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The rates of influenza-associated neurologic complications are variable among studies, and a difference has been observed between the Western and Asian countries. The study aims to evaluate the frequency and characteristics of influenza-associated neurologic complications.We performed a retrospective review of hospitalized cases of influenza infection from October 2010 to April 2017 from 3 referral hospitals.A total of 1988 influenza cases were identified. Influenza-associated neurologic complications were 161 cases (8.1%); influenza virus A was detected in 113 (70.2%) cases, B in 47 (29.2%) cases and both A and B in 1 case (0.6%). Twenty-four patients (15%) had underlying neurologic diseases. The most common diagnosis was a simple febrile convulsion (44%), followed by complex febrile convulsion (29%), fever-provoked seizure under pre-existing neurologic disease or afebrile seizure (14%), encephalopathy/encephalitis (8%) and meningitis (5%). Most of the patients fully recovered (96%). Three patients (1.9%) died of myocarditis (n = 1), encephalopathy (n = 1), and simultaneous encephalitis and myocarditis (n = 1). Pre-existing neurologic disease, age groups of 6 months to 6 years and 6-12 years were a risk factor of influenza-associated neurologic complications with an adjusted odds ratio of 5.41 (95% confidence interval [CI] 3.23-9.06, P0.001), 12.99 (95% CI 1.77-95.19, P = 0.01) and 8.54 (95% CI 1.14-64.79, P = 0.04), respectively. There was no association between neuropsychiatric adverse events and oseltamivir prescription (P = 0.17).Influenza-associated neurologic complications are not uncommon, and most patients fully recovered. The frequency of influenza-associated neurologic complications in Korean children was not significantly different from that of children in Western countries.

Objective To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC). Materials and methods This study included 287 patients aged 40-80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months). Results CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD. Conclusion CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD.

We performed a retrospective study to evaluate clinical effectiveness of vancomycin loading strategy and factors associated with achieving optimal Cmin. Patients administered vancomycin for ≥72 h from January to June 2018 were enrolled. Patients were divided into two groups: loading (LD) and non-loading (NLD). LD was defined as initial vancomycin dose ≥20 mg/kg and ≥120% of maintenance dose. During study period, 70 and 71 received initial LD (24.2 ± 2.5 mg/kg) and NLD (17.3 ± 3.3 mg/kg) doses of vancomycin, respectively (p < .001). Achievement of optimal Cmin was not different before administration of the third dose (24.4% in LD versus 18.2% in NLD, p = .484) and within 72 h (22.9% versus 28.2%, p = .759). Risk factors for failure to achieve optimal Cmin before administration of the third dose were higher creatinine clearance and higher level of serum albumin. Therefore, more sufficient loading or patient-specific dose strategies should be used to achieve optimal serum vancomycin Cmin.

Background: The possibility of an association between early menopause and the risk of non-alcoholic fatty liver disease (NAFLD) is as yet unclear.Methods: The subjects consisted of 4354 postmenopau...

BACKGROUND AND PURPOSE: Follow-up with MRA for intracranial aneurysms after stent-assisted coiling is complicated by imaging artifacts. We evaluated the usefulness of an alternative method: vessel wall MR imaging. MATERIALS AND METHODS: We conducted a single-center, retrospective review of medical records of 47 patients who underwent 3D TOF-MRA, vessel wall MRI, and DSA after stent-assisted coiling between March 2016 and January 2018. We evaluated the mean value of the signal intensity in the stented artery and the contralateral normal artery on vessel wall MRI. The quality of visualization was further compared between TOF-MRA and vessel wall MRI. Furthermore, we evaluated the diagnostic accuracy and concordance rate of TOF-MRA and vessel wall MRI for assessing the patency of the stented parent artery. DSA was used as a reference test. RESULTS: The mean signal intensities of the stented and normal arteries on vessel wall MRI were not significantly different (P = .133). The mean scores for the visualization of the stented parent artery on vessel wall MRI were significantly superior to those of TOF-MRA images (P < .001). Vessel wall MRI reached an excellent positive predictive value (100%). However, TOF-MRA had a poor positive predictive value (11%; 95% CI, 9%–12%). The likelihood ratios of vessel wall MRI and TOF-MRA were 27.36 (P < .001) and 2.98 (P = .225), respectively. The concordance rate of vessel wall MRI and TOF-MRA with DSA for evaluating the state of the stented artery was 100% (κ = 1) and 28% (κ = 0.038), respectively. CONCLUSIONS: Vessel wall MRI may be useful in evaluating the patency of stented arteries after stent-assisted coil embolization for intracranial aneurysms.

SummaryWhat is known and objective Drug therapies are critical for preventing secondary complications in acute coronary syndrome (ACS). The purpose of this study was to develop and apply a pharmaceutical care service (PCS) algorithm for ACS and confirm that it is applicable through a prospective clinical trial. Methods The ACS-PCS algorithm was developed according to extant evidence-based treatment and pharmaceutical care guidelines. Quality assurance was conducted through two methods: literature comparison and expert panel evaluation. The literature comparison was used to compare the content of the algorithm with the referenced guidelines. Expert evaluations were conducted by nine experts for 75 questionnaire items. A trial was conducted to confirm its effectiveness. Seventy-nine patients were assigned to either the pharmacist-included multidisciplinary team care (MTC) group or the usual care (UC) group. The endpoints of the trial were the prescription rate of two important drugs, readmission, emergency room (ER) visit and mortality. Results and discussion The main frame of the algorithm was structured with three tasks: medication reconciliation, medication optimization and transition of care. The contents and context of the algorithm were compliant with class I recommendations and the main service items from the evidence-based guidelines. Opinions from the expert panel were mostly positive. There were significant differences in beta-blocker prescription rates in the overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC group compared to the UC group, respectively. What is new and conclusion We developed a PCS algorithm for ACS based on the contents of evidence-based drug therapy and the core concept of pharmacist services.

Objectives Nationwide practice patterns during the implementation of novel technology, such as carotid angioplasty and stenting (CAS) and embolic protection devices (EPD), and the clinical impact thereof have received less attention. Methods The Nationwide Inpatient Sample, constituting a 20% representative sample of non-federal US hospitals, was analyzed from years 1998 to 2007. Hospital outcome was stratified into in-hospital mortality (IHM), long-term facility discharge, and home/ short-term facility discharge (HSF). Results Discharge outcome improved for CAS over the decade. However, this improvement occurred in two phases with a period of worsening (2003–2005) in between. During this transition period, the risk of IHM following CAS was increased (RR 1.29–2.43) and was lower for good outcome (HSF: RR 0.97–0.99) when compared with 2002/2003. During the same transition period, carotid endarterectomy (CEA) was associated with a lower risk of IHM (RR 0.75–1.00), but also a lower risk of HSF (RR 0.98–0.99). Conclusions The results lead to the hypothesis that the nationwide introduction of CAS-EPD may have been associated with temporary increases in in-hospital mortality and discharge morbidity. If such ‘clinical opportunity costs’ exist with the widespread introduction and adoption of new medical technology with proven efficacy in randomized trials, effective mechanisms are needed for mitigation or prevention during the transition period.

Radiotherapy is frequently indicated to treat cerebral gliomas. Accurate response evaluation after radiotherapy is essential to determine the efficacy of treatment. We retrospectively analyzed the volumetric tumor response after simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in patients with gliomas. Thirty-five patients (Grade II, 7 patients; Grade III, 12; and Grade IV, 16) were treated with SIB-IMRT with a median total dose of 55.9 Gy/26 fractions for Grade II and 60 Gy/25 fractions for Grade III-IV tumors. Tumor responses were evaluated for enhancing volume on post-gadolinium T1-weighted images (Vgd) and hyper-intensity volume on T2-weighted FLAIR images (Vfl) on serial MRIs. With the median follow-up of 24.0 months, overall response rates (RRs) were 57% for Vgd and 51% for Vfl. Tumor grade was predictive of response favoring the lower grade in Vfl with RRs of 86% for Grade II, 75% for Grade III, and 19% for Grade IV tumors (p = 0.004). Time to 50% or greater volume reduction (T50) in Vgd was 8 months for grade III. The T50 in Vfl was approximately 24 months both for Grade II and III tumors. Majority of Grade IV tumors continued to progress and never reached the T50 in Vgd or Vfl. Responders survived longer than non-responders for Vgd and Vfl. Volume response after radiotherapy was dependent upon tumor grade and time. LGGs are very responsive to radiotherapy with the RRs of 86% in Vfl. The response of Vfl is more protracted compared to Vgd. Further investigation is needed to determine the clinical significance of volumetric response evaluation.

SUMMARY Objective: Although the pathogenesis of aspirininduced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-a ,a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-a promoter polymorphisms in the development of AIU, we performed an association study of TNF-a promoter polymorphisms with AIU phenotype. Methods: Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-a gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a singlebase extension method. Haplotype analyses were done. Results: The genotype frequencies of TNF1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controlsinbothco-dominant(P =0 AE014,P =0 AE007) and dominant (P =0 AE007, P =0 AE004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P =0 AE004, Pc =0 AE02) and dominant models (P =0 AE002, Pc =0 AE01). Conclusions: These findings suggest that the two promoter polymorphisms of TNF-a at -1031T>C and -863C>A may contribute to the development of AIU.

BACKGROUND AND PURPOSE: Stent-assisted coiling of intracranial aneurysms requires antiplatelet therapy, typically aspirin and clopidogrel to prevent thromboembolic complications. There is a substantial concern that tirofiban may increase the risk of hemorrhage when used as an antiplatelet premedication in ruptured intracranial aneurysms. Our aim was to evaluate the safety and efficacy of intravenous tirofiban administration, instead of oral dual antiplatelet agents, as an antiplatelet premedication for stent-assisted coiling in patients with acutely ruptured intracranial aneurysms. MATERIALS AND METHODS: We conducted a retrospective review of a data base containing a consecutive series of patients who underwent stent-assisted coiling for acutely ruptured intracranial aneurysms between March 2010 and January 2015. Intravenous tirofiban was administered to all patients before stent-assisted coiling, instead of premedication with loading doses of aspirin or clopidogrel. RESULTS: Forty patients with 41 aneurysms received intravenous tirofiban and underwent stent-assisted coiling. None of the patients had a newly developed intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage. Intraprocedural aneurysmal rupture occurred in 2 patients (5%). Cerebral infarction developed in 2 patients (5%). Ventriculostomy-related hemorrhage was seen in 2 of 10 patients in whom ventriculostomy was performed before or after coiling. Thirty-four (85%) patients had a good outcome (Glasgow Outcome Score of 4 or 5) at the time of discharge, but 1 patient died of cardiac arrest. None of the patients developed thrombocytopenia, retroperitoneal, gastrointestinal, or genitourinary bleeding related to tirofiban administration. CONCLUSIONS: In our study, tirofiban showed a low risk of symptomatic hemorrhagic or thromboembolic complications. Tirofiban may offer a safe and effective alternative as an antiplatelet premedication during stent-assisted coiling of acutely ruptured intracranial aneurysms.

Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

BACKGROUND AND STUDY AIMS The factors that more accurately predict the detection of colorectal cancers and adenomas at colonoscopy are different. We conducted a prospective multicenter study to evaluate which indications were most closely associated with advanced colorectal neoplasm (CRN), including colorectal cancer, in a group of patients undergoing colonoscopy. PATIENTS AND METHODS The 17 468 patients were enrolled in this study between July 2003 and March 2004, from 11 tertiary medical centers in Korea. They were recruited according to 11 itemized colonoscopic indications. The term "advanced adenoma" refers here to tubular adenomas of diameter of 11 mm or more, or to tubulovillous, villous, or severely dysplastic adenomas, irrespective of their size. Cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Advanced CRN was defined as advanced adenoma or invasive cancer. RESULTS Advanced CRN was found in 1227/17 307 patients (1176 advanced adenomas plus 51 carcinomas, 7.1 %). According to univariate and multivariate analysis, the factors associated with advanced CRN included age >60 years (odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.8 - 2.4, P < 0.0001), male gender (OR 2.1, 95 %CI 1.7 - 2.7, P < 0.0001), referral for colonoscopy from primary care physician (OR 3.1, 95 %CI 2.5 - 3.7, P < 0.0001), and several other indications (OR 1.8, 95 %CI 1.5 - 2.3, P < 0.001). The yield of colonoscopy for advanced CRN was lower (2.2 %) than expected in patients with iron-deficiency anemia (OR 0.5, 95 %CI 0.2 - 0.9, P = 0.03). CONCLUSIONS Age, gender, and referral for colonoscopy from primary care physician constituted important independent predictors of advanced CRN in patients undergoing colonoscopy.

Summary To control intra-operative haemorrhage, fibrin glues are preferred by many surgeons because of their biological advantages and convenience of application. Manufacturers have developed a few kinds of fibrin glues with a little difference in their composition. This study was to compare the effectiveness of two commercially available fibrin glues; Greenplast® (Green Cross P. D. Company, Yongin, Korea ) and Tisseel® (Baxter-Immuno AG, Vienna, Austria). They were applied experimentally to several kinds of surgery in dogs – renal vessel anastomosis, partial splenectomy, intestinal anastomosis and incision skin wound – and evaluated for their haemostatic and adhesive effects. When the two glues were applied in renal vessel anastomosis, the amount of haemorrhage in artery and vein decreased significantly. They also decreased the haemorrhage in partial splenectomy. At 10 min after application of the glues to an incision skin wound, the tensile strengths developed were significantly higher than that of control. The present study indicates that two-component fibrin glues have a haemostatic effect as a mechanical barrier in renal vessel anastomosis and an adhesive effect in the early stage of incision skin wound closure, and the two glues have similar effects with no complications.

Rotation thromboelastometry (ROTEM®) is increasingly used in liver transplantation (LT). Of the ROTEM® parameters, maximum clot firmness (MCF) of EXTEM (MCFEXT) and INTEM (MCFINT) are influenced by both platelet count (PLT) and fibrinogen concentration (FIB), whereas MCF of FIBTEM (MCFFIB) is solely influenced by FIB. We aimed to determine whether using MCFs of thromboelastometry could reliably predict both PLT and FIB and to evaluate their relations in patients with thrombocytopenia and hypofibrinogenemia during LT.A total of 4100 retrospective ROTEM® assays with simultaneous standard laboratory tests performed during LT were analyzed in 295 patients. The optimal cut-off values of PLT and FIB according to the ROTEM® transfusion guideline were determined by area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis.MCFEXT and MCFINT showed good correlation with platelet count (r = 0.79 and 0.80, respectively, P.001) and with fibrinogen concentration (r = 0.67 and 0.66, respectively, P.001). MCFFIB and fibrinogen concentration were highly correlated (r = 0.84, P.001). Additionally, PLT and FIB were calculated mathematically: PLT (/μL) = 14827 + 3.93 (MCFEXT)(2.5); FIB (mg/dL) = 63 + 0.00082 (MCFEXT)(3.0); FIB (mg/dL) = 29 + 13.3 MCFFIB. MCFEXT35 mm predicted PLT of 43 × 10(3)/μL (AUC = 0.89) and FIB of 91 mg/dL (AUC = 0.78), whereas MCFEXT45 mm predicted PLT of 52 × 10(3)/μL (AUC = 0.89) and FIB of 121 mg/dL (AUC = 0.86), MCFFIB8 mm predicted FIB of 128 mg/dL (AUC = 0.94). MCFINT showed almost the same cut-off values as MCFEXT.Both PLT and FIB can be reliably quantified by MCFs of thromboelastometry, reducing the needs for additional laboratory tests to know values of thrombocytopenia and hypofibrinogenemia in patients undergoing LT.

We evaluated the expression of thymidylate synthase (TS) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients. TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients (stage IB–IV) who underwent 5-fluorouracil (5-FU) and doxorubicin-based adjuvant chemotherapy after curative resection. 65 patients (63%) had primary tumours with high TS expression (≥ 25% of tumour cells positive), and 38 patients (37%) demonstrated low TS expression (< 25% of tumour cells positive or no staining). High TS expression was associated with male gender (P = 0.002), poorly differentiated histology (P = 0.015), and mixed type in Lauren’s classification (P = 0.027). There were no statistically significant differences in 4-year disease-free survival (60.0% vs 57.2%, P = 0.548) and overall survival (59.6% vs 59.3%, P = 0.792) between high-TS group and low-TS group. In conclusion, although high TS expression was associated with poorly differentiated histology and mixed type in Lauren's classification, it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection. Further prospective studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary. © 2001 Cancer Research Campaign http://www.bjcancer.com

Background and Study Aims: Although most submucosal tumors of the esophagus are benign, reliable exclusion of leiomyosarcoma requires histological analysis. However, this is rarely possible with an endoscopic forceps biopsy. In an attempt to establish the diagnosis, and as an alternative to surgery, we present here our experience with the endoscopic removal of submucosal tumors of the esophagus using two different techniques. Patients and Methods: Sixty-two patients (38 men, 24 women, mean age 47) with submucosal tumors of the esophagus were treated endoscopically. If the tumor was less than 2 cm in diameter, polypoid, or showed a round protrusion with at least moderate elevation at endoscopy, a conventional snare polypectomy was performed. If the tumor was larger than 2 cm in diameter or only mildly elevated, the technique of modified endoscopic incisional enucleation was carried out, consisting of complete stripping of the overlying tissue followed by tumor enucleation using an electrocautery snare and a coagulation electrode. Results: Based on these criteria, 36 patients underwent conventional snare polypectomy, and 25 received endoscopic incisional enucleation; complete resection of the tumor was possible in these 61 cases. In one patient, only partial removal was possible, due to firm and wide adhesions to the surrounding tissue. The tumor diameters ranged from 0.6 cm to 7.5 cm, with a mean value of 1.9 cm; 14 tumors measured more than 3 cm. At histopathology, the resected specimens were found to be 56 leiomyomas, four granular cell tumors, one neurogenic tumor, and one cyst. No serious complications such as perforation or massive bleeding occurred, and oozing bleeding, which was encountered in three patients, was easily managed by endoscopic electrocoagulation. During the follow-up period (mean 38.4 months, range 3-107 months) no recurrence was observed in any of the 61 patients who received complete resections. Conclusion: This method of endoscopic removal of submucosal tumors of the esophagus appears to be safe and effective in experienced hands. It allows complete histopathological workup, and at the same time complete removal of the tumor. The method can be considered as an alternative to surgery in symptomatic cases.

To assess the additional value of adenosine-stress dynamic computed tomography (CT) perfusion (ASDCTP) imaging compared with coronary CT angiography (CCTA) alone to detect significant coronary artery stenosis for each threshold of 50% and 70% diameter stenosis.The study included 34 patients (65 ± 11 years, 79% men) with suspected coronary artery diseases who underwent ASDCTP imaging using a 128-section dual-source CT (DSCT) and invasive coronary angiography (ICA). Two investigators classified coronary artery stenosis on CCTA as severe or not. If appropriate image quality could not be acquired due to artefacts, the segment was classified as a lesion with significant stenosis. After the interpretation of ASDCTP imaging, the degree of stenosis was reclassified. All parameters of diagnostic accuracy were calculated before and after ASDCTP analysis for detection of significant coronary artery stenosis with ICA as the reference standard.The diagnostic accuracy parameters per vessel for the detection of ≥50% stenosis before and after ASDCTP analysis changed as follows: sensitivity, from 80% to 83%; specificity, from 83% to 98%; positive predictive value (PPV), from 87% to 98%; and negative predictive value (NPV), from 75% to 80%. The addition of ASDCTP resulted in reclassification from one class of stenosis severity to another in a significant number of vessels with threshold of 50% stenosis [net reclassification improvement (NRI), 0.176; p 0.01]. Conversely, the addition of ASDCTP did not result in significant reclassification of stenosis severity in vessels with threshold of 70% stenosis (NRI, 0.034; p = 0.51).ASDCTP imaging provides incremental value in the detection of significant coronary artery stenosis using a threshold of 50%.

Optimum dose ratios of rimabotulinumtoxinB (BTX-B) and onabotulinumtoxinA (BTX-A) have not been determined for forehead wrinkles.To compare the efficacy and safety of BTX-B and BTX-A for the treatment of forehead lines.Twenty-two women (mean age, 40 years) with symmetrical moderate to severe forehead lines were randomized to receive single intramuscular injections of BTX-A and BTX-B on either side of the forehead, at a potency ratio of 1 : 70 or 1 : 100. Subjects were followed-up for 16 weeks. Four physicians evaluated patients' photographs according to the 4-point Facial Wrinkling Grade (FWG). Clinical Improvement Scale (CIS) was calculated by subtracting FWG score at each visit from that at baseline. Patient satisfaction scores and adverse events were also recorded.Both BTX-A and BTX-B were effective for the treatment of forehead lines. At both potency ratios, BTX-A had a longer duration of action than BTX-B, while BTX-B led to faster improvement than BTX-A. There was no significant difference in CIS between 700 U and 1000 U BTX-B treatments. Adverse effects were mild and transient.Both BTX-A and BTX-B were effective and well tolerated for the treatment of forehead wrinkles at potency ratios of 1 : 70 and 1 : 100.

Administration of vasopressors or inotropes during liver transplant surgery is almost universal, as this procedure is often accompanied by massive haemorrhage, acid-base imbalance, and cardiovascular instability. However, the actual agents that should be used and the choice between a vasopressor and an inotrope strategy are not clear from existing published evidence. In this prospective, randomised, controlled and single-blinded study, we compared the effects of a vasopressor strategy on intra-operative blood loss and acid-base status with those of an inotrope strategy during living donor liver transplantation. Seventy-six adult liver recipients with decompensated cirrhosis were randomly assigned to receive a continuous infusion of either phenylephrine at a dose of 0.3-0.4 μg.kg(-1).min(-1) or dopamine and/or dobutamine at 2-8 μg.kg(-1).min(-1) during surgery. Vascular resistance was higher over time in the phenylephrine group than in the dopamine/dobutamine group. Estimated blood loss was significantly lower in the phenylephrine group than in the dopamine/dobutamine group (mean (SD) 4.5 (1.8) l vs 6.1 (3.4) l, respectively, p=0.011). Patients in the phenylephrine group had lower lactate levels in the late pre-anhepatic and the early anhepatic phase and needed less bicarbonate administration than those in the dopamine/dobutamine group (median (IQR [range]) 40 (0-100 [0-160]) mEq vs 70 (40-163 [0-260]) mEq, respectively, p=0.018). Postoperative clinical outcomes and laboratory-measured hepatic and renal function did not differ between the groups. Increased vascular resistance and reduction of portal blood flow by intra-operative phenylephrine infusion is assumed to decrease the amount of intra-operative bleeding and thereby ameliorate the progression of lactic acidosis during liver transplant surgery.

Objectives The balance between survival and death is a key point for regulation of physiology of stem cells. Recently, applications of natural products to enhance efficiencies in culturing and differentiation of stem cells are increasing. Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) has been known to be toxic to some cancer cells, but it is still unclear whether VCA has a cytotoxic or indeed a proliferative effect on mesenchymal stem cells (MSCs). Here, we have compared effects of VCA in naive placenta-derived stem cells (PDSCs), immortalized PDSCs and cancer cells (HepG2), and analysed their mechanisms. Materials and methods MTT assay was performed to analyse effects of VCA on naive PDSCs, immortalized PDSCs and HepG2. FACS, ROS, caspase-3 assay, western blotting and immunofluorescence were performed to detect signalling events involved in self-renewal of the above cell types. Results VCA had cancer cell-specific toxicity to HepG2 cells even with low concentrations of VCA (1–5 pg/ml), toxicity was observed to immortalized PDSCs and HepG2s, while proliferation of naive PDSCs was significantly increased (P

Chronic urticaria (CU) is a common skin disorder that affects the well-being and quality of life (QOL) of patients. Recently, we developed and validated a questionnaire for measuring QOL in Korean patients with CU, called the Chronic Urticaria-Specific Quality of Life (CU-QOL) questionnaire.To evaluate the clinical significance of a computerized version of the CU-QOL, in adult patients with CU.This was a cross-sectional observational study that enrolled 249 Korean patients with CU from five university hospitals and measured computerized CU-QOL scores and Urticaria Activity Score (UAS) simultaneously. The internal consistency of the computerized CU-QOL was analysed using Cronbach α. To identify clinical correlations between the CU-QOL and patient characteristics, the atopic status and serum autoantibodies, including antinuclear, antithyroglobulin and antimicrosome antibodies, were measured. Multiple linear regression models were used to identify CU-QOL predictors.Cronbach α was 0.94 for the overall computerized CU-QOL score. The CU-QOL scores correlated significantly with the UAS (r= -0.49, P0.001). Of the factors aggravating CU, delayed pressure, sunlight exposure and emotional stress significantly influenced the overall CU-QOL scores in the univariate analysis. Multivariate regression models indicated that UAS and emotional stress were significant predictors of the four domains and of the total CU-QOL scores.The computerized CU-QOL is a convenient and valid tool for measuring QOL in patients with CU. This study suggests that UAS, dermatographism and emotional stress are strong CU-QOL predictors in Korean patients with CU.

Deep cutaneous mycoses can cause significant morbidity and mortality, especially in immunocompromised patients. There have been few studies focusing on deep cutaneous mycoses and there are no data from Asian countries. This study aimed to investigate clinical characteristics, underlying predisposing factors, aetiological organisms and outcomes in patients with deep cutaneous mycoses. A retrospective medical record review of patients with deep cutaneous mycoses treated at a tertiary referral centre in Korea from 1999 to 2010. Forty-one cases of deep cutaneous mycosis were identified (median age: 49). Most patients (32/41) had impaired immunological status, and seven of the remaining nine had a history of physical trauma. Neutropenia and long-term use of antibiotics were detected in 13 and 12 patients respectively. Nodular skin lesions were the most common type (17/41) and the morphology of the lesions varied. Fungal organisms were identified by culture and histopathology of skin specimens. Candida (16/41) was the most common organism, followed by Aspergillus, Alternaria, Fusarium (4/41 each). Systemic antifungal treatment was successful in 28 patients, while nine patients died from the fungal infection. Our study may lead to improved insights into deep cutaneous mycoses as their incidence is increasing and they vary in different clinical settings.

To compare the effects of sodium lauryl sulfate (SLS)-free and SLS-containing dentifrice in patient with recurrent aphthous stomatitis (RAS).The design of this study was a double-blind crossover trial. The 90 subjects were divided into three groups: group I used SLS-free (a commercially available SLS-free dentifrice) and SLS-A (SLS-free + 1.5% SLS), group II used SLS-A and SLS-B (a commercially available 1.5% SLS-containing dentifrice), and group III used SLS-free and SLS-B. The subjects used one of the two assigned dentifrices for 8 weeks and then the other for the following 8 weeks. The order of the dentifrices used was selected at random, and there was a 2-week washout period between the two phases. The clinical parameters (number of ulcers, number of episodes, duration of ulcers, mean pain score) were compared between the two phases for each group.The number of ulcers and episodes did not differ significantly between SLS-A, SLS-B, and SLS-free. Only duration of ulcers and mean pain score was significantly decreased during the period using SLS-free.Although SLS-free did not reduce the number of ulcers and episodes, it affected the ulcer-healing process and reduces pain in daily lives in patients with RAS.

Mammalian dosage compensation requires silencing of one of the two X chromosomes in females and is controlled by the X inactivation center (Xic). Xic contains many of the regulatory elements for the mutual interplay of X-inactive specific transcript (Xist) and Tsix, the antisense counterpart of Xist. The regulatory elements control X chromosome inactivation (XCI) via the formation of DNA-DNA and DNA-protein complexes with cis- and trans-acting factors. However, the process-dependent regulation of Xist/Tsix by these elements in each XCI process remains largely unknown. In this study, a 6-thioguanine-resistant female F(1) hybrid mouse cell line (designated HOBMSKI2) was constructed from a cross between a female HPRT-deficient transgenic mouse (designated BM3) and a male wild type Mus spretus mouse (designated MS), which enabled the direct discrimination of both allele-specific expression of X-linked genes and allele-specific binding of proteins associated with XCI due to DNA polymorphisms between BM3 and MS. Using this cell line, we found that Tsix on the active X chromosome (Xa) was not expressed in somatic cells despite the fact that CTCF, which ensures Tsix expression in embryonic stem cells, was still bound to the 5' end of Tsix on Xa, implying that CTCF may function differently during each XCI process and its trans-activating activity for Tsix expression may be lost in the maintenance process. In addition, the monoallelic expression of Tsix on Xa was inhibited by epigenetic modification of the chromatin in the maintenance process, which was mediated by protein complexes recruited by MeCP2. The results indicate the value of HOBMSKI2 in directly detecting the allele-specific binding of CTCF and MeCP2 to the 5' end of Tsix. The HOBMSKI2 mouse line is a versatile and useful resource for studying the molecular mechanism of the XCI process.

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.

This study was a pen trial in which the effects of adding different rates of liquid aluminum chloride (AlCl(3)) on litter pH, total volatile fatty acids (VFAs), and ammonia (NH(3)) fluxes was evaluated. Liquid AlCl(3) treatments used in this study were sprayed on the rice hull surface at rates of 100 g, 200 g, and 300 g liquid AlCl(3)/kg rice hulls; untreated rice hulls served as controls. Litter pH, total VFAs, and NH(3) fluxes were all lowered (P0.05) by all of the liquid AlCl(3) treatments compared with controls during certain times of the 5 week study. However, there were no significant differences among treatments on litter pH at the end of the study (from 3 to 5 weeks) or NH(3) fluxes at beginning of the study (0 to 3 weeks). Total VFAs were reduced 16 %, 29 %, and 53 % by 100 g liquid AlCl(3)/kg rice hulls, 200 g liquid AlCl(3)/kg rice hulls, and 300 g liquid AlCl(3)/kg rice hulls, respectively. Liquid AlCl(3)additions reduced NH(3) fluxes by 35 %, 57 % and 67 %, respectively, at the low, medium and high rates. In summary, these results indicate that adding liquid aluminum chloride to rice hulls would be a useful tool in reducing the negative environmental impact of poultry litter. It should be noted that the decreased VFA production and NH(3) volatilization was chiefly associated with reduction in litter pH.

Metabolic syndrome has been proposed as a risk factor for stroke and transient ischaemic attack. One pathophysiological mechanism could be impairment of endothelial function. Thus, we hypothesized that cerebral vasomotor reactivity would be decreased in patients with metabolic syndrome, compared to patients without metabolic syndrome.In this retrospective analysis, 83 consecutive patients (aged 59.19 ± 15.98; 33 women) underwent Doppler examination for carotid artery disease including bi-hemispherical vasomotor reactivity assessment using transcranial Doppler monitoring. Vasomotor reactivity data were analyzed from the hemisphere with no or low-grade carotid stenosis (40%). Cerebral vasomotor reactivity was calculated as percent increase in mean flow velocity per mmHg pCO(2) during 2 min of 5% CO(2) inhalation delivered by anesthesia mask (normal if ≥ 2%/mmHg). Univariate and multivariable linear regression models were used to determine factors, including metabolic syndrome, that were independently associated with pathologic vasomotor reactivity.After adjusting for the presence of contralateral carotid stenosis and ipsilateral stroke in the multivariable model, metabolic syndrome was independently associated with lower vasomotor reactivity values (2.27 ± 1.24% vs. 2.68 ± 1.37; ß = -0.258, P = 0.033). In this model, there was no association of cerebral vasomotor reactivity with age, gender, race, cardiac disease, current statin therapy, or small vessel disease.Our findings suggest that impaired cerebral vasomotor reactivity may be a mediator of stroke in patients with metabolic syndrome, a syndrome affecting a significant and growing proportion of the population. A prospective longitudinal study is warranted to study the cerebral haemodynamic effect of metabolic syndrome.

We speculated TNF-alpha can be one of candidate gene for aspirin-intolerant asthma (AIA) because TNF-alpha is pro-inflammatory cytokine and known to be increased level in asthmatic airways. In addition, genetic interaction between TNF-alpha and human antigen leucocyte (HLA) DPB1*0301, which is a strong genetic marker for AIA, was examined for its close location within chromosome 6.To investigate genetic association of TNF-alpha with an AIA phenotype, three study groups (163 patients with AIA, 197 patients with aspirin-tolerant asthma (ATA), 257 normal control subjects) were enrolled. Single nucleotide polymorphisms (SNPs) were genotyped using a single-base extension method and HLA DPB1 genotyping was determined by high-throughput sequencing method.All five SNPs of TNF-alpha were tested; there were no significant differences in allele and genotype frequencies among the three groups. However, significant association between TNF-alpha-308GA polymorphism and atopy status was noted (P0.05). Gene to gene interaction between TNF-alpha-1031TC (or -863CA or -857CA) and HLA DPB1*0301could synergistically increase the susceptibility to AIA with odds ratio (OR) to 7.738 (or OR=8.184 for -863CA, OR=7.500 for -857CT, P0.001, respectively).TNF-alpha promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1*0301.

A randomized trial has demonstrated that concurrent chemoradiotherapy (CRT) is superior to radiotherapy (RT) alone in locally advanced nasopharyngeal cancer (NPC). Our study comprise 35 patients with locally advanced NPC (stage I: 1, II: 12, III: 7, IV: 15) with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m(2)/day and cisplatin 20 mg/m(2)/day, days 1- 4) followed by concurrent CRT starting on day 22. Concurrent CRT consisted of RT (70 Gy/35 fractions for 7 weeks) with cisplatin 20 mg/m(2)/day for 4 days on weeks 1, 4, 7 of RT. Complete response (CR) was achieved in 33 patients (94%). Four-year progression-free survival (PFS) and overall survival (OS) of all patients were 57% and 65%, respectively. In analysis of prognostic factors, low expression of bax was the most significant independent predictor of poor prognosis in both PFS (p=0.002) and OS (p=0.008). In conclusion, the outcome of patients treated with this combined therapeutical modality appears to be comparable with that of Intergroup 0099 trial with high CR rate. Low expression of bax was significantly associated with poor PFS and OS.

Background and objective The thromboxane A2 receptor (TBXA2R) is a receptor for a potent bronchoconstrictor, TBXA2 which is known to be related to bronchial asthma and myocardial infarction. TBXA2R antagonist and TBX synthase inhibitors have been found to be effective in the management of asthmatic patients. This study was aimed to evaluate whether genetic variants of TBXA2R may be related with development of acetyl salicylic acid (ASA)-intolerant asthma (AIA). Methods TBXA2R gene polymorphisms (TBXA2R+795T>C, TBXA2R+924T>C) were determined using a single-base extension method in 93 AIA patients compared with 172 patients with ASA-tolerant asthma (ATA) and 118 normal controls (NCs) recruited from the Korean population. HLA DPB1*0301 genotype was performed using a direct sequencing method. Results The rare C allele frequency of TBXA2R+795T>C was significantly higher in AIA than in ATA (P=0.03) and the TBXA2R+795T>C polymorphism was also associated with extent of percent fall in forced expiratory volume in 1 s (FEV1) after the inhalation of lysine–acetyl salicylic acid in AIA patients (P=0.009); AIA patients homozygous for the +795 C allele had a greater percent fall of FEV1 compared with individuals with TBXA2R+795 CT or TT genotypes. The frequency of patients carrying both the TBXA2R+795T>C rare allele and HLA DPB1*0301 was significantly higher in AIA patients (29.4%) than in ATA patients (7.3%) (P=0.008, odds ratio=5.3). Conclusion These results suggest that the polymorphism of TBXA2R+795T>C may increase bronchoconstrictive response to ASA, which could contribute to the development of the AIA phenotype.

Summary Background Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood. Objective In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirinintolerant asthma and normal control in a Korean population. Methods Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine–aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis. Results The allele frequencies of HLA-DRB1*1302 (18.1%) and HLA-DQB1*0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P 5 0.0004; 2.0%, P 5 0.0024) and in normal controls (8.1%, P 5 0.0005; 3.2%, P 5 0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P40.05, respectively). In haplotype analysis, the HLA-DRB1*1302DQB1*0609-DPB1*0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P 5 0.0014) and normal controls (2.0%, P 5 0.0006). Conclusion These findings suggest that the HLA-DRB1*1302-DQB1*0609-DPB1*0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.

Kikuchi-Fujimoto disease commonly presents with cervical lymphadenopathy accompanied by fever, myalgia, neutropaenia, and rarely cutaneous eruption. Most cutaneous lesions present as erythematous macules, papules, plaques, nodules, or ulcers on the upper part of the body such as trunk, upper extremities, and face. We present a case of Kikuchi-Fujimoto disease with a papulopustular eruption on the whole body including the lower extremities.

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.

Ota's naevus is among the dermal melanocytoses that show a distinct pattern involving skin innervated by the trigeminal nerve. Most cases present at birth or manifest clinically in early childhood. Cases of acquired lesions in adult onset have been reported rarely. We present two cases of late onset Ota's naevus which were confirmed by skin biopsies. Both patients underwent Q-switched alexandrite laser treatment with a dose of 8.0 J/cm2 given four or five times at 6 weekly intervals and showed some improvement.

Between August and September 2000, five 2–7-year-old cows in Korea exhibited neurologic signs and were diagnosed as infected with Akabane virus based on the results of histopathology, immunohistochemistry, serology, and reverse transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry and RT-PCR were equally effective and sensitive for diagnosing Akabane virus infection during the early stage of infection. Typical lymphohistiocytic inflammation characterized by perivascular mononuclear cell infiltration, gliosis, neuronophagia, and neuronal loss was noted in the brain and the ventral horn gray matter of the spinal cord. The lesions in the brain were most prominent in the pons and medulla oblongata. Akabane virus antigen was detected in the brain and spinal cord, mainly in degenerating neurons and glial cells. RTPCR analysis revealed a target band of expected size in four cows. This is the first report on an outbreak of natural Akabane virus infection in adult cattle.

Cutaneous metastases from carcinoma of the thyroid gland are rare and carcinoma erysipeloides is even rarer. We present the clinical, histological, and immunohistochemical features of inflammatory erysipeloid metastases arising from an anaplastic carcinoma of the thyroid gland. In this case the anaplastic carcinoma probably transformed from a pre-existing, long-standing papillary carcinoma of the thyroid gland. Although visible inflammation is a hallmark of many benign skin disorders, it is not commonly present in cutaneous malignant metastases. As a result, the significance of a marked inflammatory changes in association with metastatic skin disease may not be recognized. Dermatologists need to be aware of the potential for inflammatory manifestations in cutaneous metastases from a thyroid carcinoma.

Cutaneous manifestations of Waldenström's macroglobulinaemia (WM) include purpura, ulcers, urticaria, leukocytoclastic vasculitis, and immunobullous dermatoses. No association has been reported previously of WM and hepatitis B virus (HBV) infection. A 40-year-old female HBV carrier was admitted to hospital because of generalized oedema, oliguria, haematuria, hypertension, fever and blood-tinged sputum. Cutaneous manifestations included generalized petechiae, palpable purpura mainly on the legs, multiple necrotic ulcerations and gangrenous changes on the toes, and necrotic, giant confluent reticulate purpura on the trunk surmounted by several tense bullae. Laboratory investigations revealed monoclonal gammopathy of IgM kappa type (6.7 g/L), membranoproliferative glomerulonephritis associated with HBV infection, Bence Jones proteinuria, and an increased number of abnormal plasmacytoid cells in the bone marrow. Pathologic examination demonstrated immune complex-mediated vasculitis with deposits of IgM in the walls of dermal vessels and secondary subepidermal bulla formation. HBV infection may have caused WM or modified the clinical course in this fatal case.

Background and study aims Impacted sharp foreign bodies in the esophagus can be very difficult to manage. When attempts are made to remove such objects inappropriately, life-threatening complications such as perforation can occur. The aim of this study was to evaluate the safety and efficacy of endoscopic removal of impacted sharp foreign bodies in the esophagus using proximal dilatation with an oral side balloon or transparent cap. Patients and methods A total of 22 patients (10 men, 12 women) with impacted sharp foreign bodies in the esophagus underwent endoscopic extraction. The following technique was successfully performed at our hospital. An oral side balloon (Top Co., Japan) for esophageal variceal sclerotherapy was attached to the distal part of the endoscope. With the patient under local anesthesia, the endoscope was inserted as far as the proximal part of the esophageal foreign body. The oral side balloon was then gradually inflated. Dilatation of the proximal part of the esophagus made it possible to release the impacted sharp foreign body from the esophageal wall. A transparent cap was used for foreign bodies in the upper esophagus when there were difficulties with the oral side balloon. Results The types of foreign body removed were fish bones (n = 9), press-through packages (n = 8), chicken bones (n =3), dentures (n = 1), and a wrist watch (n = 1). Endoscopic removal was successful in all but one of the cases, in which a fish bone had to be extracted surgically. Conclusions The proximal dilatation method using an oral side balloon or transparent cap is safe and effective in removing sharp foreign bodies from the esophagus, avoiding surgery and possible perforation.

Recently, human herpesvirus 8 (HHV-8) has been isolated from almost all cases of Kaposi's sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi's sarcoma. Benign vascular lesions including Kimura's disease were not found to contain the HHV-8 DNA sequence. However, there has been contradictory data concerning the presence of HHV-8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura's disease were rare.We performed polymerase chain reaction (PCR)-based analysis to determine whether HHV-8 is present and heteroduplex analysis of rearranged T-cell receptor (TCR) gene for clonality assessment in paraffin-embedded skin biopsy samples of 7 ALHE and 2 Kimura's disease, taken from immunocompetent patients.HHV-8 could not be identified in all the cases of ALHE and Kimura's disease. Although 2 cases (2/7) of ALHE and 2 cases (2/2) of Kimura's disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex-PCR.We suggest that HHV-8 may not involve in a pathogenetic role in ALHE and Kimura's disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex-PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex-PCR is more specific than PCR as seen in our study.

Necrotizing enterocolitis (NEC) can involve any site in the gastrointestinal tract and is a fatal complication of immunosuppression. To characterize NEC, clinical and radiological characteristics were analyzed. A total of 27 cases of NEC were identified from January 1993 to August 1998, and medical records were reviewed. NEC was diagnosed by clinical and radiological criteria, and other mimicking conditions were excluded. Of the NEC cases, 22 (81.5%) occurred in patients with underlying hematologic malignancy. All patients complained of abdominal pain and fever at the time of inclusion. Escherichia coli was the most common pathogen identified. The most common finding by computed tomography was single-layered diffuse bowel wall thickening with variable density. Other findings were ascites, fascial thickening, pneumatosis, and mesenteric lymphadenopathy. Of the patients, 25 were treated with antimicrobials with or without recombinant hematopoietic growth factors, and 2 were treated with surgery because of perforation and profound bleeding. Among the 12 patients who died, NEC was the direct cause of death in 7 patients. In conclusion, computed tomography is an effective tool for early diagnosis of NEC. Bowel rest, broad-spectrum antimicrobials, and recombinant hematopoietic growth factors are important aspects of treatment. Surgery should be reserved for complicated cases.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignancies, including breast, lung, gastric, and cervical carcinoma. Its overexpression has been associated with disease progression or poor prognosis in patients with cervical carcinoma. In the present study, the levels of EGFR were determined in serum from 38 patients with cervical carcinoma [invasive or recurrent carcinoma (n = 26) and carcinoma in situ (CIS; n = 12)] and 38 healthy female controls using ELISA. The mean serum level for EGFR in patients with invasive or recurrent carcinoma (165 +/- 60 fmol/ml) was significantly elevated (P0.0001) compared with that of healthy controls (66 +/- 17 fmol/ml) and also higher (P = 0.015) than that of patients with CIS (126 +/- 25 fmol/ml). In addition, there was a significant difference in the mean serum levels of EGFR between patients with CIS and healthy controls (P0.0001). Thirty-five patients (92%) with cervical carcinoma [invasive or recurrent (n = 24) and CIS (n = 11)] had elevated serum, EGFR levels above the cutoff value of 100 fmol/ml (defined as 2 SD above the mean of the controls). In conclusion, the serum EGFR level was elevated in a significant proportion of patients with cervical carcinoma, and it demonstrated an increasing tendency according to disease progression from normal tissue through CIS to invasive cervical carcinoma. Therefore, it may have a potential usefulness as a biological marker of cervical carcinoma.

This study was to investigate a hypothesis that dietary restriction (DR) suppresses learning and memory impairments in dementia animal model SAMP8 mice. Four-week-old female SAMP8 mice were fed either ad libitum (AL) or fed restricted (40% of the food consumed by AL). Results showed that acetylcholine (ACh) levels in hippocampus at aged 12 months of age were 12% higher in DR than that of AL group. Dopamine (DA) and norepinephrine (NE) levels in cerebellum at 8 and 12 months of age were significantly higher (26~94% and 34~43%, respectively) in DR group than those in AL group. Serotonin (5-HT) levels in cerebellum at aged 12 months of age were markedly increased (~53%) in DR group. Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in cerebellum at 8 and 12 months of age were significantly increased (28~41% and 24~64%, respectively) in DR group compared with AL group. In addition, neurotransmitter-related enzymes, choline acetyltransferase (ChAT) and acetylchoinesterase (AChE) activities at 8 and 12 months of age were elevated (6~8% and 5~7%, respectively) in DR group. Monoamine oxidase-B (MAO-B) that catalyzes oxidative deamination in brain were suppressed by 7~10% in DR group. At aged 12 months of age, the generation of basal and induced reactive oxygen species (ROS) in brain significantly decreased by 20% in DR group compared with AL group. These results suggest that inhibitory effect of oxidative stress by DR may play a pivotal role in attenuating the age-related changes observed in dementia animal model SAMP8.

This study was to evaluate the effect of dietary restriction (DR) on lifespan and oxidative stress of dementia mouse model SAMP8 with impaired learning and memory. SAMP8 female mice were fed either ad libitum (AL) or fed 60% of food intake of AL. Results showed that basal metabolic rates (BMR) were significantly lower (15 to 22%) in DR with increased median and maximum lifespans, suggesting feed and gross efficiencies were significantly lower in DR than in AL. Grading score of senescence resulted in a marked improvement about 2-fold by DR compared with AL. The amounts of lipofuscin at 12 months were significantly lowered 16% in DR than that of AL. Median and maximal lifespans significantly increased (28.5% and 16.4%, respectively) by DR, and also lowered superoxide radical about 15 approximately 45% in DR compared with AL at 4, 8 and 12 months of age. On the other hand, superoxide dismutase (SOD) activities were higher (about 15 approximately 30%) in DR than those in AL group of SAMP8 except for 4 months of age. Our results suggest that 40% calorie restricted SAMP8 can effectively suppress dementia-related abnormalities during aging.

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Theophylline has been widely used to treat apnea of premature neonates. The purpose of this study was to compare the pharmacokinetic parameters of theophylline and caffeine after intravenous administration of aminophylline to seven Korean low-birthweight neonates with apnea to those in other countries. The serum concentrations of theophylline and caffeine were measured simultaneously by high-performance liquid-chromatography (HPLC). The mean (+/- S.E.M.) birth weight and gestational period were 1190 +/- 253 g and 31.5 +/- 1.99 weeks, respectively. The mean (+/- S.E.M.) theophylline maintenance dosage was 1.28 +/- 0.15 mg/kg (given as equivalent aminophylline solution) every six hours. The mean (+/- S.E.M.) volume of distribution, 0.937 +/- 0.232 l/kg, elimination rate constant, 0.0249 +/- 0.0095/h, elimination half-life, 32.1 +/- 12.1 h, and total body clearance, 21.7 +/- 6.18 ml/h/kg, of theophylline in Korean premature neonates were comparable to the values of neonates in other countries. For caffeine, the mean (+/- S.E.M.) elimination half-life was 95.1 +/- 25.4 h and the elimination rate constant was 0.0079 +/- 0.0024/h. The mean (+/- S.E.M.) serum concentrations of theophylline and caffeine on the sixth day after aminophylline infusion were 10.4 +/- 2.28 microg/ml (range, 6.38-13.4 microg/ml) and 2.94 +/- 0.98 microg/ml (range, 1.80-4.44 microg/ml), respectively. The mean (+/- S.E.M.) caffeine to theophylline concentration ratio on the day after discontinuation of aminophylline infusion was 0.71 +/- 0.23 (range, 0.39-1.03).

Nasal-type T/natural killer cell lymphoma (TNKCL) shows frequent extranodal involvement including the skin, and is associated with a poor prognosis. We have studied six patients with nasal-type TNKCL presenting with inflammatory subcutaneous nodular lesions with a subcutaneous lymphoid infiltrate. Clinical information was obtained from the medical records of the patients and at follow-up. All cases showed features of angiocentric lymphoma on histology, although there was diffuse cellular infiltration rather than an angiocentric pattern in the subcutis. All six patients were similar in immunophenotype: positive for CD56 and either cytoplasmic CD3 or CD45RO, but negative for B-cell markers and CD30. In situ hybridization using an anti-sense Epstein-Barr virus early regions probe showed a positive reaction in all cases. All patients either died with progressive disease or showed no response to combined chemotherapy. The diagnosis of nasal-type TNKCL, which has a fatal outcome, is facilitated by detection of CD56-positive tumour cells. In evaluating lobular panniculitis including apparently benign inflammatory subcutaneous nodules, nasal-type TNKCL should be considered in the differential diagnosis, especially in Asian countries.

Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.

Natural killer (NK) cells are large granular lymphocytes that mediate cytotoxic reactions which are not restricted by the major histocompatibility complex. In recent years it has become apparent that a minor proportion of malignant lymphomas expresses an NK-cell phenotype defined by its reactivity with the CD56 antibody. Primary purely cutaneous CD56 + lymphomas have rarely been reported. They share a generally aggressive course and are highly associated with Epstein-Barr virus. We describe a patient with a primary cutaneous nasal-type T/NK-cell lymphoma that presented as a haemophagocytic syndrome and showed an aggressive clinical course.