bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Growth Hormone Dosing in Children with Idiopathic Short Stature
Authors: Keni Jyotsna , Cohen Pinchas
Published: January 2009

Background: In the last 2 decades, recombinant human growth hormone (rhGH) therapy for children with idiopathic short stature (ISS) has demonstrated varying degrees of efficacy. Based on prediction models for this population developed from registry databases and extensive clinical experience, these differences have been attributed to age at diagnosis, dose of rhGH, parental height, treatment compliance, GH sensitivity, effectiveness of GH receptors, potency of the postreceptor signaling cascade, insulin-like growth factor I transcriptional and translational efficiency and epiphyseal responsiveness. Conclusions: Although there are no universally accepted biochemical criteria for determining when to initiate GH therapy for children with ISS, both molecular and biochemical factors may contribute to the success of therapy and play a significant role to maximize adult height.
Preserving Fertility in Prepubertal Children
Authors: Sauvat F. , Binart N. , Poirot C. , Sarnacki S.
Published: January 2009

Background: As a result of advances in treatment, almost 80% of children and adolescents who currently receive a diagnosis of cancer become long-term survivors. Potential adverse consequences of treatment include impaired puberty and fertility due to gonadal removal, genital tract injury or damage to germ cells from adjuvant therapy. In recent years, treatment of solid tumors and hematological malignancies has been modified in an attempt to minimize damage to the reproductive system. Simultaneously, advances in assisted reproductive technologies have led to new possibilities for the prevention and treatment of infertility. We review experimental data in animal models and clinical experience in adults and discuss strategies to preserve fertility in prepubertal children. Conclusions: Fertility preservation should now be considered in children facing cancer treatment that has a high risk of gonadal toxicity including high-dose chemotherapy and bilateral irradiation of the gonads at toxic doses.
Recent Challenges in the Diagnosis of Cushing’s Syndrome
Authors: Pecori Giraldi Francesca
Published: January 2009

Background: The diagnosis of Cushing’s syndrome still represents a challenge for the endocrinologist. Correct implementation and interpretation of diagnostic procedures require expertise and a high degree of clinical knowledge. The diagnosis should be established based on results of two or more concordant first-line tests (e.g., urinary free cortisol, midnight serum cortisol and low-dose dexamethasone testing); otherwise, second-line tests such as the dexamethasone-suppressed corticotrophin-releasing hormone (CRH) test, desmopressin stimulation or later reevaluation can confirm/exclude the diagnosis. Aetiological diagnosis requires measurement of plasma corticotrophin (ACTH) to distinguish between ACTH-dependent (pituitary or extrapituitary ACTH-secreting tumors) and ACTH-independent Cushing’s syndrome (adrenal cortisol-secreting lesions), and the possible detection of normal ACTH levels in patients with adrenal Cushing’s syndrome must be kept in mind. Lastly, the differential diagnosis between pituitary and ectopic ACTH secretion can be performed using CRH testing, high-dose dexamethasone suppression and inferior petrosal sinus sampling. Conclusions: The different epidemiology of the two entities and the incomplete diagnostic accuracy of diagnostic procedures mandate careful evaluation of test results.
Spontaneous Rupture of the Oesophagus: Boerhaave’s Syndrome in 2008
Authors: de Schipper J.P. , Pull ter Gunne A.F. , Oostvogel H.J.M. , van Laarhoven C.J.H.M.
Published: January 2009

Objective: Boerhaave’s syndrome is a spontaneous rupture of the oesophagus with a lack of diagnostic and treatment consistency in the literature. Therefore, we reviewed all published literature in order to design a treatment algorithm based on the literature. Study Design: A systematic literature review written in the English language since 1975. Results: We reviewed all known literature. Treatment of the Boerhaave syndrome was divided into three categories: conservative, endoscopic and surgical approach. The survival rate of all treatments was 75, 100 and 81%, respectively. Conclusion: Boerhaave’s syndrome should be treated endoscopically when diagnosed within 48 h and when there are no signs of sepsis. However, when a patient is diagnosed within 48 h and has a septic profile, thoracotomy with hemifundoplication and pleural/mediastinal drainage should be performed; and in case of intra-abdominal leakage, a laparotomy for local repair should be performed. When a patient is diagnosed after 48 h, conservative treatment should be followed and only when a patient gets a septic profile is surgical treatment indicated.
Relation between Videofluoroscopy of the Esophagus and the Quality of Esophageal Speech
Authors: Fouquet Marina Lang , Gonçalves Antônio José , Behlau Mara
Published: January 2009

The goal of the current study was to compare the quality of esophageal speech and voice to videofluoroscopic features of the esophagus and pharyngoesophageal (PE) segment. The speech and voice characteristics of 30 laryngectomized patients were rated by 5 speech-language pathologists. Based on these ratings, patients were divided into 3 categories: fluent (n = 9), moderately fluent (n = 10) and nonfluent (n = 11). Videofluoroscopy of the PE region was then performed during both swallowing and voice production. An insufflation test and percutaneous pharyngeal plexus block were required in 9 patients to determine the etiology of poor esophageal voice production. The strongest videofluoroscopic indicators of nonfluent speakers were: (1) small or absent air reservoir and (2) lack of a vibrating PE segment. Fluent speakers presented with shorter PE segments (1.17 mm) compared to moderately fluent speakers (17.1–29.9 mm). Perceptually, fluent speakers presented with a predominantly rough vocal quality. In contrast, moderately fluent speakers presented with a tense quality. In addition, stoma blast noise was reduced in fluent speakers. Videofluoroscopic findings highly correlated with the quality of esophageal speech.
Effects of Histamine H3 Receptor Activation on the Behavioral-Stimulant Effects of Methamphetamine and Cocaine in Mice and Squirrel Monkeys
Authors: Banks Matthew L. , Manvich Daniel F. , Bauzo Rayna M. , Howell Leonard L.
Published: January 2009

Background: Cocaine and methamphetamine (METH) are two commonly abused drugs that have behavioral-stimulant properties. These stimulant effects are partially mediated by the dopaminergic system. Recent evidence has suggested that the histamine H3 receptor (H3R) may modulate the release of dopamine induced by METH. The aim of the present study was to examine the role of H3R in the behavioral-stimulant effects of cocaine and METH in mice and monkeys. Methods: Nonhabituated, experimentally naïve mice (n = 5–6) were pretreated with the H3R agonist imetit 30 min before METH or cocaine, and activity was measured for 90 min. The behavioral-stimulant effects of METH and cocaine were also studied in squirrel monkeys (n = 3) under a fixed-interval schedule of stimulus termination. Monkeys were pretreated with imetit 30 min before the peak behavioral-stimulant doses of METH or cocaine derived from individual subjects. Results: Pretreatment with imetit did not affect basal activity in mice. Imetit significantly attenuated the behavioral-stimulant effects of METH, but not cocaine. In monkeys, no dose of imetit tested significantly altered the behavioral-stimulant effects of METH or cocaine. Conclusion: These results suggest a role of H3R in the behavioral-stimulant effects of METH, but not cocaine, in mice and no role in monkeys.
Korean Version of the Baylor Profound Mental Status Examination: A Brief Staging Measure for Patients with Severe Alzheimer’s Disease
Authors: Na H.R. , Lee S.H. , Lee J.S. , Doody R.S. , Kim S.Y.
Published: January 2009

Background: The Baylor Profound Mental Status Examination (BPMSE) was modeled to provide a brief patient-derived rating scale for staging and tracking patients with severe stages of Alzheimer’s disease (AD). Methods: The BPMSE was administered to 91 patients with probable AD (Korean version of the MMSE less than 16) according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association criteria. The patients were also evaluated using the Korean version of the Severe Impairment Battery (SIB-Ko), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Barthel Activities of Daily Living (B-ADL), the Korean version of the Instrumental Activities of Daily Living (K-IADL), the Korean version of the Neuropsychiatric Inventory (K-NPI) and the Functional Assessment Staging (FAST). Results: There were significant correlations between the BPMSE- Ko and K-MMSE scores (r = 0.66, p < 0.001) and between the BPMSE-Ko and SIB-Ko scores (r = 0.83, p < 0.001). The BPMSE-Ko correlated with the CDR, GDS, B-ADL, K-IADL, K-NPI and FAST scores (p < 0.001). The BPMSE-Ko scores continued to decline even after the K-MMSE reached values near 0. Conclusions: The BPMSE-Ko is a time efficient and useful tool to measure cognitive function in patients with severe AD.
Blockage of the Renin-Angiotensin System Attenuates Mortality but Not Vascular Calcification in Uremic Rats: Sevelamer Carbonate Prevents Vascular Calcification
Authors: Tokumoto Masanori , Mizobuchi Masahide , Finch Jane L. , Nakamura Hironori , Martin Daniel R. , Slatopolsky Eduardo
Published: January 2009

Background/Aims: Hyperphosphatemia is associated with vascular calcification and increased cardiovascular morbidity and mortality. Angiotensin-converting enzyme inhibitors are beneficial in suppressing the progression of kidney and cardiovascular disease. The present studies explore the influence of enalapril and sevelamer carbonate on renal function, vascular calcification and mortality in long-term experimental uremia. Methods: Normal and 5/6 nephrectomized rats were fed a high-phosphorus diet for 4 months and treated with enalapril or the combination of both enalapril and sevelamer carbonate. Results: The rats treated with enalapril alone or both enalapril and sevelamer had less deterioration in renal function compared to uremic control as seen by lower serum creatinine (1.6, 1.6 vs. 2.1 mg/dl, respectively, p < 0.05) and higher creatinine clearance. They also exhibited attenuated mortality (23.5, 12.5 vs. 75%, respectively, p < 0.01) and inhibition of myocardial hypertrophy. Enalapril alone did not suppress secondary hyperparathyroidism or vascular calcification. Combination therapy with both enalapril and sevelamer carbonate ameliorated secondary hyperparathyroidism and vascular calcification (calcium content: 854 ± 40 vs. 1,735 ± 479 μg/g wet tissue) compared to uremic controls. Conclusion: In these experiments, animal mortality and myocardial hypertrophy were significantly reduced by both enalapril alone and enalapril in combination with sevelamer. In addition, sevelamer carbonate induced beneficial effects on renal dysfunction, secondary hyperparathyroidism and vascular calcification.
Ganglionic Eminence Revisited: A Review Embracing Observations from Our Laboratory
Authors: Wai Maria S.M. , Zhang Lihong , Yew D.T.
Published: January 2009

This paper reviewed the progression of the ganglionic eminence in the developing human brain. After 20 weeks of gestation, strips of cells emerged from this progenitor mass towards the corpus striatum. Some went the opposite direction to the thalamus by 25 gestational weeks. The progenitor cells in the ganglionic eminence also gathered into clusters by this time. By late gestation (31/32 gestational weeks), no accumulation of heavy-stained progenitor cells was observed anymore and the subventricular zone had normal morphology as those at birth. This was compared with recent works on the rodents dealing with the origin and destination of progenitor cells in the ganglionic eminence.
Sterol Regulatory Element-Binding Proteins, Liver X Receptor, ABCA1 Transporter, CD36, Scavenger Receptors A1 and B1 in Nephrotic Kidney
Authors: Kim Hyun Ju , Vaziri Nosratola D.
Published: January 2009

Background: Accumulation of lipid in the kidney has been shown to promote renal disease. Heavy glomerular proteinuria (nephrotic syndrome) is associated with hyperlipidemia, lipiduria, and progressive kidney disease. Glomerular and tubular epithelial cells in the nephrotic kidney are exposed to large quantities of lipids bound to the filtered proteins whose uptake can raise cellular lipids. Cellular lipid homeostasis is regulated by the influx, synthesis and efflux of lipids. Methods: We studied the expression of factors involved in lipid metabolism in the kidneys of nephrotic and control rats. Results: The nephrotic rats showed heavy proteinuria, hypercholesterolemia, increased kidney tissue cholesterol, marked activation (nuclear translocation) of SREBP-2 (master regulator of cholesterol synthesis), significant upregulations of CD36 and SRA-1 (key receptors for uptake of fatty acids and oxidized LDL) and ACAT1 (enzyme catalyzing intracellular esterification, hence trapping of cholesterol), but no significant change in either ABCA1 (mediator of cholesterol/phospholipid efflux) or its regulator, liver X receptor. Conclusions: Proteinuria results in accumulation of cholesterol in the kidney. This is associated with upregulation of SRA-1, CD36 and ACAT1 and activation of SREBP-2 which can collectively raise tissue cholesterol and promote renal injury by facilitating the influx, synthesis and retention of cholesterol in the nephrotic kidney.
N-Methyl-D-Aspartate Receptors Mediate Excitotoxicity in Amyloid Beta-Induced Synaptic Pathology of Alzheimer’s Disease
Authors: Liu Jinping , Gao Xiulai , Wu Yan
Published: January 2009

Mounting evidence suggests that cognitive impairment begins with subtle alterations of synaptic efficacy prior to frank neuronal degeneration, and synaptic dysfunction may be induced by diffusible oligomeric assemblies of amyloid beta peptide (Aβ). The mechanisms underlying Aβ neurotoxicity are complex but might involve N-methyl-D-aspartate receptor (NMDAR). This review focuses on the action of NMDAR and its subunits in Aβ-induced synaptic dysfunction. The localized apoptotic mechanism that contributes to synaptic dysfunction in Alzheimer’s disease will also be discussed.
Assessment of Changes in Distribution of Lung Perfusion by Electrical Impedance Tomography
Authors: Frerichs Inéz , Pulletz Sven , Elke Gunnar , Reifferscheid Florian , Schädler Dirk , Scholz Jens , Weiler Norbert
Published: January 2009

Background: Electrical impedance tomography (EIT) is able to detect variations in regional lung electrical impedance associated with changes in both air and blood content and potentially capable of assessing regional ventilation-perfusion relationships. However, regional lung perfusion is difficult to determine because the impedance changes synchronous with the heart rate are of very small amplitude. Objectives: The aim of our study was to determine the redistribution of lung perfusion elicited by one-lung ventilation using EIT with a novel region-of-interest analysis. Methods: Ten patients (65 ± 9 years, mean age ± SD) scheduled for elective chest surgery were studied after intubation with a double-lumen endotracheal tube during bilateral and unilateral ventilation of the right and left lungs. EIT data were acquired at a rate of 25 scans/s. Relative impedance changes synchronous with the heart rate were evaluated in the right and left lung regions. Results: During bilateral ventilation, the mean right-to-left lung ratio of the sum of heart rate-related impedance changes was 1.12 ± 0.20, but the ratio significantly changed (0.81 ± 0.16 and 1.48 ± 0.37) during unilateral left- and right-lung ventilation with reduced perfusion of the non-ventilated lung. Increased perfusion most likely occurred in the ventilated lung because the impedance values summed over both regions did not change (0.62 ± 0.23 vs. 0.58 ± 0.22) compared with bilateral ventilation. Conclusions: Our results indicate that redistribution of regional lung perfusion can be assessed by EIT during one-lung ventilation. The performance of EIT in detecting changes in lung perfusion in even smaller lung regions remains to be established.
Diagnostic Accuracy and Impact of Computed Tomographic Coronary Angiography on Utilization of Invasive Coronary Angiography
Authors: Chow Benjamin J.W. , Abraham Arun , Wells George A. , Chen Li , Ruddy Terrence D. , Yam Yeung , Govas Nayia , Galbraith Phoebe Diane , Dennie Carole , Beanlands Rob S.
Published: January 2009

Background—

Computed tomographic coronary angiography (CTA), given its high negative predictive value, is a potential gatekeeper for invasive coronary angiography (ICA). Before CTA can be further accepted into clinical practice, its impact on healthcare resources needs to be better understood. We sought to determine the clinical impact of CTA on ICA referrals, CTA accuracy, and normalcy rate.

Methods and Results—

To determine the impact of CTA, consecutive patients (n=7017) undergoing ICA before and after implementing a dedicated cardiac CT program were reviewed and compared with 3 other centers (n=11 508). To determine CTA accuracy, we evaluated consecutive CTA patients who underwent ICA. For normalcy rate, we identified patients with a low pretest probability for obstructive coronary artery disease. With the implementation of a cardiac CT program, the frequency of normal ICA decreased from 31.5% (1114 of 3538 patients) to 26.8% (932 of 3479 patients) (
P
<0.001). These findings were significantly different (
P
=0.003) from the 3 centers, in which normal ICAs were unchanged (30.0% [1870 of 6224 patients] to 31.0% [1642 of 5284 patients]). CTA had excellent per-patient sensitivity (99% [CI, 95% to 100%]), positive predictive value (92% [CI, 86% to 96%]) and negative predictive value (95% [CI, 72% to 100%]). Because of referral bias, specificity (64% [CI, 44% to 81%]) was low; however, the normalcy rate of CTA was 94% (CI, 90% to 97%). After adjusting for referral bias, the adjusted sensitivity was 90% (CI, 89% to 91%), and the adjusted specificity was 95% (CI, 94% to 96%), with positive and negative predictive values of 92% (CI, 91% to 93%) and 93% (CI, 92% to 94%), respectively.

Conclusion—

The clinical implementation of CTA appears to positively impact ICA by reducing the frequency of normal ICA. The operating characteristics of CTA support its potential role as a tool useful in ruling out obstructive coronary artery disease.
Left Atrial Function in Diastolic Heart Failure
Authors: Kurt Mustafa , Wang Jianwen , Torre-Amione Guillermo , Nagueh Sherif F.
Published: January 2009

Background—

Abnormalities in left ventricular (LV) structure and function occur in patients with diastolic heart failure (DHF). The reasons for the transition from asymptomatic dysfunction to heart failure need better definition, including noninvasive measurements that can detect the transition.

Methods and Results—

In 64 patients undergoing right heart catheterization, simultaneous echocardiographic imaging was performed. As a control group, 27 healthy subjects were included. There were 25 with ejection factor (EF) <50%, 20 in DHF, and 19 with normal EF and LV hypertrophy but not in heart failure (diastolic dysfunction). LV volumes, mass, left atrial (LA) volumes and EF, annular atrial velocity (a′), and LA strain during systole (LA
S
), and atrial contraction (LA
A
) were measured. The ratio of wedge pressure to LA
S
strain was used as an index of LA stiffness, as was the ratio of E/e′ to LA
S
strain. All 3 patient groups had increased LA volumes and depressed LA EF, a′, and LA
A
strain, with no significant difference between patients with DHF and diastolic dysfunction in LA systolic function indices, LV mass, LA volumes, LV, and arterial elastance. LA
S
strain was lower in patients with DHF, and LA stiffness (invasive and noninvasive) was higher (both
P
<0.01), related well to pulmonary artery systolic pressure (
r
=0.79,
P
<0.001), and was most accurate in identifying DHF patients from those with diastolic dysfunction (invasive area under the curve: 0.93, noninvasive: 0.85).

Conclusions—

Patients with DHF have increased LV mass and LA volume in comparison with normal controls, but not versus patients with LV hypertrophy who are not in heart failure. On the other hand, LA
S
strain is significantly reduced and LA stiffness is the most accurate index in identifying patients with DHF.
Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy
Authors: Weidemann Frank , Niemann Markus , Breunig Frank , Herrmann Sebastian , Beer Meinrad , Störk Stefan , Voelker Wolfram , Ertl Georg , Wanner Christoph , Strotmann Jörg
Published: January 2009

Background—

Enzyme replacement therapy with recombinant α-galactosidase A reduces left ventricular hypertrophy and improves regional myocardial function in patients with Fabry disease during short-term treatment. Whether enzyme replacement therapy is effective in all stages of Fabry cardiomyopathy during long-term follow-up is unknown.

Methods and Results—

We studied 32 Fabry patients over a period of 3 years regarding disease progression and clinical outcome under enzyme replacement therapy. Regional myocardial fibrosis was assessed by magnetic resonance imaging late-enhancement technique. Echocardiographic myocardial mass was calculated with the Devereux formula, and myocardial function was quantified by ultrasonic strain-rate imaging. In addition, exercise capacity was measured by bicycle stress test. All measurements were repeated at yearly intervals. At baseline, 9 patients demonstrated at least 2 fibrotic left ventricular segments (severe myocardial fibrosis), 11 had 1 left ventricular segment affected (mild fibrosis), and 12 were without fibrosis. In patients without fibrosis, enzyme replacement therapy resulted in a significant reduction in left ventricular mass (238±42 g at baseline, 202±46 g at 3 years;
P
for trend <0.001), an improvement in myocardial function (systolic radial strain rate, 2.3±0.4 and 2.9±0.6 seconds
−1
, respectively;
P
for trend=0.045), and a higher exercise capacity obtained by bicycle stress exercise (106±14 and 122±26 W, respectively;
P
for trend=0.014). In contrast, patients with mild or severe fibrosis showed a minor reduction in left ventricular hypertrophy and no improvement in myocardial function or exercise capacity.

Conclusions—

These data suggest that treatment of Fabry cardiomyopathy with recombinant α-galactosidase A should best be started before myocardial fibrosis has developed to achieve long-term improvement in myocardial morphology and function and exercise capacity.
Discordant Secular Trends in Elevated Blood Pressure and Obesity in Children and Adolescents in a Rapidly Developing Country
Authors: Chiolero Arnaud , Paradis Gilles , Madeleine Georges , Hanley James A. , Paccaud Fred , Bovet Pascal
Published: January 2009

Background—

The effect of the increasing prevalence of obesity on blood pressure (BP) secular trends is unclear. We analyzed BP and body mass index secular trends between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly developing island state in the African region.

Methods and Results—

School-based surveys were conducted annually between 1998 and 2006 among all students in 4 school grades (kindergarten and 4th, 7th, and 10th years of compulsory school). We used the Centers for Disease Control and Prevention criteria to define obesity and elevated BP. The same methods and instruments were used in all surveys. Some 25 586 children and adolescents 4 to 18 years of age contributed 43 867 observations. Although the prevalence of obesity in boys and girls increased from 5.1% and 6.0%, respectively, in 1998 to 2000 to 8.0% and 8.7% in 2004 to 2006, the prevalence of elevated BP decreased from 8.4% and 9.8% to 6.9% and 7.8%. During the interval, mean age-adjusted body mass index increased by 0.57 kg/m
2
in boys and 0.58 kg/m
2
in girls. Mean age- and height-adjusted systolic BP decreased by −3.0 mm Hg in boys and −2.8 mm Hg in girls, whereas mean diastolic BP did not change substantially in boys (−0.2 mm Hg) and increased slightly in girls (0.4 mm Hg).

Conclusion—

At a population level, the marked increase in the prevalence of obesity in children and adolescents in the Seychelles was not associated with a commensurate secular rise in mean BP.
Altered Bone Morphogenetic Protein and Transforming Growth Factor-β Signaling in Rat Models of Pulmonary Hypertension
Authors: Long Lu , Crosby Alexi , Yang Xudong , Southwood Mark , Upton Paul D. , Kim Dae-Kee , Morrell Nicholas W.
Published: January 2009

Background—

Recent genetic studies have highlighted the role of the bone morphogenetic protein (BMP)/transforming growth factor (TGF)-β signaling pathways in the pathogenesis of familial pulmonary arterial hypertension (PAH). It remains unclear whether alterations in these pathways contribute to other forms of pulmonary hypertension and to what extent these changes can be exploited for therapeutic intervention.

Methods and Results—

We studied BMP/TGF-β signaling in 2 rat models of PAH due to chronic hypoxia and monocrotaline. In both models, there was a significant reduction in lung BMP type IA receptor and BMP type II receptor mRNA expression, although these changes were more pronounced in the monocrotaline model. This was accompanied by a reduction in lung levels of phospho-Smad1/5 and Id (inhibitor of DNA binding) gene expression in the monocrotaline model. In contrast, we observed increased TGF-β activity, again more marked in the monocrotaline model, as evidenced by increased phospho-Smad2/3 and increased expression of TGF-β–regulated genes. Immunohistochemistry revealed increased TGF-β
1
expression in pulmonary artery smooth muscle cells and macrophages surrounding remodeled pulmonary arteries in monocrotaline rats. Inhibition of activin receptor-like kinase-5 signaling in vivo with the selective small-molecule inhibitor IN-1233 prevented PAH, right ventricular hypertrophy, and vascular remodeling after monocrotaline injection and inhibited the progression of established PAH in this model. No significant effect was observed in hypoxic PAH. In vitro studies confirmed that TGF-β stimulated migration of distal rat pulmonary artery smooth muscle cells and that this effect was inhibited by IN-1233.

Conclusions—

Disruption of BMP/TGF-β signaling is more pronounced in the monocrotaline model of PAH than in the chronic hypoxia model. Increased TGF-β activity is associated with greater macrophage recruitment with monocrotaline treatment. Inhibition of TGF-β signaling via activin receptor-like kinase-5 prevents development and progression of PAH in the monocrotaline model and may involve inhibition of pulmonary artery smooth muscle cell migration.
Deficiency of the NR4A Neuron-Derived Orphan Receptor-1 Attenuates Neointima Formation After Vascular Injury
Authors: Nomiyama Takashi , Zhao Yue , Gizard Florence , Findeisen Hannes M. , Heywood Elizabeth B. , Jones Karrie L. , Conneely Orla M. , Bruemmer Dennis
Published: January 2009

Background—

The neuron-derived orphan receptor-1 (NOR1) belongs to the evolutionary highly conserved and most ancient NR4A subfamily of the nuclear hormone receptor superfamily. Members of this subfamily function as early-response genes regulating key cellular processes, including proliferation, differentiation, and survival. Although NOR1 has previously been demonstrated to be required for smooth muscle cell proliferation in vitro, the role of this nuclear receptor for the proliferative response underlying neointima formation and target genes
trans
-activated by NOR1 remain to be defined.

Methods and Results—

Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in NOR1
−/−
mice compared with wild-type mice. In vitro, NOR1-deficient smooth muscle cells exhibit decreased proliferation as a result of a G
1
→S phase arrest of the cell cycle and increased apoptosis in response to serum deprivation. NOR1 deficiency alters phosphorylation of the retinoblastoma protein by preventing mitogen-induced cyclin D1 and D2 expression. Conversely, overexpression of NOR1 induces cyclin D1 expression and the transcriptional activity of the cyclin D1 promoter in transient reporter assays. Gel shift and chromatin immunoprecipitation assays identified a putative response element for NR4A receptors in the cyclin D1 promoter, to which NOR1 is recruited in response to mitogenic stimulation. Finally, we provide evidence that these observations are applicable in vivo by demonstrating decreased cyclin D1 expression during neointima formation in NOR1-deficient mice.

Conclusions—

These experiments characterize cyclin D1 as an NOR1-regulated target gene in smooth muscle cells and demonstrate that NOR1 deficiency decreases neointima formation in response to vascular injury.
Effect of the Direct Renin Inhibitor Aliskiren, the Angiotensin Receptor Blocker Losartan, or Both on Left Ventricular Mass in Patients With Hypertension and Left Ventricular Hypertrophy
Authors: Solomon Scott D. , Appelbaum Evan , Manning Warren J. , Verma Anil , Berglund Tommy , Lukashevich Valentina , Cherif Papst Cheraz , Smith Beverly A. , Dahlöf Björn
Published: January 2009

Background—

Left ventricular (LV) hypertrophy, a marker of cardiac end-organ damage, is associated with an increased risk of cardiovascular morbidity and mortality. Inhibitors of the renin-angiotensin-aldosterone system may reduce LV mass to a greater extent than other antihypertensive agents. We compared the effect of aliskiren, the first orally active direct renin inhibitor, the angiotensin-receptor blocker losartan, and their combination on the reduction of LV mass in hypertensive patients.

Methods and Results—

We randomized 465 patients with hypertension, increased ventricular wall thickness, and body mass index >25 kg/m
2
to receive aliskiren 300 mg, losartan 100 mg, or their combination daily for 9 months. Patients were treated to standard blood pressure targets with add-on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone system and β-blockers. Patients underwent cardiovascular magnetic resonance imaging for assessment of LV mass at baseline and at study completion. The primary objective was to compare change in LV mass index from baseline to follow-up in the combination and losartan arms; the secondary objective was to determine whether aliskiren was noninferior to losartan in reducing LV mass index from baseline to follow-up. Systolic and diastolic blood pressures were reduced similarly in all treatment groups (6.5±14.9/3.8±10.1 mm Hg in the aliskiren group; 5.5±15.6/3.7±10.7 mm Hg in the losartan group; 6.6±16.6/4.6±10.5 mm Hg in the combination arm;
P
<0.0001 within groups,
P
=0.81 between groups). LV mass index was reduced significantly from baseline in all treatment groups (4.9-, 4.8-, and 5.8 g/m
2
reductions in the aliskiren, losartan, and combination arms, respectively;
P
<0.0001 for all treatment groups). The reduction in LV mass index in the combination group was not significantly different from that with losartan alone (
P
=0.52). Aliskiren was as effective as losartan in reducing LV mass index (
P
<0.0001 for noninferiority). Safety and tolerability were similar across all treatment groups.

Conclusions—

Aliskiren was as effective as losartan in promoting LV mass regression. Reduction in LV mass with the combination of aliskiren plus losartan was not significantly different from that with losartan monotherapy, independent of blood pressure lowering. These findings suggest that aliskiren was as effective as an angiotensin receptor blocker in attenuating this measure of myocardial end-organ damage in hypertensive patients with LV hypertrophy.
Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP)
Authors: Agarwal Rajiv , Alborzi Pooneh , Satyan Sangeetha , Light Robert P.
Published: January 2009

Volume excess is thought to be important in the pathogenesis of hypertension among hemodialysis patients. To determine whether additional volume reduction will result in improvement in blood pressure (BP) among hypertensive patients on hemodialysis and to evaluate the time course of this response, we randomly assigned long-term hypertensive hemodialysis patients to ultrafiltration or control groups. The additional ultrafiltration group (n=100) had the dry weight probed without increasing time or duration of dialysis, whereas the control group (n=50) only had physician visits. The primary outcome was change in systolic interdialytic ambulatory BP. Postdialysis weight was reduced by 0.9 kg at 4 weeks and resulted in −6.9 mm Hg (95% CI: −12.4 to −1.3 mm Hg;
P
=0.016) change in systolic BP and −3.1 mm Hg (95% CI: −6.2 to −0.02 mm Hg;
P
=0.048) change in diastolic BP. At 8 weeks, dry weight was reduced 1 kg, systolic BP changed −6.6 mm Hg (95% CI: −12.2 to −1.0 mm Hg;
P
=0.021), and diastolic BP changed −3.3 mm Hg (95% CI: −6.4 to −0.2 mm Hg;
P
=0.037) from baseline. The Mantel-Hanzel combined odds ratio for systolic BP reduction of ≥10 mm Hg was 2.24 (95% CI: 1.32 to 3.81;
P
=0.003). There was no deterioration seen in any domain of the kidney disease quality of life health survey despite an increase in intradialytic signs and symptoms of hypotension. The reduction of dry weight is a simple, efficacious, and well-tolerated maneuver to improve BP control in hypertensive hemodialysis patients. Long-term control of BP will depend on continued assessment and maintenance of dry weight.
Cyclic Agree
Authors: Béjar Susana , Rezac Milan
Published: January 2009

We propose that agreement displacement phenomena sensitive to person hierarchies arise from the mechanism of Agree operating on articulated φ-feature structures in a cyclic syntax. Cyclicity and locality derive a preference for agreement control by the internal argument. Articulation of the probe determines (a) when the agreement controller cyclically displaces to the external argument and (b) differences in crosslinguistic sensitivity to person hierarchies. The system characterizes two classes of derivations corresponding empirically to direct and inverse contexts, and predicts the existence and nature of repair strategies in the latter. The properties of agreement displacement thus reduce to properties of syntactic dependency formation by Agree.
On Certain Properties of Pied-Piping
Authors: Heck Fabian
Published: January 2009

In this article, I argue that an approach to pied-piping in terms of wh-feature percolation is problematic under minimalist assumptions. I propose an alternative theory based on Agree, arguing that wh-movement and restrictions on pied-piping follow from the interaction of the theory of phases and a violable constraint that forces wh-feature checking under Agree to be as local as possible. I present and derive three observations about pied-piping that are attested in different languages.
The Eschatological Arena: Reinscribing Roman Violence in Fantasies of the End Times
Authors: Stratton Kimberly
Published: January 2009

Eschatological fantasies of divine judgment and retribution constitute a common feature of sacred literature and often serve to legitimate violence, both physical and rhetorical, against others. This paper examines allusions to Roman spectacles of violence—which operated part and parcel of imperialist strategies to dominate and intimidate subject populations—in descriptions of final judgment. It argues that these references constitute forms of colonial mimicry, which ambivalently appropriate Roman symbols of power for their own self fashioning. This process, however, is not uniform, but serves different purposes and strategies in different texts and contexts. This article explores examples of such mimicry and asks what it means for visions of the final judgment to reinscribe the very methods of domination that these fantasies seek to displace. Additionally, it considers the role of voyeurism implicit in public disciplinary displays and the implications that imagining eschatological justice as a blood spectacle has for theological conceptions of divine surveillance and control.
The Language of War (2 Cor. 10:1-6) and the Language of Weakness (2 Cor. 11:21b-13:10)
Authors: Roetzel Calvin
Published: January 2009

This essay seeks to engage the broader discussion of religious violence by focusing on the language of war of the Apostle Paul in 2 Cor. 10:1-6. By viewing this paragraph of martial rhetoric and its afterlife through the lens provided by two theoretical models, the disciplinary and emancipatory, this essay wonders if Paul's own second thoughts and apologies for his hurtful speech and fumbling attempts to find an alternative led him to offer an alternative. The paper suggests that the mockery of his opponents of his bodily presence as weak, in other words, womanish, once adopted by Paul, provided the inspiration for the fool's speech and a new model of manhood, in other words, power, in weakness that offered a directed reading of the scars on his back as the primary rebuttal of attacks on his apostolic legitimacy and that of his gospel. The threats and bullying that remain, however, show that Paul had neither repudiated threatening speech nor thought through the implications of his inspired model of the fool. That was left to others who made this model central to martyrological traditions that subverted the prevailing ideology of manhood.
Immolating Emperors: Spectacles of Imperial Suffering and the Making of a Jewish Minority Culture in Late Antiquity
Authors: Boustan Ra'anan
Published: January 2009

This paper traces the historical development of the discourse of violent retribution in Jewish culture over the course of Late Antiquity. The paper argues that, although Jews had long engaged in anti-Roman rhetoric, Jewish anti-imperial sentiment intensified in the fifth to seventh centuries CE. This heightened level of antipathy toward the Roman state is perhaps best exemplified by a number of texts that present tableaux of graphic violence directed against the figure of the Roman emperor. The paper shows that these fantasies of revenge redeployed and inverted specific elements of Roman imperial ideology and practice, while at the same time internalizing the pervasive stereotype of Jews in sixth- and especially seventh-century Christian sources as violent troublemakers. The paper argues that, in attempting to assert some measure of control over the "symbolic weapons" of religious violence at play in their society, the Jewish creators of this vivid discourse of retributive justice colluded with their Christian counterparts in constructing the Jew as a member of an oppositional and even dangerous religious minority.
Martyrdom, Jesus' Passion and Barbarism
Authors: van Henten Jan Willem
Published: January 2009

Martyrdom passages highlight complicated webs of power relationships to which both martyrs and oppressors contribute. This article focuses upon one aspect of the nexus of martyrdom and power that is important for the analysis of torture: the failure of communication between martyr and oppressor. It applies the concept of barbarism to ancient and contemporary presentations of martyrdom (2 Maccabees 7 and the movie Paradise Now) as well as the New Testament passion narratives. Barbarism holds within itself a double tension: it carries a persistent dichotomist logic and sustains existing power-relations; at the same time barbarism also disrupts power-relations, as it also implies acts of misunderstanding, confusion, stuttering, and thereby registers and produces processes of "discursive slippage, the repetitions and doublings, that the articulation of binaries can never completely close up" (Neilson 1999). The article focuses on the prominent feature of dialogues in martyrdoms and passion narratives, which are non-dialogues at the same time. The oppressor fails to communicate his goals, scorns his victims and uses excessive force. The martyrs despise their oppressors, refuse to talk to them and revile them, address their opponents in a foreign language, and sometimes even announce a terrible punishment for them. Torture is an important tool for the oppressors in the power game with their victims, but the martyr's sustaining the tortures seems to reverse the power relationship between the two. Finally, the martyr figure itself may be considered barbaric, because being commemorated as a martyr legitimates the protagonist's actions and elevates him/her to a level that cannot be criticized.
The Prefixed Perfective and the Dating of Early Hebrew Poetry—A Re-Evaluation
Authors: Bloch Yigal
Published: January 2009

This article takes issue with the theory that those Biblical Hebrew poems, which show an extensive use of verbal forms belonging to the short prefix-conjugation (Northwest Semitic yaqtul) to signify complete situations in the past without the conjunction w-, were composed at an early date (c. 13th-10th centuries B.C.E.). The article takes as its starting point the fundamental discussion by David A. Robertson (1972) and argues that Robertson's neglect of the Masoretic spelling and vocalization, which often help to distinguish between the short and long prefix-conjugations in Biblical Hebrew, is unjustified. Then, it is shown that although in those biblical poems, which are commonly identified as early, short prefixed verbal forms are used to signify complete situations in the past more frequently without the conjunction w- than with it, the use of such forms with the conjunction w- (in the wayyiqtol construction) is also attested in those poems. And on the other hand, a similar pattern of use of short prefixed verbal forms to signify complete situations in the past—more frequently without the conjunction w- than with it—appears also in two poetic texts that are commonly dated to the 6th century B.C.E.: Isa. 41:1-5 and Ps. 44.
Simplicius and James of Viterbo on Propensities
Authors: Côté Antoine
Published: January 2009

The paper examines Simplicius's doctrine of propensities (epitedeioteis) in his commentary on Aristotle's Categories and follows its application by the late thirteenth century theologian and philosopher James of Viterbo to problems relating to the causes of volition, intellection and natural change. Although he uses Aristotelian terminology and means his doctrine to conflict minimally with those of Aristotle, James's doctrine of propensities really constitutes an attempt to provide a technically rigorous dressing to his Augustinian and Boethian convictions. Central to James's procedure is his rejection, following Henry of Ghent, of the principle that “everything that is moved is moved by another”. James uses Simplicius' doctrine of propensities as a means of extending the rejection of that principle, which Henry had limited to the case of the will, to cognitive operations and natural change. The result is a theory of cognition and volition that sees the soul as the principal cause of its own acts, and a theory of natural change that minimizes the causal impact of external agents.
John Wyclif and the Theory of Complexly Signifiables
Authors: Gaskin Richard
Published: January 2009

John Wyclif claims that there are relations of essential identity and formal distinctness connecting universals, complexly signifiables, and individuals. In some respects Wyclif's position on complexly signifiables coincides with what I call the advanced res theory, the view that complexly signifiables are really identical with but formally distinct from worldly individuals. But there is no question in Wyclif's treatment of a reduction of complexly signifiables to individuals. I argue that Wyclif populates his most fundamental ontological level with propositionally structured entities both individual and universal, and that this approach is superior to that of its nominalist rivals. But Wyclif shares with other versions of the advanced res theory an implausible theory of identity, and this affects the coherence of the claimed real identity between individuals and complexly signifiables.
Symptom burden and quality of life in end-stage renal disease: a study of 179 patients on dialysis and palliative care
Authors: Yong DSP , Kwok AOL , Wong DML , Suen MHP , Chen WT , Tse DMW
Published: January 2009

Palliative care for end-stage renal disease (ESRD) is developing in Hong Kong. This is the first local study to explore the symptom burden and quality of life (QOL) of ESRD patients on chronic dialysis and palliative care. This was a prospective cross-sectional study conducted on ESRD patients in a hospital in Hong Kong from January 2006 to April 2007. Data collected included demographics, socioeconomic status, modified Charlson Comorbidity Index (CCI), prevalence and intensity of 23 ESRD-related symptoms as rated by numerical rating scale (0–10), Brief Pain Inventory and QOL by MOS SF-36. A total of 179 ESRD patients completed the study; 45 patients (25.1%) were in the palliative care group and 134 patients (74.9%) in the dialysis group. The palliative care group were older (73.1 ± 7.1 vs 58.2 ± 11.4 years, P < 0.001), had marginally higher modified CCI (8.5 ± 1.9 vs 6.1 ± 2.4, P = 0.05), had more diabetics (62.2 vs 35.8%, P < 0.001) and were of poorer socioeconomic status than the dialysis group. The mean number of symptoms was 8.2 ± 3.9 and 9.3 ± 4.7 in the palliative care and the dialysis group, respectively ( P = NS). Fatigue, cold aversion, pruritus, lower torso weakness and difficulty sleeping were the five most prevalent symptoms in both groups, and were also among the most intense symptoms. QOL was significantly impaired in both groups. Scores of all QOL domains correlated negatively with the number of symptoms ( P < 0.001). Our ESRD patients under palliative care and dialysis had overlapping symptom prevalence and intensity, significant symptom burden and impaired QOL.
CAG Repeat Polymorphism of the MEF2A Gene is not Associated With the Risk of Coronary Artery Disease Among Taiwanese
Authors: Hsu Lung-An , Chang Chi-Jen , Teng Ming-Sheng , Semon Wu  , Hu Chiao-Feng , Chang Wen-YA , Ko Yu-Lin
Published: January 2009

A 21-bp deletion mutation of the exon 11 of the myocyte enhancer factor-2A (MEF2A) gene was shown to cause familial coronary artery disease. This finding raises the possibility that MEF2A variants may contribute to the risk of coronary artery disease. In total, 258 patients with coronary artery disease and 258 controls were analyzed for the MEF2A variants. The analysis revealed that all patients were negative for Pro279Leu and 21-bp deletion mutations in exons 7 and 11, respectively. The distribution of the allele frequencies of MEF2A exon 11 CAG repeat (CAG)n polymorphism was similar in both patients and controls; Further, no significant association was noted between MEF2A exon 11 (CAG)n polymorphism and the risk of myocardial infarction. Our data suggest that there is no evidence of an association between the MEF2A exon 11 (CAG)n polymorphism and the risk of coronary artery disease/myocardial infarction in the Chinese population in Taiwan.
Affect, Travel Motivation, and Travel Intention: a Senior Market
Authors: Jang SooCheong (Shawn) , Bai Billy , Hu Clark , Wu Chi-Mei Emily
Published: January 2009

The senior tourism market has received increased attention as the importance of this market segment becomes more evident. However, limited efforts have been devoted to understanding psychological aspects of senior tourists. The primary objectives of this research are to investigate seniors' affect and travel motivation as well as interrelationships between these two constructs and to discover the effects of affect and motivation on travel intentions of seniors aged 65 or greater. Using Taiwanese seniors as the study sample, the authors identify “novelty seeking” as the most important travel motivation factor from five extracted factors. It is also found that both positive and negative affective states have significant impacts on travel motivations and that only positive affect is significantly related to future travel intention. Among motivation factors, novelty-seeking not only can be stimulated by affect but also arouses travel intention. The findings of this exploratory study provide empirical support to understand psychological aspects of senior travelers.