Chlorhexidine sensitivity in staphylococci isolated from patients with central line-associated bloodstream infection.

Since 2011, 2% chlorhexidine in 70% isopropyl alcohol (2% chlorhexidine tincture) has been widely used in Korea. To investigate changes in chlorhexidine sensitivity of staphylococci causing central line-associated bloodstream infections, 264 blood culture isolates from adult patients treated in intensive care units of five university hospitals between 2008 and 2016 were analysed. We observed no significant changes in chlorhexidine minimum inhibitory and bactericidal concentrations, or in the prevalence of resistance-associated genes before and after introduction of 2% chlorhexidine tincture. Thus, there was no evidence of increased resistance to chlorhexidine in staphylococci causing central line-associated bloodstream infections.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.

OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Clinical application of a free radial artery superficial palmar branch flap for soft-tissue reconstruction of digital injuries.

Unsuccessful reconstruction of injured fingers can lead to poor outcomes. The aim of this article was to investigate the clinical application of the radial artery superficial palmar branch flap for soft-tissue reconstruction of the finger. We treated 125 patients with various finger injuries who underwent free radial artery superficial palmar branch flap reconstruction between October 2010 and March 2015. There were 46 distal finger injuries, 25 distal finger amputation following failed replantation and 54 palmar digital injuries with tendon, bone or joint exposure requiring soft-tissue reconstruction. Of the 125 cases, 114 flap reconstructions were considered successful. We believe that a free radial artery superficial palmar branch flap transfer is credible and useful for reconstructing various finger injuries. LEVEL OF EVIDENCE: III.

Modified anterograde pedicle advancement flap in fingertip injury.

Soft tissue reconstruction is needed to maintain the maximum length of the fingers in fingertip injury. The purpose of this study was to present an anterograde pedicle advancement flap technique, for the treatment of fingertip injuries, which involved a modification to the anterograde advancement flap by the dissection of the digital nerve and artery with a pedicle to advance the flap. This technique was used in 12 fingers in patients who had undergone soft tissue reconstruction of fingertip injuries between January 2012 and October 2013. The sizes of the flaps ranged from 8 × 7 mm to 14 × 10 mm. The mean length of advancement was 9.7 mm (range 7-13). The mean value of the static two-point discrimination test of the healed flaps was 5.1 mm (range 4-6) and the flaps survived in all the 12 cases. The modified anterograde pedicle advancement flap provides a reliable coverage of sensate soft tissue without bone shortening in fingertip injuries.Level II.

Comparison of three-dimensional isotropic and conventional MR arthrography with respect to the diagnosis of rotator cuff and labral lesions: focus on isotropic fat-suppressed proton density and VIBE sequences.

AIM: To compare the diagnostic accuracies of three-dimensional (3D) isotropic magnetic resonance arthrography (MRA) using fat-suppressed proton density (PD) or volume interpolated breath-hold examination (VIBE) sequences with that of conventional MRA for the diagnosis of rotator cuff and labral lesions. MATERIALS AND METHODS: Eighty-six patients who underwent arthroscopic surgery were included. 3D isotropic sequences were performed in the axial plane using fat-suppressed PD (group A) in 53 patients and using VIBE (group B) in 33 patients. Reformatted images were obtained corresponding to conventional images, and evaluated for the presence of labral and rotator cuff lesions using conventional and 3D isotropic sequences. The diagnostic performances of each sequence were determined using arthroscopic findings as the standard. RESULTS: Good to excellent interobserver agreements were obtained for both 3D isotropic sequences for the evaluation of rotator cuff and labral lesions. Excellent agreement was found between two-dimensional (2D) and 3D isotropic MRA, except for supraspinatus tendon (SST) tears by both readers and for subscapularis tendon (SCT) tears by reader 2 in group B. 2D MRA and 3D isotropic sequences had high diagnostic performances for rotator and labral tears, and the difference between the two imaging methods was insignificant. CONCLUSIONS: The diagnostic performances of 3D isotropic VIBE and PD sequences were similar to those of 2D MRA.

Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease.

Huntington's disease (HD) is characterized clinically by chorea, psychiatric disturbances, and dementia, while it is characterized pathologically by neuronal inclusions as well as striatal and cortical neurodegeneration. The neurodegeneration arises from the loss of long projection neurons in the cortex and striatum. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (Ask1) in the pathogenesis of HD. We analyzed the expression of Ask1 and huntingtin (htt) within the striatum and cortex and also examined the interaction of Ask1 with htt fragments in HD (R6/2) mice. Additionally, we inhibited Ask1 and analyzed the resulting changes in brain-derived neurotrophic factor (BDNF) expression, motor function, and striatal atrophy. Ask1 activity was blocked using an Ask1 antibody raised against the C-terminus of the Ask1 protein. The anti-Ask1 antibody was infused into the striatum of the HD mice for four weeks using a micro-osmotic pump. The levels of Ask1 protein and endoplasmic reticulum (ER) stress were increased in HD mice. Binding of inactivated Ask1 to htt fragments was more prevalent in the cytosol than the nucleus of cortical neurons. Binding of inactivated Ask1 to htt fragments prevented translocation of the htt fragments into the nucleus, resulting in an improvement in motor dysfunction and atrophy. In the normal state, active Ask1 may help htt fragments enter the nucleus, while inactivated Ask1 hinders this translocation by binding to but not releasing fragmented htt into the nucleus. We propose that Ask1 may interact with htt fragments and subsequently induce ER stress. BDNF depletion may be prevented by targeting Ask1; this would decrease ER stress and possibly ameliorate behavioral or anatomical abnormalities that accompany HD. Therefore, regulating the amounts and activity of the Ask1 protein is a novel strategy for treatment of HD.

A dual anteroposterior approach to the Bernese periacetabular osteotomy.

When the Bernese periacetabular osteotomy is performed through an anterior approach, the ischial and retroacetabular osteotomies and manual fracture of the incompletely osteotomized ischium are conducted with an incomplete view resulting in increased risk and morbidity. We have assessed the dual anteroposterior approach which appears to address this deficiency. We compared the results of the Bernese periacetabular osteotomy performed in 11 patients (13 osteotomies) through a single anterior approach with those in 12 patients (13 osteotomies) in whom the procedure was carried out through a dual anteroposterior approach. The estimated blood loss, the length of anaesthesia, duration of surgery and radiological parameters were measured. The mean operative time and length of anaesthesia were not significantly different in the two groups (p = 0.781 and p = 0.698, respectively). The radiological parameters improved to a similar extent in both groups after the operation but there was significantly less blood loss in the dual osteotomy group (p = 0.034). The dual anteroposterior approach provides a direct view of the retroacetabular and ischial parts of the osteotomy, within a reasonable operating time and with minimal blood loss and gives a satisfactory outcome.

Plasma ghrelin levels and their relationship with gastric emptying in patients with dysmotility-like functional dyspepsia.

BACKGROUND/AIMS: Ghrelin affects gastric motility. However, little is known about the role of ghrelin in the pathophysiology of functional dyspepsia (FD). We investigated plasma ghrelin levels and their relationship with gastric emptying time in dysmotility-like FD patients. METHODS: 42 patients with dysmotility-like FD and 14 healthy volunteers were enrolled in the study. Gastric half-emptying time was measured using a radiolabeled meal. Plasma total ghrelin levels before and after the meal were determined using a radioimmunoassay kit. RESULTS: Preprandial ghrelin levels were significantly lower in FD patients than in controls. Postprandial ghrelin levels were similar between the two groups. Abnormally low preprandial ghrelin levels were observed in 7 out of 42 patients, in whom significant postprandial decrease of ghrelin levels was absent. Delayed gastric emptying was observed in 5 out of 7 patients with abnormally low ghrelin levels. Pre- or postprandial ghrelin levels were not significantly correlated with gastric half-emptying time, both in the patient group and in the control group. CONCLUSIONS: Abnormally low preprandial ghrelin levels and absence of significant postprandial decrease of ghrelin levels are present in a subset of dysmotility-like FD patients. Further investigation on the pathogenetic implication of these alterations in FD is required.

Clinical features and treatment outcomes of advanced stage primary hepatic angiosarcoma.

BACKGROUND: Primary hepatic angiosarcoma is a very rare malignancy with a poor prognosis. While surgical resection has been validated as curative choice, most cases are diagnosed too late for resection. Nonetheless, treatment protocols have not been established and also there are very few reports on the clinical features and treatment outcomes. PATIENTS AND METHODS: Among 11,939 patients diagnosed with primary hepatic tumors from January 1985 to December 2007 at two centers, five patients were diagnosed with primary hepatic angiosarcoma. We analyzed patients' demographics, tumor characteristics, treatment modality, and outcomes using imaging, serology, and pathology. RESULTS: All five patients were diagnosed at advanced stage with distant metastases. The most common symptom was abdominal pain. The levels of the tumor markers were within the normal range and serological tests were negative for hepatitis B and C viruses. Two of four patients who received chemotherapy died <3 months after diagnosis, but the other two patients survived >6 months. CONCLUSIONS: A combination of chemotherapy resulted in an improved outcome for two of four patients, suggesting the potential usefulness of palliative chemotherapy to improve survival. This case study may aid in planning chemotherapy for patients with advanced hepatic angiosarcoma.

Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases.

BACKGROUND: The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer. METHODS: Among 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery. RESULTS: The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival. CONCLUSIONS: Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.

The incidence of Perthes' disease in Korea: a focus on differences among races.

The purpose of this study was to determine the annual incidence of Perthes' disease in Korea and compare this with other populations. A survey identified all newly diagnosed children with Perthes' disease aged 14 years or younger in South Honam, Korea, between January 1999 and December 2001. A total of 84 children were included: 29 in 1999, 28 in 2000 and 27 in 2001. The mean annual incidence was 3.8 per 100 000. This is similar to that reported in other Asian countries, but higher than in black populations and lower than in Caucasians.

Familiarity with, knowledge of, and attitudes toward epilepsy in residents of Seoul, South Korea.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the perceptions of epilepsy in Seoul, South Korea, a country where social stigma toward epilepsy is still pronounced. METHODS: We randomly selected 1000 persons living in Seoul and performed telephone interviews regarding public awareness, knowledge, and attitudes toward epilepsy. RESULTS: Among 1000 respondents, the 92% who had read or heard about epilepsy became the subjects of the study. Word of mouth was most often referenced as a source of knowledge (78%). Forty-seven percentage believed that epilepsy is inheritable, whereas 5% thought that epilepsy is a mental illness. Marriage of their children to an epileptic person, childbearing by women with epilepsy, and employing a person with epilepsy were opposed by more than 50% of respondents. The reasons for the negative attitudes were that epilepsy was hereditary and untreatable (P < 0.05, respectively). CONCLUSIONS: Our study revealed that there still remains negative attitudes regarding the marriage, childbearing, and employment of persons with epilepsy, which may stem from misconceptions about the cause and treatability of epilepsy, possibly due in part to the influence of herbal medicine, and South Korea's ethnic homogeneity. Public health education either through media or school health education is urgently needed to improve knowledge about, and attitudes toward epilepsy.

Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes.

A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7-fold increase in plasma transaminase toxicity, an indication of liver toxicity. Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors that also partly prevented cytotoxicity. The 4-HA metabolite formed by NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced toxicity whereas sorbitol, an NADH-generating nutrient, prevented the cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when 4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p-quinone rather than involving oxidative stress.

Implication of co-measured platelet factor 4 in the reliability of the results of the plasma transforming growth factor-beta 1 measurement.

We examined the possible alteration of circulating transforming growth factor-beta1 (TGF-beta1) concentrations in a time-dependent fashion in human plasma. Plasma TGF-beta1 was measured three times at 2 week-intervals from each of 12 healthy participants. Platelet factor 4 (PF4) was measured in parallel with TGF-beta1 to estimate the degree of platelet degranulation. TGF-beta1 levels of the second and third plasma samples, in which PF4s were measured as < approximately 1000 IU/ml, were relatively low and fell in a narrow range. However, TGF-beta1 levels of the first samples, in most of which PF4s were > approximately 1000 IU/ml, appeared much higher and more variable than those of the second or third samples. These results indicate that the platelet degranulation accounted for the higher TGF-beta1 levels in the first samples, and thus did not support our initial assumption. We, nevertheless, could propose a useful guidance in the assessment of TGF-beta1 levels in plasma. When the PF4 level is measured as < approximately 1000 IU/ml under our assay conditions, the TGF-beta1 level in a given plasma sample might be accepted as a reliable value considering the effect of platelet degranulation on TGF-beta1 level.

Structure-activity relationship studies of isoquinolinone type anticancer agent.

Substituted isoquinolin-1-ones (1) were synthesized to test their in vitro anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.

Thermal inactivation kinetics and application of phospho- and galactolipid-degrading enzymes for evaluation of quality changes in frozen vegetables.

Lipid-acyl hydrolases (LAHases) play significant roles in lipid degradation during the storage of vegetables. In particular, spinach contains a large portion of galactolipids (59.5%) and phospholipids (22.4%) among its fat-soluble components, which are used as substrates for LAHases. Thermal inactivation of various LAHases, including phospholipases A, C, and D, phosphatase, and galactolipase, from spinach and carrot was investigated to optimize the blanching process prior to the frozen storage of vegetables. Thermostability of phospholipase C or galactolipase was greatest among the LAHases from both spinach and carrot. Galactolipase from spinach exhibited a D value of 3.39 x 10(2) s at 80 degrees C and a z value of 8.21 degrees C, whereas phospholipase C from spinach showed D(80) of 1.72 x 10(2) s with a z value of 9.26 degrees C. In the case of LAHases from carrot, the D(65) and z values of galactolipase were 6.66 x 10(2) s and 8.69 degrees C, respectively, whereas phospholipase C displayed D(85) of 3.12 x 10(2) s and a z value of 15.8 degrees C. Highly active and thermostable galactolipase and phospholipase C in spinach and carrot made it possible for them to be used as indicator enzymes for the determination of quality deterioration of the stored vegetables.

Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.

A whole blood bactericidal assay for tuberculosis.

The bactericidal activity of orally administered antituberculosis (anti-TB) drugs was determined in a whole blood culture model of intracellular infection in which microbial killing reflects the combined effects of drug and immune mechanisms. Rifampin (Rif) was the most active compound studied and reduced the number of viable bacilli by >4 logs. Isoniazid (INH), 2 quinolones, and pyrazinamide (PZA) showed intermediate levels of activity. Ethambutol exerted only a bacteristatic effect; amoxicillin/clavulanate was inactive. The combination of INH-Rif-PZA showed strong activity against 11 drug-sensitive isolates (mean, -3.8 log) but no activity against 12 multidrug-resistant (MDR) strains. The combination of levofloxacin-PZA-ethambutol had intermediate bactericidal activity against MDR isolates (mean, -1.2 log) but failed to equal that of INH-Rif-PZA against sensitive isolates (P<.001). The whole blood BACTEC method (Becton Dickinson) may be useful for the early clinical evaluation of new anti-TB drugs and in the management of individual patients.

Serum-induced hypha formation in the dimorphic yeast Yarrowia lipolytica.

The dimorphic yeast Yarrowia lipolytica forms true hyphae in a medium containing N-acetylglucosamine. We made a new finding that serum is a very effective inducer of hypha formation of Y. lipolytica: serum induced its hyphal growth very quickly compared to N-acetylglucosamine (4 h vs. 10 h). Osmotic and oxidative stresses (0.2 M NaCl and 20 mM H2O2) inhibited the hypha formation induced by N-acetylglucosamine, but did not suppress the hypha formation triggered by serum. Serum-specific morphological mutants, which formed hyphae in the N-acetylglucosamine medium but not in serum medium, could be isolated. These results suggest that the signal triggered by serum may be transduced through a different pathway, at least in part, from that used for the N-acetylglucosamine signal in Y. lipolytica.