bluuebunny/crossref_metadata_2025 huggingface dataset:
ACROSTUDY: Status Update on 469 Patients
Authors: Brue Thierry
Published: January 2009

Background: ACROSTUDY is an international noninterventional surveillance study open to all patients with acromegaly treated with the growth hormone antagonist pegvisomant. This web-based registry contains data reflecting actual clinical care of patients, and it is being used to monitor the long-term safety and efficacy of pegvisomant therapy for acromegaly. Since ACROSTUDY was launched in 2004, there has been an increase in cumulative patient recruitment from 116 patients in 2005 to over 500 by mid-2008. As of May 2008, over 300 centers in 10 countries have contributed data from 469 patients. At the time of inclusion, 84% of patients had already been treated with pegvisomant. Of the 469 patients, the majority had received somatostatin analogue treatment (63% had received octreotide and 34% had received lanreotide); 20% reported no prior medical treatment. Overall, 74% had prior transsphenoidal surgery, 3% had undergone craniotomy and 35% had received radiation therapy (including stereotactic radiosurgery). Interestingly, 67% were treated with pegvisomant alone at study start, 4% took pegvisomant with a dopamine agonist, 26% with a somatostatin analogue and 3% took pegvisomant with both types of analogues. The starting dose of pegvisomant was 10 mg/day for 65% of patients treated with subcutaneous daily injections, and the mean insulin-like growth factor I (IGF-I) concentration at baseline was 526 ng/ml. Annual assessments since study launch in 2004 found 62–78% of patients had normal IGF-I levels after 1–4 years of pegvisomant treatment at mean doses of 18.7–22 mg/day. Adverse events were reported for 13% of patients, including 6 serious adverse events considered possibly related to the drug. An increase in tumor size relative to the size at start of pegvisomant therapy was reported for 24 of the 469 patients (5.1%). Liver function test results more than twice the upper limit of normal were observed in 7.7%. Conclusions: Further analyses of the ACROSTUDY database will provide a better understanding of pegvisomant treatment in clinical practice.
A 5-Year-Old Boy with Cryptorchidism and Pubic Hair: Investigation and Management of Apparent Male Disorders of Sex Development in Mid-Childhood
Authors: Keir L.S. , O’Toole S. , Robertson A.L. , Wallace A.M. , Ahmed S.F.
Published: January 2009

Background: Late presentation of congenital adrenal hyperplasia as a 46,XX disorder of sex development due to 11-β hydroxylase deficiency is uncommon. Such a case raises issues regarding appropriate investigation and management. Case History: A 5-year-old boy who had recently moved to the United Kingdom presented at the endocrinology clinic with recurrent abdominal pain. He was normotensive and had a history of ambiguous genitalia since birth, a relatively small penis, bilateral cryptorchidism and pubic hair. A systematic workup revealed low anti-Mullerian hormone levels for age and sex and elevated serum testosterone, androstenedione and deoxycortisol levels. A urinary steroid profile confirmed a diagnosis of 11-β hydroxylase deficiency. The child’s karyotype was 46,XX. Further genetic analysis revealed a compound heterozygote mutation in the CYP11B1 gene. Ultrasound scan showed evidence of Mullerian structures and accumulation of menstrual blood in the vagina (haematocolpos). Following discussion at a multidisciplinary clinic, the patient did not undergo sex reassignment and subsequently proceeded to surgery for removal of the Mullerian structures. Conclusions: This case emphasizes the importance of a systematic approach to investigation of older children presenting with apparent male undermasculinisation. It also raises important issues about gender reassignment in mid-childhood and the indications for removal of Mullerian organs in a 46,XX boy.
Bone and Metabolism: A Complex Crosstalk
Authors: Lieben Liesbet , Callewaert Filip , Bouillon Roger
Published: January 2009

Background: Until recently, communication from metabolism to bone was considered purely unidirectional, involving complex interactions among an adipocyte-derived factor (leptin), the sympathetic nervous system and neuropeptides. However, studies in animal models now show that bone regulates glucose metabolism and fat mass via the uncarboxylated form of an osteoblast-derived factor (osteocalcin). These findings not only demonstrate that energy metabolism regulates bone remodeling through neural relays, but also that the skeleton acts as an endocrine tissue that regulates metabolic homeostasis. Conclusions: Further study is needed to understand the physiological role of these complex interactions in man and their implications for human diseases.
Increased Plasma and Endothelial Cell Expression of Chemokines and Adhesion Molecules in Chronic Kidney Disease
Authors: Stinghen A.E.M. , Gonçalves S.M. , Martines E.G. , Nakao L.S. , Riella M.C. , Aita C.A. , Pecoits-Filho R.
Published: January 2009

Chemokines and adhesion molecules are involved in early events of atherogenesis. In the present study, we investigated the effects of the uremic milieu on the expression of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) and their relationship to cardiovascular status. Plasma samples were obtained from patients in different stages of chronic kidney disease (CKD). Cardiovascular status was evaluated by intima-media thickness and endothelial dysfunction by flow mediation dilatation and proteinuria. In vitro studies were performed using human umbilical endothelial cells exposed to uremic plasma or plasma from healthy subjects. MCP-1, IL-8, sVCAM-1 and sICAM-1 levels in plasma and in supernatant were analyzed by enzyme-linked immunosorbent assay. The population consisted of 73 (mean age 57 years; 48% males) CKD patients with glomerular filtration rate (GFR) of 37 ± 2 ml/min. MCP-1 and sVCAM-1 plasma levels were negatively correlated with GFR (ρ = –0.40, p < 0.0005 and ρ = –0.42, p < 0.0005, respectively). Fibrinogen was positively correlated with MCP-1, sICAM-1 and sVCAM-1 (ρ = 0.33, p < 0.005, ρ = 0.32, p < 0.05 and ρ = 0.25, p < 0.05, respectively) and ultra-high-sensitivity C-reactive protein was positively correlated with sICAM-1 (ρ = 0.25, p < 0.0005). Plasma IL-8 had a significant positive correlation with proteinuria (ρ = 0.31, p < 0.01). There was a time- and CKD-stage-dependent MCP-1, IL-8 and sVCAM-1 endothelial expression (p < 0.05). In summary, plasma levels of markers of endothelial cell activation (MCP-1 and sVCAM-1) are increased in more advanced CKD. Exposure of endothelial cells to uremic plasma results in a time- and CKD-stage-dependent increased expression of MCP-1, IL-8 and sVCAM-1, suggesting a link between vascular activation, systemic inflammation and uremic toxicity. Future studies are necessary to investigate whether these biomarkers add predictive value in comparison to the previously described ones. Also, endothelial response to uremic toxicity should be viewed as a potential target for intervention in order to reduce morbidity and mortality in CKD-related cardiovascular disease.
Transforming Growth Factor-β1 in Balkan Endemic Nephropathy
Authors: Đukanović Ljubica , Ležaić Višnja , Miljković Đorđe , Momčilović Miljana , Bukvić Danica , Marić Ivko , Miljković Željka , Marinković Jelena , Mostarica-Stojković Marija
Published: January 2009

Background/Aim: The aim of this study was to compare plasma and urine transforming growth factor-β1 (TGF-β1) levels in patients with different stages of Balkan endemic nephropathy (BEN) with those in patients with primary glomerulonephritis (GN) and healthy controls. Methods: The study involved 47 patients with BEN (30 with manifest BEN and 17 in the early stage of BEN), 12 patients with GN and 10 healthy controls. Plasma and urine TGF-β1 was assayed by enzyme-linked immunosorbent assay. Results: The median plasma TGF-β1 levels differed nonsignificantly between the groups (4,908–6,442 pg/ml), but individual plasma TGF-β1 levels in BEN patients exhibited the highest dispersion. Median urinary TGF-β1 excretion (pg/mg creatinine) was significantly higher in patient groups (manifest BEN: 203, early-stage BEN: 341, GN: 775) than in healthy controls (42). No correlation was found between plasma and urine TGF-β1 levels or between plasma TGF-β1 levels and creatinine clearance for any of the examined groups. Conclusion: Plasma TGF-β1 levels in BEN patients extended over the widest range, but no significant differences were found between the median values for the groups. Median urinary TGF-β1 excretion was significantly higher in patients with BEN and GN than in healthy controls.
Predictors of ESA Use in the Non-Dialysis Chronic Kidney Disease Population with Anemia
Authors: Collins Allan J. , Guo Haifeng , Gilbertson David T. , Bradbury Brian D.
Published: January 2009

Background: Anemia is a common complication of chronic kidney disease (CKD), but anemia treatment may be less comprehensive than guidelines suggest. Methods: The study population (n = 11,754) included general Medicare recipients with Parts A and B coverage before January 1, 2001, aged ≥65 years on January 1, 2001, and alive with Medicare as primary payer through December 31, 2001. Time-dependent proportional hazards models were used to investigate predictors of erythropoiesis-stimulating agent (ESA) use, adjusted for comorbid conditions and severity-of-disease variables as time-dependent, and age, sex, and race as fixed variables. ESA use was defined during 2002 and time-dependent variables during 2001–2002. Results: Only 839 patients (7%) received ESAs. Characteristics significantly predictive of ESA use (p < 0.05) were: outpatient specialty services, nephrology and hematology/oncology/medical oncology (RR 6.92); outpatient specialty services, hematology/oncology/medical oncology (RR 6.02); outpatient specialty services, nephrology (RR 3.44); inpatient principle procedure, other operations on vessels (RR 1.68); transfusions (RR 1.54), hypertension (RR 1.50); congestive heart failure (RR 1.34); home oxygen (RR 1.28). Conclusions: Access to anemia treatment may be an important marker for access to CKD care. Clinical trials are needed to assess effects of early referral and more comprehensive anemia treatment.
Encapsulating Peritoneal Sclerosis: Clinical Significance and Implications
Authors: Augustine T. , Brown P.W. , Davies S.D. , Summers A.M. , Wilkie M.E.
Published: January 2009

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). This review discusses the current understanding of the aetiology and pathogenesis of EPS, highlighting histological features which differentiate it from simple sclerosis of the peritoneal membrane which develops with time on PD. Diagnostic criteria are presented, including the role of imaging techniques. To date there are no randomised controlled trials to guide therapy; however, surgical techniques are an important treatment option. Collaborative research will be essential if this serious problem facing PD is to be solved.
Extended Left Hepatic Lobectomy for Hepatic Hilar Bile Duct Cancer: A Novel Surgical Procedure in Which the Right Hepatic Duct Is Transected before the Hepatoduodenal Ligament Is Skeletonized
Authors: Miyazawa Mitsuo , Aikawa Masayasu , Okada Katsuya , Torii Takahiro , Okamoto Kojun , Toshimitsu Yasuko , Koyama Isamu
Published: January 2009

As a general principle, the procedure of isolating a cancer region from surrounding tissues (skeletonization) is not taken until the last stage of a cancer operation. This principle is often disregarded in surgery for cancers of the hepatic hilar duct, however, as it may be mandatory to skeletonize the region before resecting the liver. Our group invented ‘extended left hepatic lobectomy’, a new surgical procedure for hepatic hilar bile duct cancer, in which we isolate the liver and transect the right hepatic duct before skeletonizing the cancer region in the hepatoduodenal ligament.
Interaction between Familial History of Obesity and Fat Intakes on Obesity Phenotypes
Authors: Paradis Ann-Marie , Godin Gaston , Pérusse Louis , Vohl Marie-Claude
Published: January 2009

Aim: To evaluate whether familial history of obesity (FHO) interacts with dietary fat intake (DFI) on obesity-related phenotypes. Methods: We recruited 664 participants aged between 18 and 55 years. A positive FHO (FHO+) was defined as having at least 1 obese first-degree relative and a negative FHO (FHO–) as no obese first-degree relative. Dietary intakes were collected from a food-frequency questionnaire. Body mass index, weight and waist girth were recorded using standard procedures. Fat mass and fat-free mass were assessed by electrical bioimpedance. Results: Significant interaction effects (FHO·DFI) were observed for body mass index, weight, waist girth and fat mass (p interaction = 0.05, 0.04, 0.04, 0.02, respectively). Among FHO+ individuals, indices of obesity increased with an increasing amount of DFI, whereas these associations were not observed in FHO– individuals. We also found that FHO+ individuals consuming a high-fat diet were at higher risk of obesity than FHO– individuals consuming a low-fat diet (3.6, CI 2.1–6.2). Conclusion: These results suggest a stronger relationship between DFI and obesity-related phenotypes in individuals with FHO+.
Use of Sealants in Pancreatic Surgery: Critical Appraisal of the Literature
Authors: Fingerhut Abe , Veyrie Nicolas , Ata Toufik , Alexakis Nicholas , Leandros Emmanuel
Published: January 2009

Background/Aims: Fibrin sealants containing both fibrin and thrombin have been used to control bleeding, reinforce suture lines and enhance tissue healing. However, the literature provides contradictory results. Methods: A systematic literature search was performed to determine the use of fibrin sealants in pancreatic surgery. These articles were then critically appraised according to their methodologies, outcomes and conclusions. Results: Twenty-four studies were found, including 6 controlled randomized trials. Of these, 16 studies were analyzed. Many methodological flaws and lack of consistency in definitions were found, making comparisons between studies difficult if not impossible. Conclusion: Because of the heterogeneity and lack of high-level evidence, the current literature does not allow us any conclusion: neither is there proof that fibrin sealants are of any real utility in pancreatic surgery, nor that they do not work. Further large-scale controlled trials are necessary before concluding that they do or do not provide any advantages in pancreatic surgery.
Successful Treatment of a Severe Second Trimester Fetomaternal Hemorrhage by Repeated Fetal Intravascular Transfusions
Authors: Votino Carmela , Mirlesse Véronique , Gourand Luc , Parnet-Mathieu Françoise , Bessières Bettina , Daffos Fernand
Published: January 2009

Objective: It was the aim of this study to report a case of fetomaternal hemorrhage (FMH) that was successfully treated with fetal intravascular transfusions in which the middle cerebral artery peak systolic velocity (MCA-PSV) detected fetal anemia. Methods: A massive FMH occurred twice in a healthy 33-year-old pregnant woman at 26 and 29 weeks of gestation with no evident cause. Four repeated intravascular transfusions were performed. The MCA-PSV increased in the presence of anemia and decreased following correction of fetal hematocrit. Results: A healthy neonate was delivered at 33 weeks of gestation. Conclusion: MCA-PSV detected fetal anemia both before the first transfusion and following the next intravascular transfusions. In our case, the change in fetal blood viscosity following transfusion with adult blood did not affect the MCA-PSV value for detection of fetal anemia.
Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage
Authors: Kolli Viswa Kalyan , Abraham Premila , Isaac Bina , Selvakumar Dhayakani
Published: January 2009

Background: Nephrotoxicity is one of the adverse side effects of methotrexate (MTX) chemotherapy. The mechanism of renotoxicity of MTX is not fully understood. It is essential to understand the mechanism of nephrotoxicity of MTX in order to diminish the side effects and hence maximize the benefits of chemotherapy. Objectives: The aim of the study was to verify whether oxidative stress and neutrophil infiltration play a role in MTX-induced renal damage using a rat model. Methods: Adult male rats were administered MTX at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the last dose. Vehicle-treated rats served as controls. The kidneys were removed and used for light microscopic and biochemical studies. Myeloperoxidase activity, a marker of neutrophil infiltration was measured in kidney homogenates along with the markers of oxidative damage including protein carbonyl content, protein thiol and malondialdehyde. The activities of the antioxidant enzymes, namely glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase, were also assayed. Results: MTX treatment induced damage to the glomeruli and tubules. Plasma creatinine levels in the MTX-treated rats were significantly elevated compared with controls. A significant increase in myeloperoxidase activity (p < 0.05) was observed in the kidneys of MTX-treated rats. Protein carbonyl content and malondialdehyde, sensitive and reliable markers of oxidative damage to proteins and lipids, respectively, were significantly elevated (p < 0.01) in the kidneys of MTX-treated rats compared with controls. The activities of the antioxidant enzymes, namely, superoxide dismutase and glutathione peroxidase, were significantly elevated (p < 0.01 and p < 0.05, respectively) in kidneys of rats following MTX treatment. Conclusion: The results of the present study provide evidence for the role of neutrophil infiltration and oxidative stress in MTX-induced renal damage. Administration of inhibitors of myeloperoxidase or scavenging hypochlorous acid, the product of myeloperoxidase, by supplementation with antioxidants as an adjuvant therapy may be promising in alleviating the renal side effect of MTX.
Pharmacokinetics and Safety of Multiple Intravenous Doses of Daptomycin in a Taiwanese Adult Population
Authors: Liang Shiou-Haur , Sheng Wang-Huei , Huang Yu-Tsung , Lin Wu Fe-Lin , Chang Shan-Chwen
Published: January 2009

Background: The pharmacokinetics (PK) and safety of daptomycin have not yet been studied in an adult Taiwanese population. Methods: A total of 13 healthy adult Taiwanese subjects (7 males and 6 females) were enrolled to receive a 5-day course of multiple intravenous daptomycin infusions at a dose of 4 mg/kg every 24 h. Both single-dose and steady-state serum PK were assessed. Results: PK evaluation showed no relevant accumulation of daptomycin based on the steady-state PK, which could be predicted from the single-dose PK. No gender effect on daptomycin, for either single- or multiple-dose PK, was observed. About 60% of the infused daptomycin was eliminated by the renal system in an unchanged form. Protein binding of daptomycin was about 93.92%. The PK parameters in healthy Taiwanese subjects were similar to those reported in healthy Caucasian subjects. No serious adverse events (AE) or deaths occurred during the study. The most frequently reported AE was leukopenia (3/19, 15.8%), followed by amblyopia (2/19, 10.5%). These AEs were considered to be mild-to-moderate in severity and resolved spontaneously. Conclusion: This study demonstrated similarities between Taiwanese and Caucasian healthy subjects in the PK profiles of daptomycin, and thus the dosage regimen used in Caucasian subjects could be applied to Taiwanese.
Cefuroxime for Empiric Treatment of Community-Acquired Pneumococcal Pneumonia: Is There a Generation Gap?
Authors: Wiener-Well Yonit , Raveh David , Schlesinger Yechiel , Yinnon Amos M. , Rudensky Bernard
Published: January 2009

Background:Streptococcus pneumoniae infection is an important cause of morbidity and mortality. The recommendations to use expanded-spectrum β-lactam drugs for patients with community-acquired pneumonia derived from the growing prevalence of penicillin-resistant pneumococci. Controversy exists regarding the use of second generation cephalosporins for empirical treatment of community-acquired pneumonia. Methods: In a retrospective study, 31 adult patients with pneumococcal pneumonia and bacteremia caused by S. pneumoniae that was intermediately resistant to penicillin were compared with 31 control patients with similar infection caused by penicillin-susceptible pneumococci. All patients were treated empirically with cefuroxime, alone or in combination with other antibiotics. Morbidity and mortality were studied. Results: All unsusceptible pneumococci isolates were intermediately resistant to penicillin. No cases of fully resistant pneumococci were isolated from blood cultures in our hospital. Two factors were significantly associated with non-susceptibility to penicillin: hematologic malignancy and immunosuppression. No significant difference in morbidity or mortality was detected between the 2 groups, and penicillin minimum inhibitory concentration was not found to be a factor associated with mortality. Conclusions: Patients with pneumococcal pneumonia caused by intermediately resistant pneumococci can be empirically treated with cefuroxime. In regions where fully resistant pneumococci are rare, the use of a second generation cephalosporin for empiric treatment of community-acquired pneumonia may be appropriate.
Organization of Major Telencephalic Pathways in an Elasmobranch, the Thornback Ray Platyrhinoidis triseriata
Authors: Hofmann Michael H. , Northcutt R. Glenn
Published: January 2009

The forebrain of elasmobranchs is well developed, and in some species the relative brain/body weight is comparable to that in mammals. However, little is known about the organization of major telencephalic pathways. We injected biotinylated dextran amines into the olfactory bulb, lateral pallium, dorsomedial pallium, and the forebrain bundles of the thornback ray, Platyrhinoidis triseriata. Secondary olfactory fibers from the bulb innervate the lateral pallium, the ventral division of the rostral telencephalon and area superficialis basalis. Retrogradely labeled cells were seen exclusively in the lateral periventricular area. The projections of the lateral pallium appeared basically similar to those of the olfactory bulb, but labeling was much denser in the superficial part of area basalis. Some fibers were also seen to innervate the posterior tuberal nucleus. Injections into the dorsomedial pallium revealed a major input from area basalis. Only a few cells were retrogradely labeled in the dorsal thalamus and posterior lateral thalamic nucleus. Major efferents of the dorsomedial pallium appear to reach the contralateral inferior lobe of the hypothalamus and the lateral mesencephalic nucleus. Tracer injections into the forebrain bundles retrogradely labeled many cells in the diencephalon and the mesencephalon and also revealed terminal fields in area superficialis basalis. In addition, a large number of cells were labeled in the dorsomedial pallium. Descending telencephalic fibers innervate heavily the inferior lobes and the lateral mesencephalic nucleus. Our results show that higher order olfactory pathway courses from the lateral pallium through area basalis to the dorsomedial pallium and that ascending non-olfactory input is integrated in area superficialis basalis and the dorsal pallium along with olfactory information, rather than being processed in separate, non-olfactory centers.
Mortality Risk in Hemodialysis Patients with Increased Arterial Stiffness Is Reduced by Attainment of Classical Clinical Performance Measures
Authors: Scholze Alexandra , Thies Christina , Cheikhalfraj Mohamed , Wittstock Antje , Pommer Wolfgang , Zidek Walter , Tepel Martin
Published: January 2009

Background: We determined whether attainment of classical clinical performance measures for hemodialysis care improves survival in hemodialysis patients with increased arterial stiffness. Methods: We performed a prospective cohort study of 538 hemodialysis patients with a median follow-up of 19 months (interquartile range 8–30). Arterial stiffness was measured using applanation tonometry. Clinical performance measure targets were hemoglobin value ≥110 g/l, serum albumin value ≥37 g/l and measured single-pool Kt/V urea value ≥1.2. Results: During follow-up, 217 patients (40%) died. In non-survivors, arterial stiffness of large arteries (S1) was significantly higher compared with survivors (p = 0.0002). An analysis of hemodialysis patients who were alive 18 months after inclusion into the study showed that survival was significantly longer in those patients that met ≥2 clinical performance measure targets compared with patients that met ≤1 target (χ2 4.13; p = 0.04). Better attainment of classical clinical performance measures showed a 54% mortality risk reduction. Conclusion: S1 predicted mortality in hemodialysis patients. However, better attainment of classical clinical performance measures significantly improved long-term outcome in hemodialysis patients despite their pronounced increase in arterial stiffness.
Amphetamine-Induced Changes in Dopamine Receptors in Early Postnatal Rat Brain
Authors: Mukda Sujira , Kaewsuk Sukit , Ebadi Manuchair , Govitrapong Piyarat
Published: January 2009

Amphetamines are among the most widely abused drugs. The user population includes a large proportion of women of child-bearing age. The early ontogeny of the axons in the neocortex and other neural structures positions them to influence the development and connectivity of non-aminergic dendrites and axons in these structures. A cascade of abnormalities in neural circuitry may result from the effects of amphetamines on the dopaminergic system. An attempt has been made to investigate the possible changes in the dopaminergic system in neonatal rats (a human third trimester equivalent model) following chronic D-amphetamine exposure. Neonatal rats were administered 5–15 mg/kg D-amphetamine subcutaneously daily from postnatal day 4 to day 10. Several parameters related to the dopaminergic system were measured. The results showed that tyrosine hydroxylase enzyme levels were significantly decreased in the prefrontal cortex, dorsal striatum and nucleus accumbens. Dopamine D1 receptor (DRD1) levels increased in the dorsal striatum whereas dopamine D2 receptor (DRD2) levels significantly decreased in both the prefrontal cortex and the dorsal striatum but significantly increased in the nucleus accumbens. In order to investigate whether these changes occurred at the transcriptional level, DRD1 and DRD2 mRNAs were detected. The results showed that DRD1 mRNA levels were significantly increased in the dorsal striatum whereas DRD2 mRNA levels were significantly increased in all three brain regions. These results indicate that early D-amphetamine exposure altered the dopaminergic system in the developing rat brain. This change may lead to abnormal perinatal stimulation that may yield long-term consequences.
Essential Role of Stem Cell Factor Signaling in Primary Sensory Neuron Development
Authors: Zhang Zhi-Jian , Sieber-Blum Maya
Published: January 2009

Here we show that stem cell factor (SCF) signaling through its receptor, c-kit, is essential for the development of c-kit-expressing small- and medium-diameter primary sensory neurons. We used the W mouse, which is c-kit deficient and has a perinatal lethal phenotype due to a naturally occurring point mutation in the c-kit gene. In c-kit-null newborn mice, 52.5% of substance P immunoreactive and 31.4% of calcitonin gene-related peptide (CGRP) immunoreactive small- and medium-diameter sensory neurons were absent, whereas large-diameter sensory neurons were unaffected. Equivalent deficits occurred during embryogenesis. There was neither a developmental delay nor degeneration of differentiated neurons. We thus conclude that, in the absence of SCF signaling, neural crest-derived progenitors do not differentiate into c-kit-expressing visceral and somatic afferent neurons.
Histone Deacetylase Inhibitor, Trichostatin A, Affects Gene Expression Patterns during Morphogenesis of Chicken Limb Buds in vivo
Authors: Zhao Wanghong , Dai Fangping , Bonafede Alexander , Schäfer Stefan , Jung Manfred , Yusuf Faisal , Gamel Anton J. , Wang Jianlin , Brand-Saberi Beate
Published: January 2009

Acetylation is one of the key chromatin modifications that control gene transcription during embryonic development and tumorigenesis. The types of genes sensitive to such modifications in vivo are not known to date. We investigated the expression of a number of genes involved in embryonic development after treatment with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, in the limbs of chicken embryos. Our results show that TSA affects the expression profiles of some genes that play important roles during limb development. The expression of BMP4, SF/HGF and Twist1 increased, whereas the expression of BMP2, FGF8, Shh, Scleraxis, Myf5 and MyoD was decreased or even inhibited. In contrast, the expression of Pax3, Paraxis, Msx1, CREB, and PCNA was not affected. Our results indicate that the chicken embryo can serve as an effective in vivo model for studying the effect of HDAC inhibitors on gene expression and can be helpful for understanding the role of chromatin remodeling and epigenetic control of gene expression.
Patient-Oriented SCORAD: A Self-Assessment Score in Atopic Dermatitis
Authors: Vourc’h-Jourdain M. , Barbarot S. , Taieb A. , Diepgen T. , Ambonati M. , Durosier V. , Sibaud V. , Stalder J.F.
Published: January 2009

Background: The SCORing Atopic Dermatitis (SCORAD) index is used worldwide to assess the severity of atopic eczema. Patient involvement in the treatment process is of major current interest. There are very few validated patient self-assessment tools for atopic dermatitis (AD). Objective: To develop a self-assessment score for AD patients, the patient-oriented SCORAD (PO-SCORAD) based on the SCORAD index, and to assess its acceptability in a pilot study. Methods:A multicenter working group decided on the initial form of the PO-SCORAD. A prospective, single-center pilot study was then carried out to assess its acceptability and validity. A SCORAD and a PO-SCORAD were applied at baseline and after 18 days; the acceptability of the tool was assessed by questionnaire, its validity by comparing SCORAD and PO-SCORAD on both visits. Results: The study involved 15 children and 18 adults. 80% of the respondents found the questions clear and the form easy to fill in; 96% spent less than 10 min on it. A correlation was found between the SCORAD and the PO-SCORAD. Conclusion:This study shows that self-assessment is feasible in AD, and that there is a correlation between the physician and the patient scores. This study was the first step in validating the PO-SCORAD.
Solar Urticaria Successfully Treated with Intravenous Immunoglobulins
Authors: Maksimovic Laurent , Frémont Guillemette , Jeanmougin Michel , Dubertret Louis , Viguier Manuelle
Published: January 2009

Background: Idiopathic solar urticaria (SU) is a rare type of physical urticaria, occurring immediately after exposure to visible or ultraviolet (UV) light. Treatment is based on sun avoidance and on high doses of antihistamines, but is sometimes inefficient. Methods: We report on a 41-year-old patient with severe SU who was successfully treated with a single course of 2 g/kg of intravenous immunoglobulins (IVIG). Results: A dramatic improvement in UVA and UVB tolerance was rapidly observed, with an increase of up to 10 times the UVA minimal urticarial dose on day 3. The treatment with terfenadine was continued. Healing of photosensitivity was persistent since 100 days after the single course of IVIG, no urticarian reaction was provoked with polychromatic irradiation rising above 8.3 J/cm2 or after UVA doses rising above 15 J/cm2. Conclusion: Use of IVIG in severe SU can be discussed when high-dose antihistamines are inefficient and quality of life is affected.
Age- and Gender-Specific Changes in the Left Ventricular Relaxation
Authors: Okura Hiroyuki , Takada Yuko , Yamabe Azusa , Kubo Tomoichiro , Asawa Koichiro , Ozaki Takeshi , Yamagishi Hiroyuki , Toda Iku , Yoshiyama Minoru , Yoshikawa Junichi , Yoshida Kiyoshi
Published: January 2009

Background—

Although left ventricular diastolic function has been shown to deteriorate with advancing age, its gender-specific change is unknown. The aim of this study was to investigate age- and gender-specific changes in tissue Doppler–derived left ventricular diastolic index, E′.

Methods and Results—

A total of 1333 healthy individual without known heart disease or hypertension (mean age, 55 years; range, 10 to 89) were enrolled and studied. Peak early mitral annular velocity (E′) and peak late mitral annular velocity (A′) were recorded and measured. As an index of the left ventricular relaxation, E′ was used. As an index of the left ventricular filling pressure, E/E′ was calculated. Although systolic indices poorly correlated with age, diastolic indices correlated well with age. Among those aged 30 to 39 and 40 to 49 years, E′ was significantly lower in males than in females. In subjects aged 50 to 59 and 60 to 69 years, E′ was similar in both genders. Among those aged 70 to 79 and 80 to 89 years, E′ was significantly lower in females than in males. Predictors of the lowest quartile of E′ among subjects aged >50 years were age (
P
<0.0001; χ
2
=66.11; odds ratio, 1.08; 95% CI, 1.058 to 1.097) and female gender (
P
=0.002; χ
2
=9.23; odds ratio, 1.68; 95% CI, 1.202 to 2.343).

Conclusion—

Age-related changes in diastolic indices were gender specific. In the elderly population, diastolic function deteriorated more significantly in the female gender than in the male gender. These results may explain the relatively higher incidence in elderly females among patients with diastolic heart failure and higher cardiovascular mortality in the female gender.
Acute Kidney Injury After Cardiac Surgery
Authors: Karkouti Keyvan , Wijeysundera Duminda N. , Yau Terrence M. , Callum Jeannie L. , Cheng Davy C. , Crowther Mark , Dupuis Jean-Yves , Fremes Stephen E. , Kent Blaine , Laflamme Claude , Lamy Andre , Legare Jean-Francois , Mazer C. David , McCluskey Stuart A. , Rubens Fraser D. , Sawchuk Corey , Beattie W. Scott
Published: January 2009

Background—

Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the present study was to identify and determine the prognostic importance of such risk factors.

Methods and Results—

Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration.

Conclusions—

AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.
Clause Structure and Verb Series
Authors: Aboh Enoch Oladé
Published: January 2009

This article argues that in V1-XP-V2 and V1-V2-XP series, V1 merges in the functional domain of the lexical verb (V2). V2 introduces the (internal) argument and is embedded under an AspP whose head is endowed with an EPP feature. Surface word order variations in Kwa (and Khoisan) result from the EPP licensing that triggers V2-object inversion, sometimes followed by V2 movement past the shifted object.
Structural Adjacency and the Typology of Interrogative Interpretations
Authors: Gribanova Vera
Published: January 2009

I point out that the generally accepted theory of single-pair versus pair-list readings for multiple wh-questions in the Slavic family, as instantiated in Bošković 2001a, predicts the wrong result for Russian multiple wh-questions and for coordinated multiple wh-questions in several languages. I suggest a reformulation of the connection between the structure and the interpretation of multiple wh-questions that relies on the structural adjacency of two or more wh-items at LF, and I discuss a number of cases in which this reformulation appears to make the right predictions for multiple wh-questions containing clitics.
Violence as Sign in the Fourth Gospel
Authors: Glancy Jennifer
Published: January 2009

The Gospel of John twins the history of Jesus' body with the history of the temple. On John's telling, intersections of those two violent histories are multiple. In the fourth Gospel, the violence directed against Jesus' body that unfolds in the passion narrative is catalyzed (on a narrative level) by Jesus' own physically enacted violence at the temple site. Jesus' action at the temple, his use of a whip to drive out his fellow Jews, is a form of symbolic communication. Jesus' appearance in the temple, whip in hand, functions as a violent epiphany, a moment of self-revelation akin to his self-revelation at Cana. Recognition of the temple incident as sign forces us to consider what, precisely, Jesus reveals about himself when he picks up a whip to clear men and goods from the space he calls his Father's house. As Roger Friedland and Richard D. Hecht argue, "Violence is a form of communication…. Symbolic violence, profanation, is used by members of one community… in order to mobilize their own communities, to make their definition of reality the dominant one…. By profaning the other's sacred place you make the other profane, an alien with no claim to possession of that space." By encoding violence as sign the Gospel of John not only records the history of violence but becomes an episode in that history.
Christian Martyrdom and the "Dialect of the Holy Scriptures": The Literal, the Allegorical, the Martyrological
Authors: Mitchell Margaret
Published: January 2009

This paper seeks to test a venerable scholarly and popular commonplace: that the ideology of religious martyrdom is based upon and further reflects a literal or even hyper-literal interpretation of Scriptures. Through two test-cases from late antique Christian writings, Tertullian's scorpiace and Origen's exhortatio ad martyrium, I seek to demonstrate the inadequacy of the literal/allegorical dichotomy to comprise and comprehend the complex, ingenious ways in which "the dialect of the holy Scriptures" (Origen's phrase) is claimed to speak in one unambiguous voice that instructs the Christian to accept martyrdom under persecution through confession. Self- and other-characterizations using the labels of "literal" and "allegorical" readings abound in these writings, but are not confined to one side or another. Via such "fighting words," the lexicon of hermeneutical claims of fidelity to or apostasy from the Scriptures is pressed into service by authors who, like Tertullian in Carthage and Origen in Caesarea, craft careful apologetic and protreptic arguments to support the claim that for Christians "it is better to prefer a religious death to an irreligious life."
kěpîr ' ărāyôt in Judges 14:5
Authors: Strawn Brent
Published: January 2009

Data culled from the Hebrew Bible (e.g., Ezek 19:19-9) and, especially, zoology casts light on the odd construct phrase in Judg 14:5, kěpîr ' ărāyôt. The phrase, which may even be a compound word, is best understood as designating a nomadic subadult lion. This makes good sense of a number of details in the narrative, including the lion's location in the vineyards of Timnah and its agressive behavior. It also underscores still further the astonishing nature of Samson's victory over precisely this kind of lion.
Who Is Speaking in Jeremiah 4:19-22? The Contribution of Unit Delimitation to an Old Problem
Authors: Korpel Marjo
Published: January 2009

Study of the unit delimitation in a number of ancient manuscripts lends extra support to the view that the speaker of the lament in Jer 4:19-21 is Lady Zion and that Jer 4:22 is a later addition.
Ezekiel LXX and Exodus Comparisons
Authors: Olley John
Published: January 2009

Ezek. 9:1-12 and 20:26 LXX provide much more explicit association with the exodus than is seen in MT. The translation reflects the late Seleucid period, with oppressive and syncretistic leaders, an interpretation reinforced by the unexpected Aβανα in 20:29.
The Inscriptions Written on Plaster at Kuntillet 'Ajrud
Authors:   Mastin
Published: January 2009

Although conclusions must to some extent remain provisional, enough is known about the inscriptions from Kuntillet 'Ajrud which were written on plaster for an estimate of their significance to be made. If the portion of text which can be studied on a photograph is typical, the script includes both Hebrew and Phoenician letters and indicates a link with north Palestine or with an area with which the Phoenicians traded. Meshel's opinion that the language of these inscriptions is Hebrew is justified. The way in which one text speaks of El, or God, is not in accordance with what is known about Phoenician practice, but is consistent with the usage of the Old Testament. Thus in this text El and Baal are not Phoenician gods. It is likely that information about the men who were in charge of this site can be deduced from these texts: they were from north Palestine.
Another Look at the Oracles about the Nations in the Hebrew Bible. A Response to A. C. Hagedorn
Authors: Geyer John
Published: January 2009

A. C. Hagedorn has suggested that the oracles about the nations in the Hebrew Bible are similar to the Greek manteia. He regards both as primarily political. The context of both is war. In the Greek world there is a close attachment of the person of the prophet/seer to his oracular speech. These speeches may be unsolicited and the prophet may be regarded as mad. This article suggests that the comparison is not valid for a number of reasons, and in particular because the Greek oracles were uttered by individuals on particular occasions whereas the Hebrew oracles are part of a structured whole, liturgical in nature and rooted in the cult.
From Joseph to Daniel: The Literary Development of the Narrative in Daniel 2
Authors: Segal Michael
Published: January 2009

Scholars have recognized the composite nature of the narrative in Daniel 2 based upon certain contradictions within the story. Additional evidence will be marshaled to bolster this claim, including variation in the use of divine names according to the evidence of the Old Greek version. Furthermore, I suggest that a more precise division of the source material can be obtained based upon a philological analysis of the expression (v. 14), and its Akkadian cognates. The earlier stratum of the story presents Daniel as a “second” Joseph, and closely parallels both the story of Genesis 41 and the tale in Daniel 5. The secondary section is analyzed in an appendix in an attempt to identify its literary and historical context, with special attention given to the relationship between the description of God in 2:21 and the depiction of Antiochus IV Epiphanes in Daniel 7:24-26.
Nocturnal Intrusions and Divine Interventions on Behalf of Judah. David's Wisdom and Saul's Tragedy in 1 Samuel 26
Authors: Adam Klaus-Peter
Published: January 2009

A literary strand of narratives about Saul in 1 Samuel emerged in a process of rewriting Israelite-Judean history. 1 Sam 26* and a number of other episodes (1 Sam 10:8; 10:17-27; 13:7a-13a; 14:24-46; parts of 1 Sam 9; 1 Sam 16:1-13; 16:14-23; 17*; 1 Sam 28*, 31*; 2 Sam 1*) present the first Israelite king as a figure that was informed by Greek tragic heroism. More specifically, the themes and the formation of the characters in the story of David's nocturnal intrusion in 1 Samuel 26 are set side by side with the post-classical drama Rhesus. 1 Sam 26 is understood as a narrative comment on Saul's destiny in prophetic tradition. Saul's tragic heroism is described with skl “to act foolishly” 1 Sam 26:21b. Also, Qohelet's royal travesty in Eccl 1:12-2:26 alludes to this notion of Saul as a tragic king who acts foolishly (skl). He is contrasted with his glorious opponent David who succeeds (śkl) in all his endeavours.
Robert Grosseteste's Conclusiones and the Commentary on the Posterior Analytics
Authors: Bloch David
Published: January 2009

This article examines the nature of Robert Grosseteste's commentary on Aristotle's Posterior Analytics with particular reference to his “conclusions” (conclusiones). It is argued (using book 1, chapter 2, of the commentary as a case study) that the simple demonstrative appearance of the commentary, which is very much the result of the 64 conclusions, is in part an illusion. Thus, the exposition in the commentary is not simply based on the strict principles of the Posterior Analytics and on the proof-procedures of Euclidean geometry; rather the commentary is a complicated mixture of different elements of twelfth-century texts and the scholarship of Grosseteste's day.
Time as a Part of Physical Objects: The Modern 'Descartes-Minus Argument' and an Analogous Argument from Fourteenth-Century Logic (William Heytesbury and Albert of Saxony)
Authors: Fitzgerald Michael
Published: January 2009

I argue in the essay that the fourteenth-century logicians William Heytesbury and Albert of Saxony developed an argument I call the Socrates-Minus Argument. Their analysis and rejection of it indicates a direction towards a pragmatic resolution to the contemporary Descartes-Minus Argument. Their resolution is similar to the view adopted today by Peter van Inwagen, namely, that “arbitrary undetached parts of physical objects,” like 'all of Socrates except his finger' simply do not exist. I conclude the fourteenth-century approach does not run afoul of Leibniz's law of the Indiscernibility of Identicals, but utilizes a form of Leibniz's Identity of Indiscernibles that, when combined with a weak “anthropic principle,” yield a pragmatic resolution to the Descartes-Minus Argument.
Defining Islamic accounting: current issues, past roots
Authors: Napier Christopher
Published: January 2009

The emergence of Islamic banks and other financial institutions since the 1970s has stimulated a modern literature that has identified itself as addressing “Islamic accounting”. Much of this literature is prescriptive, though studies of actual practice, and of attitudes to proposed alternatives, are beginning to emerge. Historical research into Islamic accounting is still in a process of development, with a range of studies based on both primary archives and manuals of accounting providing growing insight into accounting in state and private contexts in the Middle East. Other parts of the Muslim world are also the focus of historical accounting research. There is still much to discover, however, before historians can determine the influence of Middle Eastern accounting ideas and practices in other parts of the world. Moreover, the term “Islamic accounting” may simply be a convenient label to group together quite disparate accounting practices and ideas across time and space.