87 ± 72.41% (control group) to (314.23 ± 46.32%, 257.18 ± 26.5%, p < 0.01) respectively. The mRNA expressions of DNMT1, DNMT3a and DNMT3b were down-regulated FG-4592 mouse after ADO alone or combination treatment with HCY. The mRNA expressions of lncRNA-MEG3, P53, caspase-3, caspase-9, cytochrome

C were up-regulated and MDM-2 were down-regulated after ADO alone or combination treatment with HCY. Conclusion: ADO alone or combination treatment with HCY can suppress DNMTs and decreased cellular methylation metabolism. The effects of demethylation may activate lncRNA MEG3 gene, P53 pathway and the mitochondrial pathway and at last led to cell apoptosis. Key Word(s): 1. adenosine; 2. homocysteine; 3. methylation; 4. hepatocellular carcinoma; 5. apoptosis Presenting Author: I-CHEN WU Additional Authors: MING TSANG WU Corresponding Author: I-CHEN WU Affiliations: Kaohsiung Medical University Hosp Objective: This study aims to identify the novel and potential upregulated genes related to secretionary or membranous proteins for the clinical diagnosis and staging of esophageal squamous cell carcinoma (ESCC). Methods: By combining microarray-based screening, which contained at least 25,000 DNA oligonucleotide probes, of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and

17 human ESCC specimens, we further confirmed the potential candidate

genes by tissue arrays in 243 cancer tissues and 126 LY2157299 manufacturer normal tissues of esophagus from Taiwan, Korea, and USA and by ELISA in 78 serum specimens of ESCC patients from Taiwan. Results: Four candidate genes, including ATP1A1, SPINT2, CMTM8, and AGR2, were chosen by microarray-based screening of 17 paired tissues from 17 ESCC patients. Only ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) passed validation by RT-PCR and IHC staining in ESCC tissue specimens. check details We found positive ATP1A1 immunostaining in 207 (85%) of the 243 cancer tissues and 88 (70%) of the 126 normal tissues. After adjustment for age and sex, ATP1A1 overexpression had a 3.2-fold (95% CI = 1.8–5.6) to be likely in cancer tissues than in normal tissues. Using the median level of 1,465.0 pg/mL of serum ATP1A1 protein expression as the cut-off point, we found that patients with stage III-IV had a 2.91-fold (1.12–7.36) likely to have high serum ATP1A1 levels than those with stage I-II after adjustment for age and sex. Conclusion: ATP1A1 overexpression may be a potential noninvasive marker of the clinical diagnosis and staging for ESCC patients. Key Word(s): 1. ATPase Na+/K+ transporting alpha 1 polypeptide; 2. microarray-based screening; 3. N-nitrosomethylbenzylamine; 4. arecoline; 5. F344; 6.

For biomarker discovery, the latter was chosen as a control group because the risk of postprocedural pancreatitis or cholangitis ethically bans ERC from application in healthy subjects. However, as the control group consists of patients with choledocholithiasis, proteomic analysis may reflect the difference between a relatively normal PLX4032 mw biliary tree and liver, and an inflamed, cholestatic liver, which can be expected in patients with PSC and patients with a dominant stenosis due to CC. The PSC/CC model was able to distinguish CC and PSC from nonmalignant lesions with an AUC of 0.93 (P = 0.0001), a sensitivity of 93%, and a specificity of

86% as validated in an independent cohort. These findings are of clinical significance,

as in patients with suspected CC or PSC endoscopic procedures will be performed and thus bile becomes accessible. Furthermore, even in the presence of large masses suspicious of CC, a definite diagnosis often cannot be made. The surveillance of patients with PSC is of crucial importance, as those patients have an increased risk to develop CC and curative treatment such as liver transplantation or radical resection can be performed only at an early stage. Therefore, our aim was to distinguish PSC from CC in a second model. This model was established using a training Ponatinib mw set consisting of 18 patients with PSC and 16 with CC. Applied to an independent validation set (18 PSC, 25 CC) it showed an AUC of 0.87, a specificity this website of 78%, and a high sensitivity of 84%. Our findings indicate a possible role of proteomic analysis for surveillance in patients with PSC. Nevertheless, PSC-associated CC may be of different origin than sporadic cholangiocarcinoma. Ten patients within the CC group developed CC in addition to PSC. Eight of those patients were identified positive for CC by proteomic analysis. This proteomic model

reaches a high sensitivity compared to single biochemical markers. Direct comparison with the widely used CA 19-9 tumor marker is impossible, because previous studies used different cutoff values in various study populations, leading to enormous range of sensitivity (53%-92%) and specificity (50%-98%).44 Our proposed model may be of clinical relevance in diagnosing CC in patients with PSC especially if supplementary to other diagnostic methods, as a higher accuracy can be reached by a combination of different diagnostic tools.45 All in all, proteomic analysis of bile as a diagnostic tool for surveillance of patients with PSC alone or in combination with other methods may provide an early and reliable diagnosis of CC. In summary, our data indicate a possible role of proteomic analysis of bile to differentiate CC from PSC and benign lesions.

5, Supporting Information Fig. 6C). The levels of 4-HNE or 3-NT were increased ≈1.2-fold

by ablation of Srx and was increased an additional ≈1.5-fold by ethanol feeding in Srx−/− mice (Supporting Information Fig. 6B,D). Given that the damaging effect of Srx ablation was likely attributable to Prx I hyperoxidation, we investigated the role of Prx I in ethanol-induced liver damage by generating Prx I−/− mice (Supporting Information Fig. 4). As expected, immunohistochemical and immunoblot analyses of 4-HNE and 3-NT revealed that the extent of ethanol-induced liver damage was substantially greater in Prx I−/− mice than in Prx I+/+ mice (Fig. 6, Supporting Information Fig. 7B). The levels of 4-HNE or 3-NT were increased ≈1.2-fold by ablation of Prx I and was increased an additional ≈1.2- to Doxorubicin ≈1.5-fold by ethanol feeding in Prx I−/− mice (Supporting Information Fig. 7A, C). We have

shown that chronic ethanol feeding induces Srx expression at both the mRNA and protein levels in the liver of wildtype mice. Chronic exposure of Srx−/− mice to ethanol resulted in the hyperoxidation of a substantial proportion of Prx I and a smaller proportion of Prx III in the liver, whereas hyperoxidized Prx II was not detected. Given that all 2-Cys Selleckchem Tamoxifen Prxs undergo unavoidable hyperoxidation during catalytic function and that the inactivated (hyperoxidized) enzymes

can be reactivated only by the action of Srx, the observed formation of Prx I-SO2 and Prx III-SO2 suggests that, among the four 2-Cys Prxs, Prx I and III participate check details in the reduction of ethanol-induced ROS. The key antioxidant functions of Srx, the guardian of 2-Cys Prxs, and of Prx I were evident from the marked oxidative damage induced by chronic ethanol feeding in the liver of Srx−/− or Prx I−/− mice. The pathways contributing to ethanol-induced ROS production in the liver include the induction of CYP2E1,24-27 inhibition of mitochondrial function,28-30 stimulation of Kupffer cells,31 and activation of NADPH oxidase at the plasma membrane,32 and of xanthine oxidase in the cytosol.33 The generated ROS trigger the dissociation of Nrf2 from Kelch-like ECH-associated protein 1 (Keap1), and the dissociated Nrf2 then translocates to the nucleus, where it associates with other nuclear proteins and binds to the ARE of the Srx gene and activates its transcription (Fig. 7). The important role of Nrf2 in this process was shown by our observation that ethanol-induced up-regulation of Srx expression was greatly attenuated in the liver of Nrf2−/− mice. The expression of Nrf2 itself was previously shown to be increased by ethanol-induced CYP2E1 and to play a key role in prevention of alcohol-induced liver injury.

A recent account of a red fox attack on infant twins in London indicated that even screaming and lunging at the fox was not sufficient to scare it off (Anon, 2010). Rabid carnivores, particularly, act aggressively and this may increase their encounters with humans (Anon, 2008). Arguably, the coyote may be the most directly dangerous carnivore to humans due

to its reasonably large body size (10–16 kg), potential for hybridization with wolves in some part of its range (Curtis et al., 2007; Gehrt & Riley, 2010) and close association with urban areas. Urban coyotes show reduced fear of humans, even biting or acting aggressively towards them (Carrillo et al., 2007; Farrar, 2007; Schmidt & Timm, 2007; Shivik & Fagerstone, 2007). Potential hybridization with wolves may increase the incidence of this type of aggressive interaction. As the human population grows AZD3965 datasheet and urban areas expand, it is likely that a growing number of animal species will come into contact with anthropogenically

altered landscapes; the concomitant reduction in wilderness areas will make this inevitable. The availability of food and shelter resources within these landscapes will also entice species in. Beckmann & Lackey’s (2008) study of black bears is a good example: bear numbers in urban areas of Nevada have increased more than three times the recorded historical baseline, and there has been a 10-fold increase in complaints about urban bears. The bears become fatter on anthropogenic food and breed younger, but mortality is so high that urban areas are sinks, particularly as urban black bears do

check details not appear to be able to recolonize undeveloped areas. Consequently, bears are becoming concentrated around urban areas and rare in undeveloped areas. The pattern of increasing numbers of carnivore species present in towns and cities over recent decades (e.g. coyotes in the US: Gehrt, 2011; bears in the US: Beckmann & Lackey, 2008; and Europe: Quammen, 2003) may mark the future for the coexistence of carnivores with man. Understanding the biology of these animals is therefore going to become more important if we are to make the best of these unfolding circumstances towards the conservation of the carnivores learn more as well as mitigating their potential impacts upon our lives. We predict that on the outskirts of cities, more large species are likely to make use of urban resources (bears, wolves, possibly cougars and bobcats in America and Europe, and hyaenids in Africa and Asia). This may, however, be short-lived as cities become more intensively urban, the urban/wildland interface of suburbs becomes more blurred, and the extent of undeveloped land diminishes. Within cities themselves, if sufficient patches of vegetation remain, carnivores may continue to use urban habitats, as long as they are not outcompeted by established urban exploiters (e.g. cats, dogs) or destroyed through control measures due to disease concerns.

The laboratory profile was predominantly that of anicteric cholestasis but with normal liver synthetic function and platelet count: alanine aminotransferase 40 ± 29 IU/L (normal range [NR] ≥ 40), aspartate aminotransferase 40 ± 23 IU/L (NR ≤ 35), gamma-glutamyltranspeptidase 142 ± 191 IU/L (NR ≤ 40), ALP 188 ± 126 IU/L (NR ≤ 110), bilirubin

12.7 ± 7.6 μmol/L (NR ≤ 22), INR 0.97 ± 0.12 (NR 0.80-1.20), Platelet 259 ± 96 × 109/L (NR 150-400), and immunoglobulin M 3.4 ± 2 g/L (NR 0.4-2.3). Hemoglobin, thyroid-stimulating hormone, or creatinine levels did not identify a metabolic basis for fatigue in any patient reviewed. The average disease duration was 7.2 ± 5.4 years (range, 0-21). At diagnosis, 301 patients (92%) were AMA-positive. At the time of the questionnaire, only 258 patients (79%) remained AMA-positive, as evaluated by AMA-M2 enzyme-linked immunosorbent

assay, in keeping with the reported fall of Obeticholic Acid concentration AMA titers on treatment.27 Baseline histological data were available for 291 patients (89%), with most of the patients (78%) diagnosed at an early stage of fibrosis. None of the patients with PBC included had decompensated liver disease, but 31 patients had a history of esophageal varices. The overwhelming majority of patients (n = 315, 96%) were treated with UDCA. Treatment response data28-30 were available across a total of 261 patients. Of the 327 patients, 323 patients (98.8%) successfully completed selleck compound the PBC-40 in full. Scores for all domains Torin 1 were as follows: Symptoms domain 17.3 ± 4.7 (possible range, 7-3); Itch domain 4.1 ± 3.4 (possible range, 3-15); Fatigue domain 27.4 ± 11.2 (possible range, 11-55); Cognition domain 12.0 ± 5.8 (possible range, 6-30); Social and Emotional (S&E) domains 27.6 ± 11.6 (possible range, 13-65). The distributions of scores of the PBC-40 domains are as shown in Fig. 1. The most frequently seen status was none (54%) for Itch, mild for Symptoms (64%), Cognition (44%), Social and Emotional (72%), and Fatigue (50%). The scores observed in the current study are similar to, albeit numerically lower than, those previously reported from Newcastle,

UK (Table 2). There was as expected inter-domain correlation across the PBC-40 domains (Table 3), with the Fatigue domain scores showing close correlations with Symptoms, Cognition, and Social and Emotional domains score but less correlation with Itch scores. Although each domain of PBC-40 is not equally weighted, the total score similarly correlates strongly with each domain. However, the validity of a total PBC-40 score requires further evaluation. One hundred ninety-six patients completed the questionnaire for the second time, approximately 1 year later. Within the two PBC-40 domains Fatigue and Itch, there were no significant changes in the score reported, P > 0.05; in other words, the score was reproducible over time.

Those with the highest Helicobacter spp. colonisation had a higher level of mucosal fibrosis and atrophy than the others [16]. Helicobacter spp. were detected by PCR in bile samples from six cats in a case-control study designed to investigate the association between the presence of bacteria in the bile and the development of lymphocytic cholangitis in the Netherlands. No buy DMXAA significant differences were found between patient and control animals, suggesting that the presence of Helicobacter spp. and other bacteria is not associated

with this disease [17]. Two studies from the United States explored dog microbiota. Craven et al. [18] reported that Wolinella spp. rather than Helicobacter pp. are the predominant Helicobacteraceae in the oral cavity of dogs, suggesting that the oral cavity of dogs is not a zoonotically important reservoir of NHPH species for humans. Garcia-Mazcorro et al. [19] described quantitative changes in the gastrointestinal microbiota of healthy dogs after administration of a proton pump inhibitor.

Omeprazole-treated animals showed a decrease in gastric Helicobacter spp. and an increase in total bacteria in the duodenum. The genome of Helicobacter bizzozeronii strain CIII-1, isolated from a 45-year-old female patient with severe gastric symptoms, Ibrutinib manufacturer was sequenced and annotated [20]. The draft genome of another H. bizzozeronii strain (CCUG 35545T) was also subsequently sequenced [21]. In-depth comparative analysis revealed that H. bizzozeronii, as well as H. felis, and Helicobacter suis differs from H. pylori by having wider metabolic flexibility and a higher number of methyl-accepting

chemotaxis proteins. The authors proposed that the high metabolic versatility of these gastric Helicobacter species is an important feature explaining the zoonotic nature of gastric NHPH species [22]. Kondadi et al. [21] identified and characterised a novel lipopolysaccharide α2,3-sialyltransferase this website from H. bizzozeronii that showed a preference for N-acetyllactosamine as a substrate. The authors showed that the expression of a terminal 3′sialyl-LacNAc on LPS is a phase-variable characteristic of both human- and canine-derived H. bizzozeronii strains. In contrast to observations in gastric Helicobacter spp., the genome sequence of H. bilis ATCC 43879 revealed the presence of two copies of γ-glutamyltranspeptidase (ggt). Rossi et al. [23] functionally analyzed both of H. bilis ggt paralogues, named bgh1 (H. bilis ggt homologue 1) and bgh2 (H. bilis ggt homologue 2). The authors observed that only Bgh2 was responsible for γGT activity, while Bgh1 showed no activity because of lack of autoprocessing. Charoenlap et al. [24] investigated the central role of alkyl hydroperoxide reductase (AhpC) in the ability of H. cinaedi to survive during oxidative stress and to colonise BALB/c and BALB/c IL-10−/− mice. Two important articles from Carter et al.

Non-pharmacological interventions have long been perceived by patients and providers as beneficial for headaches, and strong evidence supports the useful effects of certain non-pharmacological interventions for migraine and tension-type headache (TTH). The US Headache

Consortium Guidelines for prevention of migraine identified Grade A evidence to support several specific non-pharmacological interventions including relaxation training, thermal biofeedback combined with relaxation training, electromyographic (EMG) biofeedback, and cognitive behavioral therapy (CBT)[1] (labeled as “evidence-based behavioral interventions” for this paper). The combination of preventive drug therapy and evidence-based behavioral therapies was identified as having Grade B evidence for producing added clinical benefit, although data published since these guidelines were issued is likely to change the Navitoclax molecular weight evidence

to Grade A when the guidelines are updated.[2, 3] In addition to evidence-based behavioral interventions, a recent study found that more than 50% of US adults with migraines/severe headaches reported having used complementary and alternative medicine (CAM) techniques, most commonly “mind/body therapies” such as meditation and yoga.[4] Thus, although data most strongly support evidence-based behavioral interventions, it seems that mind/body interventions are used frequently by adults with primary headache disorders. Despite their use, many

unanswered questions remain regarding these non-pharmacological interventions in the treatment of primary headache find more disorders in adults. In 2005, Headache published an entire series of peer-reviewed papers (many cited in this review) that provided in-depth analysis of numerous methodological issues and suggested solutions in behavioral headache research. Given the increased utilization of mind/body therapies and potentially similar underlying mechanisms between evidence-based selleck behavioral interventions and mind/body therapies, the goal of this paper is to identify the most pressing unanswered research questions in the field overall, describe ideal and practical ways to address these questions, and outline steps needed to facilitate these research efforts. We limit this discussion to the use of evidence-based behavioral interventions and mind/body interventions to treat the primary headache disorders of migraine and TTH in adults, as these headaches disorders are most prevalent in the population and the ones to which non-pharmacological interventions are most commonly applied. Other interventions that are sometimes referred to as non-pharmacological interventions, such as acupuncture or the use of herbal or dietary supplements, are beyond the scope of this paper. We conceptualize the differences between evidence-based behavioral interventions and mind/body interventions for headache across two domains, evidence-based and patient utilization.

The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA) expression. The best intervention concentration of Y – 27632 was detected by MTT assay; HSCs apoptosis was tested by Flow Cytometry; the expression of HGF alpha chain was determined by Immunofluorescence; RohA mRNA levels were evaluated by PCR. Protein expressions were evaluated by immunohistochemical staining and Western blot analysis. Results: ① Y-27632 at 10 μ mol/L caused obviously HSCs inhibition (P < 0.01)

compared with other concentration groups. ② The expression of the HGF-α chain showed time-dependent selleck chemicals llc increased manner (P < 0.01). However, there was no statistic difference (P > 0.05) in blank control group and control group. ③ The apoptosis rate increased over time (24 h, 48 h, 72 h) (P < 0.01). The experimental group caused the highest levels (P < 0.01). ④ The expression of RhoA mRNA in experimental group decreased over time (P < 0.01) and caused the lowest levels compared with othergroups (P < 0.01). ⑤ The

expression of RhoA proteins in experimental group decreased over time (P < 0.01) and caused the lowest levels compared with othergroups (P < 0.01). Conclusion: The activation of hepatocyte growth factor promotes the apoptosis of hepatic stellate cell via downregulating Rho pathway. Key Word(s): 1. Selleck Navitoclax hepatocyte factor; 2. RhoA; Presenting

Author: CHEN JIANG Additional Authors: GUO XIAO-ZHONG, LIU XU, XU WEN-DA Corresponding Author: GUO XIAO-ZHONG Affiliations: General Hospital of Shenyang Military Area Command; General Hospital of Shenyang Military Area Command Objective: To determine selleck screening library the safety, feasibility and therapeutic effect of in vitro-expanded autologous bone marrow-derived liver stem cells (BMDLSC) transplantation in hepatic cirrhotic rats treated with carbon – tetrachloride. Methods: Liver cirrhosis rat models were prepared and then divided randomly into three groups, 25 in each group. In rats, we analyzed the effect of different cells infusion in three experimental groups (group A, bone marrow cell infusion + CCl(4); group B, bone marrow – derived liver stem cell infusion + CCl(4); group C, bone marrow stem cell infusion + CCl(4)). Results: We observed significantly increased average serum albumin levels and higher expression of Differentiated liver cells, green fluorescent protein (GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed in group A.

Serum was collected from 545 children, aged 7–9 years (Dutch ethnicity 91.5%). Symptoms of asthma and atopy were assessed by yearly questionnaires. Chi-square tests and logistic regression were used. Results:  We found 9%H. pylori and 0.9% CagA seropositivity. Twelve (5.9%) children with reported wheezing ever were H. pylori positive, compared to 37 (10.9%) of the non-wheezers (p = .05). No significant differences in H. pylori prevalence were found between children with or without allergic rhinitis (8.5% vs 9.5%), atopic dermatitis (8.7% vs 9.2%), and physician-diagnosed asthma (7.1% vs 9.4%). Multivariate analysis showed no significant DNA Synthesis inhibitor associations between H. pylori seropositivity and wheezing (OR 0.52; 95% CI 0.25–1.06), allergic

rhinitis (OR 0.96; 95% CI 0.51–1.81), atopic dermatitis (OR 1.05; 95% CI 0.56–1.98) or physician-diagnosed asthma (OR 0.87; 95% CI 0.37–2.08). Conclusion:  We found a borderline significantly lower H. pylori seropositivity BKM120 research buy in children with wheezing compared to non-wheezers, but no association between H. pylori serum-antibody status and allergic rhinitis, atopic dermatitis, or asthma. “
“Background and aim:  Polymorphisms of Helicobacter pylori cagA and vacA genes do exist and may contribute to differences in H. pylori infection and gastroduodenal diseases among

races in the Malaysian population. This study was conducted to characterize the polymorphisms in H. pylori cagA and vacA in Malaysian population. Methods:  A total of 110 H. pylori isolates were genotyped by PCR and

sequenced for cagA and PCR-RFLP learn more for vacA. Results:  East Asian cagA was predominantly detected (64.5%), whereas vacA s1m1 and s1m2 alleles were detected in 60.9 and 37.3% of strains, respectively. A statistical association between cagA type with patients’ ethnicity (p < .0001) and age group >50 years old (p = .027) was identified. vacA alleles showed significant association with age group >50 years old (p = .017) and increased neutrophil activity in gastric mucosa (p = .028 and p = .016 for moderate and marked activity, respectively). Further identification of vacA polymorphism revealed that 84% of strains from Malays and Indians showed one RFLP pattern (RFLP-1), whereas more than one RFLP patterns (RFLP-2, 3, 4, 5, 6, and 8) were predominantly observed in strains from Chinese (82%) (p < .0001). Increasing severity of gastric inflammation was observed in gastric mucosa infected with strains carrying RFLP-2, 3, 4, 5, and 6 (p = .037). About 86.6% of H. pylori strains with East Asian cagA were vacA RFLP-2, 3, 4, 5, 6, and 8, and 88% of Western cagA strains were vacA RFLP-1 (p < .0001). Chinese and Indians are susceptible to different virulence genotypes of H. pylori, whereas Malays showed a mixed virulence genotypes. Conclusion:  Marked differences in the polymorphisms of cagA and vacA were observed among strains in Malaysian population. This provides a new insight into the pathogenicity of H. pylori in multiracial population.

In addition, those studies that report increased prevalence offer no clear explanation and there is no clear evidence of increased obesity in older individuals with haemophilia [23]. Ageing pwh who are HIV positive may also be at higher risk for IHD because of highly active retroviral therapy (HAART). While it is recognized that non-haemophilic individuals on HAART therapy are at increased risk for myocardial infarction, in the absence of specific data it is not clear whether this risk is shared by pwh http://www.selleckchem.com/products/ly2835219.html [25]. These studies demonstrate that atherosclerosis and IHD can and do occur in haemophilia. It may be that the severe deficiency of factor

VIII or IX may offer relative protection against the final thrombotic insult in the narrowed arterial lumen that often precipitates the more severe manifestations of IHD. If so, then it may be prudent to exercise caution during intensive replacement therapy such as with major surgical

procedures, particularly in elderly subjects and it may be preferable to use measures such as carefully controlled continuous infusion to avoid peaks of coagulation factor activity in this setting. This may be particularly important during replacement therapy in the setting of acute coronary syndrome [26]. Symptomatic ischaemic heart disease appears to be increasing in haemophilia [27] at least in part because of an ageing population. Acute coronary syndromes (ACS) pose a learn more particular challenge because of the need to consider the risk of bleeding when using antithrombotic therapy. Poziotinib research buy There is a paucity of data from which to create guidelines for management of

this situation. Most reports are of single cases. In general, the principle of management of these clinical cases is to correct the clotting factor deficiency by using factor replacement and then treating the patient as closely as possible to standard protocols for ACS. Recently, consensus guidelines have been published for this situation and have made recommendations specific for haemophilia such as avoidance of thrombolytic therapy, the use of bare metal stents for percutaneous coronary intervention and the use of prophylaxis during dual anti-platelet therapy [27]. While such guidelines are likely to be useful to guide treatment of individual patients, it must be recognized that such guidelines are largely based on opinion rather than evidence and it is important that they should be reviewed and updated when more robust evidence emerges. Valvular heart disease is also more prevalent in older populations [28] and it is likely that more cardiac surgery will be performed in older persons with haemophilia. Cardiac bypass has been performed safely in haemophilia [29] but requires careful planning and management. Valve prostheses should be of a material that does not necessitate anticoagulation.