bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Somatostatin and Dopamine 2 Receptors in Neuroendocrine Tumours and the Potential Role for New Biotherapies
Authors: Srirajaskanthan R. , Watkins J. , Marelli L. , Khan K. , Caplin M.E.
Published: March 2009

Introduction: Somatostatin and dopamine receptors are both G-protein-coupled receptors. Somatostatin receptor (SSTR) expression in neuroendocrine tumours has been well characterised, and there is evidence of dopamine receptor expression in neuroendocrine tumours. In this study, we examined expression of D2R, SSTR-2 and SSTR-5 using immunohistochemistry in patients with neuroendocrine tumours. Methods: Consecutive samples of formalin-fixed paraffin-embedded tumour tissue were available from 56 patients with a histologically confirmed diagnosis of neuroendocrine tumour (NET). The study population was divided into low-grade (n = 29), intermediate-grade (n = 18) and high-grade NET (n = 9). Immunohistochemical evaluation was performed for the expression of SSTR-2a, SSTR-5 and D2 receptors (D2R). Results: Both SSTR-2 and SSTR-5 were expressed in 100% of low-grade, 94.4% of intermediate-grade and 66.7% of high-grade NET. D2R was expressed in 93.1% of low-grade, 77.8% of intermediate-grade and 44.4% of high-grade tumours. Co-expression of all 3 receptors was present in 93.1% of low-grade tumours. There was an inverse correlation of SSTR-2 (r = –0.380, p < 0.005) and SSTR-5 (r = –0.472, p < 0.0001) with tumour grade. D2R was positively correlated with SSTR-2 (r = 0.269, p = 0.041) and SSTR-5 (r = 0.267, p = 0.045). Also, D2R expression was inversely correlated with grade of tumour (r = 0.395, p = 0.006). Octreoscan correlated with SSTR-2, SSTR-5 and D2R expression. Conclusion: D2R is expressed in the majority of low and intermediate grade tumours. It is co-expressed with SSTR-2 and SSTR-5 in the majority of cases. The advent of new chimeric molecules that bind both somatostatin and dopamine receptors may provide a new therapeutic option in the management of neuroendocrine patients.
Tratamiento nutricional de los síndromes colestáticos en la infancia
Authors: Socha Piotr
Published: March 2009

La hepatopatía colestática causa un riesgo serio de desnutrición, que incluye la desnutrición de proteína y energía y las carencias nutricionales específicas. El estado nutricional puede evaluarse basándose en mediciones antropométricas, que pueden ser equívocas a causa de la ascitis y el edema periférico. Las determinaciones bioquímicas del estado de las vitaminas liposolubles son importantes para evaluar las necesidades de los niños. Basándose en la evaluación del estado nutricional, debe planificarse la terapia nutricional con arreglo a una pauta bien establecida. El principio básico del tratamiento nutricional consiste en corregir el estado nutricional, así como reducir el riesgo de carencias nutricionales. Los niños con colestasis precisan habitualmente un suministro extra de energía que puede obtenerse incrementando la densidad energética de los alimentos o añadiendo lípidos y polímeros de glucosa. Para recuperar el crecimiento, suele tener que incrementarse la ingestión de proteínas. El aporte complementario de vitaminas liposolubles merece atención especial y no es fácil corregir un estado carencial de vitamina E. En algunos niños es necesario administrar la vitamina K por vía parenteral. Desde hace poco tiempo se utiliza con buen efecto terapéutico una vitamina E hidrosoluble (d-α-tocoferil polietilenglicol 1.000 succinato), administrada por vía oral. Dado que la hepatopatía progresa hacia una insuficiencia hepática en numerosas enfermedades colestáticas crónicas, el tratamiento nutricional puede considerarse a menudo como una medida para ‘salir del paso’ a la espera del trasplante hepático para mejorar el pronóstico. En consecuencia, el apoyo nutricional invasivo está justificado en la hepatopatía grave y comprende habitualmente la alimentación nocturna por sonda nasogástrica o incluso la nutrición parenteral.
Implantation: Physiologie, Pathologie und therapeutische Optionen bei Implantationsstörungen
Authors: von Wolff Michael , Germeyer Ariane , Strowitzki Thomas
Published: March 2009

Die Implantation ist ein bisher nicht vollständig verstandener Prozess, der zellbiologisch ein Paradoxon darstellt. Zum einen ist der Embryo zu 50% paternal und somit teilweise immunologisch fremd, und zum anderen sind das Endometrium und der Embryo mit epithelialen Zellen als Fusionsbarriere überzogen. Die endometriale Adhäsion und Invasion des Embryos beruhen auf einer exakten zeitlichen Abstimmung und einem fetomaternalen Dialog, der einzigartige immunologische Funktionen des Endometriums erfordert. Einen grossen klinischen Stellenwert hat die endometriale Funktion bei assistierten Reproduktionstechniken. Pathologien wie Myome, Hydrosalpingen, Endometriose und das polyzystische Ovarsyndrom vermögen die Implantation nachteilig zu beeinflussen. Diese Pathologien lassen sich jedoch meistens zielgerichtet und damit effektiv behandeln. Behandlungsstrategien zur Verbesserung der endometrialen Funktion bei einem idiopathischen Implantationsversagen entbehren jedoch häufig einer physiologischen Grundlage und sind in ihrer Wirksamkeit umstritten.
Gewichtsveränderung unter hormonalen Kontrazeptiva: Mythos oder Wahrheit?
Authors: Häni Daniela , Imthurn Bruno , Merki-Feld Gabriele S.
Published: March 2009

Viele Frauen befürchten einen Gewichtsanstieg bei der Anwendung von Hormonen zur Verhütung. Angst vor Gewichtszunahme kann besonders junge Frauen von einer sicheren Verhütung abhalten oder zum vorzeitigen Absetzen führen. Im folgenden Artikel geben wir eine Übersicht von Studien, welche die Gewichtsveränderung unter verschiedenen Verhütungsmethoden dokumentieren. Bei der Mehrheit der Frauen bleibt unter hormonalen Kontrazeptiva über die kurze Studiendauer (6–24 Monate) das Körpergewicht stabil (±3 kg). Unter Depo Provera® erfolgt jedoch bei einigen Frauen eine starke Gewichtszunahme: Der Teil an stark zunehmenden Frauen (>3 kg/Jahr) ist grösser als bei anderen hormonellen Methoden. Auch die Studien mit Trägerinnen eines Intrauterinpessars zeigen eine Gewichtszunahme, welche etwa das Doppelte der Zunahme der durchschnittlichen weiblichen Bevölkerung beträgt. Alle Frauen nehmen mit den Jahren an Gewicht zu (0,1 kg/m2 pro Jahr, entspricht etwa 0,3 kg/Jahr).
Placental Growth Factor: A Predictive Marker for Preeclampsia?
Authors: Schmidt Markus , Dogan Canan , Birdir Cahit , Kuhn Ulrich , Gellhaus Alexandra , Kimmig Rainer , Kasimir-Bauer Sabine
Published: March 2009

Background: An imbalance between angiogenic and antiangiogenic factors plays a fundamental role in the pathogenesis of preeclampsia. Serum levels of placental growth factor (PLGF), a factor promoting angiogenesis, in patients with preeclampsia are significantly lower than in nonpreeclamptic pregnancies. This study was designed to answer the question whether the measurement of PLGF at the beginning of the second trimester might be a predictive factor for the appearance of preeclampsia. Methods: Serum samples of 61 women were collected between 15 and 18 weeks of pregnancy. PLGF levels were measured using a human PLGF ELISA and correlated with the outcomes of pregnancy. Results: 7 women (11.47%) developed preeclampsia during pregnancy. Their PLGF levels between 15 and 18 weeks of pregnancy were significantly lower (p < 0.001) compared to the nonpreeclamptic pregnancies. Using a PLGF level of 41.84 pg/ml as a cutoff, this test has a sensitivity of 0.87 and a specificity of 0.83. Conclusion: Women who will develop preeclampsia in the course of pregnancy already have a significantly lower expression of PLGF between 15 and 18 weeks of pregnancy compared to those who will not. This test offers new possibilities in the prediction of preeclampsia.
Epididymoorchitis due to Brucella melitensis: Review of 19 Patients
Authors: Gul H. Cem , Akyol Ilker , Sen Bulent , Adayener Cuneyt , Haholu Abdullah
Published: March 2009

Introduction: We describe the clinical characteristics, treatment and long-term outcome of 19 patients with Brucella epididymoorchitis treated at the Department of Urology. Materials and Methods: Between 1998 and 2005, a total of 19 cases with epididymoorchitis due to Brucella melitensis were diagnosed at our hospital. The diagnosis of Brucella was made by isolating Brucella species from blood culture or epididymal aspiration or by standard tube agglutination testing and slide agglutination testing together with clinical findings. Results: Seven cases (36.8%) had undulant fever. Brucella species was isolated from blood cultures in 11 patients and from epididymal aspiration in 3 patients. Rose Bengal tests were positive in all patients. Total recovery was obtained in 12 cases with a 6-week treatment. Five patients (26.3%) did not respond to therapy and another 2 (10.5%) relapsed. Conclusions:Brucella orchitis should be considered in the differential diagnosis of scrotal pathologies where Brucella is endemic.
Outcome of End-to-End Urethroplasty: Single-Center Experience
Authors: Gupta N.P. , Mishra S. , Dogra P.N. , Hemal A.K. , Seth A. , Kumar R.
Published: March 2009

Objective: We review our experience of end-to-end urethroplasty for urethral strictures performed during the last 6 years. Material and Methods: From September 2001 to December 2006, 138 male patients underwent anastomotic urethroplasty at our center. Mean age was 28.1 years (range 6–71), average stricture length was 2.2 cm (range 0.7–6.0). One hundred and one patients (73.2%) had obliterative stricture while 37 (26.8%) still had some urethral passage. Ninety (65.2%) had a history of previous intervention. Sixty patients (43.5%) had associated complicating factors like urethrocutaneous fistula, rectourethral fistula, vesical calculus, blind tract and cavities, bony deformity, or urinary tract infection. Results: The mean operative time was 92 min (range 60–240). Average follow-up was 26.7 months (range 6–60). One hundred and fourteen (82.6%) had excellent outcome, 18 (13%) had acceptable outcome and 6 (4.3%) failed to respond. Seventeen patients developed complications: 5 developed wound infection, 3 epididymorchitis, 2 failed to void, 2 each had incontinence and perineal hematoma, and 1 each had erectile dysfunction, accidentally pulled his catheter out and had urethrocutaneous fistula. Conclusion: End-to-end urethroplasty is an ideal procedure for managing strictures of bulbous and posterior urethra in properly selected cases.
Repair of Distal Hypospadias and Preputioplasty in One Operation
Authors: Papouis Georgios , Kaselas Christos , Skoumis Konstantinos , Kaselas Vasilios
Published: March 2009

Purpose: To investigate the risk of simultaneous repair of distal hypospadias and preputioplasty in one operation and its relevance to the clinical, functional and cosmetic outcomes. Material and Method: The medical files of all patients treated for distal hypospadias from 1998 to 2006 that underwent simultaneous preputioplasty were reviewed. Postoperative complications, clinical, functional and cosmetic outcomes were assessed. Results: 78 patients were found to have been operated for distal hypospadias repair and prepuce reconstruction in one operation. Mean age at operation was 1.8 years. The ‘Mathieu’ technique was used for the repair of distal hypospadias in all patients. We found 3.8% urethral or meatal stricture. Fistulas appeared in 6.4% of the patients. Phimosis appeared in 3 patients (3.8%) and foreskin dehiscence presented in 2 patients (2.5%). Conclusion: Preputioplasty together with distal hypospadias repair is feasible without risking the success of the main operation and guaranties a satisfactory cosmetic appearance.
Health-Related Quality of Life in Patients with Hormone Refractory Prostate Cancer Receiving Gefitinib
Authors: Curigliano Giuseppe , Spitaleri Gianluca , De Cobelli Ottavio , Scardino Epifanio , Sbanotto Alberto , de Braud Filippo
Published: March 2009

Objectives: Improvements in quality of life (QoL) and disease-related symptoms are key goals in the treatment of hormone refractory prostate cancer (HRPC). Our aim was to evaluate the impact of gefitinib on QoL of patients with HRPC. Methods: Patients with HRPC received gefitinib 250 mg daily in addition to antiandrogen plus luteinizing hormone-releasing hormone (LHRH) analogue for at least 2 months or until disease progression. QoL was evaluated monthly by the European Organisation for Research on the Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Pain was assessed daily by patients and scored by visual analogue scale and analgesic consumption in a diary. Monthly pain intensity was estimated using the McGill-Melzack questionnaire. Results: Analysis of global health status according to EORTC QLQ-C30 showed an improvement of the status in only 6 patients (26%). The greatest benefit in the patients was in the subscale representing prostate-specific concerns (including appetite, pain, physical comfort, and genitourinary function). Improvement of symptoms was correlated with antiandrogen withdrawal. Global health status and QoL decreased during treatment according to tumor progression. Conclusions: Among HRPC patients treated with gefitinib, improvement of symptoms preceded evidence of biochemical response of prostate-specific antigen following antiandrogen withdrawal. These findings suggest no beneficial effect of gefitinib in QoL improvement.
Cerebral Embolism during Carotid Artery Stenting: Role of Carotid Plaque Echolucency
Authors: Rosenkranz Michael , Wittkugel Oliver , Waiblinger Christian , Thomalla Götz , Krützelmann Anna , Havemeister Stefanie , Zeumer Hermann , Gerloff Christian , Fiehler Jens
Published: March 2009

Background: Carotid artery stenting (CAS) is associated with the risk of intraprocedural stroke. A better understanding of specific risk factors could help to improve the procedure and to reduce the overall risk of CAS. We addressed the role of carotid plaque echolucency as potential risk factor for cerebral embolism during CAS. Methods: We prospectively evaluated carotid plaque echolucency by use of a computer-assisted measure of echogenicity, the gray scale median (GSM), in 31 consecutive patients with symptomatic high-grade carotid stenosis that were scheduled to undergo CAS. Dual-frequency transcranial Doppler ultrasound was used to detect solid cerebral microemboli during CAS. Results: 27 of the 31 patients met all inclusion/exclusion criteria.Solid cerebral microemboli were detected during 17 of 27 CAS procedures. The GSM of the target plaques was lower in subjects with intraprocedural embolism (37.9 ± 20.8) than in those without (58.2 ± 25.7) (p = 0.040). A receiver-operating characteristic analysis showed that the GSM that gave the greatest separation between plaques with a higher and a lower probability of intraprocedural embolism was 50: the proportion of subjects with intraprocedural embolism was 85% in CAS of echolucent plaques (GSM <50) and 42% in CAS of echogenic plaques (GSM ≥50) (p = 0.031). Conclusions: CAS of both echolucent and echogenic carotid plaques may be associated with cerebral embolism, particularly CAS of echolucent plaques. Plaque echolucency alone does not reliably identify patients at particularly high risk of intraprocedural embolism, but should be considered as one of a broad panel of risk factors of CAS.
Diagnostic Evaluation for Patients with Ischemic Stroke: Are There Sex Differences?
Authors: Watanabe Emi , Allen Norrina B. , Dostal Jackie , Sama Danny , Claus Elizabeth B. , Goldstein Larry B. , Lichtman Judith H.
Published: March 2009

Background and Purpose: Differences in the management of women and men with acute coronary symptoms are well documented, but relatively little is known about practices for patients with ischemic stroke. We sought to determine whether there are sex-associated differences in the utilization of diagnostic tests for ischemic stroke patients treated at academic hospitals in the United States. Methods: Medical records were abstracted for consecutive ischemic stroke patients admitted to 32 US academic medical centers from January through June, 2004, as part of the University HealthSystem Consortium Ischemic Stroke Benchmarking Project. We compared the utilization rates of diagnostic tests including neuroimaging (CT or MRI), electrocardiogram (ECG), ultrasound of the carotid arteries, and echocardiography (transthoracic or transesophageal) for women and men. Multivariate logistic regression was used to test for sex differences with adjustment for potential confounders. Results: The study included 1,256 ischemic stroke patients (611 women; 645 men; mean age 66.6 ± 14.6 years; 56% white). There were no differences between women and men in the use of neuroimaging (odds ratio, OR = 1.37; 95% confidence interval, CI = 0.58–3.24), ECG (OR = 1.00, 95% CI = 0.70–1.44), carotid artery ultrasound (OR = 0.93, 95% CI = 0.72–1.21) or echocardiography (OR = 0.70, 95% CI = 0.70–1.22). The results were similar after covariate adjustment. Conclusions: Women and men admitted to US academic hospitals receive comparable diagnostic evaluations, even after adjusting for sociodemographic and clinical factors.
Structural and Functional Causes of Hypernasality in Velocardiofacial Syndrome
Authors: Baylis Adriane L. , Watson Peter J. , Moller Karlind T.
Published: March 2009

Objective: Hypernasality in velocardiofacial syndrome (VCFS) is more severe, persistent, and difficult to manage compared to other populations with cleft palate or velopharyngeal (VP) dysfunction. This pilot study investigated why children with VCFS have more severe hypernasality. Methods: Pressure-flow methodology indirectly measured VP orifice size and VP closure timing during speech in a group of 5 children with VCFS, 5 children with cleft palate, and 6 normal children. Results: Children with VCFS demonstrated significant differences in VP closure timing and hypernasality. There were no significant group differences in VP orifice size. Duration of nasal airflow was the strongest predictor of judgments of hypernasality. Conclusion: This study provides preliminary evidence that VP closure timing may account for the more severe hypernasality in children with VCFS, compared to structural factors alone.
Comparison of Goldmann Applanation Tonometry and Dynamic Contour Tonometry in the Measurement of Intraocular Pressure in Eyes with Different Corneal Thicknesses
Authors: Roszkowska A.M. , De Grazia L. , Cirone M. , Ferreri G.
Published: March 2009

Purpose: To compare Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) in the evaluation of intraocular pressure (IOP) in eyes with different corneal thicknesses. Methods: GAT and DCT were performed in 70 eyes of 35 subjects aged between 21 and 59 years. Thirty eyes had normal, nonoperated corneas and 40 eyes had reduced central corneal thickness (CCT) following myopic photorefractive keratectomy. The GAT and DCT values were correlated to CCT and age and the agreement between both tonometers was determined by the Bland and Altman method. Results: GAT correlated strongly with CCT (p = 0.0002), but there was no correlation between DCT and CCT (p = 0.4388). No correlation was found between IOP values obtained with both devices and age. The Bland and Altman plot evidenced a lack of agreement between both tonometers with 95% limits of agreement between 1.6 and –5.6 mm Hg. Conclusions: GAT gives significantly lower values in the eyes with thin corneas and DCT is not influenced by CCT. DCT could be recommended to evaluate IOP in eyes with out-of-range corneal thickness.
Muscarinic Receptor Subtypes in the Lower Urinary Tract
Authors: Giglio Daniel , Tobin Gunnar
Published: March 2009

Acetylcholine acting on muscarinic M3 receptors on the detrusor muscle is the principal stimulus for inducing the contractile response for urinary bladder voiding. The urinary bladder expresses, however, all cloned muscarinic receptor subtypes (M1–M5). In terms of quantity, the M2 subtype dominates over the M3 subtype in the detrusor, and its role in contraction seems to be primarily indirect, by blocking stimuli from cAMP-coupled receptors that induce relaxation. The excitatory M1 and inhibitory M2 and/or M4 subtypes are also expressed prejunctionally. Muscarinic M1 and M2/M4 autoreceptors facilitate and inhibit, respectively, the release of acetylcholine. The urothelium had been considered to be a passive barrier; however, during the last decade, it has been shown that the urothelium is of importance for bladder function. In a state of bladder pathology, muscarinic receptor changes occur in the detrusor, prejunctionally, and in the urothelium, but the character of the change differs between disorders. The urothelium expresses all subtypes of muscarinic receptors, and upon stimulation it releases factors affecting bladder afferents and smooth muscle. During inflammation, the expression of muscarinic M5 receptors is increased, particularly in the urothelium, together with a cholinergic-induced production of nitric oxide in the mucosa. The present review describes signalling mechanisms, expression and functional effects of muscarinic receptors in the lower urinary tract. Their roles in physiological and pathophysiological conditions, as well as clinical implications of the occurrence of different muscarinic receptors, are discussed.
Scanning Laser Polarimetry with Variable Corneal Compensation to Detect Preperimetric Glaucoma Using Logistic Regression Analysis
Authors: Sánchez-Cano Ana , Baraibar Begoña , Pablo Luis E. , Honrubia Francisco
Published: March 2009

Background/Aims: To define if a new function improves the capability of the scanning laser polarimetry with variable corneal compensation (GDx-VCC) nerve fiber analyzer in detecting preperimetric glaucoma using 12 retinal nerve fiber layer (RNFL) peripapillary sectors. Methods: Data were obtained in a cross-sectional, hospital-clinic-based study in which 478 eyes from 478 glaucoma suspects were enrolled. All of them underwent ophthalmological examination, static automated perimetry (Humphrey 24-2 Swedish interactive threshold algorithm), optic nerve stereoscopic photography, red-free digital RNFL photography and GDx-VCC examination. The overall intake included 391 normal eyes and 60 preperimetric glaucoma eyes with defects in the fiber layer photographs. Results: The mean values of inferior average, temporal-superior-nasal-inferior temporal average, superior average and the number (nerve fiber indicator) were significantly lower in the eyes with RNFL defects than in the control group, when compared with the obtained linear discriminating function. The area under the curve values for receiver-operating characteristics analysis of the new parameter were 5% better than the best GDx-VCC standard values. Conclusions: Our results confirm that the new function has a better diagnostic reliability in preperimetric glaucoma and confirms the usefulness of morphological diagnosis between normal and early damaged RNFLs.
Validation of a Fully Automatic Method for the Routine Selection of the Anterior and Posterior Commissures in Magnetic Resonance Images
Authors: Pallavaram Srivatsan , Dawant Benoit M. , Koyama Tatsuki , Yu Hong , Neimat Joseph , Konrad Peter E. , D’Haese Pierre-François
Published: March 2009

The anterior and posterior commissures (AC and PC) typically form the reference points of the stereotactic coordinate system. Hence any discussion of target localization is limited by the variability of AC and PC selection. In an earlier study, which was performed using manual selections of AC and PC by 43 neurosurgeons, we showed that intersurgeon variability has a substantial impact on the localization of deep brain stimulation targets. We have developed and validated a fully automatic and robust AC and PC selection system that can be routinely used clinically. In this study, we show that this system is capable of localizing the AC and PC points with an accuracy that is better than that achieved clinically by manual selection, 0.65 mm (95% confidence interval: 0.56–0.79) versus 1.21 mm (95% confidence interval: 0.91–1.47) for AC and 0.56 mm (95% confidence interval: 0.46–0.66) versus 1.06 mm (95% confidence interval: 0.82–1.26) for PC.
Imaging of Deep Brain Stimulation Leads Using Extended Hounsfield Unit CT
Authors: Hebb Adam O. , Poliakov Andrew V.
Published: March 2009

Deep brain stimulation (DBS) has become a routine therapy for Parkinson’s disease. Standard CT imaging, often used to evaluate DBS electrodes in patients with limited benefit or significant side effects, has limitations including inability to distinguish different metallic components of the DBS lead. CT imaging with an extended Hounsfield unit (EHU) scale allows advanced image processing techniques to detect individual electrodes. EHU-CT may be co-registered to MRI volumes to provide accurate anatomical visualization of DBS lead contacts.
Observation of Hand Movements by Older Persons with Dementia: Effects on Cognition
Authors: Eggermont Laura H.P. , Swaab Dick F. , Hol Elly M. , Scherder Erik J.A.
Published: March 2009

Background/Aim: Hand movement observation activates mirror neurons, located in brain areas that are vulnerable to Alzheimer’s disease. We examined the effects of hand movement observation on cognition in older persons with dementia. Methods: Nursing home residents with dementia (n = 44) watched either videos showing hand movements or videos showing a documentary for 30 min, 5 days a week, for 6 weeks. Neuropsychological tests were performed at baseline, week 6 and week 12. Results: Linear mixed model analyses revealed a significant interaction effect on an attention test, but not on cognitive domains. Additional analyses showed that a face recognition task improved significantly. Conclusion: Although these findings do not support an overall beneficial effect of hand movement observation on cognition in dementia, specific cognitive functions improved. Future studies are warranted.
The Role of UFT in Metastatic Colorectal Cancer
Authors: Bennouna Jaafar , Saunders Mark , Douillard Jean-Yves
Published: March 2009

5-Fluorouracil (5-FU) has been the most widely used chemotherapeutic agent for metastatic colorectal cancer (mCRC) and 5-FU combination therapy improves efficacy compared with monotherapy. The oral fluoropyrimidine UFT (tegafur-uracil) with leucovorin (LV) improves tolerability and has replaced 5-FU in many regimens. The efficacy and tolerability of UFT with LV in the first-line treatment of mCRC has been demonstrated in a number of phase II studies. In two phase III studies, UFT with LV has been shown to have comparable efficacy and improved tolerability versus intravenous bolus 5-FU, with very few cases of hand-foot syndrome (HFS). Indirect comparisons of UFT and capecitabine suggest that they are comparable in terms of survival. In first-line treatment, UFT in combination with oxaliplatin (TEGAFOX) or irinotecan (TEGAFIRI) is effective and well tolerated, with similar efficacy and tolerability to the corresponding 5-FU- and capecitabine-based combinations, but with a lower incidence of HFS. Alternating cycles of TEGAFOX and TEGAFIRI are effective and well tolerated, and the combination of TEGAFIRI and the targeted monoclonal antibody cetuximab has shown promising activity, similar to that of FOLFIRI plus cetuximab. UFT can be considered a rational replacement for intravenous 5-FU in the first- and second-line treatment of patients with mCRC.
Chlorhexidine Inhibits the Proteolytic Activity of Root and Coronal Carious Dentin in vitro
Authors: Garcia M.B. , Carrilho M.R. , Nör J.E. , Anauate-Netto C. , Anido-Anido A. , Amore R. , Tjäderhane L. , Bretz W.A.
Published: March 2009

The purpose of this study was to evaluate the effect of chlorhexidine on the proteolytic activity of carious coronal and root dentin collected from patients. Sound dentin from freshly extracted human teeth was used as a control. Dentin fragments were mixed with a synthetic substrate for proteolytic enzymes (N-benzoyl-DL-arginine-naphthylamide – BANA) and the suspensions mixed with either 0.12% chlorhexidine digluconate or distilled water. These mixtures were incubated for 18 h at 37°C, color was developed by the addition of 0.1% Fast Garnet and their optical density was recorded spectrophotometrically. BANA hydrolysis measured by the optical density of incubated specimens was detected in all tested groups, but was significantly higher for carious than for sound dentin (p < 0.05). The proteolytic activity was reduced for carious coronal and root dentin by chlorhexidine (p < 0.05; 50 and 30%, respectively). Chlorhexidine also reduced the proteolytic activity in sound root dentin (p < 0.05; 20%). Conversely, changes in the proteolytic activity of sound coronal dentin were not observed in the presence of chlorhexidine. The reduction in proteolytic activity by chlorhexidine was significantly higher in carious coronal dentin than in carious root dentin (p < 0.05). In conclusion, part of the effect of chlorhexidine in controlling caries progression in humans may be due to a decrease in the proteolytic activity of carious coronal and root dentin. Because of the prolonged incubation time in the present study, similar results may be obtained clinically with prolonged dentin exposure to chlorhexidine, e.g. chlorhexidine-containing varnishes.
Does Study Design Influence Outcome?
Authors: Rutherford Bret R. , Sneed Joel R. , Roose Steven P.
Published: March 2009

Background: Clinicians and researchers synthesize data from randomized controlled trials (RCTs) of antidepressants to make conclusions about the efficacy of medications for depression. All treatments include nonspecific factors in addition to the specific effects of drugs, and study design may influence patient outcomes via nonspecific factors. This study investigated whether placebo control and treatment duration affect the outcome in antidepressant RCTs. Methods: Medline and the Cochrane Database were searched to identify RCTs of antidepressants for major depression approved by the Food and Drug Administration. Included studies enrolled outpatient participants aged 18–65, lasted 6–12 weeks, compared an antidepressant to placebo or another antidepressant and were published in English after 1985. Excluded trials enrolled inpatients, pregnant women and subjects with psychosis or mania. Mixed-effects logistic regression models including study type (placebo-controlled or comparator) and study duration (6, 8 or 12 weeks) as fixed effects determined whether these factors affected response and remission rates. Results: In the 90 trials analyzed, the odds of depression response (OR = 1.79, 95% CI = 1.45–2.17, p < 0.001) and remission (OR 1.53, 95% CI = 1.11–2.11, p < 0.001) were significantly higher in comparator relative to placebo-controlled trials. Trials lasting 8 (OR = 1.37, CI = 1.14–1.64, p = 0.001) and 12 (OR = 1.52, CI = 1.12–2.07, p = 0.008) weeks had significantly greater response rates than 6-week trials without differing themselves. Conclusions: Response and remission rates to antidepressants are significantly affected by study type and duration. Clinicians and researchers must consider the study design when interpreting and designing RCTs of antidepressant medications.
Energy and Nutrient Intakes during Different Phases of the Menstrual Cycle in Females in the United Arab Emirates
Authors: Cheikh Ismail Leila I. , Al-Hourani Huda , Lightowler Helen J. , Aldhaheri Ayesha S. , Henry C. Jeya K.
Published: March 2009

Background/Aims: Evidence related to the influence of the menstrual cycle on energy and nutrient intakes is inconclusive. The purpose of the present study was to investigate energy and nutrient intakes during different phases of the menstrual cycle in adult females in the United Arab Emirates. Methods: Forty-three females, aged between 18 and 30 years, were recruited to the study. Subjects were not using oral contraceptive pills and experienced regular menstrual cycles. Food and beverage intake was recorded, using the estimated daily record method, for 2 days of each menstrual cycle phase (pre-menstrual, menstrual and post-menstrual). Energy and nutrient intakes were analysed using Diet5 for Windows. Results: Mean energy intake was significantly lower in the menstrual phase compared to the pre-menstrual phase (p = 0.002), but not the post-menstrual phase. Intakes of macronutrients and micronutrients were higher in the pre-menstrual phase compared to the menstrual and post-menstrual phases. Intakes of carbohydrates, protein and fat were significantly higher in the pre-menstrual phase than in the menstrual phase (p = 0.008, p = 0.001, p = 0.013, respectively). Similarly, intakes of vitamin C and B vitamins were significantly higher in the pre-menstrual phase than in the menstrual phase (p = 0.019, p = 0.05, respectively). Conclusion: Energy and nutrient intakes varied during the different phases of the menstrual cycle. These results confirm the hypothesis that food intake differs between different phases of the menstrual cycle.
Supernumerary Nostril
Authors: Sun Z.-Y. , Li H. , Zhang M.-J. , Zhao H. , Xu W. , Xiao H. , Guo Y.-X. , Wen Z. , Yin G.-Q.
Published: March 2009

Supernumerary nostril is one of the rarest congenital nasal deformities, and only a limited number of articles have been published so far on this topic. We present a typical case of a supernumerary nostril located above the left nostril in a male infant. We describe the appearance, physical examination, surgical procedure and histopathological examination of this case.
MRI Correlates of Protein Deposition and Disease Severity in Postmortem Frontotemporal Lobar Degeneration
Authors: Whitwell Jennifer L. , Jack, Jr. Clifford R. , Senjem Matthew L. , Parisi Joseph E. , Boeve Bradley F. , Knopman David S. , Dickson Dennis W. , Petersen Ronald C. , Josephs Keith A.
Published: March 2009

Background: Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. Objective: To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Methods: Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). Results: The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. Conclusion: There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.
E1A Has No Effect on LPS-Induced IL-6 Secretion in Rat Alveolar Epithelial Cells
Authors: Chen Juan , Luo Jiandong , Li Bing , Ran Pixin
Published: March 2009

Background: The adenoviral protein E1A has been suggested to play a role in the pathophysiological development of chronic obstructive pulmonary disease (COPD) by inducing expression of inflammatory factors. It is well known that glucocorticoids are important inhibitors of inflammation. In the treatment of COPD corticosteroid therapy commonly has little or no anti-inflammatory effect. We hypothesized that the anti-inflammatory effect of glucocorticoids may be decreased or abolished by E1A expression, which aggravates the airway inflammation and results in the late stage of ‘corticosteroid resistance’ in COPD development. Corticosteroid therapy is a widely used method to treat respiratory inflammation. However, loss of anti-inflammatory effect is a common and serious complication during the therapy for COPD. Objectives: To test whether the E1A gene, which is 1 of the viral genes responsible for enhanced inflammatory responses, is involved in corticosteroid resistance during clinical therapy for COPD. Methods: Rat alveolar epithelial cells were transfected with an E1A gene vector. Stably transfected cells were screened by PCR amplification of the E1A gene fragment. Transcription of the E1A gene was assayed by QT-RT-PCR. Protein expression was measured by immunohistochemistry and Western blot. E1A induced interleukin (IL)-6 secretion. mRNA levels were tested by ELISA and QT-RT-PCR. E1A-positive cells and E1A-negative cells were treated with lipopolysaccharide (LPS), physiological concentrations of hydrocortisone and trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC). The activity of HDAC was confirmed by colorimetric HDAC activity assay kit. Results: In all 4 E1A-expressing transfectants, expression of the E1A 243R protein was much higher than that of the 289R protein. LPS significantly increased IL-6 secretion in both E1A-positive and E1A-negative cells and no significant differences were found. Treatment with hydrocortisone at a physiological concentration clearly decreased LPS-induced IL-6 secretion, and this down-regulation effect could be abolished in the presence of TSA. LPS significantly decreased HDAC activity, which was completely abolished by application of hydrocortisone. Hydrocortisone alone had no effect on HDAC activity in cells without LPS stimulation. There were no differences in HDAC activity or IL-6 secretion under these treatments between E1A-positive and E1A-negative cells. Conclusions: Our results indicated that a physiological concentration of glucocorticoid suppresses LPS-mediated IL-6 secretion, through the participation of HDAC. Expression of adenoviral E1A had no effect on HDAC activity and hydrocortisones induced an anti-inflammatory effect.
Fixed-Dose-Rate Gemcitabine in Combination with Oxaliplatin in Patients with Metastatic Pancreatic Cancer Refractory to Standard-Dose-Rate Gemcitabine: A Single-Institute Study
Authors: Fortune Brett E. , Li Xiaobai , Kosuri Kavitha V. , Weatherby Lynn M. , Thomas James P. , Bekaii-Saab Tanios S.
Published: March 2009

Objectives: There is a paucity of data exploring treatment options for refractory pancreatic cancer. Oxaliplatin has interesting activity in second-line therapy. Fixed-dose-rate gemcitabine (GFDR, 10 mg/m2/min) has shown promising results in patients with advanced pancreatic cancer over standard-dose-rate (30 min) gemcitabine (GSDR). Methods: We conducted a retrospective analysis of the experience of our cancer center with GFDR and oxaliplatin (GEMOX) in patients who failed GSDR. GEMOX consisted of gemcitabine 1,000 mg/m2 over 100 min on day 1 and oxaliplatin 100 mg/m2 over 2 h on day 2 every 2 weeks. Eligible patients were required to have measurable metastatic adenocarcinoma of the pancreas and to have failed prior GSDR. Results: Seventeen patients (median age 62 years) who were treated at the Ohio State University with GEMOX following GSDR failure between November 2003 and January 2008 were included in this study. Twenty-four percent of all patients had a partial response, 29% had stable disease and 47% had progressive disease. The median progression-free survival was 2.6 months and the median overall survival was 6.4 months. There were no unexpected toxicities. Conclusion: GEMOX shows interesting activity and acceptable tolerability in patients with metastatic pancreatic cancer who failed prior GSDR. Our results are consistent with previously published results.
Impact of Vascular Risk Factors and Diseases on Cognition in Persons with Mild Cognitive Impairment
Authors: Villeneuve Sylvia , Belleville Sylvie , Massoud Fadi , Bocti Christian , Gauthier Serge
Published: March 2009

Background/Aim: To investigate the impact of vascular burden (assessed by the number of vascular risk factors and diseases) on the cognition of persons with amnestic mild cognitive impairment (aMCI). Methods: This study included 145 participants; 68 meeting criteria for amnesic single-domain or multiple-domain MCI and 77 matched controls. Four cognitive domains were assessed: executive functions, processing speed, episodic memory and general cognitive functioning. Results: A larger vascular burden among aMCI is correlated with lower performance in the executive domain. In addition, persons with aMCI with high vascular burden were more frequently of the multiple domain subtype, whereas persons with no vascular burden were more frequently of the single domain subtype. Conclusion: Our findings suggest that the combined effect of multiple vascular risk factors and diseases increases the amount of executive impairment in persons with aMCI. Vascular burden may play an important role in the heterogeneity of aMCI by impairing cognitive functions other than memory.
Ironing Out the Wrinkles in Host Defense: Interactions between Iron Homeostasis and Innate Immunity
Authors: Wang Lijian , Cherayil Bobby J.
Published: March 2009

Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate immunity. In this article, we review what is currently known about the role of iron in the response to infection.
Prognostic Factors in Elderly Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy
Authors: Li Jian , Chen Ping , Dai Chun-Hua , Li Xiao-Qin , Bao Quan-Lei
Published: March 2009

Objective: The prognosis of advanced non-small cell lung cancer (NSCLC) is poor. The aim of this study was to assess the outcome of chemotherapy for elderly patients with advanced NSCLC, focusing on the prognostic factors influencing survival. Methods: We reviewed retrospectively the medical records of 109 elderly patients with advanced NSCLC treated with chemotherapy from January 1999 to December 2006. Collected data included demographic information, clinical assessment before therapy, and information on treatment and outcome. Survival was estimated using the Kaplan-Meier method, and prognostic factors were analyzed by the log-rank test and Cox regression model. Results: The median survival time for the entire group was 10.5 (95% confidence interval: 9.15–11.88) months, with 1- and 2-year survival rates of 31.2 and 9.2%, respectively. Univariate analysis showed that performance status (PS; p = 0.013), comorbidity (p = 0.006), chemotherapy cycle (p = 0.006) and second-line therapy (p = 0.002) significantly influenced overall survival. In multivariate analysis, comorbidity, chemotherapy cycles and second-line therapy were identified as independent prognostic factors. Conclusions: Survival of elderly patients with advanced NSCLC treated with chemotherapy is significantly influenced by the patient’s PS, comorbidity, chemotherapy cycle and second-line therapy. These results may help to choose the appropriate treatment in clinical practice.
Comparison of Gadofluorine-M and Gd-DTPA for Noninvasive Staging of Atherosclerotic Plaque Stability Using MRI
Authors: Ronald John A. , Chen Yuanxin , Belisle Andre J.-L. , Hamilton Amanda M. , Rogers Kem A. , Hegele Robert A. , Misselwitz Bernd , Rutt Brian K.
Published: March 2009

Background—

Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA.

Methods and Results—

Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T
1
-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.

Conclusions—

GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.
Top–Down Attentional Control in Parkinson's Disease: Salient Considerations
Authors: Cools Roshan , Rogers Robert , Barker Roger A. , Robbins Trevor W.
Published: March 2009

Cognitive dysfunction in Parkinson's disease (PD) has been hypothesized to reflect a failure of cortical control. In keeping with this hypothesis, some of the cognitive deficits in PD resemble those seen in patients with lesions in the lateral pFC, which has been associated with top–down attentional control. However, there is no direct evidence for a failure of top–down control mechanisms in PD. Here we fill this gap by demonstrating disproportionate control by bottom–up attention to dimensional salience during attentional set shifting. Patients needed significantly more trials to criterion than did controls when shifting to a low-salient dimension while, remarkably, needing significantly fewer trials to criterion than did controls when shifting to a high-salient dimension. Thus, attention was captured by bottom–up attention to salient information to a greater extent in patients than in controls. The results provide a striking reinterpretation of prior set-shifting data and provide the first direct evidence for a failure of top–down attentional control, resembling that seen after catecholamine depletion in the pFC.
On the Derivation of Material Thermal Properties Representative of Heterogeneous Urban Neighborhoods
Authors: Salamanca F. , Krayenhoff E. S. , Martilli A.
Published: March 2009

An important question arises when modeling a heterogeneous landscape (e.g., an urbanized area) with a mesoscale atmospheric model. The surface within a grid cell of the model (which has a typical dimension of one or more kilometers) can be composed of patches of surfaces of different character. The total sensible heat flux in the grid cell, then, is the aggregate of the heat fluxes from each individual surface, each one with a unique thermal response arising from its thermal properties, among other factors. Current methods to estimate the sensible heat flux consider only one (in the case of flat terrain) or three (roof, walls, and ground, for urban areas) active surfaces with thermal properties that are ideally representative of the materials present in the grid cell. The question is then how to choose the representative thermal properties such that the heat flux computed by the model most closely approximates the aggregate of the fluxes from the different patches. In this work a new way to average building material thermal properties for urban canopy parameterizations is presented, and a suite of idealized numerical simulations demonstrates its superiority to two more standard averages. Moreover, this novel approach points to a new way of determining physical properties that are representative of heterogeneous zones.