Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.
Animals ; Drug Delivery Systems ; Fluorescence ; Hyaluronic Acid ; Kidney ; Liver ; Lung ; Lymph Nodes ; Mice ; Nanoparticles ; Pharmacokinetics ; Spleen ; Sublingual Gland ; Testis ; Tissue Distribution ; Toxicokinetics

BACKGROUND: Flow cytometric immunophenotyping has been used to identify neoplastic plasma cell populations in patients with multiple myeloma (MM). Previous reports have described the use of several antigens, including CD38, CD138, CD56, CD117, CD52, CD19 and CD45, to distinguish distinct populations of plasma cells. The aim of this study was to evaluate a simplified immunophenotyping panel for MM analysis. METHODS: A total of 70 patients were enrolled in the study, 62 of which were newly diagnosed with MM (untreated), whereas the remaining 8 were undergoing bone marrow assessment as part of follow-up after treatment (treated). Treated cases included 3 patients with relapse and 5 patients with persistence of MM. Multiparametric flow cytometric immunophenotyping was performed using monoclonal antibodies against CD56, CD19, CD138 (CD38), and CD45. RESULTS: In differential counts, plasma cells in bone marrow (BM) accounted for 3.6-93.2% of the total nucleated cell count. The positive expression rates of CD56, CD19, CD138, and CD45 in neoplastic myeloma cells were 83.9%, 0%, 98.4%, and 37.1%, respectively, among the 62 untreated cases, and 75.0%, 0%, 87.5%, and 37.5%, respectively, among the 8 treated cases. CD19 expression of neoplastic plasma cells was negative in both untreated and treated cases. CONCLUSION: The simplified immunophenotyping panel, CD56/CD19/CD138(CD38)/CD45, is useful for distinguishing neoplastic myeloma cells from reactive plasma cells in clinical practice. In addition, CD19 represents the most valuable antigen for identifying neoplastic myeloma cells in patients with MM.
Antibodies, Monoclonal ; Bone Marrow ; Cell Count ; Flow Cytometry ; Follow-Up Studies ; Humans ; Immunophenotyping ; Multiple Myeloma ; Plasma ; Plasma Cells ; Recurrence

BACKGROUND: The loss of resistance technique is the most popular method for identifying the epidural space. Air or liquid is a commonly used medium for this technique. These two media have certain advantages and disadvantages. A liquid filled pressure line connected to an air syringe might have advantages of both air and liquid while preventing the drawbacks of each medium. METHODS: Twenty-five consecutive patients were scheduled to receive an epidural anesthesia for surgery and selected for study. A lidocaine filled pressure line connected to an air syringe allowed for sequential injection of lidocaine and air. The time spent on the procedure, amount of air injected into the epidural space, inadvertent puncture of the dura mater, and rate of anesthetic failure were recorded. RESULTS: The procedure took less than 2 minutes in 22 cases. The average amount of air lost from the syringe during the loss of resistance test was 0.98 +/- 0.23 ml in 22 patients. Volume of the 3-way connected pressure line was 0.95 ml. Therefore, the air volume injected into the epidural space was minimal. In the other 3 cases where previous spinal disease existed, multiple epidural approaches were needed and the procedure took relatively longer with larger injection volumes. There were no complications. CONCLUSIONS: This technique minimized injection of the air into the epidural space during identification but simultaneously, it does not disturb the feel of air compressibility in the syringe.
Anesthesia, Epidural ; Dura Mater ; Epidural Space ; Feasibility Studies ; Humans ; Lidocaine ; Punctures ; Spinal Diseases ; Syringes

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

Phospholipid hydroperoxide glutathione peroxidase(PHGPx), an antioxidative selenoprotein, is modulated byestrogen in the testis and oviduct. To examine whetherpotential endocrine disrupting chemicals (EDCs) affectthe microenvironment of the testes, the expression patternsof PHGPx mRNA and histological changes were analyzedin 5-week-old Sprague-Dawley male rats exposed to severalEDCs such as an androgenic compound [testosterone (50,200, and 1,000microg/kg)], anti-androgenic compounds [flutamide(1, 5, and 25mg/kg), ketoconazole (0.2 and 1mg/kg), anddiethylhexyl phthalate (10, 50, and 250mg/kg)], andestrogenic compounds [nonylphenol (10, 50, 100, and 250mg/kg), octylphenol (10, 50, and 250mg/kg), and diethyl-stilbestrol (10, 20, and 40microg/kg)] daily for 3 weeks via oraladministration. Mild proliferation of germ cells andhyperplasia of interstitial cells were observed in the testesof the flutamide-treated group and deletion of thegerminal epithelium and sloughing of germ cells wereobserved in testes of the diethylstilbestrol-treated group.Treatment with testosterone was shown to slightly decreasePHGPx mRNA levels in testes by the reverse transcription-polymerase chain reaction. However, anti-androgeniccompounds (flutamide, ketoconazole, and diethylhexylphthalate) and estrogenic compounds (nonylphenol,octylphenol, and diethylstilbestrol) significantly up-regulated PHGPx mRNA in the testes (p<0.05). Thesefindings indicate that the EDCs might have a detrimentaleffect on spermatogenesis via abnormal enhancement ofPHGPx expression in testes and that PHGPx is useful as abiomarker for toxicity screening of estrogenic or anti-androgenic EDCs in testes.
Androgen Antagonists/pharmacology ; Animals ; Diethylhexyl Phthalate/pharmacology ; Diethylstilbestrol/pharmacology ; Endocrine Disruptors/*pharmacology ; Estrogens, Non-Steroidal/pharmacology ; Flutamide/pharmacology ; Glutathione Peroxidase/*biosynthesis/genetics ; Histocytochemistry ; Ketoconazole/pharmacology ; Male ; Phenols/pharmacology ; RNA, Messenger/*biosynthesis/genetics ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spermatogenesis/drug effects ; Testis/*drug effects/*enzymology ; Testosterone/pharmacology

"Biliary cast syndrome" describes a cast formed from retained lithogenic material, and this cast is morphologically confined to the bile duct; this develops in 4~18% of liver transplant recipients. The pathogenesis of cast formation is not clearly understood. The proposing etiological factors for biliary cast syndrome include acute cellular rejection, a prolonged cold ischemic time, use of postoperative biliary drainage tubes and biliary infection. These casts are more likely to develop in the setting of hepatic ischemia and biliary stricture. Endoscopic and percutaneous cast extraction might achieve favorable results and this should be attempted before surgical therapy. We report here on a case of biliary cast syndrome that was secondary to orthotopic liver transplantation; this was successfully treated via percutaneous choledochoscopic removal. We also include a review of the literature.
Bile Ducts ; Cold Ischemia ; Constriction, Pathologic ; Drainage ; Humans ; Ischemia ; Liver Transplantation* ; Liver* ; Superior Mesenteric Artery Syndrome ; Transplantation

BACKGROUND: Additional tests ordered by doctors after checking abnormal routine test results for inpatients are usually delayed for one day or more, which in turn delays diagnostic and therapeutic procedures and prolongs length of stay (LOS) for the patients. We at Department of Laboratory Medicine, Asan Medical Center (AMC), established a "secondary order system for laboratory tests without additional blood sampling" to improve the conventional reflexive tests. METHODS: Oracle 8.0 (Oracle Co., Belmont, CA, USA) was used for data base software and Powerbuilder (Powersoft, Burlington, UK) for client development tool. Specimens subjected to "reflexive tests by doctors without additional blood sampling" were SST tubes for routine chemistry and EDTA for routine hematology requested in the morning of additional requests of the laboratory tests. RESULTS: Programs of registration and request for "reflexive tests by doctors without additional blood sampling" and bar code printing were developed for clinicians to check the routine test results and to order additional tests, if necessary, and for laboratory to perform the requested tests using the same samples used for routine chemistry and hematology tests in the morning. Additionally requested tests were done by finding the SST and EDTA samples, putting newly printed bar code, and processing them as usual. In February 2004, right after introducing reflexive tests by doctors without additional blood sampling, 75 additional requests were made for 50 patients, but they increased gradually up to 1,020 tests for 698 patients in December 2004. In 2005, the monthly average number of tests was 1,035 for 742 patients. CONCLUSIONS: The reflexive tests by doctors without additional blood sampling developed at AMC helped establish a rapid reporting of test results, which in turn reduced LOS related to laboratory. It also increased patient satisfactory indices by reducing repeated blood sampling and would also contribute to the financial health of the hospital.
Automatic Data Processing ; Chemistry ; Chungcheongnam-do ; Edetic Acid ; Hematology ; Humans ; Inpatients ; Length of Stay ; Reflex

Human babesiosis is a tick-borne infectious disease caused by Babesia species. The clinical diagnosis is difficult because of nonspecific symptoms like flu. Rapid diagnosis of human babesiosis is microscopic examination in peripheral blood smear (Giemsa-stain) which reveals characteristic forms of an intracellular quadruplet parasite. But differentiation between Babesia microti and Plasmodium species can be quite difficult because of the morphologic similarity. We experienced a case of human babesiosis. The patient was a 62-year old Korean male who had been in New Jersey, U.S.A for 2 months. We initially diagnosed as malaria infection because the peripheral blood smear revealed intracellular single ring form organism. But the patient was not improved significantly by the treatment with chloroquine regimen. Finally we confirmed human babesiosis by polymerase chain reaction for Babesia microti. We treated the patient successfully with a regimen of atovaquone and azithromycin which has fewer adverse reactions than a regimen of clindamycin and quinine.
Animals ; Atovaquone* ; Azithromycin* ; Babesia ; Babesia microti ; Babesiosis* ; Chloroquine ; Clindamycin ; Communicable Diseases ; Diagnosis ; Humans* ; Malaria ; Male ; Middle Aged ; New Jersey ; Parasites ; Plasmodium ; Polymerase Chain Reaction* ; Quadruplets ; Quinine