bluuebunny/crossref_metadata_2025 huggingface dataset:
Resonant Antidromic Cortical Circuit Activation as a Consequence of High-Frequency Subthalamic Deep-Brain Stimulation
Authors: Li S. , Arbuthnott G. W. , Jutras M. J. , Goldberg J. A. , Jaeger D.
Published: October 2007

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)–lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.
Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions
Authors: Mohler Peter J. , Wehrens Xander H. T.
Published: October 2007

Many cardiac ion channels exist within macromolecular signaling complexes, comprised of pore-forming subunits that associate with auxiliary subunits, regulatory enzymes, and targeting proteins. This complex protein assembly ensures proper modulation of channel activity and ion homeostasis. The association of genetic defects in regulatory and targeting proteins to inherited arrhythmia syndromes has led to a better understanding of the critical role these proteins play in ion channel modulation.
Phospho-regulation of β-Catenin Adhesion and Signaling Functions
Authors: Daugherty Rebecca Leadem , Gottardi Cara J.
Published: October 2007

β-Catenin plays a critical structural role in cadherin-based adhesions and is also an essential co-activator of Wnt-mediated gene expression. The degree to which β-catenin participates in these two functions is dictated by the availability of β-catenin binding partners, and an emerging theme is that these binding interactions are regulated by phosphorylation. Inputs from various cell-signaling events can therefore impact β-catenin function, which may be necessary for the finely tuned adhesive and signaling responses required for tissue morphogenesis.
Modulation of gene expression in hibernating arctic ground squirrels
Authors: Yan Jun , Barnes Brian M. , Kohl Franziska , Marr Thomas G.
Published: October 2007

We performed a broadscale screening of differential gene expression using both high-throughput bead-array technology and real-time PCR assay in brown adipose tissue, liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels, comparing animals sampled after two durations of steady-state torpor, during two stages of spontaneous arousal episodes, and in animals after they ended hibernation. Significant seasonal and torpor-arousal cycle differences of gene expression were detected in genes involved in glycolysis, fatty acid metabolism, gluconeogenesis, amino acid metabolism, molecular transport, detoxification, cardiac contractility, circadian rhythm, cell growth and apoptosis, muscle dystrophy, and RNA and protein protection. We observed, for the first time, complex modulation of gene expression during multiple stages of torpor-arousal cycles. The mRNA levels of certain metabolic genes drop significantly during the transition from late torpor to early arousal, perhaps due to the rapid turnover of mRNA transcripts resulting from the translational demands during thermogenesis in early arousal, whereas the mRNA levels of genes related to circadian rhythm, cell growth, and apoptosis rise significantly in the early or late arousal phases during torpor-arousal cycle, suggesting the resumption of circadian rhythm and cell cycle during arousal.
GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations
Authors: Ben-Ari Yehezkel , Gaiarsa Jean-Luc , Tyzio Roman , Khazipov Rustem
Published: October 2007

Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter γ-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABAAreceptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to “wire together” so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.
Mouse Models and the Urinary Concentrating Mechanism in the New Millennium
Authors: Fenton Robert A. , Knepper Mark A.
Published: October 2007

Our understanding of urinary concentrating and diluting mechanisms at the end of the 20th century was based largely on data from renal micropuncture studies, isolated perfused tubule studies, tissue analysis studies and anatomical studies, combined with mathematical modeling. Despite extensive data, several key questions remained to be answered. With the advent of the 21st century, a new approach, transgenic and knockout mouse technology, is providing critical new information about urinary concentrating processes. The central goal of this review is to summarize findings in transgenic and knockout mice pertinent to our understanding of the urinary concentrating mechanism, focusing chiefly on mice in which expression of specific renal transporters or receptors has been deleted. These include the major renal water channels (aquaporins), urea transporters, ion transporters and channels (NHE3, NKCC2, NCC, ENaC, ROMK, ClC-K1), G protein-coupled receptors (type 2 vasopressin receptor, prostaglandin receptors, endothelin receptors, angiotensin II receptors), and signaling molecules. These studies shed new light on several key questions concerning the urinary concentrating mechanism including: 1) elucidation of the role of water absorption from the descending limb of Henle in countercurrent multiplication, 2) an evaluation of the feasibility of the passive model of Kokko-Rector and Stephenson, 3) explication of the role of inner medullary collecting duct urea transport in water conservation, 4) an evaluation of the role of tubuloglomerular feedback in maintenance of appropriate distal delivery rates for effective regulation of urinary water excretion, and 5) elucidation of the importance of water reabsorption in the connecting tubule versus the collecting duct for maintenance of water balance.
Cellular Response to Hyperosmotic Stresses
Authors: Burg Maurice B. , Ferraris Joan D. , Dmitrieva Natalia I.
Published: October 2007

Cells in the renal inner medulla are normally exposed to extraordinarily high levels of NaCl and urea. The osmotic stress causes numerous perturbations because of the hypertonic effect of high NaCl and the direct denaturation of cellular macromolecules by high urea. High NaCl and urea elevate reactive oxygen species, cause cytoskeletal rearrangement, inhibit DNA replication and transcription, inhibit translation, depolarize mitochondria, and damage DNA and proteins. Nevertheless, cells can accommodate by changes that include accumulation of organic osmolytes and increased expression of heat shock proteins. Failure to accommodate results in cell death by apoptosis. Although the adapted cells survive and function, many of the original perturbations persist, and even contribute to signaling the adaptive responses. This review addresses both the perturbing effects of high NaCl and urea and the adaptive responses. We speculate on the sensors of osmolality and document the multiple pathways that signal activation of the transcription factor TonEBP/OREBP, which directs many aspects of adaptation. The facts that numerous cellular functions are altered by hyperosmolality and remain so, even after adaptation, indicate that both the effects of hyperosmolality and adaptation to it involve profound alterations of the state of the cells.
Plasma F2A Isoprostane Levels in Alzheimer’s and Parkinson’s Disease
Authors: Irizarry M.C. , Yao Y. , Hyman B.T. , Growdon J.H. , Praticò D.
Published: October 2007

Background: Oxidative damage is implicated in the pathophysiology of Alzheimer’s disease (AD). F2-isoprostane is a marker of lipid peroxidation which is elevated in AD CSF. Plasma F2-isoprostane has been proposed as a diagnostic marker for AD and mild cognitive impairment (MCI). Objective: To determine whether plasma F2-isoprostane levels differ between nondemented control individuals and patients with AD, MCI, or Parkinson’s disease (PD). Methods: We collected plasma from191 outpatients with a diagnosis of AD (49), MCI (47), nondemented PD (47), and no dementia (48). Plasma levels of the isoprostane iP2α-IV (F2A) were determined by gas chromatography/mass spectroscopy. Results: Mean plasma levels of F2A isoprostane did not differ significantly between the four diagnostic groups. Within the MCI and AD groups, F2A levels did not correlate with duration of memory impairment or with cognitive test scores. F2A levels were marginally lower in users of cholinesterase inhibitors and individuals with an APOE Ε4 allele. Conclusions: While CSF isoprostane levels are elevated in AD, plasma isoprostane measures were neither sensitive nor specific for the clinical diagnosis of MCI or AD.
Peripheral Inflammatory Cytokines as Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Guerreiro Rita João , Santana Isabel , Brás José Miguel , Santiago Beatriz , Paiva Artur , Oliveira Catarina
Published: October 2007

Background: Several lines of evidence in the literature have shown that inflammation is involved in the pathogenesis of Alzheimer’s disease (AD). However, the results from the evaluation of serum inflammatory markers in AD patients have been controversial. Objective: To determine if any differences exist in the monocytic secretion pattern of IL-1β, IL-6, IL-12 and TNF-α from mild cognitive impairment (MCI) and AD patients, when compared with healthy age-matched controls. Methods: To evaluate the percentage of peripheral monocytes secreting IL-1β, IL-6, IL-12 and TNF-α along with the relative levels of these proteins, a cytofluorimetric analysis was conducted under basal conditions and after lipopolysaccharide-induced cell activation. Results: We found, in AD and MCI patients, a significant raise in the percentage of monocytes producing the studied cytokines (under basal conditions and after the exposure to an inflammatory stimulus), as well as a decreased competence of these cells to respond to inflammatory challenges, when compared with controls. Conclusions: These results agree with a persistent inflammatory status in AD, reinforcing the hypothesis of a progressive impairment of the immune response in this disorder and suggesting that monocytes may be good targets to study the progression from MCI to AD.
Sp3 and Sp4 Transcription Factor Levels Are Increased in Brains of Patients with Alzheimer’s Disease
Authors: Boutillier Stéphanie , Lannes Béatrice , Buée Luc , Delacourte André , Rouaux Caroline , Mohr Michel , Bellocq Jean-Pierre , Sellal François , Larmet Yves , Boutillier Anne-Laurence , Loeffler Jean-Philippe
Published: October 2007

Background/Aims: Alzheimer’s disease (AD) is characterized by extracellular Aβ peptide deposition originating from amyloid precursor protein cleavage and intracellular neurofibrillary tangles resulting from pathological tau protein aggregation. These processes are accompanied by dramatic neuronal losses, further leading to different cognitive impairments. Neuronal death signalings involve gene expression modifications that rely on transcription factor alterations. Herein, we investigated the fate of the Sp family of transcription factors in postmortem brains from patients with AD disease and in different contexts of neuronal death. Methods/Results: By immunohistochemistry we found that the Sp3 and Sp4 levels were dramatically increased and associated with neurofibrillary tangles and pathological tau presence in neurons from the CA1 region of the hippocampus, as well as the entorhinal cortex of AD patient brains. The Sp transcription factor expression levels were further analyzed in cortical neurons in which death is induced by amyloid precursor protein signaling targeting. While the Sp1 levels remained constant, the Sp4 levels were slightly upregulated in response to the death signal. The Sp3 isoforms were rather degraded. Interestingly, when overexpressed by transfection experiments, the three Sp family members induced neuronal apoptosis, Sp3 and Sp4 being the most potent proapoptotic factors over Sp1. Conclusion: Our data evidence Sp3 and Sp4 as new hallmarks of AD in postmortem human brains and further point out that Sp proteins are potential triggers of neuronal death signaling cascades.
A Prospective Study of Familial versus Sporadic Parkinson’s Disease
Authors: Papapetropoulos Spiridon , Adi Nikhil , Ellul John , Argyriou Andreas A. , Chroni Elisabeth
Published: October 2007

Background: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Most cases are sporadic but about 10–15% of patients have a positive family history of PD. Objective: To compare clinical phenotypes between familial (fPD) and sporadic (sPD) PD patients. Methods: Fifty-nine consecutive patients with at least one first-degree relative with PD were prospectively studied. After exclusion of 9 PD patients with positive family carrying known disease causing mutations, the remaining 50 were compared with 50 age- and sex-matched sPD patients. Results: Despite our methodological approach (strict diagnostic criteria, validated scales, structured interviews, multi- and two-member group formation and exclusion of patients with identifiable mutations) no major differences in the clinical phenotype between fPD and sPD were found. Conclusion: Similar phenotypic characteristics of motor signs and symptoms suggest that at least the topography of the neurodegenerative insult leading to the parkinsonian clinical syndrome in fPD and sPD is similar. Similar etiologies are also suggested.
Axonal Degeneration in Motor Neuron Disease
Authors: Fischer Lindsey R. , Glass Jonathan D.
Published: October 2007

Growing evidence from animal models and patients with amyotrophic lateral sclerosis (ALS) suggests that distal axonal degeneration begins very early in this disease, long before symptom onset and motor neuron death. The cause of axonal degeneration is unknown, and may involve local axonal damage, withdrawal of trophic support from a diseased cell body, or both. It is increasingly clear that axons are not passive extensions of their parent cell bodies, and may die by mechanisms independent of cell death. This is supported by studies in which protection of motor neurons in models of ALS did not significantly improve symptoms or prolong lifespan, likely due to a failure to protect axons. Here, we will review the evidence for early axonal degeneration in ALS, and discuss possible mechanisms by which it might occur, with a focus on oxidative stress. We contend that axonal degeneration may be a primary feature in the pathogenesis of motor neuron disease, and that preventing axonal degeneration represents an important therapeutic target that deserves increased attention.
Ehlers-Danlos Type IV in Pregnancy
Authors: Erez Y. , Ezra Y. , Rojansky N.
Published: October 2007

Background: Ehlers-Danlos syndrome is a heterogeneous group of connective tissue disorders, characterized by a defect in the synthesis of collagen. The syndrome is subdivided into different clinical subtypes, the most hazardous of which is type IV, the vascular type. It can manifest itself in various complications such as rupture of arteries and hollow organs. The obstetrical manifestations are the risk of uterine rupture during labor, damage to the vagina and perineum, bleeding and rupture of blood vessels and colon during the puerperium. Case Report: We describe a primigravida suffering from Ehlers-Danlos type IV who was followed and successfully delivered by a cesarean section at 36 weeks of gestation and made an uneventful recovery. Conclusion: Following a thorough literature review, it seems wise to perform early delivery by cesarean section for pregnant women suffering from Ehlers-Danlos type IV.
Fetal Left Ventricular Diverticulum Presenting as Dysrhythmia: Diagnosis and Management
Authors: Pradhan Mandakini , Dalal Ashwin , Kapoor Aditya , Kumar Sudeep , Manisha R.
Published: October 2007

Congenital diverticulum of the left ventricle is amalformation, often associated with midline thoraco-abdominal defects. Here we describe a case of isolated congenital left ventricular diverticulum that presented with an abnormal four-chamber view and fetal dysrhythmia on ultrasonography. Maternal digoxin therapy was started due to significant ventricular ectopy. Restoration of fetal sinus rhythm was achieved within 48 h. Serial fetal echocardiograms were performed every week, followed by a normal vaginal delivery at term. The child is surviving at 1 year of age.
Fear of Pregnancy Loss and Fetal Karyotyping: A Place for Third-Trimester Amniocentesis?
Authors: Picone Olivier , Senat Marie-Victoire , Rosenblatt Jonathan , Audibert François , Tachdjian Gerard , Frydman Rene
Published: October 2007

Objective: To assess the complications of third-trimester amniocentesis for fetal karyotyping in women unwilling to accept the fetal loss risks of second-trimester amniocentesis. Methods: Retrospective study of singleton pregnancies that underwent a third-trimester amniocentesis for karyotyping. 150 complete charts between 1998 and 2005 were reviewed. Results: The indications were: isolated abnormal second-trimester biochemical markers (n = 57), isolated maternal age >38 years (n = 46), integrated risk (maternal age, first-trimester nuchal translucency, second-trimester maternal serum markers) >1/250 (n = 22), history of chromosomal abnormality (n = 17) or maternal choice (n = 8). The median maternal age and gestational age at sampling were: 40 years (23–48), 32.4 weeks (29.7–37.1). Median interval between amniocentesis, definitive result of amniocentesis, and delivery were 14 days (7–42), and 49 days (10–67) respectively. There were no abnormal karyotypes and no termination of pregnancy. Six women out of 150 (4%) had spontaneous labor before 36 weeks (2% after 36 weeks). Conclusion: The risk of spontaneous labor before 37 weeks after late amniocentesis is 4% (2% before 36 weeks). This technique provides a late but safe reassurance to women who are unwilling to accept the risks of earlier fetal karyotyping. This is of interest to countries such as France where legislation permits late termination of pregnancy.
Gamma 2 Actin Gene (Enteric Type) Polymorphism Is Not Associated with Obstetric Cholestasis or Preeclampsia
Authors: Laasanen Jaana , Helisalmi Seppo , Iivonen Susan , Eloranta M.-L. , Hiltunen Mikko , Heinonen Seppo
Published: October 2007

Objective: To determine whether genetic variability in the intron 1 region of the gamma 2 actin gene (enteric type) contributes to the development of obstetric complications. Study Design: The study involved 57 obstetric cholestasis and 133 preeclampsia patients and a control group of 115 healthy women in whom polymerase chain reaction detection of insertion-deletion polymorphism in the gamma 2 actin gene was investigated. χ2 analysis was used to assess genotype and allele frequency differences between the study groups. Results: The distribution of I and D alleles was equal in obstetric cholestasis (p = 0.652), preeclampsia (p = 0.609) and control groups. None of the gamma 2 actin gene genotypes were significantly overrepresented in obstetric cholestasis (p = 0.540) or preeclampsia (p = 0.680) groups compared to the control group. Conclusion: This insertion-deletion polymorphism in the intron 1 of the gamma 2 actin gene is unlikely to play any significant role in obstetric cholestasis or preeclampsia in patients from eastern Finland.
Major Sacrococcygeal Teratoma in an Extreme Premature Infant: A Multidisciplinary Approach
Authors: den Otter S.C.M. , de Mol A.C. , Eggink A.J. , van Heijst A.F.J. , de Bruijn D. , Wijnen R.M.H.
Published: October 2007

Antenatally diagnosed, large sacrococcygeal teratomas in very premature infants are associated with a very poor outcome. We present an extreme premature infant with cardiac decompensation, diagnosed at 27 weeks and 1 day of gestational age. A positive outcome could be achieved with intensive multidisciplinary planning of the delivery, postnatal stabilization and surgical resection, as demonstrated in this case report.
Maturity of the Myenteric Plexus Is Decreased in the Gastroschisis Rat Model
Authors: França Willy Marcus , Langone Francesco , de la Hoz Cristiane Lucia R. , Gonçalves Anderson , Bittencourt Daniel , Pereira Luis Violin , Sbragia Lourenço
Published: October 2007

Background: Amniotic fluid (AF) and its components, such as fetal urine and meconium, may lead to intestinal alterations in gastroschisis, which cause immaturity of the myenteric plexus and consequent intestinal hypomotility and malabsorption. In this study we identified morphological and histological alterations of the intestine and the myenteric plexus with two different times of exposure to AF. Methods: The experimental gastroschisis was achieved at two different gestational ages, on day 18.5 (E18.5) and day 19.5 (E19.5) of gestation, in fetal rats which were divided into 3 subgroups: control, sham and gastroschisis. We measured fetal body weight (BW), intestinal weight (IW) and intestinal length (IL). The layers of intestinal wall and myenteric plexus were evaluated by hematoxylin and eosin staining (HE staining) and immunofluorescence (α-internexin), respectively. Results: BW was not significantly different among the control, sham and gastroschisis groups at both ages. IW and IL were larger and shorter, respectively, in the gastroschisis fetuses (p < 0.001) at both ages. Intestinal diameters and wall layers presented significant differences among control, sham and gastroschisis fetuses at both ages (p < 0.001), but the time of exposure to AF compromised the serous membrane, D-II (diameter II, p < 0.001) and IL (p = 0.001). α-Internexin presented more intensive immunoreactivity in gastroschisis fetuses at E18.5. Conclusions: In gastroschisis, the longer the time of exposure to AF, the more severe bowel impairment will be, especially with regard to IL and the serous layer, and the more immature the myenteric plexus will be.
Fetal Asphyxia due to Cord Entanglement in a Monochorionic Diamniotic Twin Pregnancy Complicated by 2nd-Trimester Single Intrauterine Demise
Authors: Miura Naomi , Suzuki Shunji
Published: October 2007

Usually, fetal asphyxia/demise because of umbilical cord entanglement and secondary cord occlusion is a unique characteristic of monoamniotic twin pregnancies. We present here a rare case of fetal asphyxia due to cord entanglement in a monochorionic diamniotic twin pregnancy complicated by 2nd-trimester single intrauterine demise. In this case, there was no amniocentesis or any other invasive intrauterine procedure performed during pregnancy.
Prenatal Diagnosis of Sex Chromosome Abnormalities: The 8-Year Experience of a Single Medical Center
Authors: Vaknin Zvi , Reish Orit , Ben-Ami Ido , Heyman Eli , Herman Arie , Maymon Ron
Published: October 2007

Objective: To assess the indications for prenatal karyotyping of sex chromosomal abnormalities (SCAs) during pregnancy. Methods: All singleton pregnancies interrupted in our institute because of SCAs (1998–2005) were categorized into subgroups of 45,XO (Turner syndrome), 47,XXY (Klinefelter syndrome), 47,XXX and 47,XYY. The indications for prenatal diagnostic testing were recorded. Results: There were 67 SCAs pregnancies: 33% Turner syndrome, 28% Klinefelter syndrome, 21% 47,XXX and 18% 47,XYY. Maternal age was similar among the 4 groups (34 ± 5, range 25–42 years). The main indications for fetal karyotyping were abnormal Down’s syndrome (DS) screening or ultrasound findings, advanced maternal age (≧35 years), and parental request. About 2/3 of the Turner and 47,XYY cases had either abnormal DS screening tests or sonographic findings, such as: increased nuchal translucency, mainly cystic hygroma and fetal hydrops. However, fetal karyotyping in more than 2/3 of the 47,XXX and 47,XXY cases was mainly performed because of advanced maternal age, and the diagnosis of fetal SCAs was coincidental (p <0.03). Conclusions: Our recent suggestion to expand the DS screening capacity to other chromosomal abnormalities including SCAs is further supported. Prenatal detection seems to be promising for Turner syndrome and possibly for 47,XYY syndrome, while other SCAs are less likely to be detected either by ultrasound or biochemical screening.
Predictive Significance of the Six-Minute Walk Distance for Long-Term Survival in Chronic Hypercapnic Respiratory Failure
Authors: Budweiser Stephan , Heidtkamp Felix , Jörres Rudolf A. , Heinemann Frank , Arzt Michael , Schroll Stephan , Schmidbauer Kathrin , Hitzl Andre P. , Pfeifer Michael
Published: October 2007

Background: The 6-min walk distance (6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease (COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure (CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation (NIV) comprising COPD (n = 197), restrictive diseases (RD; n = 112) and obesity-hypoventilation-syndrome (OHS; n = 115), the prognostic value of 6-MWD for long-term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD (median 280 m; quartiles 204/350 m) and RD (290 m; 204/362 m) compared to OHS (360 m; 275/440 m; p < 0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s (p < 0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median [p < 0.001, hazard ratio (HR) = 3.75, 95% confidence interval (CI): 2.24–6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73–14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long-term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF.
Hindbrain Neuroglucopenia Elicits Site-Specific Transcriptional Activation of Glutamate Decarboxylase-Immunopositive Neurons in the Septopreoptic Area of Female Rat Brain
Authors: Briski Karen P. , Singh Sushma R.
Published: October 2007

Recent studies implicate the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in septopreoptic (SPO) mechanisms that suppress preovulatory pituitary luteinizing hormone (LH) secretion during neuroglucopenia. Since Fos immunolabeling of the SPO of rats treated by caudal fourth ventricular (CV4) administration of the glucose antimetabolite, 5-thioglucose (5TG), parallels the distribution of GABA neuronal perikarya, the current studies investigated the genomic responsiveness of neuroanatomically-defined populations of glutamate decarboxylase (GAD)-immunoreactive (-ir) neurons in this region of the brain to hindbrain glucoprivation. In lieu of reports that CV4 5TG enhances SPO GABA turnover via µ opioid receptor (µ-R)-dependent mechanisms and evidence that GAD- and µ-R-ir are codistributed within the SPO, patterns of cellular colocalization of these antigens were also evaluated here. Neural tissue was obtained from groups of steroid-primed ovariectomized female rats 2 h after CV4 injection of vehicle or 5TG. Neuronal cell bodies in the lateral and medial septum, medial (MPN) and median preoptic nuclei (MEPO), and rostral medial preoptic area (rMPO) were immunostained for cytoplasmic GAD-ir, but only GAD-reactive neurons in the rMPO and MEPO exhibited robust nuclear colabeling for Fos in response to 5TG. SPO GABA neurons in the vehicle-treated controls were uniformly Fos-ir-negative. Dual immunolabeling for GAD- and µ-R revealed approximately 52% and 36% colabeling of this phenotype in the MEPO and MPN, and colocalization of lesser magnitude (18%) in the rMPO. These results demonstrate site-specific genomic activation of GABAergic neurons in the female rat SPO by CV4 glucose antimetabolite administration, and implicate MEPO and rMPO GABA cell populations in neural pathways that mediate regulatory effects of hindbrain glucoprivic signaling on CNS functions, including inhibition of the steroid positive feedback-activated gonadotropin-releasing hormone/LH neuroendocrine axis. The current studies also support the view that a proportion of neuroglucoprivic-sensitive GABA neurons in the MEPO and rMPO may be direct substrates for µ-R ligand modulatory actions during this state of central substrate imbalance.
Characteristics of Academic Medical Centers and Ischemic Stroke Outcomes
Authors: Gillum Leslie Allison , Johnston S. Claiborne
Published: October 2007

Background and Purpose

—

Data supporting the efficacy of stroke center characteristics are limited.

Methods

—

A questionnaire detailing stroke treatment practices was sent to 42 academic medical centers in the University Health Systems Consortium. In-hospital mortality of all emergency department admissions for ischemic stroke at these institutions was evaluated in a database of discharge abstracts during 1997–1999. Institutional characteristics were evaluated as predictors of in-hospital mortality after adjustment for age, sex, race, hospital treatment volume of ischemic stroke, and admission status (emergent, urgent, elective). Length of stay (LOS), total hospital charges, and frequency of tissue plasminogen activator (tPA) administration were evaluated as secondary outcomes. We used a multivariable method called generalized estimating equations, which broadens confidence intervals to adjust for clustering of variables at institutions.

Results

—

Thirty-two institutions completed the questionnaire, and 29 of these were included in the database of discharge abstracts. In-hospital deaths occurred in 758 (7.0%) of the 10 880 ischemic stroke patients admitted through the emergency department. In-hospital deaths were less frequent at hospitals with a vascular neurologist (odds ratio [OR] 0.51; 95% CI, 0.36 to 0.74;
P
<0.0001) and at those with guidelines stating that only neurologists could administer tPA (OR, 0.65; 95% CI, 0.49 to 0.88;
P
=0.004). There was a trend toward fewer deaths at hospitals with a dedicated stroke team available by pager (OR, 0.76; 95% CI, 0.56 to 1.04;
P
=0.09). The presence of a dedicated neurological intensive care unit, stroke unit, and written clinical pathway for stroke were not significantly associated with in-hospital death. LOS was shorter at hospitals with a vascular neurologist (
P
=0.01).

Conclusions

—

Academic medical centers with a vascular neurologist and those with written guidelines limiting tPA administration to neurologists had lower rates of in-hospital mortality for ischemic stroke patients.
Safety of Hemodynamic Augmentation in Patients Treated With Guglielmi Detachable Coils After Acute Aneurysmal Subarachnoid Hemorrhage
Authors: Aiyagari Venkatesh , Cross III DeWitte T. , Deibert Ellen , Dacey Jr Ralph G. , Diringer Michael N.
Published: October 2007

Background and Purpose

—

Guglielmi detachable coils (GDC) used in the treatment of intracranial aneurysms do not always completely occlude the aneurysm. Thus, after an acute subarachnoid hemorrhage (SAH), there is a theoretical risk of rebleeding from coiled aneurysms, especially when blood pressure is elevated. The aim of this study is to determine whether use of hemodynamic augmentation (HA) to treat delayed ischemic deficits (DID) will increase the risk of rebleeding in these patients.

Methods

—

Delayed ischemic deficits developed in 12 (7 women and 5 men, aged 31 to 64 years) of 51 patients treated with GDC for acute SAH over a 4-year period. Aneurysms in all 12 patients were ≥80% obliterated with GDC, and there was ≥90% obliteration of 78% of the aneurysms. Hemodynamic augmentation with fluids, phenylephrine, dopamine, and/or dobutamine was used to treat DID for a mean duration of 3 days (range 1 to 11 days).

Results

—

With HA, mean arterial blood pressure (MAP) rose 15% (range 0 to 30%) and systolic blood pressure (SBP) rose 13% (range 0 to 29%) above baseline. MAP was maintained at >10% above baseline for 65% of the treatment period. The maximum MAP was 104 to 170 mm Hg (mean 140 mm Hg), and maximum SBP was 154 to 261 mm Hg (mean 210 mm Hg). No patient had rebleeding or any significant complication during the course of therapy.

Conclusions

—

Based on this limited series of patients, we believe that it may be safe to use HA in patients treated with GDC for SAH.
Endovascular Treatment of Unruptured Aneurysms
Authors: Roy Daniel , Milot Geneviève , Raymond Jean
Published: October 2007

Background and Purpose

—

We sought to better define the morbidity of endovascular Guglielmi detachable coil (GDC) treatment of unruptured cerebral aneurysms and to discuss its role in the prevention of subarachnoid hemorrhage.

Methods

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We conducted an observational study from August 1992 to June 1999 of 125 unruptured aneurysms treated with GDC in 116 patients: 91 women (78.4%) and 25 men (21.6%), aged 30 to 78 years (mean age, 50.6 years). Immediate and late clinical results were recorded for any neurological event or hemorrhage related to the treated unruptured aneurysm. Angiographic results are reported as immediate, early (2 to 12 months), intermediate (12 to 30 months), and late follow-up (>30 months).

Results

—

Immediate angiographic results showed complete obliteration (class 1) in 59 (47.2%) or residual neck (class 2) in 53 aneurysms (42.4%), leaving 6 residual aneurysms (4.8%) and 7 failures (5.6%). Early follow-up angiograms, available in 100 treated aneurysms (84%), revealed class 1 in 52% and class 2 in 41%. Intermediate angiograms, available in 53 aneurysms (44.5%), showed class 1 in 47.2% and class 2 in 43.4%, while late results, available in 37 lesions (31.1%), had class 1 and 2 in 48.6% and 37.8%, respectively. Six patients suffered a permanent neurological deficit at last follow-up (5.2%), with a good outcome in 5 patients and fair outcome in 1 patient. There was no mortality. There was no aneurysmal rupture during a mean clinical follow-up of 32.1 months.

Conclusions

—

Endovascular treatment with GDC for unruptured aneurysms is relatively safe. Its role in the prevention of aneurysmal rupture remains to be determined, preferably by a randomized study.
Parenchymal Hyperdensity on Computed Tomography After Intra-Arterial Reperfusion Therapy for Acute Middle Cerebral Artery Occlusion
Authors: Nakano Shinichi , Iseda Tsutomu , Kawano Hirokazu , Yoneyama Takumi , Ikeda Tokuro , Wakisaka Shinichiro
Published: October 2007

Background and Purpose

—

The purpose of the present study was to assess the incidence and clinical significance of the intraparenchymal hyperdense areas on the posttherapeutic CT scan just after intra-arterial reperfusion therapy.

Methods

—

Seventy-seven patients with acute middle cerebral artery occlusion were studied prospectively with post-therapeutic CT. Hyperdense areas were classified into three groups: those in the lentiform nucleus, insular cortex and cerebral cortex. We investigated the incidence of hyperdense areas and hemorrhagic transformations and assessed whether location of hyperdense areas may play a role in the incidence of hemorrhagic transformations. We also evaluated correlation between early CT signs and hyperdense areas.

Results

—

Forty-five hyperdense areas were seen in 37 of the 77 patients (48.1%): 19 of the 45 (42.2%) were confirmed to be hematomas themselves, 6 (13.4%) showed later conversion to petechial hemorrhages, and 20 (44.4%) showed rapid disappearance without hemorrhagic transformations. Eleven of the 37 patients (29.7%) had neurological worsening due to massive hematoma (symptomatic hemorrhage), whereas none of the 40 patients without hyperdense areas had symptomatic hemorrhage. The incidence of hemorrhage among hyperdense areas was significantly lower in the insular cortex than in the other 2 regions (
P
<0.01). On the other hand, hyperdense areas in the lentiform nucleus had a significantly higher incidence of neurological worsening (
P
<0.05). There was a significant correlation between early CT signs and hyperdense areas (
P
<0.0001).

Conclusions

—

The presence of hyperdense areas was a significant risk factor for severe hemorrhagic transformations, although only 29.7% of patients with hyperdense areas had symptomatic hemorrhage. On the contrary, the absence of hyperdense areas was a reliable negative predictor for symptomatic hemorrhage.
Acute Systemic Inflammatory Response Syndrome in Subarachnoid Hemorrhage
Authors: Yoshimoto Yuhei , Tanaka Yoshihiro , Hoya Katsumi
Published: October 2007

Background and Purpose

—

Systemic inflammatory response syndrome (SIRS) without infection is a well-known phenomenon that accompanies various acute cerebral insults. We sought to determine whether the initial SIRS score was associated with outcome in subarachnoid hemorrhage (SAH).

Methods

—

In 103 consecutive patients with SAH, the occurrence of SIRS was assessed according to the presence of ≥2 of the following: temperature of <36°C or >38°C, heart rate of >90 bpm, respiratory rate of >20 breaths/min, and white blood cell count of <4000/mm
3
or >12 000/mm
3
. SIRS criteria and other prognostic parameters were evaluated as predictors of dichotomous Glasgow Outcome Scale score.

Results

—

SIRS was highly related to poor clinical grade (Hunt and Hess clinical grading scale), a large amount of SAH on CT (Fisher CT group), and high plasma glucose concentration on admission. By univariate analysis, the occurrence of SIRS was associated with higher mortality and morbidity rates than was the nonoccurrence (
P
<0.001). Among individual SIRS criteria, heart rate (
P
=0.003), respiration rate (
P
=0.003), and white blood cell count (
P
=0.03) were significant outcome predictors. By multivariate logistic regression analysis, the presence of SIRS independently predicted outcome. SIRS carried an increased risk of subsequent intracranial complications such as vasospasm and normal pressure hydrocephalus, as well as systemic complications.

Conclusions

—

In SAH patients, SIRS on admission reflected the extent of tissue damage at onset and predicted further tissue disruption, producing clinical worsening and, ultimately, a poor outcome.
Effect of Cisternal and Ventricular Blood on Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage:
Authors: Claassen Jan , Bernardini Gary L. , Kreiter Kurt , Bates Joseph , Du Yunling E. , Copeland Daphne , Connolly E. Sander , Mayer Stephan A.
Published: October 2007

Background and Purpose

—

Thick cisternal clot on CT is a well-recognized risk factor for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Whether intraventricular hemorrhage (IVH) or intracerebral hemorrhage (ICH) predisposes to DCI is unclear. The Fisher CT grading scale identifies thick SAH but does not separately account for IVH or ICH.

Methods

—

We studied 276 consecutively admitted patients with an available admission CT scan performed within 72 hours of onset. Demographic, clinical, laboratory, and neuroimaging data were recorded, and the amount and location of SAH, IVH, and ICH on admission CT scans were quantified. The relationship between these variables and DCI was analyzed separately and in combination with multiple logistic regression.

Results

—

DCI developed in 20% of patients (54 of 276). Among SAH variables, thick clot completely filling any cistern or fissure was the best predictor of DCI (
P
=0.008), and among IVH variables, blood in both lateral ventricles was most predictive (
P
=0.001). These variables had independent predictive value for DCI in a multivariate analysis of CT findings, and both were included in a final multivariate model when evaluated in conjunction with other clinical risk factors: IVH (OR 4.1, 95% CI 1.7 to 9.8), SAH (OR 2.3, 95% CI 1.5 to 9.5), mean arterial pressure >112 mm Hg (OR 4.9, 95% CI 2.1 to 11.4), and transcranial Doppler mean velocity >140 cm/s within 5 days of hemorrhage (OR 3.8, 95% CI 1.5 to 9.5). Similar results were obtained in a repeat analysis with infarction due to vasospasm as the dependent variable.

Conclusions

—

SAH completely filling any cistern or fissure and IVH in the lateral ventricles are both risk factors for DCI, and their risk is additive. We propose a new SAH rating scale that accounts for the independent predictive value of subarachnoid and ventricular blood for DCI.
Long-Term Prognosis of Medically Treated Patients With Internal Carotid or Middle Cerebral Artery Occlusion
Authors: Kuroda Satoshi , Houkin Kiyohiro , Kamiyama Hiroyasu , Mitsumori Kenji , Iwasaki Yoshinobu , Abe Hiroshi
Published: October 2007

Background and Purpose
—

The importance of hemodynamic parameters for predicting outcome in patients with occlusive carotid disease remains controversial. The present study was aimed at testing the hypothesis that regional cerebrovascular reactivity (rCVR) to acetazolamide can be a reliable predictor of subsequent ischemic stroke in medically treated patients with internal carotid artery or middle cerebral artery occlusion.

Methods
—

Seventy-seven symptomatic patients were enrolled in this prospective, longitudinal cohort study. All patients met inclusion criteria of cerebral angiography, no or localized cerebral infarction on MRI or CT, and no or minimal neurological deficit. Regional cerebral blood flow (rCBF) and rCVR to acetazolamide were quantitatively determined by
133
Xe SEPCT. All patients were categorized into 4 types on the basis of SPECT studies.

Results
—

During an average follow-up period of 42.7 months, 16 total and 7 ipsilateral ischemic strokes occurred. The annual risks of total and ipsilateral stroke in patients with decreased rCBF and rCVR were 35.6% and 23.7%, respectively, risks that are higher than those in other types of patients. When strokes were categorized into patients with and without decreased rCBF and rCVR, Kaplan-Meier analysis revealed that the risks of total and ipsilateral stroke in patients with decreased rCBF and rCVR were significantly higher than in those without (
P
<0.0001 and
P
=0.0001, respectively, log-rank test). Relative risk conferred by decreased rCBF and rCVR was 8.0 (95% CI, 1.9 to 34.4) for ipsilateral stroke and 3.6 (95% CI, 1.4 to 9.3) for total stroke.

Conclusions
—

Decreased rCBF and rCVR to acetazolamide may identify a subgroup of patients who have a higher risk of subsequent ischemic stroke when treated medically.
A Double-Blind, Placebo-Controlled Study of the Use of Amphetamine in the Treatment of Aphasia
Authors: Walker-Batson Delaina , Curtis Sandra , Natarajan Rajeshwari , Ford Jean , Dronkers Nina , Salmeron Eva , Lai Jenny , Unwin D. Hal
Published: October 2007

Background and Purpose

—

A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late (days to weeks) after brain injury in animals. A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke. To determine whether these findings extend to communication deficits subsequent to stroke, we administered dextroamphetamine, paired with speech/language therapy, to patients with aphasia.

Methods

—

In a prospective, double-blind study, 21 aphasic patients with an acute nonhemorrhagic infarction were randomly assigned to receive either 10 mg dextroamphetamine or a placebo. Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions. Thirty minutes after drug/placebo administration, subjects received a 1-hour session of speech/language therapy. The Porch Index of Communicative Ability was used at baseline, at 1 week off the drug, and at 6 months after onset as the dependent language measure.

Results

—

Although there were no differences between the drug and placebo groups before treatment (
P
=0.807), by 1 week after the 10 drug treatments ended there was a significant difference in gain scores between the groups (
P
=0.0153), with the greater gain in the dextroamphetamine group. The difference was still significant when corrected for initial aphasia severity and age. At the 6-month follow-up, the difference in gain scores between the groups had increased; however, the difference was not significant (
P
=0.0482) after correction for multiple comparisons.

Conclusions

—

Administration of dextroamphetamine paired with 10 1-hour sessions of speech/language therapy facilitated recovery from aphasia in a small group of patients in the subacute period after stroke. Neuromodulation with dextroamphetamine, and perhaps other drugs that increase central nervous system noradrenaline levels, may facilitate recovery when paired with focused behavioral treatment.