bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Index of Tooth Wear
Authors: Fares J. , Shirodaria S. , Chiu K. , Ahmad N. , Sherriff M. , Bartlett D.
Published: March 2009

A modified wear index, in which the wear of enamel and dentine are recorded separately, is described. The index was applied to estimating the prevalence and extent of tooth wear in a single convenience sample of 18- to 30-year-old students attending a university in London. The subjects were examined under good lighting in a dental chair away from a dental school. A total of 707 females and 303 males were recruited with a mean age of 21.9 years (standard deviation = 0.1, range = 18–30) and examined by 3 trained and calibrated examiners. Intra-examiner intra-class correlation coefficients showed a range of 0.44–0.88. The unweighted κ scores were above 0.88 for enamel and dentine. The presence of enamel wear was common to all subjects, but 6.1% of the participants had more than one third of the tooth surface affected. Dentine was exposed on 5.3% of all surfaces, with the largest proportion accounting for less than 10% of the tooth surface (grade 1). The proportion of subjects with at least 1 surface with dentine exposed was 76.9% of the total population. The males had significantly more wear in dentine than the females (p = 0.001). The inter-examiner intra-class correlation coefficients for enamel and dentine were 0.87 and 0.92, respectively. The reproducibility of the index was comparable to other analyses and provides an opportunity to assess the prevalence of enamel wear in large population-based studies.
Performance of Laser Fluorescence for Detection of Occlusal Dentinal Caries Lesions in Permanent Molars: An in vivo Study with Total Validation of the Sample
Authors: Abalos C. , Herrera M. , Jiménez-Planas A. , Llamas R.
Published: March 2009

The objective of this in vivo study was to evaluate the performance of a laser fluorescence device in detecting dentinal caries in noncavitated occlusal surfaces. The sample included 102 first and second permanent molars, selected according to the criteria of Ekstrand et al. [Caries Res 1997;31:224–231]: 46 not suspected of having dentinal caries (score: 0–2) and 56 under suspicion (score: 3–4). Once measured by laser fluorescence, all were validated by fissurotomy (gold standard). To avoid ethical questions, the 46 teeth (score: 0–2) used were to serve as abutments for a fixed-fixed bridge. Visual inspection performed well, showing a sensitivity and specificity of 0.93 and 0.88, respectively. Laser fluorescence had an area under the receiver operating characteristic curve of Az = 0.85. The cutoff point with the highest sensitivity and specificity was 20, with a sensitivity and specificity of 0.89 and 0.75, respectively.
Major Depression, Antidepressant Medication and the Risk of Obesity
Authors: Patten Scott B. , Williams Jeanne V.A. , Lavorato Dina H. , Brown Lauren , McLaren Lindsay , Eliasziw Michael
Published: March 2009

Background: Cross-sectional studies have reported an association between major depressive episode (MDE) and obesity. The objective of this longitudinal analysis was to determine whether MDE increase the risk of becoming obese over a 10-year period. Method: We used data from the Canadian National Population Health Survey (NPHS), a longitudinal study of a representative cohort of household residents in Canada. The incidence of obesity, defined as a body mass index (BMI) of ≥30, was evaluated in respondents who were 18 years or older at the time of a baseline interview in 1994. MDE was assessed using a brief diagnostic instrument. Results: The risk of obesity was not elevated in association with MDE, either in unadjusted or covariate-adjusted analyses. The strongest predictor of obesity was a BMI in the overweight (but not obese) range. Effects were also seen for (younger) age, (female) sex, a sedentary activity pattern, low income and exposure to antidepressant medications. Unexpectedly, significant effects were seen for serotonin-reuptake-inhibiting antidepressants and venlafaxine, but neither for tricyclic antidepressants nor antipsychotic medications. Conclusions: MDE does not appear to increase the risk of obesity. The cross-sectional associations that have been reported, albeit inconsistently, in the literature probably represent an effect of obesity on MDE risk. Pharmacologic treatment with antidepressants may be associated with an increased risk of obesity, and strategies to offset this risk may be useful in clinical practice.
Changes in CREB Phosphorylation and BDNF Plasma Levels during Psychotherapy of Depression
Authors: Koch Jakob M. , Hinze-Selch Dunja , Stingele Karoline , Huchzermeier Christian , Göder Robert , Seeck-Hirschner Mareen , Aldenhoff Josef B.
Published: March 2009

Background: The cyclic adenosine monophosphate response element-binding proteins (CREB) and their interaction with brain-derived neurotrophic factor (BDNF) are essential elements in signal transduction pathways important for cellular resilience and neuroplasticity. They play a decisive role in the concept of altered neuroplasticity in major depression. We have previously demonstrated that the increase in phosphorylated CREB (pCREB) in T lymphocytes is significantly associated with clinical improvement in patients treated with antidepressants. In the present study, we focused on patients treated only with psychotherapy to exclude direct pharmacological actions. In addition to pCREB, we also measured the BDNF plasma levels. Methods: pCREB in T lymphocytes was determined by Western blot; the BDNF plasma levels with solid-phase ELISA. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Thirty patients meeting DSM-IV criteria for major depressive episodes (MDE) were recruited into this 6-week study. They received interpersonal psychotherapy (IPT) twice weekly. Results: After 6 weeks of IPT, 17 patients responded (reduction of ≥50% of baseline HAMD); after 1 week of treatment pCREB increased significantly compared to the nonresponder group. Measurement of the BDNF plasma levels revealed no differences between the responder and nonresponder groups. Furthermore, the correlations between BDNF plasma levels and pCREB were not significant. Conclusions: The early increase in pCREB is related to treatment response and does not depend on pharmacological interventions or BDNF plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.
Urodilatin and Pentoxifylline Prevent the Early Onset of Escherichia coli-Induced Acute Renal Failure in a Model of Isolated Perfused Rat Kidney
Authors: Groesdonk Heinrich V. , Bauer Alexander , Kreft Burkhard , Heringlake Matthias , Paarmann Hauke , Pagel Horst
Published: March 2009

Background/Aims: Raised cytokine levels and a hypoperfusion-associated decrease in glomerular filtration rate (GFR) are hallmarks of the genesis of septic acute renal failure (ARF). Therefore, anti-inflammatory as well as renal vasodilating therapeutic strategies may afford renal protection during septic ARF. The present study was designed to determine the effects of administration of urodilatin, pentoxifylline and theophylline to improve renal function in an ex-vivo model of ‘septic renal injury’. Methods: Eight series of experiments were performed: no intervention, perfusion with a suspension containing Escherichia coli bacteria (strain 536/21); E. coli + 10 μg/l urodilatin, E. coli + 20 μg/l urodilatin, E. coli + 100 μM theophylline, E. coli + 100 μM pentoxifylline and E. coli + URO 20 μg/l given 90 min after start of perfusion. Renal vascular and glomerular functional parameters as well as TNF-α release were analyzed up to 180 min. Results: Perfusion with E. coli caused an acute deterioration of renal vascular and glomerular function. URO 20 μg/l and PTX decreased renal vascular resistance (RVR) from 83.7 ± 18.4 to 9.2 ± 1.1 and 8.6 ± 2.2 mm Hg/ml/min/g kidney and increased renal perfusion flow rate (PFR) from 8.2 ± 1.5 to 14.6 ± 0.8 and 14.1 ± 2.2 ml/min/g kidney. As a result, GFR improved from 102.1 ± 15.6 to 442 ± 48.3 and 525.8 ± 57 μl/min/g kidney during treatment with URO 20 μg/l and PTX, respectively. Renal TNF-α release was significantly reduced by URO 20 μg/l (from 178 ± 23 to 45.2 ± 2 and 47 ± 3 pg/ml) in the E. coli + URO 20 μg/l and by PTX in the E. coli + PTX group if added to the perfusion medium upon start of perfusion. Interestingly, URO 20 μg/l also decreased RVR significantly from 62.2 ± 6.1 to 35.9 ± 6.0 mm Hg/ml/min/g kidney, improved PFR from 5.4 ± 1.0 to 8.7 ± 1.0 ml/min/g kidney, increased GFR from 160 ± 43.3 to 280.7 ± 27.9 μl/min/g kidney, and decreased TNF-α release to 122 ± 18 pg/ml if applied 90 min after induction of septic ARF. In contrast, URO 10 μg/l did not significantly increase urine flow and did not appear to significantly improve renal perfusion. Theophylline showed no beneficial effects at all. Conclusion: This suggests that urodilatin and pentoxifylline might be useful to protect renal function if given before a septic renal insult. Additionally, treatment with urodilatin is capable of restoring renal function in early Gram-negative sepsis-induced ARF even if given after the septic insult.
Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker of Nephropathy in Diabetic Patients
Authors: Bolignano Davide , Lacquaniti Antonio , Coppolino Giuseppe , Donato Valentina , Fazio Maria Rosaria , Nicocia Giacomo , Buemi Michele
Published: March 2009

Background/Aims: Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. Methods: With the present study, we aimed at evaluating the levels of neutrophil gelatinase-associated lipocalin (NGAL), a tubular stress protein, in serum (sNGAL) and urine (uNGAL) from a cohort of 56 patients with type 2 diabetes mellitus categorized into three groups (normoalbuminuria, microalbuminuria and diabetic nephropathy). Results: All groups showed increased NGAL values with respect to controls; interestingly, increased NGAL levels were already found in diabetic patients without early signs of glomerular damage (normoalbuminuric). Both sNGAL and uNGAL increased in parallel with the severity of renal disease, reaching higher levels in patients with manifest diabetic nephropathy. The assessment of Pearson coefficient evidenced significant relationships between sNGAL and, respectively, uNGAL, serum creatinine and GFR (inversely) and between uNGAL and, respectively, serum creatinine, proteinuria, albuminuria, serum albumin and GFR (both inversely). Conclusions: NGAL might play an important role in the pathophysiology of renal adaptation to diabetes, probably as a defensive mechanism aiming to mitigate tubular suffering. Furthermore, NGAL measurement might become a useful and noninvasive tool for the evaluation of renal involvement in diabetic patients as well as for the early diagnosis of incipient nephropathy.
Epidemiology of Inflammatory Bowel Disease among Children in Poland
Authors: Karolewska-Bochenek Katarzyna , Lazowska-Przeorek Izabella , Albrecht Piotr , Grzybowska Krystyna , Ryzko Jozef , Szamotulska Katarzyna , Radzikowski Andrzej , Landowski Piotr , Krzesiek Elzbieta , Ignys Iwona , Fyderek Krzysztof , Czerwionka-Szaflarska Mieczyslawa , Jarocka-Cyrta Elzbieta
Published: March 2009

Background/Aims: The incidence of pediatric inflammatory bowel disease (IBD) in Western countries is on the rise. No prospective studies have been conducted on the epidemiology of pediatric IBD in Poland. The aim of the study was to define the characteristics of new pediatric IBD and assess the incidence of new IBD among children in Poland between 2002 and 2004. Methods: Patient records from 24 pediatric gastroenterology centers servicing the whole population of Poland were collected. IBD diagnosis was based on clinical, radiological, endoscopic and histological features. Results: There were 491 new IBD patients, representing an overall incidence of IBD of 2.7 cases/100,000 children/year. The incidence of Crohn’s disease (CD) was 0.6, ulcerative colitis (UC) 1.3, and indeterminate colitis (IC) 0.8. The age-related incidence of IBD was 1.8 in the 0- to 10-year-old age group, rising to 3.7 for the 11- to 18-year age group. Conclusions: The overall incidence of IBD (as well as CD, UC and IC) in Poland is lower than that in Western countries. The relative contribution of UC and IC to the overall IBD incidence is higher in Poland than in most Western countries. These findings may suggest a tendency towards under- or misdiagnosis.
Intracerebral Periventricular Pseudocysts in a Fetus with Mitochondrial Depletion Syndrome: An Association or Coincidence
Authors: Rohrbach M. , Chitayat D. , Maegawa G. , Shanske S. , Davidzon G. , Chong K. , Clarke J.T.R. , Toi A. , Tarnopolsky M. , Robinson B. , Blaser S.
Published: March 2009

We report the prenatal ultrasound and magnetic resonance imaging finding of periventricular, large subependymal pseudocysts (SEPCs) in a patient who was later diagnosed as having mitochondrial depletion syndrome (MDS). To our knowledge, this is the first report of fetal SEPCs in a patient with MDS. These findings may provide an important diagnostic tool for prenatal diagnosis of MDS in at risk pregnancies when the gene mutation causing the condition has not been delineated. It may also direct the neonatologist in the postnatal care of the newborn detected prenatally with SEPCs in view of the association of this finding with infection, chromosome abnormalities, metabolic disorders and other abnormalities, when such findings are identified serendipitously. Further research is needed to find if the SEPCs detected in our patient is an association or a coincidental finding.
Significance of Cervical Gland Area in Predicting Preterm Birth for Patients with Threatened Preterm Delivery: Comparison with Cervical Length and Fetal Fibronectin
Authors: Asakura Hirobumi , Fukami Takehiko , Kurashina Ryuhei , Tateyama Naoko , Doi Daisuke , Takeshita Toshiyuki
Published: March 2009

Background/Aims: Absent cervical gland area (CGA) has been considered a predictor of preterm delivery (PTD) for women at low risk. Predictive efficacy was analyzed in women at high risk for PTD and compared with cervical length (CL) <20 mm and fetal fibronectin (fFN) in cervicovaginal secretions. Methods: Case notes were reviewed for 108 subjects with gestation of 22–33 weeks who had been admitted to hospital with threatened PTD. The uterine cervix was observed by vaginal sonography and fFN was sampled on admission. Relationships between findings and outcome of PTD at <34 weeks’ gestation were analyzed. Results: Delivery at <34 weeks’ gestation occurred in 14.8% of patients. Absent CGA (68.8%), short CL (75.0%), short CL without CGA (62.5%) and positive fFN (62.5%) were more frequent in these patients than in patients undelivered at <34 weeks’ gestation (p < 0.05). Logistic regression analysis identified positive fFN and short CL with absent CGA as independent predictors for PTD (p < 0.0001). The mean interval from admission to delivery was 2.9 weeks in cases with fFN and both sonographic findings, compared to 9.3 weeks in cases with fFN but both sonographic finding (p = 0.0005). Conclusion: Short CL with absent CGA represents an independent predictor for PTD, as does fFN.
Sex Differences in Brain and Plasma β-Endorphin Content following Testosterone, Dihydrotestosterone and Estradiol Administration to Gonadectomized Rats
Authors: Pluchino Nicola , Ninni Filippo , Casarosa Elena , Giannini Andrea , Merlini Sara , Cubeddu Alessandra , Luisi Michele , Cela Vito , Genazzani Andrea Riccardo
Published: March 2009

Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E2V) on brain and plasma β-endorphin (β-END) concentrations in gonadectomized rats of both sexes. Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 μg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 μg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E2V was administered subcutaneously at 0.05 mg/kg/day. β-END levels were measured in different brain areas and plasma. Results: Ovariectomy (OVX) induced a significant decrease in β-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E2V significantly increased β-END concentration in all brain areas and in plasma. In the OCX group, T and E2V did not influence β-END concentrations in different hypothalamic areas. However, they produced a significant rise in β-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect β-END levels at any dose administered, either in males or females. Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement.
Treatment of Mediastinal Fibrosis with Mycophenolate Mofetil
Authors: Witschi Michael , Gugger Mathias , Nicod Laurent P.
Published: March 2009

We present the case of a 67-year-old male patient with mediastinal and retroperitoneal fibrosis. In Europe, this is a rare disease. Treatment was established to prevent complications due to strictures or compressions. Because of his diabetes, a therapy of low-dose prednisone combined with mycophenolate mofetil, known as steroid sparing agent, was applied. As a result, the radiological follow-up showed a marked decrease in the mediastinal and retroperitoneal masses.
Pharmacology of a Novel, Orally Active PDE4 Inhibitor
Authors: Dastidar Sunanda G. , Ray Abhijit , Shirumalla Rajkumar , Rajagopal Deepa , Chaudhary Shiwani , Nanda Kamna , Sharma Pawan , Seth Mahesh Kumar , Balachandran Sarala , Gupta Nidhi , Palle Venkata
Published: March 2009

Background: Intracellular cyclic adenosine monophosphate (cAMP) in inflammatory cells and airway smooth muscle is critical to the modulation of inflammatory response generation. Phosphodiesterase 4 (PDE4), an enzyme that catalyzes cAMP degradation, is therefore being actively explored as a molecular target for the treatment of airway inflammation, particularly asthma and chronic obstructive pulmonary disease. The field has undergone major advances in optimizing generation of compounds with a safe therapeutic margin; however, most PDE4 inhibitors tested so far have unacceptable side effects, particularly nausea and vomiting. Methods: We evaluated NIS-62949 in a wide range of in vitro and ex vivo cell-based assays to ascertain its anti-inflammatory potential. The compound was evaluated in murine models of lipopolysaccharide-induced endotoxemia and pulmonary neutrophilia. Parameters of airway inflammation, airway hyperreactivity and bronchoconstriction were evaluated in a guinea pig model of antigen-induced allergy. In order to assess the emetic potential, the compound was evaluated biochemically for binding to high-affinity rolipram-binding site. Subsequently, the compound was tested in a surrogate model for emesis, and the results obtained were correlated directly to tests conducted in a Beagle dog model. Results: NIS-62949 is a potent, highly selective PDE4 inhibitor. The compound demonstrated potent ability to inhibit tumor necrosis factor-α release from human peripheral blood mononuclear cells, lymphocyte proliferation and cytokine production. The in vitro profile of NIS-62949 prompted further evaluation of the compound in vivo and the compound was found to be comparable to roflumilast in several experimental models of pulmonary inflammation. Importantly, NIS-62949 displayed a safer profile compared to roflumilast. Conclusions: Our results report the development of a promising, novel PDE4 inhibitor, NIS-62949, with a wider therapeutic window as compared to second-generation PDE4 inhibitors such as roflumilast.
Supratentorial Convexity Dural-Based Cavernous Hemangioma Mimicking a Meningioma in a Child
Authors: Joshi V. , Muzumdar D. , Dange N. , Goel A.
Published: March 2009

A case of a convexity dural-based cavernous hemangioma in a 15-year-old male child is reported. The child presented only with headaches and had no neurological deficits. MRI features were suggestive of a meningioma. The tumor was completely resected and histology was conclusive of a hemangioma. At follow-up after 2 years, the child is asymptomatic and MRI showed no evidence of the lesion. Supratentorial convexity dural-based hemangioma in a child is rare and hitherto only 1 case has been reported in the world literature. Complete resection of the lesion is curative and long-term prognosis is excellent. The uniqueness of the present case is the supratentorial convexity dural-based location, innocuous presentation and unusual radiological features on MRI. The clinical profile, radiological features and management of cavernous hemangiomas in a child are discussed and the current literature is briefly reviewed.
Decompressive Hemicraniectomy in a 19-Month-Old Female after Malignant Cerebral Infarction
Authors: Farooq Muhammad U. , Abbed Khalid M. , Fletcher Jeffrey J.
Published: March 2009

Malignant cerebral infarction is a life-threatening condition with case fatality rates of approximately 80% in adults with malignant infarction of the middle cerebral artery. No medical treatment has been proven effective for this condition. Decompressive hemicraniectomy within 48 h of massive cerebral infarction significantly reduces mortality and improves outcome in adults 18–60 years of age. However, there is very limited data available about the role of decompressive hemicraniectomy in children with acute malignant cerebral infarction. We present the case of a 19-month-old female who presented with progressive encephalopathy and right hemiparesis. Computed tomography and magnetic resonance imaging of the brain showed massive cerebral infarction in the distribution of the left carotid artery with midline shift and impeding brain stem herniation. She underwent emergent decompressive hemicraniectomy with duraplasty and placement of an intracranial pressure monitor. Intracranial pressure was controlled with sedation and the patient was extubated on postoperative day 4. Extensive stroke workup was negative. Cranioplasty was performed at 3 months post-op. At the 6-month follow-up, she had an excellent recovery (modified Rankin scale of 1). Decompressive hemicraniectomy should be considered for the treatment of cerebral edema in children with malignant cerebral infarction. This may improve mortality and functional outcome compared to medical therapy alone. Due to the rare occurrence of stroke in children, more reports of decompressive hemicraniectomy are encouraged.
Postlaminoplasty Kyphotic Deformity in the Thoracic Spine: Case Report and Review of the Literature
Authors: Amhaz Hassan H. , Fox Benjamin D. , Johnson Keyne K. , Whitehead William E. , Curry Daniel J. , Luerssen Thomas G. , Jea Andrew
Published: March 2009

In the pediatric population, a strong correlation between multilevel laminectomy and postlaminectomy spinal deformities, predominantly kyphosis, has been demonstrated. This has been observed mainly in the cervical and thoracic spine. Therefore, laminoplasty was proposed as an alternative to laminectomy with a reduced incidence of spinal deformity and need for stabilization and fusion. Moreover, to the best of our knowledge, postlaminoplasty kyphosis of the thoracic spine has not been previously described in the literature. We report the case of a pediatric patient who rapidly developed severe thoracic kyphosis 3 months after resection of a symptomatic extradural spinal arachnoid cyst and multilevel en bloc thoracic laminoplasty and review the relevant literature.
Continuous Positive Airway Pressure Treatment Increases Bronchial Reactivity in Obstructive Sleep Apnea Patients
Authors: Korczynski Piotr , Gorska Katarzyna , Przybylowski Tadeusz , Bielicki Piotr , Zielinski Jan , Chazan Ryszarda
Published: March 2009

Background: The effects of continuous positive airway pressure (CPAP) treatment on the function of the lower airways are poorly understood. One of the methods used to determine the influence of positive pressure breathing on lower airways is the bronchial hyperreactivity test. Some authors report that CPAP increases bronchial hyperreactivity, while others report decreases. Objectives: To assess the influence of CPAP treatment on bronchial reactivity and the effects of bronchial hyperreactivity on compliance to CPAP treatment. Methods: The study group consisted of 101 obstructive sleep apnea syndrome patients (88 men and 13 women) with a mean age of 51 ± 11 years, mean apnea-hypopnea index of 53 ± 20 and mean body mass index of 32.6 ± 5.4. Patients were randomly assigned to a treatment group that received 3 weeks of CPAP therapy (group 1) or to a nontreatment control group (group 2). Pulmonary function tests and the methacholine bronchial provocation test were performed at baseline and 3 weeks later. Results: There were no statistically significant differences between treated and control groups in anthropometry and polysomnography variables. At baseline, bronchial hyperreactivity was found in 6 patients from group 1 and 5 patients from group 2. A significant increase in bronchial reactivity was observed after CPAP treatment. Log PC20M decreased from 1.38 ± 0.30 at baseline to 1.26 ± 0.50 (p < 0.05). In group 2, changes were statistically insignificant. Patients with bronchial hyperreactivity during CPAP treatment were characterized by significantly lower FEV1, FVC and MEF50 values. Conclusions: CPAP produces statistically significant bronchial hyperreactivity. However, there were no clinical symptoms and it is not necessary to withdraw previous therapies.
Calcium and Phosphorus Homeostasis
Authors: Taylor Jeremy G. , Bushinsky David A.
Published: March 2009

Calcium and phosphorus homeostasis relies on a complex, tightly regulated system involving many ions and hormones. The regulation of calcium and phosphorus is controlled by the actions of these ions and hormones on the intestine, kidneys and bone. Disturbances in the serum level of calcium and/or phosphorus can lead to significant pathology, including kidney stones and bone disease. In addition to parathyroid hormone and vitamin D, recently identified factors such as fibroblast growth factors and klotho play an important role in maintaining mineral ion homeostasis. The identification of subfamily V transient receptor potential cation channels (TRPV channels), Na/Pi cotransporters, the vitamin D receptor and the calcium-sensing receptor have further advanced our understanding of this complex physiology. In this review we discuss the current understanding of the relationships between the ions, hormones, and transporters that maintain calcium and phosphorus homeostasis.
Selective Internal Radiotherapy with Yttrium-90 Microspheres for Hepatic Metastatic Neuroendocrine Tumors: A Prospective Single Center Study
Authors: Kalinowski Marc , Dressler Miriam , König Alexander , El-Sheik Michael , Rinke Anja , Höffken Helmut , Gress Thomas M. , Arnold Rudolf , Klose Klaus-Jochen , Wagner Hans-Joachim
Published: March 2009

Background: To assess prospectively the safety and efficacy of Yttrium-90 microspheres in patients with unresectable liver metastases from neuroendocrine tumors. Materials and Methods: Microspheres were administered via a temporarily placed hepatic catheter. Patients were monitored prospectively. All patients were followed with laboratory and imaging studies at regular intervals to determine response rates. Toxicity and quality of life scores were measured. Results: Nine patients (7 female) with a mean age of 58.8 years were enrolled in this prospective trial. The mean tumor load was 58.8%. The estimated percentage shunting to the lungs on MAA scans was 5.04 ± 2.4%. Visceral artery embolization of extrahepatic arteries before treatment was performed in 6 patients. The median dose of microspheres was 2.1 ± 0.4 GBq. A total of 12 therapy sessions was performed. The mean follow-up was 21.7 months. Technical success was 100%. No major complications occurred. Survival rates were 100, 57 and 57% for 1, 2 and 3 years, respectively. Three months after SIRT therapy partial response (PR) was seen in 6 patients (66%). Calculated reduction of liver metastasis volume was 49%. In 3 patients (33%) stable disease was seen with a calculated tumor reduction of 13%. The estimated time to progression was 11.1 months. Conclusion: Radioembolization with 90Y microspheres is safe and produces high response rates even with extensive tumor replacement for up to 1 year. Acute and late toxicity was very low. Further investigations compared with other local ablative techniques is warranted.
Sunitinib Treatment for Patients with Advanced Clear-Cell Renal-Cell Carcinoma after Progression on Sorafenib
Authors: Zimmermann Kaja , Schmittel Alexander , Steiner Ursula , Asemissen Anne Marie , Knoedler Maren , Thiel Eckhard , Miller Kurt , Keilholz Ulrich
Published: March 2009

Background: Sorafenib and sunitinib are tyrosine kinase inhibitors with largely overlapping specificities, approved for the treatment of metastatic renal-cell carcinoma (RCC). It was unclear whether the similarities of the two drugs would lead to complete cross-resistance, or whether sequential application would be efficacious. Methods: Patients with metastatic RCC and progression on sorafenib treatment were treated with repeated cycles of sunitinib, 50 mg for 4 weeks, followed by a 2-week break. Response (Response Evaluation Criteria in Solid Tumors, RECIST) was assessed every second cycle. Results: A total of 22 patients with progression on sorafenib were accrued. Initially, sorafenib treatment was efficacious in all patients, with 7 showing partial response (PR) and 15 stable disease (SD), and subsequent disease progression. With 4 PRs (18%) and 12 SD (55%) a disease control rate of 73% was achieved. The median progression-free survival (PFS) on sunitinib was 21.5 weeks; median overall survival (OS) was not reached. Estimated 1-year PFS and OS were 31 and 60%, respectively. There was no apparent relationship between response to sorafenib and outcome on sunitinib. Conclusion: In our cohort of patients with RCC and progression after initial efficacy of sorafenib, the efficacy data of second-line sunitinib were close to published results of first-line treatment, suggesting limited clinically relevant cross-resistance.
Phase I/II Study of Twenty-Four-Hour Infusion of Irinotecan in Combination with Oral UFT plus Leucovorin for Metastatic Colorectal Cancer
Authors: Sadahiro S. , Suzuki T. , Maeda Y. , Tanaka A. , Ishikawa K. , Makuuchi H. , Murayama C.
Published: March 2009

Objective: Irinotecan has, in general, been administered as a 90-min infusion. However, several studies have demonstrated that continuous infusion seems to be a promising method of delivering irinotecan. This phase I/II trial was performed to evaluate the efficacy and safety of continuous infusion of irinotecan combined with UFT plus leucovorin (LV) for metastatic colorectal cancer. Methods: Escalating doses of irinotecan (90–110 mg/m2) were administered by 24-hour infusion on day 1. UFT 300 mg/m2/day and LV 75 mg/day were administered orally, in 3 divided daily doses, on days 3–7 and 10–14. The treatment cycles were repeated every 2 weeks. Results: In the phase I study, the maximum tolerated dose of irinotecan was 110 mg/m2 and the recommended dose for the phase II study was determined to be 100 mg/m2. Thirty-six patients, including 3 patients at the recommended dose in the phase I study, were evaluated in the phase II study. The common grade 3/4 toxicities were leucopenia, neutropenia, diarrhea and anorexia. The response rate was 63.9%, and the median progression-free and overall survival times were 8.3 and 24.6 months, respectively. Conclusion: A 24-hour infusion of irinotecan combined with UFT/LV is feasible and active for metastatic colorectal cancer.
Adjuvant FOLFOX Chemotherapy and Splenomegaly in Patients with Stages II–III Colorectal Cancer
Authors: Angitapalli Revathi , Litwin Alan M. , Kumar Prasanna R.G. , Nasser Eiad , Lombardo Jeffrey , Mashtare Terry , Wilding Gregory E. , Fakih Marwan G.
Published: March 2009

Background: The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II–III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. Methods: Stage II–IIIcolorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between2002 and 2006were identified. Computerizedtomography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length × width × height of the spleen). Results: 40 patientswere identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. Conclusions: Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy.
Colorectal Cancer Metastatic to the Brain: Time Trends in Presentation and Outcome
Authors: Nieder Carsten , Pawinski Adam , Balteskard Lise
Published: March 2009

Objective: It was the aim of this study to compare differences in disease pattern, patient characteristics and survival in patient cohorts treated during different decades. Methods: We conducted a retrospective analysis of all patients with brain metastases from colorectal cancer treated between 1983 and June 2008 in Northern Norway. The patients were assigned to 3 different groups, based on the decade of treatment. Results: The time interval between first cancer diagnosis and brain metastases has significantly increased over time. The use of chemotherapy before development of brain metastases has also increased. Only few patients did not harbour extracranial metastases. Chemotherapy after diagnosis of brain metastases has been used exclusively in the present decade, but in only 3 patients. Combined surgical resection or radiosurgery plus whole-brain radiotherapy has increasingly been utilized, but whole-brain radiotherapy alone remained the cornerstone. Neither survival from first cancer diagnosis nor from brain metastasis treatment has improved significantly; however, with up to 17 patients, the groups were small. Three factors were significantly associated with better survival: good performance status, limited number of brain metastases (1 vs. 2–3 vs. 4 or more) and absence of extracranial metastases. The prognostic impact of the recursive partitioning analysis classes was confirmed, while the new graded prognostic assessment index performed less well. Conclusions: Median survival was maximum 6 months in all decades, despite the increasing use of more aggressive treatment. As most patients harbour extracranial metastases that threaten their lives, systemic treatment might theoretically play a role in the management of these patients, but more data need to be collected to confirm the clinical impact of this approach.
Coronary Calcium Score in Renal Transplant Recipients
Authors: Bubenicek Petr , Kautznerova Dana , Sotornik Ivo , Adamec Milos , Lanska Vera , Teplan Vladimir
Published: March 2009

Background: Coronary calcium score (CCS) is established as an index for the risk of coronary heart disease (CHD). The aim of this prospective study was to assess changes in CCS in patients 1 year after kidney transplantation (KTx). Method: A total of 221 consecutive renal transplant recipients were enrolled in our prospective study (140 males/81 females). CCS was analyzed by spiral multidetector CT at baseline and 1 year after KTx. Bone mineral density (BMD) was measured in the lumbar spine (L-BMD) and femur (F-BMD). Results: The mean CCS was 539 ± 1,033 at baseline. 33% of the patients had a CCS of 0, and 33% of patients had a CCS of >401. A negative correlation was found between F-BMD and CCS, but no correlation was found between L-BMD and CCS. Using CCS, a positive correlation was found between total cholesterol and the age of patients, but no correlation of CCS was found with other biochemical markers of bone and lipid metabolism. One year after transplantation, the mean CCS was 703 ± 1,253; in 75% of patients the CCS was the same and 25% had a higher CCS. Conclusion: A high risk of CHD was found in 33% of renal graft recipients. No improvement in CCS was found 1 year after KTx.
Edaravone (Radical Scavenger) versus Sodium Ozagrel (Antiplatelet Agent) in Acute Noncardioembolic Ischemic Stroke (EDO Trial)
Authors: Shinohara Yukito , Saito Isamu , Kobayashi Shotai , Uchiyama Shinichiro
Published: March 2009

Background: Edaravone, a free radical scavenger approved by the Japanese Ministry of Health, Labor and Welfare in 2001 for treating acute ischemic stroke, was recommended by the Japanese Guidelines for the Management of Stroke 2004. While edaravone also has a neuroprotective profile, there is no other recognized drug that can verify its effect in clinical trials despite the need for neuroprotection. We performed a postmarketing clinical trial to provide further reliable evidence concerning edaravone in patients with acute ischemic stroke. Methods: We conducted a multicenter randomized parallel-group open-label trial of edaravone intravenously and a control drug, sodium ozagrel (ozagrel), a thromboxane A2 synthase inhibitor, intravenously in acute noncardioembolic ischemic stroke. The primary endpoint was the modified Rankin Scale at 3 months after treatment initiation. Results: In total, 401 patients were initially enrolled. The rate of ‘grade 0–1’ on the modified Rankin Scale, as assessed at 3 months, was 57.1 and 50.3% in the edaravone and ozagrel groups, respectively. The intergroup difference was 6.8% (95% confidence interval = –3.1 to 16.7), indicating noninferiority of edaravone to ozagrel, since the lower limit of the confidence interval did not exceed –11.4%. There were no particular concerns over the safety of edaravone. Conclusion: This trial verified that edaravone was not inferior to ozagrel. Edaravone was at least as effective as ozagrel for the treatment of acute noncardioembolic ischemic stroke.
Sixty-Four–Slice Multidetector Computed Tomography
Authors: Andreini Daniele , Pontone Gianluca , Bartorelli Antonio L. , Agostoni Piergiuseppe , Mushtaq Saima , Bertella Erika , Trabattoni Daniela , Cattadori Gaia , Cortinovis Sarah , Annoni Andrea , Castelli Alice , Ballerini Giovanni , Pepi Mauro
Published: March 2009

Background—

The goal of this study was to assess the safety, feasibility, and diagnostic accuracy of 64-slice multidetector computed tomography (MDCT) for the evaluation of coronary arteries in dilated cardiomyopathy (DCM) of unknown etiology. Sixteen-slice MDCT is useful in patients affected by DCM. However, technical limitations, such as cardiac arrhythmias, an inability of patients to sustain a long breath-hold, and the need of a high dose of contrast agent may limit its accuracy and widespread use.

Methods and Results—

Invasive coronary angiography (ICA) and MDCT coronary angiography were performed on 132 consecutive patients (82 men; age 63�11 years) affected by DCM (ejection fraction, 34�10%) of unknown etiology. In 2 patients (1.5%), MDCT was not feasible because of atrial fibrillation. Of the remaining 130 patients, 88 exhibited normal and 42 exhibited diseased coronary arteries in both MDCT and ICA. All patients with coronary artery disease except for 1 were correctly classified by MDCT as 1-vessel (11 cases), 2-vessel (13 cases), and 3-vessel (18 cases) disease. In the segment-based analyses, the overall feasibility for MDCT was 98.5% (1902 of 1930 segments). Segment-based and patient-based analyses for the detection of luminal stenosis of >50% and >70% were performed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT for the detection of >50% stenosis were 98.1%, 99.9%, 98.7%, 99.8%, and 99.7%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT for the detection of >70% stenosis were 99.5%, 98.6%, 94.1%, 99.9%, and 99.4%, respectively.

Conclusions—

Excellent feasibility and diagnostic accuracy, combined with low invasiveness, make 64-slice MDCT an ideal imaging modality for the anatomic evaluation of coronary circulation in patients with DCM of unknown etiology.
Task-dependent Activation of Face-sensitive Cortex: An fMRI Adaptation Study
Authors: Cohen Kadosh Kathrin , Henson Richard N. A. , Cohen Kadosh Roi , Johnson Mark H. , Dick Frederic
Published: March 2009

Face processing in the human brain recruits a widespread cortical network based mainly in the ventral and lateral temporal and occipital lobes. However, the extent to which activity within this network is driven by different face properties versus being determined by the manner in which faces are processed (as determined by task requirements) remains unclear. We combined a functional magnetic resonance adaptation paradigm with three target detection tasks, where participants had to detect a specific identity, emotional expression, or direction of gaze, while the task-irrelevant face properties varied independently. Our analysis focused on differentiating the influence of task demands and the processing of stimulus changes within the neural network underlying face processing. Results indicated that the fusiform and inferior occipital gyrus do not respond as a function of stimulus change (such as identity), but rather their activity depends on the task demands. Specifically, we hypothesize that, whether the task encourages a configural- or a featural-processing strategy determines activation. Our results for the superior temporal sulcus were even more specific in that we only found greater responses to stimulus changes that may engage featural processing. These results contribute to our understanding of the functional anatomy of face processing and provide insights into possible compensatory mechanisms in face processing.
Transitive Inference: Distinct Contributions of Rostrolateral Prefrontal Cortex and the Hippocampus
Authors: Wendelken Carter , Bunge Silvia A.
Published: March 2009

The capacity to reason about complex information is a central characteristic of human cognition. An important component of many reasoning tasks is the need to integrate multiple mental relations. Several researchers have argued that rostrolateral prefrontal cortex (RLPFC) plays a key role in relational integration. If this hypothesis is correct, then RLPFC should play a key role in transitive inference, which requires the integration of multiple relations to reach a conclusion. Thus far, however, neuroscientific research on transitive inference has focused primarily on the hippocampus. In this fMRI study, we sought to compare the roles of RLPFC and the hippocampus on a novel transitive inference paradigm. Four relations between colored balls were presented on the screen together with a target relation. Participants were asked to decide whether the target relation was correct, given the other indicated relations between balls. RLPFC, but not the hippocampus, exhibited stronger activation on trials that required relational integration as compared with trials that involved relational encoding without integration. In contrast, the hippocampus exhibited a pattern consistent with a role in relational encoding, with stronger activation on trials requiring encoding of relational predicate–argument structure as compared with trials requiring encoding of item–item associations. Functional connectivity analyses give rise to the hypothesis that RLPFC draws on hippocampal representations of mental relations during the process of relational integration.
Processing of the Incentive for Social Approval in the Ventral Striatum during Charitable Donation
Authors: Izuma Keise , Saito Daisuke N. , Sadato Norihiro
Published: March 2009

Human behaviors are motivated not only by materialistic rewards but also by abstract social rewards, such as the approval of others. When choosing an action in social situations, to evaluate each action, the brain must convert different types of reward (such as money or social approval) into a common scale. Here using fMRI, we investigated the neural correlates of such valuation computations while individuals freely decided whether to donate to real charities or to take the money for themselves in the presence or absence of observers. Behavioral evidence showed that the mere presence of observers increased donation rates, and neuroimaging results revealed that activation in the ventral striatum before the same choice (“donate” or “not donate”) was significantly modulated by the presence of observers. Particularly high striatal activations were observed when a high social reward was expected (donation in public) and when there was the potential for monetary gain without social cost (no donation in the absence of observers). These findings highlight the importance of this area in representing both social and monetary rewards as a “decision utility” and add to the understanding of how the brain makes a choice using a “common neural currency” in social situations.
Span, CRUNCH, and Beyond: Working Memory Capacity and the Aging Brain
Authors: Schneider-Garces Nils J. , Gordon Brian A. , Brumback-Peltz Carrie R. , Shin Eunsam , Lee Yukyung , Sutton Bradley P. , Maclin Edward L. , Gratton Gabriele , Fabiani Monica
Published: March 2009

Neuroimaging data emphasize that older adults often show greater extent of brain activation than younger adults for similar objective levels of difficulty. A possible interpretation of this finding is that older adults need to recruit neuronal resources at lower loads than younger adults, leaving no resources for higher loads, and thus leading to performance decrements [Compensation-Related Utilization of Neural Circuits Hypothesis; e.g., Reuter-Lorenz, P. A., & Cappell, K. A. Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17, 177–182, 2008]. The Compensation-Related Utilization of Neural Circuits Hypothesis leads to the prediction that activation differences between younger and older adults should disappear when task difficulty is made subjectively comparable. In a Sternberg memory search task, this can be achieved by assessing brain activity as a function of load relative to the individual's memory span, which declines with age. Specifically, we hypothesized a nonlinear relationship between load and both performance and brain activity and predicted that asymptotes in the brain activation function should correlate with performance asymptotes (corresponding to working memory span). The results suggest that age differences in brain activation can be largely attributed to individual variations in working memory span. Interestingly, the brain activation data show a sigmoid relationship with load. Results are discussed in terms of Cowan's [Cowan, N. The magical number 4 in short-term memory: A reconsideration of mental storage capacity. Behavioral and Brain Sciences, 24, 87–114, 2001] model of working memory and theories of impaired inhibitory processes in aging.