bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychiatric Symptoms in Amnestic and Nonamnestic Mild Cognitive Impairment
Authors: Rozzini L. , Vicini Chilovi B. , Conti M. , Delrio I. , Borroni B. , Trabucchi M. , Padovani A.
Published: November 2007

Background: The information regarding neuropsychiatric symptoms in the subtypes of mild cognitive impairment (MCI) is inadequate. Objective: To describe the behavioral neuropsychiatric symptoms of MCI in two subgroups of MCI patients with different neuropsychological characteristics. Methods: MCI patients are classified as amnestic (aMCI) if they have a prominent memory impairment, either alone or with other cognitive impairments (multiple domains with amnesia), or nonamnestic (naMCI) if a single nonmemory domain is impaired alone or in combination with other nonmemory deficits (multiple domains without amnesia). The Neuropsychiatric Inventory (NPI) was administrated to detect behavioral and psychological disturbances observed by the caregiver. Results: 120 subjects were analyzed: 94 were classified as aMCI and 26 as naMCI. Subjects with aMCI were more compromised than those with naMCI on global cognitive functions. About 85% of MCI patients had some neuropsychiatric symptoms evaluated with the NPI and the most prevalent symptom was depression, followed by anxiety. A significantly higher prevalence of hallucinations and sleep disorders has been observed in the naMCI group in comparison with the aMCI group. Conclusion: Neuropsychiatric symptoms occur in the majority of persons with MCI and may be the earliest manifestation of different diseases, each one associated with different clinical profiles at the stage of MCI.
Topical Delivery of Retinyl Ascorbate
Authors: Abdulmajed Kasem , Heard Charles M.
Published: November 2007

This influence of skin stretching and hair follicle sealing on the delivery of retinyl ascorbate (RA-AsA) to the epidermis was probed in vitro. Porcine ear skin was subjected to stretching by 2 and 4 mm (3.3 and 6.7%, respectively); the hair follicles of other skin sections were located and painstakingly sealed using adhesive. After mounting in Franz cells the skin was dosed with 100 µl of 2.5 mM RA-AsA in methanol/PBS with water as receptor phase. After 24 h the diffused areas were subjected to tape stripping, and the amount of RA-AsA was determined in 5 groups of 9 strips. Statistical analysis of the resulting depth profiles showed that there was no statistical difference between unstretched skin and the skin that had the follicles sealed across the 5 depth bands. Between 0 and 2 mm stretch there were generally significant differences; between 0 and 4 mm p < 0.001 was obtained at each depth. The data from this limited exercise suggest that in native skin the follicular route does not contribute to dermal absorption, but when disturbed (as when stretched) follicular delivery can substantially increase drug delivery into the skin by up to approximately 20–40%. Skin stretching becomes difficult beyond about 7%.
Antioxidant Effect of Alpha-Lipoic Acid against Ethanol-Induced Gastric Mucosal Erosion in Rats
Authors: Şehirli Özer , Tatlıdede Elif , Yüksel Meral , Erzik Can , Çetinel Sule , Yeğen Berrak Ç. , Şener Göksel
Published: November 2007

Background/Aims: This investigation elucidates the role of free radicals in ethanol-induced gastric mucosal erosion and the protective effect of lipoic acid. Methods: After overnight fasting, Wistar albino rats were orally treated with 1 ml of absolute ethanol to induce gastric erosion. Lipoic acid (100 mg/kg) was given orally for 3 days before ethanol administration. Mucosal damage was evaluated 1 h after ethanol administration by macroscopic examination and histological analysis. Additional tissue samples were taken for measurement of malondialdehyde, glutathione (GSH), and myeloperoxidase activity. Production of reactive oxidants and oxidant-induced DNA fragmentation and Na+,K+-ATPase activity were also assayed in the tissue samples. Results: Generation of reactive oxygen species and lipid peroxidation associated with neutrophil infiltration play an important role in the pathogenesis of gastric mucosal damage induced by ethanol. Furthermore, oxidants depleted tissue GSH stores and impaired membrane structure as Na+,K+-ATPase activity was inhibited. On the other hand, lipoic acid treatment reversed all these biochemical indices as well as the histopathological changes induced by ethanol. Conclusion: These data suggest that lipoic acid administration effectively counteracts the deleterious effect of ethanol-induced gastric mucosal injury and attenuates gastric damage through its antioxidant effects.
Total Fundoplication Does Not Obstruct the Esophageal Secondary Peristalsis: Investigation with Pre- and Postoperative 24-Hour pH-Multichannel Intraluminal Impedance
Authors: del Genio G. , Tolone S. , Rossetti G. , Brusciano L. , del Genio F. , Pizza F. , Russo F. , Di Martino M. , Napolitano V. , del Genio A.
Published: November 2007

Aim: To determine the impact of total fundoplication on the spontaneous esophageal clearance, known as secondary peristalsis. Background: Although there is general agreement that total fundoplication is not an obstacle to bolus swallowing (primary peristalsis), whether it is an obstacle to spontaneous esophageal clearance (secondary peristalsis) is still not clear. Based on 24-hour monitoring, multichannel intraluminal impedance was used to calculate the time of spontaneous bolus clearance (BCT). Methods: Mean BCT was prospectively calculated in 15 consecutive patients before and after total fundoplication. BCT was calculated in seconds including all the gastroesophageal reflux episodes, whereas bolus swallows (solid meals and liquid swallows) were excluded from the analysis. Results: BCT was extrapolated from 1,057 episodes in the 623 h of study. Overall, BCT did not change after surgery (13.6 ± 4 vs. 15.2 ± 10 s; p = nonsignificant) and in the upright (12.2 ± 3 vs. 16.5 ± 7 s; p = nonsignificant) and recumbent position (22.9 ± 9 vs. 23.0 ± 9 s; p = nonsignificant). Conclusions: In this study total fundoplication did not affect the BCT by combined 24-hour ph monitoring and multichannel intraluminal impedance.
Malignant and Unclear Histological Findings in Incidentalomas
Authors: Duenschede F. , Bittinger F. , Heintz A. , Musholt T. , Korenkov M. , Kann P. , Ewald P. , Gockel I. , Junginger T.
Published: November 2007

Background: The management of incidentalomas with tumor size 3 cm and larger is still under controversial discussion. Study Design: Clinical charts of 65 patients who underwent adrenalectomy for an incidentaloma were reviewed. Results: Sixty-five patients were operated. There were 28 men and 37 women with a median age of 56.9 years. Median size of all resected lesions was 4.1 cm. Indications for surgery were tumor size equal and larger than 3 cm, recurrent pain, hormone status and patients’ fear of malignancy. In 45 patients, the adenomas did not meet the defined criteria of malignancy. There were 9 cases of adrenal hyperplasia, and two cysts and two hematomas were found in 4 patients. Moreover, 1 schwannoma and 1 myelolipoma were removed. In 3 patients, a primary adrenocortical carcinoma of 3.4, 4.0, and 5.0 cm in diameter, respectively, was identified. In 1 patient, an adrenal cortical carcinoma of 10.0 cm in diameter was operated. In 1 patient, the status (size: 4.5 cm) could not be determined conclusively. Conclusion: Hormonal activity should be determined independent of the size, and lesions with hormonal activity should be resected; in the presence of hormonally inactive masses, removal of tumors of 3 cm and larger in size is recommended.
Agents Blocking the Nuclear Factor-κB Pathway Are Effective Inhibitors of Endometriosis in an in vivo Experimental Model
Authors: González-Ramos Reinaldo , Van Langendonckt Anne , Defrère Sylvie , Lousse Jean-Christophe , Mettlen Marcel , Guillet Alain , Donnez Jacques
Published: November 2007

Background: In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-ĸB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-ĸB and the processes regulated by NF-ĸB in the initial development of endometriotic lesionsin vivo.Methods: Endometriosis was induced in nude mice by intraperitoneal injection of fluorescent-labeled menstrual endometrium. Two NF-ĸB inhibitors (BAY 11-7085 and SN-50) were injected intraperitoneally on days 0, 2 and 4 after endometriosis induction, and endometriotic lesions were recovered on day 5. Number, mass, fluorimetry and surface (morphometry) of endometriotic lesions were quantified. NF-ĸB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method. Results: Both NF-ĸB inhibitors induced a significant reduction in lesion development compared to control mice. NF-ĸB activation and ICAM-1 expression of endometriotic lesions were significantly reduced in treated mice, and cell proliferation was significantly reduced in BAY 11-7085-treated mice. Both inhibitors produced a significant increase in apoptosis of endometriotic lesions, as assessed by active caspase-3 immunostaining and the TUNEL method. Conclusion: This study demonstrates, for the first time, that the NF-ĸB pathway is implicated in the development of endometriotic lesions in vivo and that NF-ĸB inhibition reduces ICAM-1 expression and cell proliferation, but increases apoptosis of endometriotic lesions, diminishing the initial development of endometriosis in an animal model.
Patterns of Loss of Abilities in Instrumental Activities of Daily Living in Alzheimer’s Disease: The REAL Cohort Study
Authors: Lechowski Laurent , de Stampa Matthieu , Denis Bertrand , Tortrat Danièle , Chassagne Philippe , Robert Philippe , Teillet Laurent , Vellas Bruno
Published: November 2007

Background/Aims: To determine patterns of loss of abilities in instrumental activities of daily living (IADL) in community-dwelling women with Alzheimer’s disease (AD). Methods: Sixteen French university hospitals included 471 consecutive women with mild to moderately severe AD (Mini-Mental State Examination scores between 10 and 26) from April 2000 to June 2002 in the noninterventional REAL cohort. At inclusion, 6 and 12 months, IADL were assessed with the Lawton scale. Patterns of loss of abilities in the 8 IADL of the Lawton scale were described using Lawton binary grading. Results: At inclusion, 56.7% of the patients shared the same pattern of loss of abilities and 84.3% had this pattern or variants of it. Frequencies of the 8 incapacities were: 80.7% to do the grocery shopping, 76.0% to take medication, 72.2% to prepare meals, 41.4% to travel on public transportation even when assisted, 40.6% to manage purchases, 30.1% to launder small items, 14.2% to participate in some housekeeping tasks and 11.0% to answer the telephone. Conclusion: In this study including 471 community-dwelling women with AD of the French REAL cohort, the loss of the 8 IADL, assessed with the Lawton binary grading, was homogeneous for more than four fifths of the patients.
Vitreous Fluid of db/db Mice Exhibits Alterations in Angiogenic and Metabolic Factors Consistent with Early Diabetic Retinopathy
Authors: Cohen Margo P. , Hud Elizabeth , Shea Elizabeth , Shearman Clyde W.
Published: November 2007

Background: This study evaluated the postulate that the vitreous of diabetic db/db mice, a genetic model of type 2 diabetes that manifests hyperglycemia and insulin resistance, exhibits alterations in angiogenic and metabolic factors that reflect abnormalities in the retinal microvasculature participatory in the pathogenesis of diabetic retinopathy. Methods: Vitreous obtained from db/db and age-matched nondiabetic db/m mice was analyzed by Western blot for pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF), by immunoassay for type IV collagen, and by measurement of TBARs for lipid peroxide products. Results: Compared to nondiabetic db/m controls, vitreous from db/db mice contained decreased PEDF and increased VEGF (VEGF:PEDF relative ratio 2.2 ± 0.3 and 1.0 ± 0.1 in db/db vs. db/m, respectively; p < 0.05), and elevated concentrations of lipid peroxide products (187 ± 43 and 84 ± 15 ng/ml in db/db vs. db/m, respectively; p < 0.05) and type IV collagen (5.2 ± 0.7 and 3.1 ± 0.4 nmol/ml in db/db vs. db/m, respectively; p < 0.05). These changes were observed at age 18–20 weeks, consistent with an early stage in the development of retinal microvascular pathology. Conclusions: The findings support the potential usefulness of vitreous from the db/db mouse as a model tissue for investigation of pathogenetic factors and assessment of therapeutic interventions in early diabetic retinopathy.
Olmesartan Blocks Inflammatory Reactions in Endothelial Cells Evoked by Advanced Glycation End Products by Suppressing Generation of Reactive Oxygen Species
Authors: Yamagishi Sho-ichi , Matsui Takanori , Nakamura Kazuo , Inoue Hiroyoshi , Takeuchi Masayoshi , Ueda Seiji , Okuda Seiya , Imaizumi Tsutomu
Published: November 2007

Background/Aims: We have previously shown that interaction between advanced glycation end products (AGEs) and their receptor (RAGE) evokes generation of reactive oxygen species (ROS) and subsequently vascular inflammation, thus being involved in the development of diabetic retinopathy. Since there is crosstalk between the AGE-RAGE axis and the renin-angiotensin system in the pathogenesis of early diabetic retinopathy, we investigated in this study whether olmesartan, an angiotensin II type 1 receptor blocker, inhibited the AGE-evoked inflammatory reactions in endothelial cells (ECs) by suppressing ROS generation. Methods: ROS generation was evaluated by dihydroethidium staining. Gene and protein expression were analyzed by reverse-transcription polymerase chain reaction and ELISA, respectively. Results: Olmesartan significantly inhibited the AGE-evoked ROS generation and reduced the expression levels of monocyte chemoattractant protein 1 in microvascular ECs. Olme-sartan also suppressed intercellular-adhesion molecule 1 expression in, and subsequently blocked T-cell adhesion to, AGE-exposed ECs. Conclusions: The present study demonstrates for the first time that olmesartan inhibits AGE-evoked inflammatory reactions in ECs by suppressing ROS generation. Blockade of the renin-angiotensin system by olmesartan may play a protective role against diabetic retinopathy by attenuating the deleterious effects of AGEs through its antioxidative properties.
Antiangiogenic Activity in Tears: Presence of Pigment-Epithelium-Derived Factor
Authors: Abdiu O. , Van Setten G.
Published: November 2007

Background/Purpose: Pigment-epithelium-derived factor (PEDF) is of major importance to prevent neovascularization of the retina. Recently found to occur in the cornea and conjunctival tissue, its presence in tears has this far not been reported. Initial results, based on the analysis of diluted tear fluid samples, even indicated the absence of this factor in human tears. Considering the clinical importance of PEDF as regulator of corneal vascularization, we investigated undiluted human tears. Methods: Samples of 18 healthy individuals were collected and analyzed using a commercial ELISA. Samples were also collected from 5 patients with pterygium and as a positive control 2 samples of subretinal fluid from patients following retinal detachment surgery. Results: PEDF concentrations were below the detection limit (i.e. <0.1 ng/ml) in the majority of samples from the healthy individuals. However, PEDF was discovered in 3 of the samples taken, with significant concentrations of 2, 32 and 53 ng/ml. In the group of 5 patients with pterygium, there were no detectable concentrations of PEDF. Conclusion: PEDF may be found in measurable amounts in human tear fluid of healthy individuals and may therefore play a role in the effects and regulation of PEDF at the ocular surface.
Effects of the Phosphatidylinositol 3-Kinase Inhibitor in a Mouse Model of Retinal Neovascularization
Authors: Yu Wen-Zhen , Zou He , Li Xiao-Xin , Yan Zheng , Dong Jian-Qiang
Published: November 2007

Purpose: To determine the effectsof LY294002, a phosphatidylinositol 3-kinase inhibitor, on suppressing experimental retinal neovascularization in an animal model of ischemic retinopathy. Methods: The effect of LY294002 on the survival of RF/6A cells stimulated by vascular endothelial growth factor (VEGF) was investigated colorimetrically. The inhibitory activity of LY294002 on the migration of cells stimulated with VEGF was measured by cell counting. C57BL/6N mice at postnatal day (P) 7 were exposed to 75 ± 2% oxygen for 5 days (P7–P11) and then returned to room air for 5 days (P12–P17) to induce retinal neovascularization. Beginning on P12, mice received daily intraperitoneal injections of LY294002 or dimethyl sulfoxide and phosphate-buffered saline (control) through P17. Retinal neovascularization was examined by adenosine diphosphatase staining after 5 days in room air and was quantitated histologically by counting the neovascular endothelial cell nuclei anterior to the inner limiting membrane. Results: LY294002 significantly inhibited VEGF-induced survival and migration. LY294002-treated and control animals demonstrated no perfusion regions in the posterior retina. Retinas from control mice at P17 contained neovascular tufts at the junction between the perfused and nonperfused retina. The tufts contained numerous neovascular nuclei. Retinas from mice treated with LY294002 demonstrated a significant reduction in neovascular cell nuclei compared with control mice. Conclusions: LY294002 significantly inhibits retinal neovascularization in a mouse model of retinal neovascularization.
Posterior Subtenon Triamcinolone, Intravitreal Triamcinolone and Grid Laser Photocoagulation for the Treatment of Macular Edema in Branch Retinal Vein Occlusion
Authors: Ozdek Sengul , Tiftikcioglu Deren Yudum , Gurelik Gokhan , Hasanreisoglu Berati
Published: November 2007

Purpose: To evaluate the efficacy of posterior subtenon triamcinolone (PSTT), intravitreal triamcinolone (IVT) injections and grid laser photocoagulation (GLP) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). Material and Methods: Patients with macular edema due to BRVO treated with PSTT, IVT injections or GLP were evaluated retrospectively. Complete ophthalmic examination with fluorescein angiography and optic coherence tomography were noted before and in the 1st, 3rd, and 6th months of the treatment. The visual and anatomical responses were evaluated and compared between the groups using paired t test and one-way ANOVA test. Results: There were 20, 35 and 24 eyes in the PSTT, IVT and GLP groups. In the PSTT group, the mean visual acuity (VA) and central foveal thickness (CFT) were 0.23 ± 0.23 and 413.2 ± 143.5 µm before treatment and 0.23 ± 0.18 and 358.7 ± 109.2 µm at the 3rd month, respectively (p = 0.504 and p = 0.031). The mean VA increased from 0.14 ± 0.15 to 0.33 ± 0.26 and the mean CFT decreased from 518.2 ± 145 to 292.9 ± 121 µm in IVT group at the 3rd month (p = 0.001). The mean VA increased from 0.29 ± 0.25 to 0.47 ± 0.32 (p = 0.001); CFT decreased from 397.3 ± 105.9 to 307.1 ± 88.4 µm (p = 0.005) in the GLP group. VA and CFT changes were significantly different between the groups at the 3rd month (p = 0.031). VA increase was significantly greater in the IVT group than in the PSTT group. Decrease in CFT was the highest in the IVT group (Tukey, p = 0.001). Conclusions: IVT and GLP seemed to be more effective than PSTT for the treatment of BRVO-associated macular edema. Possible complications of IVT and GLP must be weighted with the advantages of each treatment modality for each patient.
No Relation between Angiotensin-Converting Enzyme Gene Polymorphism and Pseudoexfoliation
Authors: Tekeli Oya , Turaçlı M. Erol , Altınok Buket , Akar Nejat , Elhan Atilla Halil
Published: November 2007

Aims: To determine the association between the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism and pseudoexfoliation (PEX) in Turkish patients. Methods: This prospective study consisted of 89 patients with PEX, and 120 controls. The I/D polymorphism of the angiotensin-converting enzyme gene was measured with the use of the polymerase chain reaction method. Results: The distribution of the polymorphism was not significantly different in cases with PEX and controls. The frequencies of the I and D alleles were not significantly different between the groups. Conclusion: According to our findings, I/D polymorphism in the angiotensin-converting enzyme gene does not play any role in the pathogenesis of PEX.
Effects of Acetylcysteine and Dexamethasone on Experimental Corneal Wounds in Rabbits
Authors: Sarchahi A.A. , Maimandi A. , Khodakaram Tafti A. , Amani M.
Published: November 2007

Corneal wound healing often leads to the development of scar tissue with loss of transparency. Reconstitution of transparent corneal stroma depends on the regulation of the biosynthetic activities of postlesional keratocytes as well as to a large extent on the limitation of matrix degradation. It has been shown that 3% concentration of N-acetylcysteine (NAC) improves the healing time of corneal wounds but some corneal haze remains. On the other hand, topical corticosteroids may retard the corneal wound healing but decrease the haze. Thus, the aim of the study was to evaluate whether adding dexamethasone to NAC could reduce the side effects of the two drugs. In this study, experimental corneal wounds were created surgically, up to the depth of one half of the stroma in the center of both eyes of all rabbits. The left eyes were treated topically with 0.9% NaCl as controls and the right eyes were treated with a combination of one drop of 3% NAC and one drop of 0.1% dexamethasone, 6 times per day. Corneal wounds were measured by fluorescein staining every day. The results indicated that the combination of acetylcysteine and dexamethasone significantly increased the mean healing time compared to the control group (p < 0.05). Clinical and histopathologic examinations revealed that the corneal haze in the treatment group was greater than in the control group. It is concluded that treatment of the eyes by a combination of 3% acetylcysteine and 0.1% dexamethasone (if used from the first day of ulceration) may retard the corneal wound healing in rabbits.
A Novel, Local Technique for Studying Rabbit Lacrimal Gland Secretion in situ
Authors: Ding Chuanqing , Rife Lawrence , Nakamura Tamako , Wang Yu-Wen , Kopp Kimberly , Schechter Joel E.
Published: November 2007

Aim: To develop a local approach to study rabbit lacrimal secretion in situ by administering specific secretagogues directly onto the lacrimal gland (LG). Methods: After the rabbit has been anesthetized, the inferior bulbar conjunctiva and underlying connective tissue are blunt dissected. A polyethylene tube, for drug delivery, is inserted through the fibrous membrane overlying the inferior surface of the orbital cavity beneath which the LG resides. Lacrimal fluid is collected by cannulating the lacrimal duct. Results: Pilocarpine induced robust lacrimal fluid secretion from the LG that had been bathed with either pilocarpine or phenylephrine, with no detectable effect on the contralateral LG and salivary secretion. By next giving pilocarpine or phenylephrine to the control LG while the experimental gland used before served as control, we duplicated the results exactly. Conclusion: This novel approach avoids the unwanted systemic effects of intravenous injection and is a promising technique to study rabbit LG secretion in situ.
Plasma Arachidonic Acid Influences Insulin-Stimulated Glucose Uptake in Healthy Adult Women
Authors: Galgani José E. , Aguirre Carolina A. , Uauy Ricardo D. , Díaz Erik O.
Published: November 2007

Background: Fatty acids can modulate lipid metabolism, this is related to insulin resistance (IR). This study evaluated the relationship of plasma fatty acid profile with IR, fuel oxidative metabolism and plasma lipid concentration in ‘healthy’ women. Methods: Sixteen ‘healthy’, sedentary and non-obese women were evaluated under fasting conditions for fuel oxidation, plasma fatty acid profile, free fatty acids, triglycerides, glucose and insulin concentrations. IR, fuel oxidation and plasma lipids were measured under insulin-stimulated conditions. Using the Spearman test the correlation between relevant variables was assessed. Stepwise multiple regression analysis was done to identify the main clinical/metabolic and fatty acid determinants of IR. Results: Plasma arachidonic acid content (%) determined IR, and in combination with insulin-stimulated plasma triglyceride concentration explained 45% of the IR variance. IR was inversely related to physical fitness (rs = –0.48, p = 0.01). The latter was inversely associated to plasma saturated fatty acid content (%) (rs = –0.48, p < 0.01), but directly associated to plasma docosahexaenoic acid content (%) (rs = 0.40, p = 0.04). Conclusions: Support for the hypothesis that specific fatty acids influence IR is provided. Plasma arachidonic acid was associated to IR, independent on clinical/metabolic study variables. Docosahexaenoic and saturated fatty acids could potentially affect insulin action through modulating mitochondrial oxidative function.
Mosaic Evolution and Adaptive Brain Component Alteration under Domestication Seen on the Background of Evolutionary Theory
Authors: Rehkämper Gerd , Frahm Heiko D. , Cnotka Julia
Published: November 2007

Brain sizes and brain component sizes of five domesticated pigeon breeds including homing (racing) pigeons are compared with rock doves (Columba livia) based on an allometric approach to test the influence of domestication on brain and brain component size. Net brain volume, the volumes of cerebellum and telencephalon as a whole are significantly smaller in almost all domestic pigeons. Inside the telencephalon, mesopallium, nidopallium (+ entopallium + arcopallium) and septum are smaller as well. The hippocampus is significantly larger, particularly in homing pigeons. This finding is in contrast to the predictions of the ‘regression hypothesis’ of brain alteration under domestication. Among the domestic pigeons homing pigeons have significantly larger olfactory bulbs. These data are interpreted as representing a functional adaptation to homing that is based on spatial cognition and sensory integration. We argue that domestication as seen in domestic pigeons is not principally different from evolution in the wild, but represents a heuristic model to understand the evolutionary process in terms of adaptation and optimization.
Big Birds and Their Brains: Paleoneurology of the New Zealand Moa
Authors: Ashwell K.W.S. , Scofield R.P.
Published: November 2007

The moa (Dinornithiformes: Aves) are an extinct group of ratites from the North and South Islands of New Zealand. The ancestors of both the moa and the kiwi were isolated from other Gondwanan fauna as much as 80 million years ago and evolved in the absence of large mammalian predators. As such they represent a natural experiment in the removal of mammalian predation pressure on the encephalization of these two groups of ratites. We have used endocranial and skull morphometry in conjunction with high resolution CT scanning of the skulls of 8 species of moa to assess encephalization and brain morphology in moa and compare these features with extant ratites. Absolute brain size among the moa ranged from 17.0 ml for Euryapteryx curtus to 60.0 ml for female Dinornis giganteus. Values for encephalization quotients (EQ) of moa ranged from 0.205 for Euryapteryx gravis of the southern North Island to a mean (± SD) of 0.475 (± 0.026) for Anomalopteryx didiformis, partially overlapping values for extant non-New Zealand ratites (emu: 0.402 ± 0.042; rhea: 0.496 ± 0.016; ostrich: 0.474 ± 0.084). Nevertheless, mean ± SD EQ for all moa examined (0.379 ± 0.065) was significantly lower than EQ for extant non-New Zealand ratites (0.539 ± 0.141). Bending of the endocranial axis was much less among moa than either the kiwi or non-New Zealand ratites, consistent with the caudal position of the foramen magnum and the horizontal carriage of the head and upper neck during life. Endocranial morphology of the moa species examined was similar to that for non-New Zealand ratites, with proportionally similar sizes of the olfactory bulb, Wulst, vagal and maxillomandibular foramina, suggesting that the moa occupied similar diurnal niches with comparable sensory specializations to the emu, rhea and ostrich. No evidence of olfactory specialization (i.e., enlarged olfactory bulbs and increased surface area of the olfactory nasal cavity or cribriform plate) was evident in any of the moa skulls, in contrast to the remarkable nasal and olfactory bulb specializations evident in the skull and brain of the little spotted kiwi (Apteryx owenii). We cannot exclude that isolation in the absence of highly encephalized mammalian predators might have contributed to the lower EQ among moa, but it certainly did not lead to any significant reduction in EQ for kiwi; rather the kiwi embarked on a remarkable path of neurological specialization, which allowed them to exploit a niche usually occupied elsewhere by mammals.
Milk Does Not Affect the Bioavailability of Cocoa Powder Flavonoid in Healthy Human
Authors: Roura Elena , Andrés-Lacueva Cristina , Estruch Ramon , Mata-Bilbao M. Lourdes , Izquierdo-Pulido Maria , Waterhouse Andrew L. , Lamuela-Raventós Rosa M.
Published: November 2007

Background: The beneficial effects of cocoa polyphenols depend on the amount consumed, their bioavailability and the biological activities of the formed conjugates. The food matrix is one the factors than can affect their bioavailability, but previous studies have concluded rather contradictory results about the effect of milk on the bioavailability of polyphenols. Aim: The objective was to evaluate the possible interaction of milk on the absorption of (–)-epicatechin ((–)-Ec) from cocoa powder in healthy humans. Methods: 21 volunteers received three interventions in a randomized crossover design with a 1-week interval (250 ml of whole milk (M-c) (control), 40 g of cocoa powder dissolved in 250 ml of whole milk (CC-M), and 40 g of cocoa powder dissolved with 250 ml of water (CC-W)). Quantification of (–)-Ec in plasma was determined by LC-MS/MS analysis prior to a solid-phase extraction procedure. Results: 2 h after the intake of the two cocoa beverages, (–)-Ec-glucuronide was the only (–)-Ec metabolite detected, showing a mean (SD) plasma concentration of 330.44 nmol/l (156.1) and 273.7 nmol/l (138.42) for CC-W and CC-M, respectively (p = 0.076). Conclusion: Cocoa powder dissolved in milk as one of the most common ways of cocoa powder consumption seems to have a negative effect on the absorption of polyphenols; however, statistical analyses have shown that milk does not impair the bioavailability of polyphenols and thus their potential beneficial effect in chronic and degenerative disease prevention.
To Continue, Modify or Relinquish Driving: Findings from a Longitudinal Study of Healthy Ageing
Authors: Unsworth Carolyn A. , Wells Yvonne , Browning Colette , Thomas Shane A. , Kendig Hal
Published: November 2007

Background: The number and proportion of drivers among people entering later life continues to rise. More information on patterns of driving for older adults is required to improve service provision and traffic planning. Objectives: To map the changes in driving status for a sample of drivers aged 65 years or older over the period 1994–2000, and to identify factors associated with older people continuing, modifying or relinquishing their status as drivers. Methods: The 752 participants were drawn from the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA) program, a longitudinal study of people aged 65 years and older living in the community. Participants were interviewed or contacted for follow-up in 1994, 1996, 1998 and 2000 on a range of topics including their health, functional independence and driving status. Results: Although the number of recent drivers was smaller as participants died or were admitted to nursing homes over the 6-year data collection period, relatively few participants relinquished driving while remaining in the community. Many drivers reported modifying their driving habits over time, including decisions to restrict their driving to their local area during daylight only. Relationships were explored between driving status and the key variables of age, gender, marital status, instrumental activities of daily living (IADL) independence and self-rated measures of income, health, eyesight and hearing. Multivariate analyses indicated that drivers were more likely to modify their driving habits if they were older, dependent in IADL, and rated their eyesight as poor. Similar factors predicted relinquishing driving, but in addition, women were three times more likely to relinquish driving than men (even when health and disability were taken into account) and people who rated their incomes as ‘comfortable’ were more likely to relinquish driving than those with lower incomes. Conclusions: This study confirmed previous evidence that older drivers self-regulate by modifying their driving behavior as they age. However, since few drivers voluntarily relinquish driving, further research is required to identify ways of supporting older drivers to continue to drive safely.
A Systematic Review and Meta-Analysis of the Efficacy of Piracetam and Piracetam-Like Compounds in Experimental Stroke
Authors: Wheble Philippa C.R. , Sena Emily S. , Macleod Malcolm R.
Published: November 2007

Background/Objective: Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. Methods: We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Results: Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1–44.4). The median study quality was 4/10 (inter-quartile range = 4–6). Conclusion: Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias.
In-Hospital Stroke in a Statewide Stroke Registry
Authors: Farooq Muhammad U. , Reeves Mathew J. , Gargano Julia , Wehner Susan , Hickenbottom Susan , Majid Arshad
Published: November 2007

Background:In-hospital stroke (IHS) represents 5–15% of all hospitalized acute stroke cases, and is associated with poor outcomes. IHS represents an important area for prevention since many cases occur in high-risk patients undergoing cardiovascular procedures. Our objectives were to compare the quality of care, treatments, and outcomes of IHS with out-of-hospital stroke (OHS) cases. Methods: A 6-month prospective cohort of IHS and OHS stroke cases from a statewide acute stroke registry of 15 representative hospitals was assembled. Data were abstracted on demographic, clinical characteristics, in-hospital care (including tPA treatment), discharge instructions, and in-hospital outcomes (mortality and modified Rankin Scale [mRS] at discharge). Results:177 (6.5%) of the 2,743 cases in the registry were IHS cases. 40% of IHS cases were admitted with a cardiovascular or neurologically related problem, and 68% underwent an invasive diagnostic or surgical procedure prior to their stroke. IHS cases were less likely to have the cerebral vasculature examined or to have a lipid panel drawn. Compared to OHS, IHS had higher case fatality (14.6 vs. 6.9%; p = 0.04), greater functional impairment (mRS ≧4) (61 vs. 36%; p < 0.001), and were less likely to be discharged home (23 vs. 52%, p < 0.01). Conclusions:In this prospective registry, 1 in 15 acute stroke cases occurred in the hospital, and almost 70% had an invasive procedure undertaken prior to their stroke event. In-hospital cases received similar quality of care as OHS cases, but had significantly worse outcomes.
Carotid Angioplasty Stenting Revisited: Clinical and Radiological (MRI) Outcome
Authors: Ghorab Karima , Macian Francisco , Adoukounou Thierry , Magy Laurent , Chapot René , Vallat Jean-Michel
Published: November 2007

Background: Although carotid angioplasty and stenting (CAS) is widely used to treat carotid stenosis, recent studies point to the inferiority of the procedure compared with carotid endarterectomy. Methods: We present 50 consecutive cases of CAS treated in our unit. Endarterectomy was contraindicated in these patients due to high operative risk. All the patients underwent a diffusion-weighted MRI (DWI) before and after the procedure and had a neurological assessment in a stroke unit. Results: No deaths were recorded until 30 days after the procedure. Six patients [12%, confidence interval at 95% (CI95) = 3.7–20.2] had a positive DWI MRI after the procedure but only 2 (4%, CI95 = 0–9.43) had a worse neurological status. Conclusion: This study shows that CAS is feasible with a low morbid-mortality rate in patients with a high surgical risk. DWI is highly sensitive to detect neurological complications after the procedure.
Differences in Long-Term Survival in Two Lacunar Stroke Types: A 15-Year Follow-Up Study in 782 Cerebral Infarct Patients
Authors: Staals Julie , van Raak Lisette , Hilton Anne , Lodder Jan
Published: November 2007

Background: Mortality studies in lacunar (LAC) stroke are scarce and often characterized by short follow-up time, small patient groups and absence of a nonlacunar stroke group for comparison. Besides, there are no separate long-term prognostic data on LAC stroke subtypes. We performed a long-term mortality study in LAC stroke, subtyping two distinct phenotypes and including nonlacunar ischemic stroke for comparison. Methods: We performedcross-sectional follow-up, determining survival status, after a median of 15.0 years, in 333 first-ever atherothrombotic (AT), 184 cardioembolic (CE) and 265 LAC strokes, distinguishing LAC stroke with (type 2) or without (type 1) asymptomatic LAC lesions on CT. Results: End of follow-up mortality (in 30-day survivors) in LAC stroke (76.2%) was significantly lower than in CE (87.1%; OR 0.48, 95% CI 0.27–0.84), but not AT strokes (79.0%; OR 0.85, 95% CI 0.57–1.26), and was significantly lower in LAC type 1 than type 2 strokes (70.9 vs. 87.5%; OR 0.35, 95% CI 0.17–0.73). Kaplan-Meier analysis showed most favorable survival in LAC type 1 stroke. In the Cox regression analyses, LAC type 1 strokeappearedas an independent predictor of better survival versus LAC type 2, versus AT and versus CE strokes. Conclusions: LAC stroke in general cannot be considered a ‘benign’ stroke type: only long-term survival in patients without concomitant asymptomatic LAC lesions is better than in large-vessel stroke. This difference in long-term survival between the two LAC stroke subtypes should be taken into account in prognostic counselling of individual LAC stroke patients.
Blood-Borne Tissue Factor Activity Predicts Major Cerebrovascular Events in Patients Undergoing Carotid Endarterectomy: Results from a 1-Year Follow-Up Study
Authors: Krupinski Jerzy , Turu Marta M. , Font M. Angels , Catena Esther , Slevin Mark , Morchon Sergio , Rubio Francisco , Badimon Lina , Martínez-González José
Published: November 2007

Background: Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to plaque thrombogenicity. Blood-borne TF activity seems to contribute to a procoagulant state in patients with vascular risk factors. The aim of this study was to assess whether the expression of TF in carotid plaques from patients undergoing carotid endarterectomy (CEA) or/and blood-borne (‘circulating’) TF activity could predict future vascular complications. Methods: A total of 105 consecutive patients (85 male and 20 female aged 61–77years)undergoing CEA for high-grade internal carotid artery were included in the study. Carotid artery specimens were classified into active (n = 52; rich in inflammatory cells) and nonactive plaques (n = 53; poor in inflammatory cells or fibrous). TF mRNA levels in carotid plaques were assessed by real-time PCR (TaqMan Low-Density Arrays) and TF protein levels by Western blot. Blood-borne TF activity and other biochemical parameters, including low-density lipoprotein cholesterol (LDLc) levels and high-sensitivity C-reactive protein, were measured prior to surgery. Patients were followed up for 1 year and vascular and nonvascular complications were scored. Results: TF expression was higher in active CEA plaques. Patients with active CEA plaques exhibited higher plasma LDLc levels (3.6 ± 0.7 vs. 2.1 ± 1 mM, p < 0.05) that positively correlated with plaque TF mRNA levels (p = 0.0125; r = 0.9). Blood-borne TF activity did not correlate with plasma LDLc levels and was unrelated to the anatomo-pathological characteristic of the CEA plaques (thrombosis, rupture, inflammation, lipid core, necrosis or calcification). Circulating TF activity predicted vascular complications at 1 year, including fatal (OR, 1.18; 95% CI, 0.6–2.2, p < 0.01) and nonfatal ischemic stroke (OR, 1.22; 95% CI, 0.5–2.0, p < 0.05) and symptomatic peripheral vascular disease (OR, 1.48; 95% CI, 0.4–2.6, p < 0.005). Conclusions: Blood-borne TF activity prior to CEA but not local TF expression or plasma LDLc levels predict cerebrovascular and peripheral vascular disease events at 1 year in elderly patients subjected to CEA for high-grade carotid stenosis.
A Randomized, Double-Blind Study Comparing the Safety and Efficacy of Clopidogrel versus Ticlopidine in Japanese Patients with Noncardioembolic Cerebral Infarction
Authors: Fukuuchi Yasuo , Tohgi Hideo , Okudera Toshio , Ikeda Yasuo , Miyanaga Yoshitaka , Uchiyama Shinichiro , Hirano Masanori , Shinohara Yukito , Matsumoto Masayasu , Yamaguchi Takenori
Published: November 2007

Background: Patients treated with ticlopidine require careful hematologic monitoring. Clopidogrel may have greater tolerability. However, no direct comparison of these two drugs has been reported and evidence of improved safety with clopidogrel is not yet established in the Japanese population. A comparison of both agents was therefore conducted in Japanese stroke patients. Methods: Patients with noncardioembolic cerebral infarction were randomized to clopidogrel 75 mg or ticlopidine 200 mg once daily for 52 weeks. The primary endpoint was safety; the major secondary endpoint was the incidence of vascular events.Results: Clopidogrel was associated with significantly fewer safety events than ticlopidine (7.0 versus 15.1%; p < 0.001) and no significant difference in efficacy between the two treatments was seen [hazard ratio 0.977 (95% confidence interval: 0.488–1.957)].Conclusions: In Japanese stroke patients, clopidogrel 75 mg is better tolerated than ticlopidine 200 mg once daily.
Automated and Visual Scoring Methods of Cerebral White Matter Hyperintensities: Relation with Age and Cognitive Function
Authors: Tiehuis A.M. , Vincken K.L. , Mali W.P.T.M. , Kappelle L.J. , Anbeek P. , Algra A. , Biessels G.J.
Published: November 2007

Background and Purpose: A reliable scoring method for ischemic cerebral white matter hyperintensities (WMH) will help to clarify the causes and consequences of these brain lesions. We compared an automated and two visual WMH scoring methods in their relations with age and cognitive function. Methods: MRI of the brain was performed on 154 participants of the Utrecht Diabetic Encephalopathy Study. WMH volumes were obtained with an automated segmentation method. Visual rating of deep and periventricular WMH (DWMH and PWMH) was performed with the Scheltens scale and the Rotterdam Scan Study (RSS) scale, respectively. Cognition was assessed with a battery of 11 tests. Results: Within the whole study group, the association with age was most evident for the automated measured WMH volume (β = 0.43, 95% CI = 0.29–0.57). With regard to cognition, automated measured WMH volume and Scheltens DWMH were significantly associated with information processing speed (β = –0.22, 95% CI = –0.40 to –0.06; β = –0.26, 95% CI = –0.42 to –0.10), whereas RSS PWMH were associated with attention and executive function (β = –0.19, 95% CI = –0.36 to –0.02). Conclusion: Measurements of WMH with an automated quantitative segmentation method are comparable with visual rating scales and highly suitable for use in future studies to assess the relationship between WMH and subtle impairments in cognitive function.
Determinants of Change in Quality of Life from 1 to 6 Months following Acute Stroke
Authors: Rønning Ole Morten , Stavem Knut
Published: November 2007

Background and Purpose: Little information is available about change in health-related quality of life (HRQoL) during the first few months following acute stroke, and whether baseline variables can predict who will have the largest improvement in HRQoL. This study assessed the change in HRQoL from 1 to 6 months following acute stroke and the determinants of these changes. Methods:Patients >60 years of age, who had experienced an acute stroke and were admitted to hospital within 24 h of onset, were followed longitudinally. HRQoL was assessed with the Short Form 36 (SF-36) health status questionnaire. Results:Of 550 eligible stroke patients, 315 fulfilled the inclusion criteria and were alive after 30 days. At 1 month, 179 patients responded to the questionnaire, of whom also 140 responded at 6 months following acute stroke. From 1 to 6 months following stroke, all dimensions of the SF-36 improved. The magnitude of change was largest on the role-physical and role-emotional scales and lowest on the bodily pain and mental health scales. Higher physical component summary (PCS) score at 1 month was associated with lower odds of being above the 75th percentile of change in PCS score between the assessments, and higher baseline mental component summary (MCS) score was associated with lower odds of being above the 75th percentile of change in MCS. Treatment in a stroke unit was associated with an increase in the MCS score and higher neurological score with an increase in PCS score of the SF-36. Conclusion: This prospective study showed a considerable improvement in HRQoL from 1 to 6 months after stroke; however, no baseline variables except baseline scores were associated with changes in HRQoL during the 5-month period.