Efficacy of detergent-based cleaning and wiping against SARS-CoV-2 on high-touch surfaces.

Efficacy of cleaning methods against SARS-CoV-2 suspended in either 5% soil load (SARS-soil) or simulated saliva (SARS-SS) was evaluated immediately (hydrated virus, T0) or 2 hours post-contamination (dried virus, T2). Hard water dampened wiping (DW) of surfaces, resulted in 1.77-3.91 log reduction (T0) or 0.93-2.41 log reduction (T2). Incorporating surface pre-wetting by spraying with a detergent solution (D + DW) or hard water (W + DW) just prior to dampened wiping did not unilaterally increase efficacy against infectious SARS-CoV-2, however, the effect was nuanced with respect to surface, viral matrix, and time. Cleaning efficacy on porous surfaces (seat fabric, SF) was low. W + DW on stainless steel (SS) was as effective as D + DW for all conditions except SARS-soil at T2 on SS. DW was the only method that consistently resulted in > 3-log reduction of hydrated (T0) SARS-CoV-2 on SS and ABS plastic. These results suggest that wiping with a hard water dampened wipe can reduce infectious virus on hard non-porous surfaces. Pre-wetting surfaces with surfactants did not significantly increase efficacy for the conditions tested. Surface material, presence or absence of pre-wetting, and time post-contamination affect efficacy of cleaning methods.

Evaluation of surface disinfection methods to inactivate the beta coronavirus Murine Hepatitis Virus.

The list of EPA-approved disinfectants for coronavirus features many products for use on hard, non-porous materials. There are significantly fewer products registered for use on porous materials. Further, many common, high-touch surfaces fall in between non-porous materials such as glass and porous materials such as soft fabrics. The objective of this study was to assess the efficacy of selected commercially available disinfectant products against coronaviruses on common, high-touch surfaces. Four disinfectants (Clorox Total 360, Bleach solution, Vital Oxide, and Peroxide Multi-Surface Cleaner) were evaluated against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV in cell culture medium was inoculated onto four materials: stainless steel, latex-painted drywall tape, Styrene Butadiene rubber (rubber), and bus seat fabric. Immediately (T0) or 2-hr (T2) post-inoculation, disinfectants were applied by trigger-pull or electrostatic sprayer and either held for recommended contact times (Spray only) or immediately wiped (Spray and Wipe). Recovered infectious MHV was quantified by median tissue culture infectious dose assay. Bleach solution, Clorox Total 360, and Vital Oxide were all effective (>3-log10 reduction or complete kill of infectious virus) with both the Spray Only and Spray and Wipe methods on stainless steel, rubber, and painted drywall tape when used at recommended contact times at both T0 and T2 hr. Multi-Surface Cleaner unexpectedly showed limited efficacy against MHV on stainless steel within the recommended contact time; however, it showed increased (2.3 times greater efficacy) when used in the Spray and Wipe method compared to Spray Only. The only products to achieve a 3-log10 reduction on fabric were Vital Oxide and Clorox Total 360; however, the efficacy of Vital Oxide against MHV on fabric was reduced to below 3-log10 when applied by an electrostatic sprayer compared to a trigger-pull sprayer. This study highlights the importance of considering the material, product, and application method when developing a disinfection strategy for coronaviruses on high-touch surfaces.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Impact of Intra-Abdominal Adhesion on Living Donor Right Hepatectomy.

The impact of intra-abdominal adhesion (IAA) on living donor right hepatectomy (LDRH) remains to be clarified. The purpose of this study was to compare both the donor and recipient outcomes of right lobe living donor liver transplantation according to IAA detected intraoperatively. LDRH donors were identified through a prospectively maintained database at the authors' institution between March 2008 and February 2014. IAA was graded according to Beck et al (Dis Colon Rectum 2000; 43: 1749-1753). LDRH donors with IAA (group A) were matched 1:3 to those without IAA (group B) based on age, gender, and BMI. Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow-up were compared. Thirty-two (7.6%) of a total of 420 LDRH donors had IAA around the liver. Nineteen donors had previous abdominal surgery. LDRH was successfully completed under upper midline laparotomy in all donors. Compared with group B, group A had a longer operative time (270 vs. 172 min; p < 0.001), a higher wound complication rate (28.1% vs. 4.2%; p = 0.009), and a longer postoperative stay (10 vs. 7 days; p = 0.009). All donors recovered completely to their previous activities. The 1-year graft and recipient survivals of recipients were comparable between two groups. These findings support the feasibility and safety of LDRH in patients with IAA.

Sex Difference in Chronic Obstructive Lung Disease. Does it Matter? A Concise Review.

Chronic obstructive lung disease (COPD) primarily affects men; however, its epidemiology has been changing because more women have become smokers. Recently, investigators found that although women and men were exposed to the same amount of smoke fume, women tended to have more severe disease and higher mortality rate. They also complain of more dyspnoea and may experience more severe exacerbations than men. This led to the question of whether sex has an impact on COPD course and whether women have a higher susceptibility to smoke fumes than men. That may be explained by multiple complex factors highlighting the relationship between sex, epidemiology, method of diagnostics and the clinical course of the disease. In this review, sex differences in epidemiology, clinical presentation, exacerbation, co-morbidities and treatment are covered.

Successful living donor liver transplantation between septuagenarians.

We report a case of a 76-year-old female who underwent living donor right hepatectomy for her 75-year-old husband with recurrent hepatocellular carcinoma. With her voluntary decision, full medical and psychiatric assessment was performed. The operative time was 130 min in the donor and 399 min in the recipient. Both the donor and recipient had an uneventful recovery and were discharged on days 7 and 10, respectively with normal liver function. The couple has had no complication so far and is currently doing well in good health 26 months after living donor liver transplantation.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

First Report of Sclerotium Rot Caused by Sclerotium rolfsii on Yacón in South Korea.

Yacón, or ground apple (Smallanthus sonchifolius), is a perennial plant grown in the northern and central Andes from Colombia to northern Argentina for its crisp, sweet, and tuberous roots. In 2012, yacóns cultivated in the research field of the Gyeongsangnam-do Agriculture and Extension Services, Jinju, South Korea, suddenly died. The characteristic symptoms consisted of rotting, wilting, and blighting. Initial symptoms included water-soaked lesions on lower stem tissue near the soil line. Infected plants gradually withered, and white mycelial mats and sclerotia appeared on the surface of roots and stems at the soil line. The sclerotia were collected and disinfested by immersion in 1% sodium hypochlorite solution for 30 s and in sterilized distilled water for 1 min. Then, the sclerotia were placed on potato dextrose agar (PDA) and incubated at 30°C. Numerous globoid sclerotia were formed on PDA after 18 days of growth. The sclerotia (1 to 3 mm in diameter) were white at first and then gradually turned dark brown. Aerial mycelia usually formed many narrow hyphal strands 4 to 9 µm wide. The white mycelium formed a typical clamp connection after 5 days of growth. To fulfill Koch's postulates, 50-day-old healthy seedlings were transplanted individually into pots (10 × 10 × 9 cm) containing autoclaved soil. After 7 days, five seedlings were inoculated with colonized agar discs (6 mm in diameter) directly on the base of the plant, and five yacón seedlings were inoculated similarly with PDA discs as the control treatment. The inoculated and non-inoculated plants were incubated in a humid growth chamber at 28°C for 24 h and then maintained in a greenhouse. Eight days after inoculation, the yacón seedlings inoculated with the fungus died, whereas those treated with PDA discs were symptomless. The fungus was re-isolated from the artificially inoculated plants. To confirm the identity of the causal fungus, the complete internal transcribed spacer (ITS) rDNA region of the fungus was amplified using the primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3') (2), and the PCR amplicons were cloned into the pGEM-T Easy vector. The resulting plasmid (pOR119) was sequenced in both directions with the primers M13F and M13R. The resulting 684 bp of ITS rDNA sequence was deposited in GenBank (Accession No. KJ944395). A DNA analysis revealed that it was 100% identical to Sclerotium rolfsii (HM355751). Cultures of S. rolfsii have been deposited with the Korean Agricultural Culture Collection (KACC 47750), National Academy of Agricultural Science, Suwon, South Korea. On the basis of symptoms, fungal colonies, the ITS sequence, and pathogenicity to the host, this fungus was identified as S. rolfsii Saccardo (1). This is the first report of sclerotium rot on yacón caused by S. rolfsii in South Korea. References: (1) J. E. M. Mordue. CMI Descriptions of Pathogenic Fungi and Bacteria, No. 410, 1974. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

Effects of exercise training on cardiac apoptosis in obese rats.

BACKGROUND AND AIM: The purpose of this study was to evaluate the effects of exercise training on cardiac apoptotic pathways in obesity. METHODS AND RESULTS: Sixteen lean Zucker rats (LZR) and sixteen obese Zucker rats (OZR) of 5-6 months of age as well as the other sixteen obese rats were subjected to treadmill running exercise for 1 h everyday for 3 months (OZR-EX). After exercise training or sedentary status of the rats, the excised hearts from the three groups were measured by heart weight index, H&E staining, TUNEL assays and Western blotting. Cardiac TUNEL-positive apoptotic cells, the protein levels of TNF alpha, Fas ligand, Fas receptors, Fas-associated death domain (FADD), Bad, Bax, activated caspase 8, activated caspase 9, and activated caspase 3 were higher in OZR than those in LZR. The protein levels of TNF alpha, Fas ligand, Fas receptors, FADD, activated caspase 8, and activated caspase 3 (Fas pathway) and the protein levels of Bad, Bax, Bax-to-Bcl2 ratio, activated caspase 9, and activated caspase 3 (mitochondria pathway) were lower in OZR-EX than those in OZR. CONCLUSION: Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways become more activated in obesity. Exercise training can prevent obesity-activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways. Our findings demonstrate a new therapeutic effect of exercise training to prevent delirious cardiac Fas-mediated and mitochondria-mediated apoptosis in obesity.

Initial phase establishment of an in vitro method for developmental neurotoxicity test using Ki-67 in human neural progenitor cells.

Building a precise alternative neurotoxicological test is of great importance to respond to societal and ethical requirements. In this study, a new developmental neurotoxicity test (DNT) was established with the human neural progenitor cell line. ReNcell CX cells were exposed to neurotoxic chemicals (aphidicolin, hydroxyurea, cytosine arabinoside, 5-fluorouracil, and ochratoxin A) or non-neurotoxic chemicals (sodium gluconate, sodium bicarbonate, penicillin G, and saccharin). Propidium iodide (PI) was used to evaluate cell viability. BrdU and Ki-76 were employed to determine cell proliferation. Based on the cell viability and proliferation, mathematical models were built by linear discriminant analysis. Furthermore, the neurotoxic-considered chemicals inhibited cell cycle progression at the protein level, supporting the biomolecular rationale for the predictive model. Overall, these results show that the new test method can be used to determine the potential developmental neurotoxicants or new drug candidates.

Prognostic significance of peritoneal washing cytology in patients with gastric cancer.

BACKGROUND: Positive peritoneal washing cytology is a poor prognostic factor in patients with gastric cancer. The right therapeutic approach for this condition has not been well documented. METHODS: Patients who underwent surgery for gastric cancer with suspected serosal invasion and peritoneal washing cytology at the Korean National Cancer Centre between May 2001 and December 2009 were included in this retrospective study. Clinicopathological factors and overall survival were analysed with respect to the cytological results and presence of peritoneal metastases. Prognostic factors were analysed in patients with positive cytology but without overt peritoneal metastases. RESULTS: A total of 1072 patients were included in the analysis, of whom 900 had negative cytology (C0 group) and 172 had positive cytology (C1 group). No peritoneal metastases (P0) were found in 830 patients (92·2 per cent) in the C0 group. Peritoneal metastases (P1) were found in 76 patients (44·2 per cent) in the C1 group. Median overall survival times in the P0 C1, P1 C0 and P1 C1 subgroups were 20·0, 14·0 and 10·0 months respectively. Multivariable analysis of the P0 C1 subgroup revealed that clinical N0-2 category and gastric resection were significantly associated with better prognosis (median survival 24·0 versus 13·0 months for N0-2 versus N3, and 21·0 versus 4·0 months for resected versus non-resected). CONCLUSION: Positive washing cytology in patients with gastric cancer is a negative prognostic factor for patients with, as well as those without, overt peritoneal metastases. Resection is an option in patients with clinical stage N0-2 disease without peritoneal metastases but with a positive washing cytology finding.

Increased striatal dopamine transporter density in moderately severe old restless legs syndrome patients.

BACKGROUND AND PURPOSE: Dopamine dysregulation in restless legs syndrome (RLS) may be varied by the severity of RLS, which could contribute to the conflicting results from previous functional neuroimaging studies on the central dopaminergic neurotransmission of RLS. The aim of this study was to observe whether reduced striatal dopaminergic neurotransmission is associated with moderate to moderately severe RLS. METHODS: Thirteen elderly patients with RLS and 12 normal elderly controls were enrolled in the study. All the subjects were dopaminergic-drug naïve and twelve patients with RLS had the severity of moderate to moderately severe degree based on the International Restless Legs Syndrome Study Group (IRLSSG) Severity Scale. We compared dopamine transporter density (DAT) availability and D2 receptor density in the striatum between patients with RLS and controls using [(123)I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane single-photon emission computed tomography (SPECT) and [(123)I]iodobenzamide SPECT. RESULTS: Dopamine transporter density of patients with RLS was increased in the caudate (P = 0.037), posterior putamen (P = 0.041), and entire striatum (P = 0.046) compared with that of normal controls. DAT density was higher in the anterior putamen of patients with RLS than controls, although statistically not significant (P = 0.079). There was no difference in the D2 receptor density between patients with RLS and normal controls in the whole striatum or any of subregions. CONCLUSIONS: Dysregulation rather than simple upregulation or downregulation of central dopaminergic neurotransmission may underlie the pathogenesis of RLS, and decreased dopaminergic neurotransmission may cause moderate to moderately severe RLS in the elderly.

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy.

AIMS: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). MATERIALS AND METHODS: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. RESULTS: After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count ≤10(5)/mm(3) (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. CONCLUSIONS: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

Effects of Dietary Fat Types on Growth Performance, Pork Quality, and Gene Expression in Growing-finishing Pigs.

This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace×Large White×Duroc) were used at 71±1 kg body weight (about 130 d of age) in 24 pens (320×150 cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of 14±3 d and the finishing diet was given for periods of 28±3 d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.

Characterization of filamentous bacteriophage PE226 infecting Ralstonia solanacearum strains.

AIMS: The aim of this study was to isolate and characterize new bacteriophages that infect a wide range of plant pathogenic Ralstonia solanacearum strains. METHODS AND RESULTS: Fifteen bacteriophages were isolated from pepper, tomato and tobacco plant rhizospheres infected with R. solanacearum. A host specificity analysis of the isolated phages using nine strains of R. solanacearum indicated great phage diversity in a single soil. Two phages, PE226 and TM227, showed clear plaques on all nine bacterial hosts tested and were virtually identical in morphology and genome. PE226, an Inovirus, is a long, flexible, filamentous phage carrying a circular (+) sense single-strand DNA genome of 5475 nucleotides. DNA sequences of PE226 exhibited nine open reading frames (ORF) that were not highly similar to those of other phages infecting R. solanacearum. The genome organization of PE226 was partially similar to that of p12J of Ralstonia pickettii. One ORF of PE226 showed identity to the zot gene encoding zonula occludens toxin of Vibrio cholera. Orf7 of PE226 was also present in the genome of R. solanacearum strain SL341. However, SL341, a highly virulent strain in tomato, was still sensitive to phage PE226. CONCLUSIONS: A new, flexible, filamentous phage PE226 infected wide range of R. solanacearum strains and carried unique circular single-strand DNA genome with an ORF encoding Zot-like protein. SIGNIFICANCE AND IMPACT OF THE STUDY: PE226 may be a new type of temperate phage, based on its lytic nature on a wide range of hosts and the presence of a zot homologue in a host bacterial genome.

Association of the G-protein and α2-adrenergic receptor gene and plasma norepinephrine level with clonidine improvement of the effects of diuretics in patients with cirrhosis with refractory ascites: a randomised clinical trial.

OBJECTIVE: Clonidine is an α(2)-adrenoceptor agonist which, by coupling with G-protein, has been proposed as an alternative treatment for refractory ascites of patients with cirrhosis for several years. Genetic polymorphisms of ß-adrenoceptor and angiotensin II type 1 receptor blockers have been reported to affect drug response in patients with cirrhosis. This study evaluated the clonidine-diuretic response rate, favourable predictors and genetic components of the clonidine-diuretic response in patients with cirrhosis with refractory ascites. METHODS: 270 patients with cirrhosis with refractory ascites were randomised equally into two treatment groups to receive diuretics alone or the clonidine-diuretics association. The primary end point was clonidine-diuretic response rate. Secondary end points were mean daily dose of diuretics, times of paracentesis, ascites-related readmission and 1-year survival rate. RESULTS: Good clonidine responders had better natriuresis and diuresis as well as a significant decrease in abdominal circumference, plasma renin, aldosterone and norepinephrine levels. The overall clonidine-diuretics response rate was 55-60%. In patients with cirrhosis, the prevalence of ARDA(2)C WD/DD and GNB3 CT/TT genotypes was 71% and 77%, respectively. Among the responders, 71% of patients with cirrhosis had the ARDA(2)C WD/DD genotype and 67% has the GNB3 CT/TT genotype. Besides higher baseline norepinephrine levels, the presence of both ARDA(2)C WD/DD and GNB3 CT/TT genotypes showed a positive predictive value of 82% and a negative predictive value of 79% for good clonidine response. CONCLUSIONS: These results suggest that neurohormonal and genetic testing may be used as predictive factors for the additive effects of clonidine on the diuresis and natriuresis effects of diuretics in patients with cirrhosis with refractory ascites.

The effect of myocardial injury on the clinical course of snake envenomation in South Korea.

CONTENT: This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. METHODS: The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. RESULTS: The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07-0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. DISCUSSION AND CONCLUSION: Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.

Coagulopathy after snake envenomation in South Korea.

OBJECTIVE: This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by South Korea's snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation. METHODS: Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed. RESULTS: One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5-83.5)% in the complete VICC group; factor X:94 (83-102) in the non-VICC group vs. 70 (66.5-79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups. DISCUSSION AND CONCLUSION: VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC.

Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia.

Hepatocyte growth factor (HGF) has been shown to induce angiogenesis in vivo and has potential as a candidate gene for 'therapeutic angiogenesis'. In vivo, two isoforms of HGF, HGF723 and HGF728, consisting of 723 and 728 amino acids, are generated through alternative splicing between exons 4 and 5, but the biological effects of their coexpression have not yet been elucidated. In this study, we generated a series of genomic-complementary DNA (cDNA) hybrids of the HGF gene by inserting various truncated intron 4 into the junction of exons 4 and 5 of HGF cDNA and analyzed the biological activities of these hybrid constructs. We showed that: (1) the hybrid called HGF-X7, which contained 1502 base pairs of intron 4, could drive a higher level of HGF expression than other hybrid constructs and cDNAs of each isoform alone; (2) the pCK vector was most efficient for the gene expression of HGF-X7; (3) coexpression of both isoforms of HGF could more efficiently induce the migration of human umbilical vein endothelial cell (HUVEC) and of the mouse myoblast cell line C2C12 myoblasts than a single isoform of HGF and human vascular endothelial growth factor (VEGF)165 at a given concentration; (4) intramuscular administration of pCK-HGF-X7 resulted in transient and localized HGF expression in the injected muscle without an increase in the HGF protein levels in other tissues including serum; and (5) intramuscular injection of pCK-HGF-X7 could more efficiently increase the number of angiographically recognizable collateral vessels, as well as improve an intra-arterial Doppler wire-measured blood flow in the rabbit model of hindlimb ischemia when compared with the identical vector encoding VEGF165 gene. These results showed that transfer of the genomic-cDNA hybrid of the HGF gene could be used as a potential therapeutic approach to human vascular diseases.