bluuebunny/crossref_metadata_2025 huggingface dataset:
SELECTION OF PATIENTS FOR SURGERY FOR PRIMARY ALDOSTERONISM
Authors: Plouin Pierre‐François , Rossignol Patrick , Amar Laurence
Published: February 2008

Primary aldosteronism is a condition characterized by renin suppression and various degrees of hypertension and hypokalemia caused by aldosterone hypersecretion.

The adoption of the aldosterone‐to‐renin ratio determination as a screening test has led to an increase in the prevalence of diagnosed cases of primary aldosteronism.

Primary aldosteronism is confirmed by the demonstration of either sustained absolute aldosterone hypersecretion, or non‐suppressible aldosterone hypersecretion.

Computed tomography and adrenal vein sampling can then be used to distinguish between idiopathic primary aldosteronism and the surgically remediable forms: aldosterone‐producing adenoma and primary adrenal hyperplasia.

In patients with aldosterone‐producing adenoma or primary adrenal hyperplasia, unilateral adrenalectomy generally results in the normalization of aldosterone secretion and kalemia, but normotension is achieved in only half of the cases. Nevertheless, in many cases without hypertension cure, adrenalectomy leads to an improvement in hypertension control with lower blood pressure levels and/or less antihypertensive medication.
TRANSLATIONAL RESEARCH GOES BOTH WAYS: LESSONS FROM CLINICAL STUDIES
Authors: Funder John W
Published: February 2008

It is currently assumed that translational research goes from benchtop to bedside; that aldosterone elevates blood pressure via its effects on salt and water homeostasis; that mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) share a common immediate ancestor; and that aldosterone plays a deleterious role in essential hypertension and heart failure.

Meta‐analysis of clinical trials in essential hypertension, in which eplerenone was dose‐titrated to attain diastolic blood pressure < 90 mmHg, showed no relationship between blood pressure response and electrolyte effects, as judged by change in plasma (K).

Reexamination of sequence data, and insights from the S810L MR mutant gene causing juvenile hypertension exacerbated by pregnancy, suggest that MR were the first to branch off the primordial ancestor for MR, GR, androgen receptors (AR) and progesterone receptors (PR).

In clinical trials of MR blockade in heart failure and essential hypertension baseline aldosterone levels are in the low to normal range and sodium status unremarkable. Under such circumstances cortisol appears to be responsible for MR activation, thus exculpating aldosterone in these conditions.

On the basis of these clinical studies, there is need to revisit the basic biology of aldosterone and MR as translational research very clearly goes both ways.
CARDIOVASCULAR RISK ASSESSMENT THROUGH TARGET ORGAN DAMAGE: ROLE OF CAROTID TO FEMORAL PULSE WAVE VELOCITY
Authors: Boutouyrie Pierre , Vermersch Sebastian , Laurent Stéphane , Briet Marie
Published: February 2008

Cardiovascular risk prediction relies on classical risk factors such as age, gender, lipids, hypertension, smoking and diabetes. Although the value of such scales of risk is high for populations, its value for individuals is reduced and much influenced by non‐modifiable risk factors (age and sex).

Biomarkers of risk have been deceiving and the genome‐wide scan approach is too recent to have been useful. Target‐organ damage may help in selecting patients at high risk and determine the necessity of intervention.

Aortic pulse wave velocity, an index of aortic stiffness, has been widely validated as providing additional risk prediction above and beyond classical risk factors and has now entered the 2007 guidelines for hypertension of the European Society of Hypertension.

We aim to show that individual prediction of cardiovascular‐related death can be improved by taking aortic stiffness into account in a cohort of patients during a longitudinal follow‐up.

Points to be improved are the homogenization and spreading of the technique of measurement, the establishment of a reference value database and the demonstration of the added value of aortic stiffness screening and stratification in interventional trials.
Management of metastatic prostate cancer: the crucial role of geriatric assessment
Authors: Droz Jean‐Pierre , Chaladaj Agnieska
Published: February 2008

Prostate cancer predominantly affects older men, with a median age at diagnosis of 68 years. Due to the increased life expectancy, management of prostate cancer in senior adults (aged >70 years) represents a major public health problem. This patient population may not receive optimal therapy for their disease, if decisions are made based on their chronological age alone. More so than age alone, health status is a major factor affecting individual life expectancy. Comorbidity is the key predictor of health status and should weigh more heavily on the treatment decision than age alone. Other important parameters to consider in senior adults are the degree of dependence in activities of daily living, the nutritional status and the presence or not of a geriatric syndrome. Although clinical trials are rarely designed specifically for senior adults, evidence suggests that healthy senior adults have similar treatment outcomes to their younger counterparts.

The urological approach in senior adults with advanced prostate cancer should be fundamentally the same as in younger patients. In hormone‐sensitive metastatic prostate cancer, androgen deprivation represents the first‐line treatment. In senior adults, care should be given to the increased risk of metabolic syndrome, cardiovascular mortality and bone fracture. In hormone‐refractory metastatic prostate cancer, chemotherapy with docetaxel (75 mg/m2 every 3 weeks) plus low‐dose prednisone is the standard and shows the same efficacy in healthy senior adults as in younger patients. The tolerance of docetaxel (3‐weekly schedule) has not been specifically studied in vulnerable and frail senior adults. The place of weekly docetaxel in this setting should be further evaluated. Palliative treatments (palliative surgery, radiopharmaceutics, radiotherapy, medical treatments for pain and symptoms, pharmacological palliative therapies) should also be integrated in the global management of these patients.

In conclusion, treatment decisions in senior adults should be adapted to health status. Healthy senior adults should be treated the same as younger patients. The development of guidelines for the management of localized and advanced prostate cancer in senior adults is underway.
On‐market share buybacks, exercisable share options and earnings management
Authors: Balachandran Balasingham , Chalmers Keryn , Haman Janto
Published: February 2008

Chan et al. (2006b) suggest that managers might announce a share buyback to manipulate investors’ perceptions and capitalize on the positive price reaction usually associated with the announcement. The incentive to do so is greater when managers have exercisable options. Prior studies document that managers engage in upwards earnings management for opportunistic reasons related to option holdings (Bergstresser and Philippon, 2006). We examine the association between earnings management and exercisable option holdings for buyback firms to investigate if earnings management in the pre‐buyback period is greater for firms with equity incentives to increase share price. Our results, using 138 buybacks over the period 1996–2003, support our prediction. We find that buyback firms with both exercisable options that are in‐the‐money prior to the buyback announcement as well as options that are exercised in the buyback period have higher discretionary current accruals than buyback firms with no exercisable options, unexercised options or with out‐of‐the‐money options. Overall, our results are consistent with buyback firms with exercisable options using earnings management and buyback announcements to maximize option payoffs, and buyback firms without exercisable options signalling undervaluation.
Does accounting choice influence US investment in non‐US companies? Evidence from US institutional investment in Australian companies
Authors: Chugh Shrutika , Fargher Neil
Published: February 2008

Previous research asserts that companies that choose accounting methods more familiar to investors reduce information asymmetry and increase credibility of their financial statements to those investors, thereby attracting higher levels of foreign investment. This study examines the variation in accounting policies associated with institutional investment in Australian equity. The results suggest that large US institutional holdings in Australian companies are associated with American Depositary Receipt listing and, incrementally, choice of accounting methods that conform to US Generally Accepted Accounting Principles (GAAP). Although making accounting choices in compliance with US GAAP is significantly associated with higher levels of institutional ownership in a statistical sense, examination of the specific differences in accounting choices suggests that the differences in informational content are relatively minor.
Financial analysts and price discovery
Authors: Aitken Michael , Almeida Niall , Harris Frederick H. deB. , McInish Thomas H.
Published: February 2008

We show that whether or not a bank/brokerage firm has top‐rated financial analysts and high Wall Street Search rankings for their research is significantly related to that firm's contribution to price discovery, the process by which information is incorporated into stock prices. Our study relates cross‐sectional characteristics of the quality of brokerage research, the asymmetric information environment, and order flow volume to a microstructure measure of price discovery developed by Granger and Gonzalo. We measure analysts’ research quality with an industry‐specific ranking by institutional investors, with an opinion survey of trading desk personnel, and with the number of top 3 analysts across all industries employed by the bank/brokerage firm.
The fundamental drivers of the obesity epidemic
Authors: James W. P. T.
Published: February 2008

Most policy makers do not yet understand that the obesity epidemic is a normal population response to the dramatic reduction in the demand for physical activity and the major changes in the food supply of countries over the last 40 years. A national focus on individual behaviour reflects a failure to confront the facts. Thus, the changes in food supply and physical environment are socioeconomically driven, and the health sector simply picks up the consequences. Urbanization alone in China has reduced daily energy expenditure by about 300–400 kcal d−1 and cycling/bussing or going to work by car determines another variation of 200 kcal d−1. Thus, energy demands may have dropped with additional TV/media, mechanization and computerized changes by 400–800 kcal d−1, so weight gain and obesity are inevitable for most or all the population. Food intake should have fallen substantially despite the community's focus on the value of food after all the food crises of the past. Yet, Chinese fat and sugar intakes are escalating, and these policy‐mediated features are amplified by the primeval biological drive for those commodities with specialized taste buds for fatty acids, meat, sugar and salt. Yet, traditionally, Chinese diets had negligible sugar, and 25‐year‐old data show that the optimum diet for Chinese contains 15% fat. Policies relating to food imports, agriculture, food quality standards, appropriate food traffic light labelling, price adjustments and controlled access to unhealthy foods are all within the grasp of the Chinese government. China has traditionally been far more responsive to the value of policies which limit inequalities and establish standards of care than many western governments, who have yet to recognize that the individualistic free‐market approach to obesity prevention is guaranteed to fail. China could therefore lead the way: if it follows western approaches, the health and economic burden will become unsustainable.
Obesity and its related diseases in Taiwan
Authors: Huang K.‐C.
Published: February 2008

Obesity is related to increased morbidity and mortality, and prevails worldwide. It has become an important health issue and requires urgent attention. In Taiwan, overweight and obesity are defined as body mass index ≥24 and 27 kg m−2, respectively. These cut‐offs differ from Caucasian standards, as Asians have higher comorbidities and fat mass at lower BMI levels than Caucasians. The prevalence of obesity and overweight in Taiwan are 19.2% and 30.5% in men, 13.4% and 21.3% in women. This implies that a more profound increase in obesity prevalence is found in men than in women. A high‐fat diet, sedentary lifestyle and betel nut chewing may increase substantially this obesity epidemic. Recently, type 2 diabetes mellitus has been found to be the most common type of diabetes, and obesity is significantly related to type 2 diabetes in children. In addition, obesity is associated with cardiovascular diseases risk factors and cannot be neglected in elderly. Therefore, a comprehensive prevention and management programme of obesity is urgently warranted for controlling the growing obesity trend and its related diseases in Taiwan.
Ethnic comparisons of the cross‐sectional relationships between measures of body size with diabetes and hypertension
Authors: Huxley R. , James W. P. T. , Barzi F. , Patel J. V. , Lear S. A. , Suriyawongpaisal P. , Janus E. , Caterson I. , Zimmet P. , Prabhakaran D. , Reddy S. , Woodward M. ,   the Obesity in Asia Collaboration
Published: February 2008

Recent estimates indicate that two billion people are overweight or obese and hence are at increased risk of cardiovascular disease and its comorbidities. However, this may be an underestimate of the true extent of the problem, as the current method used to define overweight may lack sensitivity, particularly in some ethnic groups where there may be an underestimate of risk. Measures of central obesity may be more strongly associated with cardiovascular risk, but there has been no systematic attempt to compare the strength and nature of the associations between different measures of overweight with cardiovascular risk across ethnic groups. Data from the Obesity in Asia Collaboration, comprising 21 cross‐sectional studies in the Asia‐Pacific region with information on more than 263 000 individuals, indicate that measures of central obesity, in particular, waist circumference (WC), are better discriminators of prevalent diabetes and hypertension in Asians and Caucasians, and are more strongly associated with prevalent diabetes (but not hypertension), compared with body mass index (BMI).

For any given level of BMI, WC or waist : hip ratio, the absolute risk of diabetes or hypertension tended to be higher among Asians compared with Caucasians, supporting the use of lower anthropometric cut‐points to indicate overweight among Asians.
Developmental origin of metabolic syndrome: interaction of thinness at birth and overweight during adult life in Chinese population
Authors: Mi J. , Cheng H. , Zhao X.‐Y. , Hou D.‐Q. , Chen F.‐F. , Zhang K.‐L.
Published: February 2008

In the present study we explore the association between the ponderal index (PI) at birth and the metabolic syndrome (MetS) in middle‐aged population in China. A total of 975 men and women aged 41–52 years with detailed birth records were followed up and recruited for clinic examinations, involving anthropometry and measurements of blood pressure, fasting plasma glucose, serum lipid profile. The MetS was diagnosed according to the National Cholesterol Education Program (Adult Treatment Panel III) definition. Multivariate logistic regression analysis estimated the effect of PI on MetS and the interaction between PI at birth and adult body mass index (BMI). The average prevalence of MetS was 19.3%, with rates of 23.7%, 22.9%, 16.9% and 16.5% in those who at birth were <25th percentile, the 25th−50th percentile, the 50th−75th percentile and >75th percentile PI respectively, with a significant decreasing trend (x2for trend = 5.661, P = 0.017). Logistic regression analysis showed that 25.7% of the occurrence of MetS was attributable to PI at birth and adult BMI both acting independently and synergistically.

In summary thinness at birth predicts the later occurrence of MetS, as well as modifying the association between later BMI and MetS. Overweight later in life was most deleterious for those with growth retardation at birth.
Closing the energy gap to prevent weight gain in China
Authors: Zhai F. , Wang H. , Wang Z. , Popkin B. M. , Chen C.
Published: February 2008

To estimate the energy gap (i.e. degree of positive energy balance) that is causing weight gain in the population of China in order to provide a quantitative goal for how much behaviour change is required to prevent excess weight gain in the population. This is based on data collected in the China Health and Nutrition Survey. 2288 adults (20–45 years) who took part in both the 1989 and 2000 surveys were selected. Results: from 1989 to 2000, the average weight of this population increased from 55.4 kg to 59.1 kg. The medium increasing rate was 0.33 kg year−1. During this time, the prevalence of overweight in the population increased dramatically from 9.0% to 23.2%. By assuming that each kilogram of body weight gained represents 7700 kcal, the estimated medium energy accumulation in the sample was 7.0 kcal day−1 and the 90th percentile was 22.5 kcal d−1. Further, assuming that the energy derived from mixed composition diets is stored with an average efficiency of 50%, the estimated energy gap for the population was 45 kcal day−1. This is the degree of positive energy balance that is causing weight gain in 90% of the population. The estimate suggests that the behaviour change needed to close the energy gap is small and achievable without dramatically altering current lifestyle in China. For example, reducing energy intake by just 2–3% less each day or walking an extra 10–15 minutes each day could offset weight gain in roughly 90% of the population in China. By providing an estimate of the energy gap it can be predicted that weight gain in most of the population of China could be prevented with small lifestyle changes. It is critical that these lifestyle changes be implemented in order to prevent acceleration of the obesity epidemic in China.
Effect of supervised exercise intervention on metabolic risk factors and physical fitness in Chinese obese children in early puberty
Authors: Chang C. , Liu W. , Zhao X. , Li S. , Yu C.
Published: February 2008

The aim of this paper was to study the effect of long‐term supervised exercise‐induced weight maintenance on metabolic risk factors and physical fitness in obese children in early puberty. A total of 49 obese children aged 12–14 years were divided into control and exercise groups. The children in the exercise group accepted exercise intervention supervised by a professional sports teacher for 9 of the 12 months. All participants in both groups received health education once every 3 months. Anthropometry and fasting serum lipids, glucose, insulin and homeostatic model assessment for insulin resistance (HOMA‐IR) were measured at months 0, 3, 9, 12 of the intervention. Physical fitness was determined before and after intervention. After the intervention (i) BMI was reduced by 0.6 (P < 0.05) in the exercise group, but increased by 0.5 (P < 0.05) in the control group, compared with the pre‐intervention level at the end of 9‐month intervention; (ii) Triglyceride levels in the exercise group significantly decreased by 23.1% by 3 months (P < 0.05), and by 30.2% after 9 months (P < 0.05), but increased by 50% (P < 0.05) in the control group; high density lipoprotein‐cholesterol (HDL‐C) decreased more by 35% (P < 0.05) in the controls than in the exercise group (P < 0.05); (iii) Fasting serum glucose, insulin level and HOMA‐IR decreased, respectively, by 23.1%, 36.6% and 48.5% in the exercise group at 9 months (P < 0.05), whereas glucose levels increased by 10.9% (P < 0.05) in the control group; (iv) Exercise performance, such as upper‐ and lower‐limb strength, flexibility and endurance, were enhanced by 17.9%, 12.3%, 22.3% and 20.4% (P < 0.01), respectively and (v) At 12 months, i.e. 3 months after terminating the supervised exercise, serum triglycerides, glucose, insulin and HOMA‐IR level all returned to the pre‐intervention level. Supervised decrement exercise can effectively slow the progress of obesity, improve insulin sensitivity and metabolic risk factors, but once the supervised exercise is stopped, the health benefits weaken or vanish. The key to helping these obese children is for them to cultivate good exercise habits which are sustained throughout their lives.
The representation of language within language: a syntactico‐pragmatic typology of direct speech*
Authors: De Vries Mark
Published: February 2008

Abstract. The recursive phenomenon of direct speech (quotation) comes in many different forms, and it is arguably an important and widely used ingredient of both spoken and written language. This article builds on (and provides indirect support for) the idea that quotations are to be defined pragmatically as (quasi‐)linguistic demonstrations. Such a perspective sheds new light on constructions involving denomination, identification and typification – all of which are related to autonymy – and also on the possibility of quoting extralinguistic matters like sounds and even emotions. Based on these possibilities, a syntactic typology of direct speech is developed, including independent, embedded, and parenthetic quotations, with several subtypes. It is shown that quotations are grammatically opaque, and that embedded quotations are assigned a nominal categorial status upon insertion into a syntactic derivation. Thus, it is explained that a quotation can be used not only as a full argument, but also as a nominal head – even as a part of a compound.
BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation
Authors: Hu Yinghui , Russek Shelley J.
Published: February 2008

It is clear that brain‐derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, epilepsy, Rett’s syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF‐driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities.
A case of vascular depression associated with musical hallucinations successfully treated with paroxetine and a low dose of risperidone
Authors: UMENE Wakako , YOSHIMURA Reiji , HORI Hikaru , NAKAMURA Jun
Published: February 2008

Herein, we report a case of an 83‐year‐old man with vascular depression associated with musical hallucinations. Brain magnetic resonance imaging disclosed diffuse brain atrophy with multiple higher‐density zones in the white matter and basal ganglia. Single photon emission computed tomography images showed areas of hypoperfusion in the bilateral temporal lobe and basal ganglia. Combination treatment with paroxetine and a low dose of risperidone rapidly improved both the depressive symptoms and musical hallucinations.
Learning Disability Prevalence and Adult Education Program Characteristics
Authors: Patterson Margaret Becker
Published: February 2008

This study identifies adult education program characteristics associated with learning disability (LD) prevalence through statistical analyses of data from a single U.S. state (Kansas). Data indicate that several variables at the adult education (AE) program level are linked to LD prevalence, including disability incidence, educational background of learners, and learner age. In addition, after participation in AE services, learner outcomes associated with LD prevalence are adult basic and secondary learning gains, GED outcomes, and entering employment. Learner skill level on entering the AE program, learner outcomes of retaining employment, and program characteristics related to staffing and funding did not consistently associate with LD prevalence. These results have implications for AE program staff and policy makers and suggest a need for further research of individual characteristics of adult learners with LD.
Alcohol Intake is Significantly Associated with Atrial Flutter in Patients under 60 Years of Age and a Shorter Right Atrial Effective Refractory Period
Authors: MARCUS GREGORY M. , SMITH LISA M. , WHITEMAN DEAN , TSENG ZIAN H. , BADHWAR NITISH , LEE BYRON K. , LEE RANDALL J. , SCHEINMAN MELVIN M. , OLGIN JEFFREY E.
Published: February 2008

Background: Although evidence suggests that alcohol is associated with atrial fibrillation (AF), the association between alcohol and atrial flutter (AFL) has not been examined. The mechanism connecting alcohol and atrial arrhythmias is unknown.

Methods: Alcohol intake was determined in 195 consecutive patients with AF and AFL. Control subjects included patients with other supraventricular arrhythmias (n = 132) and healthy subjects (n = 54). Because of important competing risk factors for atrial arrhythmias in the elderly, stratification by age was performed. In a subset, atrial effective refractory periods (AERPs) were obtained from the high right atrium and proximal and distal coronary sinus.

Results: AF and AFL patients were significantly more likely to be daily alcohol drinkers (27% vs 14% of controls, P = 0.001). In multivariable analysis, AFL patients ≤ 60 years of age were significantly more likely to be daily drinkers than to drink no alcohol compared to controls (odds ratio 17, 95% confidence interval 1.6–192.0, P = 0.019). Progressively more frequent alcohol intake was significantly associated with a progressively greater odds of AFL in patients ≤ 60 years of age (P = 0.045). Neither AF subjects of any age nor AFL subjects > 60 years of age exhibited significant associations with alcohol after multivariable adjustment. Right AERPs shortened significantly with increasing amounts of alcohol intake (P = 0.025), whereas left AERPs were not associated with alcohol intake.

Conclusions: Alcohol intake is positively associated with AFL in younger patients. The mechanism may be related to a shortening of the right AERP.
The Acute Effect of Cardiac Pacing Mode on Endothelial Vasodilation: Prospective, Double‐Blind, Cross‐Over, Comparative Clinical Study
Authors: FAK ALI SERDAR , OZBEN BESTE , TOPRAK AHMET , CINCIN A. ALTUG , PAPILA NURDAN , TANRIKULU M. AZRA , OKTAY AHMET
Published: February 2008

Background: Compared to atrioventricular sequential pacing, ventricular demand pacing is known to have somewhat more deleterious hemodynamic effects, which probably arise from increased sympathetic tonus and inappropriate baroreceptor activation. Endothelial function is affected by various local and systemic factors including baroreceptor activity. The aim of this study was to explore whether cardiac pacing would have any effect on endothelial functions.

Methods: Twelve patients (six male, mean age: 75 ± 9 years) with previously implanted DDD or VDD
cardiac pacemakers were included. All patients had stable atrial rhythms during the study. Patients were randomized to either atrial‐based pacing mode (VDD or DDD) or ventricular demand pacing mode (VVI) first, and then cross‐over was performed with the other pacing mode. Endothelial function was assessed by brachial artery ultrasonography. Basal diameter of the brachial artery, and both flow‐mediated dilation (FMD) and endothelium‐independent vasodilation with nitroglycerin were measured 1 hour after each pacing mode.

Results: Compared to atrial‐based pacing mode, ventricular demand pacing was associated with a significantly worse FMD both as absolute and percentage values (0.17 ± 0.09 mm vs 0.28 ± 0.11 mm, P = 0.015 and 4.84 ± 2.37 % vs 7.00 ± 2.88 %, P = 0.028, respectively). However, there was no significant difference in nitroglycerin‐mediated vasodilation values between the two pacing sessions.

Conclusions: Acute ventricular demand pacing (VVI pacing) is clearly associated with attenuation of FMD in patients with atrial‐based pacing systems. The attenuation of endothelial vasodilation might have a role in hemodynamic and clinical deterioration in patients with VVI pacemakers.
Ablation of Ventricular Tachycardia in Patients with Structural Heart Disease
Authors: ZEPPENFELD KATJA , STEVENSON WILLIAM G.
Published: February 2008

Catheter ablation is an important therapeutic option for controlling recurrent ventricular arrhythmias in patients with heart disease. Although implantable defibrillators are generally first line therapy in this patient population, a substantial number of patients require additional therapy with either antiarrhythmic drugs, ablation, or both. Studies of mapping and ablation have produced further insights into pathophysiologic mechanisms of these arrhythmias, which are now well characterized. The majority is due to reentry through regions of ventricular scar. Methods for identifying scar based on electrogram characteristics now allow arrhythmogenic areas to be targeted for ablation during stable sinus rhythm, such that ablation is often an option even when multiple and unstable ventricular tachycardia are present. Ablation failure can also be due to anatomical obstacles; however, methods for accessing the pericardial space for mapping and ablation and technological progress can be expected to further improve its efficacy.
Three‐Dimensional Mapping of Atypical Right Atrial Flutter Late after Chest Stabbing
Authors: STEVEN DANIEL , ROSTOCK THOMAS , LUTOMSKY BORIS , WILLEMS STEPHAN
Published: February 2008

We present the case of a female patient who previously underwent cardiac surgery for traumatic anterior right atrial perforation after a stabbing attack. Four years later the patient presented with right atrial common type flutter and isthmus ablation was performed subsequently. However, three years after isthmus ablation the patient was readmitted with atypical right atrial flutter. Electrophysiological study revealed persistent bidirectional isthmus block. Three‐dimensional mapping (NavX, St. Jude Medical, St. Paul, MN, USA) demonstrated an incisional tachycardia with the critical isthmus at the border of the anterior area of scar in a close proximity to the superior tricuspid annulus. After ablation of this isthmus the patient was arrhythmia free after a follow‐up of 9 months. This case illustrates that three‐dimensional scar mapping may help to identify unusual isthmus sites that may be simultaneously responsible for both typical and atypical atrial flutter.
Pause Dependent Ventricular Tachycardia Resultant from Carotid Sinus Massage
Authors: FOX MARSHAL , VERGA TREVOR , JADONATH RAM , BELDNER STUART
Published: February 2008

In this report we describe a case of atrial flutter degenerating into ventricular fibrillation after carotid sinus pressure. Carotid sinus massage is an extremely valuable and widely used diagnostic and therapeutic modality. Although generally considered a rather benign maneuver, it is not without potential risk.
Cyclic Cluster Study on the Bulk Modulus and Hydration Pressure of Magnesia Expansion
Authors: Jug Karl , Heidberg Bettina , Bredow Thomas , Littmann Klaus
Published: February 2008

Cyclic cluster studies with the quantum chemical method MSINDO were performed to elucidate the key properties of brucite concerning the magnesia expansion. A model is presented that allows the calculation of the compressibility of brucite under hydrostatic pressure. In this way, the bulk modulus of brucite can be determined via the binding energy. The elastic constants, Poisson's ratios, volume compressibility, and finally the bulk modulus were calculated and compared with the experimental values. Except for the component Ka of the compressibility, there is good agreement with the experimental values. Based on the bulk modulus, an expression for the volume change of brucite under pressure is derived. The hydration pressure of the periclase reaction with water to form brucite is related to the partial water vapor pressure. In this way, the maximum hydration pressure was determined.
Natural history of choroidal neovascularization after surgical induction in an animal model
Authors: Lassota Nathan , Kiilgaard Jens Folke , La Cour Morten , Scherfig Erik , Prause Jan Ulrik
Published: February 2008

Purpose:  To study an expanded time course of surgically induced choroidal neovascularization (CNV) in a porcine model applying fluorescence angiography and immunohistology.

Methods:  Twenty‐two porcine eyes underwent vitrectomy, a retinal bleb was raised and the detached retina perforated using endodiathermy. Bruch’s membrane was perforated with a retinal perforator at a site where the overlying neuroretina was normal. Eyes were enucleated in a time interval between 30 min and 42 days after the perforation, and the pigs were subsequently killed. Immediately prior to enucleation, fundus photographs and fluorescein angiograms were obtained. Sections of paraffin‐embedded eyes were immunohistochemically stained.

Results:  On fluorescein angiography, membranes aged 14 days or less exhibited leakage in 10/11 cases while the remaining showed persistent staining. The propensity to leak diminished with time and only 1/3 of the oldest membranes leaked. In eyes enucleated immediately after surgery, neuroretinas overlying the induced lesions were intact without apparent atrophy of cells. At day 3, macrophages and myofibroblasts formed membrane‐like structures in the subretinal space. At day 7, the outer surface of the membrane was covered by retinal pigment epithelium (RPE) cells and the neuroretinas had suffered damage in the form of outer segment loss. In the time period 14–42 days, the CNV membrane became completely enveloped by RPE cells. The degree of membrane vascularization increased with time and was at its maximum after 42 days. Intact outer segments were identified over the oldest membranes.

Conclusion:  The formation of surgical CNV membranes followed the normal reparatory pathway and the degree of vascularization of CNV membranes continued to increase during the 42 days. However, propensity to leak diminished with time. We believe that this was because of the fact that RPE cells completely enveloped older membrane and thus prevented leakage from the newly formed vessels. Photoreceptor outer segments, which had atrophied after 7 days, were able to regenerate over CNV membranes and could be identified again after 42 days.
Absence of amplification of CD4+CD25high regulatory T cells during in vitro expansion of tumor‐infiltrating lymphocytes in melanoma patients
Authors: Knol Anne Chantal , Lemaître Fabrice , Pandolfino Marie Christine , Volteau Christelle , Quéreux Gaëlle , Saiagh Soraya , Khammari Amir , Viguier Manuelle , Dréno Brigette
Published: February 2008

Abstract:  The exact role of CD4+CD25high regulatory T cells (Treg) in adoptive immunotherapy of melanoma is still to be determined, and an association between an expansion of Treg cells and the expansion of therapeutic tumor‐infiltrating lymphocytes (TIL) remains unelucidated. In this context, the aim of our study was to determine whether functional Treg cells were detectable and amplified among in vitro‐expanded TIL from 10 metastatic melanoma lymph nodes (LNs). In this study, we investigated the expression of forkhead/winged helix transcription factor 3 (Foxp3) in melanoma‐invaded LNs and determined proportion and functionality of Treg cells among TIL extracted from these 10 metastatic melanoma LNs at different steps of their in vitro expansion. We found that metastatic melanoma LNs expressed very heterogeneous levels of Foxp3 and that CD4+CD25high Treg cells extracted from these LNs were detectable at each step of the in vitro culture of TIL but decreasing during the culture. In addition, functional assays demonstrated that these CD4+CD25high T cells were capable of suppressing autologous CD8+ and CD4+CD25‐ T cell proliferation. These cells were indeed Treg cells as they expressed Foxp3. In conclusion, our work suggests that CD4+CD25high Foxp3 expressing T cells are not expanded during in vitro amplification of TIL obtained from melanoma‐invaded LNs.
Nucleofection is a highly effective gene transfer technique for human melanoma cell lines
Authors: Han Sandra Y. , Gai Weiming , Yancovitz Molly , Osman Iman , Di Como Charles J. , Polsky David
Published: February 2008

Abstract:  Despite the increasing use of gene transfer strategies in the study of cellular and molecular biology, melanoma cells have remained difficult to transfect in a safe, efficient, and reproducible manner. In the present study, we report the successful use of nucleofector technology to transfect human melanoma cell lines. This technology uses an empirically derived combination of cell line‐specific solutions and nucleofector programmes to electroporate nucleic acid substrates directly into the cell nucleus. Using a colorimetric β‐galactosidase assay, we optimized nucleofection parameters for 13 melanoma cell lines, leading to maximum transfection efficiency and cell survival. The combinations of cell solutions NHEM or T and nucleofector programmes A‐24 or U‐20 produced the best results. We compared nucleofection with two commercially available lipid‐based gene transfer systems, effectene and lipofectamine 2000 using a green fluorescent protein reporter vector. Nucleofection demonstrated a 3‐ to 40‐fold improvement in transfection efficiency when compared with the lipid‐based counterparts. Nucleofection was also superior in transfecting small‐interfering RNA (siRNA) as determined by Western blot analysis. Lastly, we applied nucleofection to the simultaneous transfection of a p53‐dependent luciferase plasmid and p53‐siRNA. Experiments using dual transfection showed knockdown of p53 expression and silencing of the reporter plasmid. In conclusion, nucleofection is highly effective for the transfer of nucleic acid substrates, singly or in combination, into human melanoma cell lines.
Terlipressin as rescue treatment of refractory shock in a neonate
Authors: Filippi Luca , Poggi Chiara , Serafini Lisa , Fiorini Patrizio
Published: February 2008

Patients with septic shock may develop refractory hypotension despite maximal inotropic support with impairment of clinical outcome. Terlipressin, a long‐acting vasopressin analogue, is reported to be effective as rescue treatment of refractory septic shock in adult and paediatric patients, while clinical experience in neonates is definitely scarce. We report a neonate with systemic inflammatory response syndrome after surgery for abdominal neuroblastoma who received terlipressin as rescue treatment after failure of volume load and catecholamines. Terlipressin promptly reversed hypotension and improved tissue perfusion without adverse effects.

Conclusion: Terlipressin appears an effective rescue treatment in patients with refractory vasodilatory septic shock. Further studies are required to assess its efficacy and safety in neonatal population.
Unexplained seizures, confusion or hallucinations: think Hashimoto encephalopathy
Authors: Alink Jorien , De Vries Tjalling W.
Published: February 2008

Aim: Hashimoto encephalopathy (HE) is a serious but treatable condition that is probably underdiagnosed. We summarize and review all published cases to delineate the disease and to alert paediatricians so that they recognize the disease in children.

Methods: We searched three data sources, PubMed, Cochrane and Embase, to find the articles on the subject.

Results: Twenty‐five children (85.8% girls) were reported being diagnosed with HE. The median age was 14 years (range 9–18 years). The most frequent clinical symptoms were seizures (80%), confusion (52%), headache (40%), hallucinations (32%) and ataxia (36%). Antimicrosomal antibodies were demonstrated in all patients, other diagnostic methods were not specific. Treatment with steroids was effective with 55% of patients showing complete recovery.

Conclusion: We recommend measuring antimicrosomal antibodies in all children with unexplained seizures, hallucinations or confusion and, if positive, initiating treatment with prednisolone.
Digital phonocardiography as a screening tool for heart disease in childhood
Authors: Germanakis Ioannis , Dittrich Sven , Perakaki Rousa , Kalmanti Maria
Published: February 2008

Aim: To evaluate the performance of experienced cardiologists by use of digital phonocardiography for the correct identification of heart disease and innocent murmurs in children.

Methods: Two independent paediatric cardiologists blindly evaluated 83 digital phonocardiograms obtained from consecutive paediatric cardiology outpatients. Each observer had to document the presence and characteristics of murmurs (intensity, quality, location), the presence of additional abnormal auscultatory findings (systolic click, second heart tone abnormalities) and whether he would recommend echocardiography (ECHO). The accuracy of their diagnoses was tested against the ECG diagnosis within two severity levels of heart disease.

Results: Twenty‐three out of 24 cases (95.8%) with moderate‐to‐severe heart defects and 12 to 13 out of 19 cases (63.2%–68.4%) with trivial‐to‐mild heart defects were correctly identified by phonocardiography. Additionally, 37 to 38 out of 40 cases (92.5%–95.0%) without ECHO evidence of heart disease were correctly interpreted as having innocent murmurs. The level of agreement between the two observers was substantial regarding their recommendations for ECHO (kappa, κ= 0.83) and in identifying abnormal murmurs (κ= 0.78).

Conclusion: Evaluation of digital phonocardiography by experienced cardiologists could allow for correct identification of moderate‐to‐severe forms of heart disease while preventing the majority of children with innocent murmurs from unnecessary referral.
Correlation between MRI evidence of degenerative condylar surface changes, induction of articular disc displacement and pathological joint sounds in the temporomandibular joint
Authors: Honda Kosuke , Natsumi Yoshiko , Urade Masahiro
Published: February 2008

Objectives:  The relationship of bony changes in the condylar surfaces in articular disc displacement without reduction in temporomandibular joint (TMJ) was investigated using diagnostic imaging. The study also evaluated whether the bony changes in the condylar surfaces limit disc and condyle motion, and produce pathological joint sounds.

Materials and methods:  Thirty‐seven joints in 28 patients diagnosed with degenerative bony changes in the condylar surfaces radiographically and anterior disc displacement without reduction using magnetic resonance imaging (MRI) were studied. The bony changes were assessed by radiographic examination and classified into two types: pathological bone changes (PBCs) including erosion, osteophyte formation and deformity, and adaptive bone changes (ABCs) including flattening and concavity. MRI was performed on the TMJ to examine the configuration and position of the discs. Joint sounds in the TMJ were determined using electrovibratograghy with a joint vibration analysis.

Results:  The articular disc motion to the condyle in the PBC group was smaller than in the ABC group irrespective of the configuration of the disc, even though there were no significant differences between the two types of bony changes in the disc position during jaw closing. The joint vibration analysis of the TMJ showed that joint sounds with a higher frequency were observed in the PBC group than in the ABC group. High energy levels needed to produce the higher frequencies (over 300 Hz) were observed only in the PBC group.
Changes of Leaf Morphological, Anatomical Structure and Carbon Isotope Ratio with the Height of the Wangtian Tree (Parashorea chinensis) in Xishuangbanna, China
Authors: He Chun‐Xia , Li Ji‐Yue , Zhou Ping , Guo Ming , Zheng Quan‐Shui
Published: February 2008

Leaf morphological and anatomical structure and carbon isotope ratio (δ13C) change with increasing tree height. To determine how tree height affects leaf characteristics, we measured the leaf area, specific leaf mass (ratio of leaf mass to leaf area [LMA]), thickness of the total leaf, cuticle, epidermis, palisade and sponge mesophyll, stomata traits and δ13C at different heights of Parashorea chinensis with methods of light and scanning electron microscopy (SEM) and isotope‐ratio mass spectrometry. The correlation and stepwise regression between tree height and leaf structure traits were carried out with SPSS software. The results showed that leaf structures and δ13C differed significantly along the tree height gradient. The leaf area, thickness of sponge mesophyll and size of stomata decreased with increasing height, whereas the thickness of lamina, palisade mesophyll, epidermis, and cuticle, ratios of palisade to spongy thickness, density of stomata and vascular bundles, LMA and δ13C increased with tree height. Tree height showed a significant relationship with all leaf indices and the most significant relationship was with epidermis thickness, leaf area, cuticle thickness, δ13C. The δ13C value showed a significantly positive relationship with LMA (R = 0.934). Our results supported the hypothesis that the leaf structures exhibited more xeromorphic characteristics with the increasing gradient of tree height.
RAPID DETECTION OF FRANCISELLA TULARENSIS BY THE IMMUNOAFFINITY ASSAY ABICAP IN ENVIRONMENTAL AND HUMAN SAMPLES
Authors: GRUNOW ROLAND , MIETHE PETER , CONLAN WAYNE , FINKE ERNST‐JÜRGEN , FRIEDEWALD STEFFEN , PORSCH‐ÖZCÜRÜMEZ MUSTAFA
Published: February 2008

Francisella tularensis is the causative agent of tularemia, a severe zoonotic infectious disease. The natural reservoir of the bacteria is not yet known precisely, but it may persist for over a year in water or mud. It is naturally maintained and spread by various terrestrial and aquatic mammals, and outbreaks in humans are often paralleled by enzootics or epizootics.

The reasons for this seem to be multifactorial, though not well understood. Therefore, for epidemiological and outbreak investigations, a rapid hand‐held assay would be helpful.

Here we described a column‐based immunofiltration assay called ABICAP, which has several characteristics that permit its application under field conditions. The assay can be performed within 25 min, with a detection limit of 103 bacteria. Further validation of the assay included the analytical range, precision, detection limit and performance for different human, animal and environmental sample matrices, accuracy, recovery, reproducibility and stability.

PRACTICAL APPLICATIONS

The assay is an interesting tool applicable for the rapid detection of F. tularensis in various specimens under laboratory and field conditions. It can be used for the identification of reservoirs of F. tularensis in epidemiological studies, for the detection of sources of infection in outbreak situations of tularemia and in laboratory investigation of animal and human specimens. The methodological platform can be adapted to the detection of other microbiological agents and antigens.