea

The purpose of this work is an update of the pharmacological treatment of dystrophinopathic cardiomyopathy combined with personal results. Steroids treatment In 2004, Manzur et al. (10) described the major findings of the Cochrane review regarding the results of five randomized controlled trials of the use of steroids in DMD. These trials presented evidence that use of daily prednisolone (0.75 mg/kg/day) or Inhibitors,research,lifescience,medical deflazacort (DFZ) (0.9 mg/kg/day) is able to increase strength in DMD with slightly different side effect profiles. Deflazacort appears to cause less weight gain

and less bone mass deterioration, but more often it is associated with the development of asymptomatic cataracts. Long-term follow up Inhibitors,research,lifescience,medical of cohorts of patients treated under one or other of these drugs, and continuing the use of steroids beyond the loss of independent ambulation, showed that the increase in muscle strength was mirrored by improvement and possible preservation of cardiac function. The first study examining the effects of deflazacort treatment

on left ventricular cardiac function Inhibitors,research,lifescience,medical in DMD was published in 2003 by the group of D.W. Biggar (11). The study included 33 DMD patients, 21 of them taking DFZ for at least 3 years. The authors found that patients who have received DFZ for ≥ 3 years had a more preserved cardiac function than those who had not received the medication. In fact the prevalence of cardiomyopathy in the treated older patients was 5% compared with 58% in patients not treated. Preservation of cardiac muscle function was invariably associated with a better pulmonary and skeletal muscle function. Few and minor adverse effects were reported. Two years later Markham et al. (12) Inhibitors,research,lifescience,medical published a retrospective cross-sectional study reviewing the echocardiograms of 111 Duchenne patients aged ≤ 21 years, in order to evaluate the effect of the steroid treatment on the natural history of cardiac function in DMD patients. Inhibitors,research,lifescience,medical Forty-eight out of 111 DMD patients had received steroids, prednisone [29] or DFZ [19]. Untreated and

steroids-treated subjects did not differ in age, click here height, weight, body mass index, systolic and diastolic blood pressure or left ventricular mass. The shortening fraction (SF) was used as a marker of left ventricular dysfunction and considered normal if it was greater than 28%. The results Levetiracetam showed that FS was lower in the untreated group than in steroid-treated group (30% ± 7% vs. 36% ± 5%; p < 0.001). Furthermore, in the second decade there was a dramatic increase in the number of boys – mainly those untreated – with demonstrable abnormalities in cardiac function. Although this work did not satisfy the essential causal relationship criterion of temporality – cardiac evaluations were performed after steroid treatment – nevertheless it was the first study that compared the type of steroid and demonstrated the same beneficial effect on cardiac function with both drugs.

In some cases where data are lacking or inadequate, the opinion o

In some cases where data are lacking or inadequate, the opinion of ACIP members or other experts are used to make recommendations. Information about new ACIP recommendations that is published in official letters or in the official immunization reference book usually does not describe in detail the methods used in developing recommendations, but does describe the evidence used to inform these recommendations, such as the results of clinical trials, case–control studies, case series, expert opinion, or cost-effectiveness analyses. After formulation

by the Working Group, the draft recommendations are subjected to further extensive review by ACIP members, staff of the DDC, and members of the Working Group. Working Group or ACIP members may identify a need for additional data, corrections in the data, or modifications in the interpretation of the data, and members may critique Mdm2 inhibitor and challenge the opinions of experts. selleck The Working Group then compiles all of these comments and views in an iterative process and presents options for action to the ACIP for final consideration. While the government is not obligated to implement recommendations made by the ACIP, to date it has never rejected any ACIP recommendation. However, sometimes the recommendation cannot be implemented immediately, due to operational or programmatic considerations. For example,

the ACIP agreed in 1999 that the EPI use the combination DPT-hepatitis Unoprostone B vaccine in place of separate DPT and hepatitis B vaccines. However, due to concerns about the programmatic feasibility of this change, including the high vaccine price and supply issues, since there was only one manufacturer producing the combination

vaccine at that time, the DDC requested that the implementation of the new recommendation be delayed. The switch to the combination vaccine was subsequently implemented nation-wide in 2007, after the vaccine price had been reduced and more manufacturers had entered their DPT-hepatitis B vaccine onto the market. The minutes of each ACIP meeting are distributed to all Committee members, who are allowed to suggest revisions before the minutes are finalized. These minutes are reviewed again at the next ACIP meeting. The meeting minutes are not posted for the public, but individuals and organizations can request them in Libraries writing, if they clearly state the specific reasons for their request. Most requests are from researchers conducting research on related topics, but such requests are rare. If a new vaccine is recommended for introduction, the Department of Disease Control will then prepare a proposal and budget for approval by the MoPH and then by the NHSO, which oversees the national health insurance plan. As shown in Fig. 2, the budget for introduction of the new vaccine must be approved by the Cabinet and finally by the Parliament.

58 Third, the urge to void is a frequently experienced behavioral

58 Third, the urge to void is a frequently experienced behavioral state, and

generally increases with bladder distention in a complex manner. For example, at moderate bladder filling, urge to void appears to be under cognitive control and leads to a fluctuation of the conscious urge sensation. A recent fMRI study found significant brain activity associated with an increased urge to void in the insular cortex, frontal opercula, supplementary motor area, cingulate motor area, right posterior parietal cortex, left prefrontal cortex, and cerebellum.59 Fourth, Inhibitors,research,lifescience,medical anorectal continence is another urge-driven behavior that is under complex cerebral control A recent neuroimaging study showed that Raf inhibitor subjective sensation of discomfort increased during repeated rectal distension was associated with activation in the anterior cingulate gyrus, insula, Inhibitors,research,lifescience,medical thalamus, and

secondary somatosensory cortex. Moreover, voluntary contraction of the anal sphincter in response to anal distention was associated with activation of motor cortex and increased activity in supplementary motor as Inhibitors,research,lifescience,medical well as insular cortex.60 Thus, these neuroimaging studies have in common the involvement of the interoceptive system in the expression of diverse urge-related behaviors. Imagery-based techniques are frequently used to elicit memory of drug-related craving experiences,61 and some have even argued that stress imagery testing procedures may function as provocative tests for stress-induced drug craving.62 Inhibitors,research,lifescience,medical Several brain systems have been implicated in modulating the degree of drug-induced cravings. For example, the degree of drug-related craving by means of administration of presentation of conditioned stimuli has been related to activity in striatum,63 Inhibitors,research,lifescience,medical thalamus,64 anterior cingulate,65 inferior frontal cortex,66,67 and orbitofrontal cortex,68,70 but also with insula,71,72 amygdala,73 and cerebellum.74 For example, when viewing videos that display cocaine-related

stimuli users experience craving, which is associated with increases in amygdala and anterior cingulate cerebral MycoClean Mycoplasma Removal Kit blood flow relative to their responses to a nondrug video.75 Similarly, imagery-induced drug craving has been associated with bilateral activation of amygdala, insula, and anterior cingulate gyrus as well as the nucleus accumbens area.76 In alcohol-dependent individuals, cue-induced craving has been associated with activation in amygdala and hippocampal area as well as the cerebellum,77 but also visual and other limbic areas.78 Smoking-induced craving was associated with increased activation in left inferior frontal gyrus, left ventral anterior cingulate, and bilateral middle frontal gyrus.

A history of PHI among the patients further significantly affecte

A history of PHI among the patients further significantly affected the EBV-host relationship, which was not observed in non-vaccinated PHI patients [31]. Although we followed several of the vaccinated patients for 2–3 years, we cannot make any conclusion concerning the persistent effect of immunisation on EBV DNA load. All analysed patients were introduced on cART soon after ending the vaccine trials. The introduction OSI-906 in vitro of cART affects the EBV host balance via the restoration of the CD4+ positive

cells. This is most likely a strong confounding factor on the effect of immunisation on the EBV DNA load. The immune stimulation caused by rgp160/alum may affect EBV in two ways. It may be either through influence on EBV replication resulting in ON-01910 price infection of more B cells, or EBV infected B lymphocytes may be

stimulated to proliferate through the activation of helper T-cells as a result of a Th2 enhancement by the vaccine. It has been shown that gp160 HIV-vaccination up-regulates immune activation T-cell markers, such as MHC class II and CD38 helper T-cells [32]. In an experimental prophylactic vaccination with gp120 in mice, the Th2-arm was activated [33]. The effects of therapeutic vaccination on T-cells might generate B-cell activation through non-specific immune stimulation in HIV infected individuals, as also shown for patients with autoimmune disease [15] and [32]. Our method detects B cell-associated EBV genome load. The method does not distinguish whether an expansion of EBV load in infected cells was caused by an increased copy-number or if it was caused by an increased number of infected cells. Using the same PCR method

in a study of blood from healthy donors, we have shown that the number of EBV genome copies vary between 1–5 copies per B cell in different B-cell subsets [34]. It is not known if this is also valid in HIV-1 infected patients. EBV-DNA PCR is a useful tool Sodium butyrate for monitoring clinical course of lymphoproliferative disease and for identifying patients at risk for tumours [11] and [35]. Measurement of EBV genome levels is then usually performed in extra-cellular plasma as cell free virus DNA [35] and [36]. However, Stevens et al. [11] concluded that serum may not be an optimal clinical specimen for EBV DNA load-monitoring because it does not consider the Libraries presence of cell-associated virus, and uncontrolled cell lysis may give irreproducible results or overestimation of the DNA load. However, we could not detect any EBV-DNA in plasma from our patients, which might reflect their relatively intact immune status. EBV DNA is rarely if ever detected in plasma from healthy individuals [37]. Cell-free virus DNA is probably only detected when released from dying cells in EBV carrying tumours or when the EBV host balance is significantly disturbed. Free virus may also be derived due to the replication of virus in sites outside blood in hosts with relaxed control of EBV-latency.

Instead, normal age-related changes in gene function may represen

Instead, normal age-related changes in gene function may represent latent vulnerability Ibrutinib factors that are promoted by aging, and that may directly contribute in the disease process (ie, causing or associated with disease) in the context of additional genetic and/or environmental

risk factors, which exacerbate age-dependent trajectories. Conversely, moderating factors that delay age-dependent trajectories may promote resiliency not only against age-related Inhibitors,research,lifescience,medical declines but also against multiple brainrelated disorders. Molecular interaction between depression and aging: the cases of BDNF, SST, and dendritic inhibition An example of a putative interaction between age and disease is provided by the investigation of BDNF and BDNF-dependent genes. BDNF is a signaling neuropeptide that is critical during development Inhibitors,research,lifescience,medical and adulthood, specifically in maintaining plasticity and proper functioning of many targeted neuronal cells. Reduced BDNF levels and/or

functions have been implicated in multiple brain-related disorders, including major depression,10,13,14 bipolar depression, schizophrenia, Huntington’s disease, and Alzheimer’s disease,9-16 Interestingly, Inhibitors,research,lifescience,medical BDNF is also downregulated with increasing age. A normal non-psychiatric control subject may lose as much as 60% of BDNF expression between the ages of 20 and 60 years.7,17 We have reported evidence of decreased BDNF levels and/or signaling in the amygdala and anterior cingulate cortex of subjects affected with depression compared

to controls.10,14,62 We have also reported reduced expression of SST, cortistatin (CORT), and neuropeptide Y (NPY) in the same cohorts. SST, CORT, and NPY are neuropeptides that Inhibitors,research,lifescience,medical are expressed in subtypes of γ-aminobutyric acid (GABA) interneurons, which specifically target Inhibitors,research,lifescience,medical the dendrites of pyramidal neurons (Figure 3a). SST, CORT, and NPY expressions are dependent on BDNF signaling, as demonstrated by reduced levels in mice with genetically-induced reduction in BDNF functions.14,62,-63 Together, these findings have Endonuclease suggested the presence of a depression-related pathogenic mechanism linking reduced BDNF function to reduced markers of GABA interneurons that provide dendritic inhibition. Figure 3. Dendritic inhibition, a biological module at the intersection of age and psychiatric disorders. A) Excitatory pyramidal neurons (PYR) are regulated by different types of inhibitory γ-aminobutyric acid (GABA) neurons. Somatostatin (SST)-, neuropeptide … Given that not all elderly subjects develop depression, additional factors must be at play. Indeed, the cross-sectional slope of decrease in BDNF expression in subjects with depression appears to parallel that of control subjects, but at a lower level, demonstrating reduced expression at most ages (Figure 3b).

6% alive at one year in the RT (+) group versus 37 5% in the RT (

6% alive at one year in the RT (+) group versus 37.5% in the RT (-) group (P=0.15). Median OS was 12.5 versus 9.1 months for the RT (+) group and RT (-) groups, respectively (Figure 2). Figure 1 Progression free survival (months) Figure 2 Overall survival (months) In patients

with good or excellent performance status (ECOG 0-1), subset analysis showed that PFS was 10.5 months compared to 7.6 months for the RT (+) and RT (-) groups, respectively (P=0.7574). The median OS was 12.2 months versus 7.6 months for the RT (+) groups and RT (-) groups, Inhibitors,research,lifescience,medical respectively (P=0.54) in the ECOG 0-1 subset. Discussion The role of combined therapy for LAPC continues to evolve. The goals of radiotherapy in LAPC include improvement in local control and palliation of pain and/or obstructive symptoms. Trials of chemoradiation versus chemotherapy alone in LAPC

have reported mixed findings regarding survival and are summarized in Table 4 (4-6,9,10). In a trial conducted by the Gastrointestinal Tumor Study Inhibitors,research,lifescience,medical Group (5), the effect of GSK1120212 concurrent chemoradiotherapy versus chemotherapy alone in LAPC was evaluated and a benefit in survival from combined modality therapy Inhibitors,research,lifescience,medical was noted. The chemoradiation arm consisted of radiation combined with 5-fluorouracil to a total dose of 54 Gy in 1.8 Gy fractions followed by maintenance streptozocin, mitomycin and 5-fluorouracil (SMF). The chemotherapy-only arm was SMF combination chemotherapy for two years or until progression. In this trial, the one-year OS was 41% in the chemoradiation arm compared to 19% in the chemotherapy-alone arm (P<0.02). Table 4 Randomized trials comparing chemoradiation versus chemotherapy Modern chemotherapy and radiation techniques have been tested in two recent phase III trials evaluating the efficacy Inhibitors,research,lifescience,medical of chemoradiation. In the trial by the Eastern Cooperative Oncology Group (E4201), patients with LAPC were randomly assigned to chemoradiation (50.4 Gy in 28 fractions) with concurrent gemcitabine (600 mg/m2 weekly ×6) followed by 5 cycles of gemcitabine alone (1,000 mg/m2 weekly ×3 every 4 wks) versus

Inhibitors,research,lifescience,medical gemcitabine alone (1,000 mg/m2 weekly ×3 every 4 wks) for 7 cycles. This trial showed that chemoradiation was associated with a slightly improved Liothyronine Sodium survival (11 versus 9.2 months, P=0.044) (4). In a second recent study by Chauffert et al. reported in 2008 (10), chemoradiation was delivered to a total dose of 60 Gy concurrently with cisplatin (20 mg/m2/day, days 1-5 during weeks 1 and 5) and 5-fluorouracil (300 mg/m2/day, days 1-5 for 6 weeks). The chemotherapy-alone arm consisted of gemcitabine (1,000 mg/m2 weekly for 7 weeks). Maintenance gemcitabine (1,000 mg/m2 weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. Overall survival in this trial was shorter in the chemoradiotherapy arm (13.0 vs. 8.6 months, P=0.044) and these patients experienced a higher rate of grade 3-4 toxicity compared with the chemotherapy arm (66% vs. 40% respectively; P=0.0008).