bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dietary Tomato Supplement Prevents Prostate Cancer in TRAMP Mice
Authors: Pannellini Tania , Iezzi Manuela , Liberatore Marcella , Sabatini Federica , Iacobelli Stefano , Rossi Cosmo , Alberti Saverio , Di Ilio Carmine , Vitaglione Paola , Fogliano Vincenzo , Piantelli Mauro
Published: August 2010

Transgenic adenocarcinoma of the mouse prostate (TRAMP) is a model for progressive prostate cancer that mirrors the stages of the human form. In this study, the effects of a diet enriched with processed whole tomatoes on survival, tumorigenesis, and progression of prostate cancer, and the antioxidant and inflammatory status of TRAMP mice were investigated. Tomato diet significantly increased overall survival (P < 0.01), delayed progression from prostatic intraepithelial neoplasia to adenocarcinoma, and decreased the incidence of poorly differentiated carcinoma. Biochemical data disclosed an increase in serum antioxidant activity and a reduction of serum inflammation/angiogenesis biomarkers of particular importance in prostate carcinogenesis. Cancer Prev Res; 3(10); 1284–91. ©2010 AACR.
Molecular Alterations Associated with Sulindac-Resistant Colon Tumors in ApcMin/+ Mice
Authors: Greenspan Emily J. , Nichols Frank C. , Rosenberg Daniel W.
Published: August 2010

Although nonsteroidal anti-inflammatory drugs (NSAID), including sulindac, have been used extensively as chemopreventive agents for colorectal cancer, results are not consistent. NSAIDs, most reportedly sulindac, often do not cause a complete regression of adenomas and some patients develop resistance to NSAID treatment. In this study, we evaluated the effect of sulindac on colon tumorigenesis in the ApcMin/+ mouse model. Sulindac (180 ppm) given in drinking water for 9 weeks to ApcMin/+ mice significantly reduced the size of colon tumors, but actually caused an increase in colon tumor multiplicity relative to untreated controls (average of 5.5 versus 1.6 tumors per mouse, respectively; P < 0.0001). This indicated that the drug could inhibit colon tumor progression but not initiation. As expected, in the small intestine, sulindac significantly reduced tumor size and multiplicity relative to untreated controls (average of 2.3 versus 42.0 tumors per mouse, respectively; P < 0.0001). Generation of a panel of prostanoids was comparably suppressed in the small intestine and colon by sulindac treatment. Sulindac is also known to exert its growth inhibitory effects through regulation of many noncyclooxygenase targets, including p21, β-catenin, E-cadherin, mitochondrial apoptotic proteins, and peroxisome proliferator–activated receptor-γ. We found that sulindac treatment protected against E-cadherin loss in colon tumors, with associated inhibition of nuclear β-catenin accumulation. Importantly, p21WAF1/cip1 and peroxisome proliferator–activated receptor-γ expression were absent in colon tumors from sulindac-treated mice, suggesting that loss of these proteins is necessary for drug resistance. Together, these observations may be translatable to designing novel clinical therapies using combinations of agents that target multiple molecular pathways to overcome sulindac resistance. Cancer Prev Res; 3(9); 1187–97. ©2010 AACR.
Low-Carbohydrate Diets and Prostate Cancer: How Low Is “Low Enough”?
Authors: Masko Elizabeth M. , Thomas Jean A. , Antonelli Jodi A. , Lloyd Jessica C. , Phillips Tameika E. , Poulton Susan H. , Dewhirst Mark W. , Pizzo Salvatore V. , Freedland Stephen J.
Published: August 2010

Previous studies indicate that carbohydrate intake influences prostate cancer biology, as mice fed a no-carbohydrate ketogenic diet (NCKD) had significantly smaller xenograft tumors and longer survival than mice fed a Western diet. As it is nearly impossible for humans to consume and maintain NCKD, we determined whether diets containing 10% or 20% carbohydrate kcal showed similar tumor growth as NCKD. A total of 150 male severe combined immunodeficient mice were fed a Western diet ad libitum, injected with the human prostate cancer cell line LAPC-4, and then randomized 2 weeks later to one of three arms: NCKD, 10% carbohydrate, or 20% carbohydrate diets. Ten mice not injected were fed an ad libitum low-fat diet (12% fat kcal) serving as the reference in a modified-paired feeding protocol. Mice were sacrificed when tumors reached 1,000 mm3. Despite consuming extra calories, all mice receiving low-carbohydrate diets were significantly lighter than those receiving a low-fat diet (P < 0.04). Among the low-carbohydrate arms, NCKD-fed mice were significantly lighter than the 10% or 20% carbohydrate groups (P < 0.05). Tumors were significantly larger in the 10% carbohydrate group on days 52 and 59 (P < 0.05), but at no other point during the study. Diet did not affect survival (P = 0.34). There were no differences in serum insulin-like growth factor-I or insulin-like growth factor binding protein-3 at sacrifice among the low-carbohydrate arms (P = 0.07 and P = 0.55, respectively). Insulin was significantly lower in the 20% carbohydrate arm (P = 0.03). LAPC-4 xenograft mice fed a low-carbohydrate diet (10–20% carbohydrate kcal) had similar survival as mice consuming NCKD (0% carbohydrate kcal). Cancer Prev Res; 3(9); 1124–31. ©2010 AACR.
Clinical Guidelines and Professional Liability: A Short Comment from the Legal Side
Authors: Guillod Olivier
Published: August 2010

The paper explores the relationship between clinical guidelines and medical liability. In order to ascertain the standard of care required for example in ear surgery, courts rely on expert opinions and on existing clinical guidelines from medical societies. They assume that clinical guidelines express the reasonable standard of care that, when followed, insulates surgeons from liability. But judges keep the right to find that a set of clinical guidelines does not sufficiently protect the patient’s health interests. If in contrast clinical guidelines are overly cautious (e.g. by requiring a scientifically questionable examination), there is no incentive stemming from the legal rules on medical liability to deter surgeons from following the guidelines. However, a growing concern about health costs may in the future influence professional behaviour as much as fear of a malpractice suit today.
IRF6 Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign
Authors: Desmyter L. , Ghassibe M. , Revencu N. , Boute O. , Lees M. , François G. , Verellen-Dumoulin C. , Sznajer Y. , Moncla A. , Benateau H. , Claes K. , Devriendt K. , Mathieu M. , Van Maldergem L. , Addor M.-C. , Drouin-Garraud V. , Mortier G. , Bouma M. , Dieux-Coeslier A. , Genevieve D. , Goldenberg A. , Gozu A. , Makrythanasis P. , McEntagart M. , Sanchez A. , Vilain C. , Vermeer S. , Connell F. , Verheij J. , Manouvrier S. , Pierquin G. , Odent S. , Holder-Espinasse M. , Vincent-Delorme C. , Gillerot Y. , Vanwijck R. , Bayet B. , Vikkula M.
Published: August 2010

Van der Woude syndrome (VWS), caused by dominant IRF6 mutation, is the most common cleft syndrome. In 15% of the patients, lip pits are absent and the phenotype mimics isolated clefts. Therefore, we hypothesized that some of the families classified as having non-syndromic inherited cleft lip and palate could have an IRF6 mutation. We screened in total 170 patients with cleft lip with or without cleft palate (CL/P): 75 were syndromic and 95 were a priori part of multiplex non-syndromic families. A mutation was identified in 62.7 and 3.3% of the patients, respectively. In one of the 95 a priori non-syndromic families with an autosomal dominant inheritance (family B), new insights into the family history revealed the presence, at birth, of lower lip pits in two members and the diagnosis was revised as VWS. A novel lower lip sign was observed in one individual in this family. Interestingly, a similar lower lip sign was also observed in one individual from a 2nd family (family A). This consists of 2 nodules below the lower lip on the external side. In a 3rd multiplex family (family C), a de novo mutation was identified in an a priori non-syndromic CL/P patient. Re-examination after mutation screening revealed the presence of a tiny pit-looking lesion on the inner side of the lower lip leading to a revised diagnosis of VWS. On the basis of this data, we conclude that IRF6 should be screened when any doubt rises about the normality of the lower lip and also if a non-syndromic cleft lip patient (with or without cleft palate) has a family history suggestive of autosomal dominant inheritance.
Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter – Case Report
Authors: Preda L. , Dinca O. , Bucur A. , Dragomir C. , Severin E.
Published: August 2010

Cherubism is a particular form of fibrous dysplasia of the jaws. Familial occurrence was reported in most cases. The condition is a rare hereditary disorder with autosomal dominant inheritance, with complete penetrance in males and incomplete penetrance in females and variable expressivity. It is known to be caused by mutations in the gene encoding SH3-domain binding protein 2, SH3BP2 gene. Major diagnostic criteria are cherubic facial appearance, painless hard enlargement of the jaws, and frequently associated dental abnormalities. The aim of the study was to analyze clinical and genetic features of cherubism in a family with 3 daughters in which the youngest one was affected. Clinical and radiographic examinations, hematological and biochemical evaluations and biopsy were performed. Molecular genetic analysis consisted of PCR amplification and direct sequencing of selected exons of the SH3BP2 gene. Cherubism was suspected based on clinical and radiographic examinations of the 9-year-old daughter. She presented asymmetrical enlargement of the mandible, speech and swallowing problems and dental abnormalities on the lower jaw. There was no history of similar clinical findings in any of the daughters or the parents of the affected girl. Abnormal results were obtained by genetic analysis. A c.1244G>A mutation was identified in exon 9 of the SH3BP2 gene in the asymptomatic mother and her affected daughter. The identified mutation in the SH3BP2 gene is probably disease-causing. The asymptomatic mother transmitted the gene mutation to her affected daughter. Our results confirm the reduced penetrance and variable expression of the gene mutation.
The Prognostic Value of the Wuerzburg Bleb Classification Score for the Outcome of Trabeculectomy
Authors: Klink Thomas , Kann Gunda , Ellinger Patrick , Klink Janine , Grehn Franz , Guthoff Rainer
Published: August 2010

Background: The Wuerzburg bleb classification score (WBCS) aims at an objective and standardized assessment of the developing filtering bleb after trabeculectomy, in order to detect and treat bleb scarring at the earliest possible stage of development. The purpose of this retrospective study was to evaluate the prognostic value of the early postoperative WBCS for the long-term outcome of trabeculectomy. Methods: The WBCS is a grading system for clinical bleb morphology. It evaluates the following parameters: vascularization, corkscrew vessels, encapsulation and microcysts. The WBCS of 113 eyes of 113 consecutive patients after trabeculectomy was determined 1 day, 1 and 2 weeks, 3, 6 and 12 months after surgery. Complete success was defined as an intra-ocular pressure (IOP) <21 mm Hg and >20% pressure reduction without glaucoma medication after 1 year. Results: A complete success rate of 73.9% and a qualified success rate of 82.4% were achieved 1 year after surgery. The average total bleb score during follow-up in the success group was always higher than in the failure group, but there was no statistically significant difference at any time. The bleb average score for eyes with an IOP of ≤12 mm Hg after 2 weeks was significantly higher (p = 0.005) than for eyes with an IOP ≧13 mm Hg at the end of follow-up. Conclusion: Patients with a higher early WBCS postoperatively had a significantly lower IOP 1 year after surgery. However, the study could not reveal a certain prognostic value of the early total bleb score using the WBCS for the long-term complete success of trabeculectomy.
Molecular Systematics and Phylogeography of the Genus Lagothrix (Atelidae, Primates) by Means of the Mitochondrial COII Gene
Authors: Ruiz-Garcia Manuel , Pinedo-Castro Myreya Omayra
Published: August 2010

We propose the first molecular systematic hypothesis on the origin and evolution of Lagothrix taxa based on an analysis of 720 base pairs of the cytochrome c oxidase subunit II mitochondrial gene in 97 Lagothrix specimens. All the current Lagothrix forms probably descended from the ancestor L. poeppigii or perhaps (less probably) that of L. lugens. We detected at least 2 lineages in L. poeppigii. L. cana and L. lagotricha were determined to be monophyletic and had lower gene diversity levels compared to L. poeppigii and L. lugens. The most basal ancestors of the current L. poeppigii lineages diverged from the other Lagothrix taxa around 2.5 million years ago, at the end of the Pliocene or at the beginning of the Pleistocene. Clearly, L. cana and L. lagotricha were the 2 most recently derived Lagothrix taxa. The diversification within L. lugens and L. poeppigii may coincide with the first and second Pleistocene glacial periods, respectively, while the diversification within L. cana and L. lagotricha could have occurred in the last 400,000 years, coinciding with the climatological changes provoked by the Illinois-Riss (third) and Wisconsin-Würm (fourth) glaciations.
The Multifactorial Nature of Retinal Vascular Disease
Authors: Kleinman Mark E. , Baffi Judit Z. , Ambati Jayakrishna
Published: August 2010

Retinal vascular disease is the most common cause of macular edema (ME). While there are several etiologies of vascular compromise and subsequent macular leakage, diabetic retinopathy is the most prevalent and continues to challenge ophthalmologists and frustrate patients due to its refractory nature. In response to this epidemic, diabetic ME (DME) along with cystoid ME (CME) have been areas of active investigation both in the clinic and the laboratory. Several decades of basic science research have revealed a growing and complex array of cytokine growth factors and proinflammatory mediators which are capable of inciting the cellular changes that result in accumulation of fluid within the retina. Much of this new molecular foundation provides the current and fundamental scaffold for understanding the pathologic process of ME while simultaneously identifying potential therapeutic targets. Whereas CME has classically been treated with corticosteroids and nonsteroidal antiinflammatory drugs, recent clinical studies have demonstrated improved visual outcomes for DME treatment with light focal/grid laser, corticosteroids and anti-vascular endothelial growth factor antibodies. Yet, each of these treatments has differential effects on the multifactorial mechanisms of ME. This article reviews the anatomical, cellular and molecular derangements associated with ME and highlights specific pathways targeted by current treatments.
Pathophysiology of Macular Edema
Authors: Scholl Stefan , Kirchhof Janna , Augustin Albert J.
Published: August 2010

Macular edema is defined as an accumulation of fluid in the outer plexiform layer and the inner nuclear layer as well as a swelling of Müller cells of the retina. It consists of a localized expansion of the retinal extracellular space (sometimes associated with the intracellular space) in the macular area. Macular edema is a common cause of a sudden or chronic decrease in visual acuity occurring in many ocular diseases such as age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. As a nonspecific sign of many intraocular and systemic diseases, macular edema represents a common final pathway. The existence of the blood-retinal barrier (BRB) formed by intercellular junctions is the precondition required to maintain this physiological status. This status may become severely disturbed by many diseases, finally resulting in macular edema. In this article, the development of macular edema will also be classified by its pathophysiological and pathobiochemical pathways. Vascular components, the dysfunctional BRB, the role of proteins and water fluxes as well as the role of several inflammatory mediators (e.g. angiotensin II, vascular endothelial growth factor, prostaglandins) in the retina will be discussed as responsible mechanisms leading to the development of macular edema.
Differentiating Intraocular Glucocorticoids
Authors: Edelman Jeffrey L.
Published: August 2010

Background: Natural corticosteroids (e.g. hydrocortisone) and synthetic selective glucocorticoid (GC) agonists have been used by ophthalmologists for decades to treat various forms of ocular inflammation. More recently, increased clinical use of locally delivered GC has shown significant benefit for the treatment of multiple retinal indications including macular edema associated with uveitis, retinal vascular occlusions and diabetes. Our current understanding of the clinical utility of specific intraocular GC far surpasses our knowledge of their biologic and pharmacologic activities in the eye. Objective: To present an update on GC receptor (GR) biology in general and as it applies to the eye, and discuss the pharmacokinetics, delivery and pharmacology of the commonly used intraocular GC dexamethasone (DEX), triamcinolone acetonide (TA) and fluocinolone acetonide (FA). Results: DEX, TA and FA are structurally similar but significantly differentiated by their aqueous and lipid solubility, delivery system requirements, pharmacokinetics and interactions with functional GR. Culture of human trabecular meshwork cells and full transcriptome microarray analysis reveals that DEX, TA and FA generate unique gene transactivation and repression profiles as well as potentially distinct biologic responses that are not only steroid structure dependent, but also dose and time dependent. Finally, DEX and FA markedly protect photoreceptors from degenerating in animal models of excessive light and retinitis pigmentosa, respectively. Conclusion: It is tempting to speculate that the unique pharmacokinetic and pharmacologic profiles of the commonly used intraocular steroids and novel future drugs may reveal significant differences in their therapeutic value in patients with macular edema or other inflammatory disease, in their ocular adverse side effect profile, and their ability to normalize glial and neuronal function in diseased retina.
Steroids as Part of Combination Treatment: The Future for the Management of Macular Edema?
Authors: Bandello F. , Battaglia Parodi M. , Tremolada G. , Lattanzio R. , De Benedetto U. , Iacono P.
Published: August 2010

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, plays a major role in vision loss related to diabetic retinopathy. This article presents an in-depth analysis of therapeutic perspectives on DME by means of an approach based on combination therapy with steroids. Corticosteroid drugs have been demonstrated to both inhibit the expression of vascular endothelial growth factor (VEGF) and the VEGF gene, and to have antiinflammatory properties. A treatment algorithm is provided regarding the management of DME. While grid laser photocoagulation remains the first-line therapy for focal vasogenic DME, diffuse DME can be effectively treated by means of intravitreal injections of corticosteroids. Recalcitrant DME can also be managed beneficially with intravitreal steroids. The management of DME is complex, and often multiple treatment approaches are needed. Each form of DME should be properly classified and specifically treated. The combination treatment has still an important role in the combined treatment options for DME.
A Retrospective Longitudinal Study of Caries Development in an Australian Aboriginal Birth Cohort
Authors: Jamieson L.M. , Armfield J.M. , Roberts-Thomson K.F. , Sayers S.M.
Published: August 2010

There are a limited number of longitudinal investigations that examine the progression of dental disease in an indigenous population. Dental examinations of a cohort of indigenous Australians born in Darwin (Australia) between 1987 and 1990 were conducted at ages 6–8 and 11–13 years as part of the Child Dental Health Survey, and 18–20 years as part of the longstanding prospective Aboriginal Birth Cohort (ABC) study. Data was available at all ages for 145 participants. The percent DMFT >0 increased from 17.2 to 44.1 to 81.4%, representing a linear trajectory, whereas mean DMFT increased from 0.3 to 1.0 to 5.6, representing an exponential trajectory. Both trends were significant. At age 18–20 years, the percent DMFT >0 among ABC study participants was 1.2 times that of their counterparts at a national level. The differences were more marked when dental caries severity was considered, with mean DMFT among 18- to 20-year-old ABC study participants being 1.7 times that of similarly aged adults at a national level. Most of this disparity was constituted by the decayed component, with ABC study participants having eight times the mean DT of their national-level counterparts. The findings indicate that Aboriginal young adults in this birth cohort experience a disproportionate amount of dental disease relative to their non-indigenous counterparts, and that this pattern is consistent across the life course.
Use of the Double-Pass Technique to Quantify Ocular Scatter in Patients with Uveitis: A Pilot Study
Authors: Nanavaty Mayank A. , Stanford Miles R. , Sharma Rohit , Dhital Anish , Spalton David J. , Marshall John
Published: August 2010

Purpose: To assess whether the double-pass technique can be employed to quantify the amount of light scattering in patients with uveitis. Methods: 56 eyes of 44 patients with intraocular inflammation were consecutively recruited from the uveitis clinic over 9 months. The degree of intraocular inflammation was recorded according to the Standardization of Uveitis Nomenclature criteria and the eyes were grouped as having anterior, intermediate, posterior or panuveitis. Objective scatter index (OSI) was assessed using a double-pass technique with the Optical Quality Analysis System II. Results: Twenty-four eyes had anterior uveitis, 9 eyes had intermediate uveitis, 10 eyes had posterior uveitis and 13 eyes had panuveitis. The OSI was significantly different between all 4 groups (p = 0.0005). The mean OSI was highest in eyes with anterior uveitis (2.6 ± 3.1) and lowest in posterior uveitis (1.9 ± 1.3). Anterior chamber cells significantly correlated with OSI (R2 = 0.8726, p = 0.007), unlike posterior chamber cells (R2 = 0.0189, p = 0.588) and flare (R2 = 0.0048, p = 0.471). Conclusion: Patients with anterior uveitis have more ocular scatter, and anterior chamber cells scatter more light. This pilot study opens new avenues for research in use of the double-pass technique to assess light scattering in uveitis.
Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo: Effectiveness of Two Different Methods of Treatment
Authors: Casani Augusto Pietro , Nacci Andrea , Dallan Iacopo , Panicucci Erica , Gufoni Mauro , Sellari-Franceschini Stefano
Published: August 2010

The aim of this study is to compare the results obtained using 2 methods of treatment for horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV): the barbecue maneuver + forced prolonged position (FPP) versus the Gufoni maneuver. In a randomized prospective clinical trial, we recruited 147 patients affected by HSC-BPPV. The primary outcome was the absence of vertigo and nystagmus upon application of the supine roll test during the follow-up examination. A statistical evaluation was performed in order to assess whether any parameters (e.g. age, duration of nystagmus and symptoms) could influence in any way the results obtained with the 2 methods of treatment. One hundred and three of the 147 patients affected by HSC-BPPV had the geotropic form and 44 had the apogeotropic type. We were able to transform 29 cases of HSC-BPPV from apogeotropic to geotropic. Finally, we obtained a group of 112 patients who were randomized either to the barbecue + FPP procedure (54 patients) or to the Gufoni maneuver (58 patients). The most evident result is the higher percentage of success (statistically significant) with the Gufoni maneuver at the first session of treatment (86 vs. 61%). The final control showed that 44 out of 54 (81%) patients treated with the barbecue maneuver + FPP were symptom free compared to 54 out of 58 (93%) treated with the Gufoni maneuver. Both the barbecue maneuver + FPP and the Gufoni maneuver are valid methods for treating HSC-BPPV (geotropic forms). However, our results also indicate that the Gufoni maneuver has a significant advantage: the success rate shown at the follow-up, although without statistical significance, is undoubtedly higher (93 vs. 81%). This result, together with the fact that it is very easy to perform and that patient compliance is better, make the Gufoni maneuver the method of choice in HSC-BPPV treatment.
Differential Effects of ICA-27243 on Cloned KV7 Channels
Authors: Blom Sigrid Marie , Schmitt Nicole , Jensen Henrik Sindal
Published: August 2010

Background/Aims: The neuronal KV7 family members (KV7.2–5) are important regulators of neuronal excitability. KV7 channel openers are therefore attractive drug candidates for the treatment of several hyperexcitability disorders. While most described KV7 channel openers discriminate poorly between KV7.2–5, Icagen’s N-(6-chloropyridin- 3-yl)-3,4-difluorobenzamide (ICA-27243) is more potent at KV7.2/3 than at KV7.4 and KV7.3/5 and offers some progress towards subtype selectivity. We have investigated its mode of action on KV7.2 and KV7.4, compared its effect to that of retigabine and studied the combinatorial effect of retigabine and ICA-27243, as these two compounds recognize different binding sites in the channels. Methods: The effects of ICA-27243 and retigabine were studied using voltage-clamp electrophysiology in Xenopus laevis oocytes and rubidium flux in Chinese hamster ovary cells. Results: We found that in contrast to retigabine’s voltage-dependent action on KV7.2, ICA-27243 induced a voltage-independent current on this subtype, which was not observed on KV7.4. Additionally, the combined treatment of KV7.2 and KV7.4 with retigabine and ICA-27243 revealed that the effect of ICA-27243 on KV7.2 dominates that of retigabine, while the compounds act additively and synergistically on KV7.4. Conclusions: These results offer further detailed insight into pharmacological activation of KV7 channels and offer evidence of differential functional and subtype-specific effects by activation of different binding sites in the KV7 channels.
Cross-Cultural Considerations in Administering the Center for Epidemiologic Studies Depression Scale
Authors: Lee Jung Jae , Kim Ki Woong , Kim Tae Hui , Park Joon Hyuk , Lee Seok Bum , Park Jin Woo , McQuoid Douglas R. , Steffens David C.
Published: August 2010

Background: Cultural biases may affect the individual responses to questionnaires for depression and thus confound the international or multiethnic researches on depression. Objective: We compared the diagnostic accuracy of the Center for Epidemiologic Studies Depression Scale (CES-D) for major depressive disorder (MDD) in late life between Korean and US Caucasian elderly. Methods: This study included 332 US Caucasian MDD patients, 116 Korean MDD patients, 125 US Caucasian nondepressed subjects and 700 Korean nondepressed subjects. Differential item functioning and factor analyses were conducted to examine the differences in the response patterns to the CES-D between the US Caucasian and Korean elderly. Diagnostic accuracy of the CES-D for MDD was compared using the area under the receiver-operating characteristic curves (AUC). Results: The Korean elderly were more likely to endorse 6 items compared to the US Caucasians, and the US Caucasian elderly were more likely to endorse 5 items compared to the Koreans. The factor solutions from both ethnic groups were not comparable since the congruence coefficient for the second factor was below 0.46 and that for the first factor did not reach 0.90. The AUC of the CES-D for MDD in Koreans (AUC = 0.850, 95% CI = 0.801–0.899) was significantly smaller than that in US Caucasians (AUC = 0.973, 95% CI = 0.960–0.987), and the optimal cutoff score of the CES-D in the Korean elderly (21/22) was 2 times higher than that in the US Caucasian elderly (10/11). Conclusion: Cross-cultural issues may significantly influence the diagnostic accuracy of depression questionnaires and thus should be considered more carefully than before in both clinical and research settings on multiethnic populations.
Interaction of Kisspeptin and the Somatotropic Axis
Authors: Whitlock B.K. , Daniel J.A. , Wilborn R.R. , Maxwell H.S. , Steele B.P. , Sartin J.L.
Published: August 2010

Kisspeptin, a regulator of gonadotropin-releasing hormone, has been hypothesized as an integrator of nutrition and hormones critical to metabolism and the regulation of reproduction. Growth hormone (GH) is necessary for optimal reproduction and recent evidence suggests that its secretion may be influenced by kisspeptin. The objectives of this study were to determine whether the effect of kisspeptin to stimulate GH release is due to an interaction with growth hormone-releasing hormone (GHRH) or somatostatin (SS), or an effect at the hypothalamus. Intravenous injection and infusion of kisspeptin [500 pmol/kg BW (650 ng/kg)/h × 5 h] to cows (n = 5) increased serum concentrations of luteinizing hormone (LH) but not GH. Pretreatment with kisspeptin injection and infusion in cows (n = 5) reduced the stimulatory effect of GHRH (0.05 µg/kg BW) on GH secretion. However, the magnitude of the GH response to GHRH (assessed by incremental AUC) was not affected by kisspeptin. In these same cows, administration of kisspeptin prevented the increase in GH induced by SS infusion (0.5 µg/kg BW/ h × 1.5 h) withdrawal. Peripheral administration of kisspeptin [200 and 1,000 pmol/kg BW (260 and 1,300 ng/kg)] increased serum concentrations of LH but not GH in ewes (n = 8). However, concentrations of GH were stimulated by central kisspeptin treatment [100 and 200 pmol/kg BW (130 and 260 ng/kg)] in ewes. In addition to activating the gonadotropic axis, kisspeptin can activate the somatotropic axis in ruminants. Present data support the concept of a central site of action for this effect.
Cocaine Use and Abuse Triggering Sporadic Young-Onset Amyotrophic Lateral Sclerosis
Authors: Argyriou Andreas A. , Karanasios Panagiotis , Makridou Alexandra , Vlachou Maria , Giannakopoulou Fotini , Makris Nicolaos
Published: August 2010

To our knowledge, we describe for the first time the case of a male patient with sporadic young-onset amyotrophic lateral sclerosis, most likely attributed to chronic regular cocaine use and abuse. Our case supports the view that cocaine use and abuse may trigger a process of motor neuron degeneration by mechanisms implicating alterations in the neurobiology of the excitatory neurotransmitter glutamate and its receptors.
Aneurysm-Express: Human Abdominal Aortic Aneurysm Wall Expression in Relation to Heterogeneity and Vascular Events – Rationale and Design
Authors: Hurks R. , Hoefer I.E. , Vink A. , de Vries J.-P.P.M. , Heijmen R.H. , Schoneveld A.H. , Kerver M. , Pasterkamp G. , Moll F.L.
Published: August 2010

Objective: Elective repair of abdominal aortic aneurysms (AAA) is associated with significant morbidity and mortality. Large amounts of AAA tissue are necessary to assess heterogeneity among AAA and to correct for potential confounders such as known risk factors. The Aneurysm-express study aims to identify different types of AAA using inflammatory markers in the aneurysm wall that predict postoperative cardiovascular adverse events and mortality, therefore allowing individual risk assessment. Methods: The Aneurysm-express is an ongoing prospective cohort study including AAA patients undergoing open repair. At baseline, blood is drawn, relevant clinical data are collected and the standard diagnostic modalities are performed. During surgery a specimen of the ventral AAA wall is collected and processed to study protein expressions and histology. Interim Results: The study commenced in 2003 in 2 medical centers and currently holds information and material of >300 AAA patients, making it the largest reported aneurysm biobank. Patients are followed for 3 years after surgery for occurring cardiovascular events. The current mean follow-up is 2.1 ± 1.3 years with an event rate of 27%. Conclusion: The large amount of structurally stored tissue and blood combined with clinical characteristics and follow-up provide an excellent soil for indepth pathophysiological analyses, with assessment of AAA heterogeneity in combination with postoperative clinical outcome.
Two-Year Treatment with Cyclosporine Microemulsion for Responder Myasthenia Gravis Patients
Authors: Nagane Yuriko , Suzuki Shigeaki , Suzuki Norihiro , Utsugisawa Kimiaki
Published: August 2010

Background: Cyclosporine (CsA) microemulsion pre-concentrate (MEPC) is a potential steroid-sparing agent for myasthenia gravis (MG) patients; however, there is a paucity of information on the long-term use of CsA MEPC in these patients. Objectives: We examined the efficacy and safety of CsA MEPC therapy administered to MG patients in a 2-year prospective open trial. Methods: From Hanamaki General Hospital and Keio University Hospital, 28 patients provided informed consent. They were enrolled in a prospective open study of CsA MEPC for the initial 6-month observation period; after this 9 were defined as poor responders and excluded from the long-term analysis. Results: The proportion of patients with minimal manifestations or pharmacologic remission status increased significantly. Among 18 patients taking oral prednisolone, 16 (88.9%) achieved a ≧50% reduction in prednisolone dose. Time to attain the minimal quantitative MG (QMG) score (4.2 ± 2.6) was 4.2 ± 4.2 months. Time to attain the minimal dose of prednisolone (2.9 ± 3.1 mg/day) was 9.3 ± 6.9 months. The dose of CsA MEPC was reduced to 2.6 mg/kg/day 2 years after starting the drug. Both total and ocular QMG scores were significantly decreased at 6 months and were generally maintained thereafter. The dose of prednisolone was significantly reduced at 1 year, and further reduced at 2 years. BMI decreased significantly, and 9 of 12 (75%) patients complaining of moon face reported that this had resolved on exit. All patients tolerated CsA MEPC without significant side effects. Conclusion: CsA MEPC therapy in responder MG patients suppressed disease severity, reduced steroid requirements, and alleviated steroid-related side effects. These findings should be confirmed by prospective controlled double-blind trials.
Association of Hospital Arrival Time with Modified Rankin Scale at Discharge in Patients with Acute Cerebral Infarction
Authors: Kwon Young Dae , Yoon Sung Sang , Chang Hyejung
Published: August 2010

This study evaluated the time interval from the development or recognition of a symptom to hospital arrival and investigated its association with the modified Rankin Scale (mRS) at discharge in patients with acute cerebral infarction. A registry was established with ischemic stroke patients admitted to an academic medical center in Korea from January 2005 to March 2009. The time interval between symptom onset and hospital arrival was recorded for each patient and analyzed along with the patient’s clinical characteristics and mRS at discharge. Regardless of initial severity at admission, mRS was significantly different between two groups of hospital arrival: within 3 h and beyond 3 h. Multiple regression analysis also showed more positive mRS scores for patients within the 3-hour arrival, controlling for other significant factors. The findings provided patients’ initiatives for early hospital arrival.
The Relationship between Insulin Resistance and Hypercoagulability in Acute Ischemic Stroke
Authors: Ozkul Ayca , Turgut Eylem Telli , Akyol Ali , Yenisey Cigdem , Kadikoylu Gurhan , Tataroglu Cengiz , Kiylioglu Nefati
Published: August 2010

Aim: Insulin resistance has effects on the coagulation system, which is important in the acute phase of infarct. We examined the relationships between insulin resistance, hemostatic markers and stroke severity in acute ischemic stroke patients. Methods: Protein C (PC), protein S (PS), fibrinogen, von Willebrand factor and antithrombin III (AT III) were studied in 75 acute ischemic stroke patients with and without insulin resistance. Results: The PC and PS levels of insulin-resistant patients were significantly lower than those of non-insulin-resistant patients (PC: 87 ± 19.23 vs. 97.89 ± 13.3%, p = 0.007; PS: 84.75 ± 15.72 vs. 93.21 ± 15.02%, p = 0.02), and both of the anticoagulants were correlated with the homeostasis model assessment (HOMA; r = –0.339, p = 0.003 and r = –0.481, p = 0.000, respectively). Additionally, the NIH Stroke Scale (NIHSS) score correlated negatively with PS (r = –0.329, p = 0.004) and AT III levels (r = –0.235, p = 0.04). The parameters with positive correlations with NIHSS were fibrinogen (r = 0.270, p = 0.019), fasting glucose (r = 0.358, p = 0.008) and HOMA (r = 0.286, p = 0.013). Conclusions: The significant associations between insulin resistance and hemostatic markers may be relevant to stroke severity by causing a procoagulant tendency in acute ischemic stroke.
Cri-du-Chat Syndrome Cytogenetically Cryptic Recombination Aneusomy of Chromosome 5: Implications in Recurrence Risk Estimation
Authors: Ohnuki Y. , Torii C. , Kosaki R. , Yagihashi T. , Sago H. , Hayashi K. , Yasukawa K. , Takahashi T. , Kosaki K.
Published: August 2010

Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry. Most cri-du-chat syndrome cases result from a sporadic de novo deletion that is associated with a low recurrence risk. On rare occasions, however, cri-du-chat syndrome with 5p monosomy can be accompanied by 5q trisomy. This combination is virtually always associated with parental large pericentric inversions. Among previously reported cri-du-chat syndrome cases with 5p monosomy accompanied by 5q trisomy, the aneusomy of chromosome 5 in all but one case was cytogenetically visible using G-banding. When an accompanying 5q trisomy is detected, a significant recurrence risk is expected. We here report on a patient with cri-du-chat syndrome phenotype who initially exhibited a normal karyotype on G-banding but in whom molecular analysis using multiplex ligation-dependent probe amplification and array comparative genomic hybridization revealed a 5p deletion accompanied by a 5q duplication. Parental chromosomal testing led to the identification of a very large pericentric inversion, of which breakpoints resided at the terminal regions of 5p15.31 and 5q35.1. This information was vital for counseling the family regarding the significantly high recurrence risk.
Heritability of Renal Function and Inflammatory Markers in Adult Male Twins
Authors: Raggi Paolo , Su Shaoyong , Karohl Cristina , Veledar Emir , Rojas-Campos Enrique , Vaccarino Viola
Published: August 2010

Background: Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design: We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results: The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways. Conclusion: We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration.
Associations of Local Release of Inflammatory Biomarkers during Carotid Artery Stenting with Plaque Echogenicity and Calcification
Authors: Abe Yuko , Sakaguchi Manabu , Furukado Shigetaka , Okazaki Shuhei , Fujinaka Toshiyuki , Sakoda Saburo , Yoshimine Toshiki , Kitagawa Kazuo
Published: August 2010

Background and Purpose: The purpose of this study is to evaluate whether release of inflammatory markers locally from an atherosclerotic plaque after carotid artery stenting (CAS) is associated with plaque echogenicity and calcification. Methods: The study consisted of 36 patients with 42 severely stenotic carotid arteries who underwent CAS with the distal balloon occlusion. Before CAS, the plaque echogenicity was evaluated by acoustic densitometry and the distribution of calcification was investigated. Systemic blood samples were obtained from the aorta before CAS and local blood samples under distal balloon occlusion just after CAS. Results: The interleukin (IL)-6 and osteopontin (OPN) levels markedly increased at the plaque site in comparison to the systemic values (p < 0.001). Moreover, the local IL-18 level slightly increased compared to the systemic values. In contrast, the local high-sensitive C-reactive protein level slightly decreased. The local matrix metalloproteinase (MMP)-2, tissue inhibitor of MMP-1 and soluble intercellular adhesion molecule 1 levels were not changed. The levels of local IL-6 release were associated with lower echogenicity and less calcification (p < 0.05), while those of local OPN release were independent of plaque characteristics. Conclusions: Our observations show that IL-6 and OPN were released from carotid stenotic lesions after CAS. The association between high levels of IL-6 release and lower plaque echogenicity and less plaque calcification suggests that IL-6 is prone to be released from vulnerable carotid plaques after CAS.
Associations between Brain-Derived Neurotrophic Factor Plasma Levels and Severity of the Illness, Recurrence and Symptoms in Depressed Patients
Authors: Dell’Osso Liliana , Del Debbio Alessandro , Veltri Antonello , Bianchi Carolina , Roncaglia Isabella , Carlini Marina , Massimetti Gabriele , Catena Dell’Osso Mario , Vizzaccaro Chiara , Marazziti Donatella , Piccinni Armando
Published: August 2010

Background: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness. Method: BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale. Results: BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD. Conclusion: These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis.
Serum Brain-Derived Neurotrophic Factor in Euthymic Bipolar Patients on Prophylactic Lithium Therapy
Authors: Suwalska A. , Sobieska M. , Rybakowski J.K.
Published: August 2010

Aim: The aim of the study was to evaluate serum brain-derived neurotrophic factor (BDNF) levels in a group of euthymic bipolar patients on long-term prophylactic lithium treatment and to delineate putative relationships between lithium efficacy and BDNF concentrations. Methods: 141 euthymic bipolar patients (51 male, 90 female) on long-term lithium treatment were studied. Three categories of prophylactic lithium response were delineated: excellent lithium responders (ER; 30 patients), partial lithium responders (PR; 61 patients) and lithium nonresponders (NR; 50 patients). The control group consisted of 75 age- and gender-matched healthy subjects. Results: The lithium-treated patients as a whole group had lower BDNF levels compared to the healthy controls. However, after breaking down the patients into ER, PR and NR, it appeared that only NR had significantly lower BDNF levels compared with the healthy control subjects. No association between the age of the patients, duration of bipolar illness, and serum lithium and BDNF levels was found. Conclusion: The results point to a relationship between lithium prophylactic efficacy and plasma BDNF levels in euthymic bipolar patients where lithium NR had reduced BDNF levels. These findings suggest that serum BDNF is associated with lithium efficacy in bipolar disorder.
Less Is More: Adaptation of Voltage after Battery Replacement in Deep Brain Stimulation for Dystonia
Authors: Blahak Christian , Capelle Hans-Holger , Bäzner Hansjörg , Kinfe Thomas , Hennerici Michael G. , Krauss Joachim K.
Published: August 2010

Background: To maintain the efficacy of deep brain stimulation (DBS) on dystonic symptoms, slight incremental increase in voltage may be necessary over years after a steady state has been reached following the initial programming of optimal settings. So far however, no data are available regarding the adjustment of voltage after implantable pulse generator (IPG) replacement to achieve sustained optimal control of dystonia with the least side effects. Methods: We analyzed stimulation settings before and after IPG replacement for battery depletion (n = 61) in 18 patients with chronic DBS of the globus pallidus internus or the ventral intermediate nucleus of the thalamus for dystonia. Results: The stimulation intensity could be significantly reduced by 24.8% after IPG replacement. The amount of voltage reduction was equal between bipolar and monopolar stimulation modes (24.9 vs. 24.3%, p = 0.89) and significantly correlated with the magnitude of stimulation intensity before IPG replacement (ρ = 0.429, p = 0.001). Conclusions: After IPG replacement, in patients with DBS for segmental dystonia the voltage can be reduced by approximately 25%. This phenomenon might be explained by a gradual decrease in the electrical energy effectively delivered by the IPG in the course of the lifetime of the battery or neuroplastic processes in particular in the period around battery replacement.