bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, Tolerability and Pharmacokinetics of MCI-186 in Patients with Acute Ischemic Stroke: New Formulation and Dosing Regimen
Authors: Kaste Markku , Murayama Satoru , Ford Gary A. , Dippel Diederik W.J. , Walters Matthew R. , Tatlisumak Turgut ,   for the MCI-186 study group
Published: October 2013

Background and Purpose: MCI-186 (edaravone) is a free radical scavenger approved in Japan since 2001 for the treatment of patients with acute ischemic stroke within 24 h from the onset of symptoms. It was recommended by the Japanese Guidelines for the Management of Stroke 2004. Our aim was to investigate the safety, tolerability and pharmacokinetics of a new formulation and dose regimen (intravenous bolus plus infusion) of MCI-186 suitable for the treatment of acute ischemic stroke in Europe because the Japanese treatment protocol includes twice-a-day intravenous infusion of MCI-186 for a maximum of 14 days. Such a treatment protocol is not very practical in Europe, where hospital stay is much shorter in acute hospitals. Methods: In a double-blind, placebo-controlled randomized clinical trial we studied two dosing regimens, each in a cohort of 18 patients. Patients were randomized in a 2:1 ratio in both cohorts to receive MCI-186 or placebo. Review of safety and plasma concentration data from the first cohort (loading dose 0.08 mg/kg + 0.2 mg/kg/h infusion) preceded the second cohort (loading dose 0.16 mg/kg + 0.4 mg/kg/h infusion). Safety parameters included adverse events, severe adverse events, physical examinations, local reactions at infusion site, ECG, clinical chemistry and hematology, modified Total Neuropathy Score and CT scans. Results: Mean age and National Institutes of Health Stroke Scale (NIHSS) score on admission of patients in cohorts 1 and 2 and the placebo group were 64, 63, and 69 years and 5, 5, and 6, respectively. The number of treatment emergent adverse events that occurred was 109, most of which were transient, mild or moderate. Both doses of the new formulation and dosing regimen were well tolerated. After the initiation of the infusion, plasma concentrations of MCI-186 reached or exceeded prespecified target levels within 24 h in both MCI-186 cohorts, which were in the putative therapeutic range in humans. Geometric mean values of MCI-186 plasma concentration at the end of the infusion in cohorts 1 and 2 were 391 and 1,595 ng/ml, respectively. Conclusions: The primary objective of the present study, safety and tolerability of the new formulation and dosing regimen, was achieved. The new formula and both dosing regimens were well tolerated and achieved intended plasma concentrations suitable for larger safety studies before pivotal trials.
Correlation between Protoporphyrin IX Fluorescence Intensity, Photobleaching, Pain and Clinical Outcome of Actinic Keratosis Treated by Photodynamic Therapy
Authors: Piffaretti Filippo , Zellweger Matthieu , Kasraee Behrooz , Barge Jérôme , Salomon Denis , van den Bergh Hubert , Wagnières Georges
Published: October 2013

Background: Photodynamic therapy (PDT) with Metvix® is a good therapeutic option to treat actinic keratosis, but it presents drawbacks (pain, lesion recurrences, heterogeneous outcome), emphasizing the possible need to individualize treatment. Objective: We assessed whether PDT clinical outcome and pain during treatment were correlated with protoporphyrin IX fluorescence intensity and photobleaching. Methods: 25 patients were treated by Metvix PDT. The outcome was evaluated after 1.3 (±0.4), 7.6 (±1.8), 13.2 (±1.2) and 33.6 (±3.0) months. After administration of Metvix, red light (632 ± 10 nm) was delivered with a light-emitting diode panel device. The outcome was assessed on a cosmetoclinical scale. Results: All patients who showed a fluorescence level before PDT treatment above a certain threshold had a complete recovery at 33.6 (±3.0) months. Conclusion: Our approach could be used to individualize PDT treatment based on the pretreatment fluorescence level, and to predict its long-term outcome.
Neurothrombectomy for the Treatment of Acute Ischemic Stroke: Results from the TREVO Study
Authors: Jansen Olav , Macho Juan M. , Killer-Oberpfalzer Monika , Liebeskind David , Wahlgren Nils ,   on behalf of the TREVO Study Group
Published: October 2013

Background: Fast recanalization has been shown to be one of the most important factors for good clinical outcome in stroke patients with acute large vessel occlusion. While intravenous thrombolysis has been shown to be of limited effect in patients with large clot burden, intra-arterial neurothrombectomy offers a new and promising possibility to achieve high recanalization rates within a short time. The Trevo device is a stent-like retriever and was primarily designed to remove thrombus in patients experiencing an acute ischemic stroke. We report on the results of the TREVO Study, which was a prospective, multicenter study in acute stroke patients treated with the Trevo device. Methods: Patients were recruited in seven European centers under the control of an external monitor. Centers were selected because of their long experience with interventional stroke therapy especially with neurothrombectomy. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and NIHSS scores of 8-30 and treatable within 8 h of symptom onset. The primary endpoint was revascularization, defined as at least TICI (thrombolysis in cerebral infarction) 2a. The revascularization scores were assessed by an independent core lab. Secondary endpoints were clinical outcome at 90 days (mRS 90), any device-related serious adverse events and the rate of symptomatic intracerebral hemorrhages. Results: 60 patients were enrolled. The overall recanalization rate (≥TICI 2a) was 91.7% and TICI 2b and 3 was achieved in 78.3%. At 90 days, 55% of the patients had a favorable neurological outcome (mRS 0-2) and 20% had died. Patients with successful recanalization (TICI 2a,b/3) had a good 90-day neurological outcome (mRS 0-2) in 60%, whereas no patient without recanalization had a mRS 90 <3. The overall rate of symptomatic intracerebral hemorrhage according to the SITS-MOST criteria was 5% (3/60). Conclusions: The study suggest that the Trevo Stentriever™ is a safe and effective device, which may offer the possibility of a high reperfusion rate and a high rate of patients with good clinical outcome after acute ischemic stroke due to proximal arterial occlusion. Randomized trials comparing intravenous thrombolysis with neurothrombectomy are now urgently needed to evaluate this new approach of interventional stroke therapy.
Neuropsychiatric Symptom Profile Differs Based on Pathology in Patients with Clinically Diagnosed Behavioral Variant Frontotemporal Dementia
Authors: Léger Gabriel C. , Banks Sarah J.
Published: October 2013

Background: Behavioral variant frontotemporal dementia (bvFTD) is pathologically heterogeneous. With emerging therapeutics, determining underlying pathology during life is increasingly important. Neuropsychiatric symptoms are prevalent and diagnostic in bvFTD. Methods: We assessed the neuropsychiatric profile of patients with clinically diagnosed bvFTD as a function of pathology at autopsy. Patients with a clinical diagnosis of bvFTD at the initial visit were selected from the National Alzheimer's Coordinating Center (NACC) database. Neuropsychiatric symptoms endorsed on the Neuropsychiatric Inventory Questionnaire (NPI-Q) were analyzed. Results: Of 149 patients with clinically diagnosed bvFTD, pathology was primarily Alzheimer's disease (AD) in 20.5%. These patients differed from those with underlying frontotemporal lobar degeneration: patients with AD pathology (plaques and tangles) were more likely to have hallucinations, delusions, or agitation. Patients were further differentiated into tau-positive (30% of cases, including Pick's disease, FTD and parkinsonism with tau-positive or argyrophilic inclusions, and other tauopathies) or tau-negative cases (70% of cases, including bvFTD tau-negative ubiquitin-positive inclusions). These patients also differed in some of the neuropsychiatric symptoms seen. Tau-negative cases were more likely to demonstrate depression, delusions, and changes in appetite and eating. Conclusions: These preliminary findings contribute to our increasing ability to predict, using simple clinical tools, the neuropathological underpinnings of bvFTD during life.
The Procyonid Social Club: Comparison of Brain Volumes in the Coatimundi (Nasua nasua, N. narica), Kinkajou (Potos flavus), and Raccoon (Procyon lotor)
Authors: Arsznov Bradley M. , Sakai Sharleen T.
Published: October 2013

The present study investigated whether increased relative brain size, including regional brain volumes, is related to differing behavioral specializations exhibited by three member species of the family Procyonidae. Procyonid species exhibit continuums of behaviors related to social and physical environmental complexities: the mostly solitary, semiarboreal and highly dexterous raccoons (Procyon lotor); the exclusively arboreal kinkajous (Potos flavus), which live either alone or in small polyandrous family groups, and the social, terrestrial coatimundi (Nasua nasua, N. narica). Computed tomographic (CT) scans of 45 adult skulls including 17 coatimundis (9 male, 8 female), 14 raccoons (7 male, 7 female), and 14 kinkajous (7 male, 7 female) were used to create three-dimensional virtual endocasts. Endocranial volume was positively correlated with two separate measures of body size: skull basal length (r = 0.78, p < 0.01) and basicranial axis length (r = 0.45, p = 0.002). However, relative brain size (total endocranial volume as a function of body size) varied by species depending on which body size measurement (skull basal length or basicranial axis length) was used. Comparisons of relative regional brain volumes revealed that the anterior cerebrum volume consisting mainly of frontal cortex and surface area was significantly larger in the social coatimundi compared to kinkajous and raccoons. The dexterous raccoon had the largest relative posterior cerebrum volume, which includes the somatosensory cortex, in comparison to the other procyonid species studied. The exclusively arboreal kinkajou had the largest relative cerebellum and brain stem volume in comparison to the semi arboreal raccoon and the terrestrial coatimundi. Finally, intraspecific comparisons failed to reveal any sex differences, except in the social coatimundi. Female coatimundis possessed a larger relative frontal cortical volume than males. Social life histories differ in male and female coatimundis but not in either kinkajous or raccoons. This difference may reflect the differing social life histories experienced by females who reside in their natal bands, and forage and engage in antipredator behavior as a group, while males disperse upon reaching adulthood and are usually solitary thereafter. This analysis in the three procyonid species supports the comparative neurology principle that behavioral specializations correspond to an expansion of neural tissue involved in that function.
Head Injury Incidence and Mortality in New Zealand over 10 Years
Authors: Kool Bridget , Chelimo Carol , Ameratunga Shanthi
Published: October 2013

Background: Although reducing the burden of head injuries is an important focus of several injury prevention initiatives, they remain a large proportion of injury-related deaths. In New Zealand, trends over time and the socio-economic distribution of the cause-specific incidence of head injuries have received little attention. Methods: We analyzed primary hospitalizations (2000-2009) and deaths (1999-2008) due to head injury using national mortality and hospital discharge databases, specifically exploring variations in age-specific rates by major causes over time and by socio-economic deprivation. Population-based incidence rate estimates were calculated using census denominators. Results: Children aged <5 years and adults aged ≥65 years had the highest rates of hospitalization and mortality, respectively. Transport-related incidents and falls were the leading causes, with most fatal injuries occurring on roads and most hospitalized injuries occurring at home. There was a significant increase in mortality rates among older adults over the decade, and in most age groups, mortality rates increased with increasing levels of socio-economic deprivation. Conclusions: The findings of this review alongside the significant risks of premature death and disability reinforce the need to explore policies that address the specific causes as well as socio-economic inequalities in their distribution in New Zealand.
A Comparative Study on Culture Conditions and Routine Expansion of Amniotic Fluid-Derived Mesenchymal Progenitor Cells
Authors: Gucciardo L. , Ochsenbein-Kölble N. , Ozog Y. , Verbist G. , Van Duppen V. , Fryns J.P. , Lories R. , Deprest J.
Published: October 2013

Background: Amniotic fluid (AF) cell populations will be applied in perinatology. We aimed to test the feasibility of large-scale cell expansion. Study Methods: We determined the best out of three published expansion protocols for mesenchymal progenitors (AF samples, n = 4) in terms of self-renewal ability. Characterization was performed based on morphology, surface marker analysis, cytogenetic stability, and differentiation potential. The conditions for the best self-renewal ability were further determined in a consecutive series (n = 159). Results: The medium containing fetal bovine serum (FBS), epidermal growth factor, insulin, transferrin, and tri-iodothyronine, combined with seeding on gelatin-coated wells, best stimulated the growth of cells with mesenchymal features, as demonstrated by flow cytometry; however, only osteogenic differentiation was possible. Large-scale testing (n = 44) failed to confirm a robust self-renewal ability. Better results were obtained (n = 88) using optimized FBS or an increased initial cell density. Eventually over 81% of cultures continued growing after the initial medium change and had mesenchymal features but failed differentiation assays. Discussion: Routine in vitro expansion of AF-derived mesenchymal cells remains problematic. Despite an increase in successful cell cultures from 40 up to 80% using optimized serum and an increased cell density, eventually cells failed to demonstrate differentiation abilities. Routine isolation and expansion from unselected AF samples remains a challenge.
Glycine 1.5% for Irrigation Should Be Abandoned
Authors: Hahn Robert G.
Published: October 2013

Background: Glycine 1.5% has long maintained a dominating role as an irrigating solution for monopolar transurethral resection of the prostate (TURP), as well as for certain other transurethral procedures. Materials and Methods: This review summarizes the findings of systematic experimental and clinical studies in which glycine 1.5% for irrigation was infused/absorbed and the outcome compared to at least one other irrigating fluid, including the isotonic saline used for bipolar TURP. Results: There were 11 studies in animals, 3 in volunteers and 6 in patients undergoing TURP. With only one exception, which is probably due to low power, these studies either show a poorer outcome after administration or absorption of glycine solution or else that glycine 2.2% is more toxic than glycine 1.5%. The poorer outcomes consisted of more tissue damage or higher mortality (animals) or more symptoms (volunteers and patients). Conclusion: The safety of monopolar TURP would be improved by replacing glycine 1.5% with some other electrolyte-free fluid. The author argues that glycine 1.5% should be abandoned completely.
Mild Cognitive Impairment: Clinical and Imaging Profile in a Memory Clinic Setting in India
Authors: Alladi Suvarna , Shailaja Mekala , Mridula Kandadai Rukmini , Haritha Chowdary Arikaudi , Kavitha Nallapareddy , Khan Shujath Ali , Divyaraj Gollahalli , Kaul Subhash
Published: October 2013

Background: Despite the increasing burden of dementia in developing countries, mild cognitive impairment (MCI) continues to be underexplored. MCI has conventionally been identified based on clinical profile, but recently, biomarkers suggestive of Alzheimer's disease pathology have been included in the revised National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria. In this study, we evaluated the profile of MCI in a memory clinic in India and explored the applicability of the revised NIA-AA criteria in a limited resource setting. Methods: Consecutive subjects evaluated at the memory clinic for mild memory complaints were included and underwent clinical and neuropsychological examination as well as standard brain imaging. A subset of patients was subjected to imaging biomarker studies as a part of routine clinical practice. Results: Among the 1,190 patients evaluated during the study period, 226 (19.0%) presented with mild memory complaints. Cerebrovascular disease was a common secondary cause. Nearly half of the patients (109 of 226) had MCI according to the modified Petersen criteria. All MCI subjects were educated and the majority were male. A total of 12% of the cohort was classified by imaging biomarkers as having MCI with intermediate likelihood of AD according to the NIA-AA criteria. Conclusion: In the setting of urban India, MCI is an emerging problem; therefore, it was feasible to operationalise the revised NIA-AA criteria in identifying subjects with MCI with intermediate likelihood of AD.
Clinical Utility of Short Social Cognitive Tests in Early Differentiation of Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease
Authors: Buhl Christian , Stokholm Jette , Gade Anders
Published: October 2013

Background: Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can be found in bvFTD. Aim: The objective of this study is to investigate whether short and easily administered tests of social cognition are useful in providing clinical information which might aid in the differentiation of bvFTD from AD in the early stages of bvFTD. Methods: 11 patients diagnosed with bvFTD and 10 patients diagnosed with AD completed a neuropsychological assessment comprising global, executive and social cognitive tasks. Results: Measures of global cognitive function showed no significant difference between the two groups, whereas even the short social cognitive measures (the Reading the Mind in the Eyes Test and the Emotion Hexagon) showed significant group differences, reflecting a poorer performance by the bvFTD group. Conclusion: Our results suggest that it may indeed be relevant to include short and easily administered measures of social cognition in the differential diagnosis of early bvFTD and AD.
A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis
Authors: Kato Akihiko , Tsuji Takayuki , Sakao Yukitoshi , Ohashi Naro , Yasuda Hideo , Fujimoto Taiki , Takita Takako , Furuhashi Mitsuyoshi , Kumagai Hiromichi
Published: October 2013

Background/Aims: Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods: We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI)], which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results: Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01). Conclusion: GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients.
The Tilapias' Chromosomes Influencing Sex Determination
Authors: Cnaani A.
Published: October 2013

The sex chromosomes of tilapias (family Cichlidae; genera Oreochromis, Sarotherodon and Tilapia) have been studied for over 50 years, which has gained interest from both agricultural and basic scientific perspectives. Several closely related tilapia species which can interbreed have been studied, and it has been repeatedly demonstrated that there is variation within and between species in the chromosomal sex-determination mechanism. Both male and female heterogametic sex-determination systems have been characterized, as well as epistatic and environmental influences on sex determination. Three different linkage groups (LG1, LG3 and LG23) have been identified as sex-associated chromosomes and have been subjected to further cytogenetic research and analyses of the genes located around the sex-determining region. Variation in the genetic and physical characteristics of the sex chromosomes makes tilapias an excellent model system for studying the evolution of vertebrate sex chromosomes. This review summarizes the progress made along 5 decades of research and the current knowledge of the tilapias' sex chromosomes.
Negative g-Force Ocular Trauma Caused by a Rapidly Spinning Carousel
Authors: Moisseiev Elad , Dotan Gad
Published: October 2013

We present a case of a 10-year-old boy who presented with bilateral diffuse subconjunctival hemorrhages after spinning rapidly on a carousel attached to an electrical scooter. We present his clinical course and discuss the physics and pathophysiology of this unique mechanism of ocular trauma.
Branchio-Otic Syndrome Caused by a Genomic Rearrangement: Clinical Findings and Molecular Cytogenetic Studies in a Patient with a Pericentric Inversion of Chromosome 8
Authors: Schmidt T. , Bierhals T. , Kortüm F. , Bartels I. , Liehr T. , Burfeind P. , Shoukier M. , Frank V. , Bergmann C. , Kutsche K.
Published: October 2013

Branchio-oto-renal (BOR) syndrome is an autosomal dominantly inherited developmental disorder, which is characterized by anomalies of the ears, the branchial arches and the kidneys. It is caused by mutations in the genes EYA1,SIX1 and SIX5. Genomic rearrangements of chromosome 8 affecting the EYA1 gene have also been described. Owing to this fact, methods for the identification of abnormal copy numbers such as multiplex ligation-dependent probe amplification (MLPA) have been introduced as routine laboratory techniques for molecular diagnostics of BOR syndrome. The advantages of these techniques are clear compared to standard cytogenetic and array approaches as well as Southern blot. MLPA detects deletions or duplications of a part or the entire gene of interest, but not balanced structural aberrations such as inversions and translocations. Consequently, disruption of a gene by a genomic rearrangement may escape detection by a molecular genetic analysis, although this gene interruption results in haploinsufficiency and, therefore, causes the disease. In a patient with clinical features of BOR syndrome, such as hearing loss, preauricular fistulas and facial dysmorphisms, but no renal anomalies, neither sequencing of the 3 genes linked to BOR syndrome nor array comparative genomic hybridization and MLPA were able to uncover a causative mutation. By routine cytogenetic analysis, we finally identified a pericentric inversion of chromosome 8 in the affected female. High-resolution multicolor banding confirmed the chromosome 8 inversion and narrowed down the karyotype to 46,XX,inv(8)(p22q13). By applying fluorescence in situ hybridization, we narrowed down both breakpoints on chromosome 8 and found the EYA1 gene in q13.3 to be directly disrupted. We conclude that standard karyotyping should not be neglected in the genetic diagnostics of BOR syndrome or other Mendelian disorders, particularly when molecular testing failed to detect any causative alteration in patients with a convincing phenotype.
Interdisciplinary European Guidelines on Metabolic and Bariatric Surgery
Authors: Fried Martin , Yumuk Volkan , Oppert Jean-Michel , Scopinaro Nicola , Torres Antonio J. , Weiner Rudolf , Yashkov Yuri , Frühbeck Gema
Published: October 2013

In 2012, an outstanding expert panel derived from IFSO-EC (International Federation for the Surgery of Obesity - European Chapter) and EASO (European Association for the Study of Obesity), composed by key representatives of both Societies including past and present presidents together with EASO's OMTF (Obesity Management Task Force) chair, agreed to devote the joint Medico-Surgical Workshop of both institutions to the topic of metabolic surgery as a pre-satellite of the 2013 European Congress on Obesity (ECO) to be held in Liverpool given the extraordinarily advancement made specifically in this field during the past years. It was further agreed to revise and update the 2008 Interdisciplinary European Guidelines on Surgery of Severe Obesity produced in cooperation of both Societies by focusing in particular on the evidence gathered in relation to the effects on diabetes during this lustrum and the subsequent changes that have taken place in patient eligibility criteria. The expert panel composition allowed the coverage of key disciplines in the comprehensive management of obesity and obesity-associated diseases, aimed specifically at updating the clinical guidelines to reflect current knowledge, expertise and evidence-based data on metabolic and bariatric surgery.
Tissue Advanced Glycation End Product Deposition after Kidney Transplantation
Authors: Crowley Lisa E. , Johnson Catherine P. , McIntyre Natasha , Fluck Richard J. , McIntyre Christopher W. , Taal Maarten W. , Leung Janson C.H.
Published: October 2013

Background: Tissue advanced glycation end products (AGEs) accumulate in chronic kidney disease (CKD) and are a measure of cumulative metabolic stress. Measurement of tissue AGEs by skin autofluorescence (SAF) correlates well with cardiovascular outcomes in dialysis patients. SAF levels in transplant recipients relative to CKD and dialysis patients have not been previously studied, and the impact of transplantation on SAF levels in dialysis patients is unknown. Methods: SAF was measured using an AGE reader in 66 patients who had received a kidney transplant. Values were compared to those obtained in 1,707 patients with CKD stage 3 and in 115 patients on dialysis. Results: Mean SAF in transplant recipients [2.81 ± 0.64 arbitrary units (AU)] was significantly lower than in patients on haemodialysis (3.73 ± 0.88 AU) and peritoneal dialysis (3.57 ± 0.75 AU; p < 0.001), but was no different from CKD stage 3 (2.79 ± 0.66 AU; p = 0.42). In the transplant group, SAF correlated most strongly with age (r = 0.316). There was no correlation between SAF and estimated glomerular filtration rate or renal replacement therapy vintage. A small cohort of patients with SAF recorded on dialysis and following transplantation showed a drop in SAF over a mean time of 16 months after transplantation. Discussion: Tissue AGE values in kidney transplant recipients are significantly lower than in patients receiving dialysis and similar to those in patients with CKD stage 3. Our data suggest that transplantation may be associated with a reduction in tissue AGEs, and this might be an important component of the observed reduction in cardiovascular risk in transplant recipients compared to patients on dialysis.
Type of Vascular Access and Survival among Very Elderly Hemodialysis Patients
Authors: Praga Manuel , Merello José Ignacio , Palomares Ines , Bayh Inga , Marcelli Daniele , Aljama Pedro , Luño José
Published: October 2013

The use of central venous catheters (CVC) for hemodialysis (HD) is associated with higher mortality compared to arteriovenous access (AV). However, studies analyzing the influence of the type of vascular access on the survival of very elderly patients (≥75 years) initiating HD are few and involve only a limited number of patients. We studied a cohort of 5,466 incident patients who started HD; of these, 1,841 were aged ≥75. Types of vascular access for HD were classified as either CVC, which included both tunneled and non-tunneled catheters, or AV, which included AV fistula and grafts. The outcome of the study was all-cause mortality during the follow-up period. In the whole cohort, AV use was associated with a survival advantage over CVC use (88 and 63% at 2 and 5 years, respectively, in patients with an AV as compared to 75 and 48% in patients with a CVC) (p < 0.0001). Among patients ≥75, CVC use was associated with a higher number of deaths compared to AV use. Patients ≥75 with an AV showed a greater survival as compared to patients ≥75 with a CVC (80 and 53% at 2 and 5 years, respectively, vs. 68 and 43%; p < 0.0001). Multivariate analysis revealed that CVC use and the presence of arrhythmia were independent risk factors of death in patients ≥75, whereas obesity was associated with greater survival. In conclusion, the type of vascular access has a significant influence on the survival of very elderly patients (≥75) initiating HD. CVC use was associated with poorer survival compared to AV access.
Effect of Avocado Soybean Unsaponifiables on Insulin Secretion and Insulin Sensitivity in Patients with Obesity
Authors: Martínez-Abundis Esperanza , González-Ortiz Manuel , Mercado-Sesma Arieh R. , Reynoso-von-Drateln Claudia , Moreno-Andrade Aureliano
Published: October 2013

Aim: To evaluate the effect of avocado soybean unsaponifiables (ASU) on insulin secretion and insulin sensitivity in patients with obesity. Methods: A randomized, double-blind, placebo-controlled, clinical trial was carried out in 14 obese adult volunteers. After random allocation of the intervention, 7 patients received 300 mg of ASU or placebo during a fasting state for 3 months. A metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels was carried out prior to the intervention. A hyperglycemic-hyperinsulinemic clamp technique was used to assess insulin secretion and insulin sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for statistical analyses. The study was approved by the local ethics committee of our institution. Results: At baseline, both groups were similar according to clinical and laboratory characteristics. There was no significant difference in insulin secretion and insulin sensitivity with ASU. Conclusions: ASU administration for 3 months did not modify insulin secretion and insulin sensitivity in patients with obesity.
Effectiveness of a Low-Calorie Weight Loss Program in Moderately and Severely Obese Patients
Authors: Winkler Julia K. , Schultz Jobst-Hendrik , Woehning Annika , Piel David , Gartner Lena , Hildebrand Mirjam , Roeder Eva , Nawroth Peter P. , Wolfrum Christian , Rudofsky Gottfried
Published: October 2013

Aims: To compare effectiveness of a 1-year weight loss program in moderately and severely obese patients. Methods: The study sample included 311 obese patients participating in a weight loss program, which comprised a 12-week weight reduction phase (low-calorie formula diet) and a 40-week weight maintenance phase. Body weight and glucose and lipid values were determined at the beginning of the program as well as after the weight reduction and the weight maintenance phase. Participants were analyzed according to their BMI class at baseline (30-34.9 kg/m2; 35-39.9 kg/m2; 40-44.9 kg/m2; 45-49.9 kg/m2; ≥50 kg/m2). Furthermore, moderately obese patients (BMI < 40 kg/m2) were compared to severely obese participants (BMI ≥ 40 kg/m2). Results: Out of 311 participants, 217 individuals completed the program. Their mean baseline BMI was 41.8 ± 0.5 kg/m2. Average weight loss was 17.9 ± 0.6%, resulting in a BMI of 34.3 ± 0.4 kg/m2 after 1 year (p < 0.001). Overall weight loss was not significantly different in moderately and severely obese participants. Yet, severely obese participants achieved greater weight loss during the weight maintenance phase than moderately obese participants (-3.1 ± 0.7% vs. -1.2 ± 0.6%; p = 0.04). Improvements in lipid profiles and glucose metabolism were found throughout all BMI classes. Conclusion: 1-year weight loss intervention improves body weight as well as lipid and glucose metabolism not only in moderately, but also in severely obese individuals.
Cauda Equina Syndrome Secondary to Complicated Diverticulitis
Authors: ter Horst M. , Stam M.A.W. , Bouman D.E. , Klaase J.M.
Published: October 2013

A 58-year-old woman presented to the emergency department with cauda equina syndrome and sepsis. The symptoms were attributed to a complicated episode of sigmoid diverticulitis. MRI showed that the diverticulitis had caused an intra-abdominal fistula to a presacrally localized abscess expanding into the spinal canal, compressing the cauda equina nerves. Although Hartmann's procedure was performed, the neurological symptoms persisted, causing the patient to remain partially paraplegic. This case report illustrates that cauda equina syndrome is a condition that can also be caused by intra-abdominal pathology such as diverticulitis.
A Case of Acute Posterior Multifocal Placoid Pigment Epitheliopathy Demonstrating Vogt-Koyanagi-Harada Disease-Like Optical Coherence Tomography Findings in the Acute Stage
Authors: Tanigawa Minoru , Tsukahara Yoko , Yamanaka Hiromitsu
Published: October 2013

Purpose: We report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE), which was difficult to differentiate from posterior pole-type Vogt-Koyanagi-Harada (VKH) disease because the lesions were mainly located in the macula bilaterally. Case Report: A 33-year-old man presented with rapid bilateral loss of vision. Fundoscopy revealed yellow-white subretinal lesions in the posterior pole of both eyes. Optical coherence tomography (OCT) revealed the presence of subretinal fluid with a subretinal septum. After initiation of systemic steroids, OCT revealed that the amount of subretinal fluid decreased immediately. However, vision loss was less responsive to the therapy, and OCT revealed partial reorganization of the inner segment/outer segment (IS/OS) line in the bilateral macular areas after therapy. Discussion: In our case, the location of the macular lesions made it difficult to differentiate APMPPE from VKH disease by fluorescein angiography. OCT images showed VKH disease-like findings of serous retinal detachment with a subretinal septum. The outer nuclear layer disappeared and the IS/OS line in the affected area was disorganized in the acute stage of the disease. In this case, the rapid loss of vision was specific to the onset pattern of APMPPE, and the slow response to therapy was very different from the response typically observed in VKH disease. Thus, careful consideration of the clinical course is important for diagnosing APMPPE.
Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy
Authors: Gold Michael R. , Daubert Jean-Claude , Abraham William T. , Hassager Christian , Dinerman Jay L. , Hudnall J. Harrison , Cerkvenik Jeff , Linde Cecilia
Published: October 2013

Background—

Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT-D). However, there are little data comparing mortality between these 2 device types.

Methods and Results—

REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) was a multicenter, randomized trial of CRT among patients with mild heart failure. Long-term annual follow-up for 5 years was preplanned. The present analysis was confined to the 419 patients who were randomized to active CRT group. CRT-pacemakers or CRT-D devices were implanted based on national guidelines at the time of enrollment, with 74 patients receiving CRT pacemaker devices and the remaining 345 patients receiving CRT-D devices. After 12 months of CRT, changes in the clinical composite score, left ventricular end systolic volume index, 6-minute walk time, and quality of life indices were similar between CRT pacemaker and CRT-D patients. However, long-term follow-up showed lower morality in the CRT-D group. Specifically, multivariable analysis showed that CRT-D (hazard ratio, 0.35;
P
=0.003) was a strong independent predictor of survival. Female sex, longer unpaced QRS duration, and smaller baseline left ventricular end systolic volume index also were also associated with better survival.

Conclusions—

REVERSE demonstrated that the addition of implantable cardioverter-defibrillator therapy to CRT is associated with improved long-term survival compared with CRT pacing alone in mild heart failure.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00271154.
Correlation of Ventricular Arrhythmias With Genotype in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Bao Jingru , Wang Jizheng , Yao Yan , Wang Yilu , Fan Xiaohan , Sun Kai , He Ding Sheng , Marcus Frank I. , Zhang Shu , Hui Rutai , Song Lei
Published: October 2013

Background—

Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics.

Methods and Results—

Ninety subjects diagnosed with ARVC who underwent electrophysiological study were recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations were identified in 57 (63%) subjects. Mutation carriers had more frequent clinical ventricular tachycardia (VT; 89% versus 55%;
P
<0.001) and negative T waves in V
1
to V
3
(61% versus 33%;
P
=0.016). Subjects with plakophilin-2 (
PKP2
) mutations also had more frequent VT than those without mutations in
PKP2
. Comparison between subjects with multiple and single mutations showed that syncope occurred more often in the former group (58% versus 24%;
P
=0.018). VT was significantly more often induced in mutation carriers compared with noncarriers (75% versus 39%;
P
=0.001), as well as in
PKP2
mutation carriers compared with subjects without
PKP2
mutations (80% versus 48%;
P
=0.002). Induced VT with a rate ≥200 bpm was more often documented in mutation carriers (88% versus 54%;
P
=0.013), as well as in
PKP2
mutation carriers (91% versus 67%;
P
=0.041).

Conclusions—

Pathogenic gene mutations were found in nearly two thirds of subjects diagnosed with ARVC. Mutation carriers, especially
PKP2
, had a higher proportion of a history of VT and more inducible fast VT.
Resistance Artery Creatine Kinase mRNA and Blood Pressure in Humans
Authors: Karamat Fares A. , Oudman Inge , Ris-Stalpers Carrie , Afink Gijs B. , Keijser Remco , Clark Joseph F. , van Montfrans Gert A. , Brewster Lizzy M.
Published: October 2013

Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6–1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1),
P
=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature’s pressor responses.
Myocardial Mineralocorticoid Receptor Activation by Stretching and Its Functional Consequences
Authors: Díaz Romina G. , Pérez Néstor G. , Morgan Patricio E. , Villa-Abrille María C. , Caldiz Claudia I. , Nolly Mariela B. , Portiansky Enrique L. , Ennis Irene L. , Cingolani Horacio E.
Published: October 2013

Myocardial stretch triggers an angiotensin II–dependent autocrine/paracrine loop of intracellular signals, leading to reactive oxygen species–mediated activation of redox-sensitive kinases. Based on pharmacological strategies, we previously proposed that mineralocorticoid receptor (MR) is necessary for this stretch-triggered mechanism. Now, we aimed to test the role of MR after stretch by using a molecular approach to avoid secondary effects of pharmacological MR blockers. Small hairpin interference RNA capable of specifically knocking down the MR was incorporated into a lentiviral vector (l-shMR) and injected into the left ventricular wall of Wistar rats. The same vector but expressing a nonsilencing sequence (scramble) was used as control. Lentivirus propagation through the left ventricle was evidenced by confocal microscopy. Myocardial MR expression, stretch-triggered activation of redox-sensitive kinases (ERK1/2-p90
RSK
), the consequent Na
+
/H
+
exchanger–mediated changes in pH
i
(HEPES-buffer), and its mechanical counterpart, the slow force response, were evaluated. Furthermore, reactive oxygen species production in response to a low concentration of angiotensin II (1.0 nmol/L) or an equipotent concentration of epidermal growth factor (0.1 μg/mL) was compared in myocardial tissue slices from both groups. Compared with scramble, animals transduced with l-shMR showed (1) reduced cardiac MR expression, (2) cancellation of angiotensin II–induced reactive oxygen species production but preservation of epidermal growth factor–induced reactive oxygen species production, (3) cancellation of stretch-triggered increase in ERK1/2-p90
RSK
phosphorylation, (4) lack of stretch-induced Na
+
/H
+
exchanger activation, and (5) abolishment of the slow force response. Our results provide strong evidence that MR activation occurs after myocardial stretch and is a key factor to promote redox-sensitive kinase activation and their downstream consequences.
Potent Antihypertensive Action of Dietary Flaxseed in Hypertensive Patients
Authors: Rodriguez-Leyva Delfin , Weighell Wendy , Edel Andrea L. , LaVallee Renee , Dibrov Elena , Pinneker Reinhold , Maddaford Thane G. , Ramjiawan Bram , Aliani Michel , Guzman Randolph , Pierce Grant N.
Published: October 2013

Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈10 mm Hg lower, and DBP was ≈7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.
High Blood Pressure After Acute Ischemic Stroke Is Associated With Poor Clinical Outcomes
Authors: Ishitsuka Koji , Kamouchi Masahiro , Hata Jun , Fukuda Kenji , Matsuo Ryu , Kuroda Junya , Ago Tetsuro , Kuwashiro Takahiro , Sugimori Hiroshi , Nakane Hiroshi , Kitazono Takanari
Published: October 2013

The relationship between the poststroke blood pressure (BP) and functional outcomes in patients with acute ischemic stroke is still controversial. The aim of the present study was to elucidate the impact of the poststroke BP on the clinical outcomes of acute ischemic stroke. Among the patients in the Fukuoka Stroke Registry, 1874 patients with first-ever acute ischemic stroke (within 24 hours of onset) who had been functionally independent before onset were prospectively enrolled in the present study. The poststroke BP levels were defined as the average values during the 48 hours after onset. The study outcomes were a good neurological recovery, neurological deterioration, and a poor functional outcome. The higher poststroke BP levels were significantly associated with a lower probability of a good neurological recovery and elevated risks of neurological deterioration and a poor functional outcome after adjusting for potential confounding factors. The multivariate-adjusted odds ratios (95% confidence interval) in the highest quintile of systolic BP (versus the lowest quintile as a reference) were 0.51 (0.37–0.71) for a good neurological recovery, 1.92 (1.15–3.27) for neurological deterioration, and 2.51 (1.69–3.74) for a poor functional outcome. Similar associations were observed when we applied the poststroke diastolic BP or pulse pressure. No evidence of the J-curve phenomenon was observed for each association. These results suggest that a high poststroke BP was significantly associated with unfavorable clinical outcomes in patients with acute ischemic stroke. There was no evidence of the J-curve phenomenon between the poststroke BP levels and the clinical outcomes.