Blood lactate concentration and shock index associated with massive transfusion in emergency department patients with primary postpartum haemorrhage.

BACKGROUND: We hypothesised that lactate concentrations are independently associated with massive transfusion in patients with primary postpartum haemorrhage. Moreover, combining lactate concentrations with the shock index, defined as the ratio of heart rate to systolic arterial blood pressure, can improve the predictive performance for massive transfusion. METHODS: We retrospectively analysed patients with primary postpartum haemorrhage in the emergency department of a tertiary referral centre in Korea between January 1, 2004 and December 31, 2015. RESULTS: Of the 302 patients, 101 (33.4%) patients required massive transfusion. Lactate concentration was independently associated with the requirement for massive transfusion [odds ratio, 1.56; 95% confidence interval (CI), 1.31-1.87; P<0.01]. The area under the receiver operating characteristic curve of lactate concentration and shock index for massive transfusion was 0.788 (95% CI: 0.736-0.840; P<0.01) and 0.776 (95% CI: 0.717-0.836; P<0.01), respectively. Lactate elevation (>4.0 mM L-1) was associated with 86.1% specificity and 67.8% positive predictive value for massive transfusion. When combining elevated lactate concentrations (>4.0 mM L-1) with a shock index >1.0, the specificity and positive predictive value increased to 95.5% and 82.4%, respectively. CONCLUSIONS: Point-of-care testing of lactate concentrations in the emergency department may be useful to predict massive transfusion requirements in primary postpartum haemorrhage. Combining initial lactate concentrations with the shock index improves the predictive performance for massive transfusion requirements and may contribute to rapid risk stratification of patients with primary postpartum haemorrhage in need of transfusion and further focus on early interventions to control bleeding.

Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (Ne ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and Ne in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small Ne values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and Ne for each breed reflect the breeding strategy applied. The Ne for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract.

A Major Locus for Quantitatively Measured Shank Skin Color Traits in Korean Native Chicken.

Shank skin color of Korean native chicken (KNC) shows large color variations. It varies from white, yellow, green, bluish or grey to black, whilst in the majority of European breeds the shanks are typically yellow-colored. Three shank skin color-related traits (i.e., lightness [L*], redness [a*], and yellowness [b*]) were measured by a spectrophotometer in 585 progeny from 68 nuclear families in the KNC resource population. We performed genome scan linkage analysis to identify loci that affect quantitatively measured shank skin color traits in KNC. All these birds were genotyped with 167 DNA markers located throughout the 26 autosomes. The SOLAR program was used to conduct multipoint variance-component quantitative trait locus (QTL) analyses. We detected a major QTL that affects b* value (logarithm of odds [LOD] = 47.5, p = 1.60×10-49) on GGA24 (GGA for Gallus gallus). At the same location, we also detected a QTL that influences a* value (LOD = 14.2, p = 6.14×10-16). Additionally, beta-carotene dioxygenase 2 (BCDO2), the obvious positional candidate gene under the linkage peaks on GGA24, was investigated by the two association tests: i.e., measured genotype association (MGA) and quantitative transmission disequilibrium test (QTDT). Significant associations were detected between BCDO2 g.9367 A>C and a* (PMGA = 1.69×10-28; PQTDT = 2.40×10-25). The strongest associations were between BCDO2 g.9367 A>C and b* (PMGA = 3.56×10-66; PQTDT = 1.68×10-65). However, linkage analyses conditional on the single nucleotide polymorphism indicated that other functional variants should exist. Taken together, we demonstrate for the first time the linkage and association between the BCDO2 locus on GGA24 and quantitatively measured shank skin color traits in KNC.

Genetic Diversity and Phylogenetic Analysis of South-East Asian Duck Populations Based on the mtDNA D-loop Sequences.

The maternally inherited mitochondrial DNA (mtDNA) D-loop region is widely used for exploring genetic relationships and for investigating the origin of various animal species. Currently, domestic ducks play an important role in animal protein supply. In this study, partial mtDNA D-loop sequences were obtained from 145 samples belonging to six South-East Asian duck populations and commercial duck population. All these populations were closely related to the mallard duck (Anas platyrhynchos), as indicated by their mean overall genetic distance. Sixteen nucleotide substitutions were identified in sequence analyses allowing the distinction of 28 haplotypes. Around 42.76% of the duck sequences were classified as Hap_02, which completely matched with Anas platyrhynchos duck species. The neighbor-joining phylogenetic tree also revealed that South-East Asian duck populations were closely related to Anas platyrhynchos. Network profiles were also traced using the 28 haplotypes. Overall, results showed that those duck populations D-loop haplotypes were shared between several duck breeds from Korea and Bangladesh sub continental regions. Therefore, these results confirmed that South-East Asian domestic duck populations have been domesticated from Anas platyrhynchos duck as the maternal origins.

Sequence-based characterization of five SLA loci in Asian wild boars.

Two swine leucocyte antigen (SLA) class I (SLA-1 and SLA-2) and three class II (DRB1, DQB1 and DQA) genes were investigated for their diversity in Asian wild boars using a sequence-based typing method. A total of 15 alleles were detected at these loci, with eleven being novel. The findings provide one of the first glimpses of the SLA allelic diversity and architecture in the wild boar populations.

Lateral spread response monitoring during microvascular decompression for hemifacial spasm. Comparison of two targets of partial neuromuscular blockade.

AIM: The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal. MATERIAL AND METHODS: A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50 % (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups. RESULTS: Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n = 15 (50.0 %) in group TOF versus n = 24 (82.8 %) in group T1 (P = 0.008), corresponding to a 32.8 % higher success rate in group T1 than group TOF (95 % CI: 13.9-51.7 %). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count = 2 (1) in group TOF versus 3 (1) in group T1 (P = 0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group. CONCLUSION: Maintenance of partial NMB with a target T1/Tc ratio of 50 % resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50 % rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.

Phylogenetic analysis between domestic and wild duck species in Korea using mtDNA D-loop sequences.

Recently, the consumption of duck meat has increased; therefore, we need to reveal the origin and gene flow of domestic ducks in Korea. In order to discriminate between duck species, D-loop variations in mitochondrial DNA (mtDNA) have been investigated. In this study, 45 individuals from seven species of wild and domestic ducks in Korea were considered for the D-loop region sequences. With the participation of all the sequences, a phylogenetic neighbor-joining tree was constructed to differentiate between the wild and domestic duck species. In consideration of these sequences, a total 66 haplotypes were obtained (indel included) with an average haplotype of 76.9%, and a haplotype and nucleotide diversity of 0.91 and 0.01, respectively. Also, an estimation of the sequence divergence within and between species was measured in 0.045 and 0.013-0.095, respectively. Meanwhile, the lowest distances of 0.024, 0.013 and 0.018 were observed in three species, including the Mallard, Spot-billed and domestic duck, respectively, which have relatively close genetic relationships. All haplotypes were used for the median-joining network analysis to differentiate all duck species, while three duck species were closely related. Moreover, 26 indel polymorphisms were identified which could be used for the discrimination among the duck species. Based on our results, duck species were effectively discriminated in a D-loop region, which could then be used for an appropriate genetic conservation program for the wild duck and domestic duck breeds in Korea.

Life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite in the construction sites.

CONTEXT: Construction workers are exposed to a wide variety of health hazards such as poisoning at the construction sites. Various forms of poisoning incidents in construction workers have been reported. However, studies on methemoglobinemia caused by unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites have not been reported yet. OBJECTIVE: The aim of this study was to evaluate life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites and describe similar incidents involving ingestion of antifreeze admixtures in Korea. MATERIALS AND METHODS: Retrospective observational case series study on patients with methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite admitted to the emergency department (ED) from January 1, 2010 to December 31, 2012 and cases reported to the Korea Occupational Safety and Health Agency (KOSHA) was performed. Results. Six victims were admitted to our ED. They had methemoglobin levels ranging from 32.4% to 71.5% and all of them recovered after receiving one (2 mg/kg) or two doses infusion of methylene blue. From the data of the KOSHA, six incidents that caused 27 victims were identified. Of 27 victims, five were included in the ED cases. For all incidents, antifreeze admixtures were not contained in their original containers and all new containers did not have a new label. All workers mistook antifreeze admixtures for water. Among the 28 victims included in this study, four died. CONCLUSION: Unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites can cause life-threatening methemoglobinemia. There is a need to store and label potentially hazardous materials properly to avoid unintentional ingestion at the construction sites.

The impact of saddle embolism on the major adverse event rate of patients with non-high-risk pulmonary embolism.

OBJECTIVE: Wider application of CT angiography (CTA) improves the diagnosis of acute pulmonary embolism (PE). It also permits the visualisation of saddle embolism (SE), namely thrombi, which are located at the bifurcation of the main pulmonary artery. The aim of this study was to assess the prevalence of SE and whether SE predicts a complicated clinical course in patients with non-high-risk PE. METHODS: In total, 297 consecutive patients with non-high-risk PE confirmed using CTA in the emergency department were studied. The presence of SE and its ability to predict the occurrence of major adverse events (MAEs) within 1 month were determined. RESULTS: Of the 297 patients, 27 (9.1%) had an SE. The overall mortality at 1 month was 12.5%; no significant difference was observed between the SE and non-SE groups (18.5% vs 11.9%, p=0.32). However, patients with SE were more likely to receive thrombolytic therapy (29.6% vs 8.1%, p<0.01) and had significantly more MAEs (59.3% vs 25.6%, p<0.01). CONCLUSION: At the time of diagnosis, SE, as determined using CTA, is associated with the development of MAE within 1 month. It may be a simple method for risk stratification of patients with non-high-risk PE. ADVANCES IN KNOWLEDGE: The prognosis of patients with SE, especially those who are haemodynamically stable, is unclear. This study shows that patients with SE, determined with CTA, is associated with the development of MAE.

Comparison of motor-evoked potentials monitoring in response to transcranial electrical stimulation in subjects undergoing neurosurgery with partial vs no neuromuscular block.

BACKGROUND: There have been no evidence-based comparisons of motor-evoked potential (MEP) monitoring with no and partial neuromuscular block (NMB). We compared the effects of different levels of NMB including no NMB on MEP parameters. METHODS: MEP-monitored 120 patients undergoing neurosurgery were enrolled. The patients were randomly allocated to four groups: Group A was to maintain two train-of-four (TOF) counts; Group B was to maintain a T(1)/Tc of 0.5; Group C was to maintain a T(2)/Tc of 0.5 (T(1,2), first or second twitch height of TOF; Tc, control twitch height); Group D did not maintain NMB. The mean MEP amplitude, coefficient of variation (CV), the incidence of spontaneous respiration or movement, the efficacy of MEP, and haemodynamic parameters were compared. RESULTS: The median [inter-quartile range (IQR)] amplitudes of the left leg for Groups A, B, C, and D were 0.23 (0.15-0.57), 0.44 (0.19-0.79), 0.28 (0.15-0.75), and 0.75 (0.39-1.35) mV, respectively. The median (IQR) CVs of the left leg were 71.1 (56.9-88.8), 76.1 (54.2-93.1), 59.8 (48.6-95.6), and 25.2 (17.3-35.0), respectively. The differences between groups of the mean amplitudes of the left arm and both legs were statistically significant (Kruskal-Wallis test, P=0.011 for the left leg). For all limbs, the differences between groups of the CVs were significant (P<0.001, for the left leg). Other parameters were not different. CONCLUSIONS: If NMB is used during MEP monitoring, a target T(2)/Tc of 0.5 is recommended. In terms of the MEP amplitude and variability, no NMB was more desirable than any level of partial NMB.

Discrimination of korean native chicken lines using fifteen selected microsatellite markers.

In order to evaluate the genetic diversity and discrimination among five Korean native chicken lines, a total of 86 individuals were genotyped using 150 microsatellite (MS) markers, and 15 highly polymorphic MS markers were selected. Based on the highest value of the number of alleles, the expected heterozygosity (He) and polymorphic information content (PIC) for the selected markers ranged from 6 to 12, 0.466 to 0.852, 0.709 to 0.882 and 0.648 to 0.865, respectively. Using these markers, the calculated genetic distance (Fst), the heterozygote deficit among chicken lines (Fit) and the heterozygote deficit within chicken line (Fis) values ranged from 0.0309 to 0.2473, 0.0013 to 0.4513 and -0.1002 to 0.271, respectively. The expected probability of identity values in random individuals (PI), random half-sib (PI half-sibs ) and random sibs (PI sibs ) were estimated at 7.98×10(-29), 2.88×10(-20) and 1.25×10(-08), respectively, indicating that these markers can be used for traceability systems in Korean native chickens. The unrooted phylogenetic neighbor-joining (NJ) tree was constructed using 15 MS markers that clearly differentiated among the five native chicken lines. Also, the structure was estimated by the individual clustering with the K value of 5. The selected 15 MS markers were found to be useful for the conservation, breeding plan, and traceability system in Korean native chickens.

Characterization of insertional variation of porcine endogenous retroviruses in six different pig breeds.

Pigs may need to be exploited as xenotransplantation donors due to the shortage of human organs, tissues and cells. Porcine endogenous retroviruses (PERVs) are a significant obstacle to xenotransplantation because they can infect human cells in vitro and have the potential for transmission of unexpected pathogens to humans. In this research, 101 pigs, including four commercial breeds (23 Berkshire, 13 Duroc, 22 Landrace and 14 Yorkshire pigs), one native breed (19 Korean native pigs) and one miniature breed (10 NIH miniature pigs) were used to investigate insertional variations for 11 PERV loci (three PERV-A, six PERV-B and two PERV-C). Over 60% of the pigs harbored one PERV-A (907F8) integration and five PERV-B (B3-3G, B3-7G, 742H1, 1155D9 and 465D1) integrations. However, two PERV-A loci (A1-6C and 1347C1) and one PERV-B locus (B3-7F) were absent in Duroc pigs. Moreover, two PERV-C loci (C2-6C and C4-2G) only existed in Korean native pigs and NIH miniature pigs. The results suggest that PERV insertional variations differ among pig breeds as well as among individuals within a breed. Also, the results presented here can be used for the selection of animals that do not have specific PERV integration for xenotransplantation research.

Outcomes of endoscopic transpapillary gallbladder stenting for symptomatic gallbladder diseases: a multicenter prospective follow-up study.

BACKGROUND AND STUDY AIMS: Endoscopic transpapillary gallbladder drainage for symptomatic gallbladder disease is a safe and effective bridge therapy in patients at high risk for surgery or who have terminal liver disease and are awaiting transplantation. However, there are few reports on long-term results in terms of stent patency and clinical course. Our study was designed to investigate the long-term patency and clinical course after endoscopic transpapillary gallbladder stenting (ETGS) in patients with symptomatic gallbladder disease. PATIENTS AND METHODS: A total of 29 patients who were unsuitable for cholecystectomy underwent ETGS from June 2006 to March 2010 using a 7-Fr double-pigtail stent between the gallbladder and the duodenum. Their clinical progress, adverse events, and stent patency after ETGS were recorded prospectively in two tertiary referral centers. RESULTS: Technically, ETGS was successful in 23 (79.3%) of the 29 patients. The mean procedure time was 22.4 ± 11.5 min. Postprocedure adverse events were mild pancreatitis (8.7%) and cholestasis (8.7%), all of which resolved with conservative management. During the follow-up period (median 586 days, range 11-1403 days), 20 patients were analyzed as per protocol, and scheduled follow-up was performed. Late adverse events developed in four patients (20%), including distal migration (n = 2), cholangitis (n = 1), and recurrent biliary pain (n = 1). The remaining 16 patients were followed for more than 12 months (nine patients were followed for more than 24 months). Median stent patency was 760 days, as determined by the Kaplan-Meier method. CONCLUSIONS: As a primary therapy, ETGS is technically feasible and effective in patients who are unsuitable for cholecystectomy. ETGS may also provide long-term stent patency without the need for scheduled stent exchanges.

A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer.

BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m(-2); days 1 and 3), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m(-2); day 1), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n=31) or mFOLFOX (n=30) regimen. The six-month survival rates were 27% (95% confidence interval (CI)=13-46%) and 30% (95% CI=15-49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI=10-42%) and 17% patients (95% CI=6-35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.

Endoscopic ultrasound-guided versus conventional transmural drainage for pancreatic pseudocysts: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Although endoscopic ultrasound (EUS)-guided transmural drainage (EUD) is preferred over conventional transmural drainage (CTD) of pancreatic pseudocysts by endoscopy in many centers, its superiority with respect to technical success and clinical outcome has not yet been demonstrated in a prospective randomized trial. We conducted this prospective randomized trial to compare the technical success and clinical outcomes of EUD and CTD in treating pancreatic pseudocysts. PATIENTS AND METHODS: A total of 60 consecutive patients with pancreatic pseudocysts were randomly divided into two groups to undergo either EUD (n = 31) or CTD (n = 29) of pancreatic pseudocysts. The technical success rate, complications, and short-term and long-term results were prospectively evaluated. RESULTS: The rate of technical success of the drainage was higher for EUD (94 %, 29/31) than for CTD (72 %, 21/29; P = 0.039) in intention-to-treat analysis. In cases where CTD failed (n = 8), because the pseudocysts were nonbulging, a crossover was made to EUD, which was successfully performed in all these patients. Complications occurred in 7 % of the EUD and 10 % of the CTD group ( P = 0.67). During short-term follow-up, pseudocyst resolution was achieved in 97 % (28/29) in the EUD group and in 91 % (19/21) in the CTD group ( P = 0.565). Long-term results analyzed on a per-protocol basis showed no significant difference in clinical outcomes between EUD (89 %, 33/37) and CTD (86 %, 18/21, P = 0.696). CONCLUSIONS: We found that EUD and CTD can both be considered first-line methods of endoscopic transmural drainage of bulging pseudocysts, whereas EUD should be preferred for nonbulging pseudocysts.

Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study.

BACKGROUND: Autoimmune pancreatitis (AIP) is a peculiar type of chronic pancreatitis that responds dramatically to steroid therapy. To date, there are no worldwide consensus criteria for AIP. Different criteria with institutional preference (HISORt, revised Kim and the revised Japanese criteria) are being used to diagnose AIP, and there is controversy regarding the inclusion of steroid responsiveness in the diagnostic criteria. In contrast to the HISORt and revised Kim criteria, the revised Japanese criteria do not include steroid responsiveness as a diagnostic component. AIMS: This study was performed to evaluate whether "a 2-week steroid trial and subsequent assessment of its response" is a useful diagnostic tool for the differentiation of AIP from pancreatic cancer. A further aim was to discover the surgical and clinical outcome for a patient who followed the treatment algorithm based on the steroid responsiveness. PATIENTS AND METHODS: From January 2004 to June 2007, in the setting of clinically suspected AIP, 22 consecutive patients with atypical imaging for AIP, while not meeting the classic imaging criteria for pancreatic cancer, were challenged to undergo 2 weeks of steroid therapy (0.5 mg/kg of oral prednisolone per day). After the 2-week steroid trial, steroid responsiveness was assessed based on a marked improvement of narrowing of the main pancreatic duct and a reduction of the pancreatic mass. The steroid trial was continued in the case of positive steroid responsiveness, whereas surgical exploration was conducted in the case of negative steroid responsiveness. The final diagnosis was made by surgical exploration or long-term clinical and radiological follow-up. RESULTS: All patients (n = 15) who responded to steroids were diagnosed as having AIP, whereas all patients (n = 7) who did not show a response to steroids were confirmed as having pancreatic cancer. Complete resection was possible in all (6/6; 100%), except one individual who refused surgery. CONCLUSION: In the clinical setting of suspected AIP with the continued need for differentiation from pancreatic cancer due to atypical imaging for AIP, "a 2-week steroid trial and subsequent assessment of its response" may be helpful in confirming the diagnosis of AIP without negative consequences for resectable pancreatic cancer. However, a steroid trial should be performed carefully only by specialists in pancreatology.

Histone deacetylase inhibitor apicidin downregulates DNA methyltransferase 1 expression and induces repressive histone modifications via recruitment of corepressor complex to promoter region in human cervix cancer cells.

Dysregulation of DNA methyltransferase (DNMT)1 expression is associated with cellular transformation, and inhibition of DNMT1 exerts antitumorigenic effects. Here, we report that DNMT1 abnormally expressed in HeLa cells is downregulated by a histone deacetylase (HDAC) inhibitor apicidin, which is correlated with induction of repressive histone modifications on the promoter site. Apicidin selectively represses the expression of DNMT1 among DNMTs in HeLa cells, independent of cell cycle arrest at G0/G1. Furthermore, apicidin causes a significant reduction in the recruitment of RNA polymerase II into the promoter. Chromatin immunoprecipitation analysis shows that even though apicidin causes global hyperacetylation of histone H3 and H4, localized deacetylation of histone H3 and H4 occurs at the E2F binding site, which is accompanied by the recruitment of pRB and the replacement of P/CAF with HDAC1 into the sites. In addition, K4-trimethylated H3 on nucleosomes associated with the transcriptional start site is depleted following apicidin treatment, whereas repressive markers, K9- and K27-trimethylation of H3 are enriched on the site. The downregulation of DNMT1 expression seems to require de novo protein synthesis, because the apicidin effect is antagonized by cycloheximide treatment. Moreover, knock down of DNMT1 with siRNA induces the apoptosis of HeLa cells, indicating that downregulation of DNMT1 might be a good strategy for therapeutics of human cervix cancer. Collectively, our findings will provide a mechanistic rationale for the use of HDAC inhibitors in cancer therapeutics.

Analysis of percutaneous transhepatic cholangioscopy-related complications and the risk factors for those complications.

BACKGROUND AND STUDY AIMS: Percutaneous transhepatic cholangioscopy (PTC) is being increasingly used for patients with biliary tract diseases. The aim of this study was to assess the safety of this procedure, and we systematically analyzed PTC-related complications and the risk factors for those complications. PATIENTS AND METHODS: A total of 364 patients who underwent PTC were included in the study. The initial diagnoses, the indications for PTC, the complications that occurred during the procedures, and the risk factors for these complications were retrospectively analyzed. RESULTS: The overall incidence of complications was 12.9 % for percutaneous transhepatic biliary drainage (PTBD), 12.8 % for tract dilation, and 6.9 % for tract maturation. Complications developed in 58/848 PTC sessions (6.9 %). Cholangitis and bacteremia were associated with PTBD and tract dilation, catheter migration and blockage with tract maturation, and bile duct injury with PTC. Mild complications occurred in 80 patients (22.2 %) during the preparation stages and in 43 sessions (5.1 %) during the PTC itself. Severe complications, including severe hemobilia, hemoperitoneum, rupture of the sinus tract, and ductal injury developed in 17 patients (4.7 %) during the preparation period, and in 15 patients (4.1 %) during PTC. The overall incidence of severe complications along the entire course was 8.2 % (30/364 patients). No patient died or required surgery. Intraductal manipulations, such as electrohydraulic lithotripsy or balloon dilation, and the first session of PTC were risk factors for procedure-related complications. CONCLUSIONS: PTC is a relatively safe and well-tolerated method for treating certain biliary tract diseases. Meticulous patient selection and a cooperative team approach are required in order to minimize the incidence of complications and to provide effective management.