Ntcp has a high capacity for transporting T- and G-conjugated bil

Ntcp has a high capacity for transporting T- and G-conjugated bile acids,16, 17 whereas hydrophobic bile acids are thought to pass the cell membrane by passive diffusion.18, 19 Oatp1a1, Oatp1a4, and Oatp1b2 are all able to transport in vitro both conjugated and unconjugated BAs.16 In Oatp1b2-null mice, the hepatic expression MG-132 in vitro of Oatp1a1 remains unchanged, whereas that of

Ntcp, Oatp1a4, and Oatp2b1 tends to be higher (Fig. 5), similar to previous studies.6, 20 Thus, the marked accumulation of unconjugated BAs in the plasma of Oatp1b2-null mice is unlikely due to secondary changes in other BA transporters. Decrease of BA-conjugating enzymes could also contribute to the observed elevation of serum-unconjugated BAs. However, the possibility of decreased activity of conjugating enzymes is very low, because there are no significant differences in either mRNA expression of bile acid–coenzyme A ligase and bile acid coenzyme A:amino acid:N-acyltransferase

(Supporting Information Fig. 1) or the concentrations of conjugated and unconjugated BAs in livers of WT and Oatp1b2-null mice. The concentration of total serum BAs SB203580 order is approximately seven-fold higher in Oatp1b2-null mice than in WT mice, which is due to the marked accumulation (10- to 45-fold) of αMCA, βMCA, CA, HDCA, and UDCA in plasma of Oatp1b2-null mice. However, absence of the Oatp1b2 transporter does not increase the plasma concentration of conjugated bile acids, except for T-DCA. This indicates that Oatp1b2 is essential for the hepatic uptake of unconjugated hydrophilic bile acids. Recently, Xiang et al.21 reported that humans carrying low-activity OATP1B1 polymorphisms have higher blood levels of BAs. Therefore, concentrations of BAs in 12-month-old male Oatp1b2-null, heterozygous, and WT mice were Rolziracetam quantified. The 12-month-old Oatp1b2-heterozygous mice have blood levels of α-MCA, β-MCA, and CA that are intermediate between WT and Oatp1b2-null mice (Supporting Information Fig. 2). The clear gene-dosage effects of

Oatp1b2 on blood levels of BAs is consistent with the many changes in the pharmacokinetics of drugs and blood levels of endogenous molecules found in humans with low-activity OATP1B1 polymorphisms.22-24 Surprisingly, the increase in plasma concentrations of BAs in Oatp1b2-null mice is not reflected by decreases in hepatic concentrations of BAs. Interestingly, in livers of Oatp1b2-null mice, the mRNA expression of the basolateral efflux transporters, Mrp4 and Ost-α, is 40% and 50% lower, respectively, which might help to retain the BAs in the liver. The biliary excretion of BAs by Oatp1b2-null mice is about the same as in WT mice, except for less αMCA and DCA in the null mice. In Oatp1b2-null mice, there are no changes in the mRNA expression of canalicular efflux transporters, which are responsible for maintaining bile flow and the biliary excretion of BAs.

There will be a great need for well-designed, prospective, multi-

There will be a great need for well-designed, prospective, multi-centred studies that look closely at outcomes, quality of life and cost. Of course with any new product there

must remain an ongoing scrutiny to look for any potential safety issues with these agents. Long-acting factor concentrates represent a major advance in the management of haemophilia. And yet these molecules are likely to be only stepping stones, given the future potential of manufactured products with even longer half-lives, of these products being partnered with therapies such as tissue factor pathway inhibitors (TFPI), and of subcutaneous or even oral delivery of such products. In addition to this, gene therapy is PARP inhibitor becoming a closer reality. As such, the next 10–20 years are likely to bring a plethora of activity in the area of prophylaxis in haemophilia and hopefully will further improve the lives of people with haemophilia. I am grateful to the following people who reviewed this paper and

provided some helpful feedback: Len Valentino and Bruce Ewenstein (Baxter); Prasad Mathew (Bayer); Glenn Pierce (Biogen); Debbie Bensen-Kennedy and Henry Mead (CSL Behring); and Karin Knobe and Stephanie Seremetis SB525334 solubility dmso (Novo Nordisk). M. Carcao has received honoraria/speaker fees and grant support from Bayer, Baxter, Biogen, CSL Behring, Novo Nordisk, Octapharma and Pfizer. He has also participated in industry sponsored research studies on long acting factor concentrates from Bayer, Biogen and Novo Nordisk. “
“Summary.  Haemostasis management in people with haemophilia can present a range of challenges to physicians. Specific challenges that may be encountered PAK5 relate to regimens for immune tolerance induction, use of central venous access devices, optimizing care of paediatric patients with inhibitors

and improving outcomes in acquired haemophilia. There are also challenges related to performing surgery, and the establishment of specialist centres is valuable with regard to this. These challenges are considered in the light of available data, and with perspectives gained from the experience of experts treating patients around the world. Sharing this knowledge may help to improve patient management. “
“The objective of this study was to teach a small group of Chinese physiatrists and physiotherapists to: (i) become trainers and leaders in haemophilia physiotherapy (PT) care in China and (ii) to acquire rapid proficiency in using the reliable and validated Hemophilia Joint Health Score (HJHS) for evaluating musculoskeletal health in boys with haemophilia. Two experienced Canadian physiotherapists and co-developers of the HJHS moderated a 4-day PT training workshop with six Chinese participants. Emphasis was placed on instruction and practice in administering the HJHS. Practical sessions with haemophilia patients were interchanged with theory (power point presentations) and interactive question and answer periods.

pylori

infection Gastric biopsies were collected by endo

pylori

infection. Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal click here pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α. “
“Helicobacter pylori dupA can be divided into

two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5′ region (presence; long-type and absence; short-type), which has not been Seliciclib chemical structure taken into account in previous studies. A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only six cases

(7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA, was significantly associated with gastric ulcer and gastric cancer than gastritis (p = .001 and p = .019, respectively). After adjustment by age, gender, and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds Tenoxicam ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55–7.24 and OR = 4.14, 95% CI = 1.23–13.94, respectively). Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution. “
“Background:  We hypothesize that pH difference between acid-secreting corpus and non-secreting antrum might influence the activity of H. pylori’s urease and/or related genes. We therefore measured urease activity and the expression of amiE whose encoded protein that hydrolyzes short-chain amides to produce ammonia. Materials and Methods:  Fifty-four patients were recruited into this study.

Hispanic race and amount of healthcare resource utilization may h

Hispanic race and amount of healthcare resource utilization may have a role in explaining this variation.

Table 1. Regional data regarding THC, length of stay and number of procedures for inpatients with AH (n=11,304) *denotes significantly greater result relative to other regions (p<0.05) Disclosures: Ashwini Lakshmanan - Advisory Committees or Review Panels: Salix Pharmaceuticals Vinay Sundaram - Advisory Committees or Review Panels: Salix, Gilead, Jansen; Speaking and Teaching: Salix The following people have nothing to disclose: Folasade P. May, Vineet Syan BACKGROUND AND AIM: New interferon-free regimens for treatment of CHC have high efficacy and favorable safety profile. Our aim was to Cabozantinib assess PROs in CHC with different stages of hepatic fibrosis treated with SOF+LDV regimens. METHODS: PRO questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Index: Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and post-treatment to genotype 1 CH-C subjects

treated with SOF+LDV+RBV or SOF+LDV for 8, 12 and 24 weeks (ION-1, 2 and 3 clinical trials). METAVIR fibrosis stage was determined from pretreatment liver biopsies. RESULTS: 1,005 subjects who had undergone liver biopsies were included (94 – stage 0 fibrosis, 311 – stage 1, 301 – stage 2, 197 – this website stage 3, and 102 – stage 4). Patients with earlier stages of fibrosis were younger (p=0.0043) with lower BMI (p=0.0015) and lower ALT (p<0.0001). At baseline, patients with more advanced fibrosis had greater PRO impairments; this difference was most prominent for PROs related to physical functioning Tideglusib including the physical component of SF-36, physical and emotional well-being and fatigue scale of FACIT-F, activity impairment of WPAI:SHP (up to 12.6% less impairment in stage 0 vs. stage 4, p<0.0001). In multivariate analysis, the stage of fibrosis was independently associated with impairment of PROs (CLDQ-HCV, physical component of SF-36, total FACIT-F and activity impairment

of WPAI scores: beta up to -2.4% per each additional stage, p<0.05). During and post-treatment, these PROs remained lower in patients with advanced fibrosis. Nevertheless, significant improvements (p<0.05) in most PROs were observed at SVR-12, regardless of fibrosis stage (by 2.4%-10.3% from baseline; all p>0.05 across fibrosis stages). In particular, patients with stages 0-2 (early fibrosis) had similar PRO improvements as compared to those with advanced fibrosis [e.g., improvement in vitality of SF-36 from baseline: +7.94% in stages 0-2 (p<0.0001), +8.08% in stages 3-4 (p<0.0001), (p>0.05 between fibrosis groups)]. In multivariate analysis, improvement of PROs after SVR-12 was not related to the stage of fibrosis (all p>0.05).

Results:  Thirty-two studies could be included in the review Ann

Results:  Thirty-two studies could be included in the review. Annual incidence was lower than 1.0 % in 17 studies; no correlation between length of follow-up and cumulative incidence was observed. Apparent cumulative incidences of the magnitudes observed in most studies would be expected, because of less than perfect sensitivity and specificity of the diagnostic tests, even in the absence of any true new infections. Conclusion/Impact:  Apparent incidence rates of H. pylori infection among adults in Western populations should be

interpreted with utmost caution. “
“Helicobacter felis belongs to the fastidious Autophagy Compound high throughput screening gastric non-Helicobacter pylori helicobacter species that are typically found in the stomach of cats and dogs. These bacteria have the potential to colonize the human stomach and Y27632 are then associated with gastritis, gastroduodenal ulcers, and MALT lymphoma. Strains cultured from the human stomach are rare. Here, we present the first isolation of H. felis from a gastric biopsy specimen of a 14-year-old girl who presented with persistent epigastric pain. The strain was cultured using our routine protocol for H. pylori and identified by phylogenetic analyses

of partial urease AB and gyrB gene sequences. “
“Background:  The seroprevalence rate of Helicobacter pylori in the Kingdom of Saudi Arabia (KSA) was reported to be in the range of 50–80% among mostly symptomatic patients in non-community-based studies. However, the seroprevalence of viral hepatitis A (HAV) underwent a marked decline in the last two decades from over 50%

in 1989 to 25% in 1997 among Saudi children under the age of 12 years. The aim of this paper was to study seroprevalence Docetaxel concentration rates of H. pylori and HAV among the adolescent population in three regions of KSA and to determine whether there was any correlation between them. Materials and methods:  We randomly selected 1200 16–18-year-old students from three regions around KSA. Demographic data, including socioeconomic status (SES), were recorded, and each student was tested for the presence of H. pylori-IgG antibodies and anti-HAV-IgG. Results:  The results indicate a high H. pylori infection rate (47%) among this age group. Boys had a higher prevalence than girls (p = .03), and the Al-Qaseem region had the highest prevalence (51%, p = .002). SES did not contribute to the high prevalence rates (p = .83). A cross-tabulation of data showed that 88 (8%) of the teenagers were seropositive and that 512 (44%) were negative for both H. pylori and HAV antibodies (χ2 = 0.03, OR = 0.97, CI = 0.70–1.34). The agreement between H. pylori and HAV seropositivity was lower than would be predicted by chance (κ = −0.03). The variables that were independently associated with seropositivity to H. pylori were being female (OR = 0.75, 95% CI = 0.60–0.95) and living in the Madinah region (OR = 0.72, 95% CI = 0.55–0.94).

We also examined

the relationship between illness duratio

We also examined

the relationship between illness duration and survival, because outcome has been inversely related to the tempo of development of ALF.25 The intervals between onset of symptoms and stage 1 coma (or stage 2 coma; data not shown), or between jaundice and stage 1 coma, respectively, were shorter in transplant-free survivors than in those who BGJ398 ic50 underwent transplantation, those who died, and those who underwent transplantation or died, respectively (Table 4 and 5), but not statistically significant by univariate (Table 4) or multivariate (Table 5) analysis. Severity of coma, MELD score, and NAC use were entered into a multivariable logistic regression model. MELD met the requirements for linearity in the log odds for rate of transplant-free survival, and neither colinearity I-BET-762 chemical structure nor interaction was present among the covariates. Both MELD score (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.99; P = 0.01) and coma severity (OR, 0.33; 95%CI, 0.14-0.79; P = 0.01) predicted poor outcomes; however, NAC use was no longer predictive (OR, 1.89; 95%CI, 0.79-4.51; P = 0.15); the model fit was adequate by the Hosmer-Lemeshow goodness-of-fit test

(P = 0.88). This study prospectively explores the causes and consequences of the most serious form of DILI, namely ALF. DILI ALF is characterized by deep jaundice, fluid retention, advanced coagulopathy, and coma (but only moderate elevations of aminotransferases), indicating a slowly evolving or “subacute” condition. This biochemical profile of DILI ALF contrasts with acetaminophen-induced and most other identifiable causes of ALF, which show much higher aminotransferases21, 26, 27 and, in the case of acetaminophen, much less hyperbilirubinemia.26 One-quarter of DILI ALF subjects exhibited an immunoallergic reaction, i.e., rash, Fluorometholone Acetate eosinophilia, or autoantibody positivity. Despite polypharmacy, it was relatively easy to decide which drug or group of drugs was the likely culprit. The most common causes of DILI ALF were antimicrobials, but neuroactive drugs, various CAMs, illicit substances, and statins were frequently

implicated. The outcome of DILI ALF is predicted by the degree of liver dysfunction—as judged by the severity of coma, hyperbilirubinemia, and coagulopathy—but not by the class of drugs, drug injury pattern, age, gender, obesity, or timing of cessation of drug use. When transplant-free recovery from DILI ALF is combined with the excellent results of liver transplantation, overall survival approaches 70%. In the current study, the high female predominance is similar to the gender imbalance seen in DILI ALF in Spain,28 in acetaminophen-induced ALF in Sweden,29 and in U.S. ALF patients of any cause,21, 30, 31 including DILI transplant recipients,17 suggesting that women with acute liver injury are either more predisposed to develop ALF or use more prescription drugs than men.

By asking whether caffeine consumption patterns had changed in th

By asking whether caffeine consumption patterns had changed in the selleck past 6 months or 5 years, an attempt was made to discern whether patients with more advanced fibrosis were decreasing

their caffeine intake. Most patients did not report a change in caffeine consumption patterns over time, but this is clearly an imperfect measure of this trend. Importantly, however, of patients reporting a change in intake over the past 5 years, there were similar numbers with and without advanced fibrosis, suggesting that worsening liver disease was not the impetus to alter consumption of caffeine. Other factors that may affect caffeine consumption such as socioeconomic status, education level, and recreational drug use, were also not considered in this analysis. A useful instrument for a comprehensive evaluation of caffeine consumption was developed, which proved easy to use and highly reproducible. Caffeine consumption was associated with a lower risk of advanced liver fibrosis, particularly in patients with HCV infection;

however, the data suggest that a beneficial effect requires caffeine consumption above a threshold of approximately 2 coffee-cup equivalents per day. The effect seemed to be most pronounced with caffeinated coffee as opposed to other caffeine-containing products. With accumulating data on the beneficial role of coffee and AZD1208 molecular weight caffeine in liver disease, as well as the supporting in vitro data, it may now be time to consider Tobramycin a prospective study of coffee or caffeine on hepatic fibrogenesis. Additional Supporting Information may be found in the online version of this article. “
“In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma

(HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups. We followed 309 consecutive HCC patients who achieved CR following TACE (n = 220) or RFA (n = 89) for a median of 68 months. Recurrence patterns were classified as local recurrence and secondary tumor according to location of recurrence (≤2 cm and >2 cm from primary tumor). Recurred HCC had been found in 231 out of 309 patients (75%) with CR by TACE or RFA; 112 local recurrences (48%), 100 secondary tumor (43%) and 19 both (9%). The cumulative recurrence rates at 1, 3 and 5 years were 22%, 64% and 79%, respectively.

Decreased association of MAVS with mitochondria and increased cyt

Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA polyinosinic:polycytidylic acid [poly(I:C)], but not lipopolysaccharide or cytidine–phosphate–guanosine-rich DNA, resulted in impaired induction of type I interferons (IFNs) and proinflammatory cytokines in steatohepatitis. Consistent with a defect in helicase receptor-induced signaling, there was loss of poly(I:C)-induced translocation of MAVS to the cytosol and decreased IFN regulatory factor 3 phosphorylation. Caspases Idasanutlin 1 and 8, both of which cleave MAVS, were increased in MCD diet–fed mice. At baseline,

steatohepatitis was associated with increased serum alanine aminotransferase (ALT), apoptosis and caspase 3 activation compared with controls.

In contrast to apoptosis in controls, necrosis was induced by poly(I:C) stimulation in steatohepatitis. Hepatocyte ICG-001 ic50 necrosis was indicated by elevated serum high-mobility group box protein-1 and ALT and was correlated with increased expression of receptor-interacting protein 3 (RIP3), a master regulator of necrosis. Increased expression of MAVS, PSMA7, and RIP3 messenger RNA was also present in human NASH livers. Conclusion: Our novel findings suggest that mitochondrial damage in steatohepatitis extends to MAVS, an adapter of helicase receptors, resulting in inefficient type I IFN and inflammatory cytokine response but increased hepatocyte necrosis and RIP3 induction in response to a dsRNA viral challenge. These mechanisms may contribute

to progressive liver damage and impaired viral clearance in NASH. (HEPATOLOGY 2011;) Nonalcoholic fatty liver disease is the most rapidly increasing cause of liver disease in the western world.1 The spectrum of nonalcoholic fatty liver disease spans from steatosis to nonalcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular cancer.1 Although the factors determining progression of NASH are yet Thalidomide to be fully defined, the clinical importance of increased susceptibility of the fatty liver to ischemia,2 bacterial lipopolysaccharide (LPS),3 viral infections,1 and drug-induced liver damage4 is emerging. Comorbidity of NASH with viral infections caused by RNA viruses, such as hepatitis C and human immunodeficiency virus (HIV) remains a clinical challenge.1 Hepatitis C virus (HCV)-infected patients with significant steatosis or superimposed NASH have rapid progression of liver disease, increased rate of fibrosis, and a decreased likelihood of sustained virological response to standard antiviral therapy.5 In HIV infection, highly active antiretroviral therapy induces extensive alterations to liver lipid metabolism, including liver damage and even liver failure.

The percentage of NK cells in the liver lymphocytes was markedly

The percentage of NK cells in the liver lymphocytes was markedly higher than that in peripheral blood (Fig. 7A). Hepatic NK cells also expressed higher levels of activation markers HLA-DR, CD38, and CD69 (Fig. 7B) and activation receptors NKp30,

NKp44, NKp46, NKG2A, and NKG2D but lower levels of inhibitory receptors CD158a and CD158b (Fig. 7C) in comparison with peripheral NK compartments. Furthermore, hepatic NK cells produced more CD107a than peripheral NK cells with all four stimulations, as described in Fig. 7D. In comparison with peripheral NK cells, hepatic NK cells produced higher levels of IFN-γ only upon PMA/ionomycin stimulation and produced less IFN-γ upon P815/anti-NCR stimulation. These data indicate that hepatic NK cells displayed higher levels of activation and cytotoxic functions than peripheral NK cells in these IA patients. We subsequently Cytoskeletal Signaling inhibitor analyzed the associations between hepatic NK cell activation status and degranulation capacity and liver injury scores in IA patients. As LDE225 shown in Fig. 8A, the expression levels of HLA-DR and CD38 on freshly isolated

hepatic NK cells and CD107a degranulation in response to anti-ALS or anti-NCR were higher in IA patients with inflammation scores of G2 to G3 versus those with a score of G1. On the contrary, CD69 expression on liver NK cells and PMA/ionomycin

and K562 induction of CD107a degranulation were similar between these groups. The correlation Megestrol Acetate analysis further illustrated that the expression of CD38, NKp30, and NCR-redirected CD107a on hepatic NK cells correlated positively with serum ALT levels (all P < 0.05; Fig. 8B). These data suggest that the presence of activated NK cells is closely associated with liver necroinflammation in IA patients. The current study has characterized hepatic and peripheral NK cells in HBV-infected subjects and has demonstrated that (1) activated NK cells preferentially accumulate in the livers of IA patients, in which they are skewed toward cytolytic activity dependent on increased hepatic IL-12, IL-15, and IL-18 expression and decreased IL-10 expression, and (2) the elevated NK cytolytic activity is associated with liver injury, whereas concomitant inefficient IFN-γ production may favor viral persistence in these IA patients. These findings clearly describe the immune status of NK cells in vivo and further define the potential roles of NK cells in liver injury in CHB patients. Although the hepatic NK cell frequency was reduced in IA patients, the total number of hepatic NK cells from these patients was significantly increased, as demonstrated by immunohistochemistry analyses.

The authors stated that they had no interests which might be perc

The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“The goal of gene therapy for the hemophilias is to develop a product that can direct long-term expression of a clotting factor from a single administration. This has now been achieved in the setting of hemophilia

B, using an adeno-associated viral (AAV) vector expressing MK0683 nmr wild-type factor IX under the control of a liver-specific promoter. Use of an AAV8 capsid, with strong tropism for liver, allows intravenous infusion of vector, simplifying administration to an outpatient procedure. The human immune response presents obstacles to infusion of AAV vectors when administered through the circulation, but these are now understood well enough to allow successful management, through prescreening for anti-AAV antibodies to avoid a humoral immune barrier, and through use of a short course of steroids to dampen a T-cell-mediated immune response

to AAV capsid when indicated. Successful development of AAV-mediated, liver-directed gene transfer may add new treatment options for people with hemophilia. “
“Summary.  Desmopressin (DDAVP) is commonly used for treatment and prevention of bleeding complications in patients with bleeding disorders including haemophilia A, von Willebrand’s disease (VWD) and other less common disorders. Anti-infection Compound Library ic50 This article reviews the current evidence for the use of DDAVP in pregnancy to clarify its efficacy and safety with regard to maternal and foetal outcome. A search of the literature found 30 studies that reported DDAVP use in pregnancy for prophylaxis or treatment of bleeding complications with 216 pregnancies reported in total. The most common indication was prophylaxis for prevention of bleeding during pregnancy

and postpartum triclocarban haemorrhage. DDAVP was used successfully in the first and early second trimester for bleeding prophylaxis in 50 pregnancies. No postpartum bleeding complications were reported in 167 out of 172 pregnancies when DDAVP was used for peripartum haemostatic cover. Twenty-nine studies reported no significant adverse events as a result of treatment with DDAVP. One case of water intoxication seizure and one case of premature labour following the use of DDAVP was reported in a single study. Other maternal side effects included facial flushing and headache and were reported by one study. These side effects were generally well tolerated by patients. There were no other significant adverse events reported in any of the studies as a result of DDAVP use. Foetal outcome was recorded in ten studies with no adverse foetal outcomes.