Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB-MITF-tyrosinase signalling pathway in melanocytes.

Ginsenosides are major active components of ginseng, and have diverse pharmacological properties in traditional medicine. Recent reports have shown that ginsenosides modify skin physiology and mitigate skin disorders such as photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of protopanaxatriol, a major category of ginsenosides, as a depigmenting agent. Protopanaxatriol significantly reduced intracellular and extracellular melanin content in a concentration-dependent manner in B16 melanoma cells treated with α-melanocyte-stimulating hormone. In normal human epidermal melanocytes, protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In addition, protopanaxatriol dramatically suppressed the expression of genes encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and -2, and microphthalmia-associated transcription factor through dephosphorylation of cAMP response element-binding protein. These results suggest that protopanaxatriol could be an effective candidate anti-melanogenic agent.

Viral activity and outcome of hepatitis B surface antigen-positive grafts in deceased liver transplantation.

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)-positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg-positive deceased grafts transplanted to HBsAg-positive recipients. Eleven HBsAg-positive deceased grafts were transplanted to HBsAg-positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end-stage liver disease score for the recipients was 19 (16-32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg-positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg-positive deceased grafts is feasible and increases the donor pool to rescue dying patients.

Do stillbirth, miscarriage, and termination of pregnancy increase risks of attempted and completed suicide within a year? A population-based nested case-control study.

OBJECTIVE: To investigate the risks of attempted and completed suicide in women who experienced a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally and compare this risk with that in women who experienced a live birth. DESIGN: A nested case-control study. SETTING: Linking three nationwide population-based data sets in Taiwan: the National Health Insurance Research Database, the National Birth Registry and the National Death Registry. SAMPLE: In all, 485 and 350 cases of attempted and completed suicide, respectively, were identified during 2001-11; for each case, ten controls were randomly selected and matched to the cases according to the age and year of delivery. METHODS: Conditional logistic regression. MAIN OUTCOME MEASURES: Attempted and completed suicidal statuses were determined. RESULTS: The rates of attempted suicide increased in the women who experienced fetal loss. The risk of completed suicide was higher in women who experienced a stillbirth [adjusted odds ratio (aOR) 5.2; 95% CI 1.77-15.32], miscarriage (aOR 3.81; 95% CI 2.81-5.15), or termination of pregnancy (aOR 3.12; 95% CI 1.77-5.5) than in those who had a live birth. Furthermore, the risk of attempted suicide was significantly higher in women who experienced a miscarriage (aOR 2.1; 95% CI 1.66-2.65) or termination of pregnancy (aOR 2.5; 95% CI 1.63-3.82). In addition to marital and educational statuses, psychological illness increased the risk of suicidal behaviour. CONCLUSIONS: The risk of suicide might increase in women who experience fetal loss within 1 year postnatally. Healthcare professionals and family members should enhance their sensitivity to care for possible mental distress, particularly for women who have experienced a stillbirth. TWEETABLE ABSTRACT: Suicide risk increased in women who had a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally.

Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus.

We measured plasma levels of the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and leucocyte mRNA expression levels of the genes encoding the 8-OHdG repair enzyme human 8-oxoguanine DNA glycosylase 1 (hOGG1), the anti-oxidant enzymes copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase-1 (GPx-1), GPx-4, glutathione reductase (GR) and glutathione synthetase (GS), the mitochondrial biogenesis-related proteins mtDNA-encoded ND 1 polypeptide (ND1), ND6, ATPase 6, mitochondrial transcription factor A (Tfam), nuclear respiratory factor 1(NRF-1), pyruvate dehydrogenase E1 component alpha subunit (PDHA1), pyruvate dehydrogenase kinase isoenzyme 1 (PDK-1) and hypoxia inducible factor-1α (HIF-1α) and the glycolytic enzymes hexokinase-II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase A (LDHa). We analysed their relevance to oxidative damage in 85 systemic lupus erythematosus (SLE) patients, four complicated SLE patients undergoing rituximab treatment and 45 healthy individuals. SLE patients had higher plasma 8-OHdG levels (P < 0·01) but lower leucocyte expression of the genes encoding hOGG1(P < 0·01), anti-oxidant enzymes (P < 0·05), mitochondrial biogenesis-related proteins (P < 0·05) and glycolytic enzymes (P < 0·05) than healthy individuals. The increase in plasma 8-OHdG was correlated positively with the elevation of leucocyte expression of the genes encoding hOGG1 (P < 0·05), anti-oxidant enzymes (P < 0·05), several mitochondrial biogenesis-related proteins (P < 0·05) and glycolytic enzymes (P < 0·05) in lupus patients. The patients, whose leucocyte mtDNA harboured D310 heteroplasmy, exhibited a positive correlation between the mtDNA copy number and expression of ND1, ND6 and ATPase 6 (P < 0·05) and a negative correlation between mtDNA copy number and systemic lupus erythematosus disease activity index (SLEDAI) (P < 0·05), as well as plasma 8-OHdG (P < 0·05). In particular, four complicated SLE patients with increased expression of the genes encoding the anti-oxidant enzymes, GAPDH, Tfam and PDHA1, experienced better therapeutic outcomes after rituximab therapy. In conclusion, higher oxidative damage with suboptimal increases in DNA repair, anti-oxidant capacity, mitochondrial biogenesis and glucose metabolism may be implicated in SLE deterioration, and this impairment might be improved by targeted biological therapy.

"Passing loop" technique: a new modification of the piggyback technique tailored to voluminous liver grafts--case report.

BACKGROUND: The modified piggyback technique with side-to-side cavocavostomy decreases the risk of outflow obstruction compared with the standard piggyback method. However, this modification is not ideal for recipients who receive a graft that is voluminous or bears an enlarged caudate lobe. METHODS: We modified the inferior vena cava (IVC) preservation technique against deleterious complications of compression by using a passing loop. CASE PRESENTATION: A 49-year-old woman, who underwent orthotopic liver transplantation for hepatic failure, was allocated a large-size liver. In anticipation of serious caval compression due to the voluminous grafts, we kept the suprahepatic or infrahepatic donor caval cuffs open for an anastomosis. The first anastomosis was performed between suprahepatic donor IVC cuff and recipient middle-left hepatic vein common channel; the second anastomosis was a terminolateral cavocavostomy between infrahepatic donor IVC cuff and the anterior wall of the recipient's IVC. DISCUSSION: When the liver circulation was restored, the donor retrohepatic vena cava served as a passing loop for both hepatic venous outflow and infra-diaphragmatic venous return to bypass possible IVC compression. Our technique may solve a dilemna for patients receiving voluminous liver grafts.

Impact of acute kidney injury on mortality and medical costs in patients with meticillin-resistant Staphylococcus aureus bacteraemia: a retrospective, multicentre observational study.

BACKGROUND: Despite the frequent occurrence of acute kidney injury (AKI) associated with meticillin-resistant Staphylococcus aureus (MRSA) infection during treatment, the adverse impact of renal injury on clinical and economic outcomes has not been evaluated. AIM: To study the clinical and economic burdens of MRSA bacteraemia and the impact of AKI occurring during treatment on outcomes. METHODS: Medical records of patients hospitalized for MRSA bacteraemia between March 2010 and February 2011 in eight hospitals in Korea were reviewed retrospectively to evaluate the risk factors for AKI and mortality. Direct medical costs per patient of MRSA bacteraemia during treatment were estimated from the medical resources consumed. FINDINGS: In all, 335 patients were identified to have MRSA bacteraemia. AKI occurred in 135 patients (40.3%) during first-line antibiotic therapy. Independent risk factors for AKI were male sex, underlying renal disease, intra-abdominal and central venous catheter infection, and increase in Pitt bacteraemia score. Seventy-seven (23.0%) patients died during the study period. Underlying solid tumour, high Pitt bacteraemia score, and occurrence of AKI were independent risk factors for mortality. The mean total medical cost per MRSA patient was estimated as South Korean Won 5,435,361 (US$4,906), and occurrence of AKI and ICU admission were identified as independent predictors of increased direct medical costs. Compared with patients who retained their baseline renal function, patients with AKI had a 45% increase in medical costs. CONCLUSIONS: Patients who developed AKI showed significantly higher mortality rate and greater direct medical costs compared with patients who retained baseline renal function.

Analysis of the association between air pollution and allergic diseases exposure from nearby sources of ambient air pollution within elementary school zones in four Korean cities.

The objectives of this study were to survey elementary school students regarding the environmental conditions of their elementary schools and to assess the relationship between air pollution and allergic disease using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Therefore, this study was designed as a cross-sectional study. In this study, seven elementary schools were selected and they were classified into three categories. The selection included one school with no traffic-related or other pollutants, three with traffic-related pollutants, and three with traffic-related and other pollutants from industrial and filling station sources. The ISAAC questionnaire survey was given to all of the students except to those in the 1st grade who were presumed to be less likely to be exposed to the school environment than the remainder of the students attending those seven schools. The assessment of allergic disease was conducted on a total of 4,545 students. Three school zones with critical exposure were selected within each school and they were evaluated based on the levels of black carbon (BC), PM10, SO2, NO2, and O3. There was a significant increase in the risks based on the odds ratios of treatment experiences (within 1 year) for allergy-related diseases such as asthma and allergic rhinitis (a) in the school group with traffic-related pollutants and the school group with complex pollutants were 2.12 (1.41-3.19) and 1.59 (1.06-2.37), respectively, in comparison to the school groups with no exposure to pollutants. This was determined based on the odds ratio of symptoms and treatment experiences for allergy-related diseases by group based on the home town zone as a reference. Also, in the case of atopic dermatitis, the odds ratio of treatment experiences (within 1 year) was 1.42 (1.02-1.97), which indicated elevated risks compared to the students in the S1 school. A regression analysis was used to assess the relationship between the substances and the symptomatic experiences within the last year. There were significant increases in the odds ratio of the symptoms associated with allergic rhinitis and the BC and SO2 in the complex pollution areas. The results of the assessment of the relationship between atopic dermatitis-associated symptoms and O3 showed that the odds ratio increased with statistical significance.

p21-Activated kinase 4 promotes prostate cancer progression through CREB.

Prostate cancer is initially androgen-dependent but, over time, usually develops hormone- and chemo-resistance. The present study investigated a role for p21-activated kinase 4 (PAK4) in prostate cancer progression. PAK4 activation was markedly inhibited by H89, a specific protein kinase A (PKA) inhibitor, and PAK4 was activated by the elevation of cAMP. The catalytic subunit of PKA interacted with the regulatory domain of PAK4, and directly phosphorylated PAK4 at serine 474 (S474). Catalytically active PAK4 enhanced the transcriptional activity of CREB independent of S133 phosphorylation. Stable knockdown of PAK4 in PC-3 and DU145 prostate cancer cells inhibited tumor formation in nude mice. Decreased tumorigenicity correlated with decreased expression of CREB and its targets, including Bcl-2 and cyclin A1. Additionally, in androgen-dependent LNCap-FGC cells, PAK4 regulated cAMP-induced neuroendocrine differentiation, which is known to promote tumor progression. Finally, PAK4 enhanced survival and decreased apoptosis following chemotherapy. These results suggested that PAK4 regulates progression toward hormone- and chemo-resistance in prostate cancer, and this study identified both a novel activation mechanism and potential downstream effector pathways. Therefore, PAK4 may be a promising therapeutic target in prostate cancer.

Orthotopic administration of (213)Bi-bevacizumab inhibits progression of PC3 xenografts in the prostate.

AIM: To investigate orthotopic targeted α-radioimmunotherapy for the control of early-stage PC3 prostate cancer nude mouse xenografts using the radiolabeled bevacizumab (BZ) immunoconjugate ((213)Bi-BZ), which emits short-range α-radiation. MATERIALS & METHODS: 10(6) PC3 human prostate cancer cells were injected into the lower capsule of the mouse prostate gland 1 week prior to α-radioimmunotherapy. Mice were euthanized and assessed for tumour growth at 2 (two mice), 4 (two mice) and 6 weeks (three mice) post-therapy. The no-therapy control mice received a saline injection in equal volume to each BZ administration. RESULTS: (213)Bi-BZ is significantly more efficacious in inhibiting xenograft progression in the prostate gland compared with BZ alone (p = 0.009) and when compared with the 'no therapy' protocol (p < 0.0001). CONCLUSION: Orthotopic administration of (213)Bi-BZ greatly improves the early control of organ-confined prostate cancer compared with BZ alone (p < 0.01).

Zona conoidea of the elbow: another articulation between the radial head and lateral trochlear of the elbow.

The zona conoidea comprises the area of the lateral trochlear ridge of the humerus. The purpose of this study is to reintroduce this term 'zona conoidea' to the discussion of the human elbow and to investigate its significance in the development of osteoarthritis of the elbow. The upper extremities of 12 cadavers were prepared. With the forearm in neutral, pronation and supination, the distance between the bevel of the radial head and zona conoidea was inspected. A total of 12 healthy volunteers had a CT scan. The distance between the zona conoidea and the bevelled rim of the radial head was measured in these positions. In the anatomical specimens, early osteo-arthritic changes were identified in the posteromedial bevelled rim of the radial head, and the corresponding zona conoidea in supination. Measurement in the CT study showed that in full supination, the distance between the bevel of the radial head and the zona conoidea was at a minimum. This study suggests that the significant contact between the bevel of the radial head and the zona conoidea in supination is associated with the initiation of osteoarthritis of the elbow in this area.

The usefulness of arbekacin compared to vancomycin.

The bacteriological efficacy response (improved, arbekacin vs. vancomycin; 71.2% vs. 79.5%) and clinical efficacy response (improved, arbekacin vs. vancomycin; 65.3% vs. 76.1%) were not statistically different between the two groups. The complication rate was significantly higher in the vancomycin group (32.9%) compared to the arbekacin group (15.1%) (p=0.019). Arbekacin was not inferior to vancomycin, and it could be a good alternative drug for vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) treatment.

Outcomes after endovascular treatment of symptomatic patients with Takayasu's arteritis.

We report our experience with endovascular treatment of supra-aortic arteries and follow-up results in patients with Takayasu's arteritis (TA) presenting with neurological symptoms. Of the 20 patients with TA who underwent cerebral angiography for neurological manifestations between May 2002 and May 2009, 12 (11 females, one male; mean age, 39 years; range 31-56 years) underwent endovascular treatment and evaluated outcome for 21 lesions, including nine common carotid arteries, four vertebral arteries, four subclavian arteries, two internal carotid arteries, and one brachiocephalic artery. Eight patients underwent multiple endovascular procedures for different lesions in single or multiple stages. Mean angiographic and clinical follow-up durations were 34 months (range, 11-79 months) and 39 months (range 11-91 months), respectively. Technical success was achieved for 20 procedures in 11 patients. One procedure failed, with 50% residual stenosis after stenting due to dense calcification of vessel walls. There were no procedure-related complications. Restenosis occurred at two lesions in two patients were treated by re-stenting. Asymptomatic occlusion occurred at two lesions in one patient. Ten patients remained in 0-1 on the modified Rankin scale (mRs) during mean 39 months. One patient, however, had a score of 3 on mRs due to a traumatic contusion during follow-up. One patient died from cardiac failure 36 months after successful angioplasty.Our data suggest that endovascular treatment of symptomatic supra-aortic lesions of TA is effective and durable in selected patients with neurologic symptoms.

Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells.

Soluble TRAIL and adenovirus (ad)-TRAIL exhibit a strong antitumor effect by inducing apoptosis. Vorinostat is the histone deacetylase (HDAC) inhibitor that induces cell death in cancer cell lines and regulates the expression of epigenetically silenced genes, such as Coxackie adenoviral receptor (CAR), the receptor for adenoviral entry. We propose a new strategy in which vorinostat will induce high expression of ad-TRAIL and a strong antitumor response, and investigated the mechanism involved. The effect of vorinostat on transcription and expression of TRAIL from ad-TRAIL-transduced lung cancer cells were confirmed by reverse transciption-PCR (RT-PCR), quantitative real time-PCR and western blot assay. Anti-tumor effects were measured after cotreatment of vorinostat and ad-TRAIL, and the drug interactions were analyzed. After combined treatment of vorinostat and ad-TRAIL, apoptosis and western blot assays for Akt, Bcl-2 and caspase were performed. Vorinostat increased the expression of CAR in lung cancer cell lines and increased the expression of luciferase (luc) from ad-luc-transduced cells and TRAIL from ad-TRAIL-transduced cells. RT-PCR and quantitative real time-PCR, after sequential vorinostat treatment, revealed that vorinostat may enhance TRAIL expression from ad-TRAIL by increasing transduction through enhanced CAR expression and increasing adenoviral transgene transcription. Combined vorinostat and ad-TRAIL treatment showed the synergistic anti-tumor effect in lung cancer cell lines. Combined vorinostat and ad-TRAIL induced stronger apoptosis induction, suppression of NF-κB activation and breakdown of the anti-apoptotic molecule Bcl-2. In conclusion, the vorinostat synergistically enhanced the anti-tumor effect of ad-TRAIL by (1) increasing adenoviral transduction through the increased expression of CAR and (2) increasing adenoviral transgene (TRAIL) transcription in lung cancer cell lines.

Nafamostat mesilate attenuates Postreperfusion Syndrome during liver transplantation.

Postreperfusion syndrome (PRS), an acute decrease in blood pressure after reperfusion of the liver graft, occurs frequently during liver transplantation surgery. We supposed that the activation of the kallikrein-kinin system leading to extensive systemic vasodilatation was a possible cause. The effect of pretreatment with nafamostat mesilate (NM), a broad spectrum serine protease inhibitor, on the occurrence of PRS was evaluated. Sixty-two adult liver recipients were randomized to receive an intravenous bolus of either 0.02 mg/kg of NM (NM group, n = 31) or an equal volume of normal saline (control group, n = 31) just before reperfusion of the liver graft. Occurrence of PRS and intraoperative use of vasoactive drugs were compared between the two groups. Postoperative recovery was also compared. PRS was significantly less frequent (48% vs. 81%, p = 0.016) requiring less vasopressors in the NM group compared to the control group. The NM group also showed faster recovery of the mean arterial pressure. Perioperative laboratory values were similar between the two groups. Pretreatment with 0.02 mg/kg of NM immediately before reperfusion decreases the frequency of PRS and vasopressor requirements during the reperfusion period in liver transplantation.

2009 H1N1 influenza infection in Korean healthcare personnel.

Healthcare personnel (HCP) can acquire influenza and transmit it to patients and other hospital staff. The aim of this study was to evaluate the attack rate of HCP by the 2009 H1N1 influenza virus during the 2009 pandemic influenza season in Korea. HCP infected with H1N1 virus were asked to fill out a questionnaire, which included job type, method of diagnosis, facility type, history of contact with patients infected by H1N1 virus, vaccination status, and use of personal protective equipment. A total of 328 HCP (female 68.6%, 225/328) were infected with H1N1 virus at the nine study centers. The highest attack rate was in physicians, followed by nurses and nurses' aides. Transmission occurred primarily after contact with outpatients (27.8%), followed by contact with inpatients (21.6%). Most (77.3%) of the infected HCP never used an N95 mask during contact with patients. Surgical masks were always used by 29.4% of the subjects and usually or intermittent used by 46.9%. The peak incidence of the H1N1 infection among HCP preceded that among the general population. Among HCPs, physicians, nurses, and nurses' aides were at the greatest risk of H1N1 infection. HCP should be more vigilant and protect themselves with appropriate personal protective equipment during the influenza season.

Monitoring of viruses in chum salmon (Oncorhynchus keta) migrating to Korea.

It is important to investigate the prevalence of salmonid pathogens because they can affect the amount of release of salmonid fry and the migration rate of adult salmonids. In this study, routine surveys were conducted for investigating virus distribution in migrating chum salmon spawners (Oncorhynchus keta) and their offsprings at the Namdae River, Yangyang, Korea, during 2006-2008. Anterior kidneys were removed from chum salmon spawner individuals, homogenized with minimal essential medium, and centrifuged to make supernatants for conducting RT-PCR. Five offspring were pooled to for conducting RT-PCR. Infectious pancreatic necrosis virus (IPNV), infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) were the target viruses for monitoring. In 2006, only spawners were investigated, and 27.5% of fish (22/80) were found to be IHNV-positive by nested PCR. In 2007, 65.6% of pooled fry (21/32) were IHNV-positive, and 9.4% (3/32) were IPNV-positive by one-step PCR. When nested PCR was conducted, 84.4% (27/32) were IHNV-positive, and 28.1% (9/32) were IPNV-positive. However, only 1.3% of spawners (1/80) were IHNV-positive by nested PCR. In 2008, 25% (8/32) of pooled fry were IHNV-positive by one-step PCR, but 59.4% (19/32) were IHNV-positive and 12.5% (4/32) were IPNV-positive by nested PCR. All of the samples tested were VHSV-negative. Although all viruses detected in this study were from chum salmon, phylogenetic analysis showed that they possibly originated from rainbow trout or clustered with the rainbow trout isolates. More extensive long-term studies are needed to clarify the origins of these viruses and their potential effects on chum salmon migration in Korea.

Indicators and outcome of liver transplantation in acute liver decompensation after flares of hepatitis B.

Non-cirrhotic patients having acute liver decompensation in flares of hepatitis B can recover spontaneously or die without liver transplantation. Criteria for identifying patients in need of liver transplantation are lacking. Fifty-one non-cirrhotic patients having acute liver decompensation in flares of hepatitis B were retrospectively reviewed. The patients were divided into three groups: group A patients (n=18) recovered from acute liver decompensation spontaneously; group B patients (n=22) died of acute liver failure; and group C patients (n=11) had liver transplantation. Model of end-stage liver disease (MELD) scores were evaluated to identify the criteria for liver transplantation. The cut-off point of MELD scores for liver transplantation was evaluated by receiver operating characteristic (ROC) curve. Comparing group A and B patients, MELD score was an independent factor to predict prognosis. By analysing ROC curve, a MELD score>30 was the most optimal cut-off point to indicate liver transplantation; however, the false positive rate was 11.1%. By weekly measurement of MELD scores, subsequent increase in MELD scores could help to avoid false positives. Moreover, a MELD score>34 yielded 0% false positive rate and indicated the necessity of definite liver transplantation. For group C patients, ten of 11 patients were saved by liver transplantation. In conclusion, for the patients having acute liver decompensation in flares of hepatitis B, liver transplantation is definitely indicated by MELD scores>34. Liver transplantation is also indicated if the MELD score increases in the subsequent 1-2 weeks. Liver transplantation has a good outcome if performed on time.

Dynamics of clinical symptoms in patients with pandemic influenza A (H1N1).

We evaluated the dynamics of clinical symptoms of 2009 pandemic influenza A (H1N1) using a four-point scale sheet. The most frequent symptoms were fever and cough. The sum of symptom score was high during the first 4 days. Systemic symptoms peaked earlier, by day 2, and resolved faster than upper respiratory symptoms and lower respiratory symptoms after oseltamivir treatment. The lower respiratory symptoms resolved slowly over 2 weeks. The 2009 pandemic influenza A (H1N1) virus might involve primarily lower respiratory tract and could be the main cause of pneumonia.

Scrub typhus in patients with liver cirrhosis: a preliminary study.

Scrub typhus is a potentially fatal infectious disease caused by the organism Orientia tsutsugamushi. However, to date, there have been no clearly identified determinants or reports published on the clinical severity of scrub typhus in liver cirrhosis (LC) patients. This study was carried out by retrospectively reviewing medical records accumulated over 7 years at a tertiary hospital. Sixteen patients of 160 had underlying LC, and they were defined as 'cases'; those without underlying LC were defined as 'controls'. The duration of hospital stay (23.0 +/- 24.8 days for cases and 6.8 +/- 7.0 days for controls, p 0.020) and APACHE II scores (14.1 +/- 6.0 for cases and 7.2 +/- 4.6 for controls, p <0.001) were, respectively, significantly longer and significantly higher on admission in the cases than in the controls. Surprisingly, hospital mortality was significantly higher in the cases than in the controls (31.3% and 3.5%, respectively, p 0.001). Among the LC group, the highest Model for End-stage Liver Disease (MELD) score during hospitalization (MELD-Peak) (p 0.024) and the lowest blood sodium concentration during hospitalization (MELD-Na-Lo) (p 0.003) were higher in fatal cases than in the survivors (MELD-Na-to). Physicians should be aware of an adverse relationship between LC and scrub typhus, and patients with LC should be advised to avoid exposure to O. tsutsugamushi, particularly in endemic areas and epidemic seasons.