bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional helical computed tomography cholangiography with minimum intensity projection in gallbladder carcinoma patients with obstructive jaundice: Comparison with magnetic resonance cholangiography and percutaneous transhepatic cholangiography
Authors: RAO NARAYANA DLV , SINGH GULATI MANPREET , PAUL SHASHI BALA , PANDE GIRISH KUMAR , SAHNI PEUSH , CHATTOPADHYAY TUSHAR KANTI
Published: January 2005

Objective:  Computed tomography (CT) is traditionally used for evaluation and staging of gallbladder carcinoma (GC). However, in the subgroup of patients with obstructive jaundice, magnetic resonance cholangiography (MRC) is generally required to assess the level of biliary obstruction. The present study was  undertaken  to  evaluate  the  diagnostic potential of three‐dimensional helical CT cholangiography (3‐D CTC) with minimum intensity projection (minIP), to determine the presence and level of biliary obstruction.

Materials and Methods:  Twenty‐five consecutive patients with proven GC, presenting with clinical and biochemical features of obstructive jaundice, over a 1‐year period were included in the study. Dual phase helical CT data was obtained in the arterial and venous phases, respectively, after intravenous contrast injection using a pressure injector. Axial CT data (both arterial and venous phase) was studied for staging and resectability of tumor. Three‐dimensional helical CT cholangiography using minIP obtained from the venous phase data set, was used to assess the level of biliary obstruction and isolation of hepatic segmental ducts. Three‐dimensional helical CT cholangiography findings were compared with MRC and percutaneous transhepatic cholangiography (PTC) (gold standard). None of the patients were operated on as they were all considered inoperable on axial CT images due to extensive local disease or distant metastasis.

Results:  In all patients, 3‐D CTC demonstrated dilated intrahepatic ducts up to tertiary branch level. The 3‐D CTC correctly diagnosed the level of biliary obstruction and demonstrated isolated segmental ducts in all patients and correlated well in all cases with MRC and PTC findings in this regard. However, the 3‐D CTC did not add any additional information over the axial source images.

Conclusion:  Three‐dimensional helical CT cholangiography with minIP can correctly determine the level of biliary obstruction in patients with GC and may be a strong competitor with MRC, because it gives equivalent information with regard to the level of ductal obstruction even while being a part of an overall comprehensive CT staging study. Even though 3‐D CTC did not provide additional information on top of the source images, the referring physicians found them very useful for conceptualization of the 3‐D biliary anatomy.
Iron overload in patients with chronic hepatitis C virus infection: Clinical and histological study
Authors: SILVA IVONETE SS , PEREZ RENATA M , OLIVEIRA PEDRO V , CANTAGALO MARIA INÊS , DANTAS ELIZABETE , SISTI CRISTINA , FIGUEIREDO‐MENDES CLÁUDIO , LANZONI VALERIA P , SILVA ANTONIO EB , FERRAZ MARIA LUCIA G
Published: January 2005

Background:  Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)‐infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV‐infected carriers.

Methods:  Patients presenting with anti‐HCV and HCV‐RNA were included. Hepatic iron concentration was determined in liver tissue by atomic absorption spectrophotometry. The association between HIC and age, gender, risk factor of transmission, duration of infection, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, iron and serum ferritin, transferrin saturation, HCV‐RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann–Whitney test and a multiple linear regression model.

Results:  Ninety‐six patients (58% male) with a mean age of 44 ± 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 28%, 27% and 12.5% of patients, respectively. Stainable iron was detected in few patients (15.6%). Higher grades of stainable iron (2 and 3) were observed in only 7%. The HIC (>30 mmol/g dry weight) was elevated in five patients (5%). Neither grading nor staging were related to HIC. Higher HIC were observed in male patients (P < 0.001), in patients with elevated serum ferritin (P = 0.001) and in patients with stainable iron (grades 2 and 3; P = 0.001). Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC (P = 0.003).

Conclusions:  Iron overload in chronically HCV‐infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC.
Selective adenosine A2A receptor agonist, ATL‐146e, attenuates stress‐induced gastric lesions in rats
Authors: ODASHIMA MASARU , OTAKA MICHIRO , JIN MARIO , KOMATSU KOGA , WADA ISAO , MATSUHASHI TAMOTSU , HORIKAWA YOUHEI , HATAKEYAMA NATSUMI , OYAKE JINKO , OHBA REINA , LINDEN JOEL , WATANABE SUMIO
Published: January 2005

Background:  Activation of adenosine A2A receptors reduces the production of various pro‐inflammatory cytokines and suppresses neutrophil activation. Water‐immersion restraint is well known to cause gastric mucosal lesions due to stress. The pathogenesis of stress‐induced gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A2A receptors are known to be anti‐inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A2A receptor agonist, ATL‐146e, on water‐immersion stress‐induced gastric mucosal lesions was studied.

Methods:  Rats were subjected to water‐immersion stress with or without pretreatment with a single intraperitoneal injection of a potent and selective agonist of the adenosine A2A receptor. The gastric concentrations of myeloperoxidase (MPO), as an index of neutrophil accumulation, and the pro‐inflammatory cytokines, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), were measured.

Results:  The total length of gastric erosions (ulcer index) in control rats was 21.6 ± 3.23 mm and was reduced by 86% to 3.1 ± 0.83 mm by pretreatment with 5.0 µg/kg ATL146e (P < 0.001). The gastric content of MPO, TNF‐α and IL‐1β were all increased after water‐immersion stress and reduced to near normal levels by ATL‐146e.

Conclusion:  A specific adenosine A2A agonist inhibits stress‐induced gastric inflammation and damage. A2A agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation.

© 2004 Blackwell Publishing Asia Pty Ltd
Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: An in vitro study
Authors: IMAI YOSHIHITO , KUBOTA YOSHITSUGU , YAMAMOTO SHIN , TSUJI KAZUYUKI , SHIMATANI MASAAKI , SHIBATANI NOBUYUKI , TAKAMIDO SHOICHIROH , MATSUSHITA MASANORI , OKAZAKI KAZUICHI
Published: January 2005

Background and Aim:  Tumor–mesenchymal interactions are involved in the mechanism of tumor invasion in several types of carcinoma. Mutual interactions between carcinoma cells and neutrophils, however, have been poorly understood. In the present study we examined the effect of neutrophils on invasion activities of carcinoma cells in vitro. Role of hepatocyte growth factor (HGF) as a mediator was also evaluated.

Methods:  Using a Matrigel invasion chamber, invasion activities of HuCC‐T1 human cholangiocellular carcinoma cells and HepG2 hepatocellular carcinoma cells in response to recombinant HGF or neutrophils were evaluated.

Results:  Recombinant HGF dose‐dependently increased invasion activities of HuCC‐T1 and HepG2 cells. Neutrophils significantly enhanced invasion activities of these cells, which were suppressed to the respective basal levels with anti‐HGF antibody. The carcinoma cells did not secrete HGF. Neutrophils cultivated in tumor condition medium (TCM) of HuCC‐T1 or HepG2 cells secreted a significant level of HGF protein without increasing HGF mRNA expression. Treatment with heat or ultrafiltration of TCM of HuCC‐T1 or HepG2 cells suggested carcinoma cell‐derived HGF inducer(s) to be certain protein(s) with a molecular weight of more than 30 000.

Conclusions:  The present study suggests the presence of mutual interactions between HuCC‐T1/HepG2 carcinoma cells and neutrophils in tumor invasion via paracrine regulation mediated by neutrophil‐derived HGF.
Criminality in men with major mental disorder with and without comorbid substance abuse
Authors: MODESTIN JIRI , WUERMLE OTHMAR
Published: January 2005

Abstract  Violent and criminal behavior in the mentally ill remains an issue of major importance and in this context the role of comorbid substance abuse must be addressed. Data on criminal behavior in 282 men with schizophrenia and 261 men with affective disorder were studied. Samples of patients with and without additional substance abuse were compared. Also, non‐abusing patients from both diagnostic groups were compared with matched controls from the general population. Substance abuse was found in half of all men in both groups of major mental disorders, and substance abusers had twice as high a probability of having a criminal record. However, compared with the matched sample from the general population, violent criminality was increased in schizophrenic patients without comorbid substance abuse, and patients with affective disorders without substance abuse had a higher probability of committing crimes against property. Men with major mental disorder have an increased probability of becoming criminal even when there is no comorbid substance abuse.
Intellect declines in healthy elderly subjects and cerebellum
Authors: LEE JUN‐YOUNG , LYOO IN KYOON , KIM SEON‐UK , JANG HONG‐SUK , LEE DONG‐WOO , JEON HONG‐JIN , PARK SANG‐CHUL , CHO MAENG JE
Published: January 2005

Abstract  Scores of the performance scale of the Wechsler Adult Intelligence Scale (WAIS) declined linearly with age from the 6th decade, whereas those of the verbal scale did not. This decrease in performance intelligence was thought to be related to an age‐related frontal atrophy. The relationship between scores of the WAIS and changes in regional cortical gray matter density were examined in healthy elderly subjects using voxel‐based morphometry. Thirty healthy non‐demented individuals >50 years of age were tested with the WAIS and scanned with brain magnetic resonance imaging (MRI). The right neocerebellum was significantly associated with scores of the performance intelligence scale while frontal lobes were not. The current study suggests that the cerebellum may play an important role in changes of intellectual capacity in old age.
Lorazepam and diazepam rapidly relieve catatonic signs in patients with schizophrenia
Authors: HUANG TIAO‐LAI
Published: January 2005

Abstract  The uses of lorazepam and electroconvulsive therapy (ECT) have been proven to be effective in treating catatonia. In the present study a modified treatment strategy (i.e. lorazepam i.m. injection or diazepam infused i.v. if lorazepam failed, not with ECT) was proposed to rapidly relieve catatonic signs in patients with schizophrenia. During a 3‐year period, 14 patients with catatonic schizophrenia in Chinese ethnic background Taiwanese were brought to the emergency unit of a general hospital. First, the patients were immediately treated with lorazepam 1 or 2 ampules (2 mg/mL per ampule) i.m. injection (IMI) during 2 h. Second, if the previous 2 ampules of lorazepam IMI failed, diazepam infused i.v. (10 mg/2 mL per ampule) in normal saline 500 mL every 8 h would be done during 1 day. The response rate of catatonic signs in these 14 patients with lorazepam IMI during the first 2 h was 85.7% (12/14). However, according to the results of this method, the total response rate to benzodiazepines during 1 day was 100%(14/14). These results suggested that this modified treatment strategy could rapidly and completely relieve catatonic signs, even without the use of ECT.
Acculturation and eating disorders in Asian and Caucasian Australian adolescent girls
Authors: JENNINGS PIANGCHAI S. , FORBES DAVID , MCDERMOTT BRETT , JUNIPER SATO , HULSE GARY
Published: January 2005

Abstract  The present study aimed to compare the attitudes and psychopathology of eating disorders between Asian and Caucasian adolescent girls; and investigate the relationship between acculturation and the attitudes and psychopathology of eating disorders in subgroups of Asian girls. Two groups of non‐clinical adolescent girls in Perth, Western Australia, were compared using a survey method. There were 17 Asian and 25 Caucasian adolescent girls, aged 14–17 drawn from private high schools in Perth who were screened using the Eating Attitudes Test (EAT‐26), the Eating Disorders Inventory (EDI‐2), and an acculturation index. The psychopathology scores for eating disorders of the Asian group were significantly higher than that of the Caucasian group in terms of total EDI‐2 score, Interpersonal Distrust, Maturity Fears, Impulse Regulation and Social Insecurity subscales. Eating attitudes measured by Dieting subscale of the EAT‐26 was significantly different. Within the Asian group, the less acculturated girls had higher scores on the EAT‐26 and the EDI‐2 than the more acculturated. Less acculturated Asian girls appeared to have unhealthier attitudes and psychopathology toward eating.
Relapse antecedents for methamphetamine use and related factors in Taiwanese adolescents
Authors: YEN CHENG‐FANG , CHANG YU‐PING
Published: January 2005

Abstract  The purpose of the present study was to identify the relapse antecedents for methamphetamine (MAMP) use in Taiwanese youth, and to examine the relationships between attribution of these antecedents, demographic variables, psychiatric disorders, characteristics of MAMP use, attitudes toward MAMP use, and personality. A total of 60 Taiwanese adolescents who had previously experienced MAMP relapse were studied. Their relapse antecedents for MAMP use were evaluated using the Questionnaire for Relapse Antecedents of Methamphetamine Use. Their psychiatric disorders were also assessed. The relationships among the relapse antecedents of MAMP use, demographic variables, MAMP‐use characteristics, psychiatric disorders, attitudes toward MAMP use and personality were analyzed. The results of the analysis reveal that social pressure to use MAMP was the leading antecedent of relapse. Social adaptation, emotional stability, and education level were the factors that influenced adolescents’ attributions of relapse antecedents for MAMP use. However, psychiatric disorder status and attitudes toward MAMP use were not related to any of the relapse antecedents. The results indicate that multiple factors influenced adolescents’ attributions of relapse antecedents for MAMP use, and may serve as a basis for construction of models for teaching adolescents to manage the antecedents and reduce the risk of relapse of MAMP use.
Morphological differences among cavum septi pellucidi obtained in patients with schizophrenia and healthy individuals: Forensic implications. A post‐mortem study
Authors: FILIPOVIĆ BRANISLAV , KOVAČEVIĆ SLOBODAN , STOJIČIĆ MILAN , PROSTRAN MILAN , FILIPOVIĆ BRANKA
Published: January 2005

Abstract  Cavum septi pellucidi (CSP), especially when longer than 6 mm, has been recognized as a neurodevelopmental anomaly associated with schizophrenia. The present post‐mortem study was designed to determine the importance of linear parameters of CSP and to evaluate the possible differences of CSP in schizophrenic patients (n = 25 out of 110 CSP+ brains) and normal persons (n = 40 out of 110 CSP+ brains). According to our results, schizophrenia patients had significantly longer and wider CSP than normal individuals. Also, statistical analysis revealed a higher suicide rate in CSP‐positive patients with schizophrenia.
A Decomposition Analysis of Regional Poverty in Russia
Authors: Kolenikov Stanislav , Shorrocks Anthony
Published: January 2005

The paper applies a new decomposition technique to the study of variations in poverty across the regions of Russia. The procedure, which is based on the Shapley value in cooperative game theory, allows the deviation in regional poverty levels from the all‐Russia average to be attributed to three proximate sources: per capita income, inequality, and local prices. Contrary to expectation, regional poverty variations turn out to be due more to differences in inequality across regions than to differences in real income per capita. However, when real income per capita is split into nominal income and price components, differences in nominal incomes emerge as more important than either inequality or price effects for the majority of regions.
Fifty Years of Regional Inequality in China: a Journey Through Central Planning, Reform, and Openness
Authors: Kanbur Ravi , Zhang Xiaobo
Published: January 2005

The paper constructs and analyzes a long‐run time series for regional inequality in China from the Communist Revolution to the present. There have been three peaks of inequality in the last fifty years, coinciding with the Great Famine of the late 1950s, the Cultural Revolution of the late 1960s and 1970s, and finally the period of openness and global integration in the late 1990s. Econometric analysis establishes that regional inequality is explained in the different phases by three key policy variables—the ratio of heavy industry to gross output value, the degree of decentralization, and the degree of openness.
Spatial–Horizontal Inequality and the Maoist Insurgency in Nepal
Authors: Murshed S. Mansoob , Gates Scott
Published: January 2005

The Maoist insurgency in Nepal is one of the highest intensity internal conflicts in recent times. Investigation into the causes of the conflict would suggest that grievance rather than greed is the main motivating force. The concept of horizontal or intergroup inequality, with both an ethnic and caste dimension, is highly relevant in explaining the Nepalese civil war. There is also a spatial aspect to the conflict, which is most intense in the most disadvantaged areas in terms of human development indicators and land holdings. Using the intensity of conflict (fatalities) as the dependent variable and HDI indicators and landlessness as explanatory variables, the authors find that the intensity of conflict across the districts of Nepal is significantly explained by the degree of inequalities.
Effects of Transient Myocardial Ischemia on the Ventricular Defibrillation Threshold
Authors: ANASTASIOU‐NANA MARIA I. , TSAGALOU ELEFTHERIA P. , CHARITOS CHRISTOS , SIAFAKAS KOSTANTINOS X. , DRAKOS STAVROS , TERROVITIS JOHN V. , NTALIANIS ARGIRIOS , DOUFAS ANTONIOS , MAVRIKAKIS JOHN , NANAS JOHN N.
Published: January 2005

Background: Acute myocardial ischemia and the mode of ventricular fibrillation (VF) induction influence the ventricular defibrillation threshold (DFT).

Objectives: The purpose of this study was to determine the effects of transient regional left ventricular (LV) ischemia on the DFT.

Methods: Ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and DFT were measured under nonischemic conditions (control) in 26 pigs weighing 25–35 kg. Myocardial ischemia was then induced by occlusion of the mid left anterior descending coronary artery, and measurements of ERP and VFT were repeated after 2 minutes of occlusion. The coronary artery ligation was released immediately after the onset of VF and DFT was measured.

Results: LV ERP was unchanged by ischemia (199 ± 19 ms at control vs. 200 ± 22 ms under ischemic conditions, P = 0.799), whereas VFT was significantly lower during coronary occlusion (10.7 ± 5.4 mA vs. 37.7 ± 13 mA, P = 0.000). Brief myocardial ischemia caused a significant increase in DFT (13.5 ± 12.6 J after coronary occlusion vs. 6.8 ± 6.8 J at control, P = 0.023). The duration of coronary occlusion was not correlated with the amounts of energy required to defibrillate (P = 0.526).

Conclusions: This experimental study shows that transient myocardial ischemia markedly increases the DFT, suggesting that specific defibrillation algorithms should be designed for recipients of implantable defibrillators at risk of myocardial ischemia.
Electrophysiological Characteristics of Junctional Rhythm During Ablation of the Slow Pathway in Different Types of Atrioventricular Nodal Reentrant Tachycardia
Authors: LEE SHIH‐HUANG , TAI CHING‐TAI , LEE PI‐CHANG , CHIANG CHERN‐EN , CHENG JUN‐JACK , UENG KOW‐CHANG , CHEN YI‐JEN , HSIEH MING‐HSIUNG , TSAI CHIN‐FENG , CHIOU CHUEN‐WANG , YU WEN‐CHUNG , KUO JEN‐YUAN , TSAO HSUAN‐MING , LEE KUN‐TAI , CHEN SHIH‐ANN
Published: January 2005

Background: Junctional rhythm (JR) is commonly observed during radiofrequency (RF) ablation of the slow pathway for atrioventricular (AV) nodal reentrant tachycardia. However, the atrial activation pattern and conduction time from the His‐bundle region to the atria recorded during JR in different types of AV nodal reentrant tachycardia have not been fully defined.

Methods: Forty‐five patients who underwent RF ablation of the slow pathway for AV nodal reentrant tachycardia were included; 27 patients with slow‐fast, 11 patients with slow‐intermediate, and 7 patients with fast‐slow AV nodal reentrant tachycardia. The atrial activation pattern and HA interval (from the His‐bundle potential to the atrial recording of the high right atrial catheter) during AV nodal reentrant tachycardia (HASVT) and JR (HAJR) were analyzed.

Results: In all patients with slow‐fast AV nodal reentrant tachycardia, the atrial activation sequence recorded during JR was similar to that of the retrograde fast pathway, and transient retrograde conduction block during JR was found in 1 (4%) patient. The HAJR was significantly shorter than the HASVT (57 ± 24 vs 68 ± 21 ms, P < 0.01). In patients with slow‐intermediate AV nodal reentrant tachycardia, the atrial activation sequence of the JR was similar to that of the retrograde fast pathway in 5 (45%), and to that of the retrograde intermediate pathway in 6 (55%) patients. Transient retrograde conduction block during JR was noted in 1 (9%) patient. The HAJR was also significantly shorter than the HASVT (145 ± 27 vs 168 ± 29 ms, P = 0.014). In patients with fast‐slow AV nodal reentrant tachycardia, retrograde conduction with block during JR was noted in 7 (100%) patients. The incidence of retrograde conduction block during JR was higher in fast‐slow AV nodal reentrant tachycardia than slow‐fast (7/7 vs 1/11, P < 0.01) and slow‐intermediate AV nodal reentrant tachycardia (7/7 vs 1/27, P < 0.01).

Conclusions: In patients with slow‐fast and slow‐intermediate AV nodal reentrant tachycardia, the JR during ablation of the slow pathway conducted to the atria through the fast or intermediate pathway. In patients with fast‐slow AV nodal reentrant tachycardia, there was no retrograde conduction during JR. These findings suggested there were different characteristics of the JR during slow‐pathway ablation of different types of AV nodal reentrant tachycardia.
Twin AV Node and Induced Supraventricular Tachycardia in Fontan Palliation Patients
Authors: BAE EUN‐JUNG , NOH CHUNG‐IL , CHOI JUNG‐YUN , YUN YONG‐SOO , KIM WOONG‐HAN , LEE JEONG‐RYUL , KIM YONG‐JIN
Published: January 2005

Introduction: The coexistence of two distinct atrioventricular (AV) nodes has been described in congenital heart disease requiring Fontan type palliation. The purpose of this study was to evaluate the occurrence of twin AV node according to anatomical subgroups, and to determine its relation to tachycardia.

Methods: From 2001 to 2003, we performed an electrophysiologic (EP) study upon 52 consecutive patients who had undergone cardiac catheterization after Fontan completion. Atrial pacing was performed at three or more different atrial sites.

Results: In 10/52 patients, two different QRS complexes were recorded at different pacing sites, suggesting twin AV node (9/20 in right isomerism, 1/8 discordance AV connections, 0/24 other complex anomalies). AV reciprocating tachycardia (AVRT), presumably involving two AV nodes and a connecting sling, was induced in 6 of 10 patients who had twin AV node (4/6 used posterior AV node as an antegrade limb, 2/6 used an anterior AV node as an antegrade limb). Heterotaxy syndrome (P < 0.001) and complete AV septal defect (P = 0.002) were found to be risk factors for twin AV node. Junctional tachycardia (JT; HR > 150/min) with either VA dissociation (7/9) or second degree VA block (2/9) were induced by pacing or isoproterenol infusion in 9/52 patients.

Conclusion: JT induction was associated with a twin AV node (P = 0.04), or a history of early postoperative junctional ectopic tachycardia (P = 0.02). A complicated AV node conduction system such as twin AV node was frequent in heterotaxy syndrome. Both AVRT and JT with VA block may be important causes of tachyarrhythmia in this patient group.
History of Wolff‐Parkinson‐White Syndrome
Authors: SCHEINMAN MELVIN M.
Published: January 2005

While Drs. Wolff, Parkinson, and White fully described the syndrome that bears their names in 1930, prior case reports had already described the essentials. Over the ensuing century this syndrome has captivated the interest of anatomists, clinical cardiologists, and cardiac surgeons. Stanley Kent described lateral muscular connections over the atrioventricular (AV) groove, which he felt were the normal AV connections. The normal AV connections were, however, clearly described by His and Tawara. True right‐sided AV connections were initially described by Wood et al., while Öhnell first described left free wall pathways. David Scherf is thought to be the first to describe our current understanding of the pathogenesis of the Wolff‐Parkinson‐White (WPW) syndrome in terms of a reentrant circuit involving both the AV node—His axis as well as the accessory pathway. This hypothesis was not universally accepted and many theories were applied to explain the clinical findings. The basics of our understandings were established by the brilliant work of Pick, Langendorf, and Katz who by using careful deductive analysis of ECGs were able to define the basic pathophysiological processes. Subsequently, Wellens and Durrer applied invasive electrical stimulation to the heart in order to confirm the pathophysiological processes. Sealy and his colleagues at Duke University Medical Center were the first to successfully surgically divide an accessory pathway and ushered in the modern area for curative therapy for these patients. Morady and Scheinman were the first to successfully ablate an accessory pathway (posteroseptal) using high‐energy direct‐current shocks. Subsequently, Jackman, Kuck, Morady, and a number of groups proved the remarkable safety and efficiency of catheter ablation for pathways in all locations using radiofrequency energy. More recently, Gallob et al. first described the gene responsible for a familial form of WPW. The current ability to cure patients with WPW is due to the splendid contributions of individuals from diverse disciplines from throughout the world.
Induction by kainate of theta frequency rhythmic activity in the rat medial septum–diagonal band complex in vitro
Authors: Garner Helen L. , Whittington Miles A. , Henderson Zaineb
Published: January 2005

The medial septum–diagonal band (MSDB) complex, via the septohippocampal pathway, is thought to be critical for the generation and/or maintenance of the hippocampal theta rhythm in vivo. The aim was to determine whether the MSDB is capable of generating and maintaining its own rhythmic firing activity, a mechanism by which it could impose a theta frequency oscillatory activity on the hippocampus. Bath application of 50–300 nm kainate to an in vitro preparation of 20‐ to 25‐day‐old rat MSDB elicited rhythmic extracellular field activity primarily within the theta frequency band (4–12 Hz). This activity was observed both at 33°C and at 37°C, and was localized to the midline part of the MSDB that is rich in parvalbumin‐containing neurones. The application of neurotransmitter receptor antagonists and putative gap junction blockers showed that the oscillatory field activity was dependent upon the activation of GABAA receptors and possibly gap junctions, but not on the activation of NMDA, GABAB, muscarinic or nicotinic receptors. The frequency of the oscillatory activity was reduced by the application of diazepam or low doses of baclofen. Intracellular recording showed that concomitant action potential firing activity in putative GABAergic and cholinergic neurone populations was of a single spiking rather than a bursting firing nature, and was coherent with extracellularly recorded oscillatory field activity. We conclude that kainate activation of neuronal circuitry in the MSDB is capable of synchronization of rhythmic activity in the MSDB, and that this may underlie the mechanism for phase‐locking rhythmic burst activity in the MSDB in vivo.
Regional variation in ICC distribution, pacemaking activity and neural responses in the longitudinal muscle of the murine stomach
Authors: Song Guizhi , David G. , Hirst S. , Sanders Kenton M. , Ward Sean M.
Published: January 2005

Intramuscular interstitial cells of Cajal (ICC‐IM) play a critical role in enteric neural regulation of the circular muscle layer in the stomach, but no studies have been performed on the longitudinal layer. Kit immunohistochemistry was used to examine ICC‐IM in the longitudinal muscle layer of the murine corpus and antrum, and it revealed marked heterogeneity in the distribution of ICC‐IM in longitudinal muscles. In the corpus, ICC‐IM were found along the greater curvature near the fundus. ICC‐IM decreased in density in the circumferential axis toward the lesser curvature and in the longitudinal axis toward the antrum. ICC‐IM were absent from the longitudinal layer of the antrum. Double labelling with markers for specific classes of enteric motor neurones revealed that cholinergic and nitrergic motor neurones formed close contacts with ICC‐IM in the corpus but not in the antrum. Enteric nerve stimulation evoked prominent cholinergic excitatory and nitrergic inhibitory responses in longitudinal muscles of the corpus, but not in the antrum of wild‐type animals. Cholinergic and nitrergic nerves were also present in W/WV mice, but functional innervation of the longitudinal muscle layer by these nerves in the corpus and antrum were absent. The data show that cholinergic and nitrergic neurotransmission only occurs in the gastric longitudinal layer in regions where ICC‐IM are present. In regions, such as the corpus, where ICC‐IM are common, robust neural responses are present, but the reduced density of ICC‐IM near the lesser curvature and in the distal stomach leads to reduced neural regulation in these gastric regions.
Compound‐specific Na+ channel pore conformational changes induced by local anaesthetics
Authors: Fukuda Koji , Nakajima Tadashi , Viswanathan Prakash C. , Balser Jeffrey R.
Published: January 2005

Upon prolonged depolarizations, voltage‐dependent Na+ channels open and subsequently inactivate, occupying fast and slow inactivated conformational states. Like C‐type inactivation in K+ channels, slow inactivation is thought to be accompanied by rearrangement of the channel pore. Cysteine‐labelling studies have shown that lidocaine, a local anaesthetic (LA) that elicits depolarization‐dependent (‘use‐dependent’) Na+ channel block, does not slow recovery from fast inactivation, but modulates the kinetics of slow inactivated states. While these observations suggest LA‐induced stabilization of slow inactivation could be partly responsible for use dependence, a more stringent test would require that slow inactivation gating track the distinct use‐dependent kinetic properties of diverse LA compounds, such as lidocaine and bupivacaine. For this purpose, we assayed the slow inactivation‐dependent accessibility of cysteines engineered into domain III, P‐segment (μ1: F1236C, K1237C) to sulfhydryl (MTSEA) modification using a high‐speed solution exchange system. As expected, we found that bupivacaine, like lidocaine, protected cysteine residues from MTSEA modification in a depolarization‐dependent manner. However, under pulse‐train conditions where bupivacaine block of Na+ channels was extensive (due to ultra‐slow recovery), but lidocaine block of Na+ channels was not, P‐segment cysteines were protected from MTSEA modification. Here we show that conformational changes associated with slow inactivation track the vastly different rates of recovery from use‐dependent block for bupivacaine and lidocaine. Our findings suggest that LA compounds may produce their kinetically distinct voltage‐dependent behaviour by modulating slow inactivation gating to varying degrees.
Hypoxia modulates early events in T cell receptor‐mediated activation in human T lymphocytes via Kv1.3 channels
Authors: Robbins Jennifer R. , Lee Susan Molleran , Filipovich Alexandra H. , Szigligeti Peter , Neumeier Lisa , Petrovic Milan , Conforti Laura
Published: January 2005

T lymphocytes are exposed to hypoxia during their development and when they migrate to hypoxic pathological sites. Although it has been shown that hypoxia inhibits Kv1.3 channels and proliferation in human T cells, the mechanisms by which hypoxia regulates T cell activation are not fully understood. Herein we test the hypothesis that hypoxic inhibition of Kv1.3 channels induces membrane depolarization, thus modulating the increase in cytoplasmic Ca2+ that occurs during activation. Hypoxia causes membrane depolarization in human CD3+ T cells, as measured by fluorescence‐activated cell sorting (FACS) with the voltage‐sensitive dye DiBAC4(3). Similar depolarization is produced by the selective Kv1.3 channel blockers ShK‐Dap22 and margatoxin. Furthermore, pre‐exposure to such blockers prevents any further depolarization by hypoxia. Since membrane depolarization is unfavourable to the influx of Ca2+ through the CRAC channels (necessary to drive many events in T cell activation such as cytokine production and proliferation), the effect of hypoxia on T cell receptor‐mediated increase in cytoplasmic Ca2+ was determined using fura‐2. Hypoxia depresses the increase in Ca2+ induced by anti‐CD3/CD28 antibodies in ∼50% of lymphocytes. In the remaining cells, hypoxia either did not elicit any change or produced a small increase in cytoplasmic Ca2+. Similar effects were observed in resting and pre‐activated CD3+ cells and were mimicked by ShK‐Dap22. These effects appear to be mediated solely by Kv1.3 channels, as we find no influence of hypoxia on IKCa1 and CRAC channels. Our findings indicate that hypoxia modulates Ca2+ homeostasis in T cells via Kv1.3 channel inhibition and membrane depolarization.
PIP2 hydrolysis underlies agonist‐induced inhibition and regulates voltage gating of two‐pore domain K+ channels
Authors: Lopes Coeli M. B. , Rohács Tibor , Czirják Gábor , Balla Tamás , Enyedi Péter , Logothetis Diomedes E.
Published: January 2005

Two‐pore (2‐P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5‐bisphosphate (PIP2) gating underlies several aspects of 2‐P channel regulation. Our results demonstrate that all four 2‐P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP2. We show that mechanical stimulation may promote PIP2 activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP2 scavenger polylysine, and the inhibition by the phosphatidylinositol 4‐kinase inhibitor wortmannin correlated with the level of agonist‐induced inhibition. This finding suggests that the strength of channel PIP2 interactions determines the extent of PLC‐induced inhibition. Finally, we show that PIP2 hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage‐dependent KCNQ1 channels. Our results suggest that PIP2 is a common gating molecule for K+ channel families despite their distinct structures and physiological properties.
BZR1 Is a Transcriptional Repressor with Dual Roles in Brassinosteroid Homeostasis and Growth Responses
Authors: He Jun-Xian , Gendron Joshua M. , Sun Yu , Gampala Srinivas S. L. , Gendron Nathan , Sun Catherine Qing , Wang Zhi-Yong
Published: January 2005

Brassinosteroid (BR) homeostasis and signaling are crucial for normal growth and development of plants. BR signaling through cell-surface receptor kinases and intracellular components leads to dephosphorylation and accumulation of the nuclear protein BZR1. How BR signaling regulates gene expression, however, remains unknown. Here we show that BZR1 is a transcriptional repressor that has a previously unknown DNA binding domain and binds directly to the promoters of feedback-regulated BR biosynthetic genes. Microarray analyses identified additional potential targets of BZR1 and illustrated, together with physiological studies, that BZR1 coordinates BR homeostasis and signaling by playing dual roles in regulating BR biosynthesis and downstream growth responses.
Membrane Insertion of a Potassium-Channel Voltage Sensor
Authors: Hessa Tara , White Stephen H. , von Heijne Gunnar
Published: January 2005

The mechanism of voltage gating in K+ channels is controversial. The paddle model posits that highly charged voltage-sensor domains move relatively freely across the lipid bilayer in response to membrane depolarization; competing models picture the charged S4 voltage-sensor helix as being shielded from lipid contact by other parts of the protein. We measured the apparent free energy of membrane insertion of a K+-channel S4 helix into the endoplasmic reticulum membrane and conclude that S4 is poised very near the threshold of efficient bilayer insertion. Our results suggest that the paddle model is not inconsistent with the high charge content of S4.
Heat Capacity of a Strongly Interacting Fermi Gas
Authors: Kinast Joseph , Turlapov Andrey , Thomas John E. , Chen Qijin , Stajic Jelena , Levin Kathryn
Published: January 2005

We have measured the heat capacity of an optically trapped, strongly interacting Fermi gas of atoms. A precise addition of energy to the gas is followed by single-parameter thermometry, which determines the empirical temperature parameter of the gas cloud. Our measurements reveal a clear transition in the heat capacity. The energy and the spatial profile of the gas are computed using a theory of the crossover from Fermi to Bose superfluids at finite temperatures. The theory calibrates the empirical temperature parameter, yields excellent agreement with the data, and predicts the onset of superfluidity at the observed transition point.
Ethical issues concerning New Zealand sports doctors: Figure 1
Authors: Anderson L C , Gerrard D F
Published: January 2005

Success in sport can provide a source of national pride for a society, and vast financial and personal rewards for an individual athlete. It is therefore not surprising that many athletes will go to great lengths in pursuit of success. The provision of healthcare for elite sports people has the potential to create many ethical issues for sports doctors; however there has been little discussion of them to date. This study highlights these issues. Respondents to a questionnaire identified many ethical matters, common to other areas of medicine. However they also raised problems unique to sports medicine. Some of these ethical difficulties arise out of the place of the sports doctor within the hierarchy of sport. Yet others arise out of the special relationship between sports doctors and individual players/athletes. This study raises some important questions regarding the governance of healthcare in sport, and what support and guidance is available to sports doctors. As medical and scientific intervention in sport escalates, there is a risk that demands for enhanced performance may compromise the health of the athlete, and the role the sports doctor plays remains a critical question.
Clinical ethics, information, and communication: review of 31 cases from a clinical ethics committee: Table 1
Authors: Førde R , Vandvik I H
Published: January 2005

Objectives:To summarise the types of case brought to the Clinical Ethics Committee of the National Hospital of Norway from 1996 to 2002 and to describe and discuss to what extent issues of information/communication have been involved in the ethical problems.

Design:Systematic review of case reports.

Findings:Of the 31 case discussions, (20 prospective, 11 retrospective), 19 cases concerned treatment of children. Twenty cases concerned ethical problems related to withholding/withdrawing of treatment. In 25 cases aspects of information/communication were involved in the ethical problem, either explicitly (n = 3) or implicitly (n = 22).

Conclusion:Problems related to information/communication may underlie a classic ethical problem. Identification of these “hidden” problems may be important for the analysis, and hence, the solution to the ethical dilemma.
Extended antipaternalism
Authors: Hansson S O
Published: January 2005

Extended antipaternalism means the use of antipaternalist arguments to defend activities that harm (consenting) others. As an example, a smoker’s right to smoke is often invoked in defence of the activities of tobacco companies. It can, however, be shown that antipaternalism in the proper sense does not imply such extended antipaternalism. We may therefore approve of Mill’s antipaternalist principle (namely, that the only reason to interfere with someone’s behaviour is to protect others from harm) without accepting activities that harm (consenting) others. This has immediate consequences for the ethics of public health. An antipaternalist need not refrain from interfering with activities such as the marketing of tobacco or heroin, boxing promotion, driving with unbelted passengers, or buying sex from “voluntary” prostitutes.
The ethics of using genetic engineering for sex selection
Authors: Liao S Matthew
Published: January 2005

It is quite likely that parents will soon be able to use genetic engineering to select the sex of their child by directly manipulating the sex of an embryo. Some might think that this method would be a more ethical method of sex selection than present technologies such as preimplantation genetic diagnosis (PGD) because, unlike PGD, it does not need to create and destroy “wrong gendered” embryos. This paper argues that those who object to present technologies on the grounds that the embryo is a person are unlikely to be persuaded by this proposal, though for different reasons.
Savulescu’s objections to the future of value argument
Authors: Marquis D
Published: January 2005

This essay is a response to Julian Savulescu’s objections to the future of value argument for the immorality of abortion published in theJournal of Medical Ethics, June 2002. Firstly, Savulescu’s claim that the future of value argument has implausible implications is considered. The author argues that the argument does not have these implications. Secondly, properties which, according to Savulescu, could underwrite the wrongness of killing and that are acquired only after implantation, are considered. It is argued that none of these properties is an adequate basis for the distinction between wrongful and permissible killing.
Principlism and moral dilemmas: a new principle
Authors: DeMarco J P
Published: January 2005

Moral conflicts occur in theories that involve more than one principle. I examine basic ways of dealing with moral dilemmas in medical ethics and in ethics generally, and propose a different approach based on a principle I call the “mutuality principle”. It is offered as an addition to Tom Beauchamp and James Childress’ principlism. The principle calls for the mutual enhancement of basic moral values. After explaining the principle and its strengths, I test it by way of an examination of three responses—in the recentFestschriftfor Dr Raanon Gillon—to a case involving parental refusal of a blood transfusion. The strongest response is the one that comes closest to the requirements of the mutuality principle but yet falls short. I argue that the mutuality principle provides an explicit future orientation in principlism and gives it greater moral coherence.
A NEURAL NETWORK MODEL WITH FEATURE SELECTION FOR KOREAN SPEECH ACT CLASSIFICATION
Authors: KIM KYUNGSUN , KIM HARKSOO , SEO JUNGYUN
Published: January 2005

A speech act is a linguistic action intended by a speaker. Speech act classification is an essential part of a dialogue understanding system because the speech act of an utterance is closely tied with the user's intention in the utterance. We propose a neural network model for Korean speech act classification. In addition, we propose a method that extracts morphological features from surface utterances and selects effective ones among the morphological features. Using the feature selection method, the proposed neural network can partially increase precision and decrease training time. In the experiment, the proposed neural network showed better results than other models using comparatively high-level linguistic features. Based on the experimental result, we believe that the proposed neural network model is suitable for real field applications because it is easy to expand the neural network model into other domains. Moreover, we found that neural networks can be useful in speech act classification if we can convert surface sentences into vectors with fixed dimensions by using an effective feature selection method.
ABERRANT DNA METHYLATION AS A CANCER-INDUCING MECHANISM
Authors: Esteller Manel
Published: January 2005

▪ Abstract  Aberrant DNA methylation is the most common molecular lesion of the cancer cell. Neither gene mutations (nucleotide changes, deletions, recombinations) nor cytogenetic abnormalities are as common in human tumors as DNA methylation alterations. The most studied change of DNA methylation in neoplasms is the silencing of tumor suppressor genes by CpG island promoter hypermethylation, which targets genes such as p16INK4a, BRCA1, and hMLH1. There is a profile of CpG island hypermethylation according to the tumor type, and genes silent by methylation represent all cellular pathways. The introduction of bisulfite-PCR methodologies combined with new genomic approaches provides a comprehensive spectrum of the genes undergoing this epigenetic change across all malignancies. However, we still know very little about how this aberrant DNA methylation “invades” the previously unmethylated CpG island and how it is maintained through cell divisions. Furthermore, we should remember that this methylation occurs in the context of a global genomic loss of 5-methylcytosine (5mC). Initial clues to understand this paradox should be revealed from the current studies of DNA methyltransferases and methyl CpG binding proteins. From the translational standpoint, we should make an effort to validate the use of some hypermethylated genes as biomarkers of the disease; for example, it may occur with MGMT and GSTP1 in brain and prostate tumors, respectively. Finally, we must expect the development of new and more specific DNA demethylating agents that awake these methyl-dormant tumor suppressor genes and prove their therapeutic values. The expectations are high.