Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

Radiologist performance in the interpretation of contrast enemas performed for Hirschsprung's disease in children >1 year of age.

AIM: To evaluate the diagnostic performance of contrast enemas (CEs) for the diagnosis of Hirschsprung's disease (HD). METHODS AND MATERIALS: CE studies performed as part of an HD workup in patients 1-18 years of age over a 10-year period were identified. All abnormal CE studies and an equal number of age-matched controls were included in the final study group. Two radiologists independently and blindly reviewed all CE studies for quality (scale of 0-3) and the presence of large colon calibre, colon redundancy, transition zone, rectosigmoid ratio, and abnormal contractions. Readers also determined whether a rectal biopsy would be recommended to confirm an HD diagnosis. Discrepancies were resolved in consensus. Findings were correlated with surgery and biopsy data. RESULTS: Out of 834 CE studies, 38 abnormal CE studies were identified (mean age 5.9 years) and included 38 matched controls. Seventeen of 76 patients were recommended for rectal biopsy, of which five were confirmed to have HD. Twelve of 70 (17.1%) were false positives, and were clinically confirmed not to have HD. The proportion of HD in the present population was 6/834 (0.72%). Of the 17 recommended for biopsy, CE studies showed 17/17 (100%) with an abnormal rectosigmoid ratio, 16/17 (94.1%) with redundant colon, and 15/17 (88%) with large colon. Of patients not recommended for biopsy, one was diagnosed with HD, (false negative, 16.7%). The diagnostic performance of CE was 83.3% sensitivity and 82.9% specificity. CONCLUSION: Few children >1 year of age were found to have HD and the diagnostic performance of the CE is moderately high. The CE examination is a valuable non-invasive imaging study to help exclude older children who may not have HD, thereby obviating the need for invasive rectal biopsy and surgery.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

OBJECTIVES: This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. RESULTS: Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. CONCLUSIONS: The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.

Impact of personality and depression on quality of life in patients with severe haemophilia in Korea.

Among reports on the psychological variables that influence quality of life (QoL), none has addressed the impact of personality on QoL in patients with haemophilia. We investigated the impact of psychosocial variables including depression and personality on QoL in patients with severe haemophilia. A cross-sectional survey examining psychosocial and clinical characteristics was administered to Korean patients with severe haemophilia. Personality traits were ascertained using the 10-item short version of the Big Five Inventory, which quantifies five personality dimensions including extraversion, agreeableness, conscientiousness, neuroticism and openness. Patient QoL and depression were measured by the World Health Organization Quality of Life-abbreviated version and the Beck Depression Inventory (BDI) respectively. Multivariate linear regression analyses were used for each domain to determine the impact of psychological variables on QoL. Of the 53 subjects who consented to participate, 46 cases were finally analysed. Multivariate linear regression analyses demonstrated that agreeableness was significantly and positively associated with the physical health domain of QoL. Openness was independently and positively associated with the psychological and social relationship domains of QoL. BDI scores were significantly and negatively associated with all four domains of the QoL. Persistent pain and joint impairment showed strong associations with all domains in a univariate analysis, but the impact was attenuated after adjusting for psychosocial variables. Personality and depression had strong impacts on QoL independent of physical status in patients with severe haemophilia. Providing psychological screening and intervention are recommended for enhancing QoL in patients with severe haemophilia.

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Fenfluramine-induced serotonin release decreases [11C]AZ10419369 binding to 5-HT1B-receptors in the primate brain.

The need for positron emission tomography (PET)-radioligands that are sensitive to changes in endogenous serotonin (5-HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [(11)C]AZ10419369 that is highly selective for the 5-HT(1B) receptor. In this PET-study in three cynomolgus monkeys, we examined the sensitivity of [(11)C]AZ10419369 to altered endogenous 5-HT levels. Fenfluramine-induced 5-HT release decreased radioligand binding in a dose-dependent fashion with a regional average of 27% after 1 mg/kg and 50% after 5 mg/kg. This preliminary study supports that [(11)C]AZ10419369 is sensitive to endogenous 5-HT levels in vivo and may serve as a tool to examine the pathophysiology and treatment of major psychiatric disorders.

Narrow-band imaging with magnifying endoscopy for the screening of esophageal cancer in patients with primary head and neck cancers.

BACKGROUND AND STUDY AIM: Although narrow-band imaging (NBI) in endoscopy can improve detection of early-stage esophageal malignancies in patients with head and neck cancers, false-positive results may be obtained in areas with nonspecific inflammatory changes. This study evaluated the feasibility of primary screening with NBI and magnification for the presence of esophageal malignancies in these cancer patients. PATIENTS AND METHODS: Sixty-nine patients with documented head and neck cancers were enrolled from April 2008 to January 2009. All patients underwent a meticulous endoscopic examination of the esophagus using a conventional white-light system followed by re-examination using the NBI system and final confirmation with NBI plus magnification. RESULTS: Twenty-one patients (30.4 %) were confirmed to have esophageal neoplasia. Among these 21, 16 (76.2 %) had synchronous lesions, 9 (42.9 %) were asymptomatic, and 10 (47.6 %) had early-stage neoplasia. The incidence of multiple esophageal neoplasia was 57.1 %. NBI was more effective than conventional endoscopy in detecting neoplastic lesions (35 lesions in 21 patients vs. 22 lesions in 18 patients) and was particularly effective in patients with dysplasia (13 lesions in 9 patients vs. 3 lesions in 3 patients). The sensitivity and accuracy of detection were 62.9 % and 64.4 % for conventional endoscopy, 100 % and 86.7 % for NBI alone, and 100 % and 95.6 % for NBI with high magnification, respectively. CONCLUSIONS: Compared with current approaches, NBI followed by high magnification significantly increases the accuracy of detection of esophageal neoplasia in patients with head and neck cancers. The result warrants conducting prospective randomized controlled study to confirm its efficacy.

Effect of cigarette taxes on the consumption of cigarettes, alcohol, tea and coffee in Taiwan.

OBJECTIVES: To analyse whether a health tax of 10 New Taiwan Dollars (NT$) (US$0.3) imposed on cigarettes in 2009 will help to reduce cigarette consumption, and whether or not the cigarette tax will affect consumption of alcohol, coffee and tea. STUDY DESIGN: Time series data for consumption and retail prices of tobacco, alcohol, tea and coffee were collected and analysed for the period 1973-2007. METHODS: To establish the Central Bureau of Statistics demand function to estimate the overall demand price elasticities of cigarettes, alcohol, tea and coffee, a seemingly unrelated regression analysis was used. The independent variables were annual consumption of cigarettes, alcohol, tea and coffee. The dependent variables were prices of and expenditures on cigarettes, alcohol, tea and coffee. RESULTS: The estimated own-price elasticities for cigarettes and alcohol are close to -0.726. The own-price elasticities for tea and coffee are less than those for cigarettes and alcohol. Hence, it is predicted that the NT$10 health tax on cigarettes will reduce cigarette consumption by a significant 13.19%. Analysis of cross-price elasticity reveals that alcohol is complementary to cigarettes. CONCLUSIONS: Taxation is an effective smoking control policy tool that not only helps to reduce consumption of cigarettes, but also reduces consumption of alcoholic beverages.

Downstream changes in river avulsion style are related to channel morphology.

One of the most dramatic events in river environments is the natural diversion, or avulsion, of a channel across its floodplain. Though rarely witnessed, avulsions can cause massive floods, and over geologic time they create most of the fluvial stratigraphic record. Avulsions exhibit behavior ranging from reoccupying abandoned channels to constructing new channels and splay complexes. To quantify avulsion behavior, or style, we measure avulsion-related floodplain disturbance in modern environments. We show that for 63 avulsions from Andean, Himalayan, and New Guinean basins, avulsion style correlates with channel morphology and changes systematically downstream. Avulsions in braided rivers reoccupy abandoned channels, whereas avulsions in meandering rivers often produce flooding and sediment deposition during channel construction. These downstream changes in avulsion style can explain the abrupt transition from channel-dominated to floodplain-dominated facies commonly observed in foreland basin stratigraphy. These dynamics also explain why some avulsions are more hazardous than others.

Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women.

OBJECTIVE: Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. STUDY SUBJECTS: Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. DESIGN: Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. RESULTS: Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. CONCLUSION: Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.

A Ubiquitous Chronic Disease Care system using cellular phones and the internet.

AIMS: The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension. METHODS: We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre. RESULTS: After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group. CONCLUSIONS: The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.

Cl- channels in CF: lack of activation by protein kinase C and cAMP-dependent protein kinase.

Secretory chloride channels can be activated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in normal airway epithelial cells but not in cells from individuals with cystic fibrosis (CF). In excised, inside-out patches of apical membrane of normal human airway cells and airway cells from three patients with CF, the chloride channels exhibited a characteristic outwardly rectifying current-voltage relation and depolarization-induced activation. Channels from normal tissues were activated by both cAMP-dependent protein kinase and protein kinase C. However, chloride channels from CF patients could not be activated by either kinase. Thus, gating of normal epithelial chloride channels is regulated by both cAMP-dependent protein kinase and protein kinase C, and regulation by both kinases is defective in CF.

Rapid dose-dependent effect of clozapine on a schizophrenic patient's lipid profile.

Clozapine is known to be associated with higher risk of metabolic syndrome, including dyslipidaemia, but the mechanisms of such a relationship are still under debate. The case we reported shows a seemingly dose-dependent effect of clozapine on a patient's lipid profiles with no influence on his blood sugar in a relatively short period of time. A direct effect of clozapine on lipid metabolism, independent of insulin or obesity-related metabolic changes, is suggested. The rapid effect of clozapine on lipid profile allows fine-tuning in dose adjustment while treating refractory schizophrenia complicated with drug-related dyslipidaemia but worrying about psychotic rebound during clozapine discontinuation.

Simultaneous regeneration of calcium lactate and cellulose into PCL nanofiber for biomedical application.

Synthetic polymers are easy to process and have excellent mechanical properties but low wettability and poor cell compatibility limit their applications in tissue scaffolding. In this study, a facile procedure was established to regenerate cellulose and calcium lactate (CaL) into a polycaprolactone (PCL) nanofibrous scaffold for tissue engineering applications. Briefly, varying amounts of lactic acid (LA) was mixed with the blend of PCL and cellulose acetate (CA) solutions and electrospun to fabricate an optimal composite PCL/CA/LA fibrous membrane. Later on, as-prepared membranes were treated with calcium hydroxide solution. This process simultaneously converted CA and LA contents into Cellulose and CaL, respectively. In situ regeneration of Cellulose and CaL into the composite fiber remarkably enhanced the biological and physicochemical properties of the composite fiber. This work provides a novel dual-channel strategy for simultaneous regeneration of biopolymer and bioactive molecule into the PCL nanofiber for regenerative medicine and tissue engineering applications.

Coupling of CFTR Cl- channel gating to an ATP hydrolysis cycle.

For cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels to open, they must be phosphorylated by protein kinase A and then exposed to a hydrolyzable nucleoside triphosphate, such as ATP. To test whether channel opening is linked to ATP hydrolysis, we applied VO4 and BeF3 to CFTR channels in inside-out patches excised from cardiac myocytes. These inorganic phosphate analogs interrupt ATP hydrolysis cycles by binding tightly in place of the released hydrolysis product, inorganic phosphate. The analogs acted only on CFTR channels opened by ATP and locked them open, increasing their mean open time by 2-3 orders of magnitude. These findings establish that opening and closing of CFTR channels are coupled to an ATP hydrolysis cycle.

ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction.

OBJECTIVES: Angiotensin-converting enzyme (ACE) polymorphism may play a role in stroke and silent brain infarction (SBI) susceptibility, but the results among the populations studied to date have not been consistent. Thus, we investigated the association between ACE genotypes and ischemic stroke and SBI in Korean patients. SUBJECTS AND METHODS: DNA samples from 237 stroke patients, 264 SBI patients and 234 age-matched controls were amplified using polymerase chain reaction to detect the ACE ins/del (I/D) polymorphism. Genotype was determined by the presence of a 490-bp band (I allele) or a 190-bp band (D allele) in agarose gel electrophoresis. RESULTS: Odds ratios of the I/D and D/D genotypes and the overall (I/D + D/D) for the I/I genotype were significantly different between stroke patients and normal controls. However, there was no significant difference between patients with SBI and controls. CONCLUSIONS: This study is the first report of a significant association between ACE polymorphism and ischemic stroke in the Asian population. Although no consistent associations have been found between ACE polymorphism and stroke in the populations studied to date, the ACE polymorphism may be a genetic determinant of ischemic stroke, at least in Korean patients.

Candida parapsilosis peritonitis complicated with infected pancreatic pseudocysts in a peritoneal dialysis patient: a challenge for nephrologists.

In continuous ambulatory peritoneal dialysis (CAPD)-related cases of fungal peritonitis, Candida parapsilosis (C. parapsilosis) has become as common as Candida albicans (C. albicans) in fungal isolates. This report describes a 74-year-old male CAPD patient who received bypass surgery for coronary artery disease, followed by an episode of bacterial peritonitis. The peritonitis was successfully treated with intraperitoneal antibiotics. However, C. parapsilosis peritonitis with concomitant pancreatitis and infected pseudocysts occurred one month later. Despite surgical drainage and intravenous administration of fluconazole, fungal peritonitis persisted. Finally, he died of nosocomial pneumonia. This case demonstrates the poor outcome of C. parapsilosis peritonitis, suggesting a more aggressive treatment in peritoneal dialysis patients.