bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between oscillatory activity and motor reaction time in the parkinsonian subthalamic nucleus
Authors: Williams David , Kühn Andrea , Kupsch Andreas , Tijssen Marina , Van Bruggen Gerard , Speelman Hans , Hotton Gary , Loukas Constantinos , Brown Peter
Published: January 2005

Averaging techniques have demonstrated that movement preparatory cues and movement itself are associated with marked reductions in the oscillatory synchrony of local neuronal populations in the area of the human parkinsonian subthalamic nucleus (STN), as indexed by 8–30 Hz local field potential (LFP) activity. In order to examine the detailed nature and strength of the relationship between reductions in oscillatory activity and movement we examined single‐trial LFP activity recorded from the STN area of parkinsonian subjects engaged in a choice reaction task. In this task an initial warning cue was either fully predictive or non‐predictive of the hand required to make a later motor response. This motor response was elicited by a second go cue to which data were aligned. We observed a significant linear relationship between the onset time of oscillation reduction after go cues and subsequent motor response time across single trials within subjects. Consistent with this observation we also found a positive correlation of power with response time following go cues. In addition, we observed shorter durations of suppression in fully predictive trials where selection of the response could precede go cue presentation. The results are consistent with the hypothesis that reductions in 8–30 Hz population synchrony in the STN area are related to the processing required for motor preparation, particularly response selection.
Motor cortex plasticity induced by extensive training revealed by transcranial magnetic stimulation in human
Authors: Tyč F. , Boyadjian A. , Devanne H.
Published: January 2005

This study examines the effect of high‐level skilled behaviour on motor cortex representations of upper extremity muscles of ten sportswomen. We used transcranial magnetic stimulation to map proximal medial deltoid and distal extensor carpi radialis muscle representations on both hemispheres during low‐level voluntary contraction. We compared cortical representation areas between two groups of subjects and between hemispheres within subjects. The first group comprised five elite volleyball attackers and the second group five runners. Four stimuli were delivered on multiple scalp sites (1.5 cm apart) to induce motor‐evoked potentials recorded by surface EMG. Maps were described in terms of excitable scalp positions and of motor‐evoked potentials. We observed differences in map areas between the two groups. Volleyball players had larger cortical representations of the proximal medial deltoid muscle than runners. Furthermore, the volleyball players had larger map areas for dominant muscles compared with non‐dominant muscles. There was no difference, however, in map area for either muscle between the dominant and non‐dominant arm in the runner group. Our results show that heavy training in a specific skill induces an expansion of proximal muscle representation in the contralateral primary motor cortex. This enlarged map area for proximal muscle is accompanied by an increase in the overlapping of proximal and distal muscle representations. This could reflect the fact that motor learning of co‐ordinated movement involves a common control of both muscles. This reorganization supports the hypothesis of a cortical plasticity driven by activity.
Transsynaptic virus tracing from host brain to subretinal transplants
Authors: Seiler Magdalene J. , Sagdullaev Botir T. , Woch Gustaw , Thomas Biju B. , Aramant Robert B.
Published: January 2005

The aim of this study was to establish synapses between a transplant and a degenerated retina. To tackle this difficult task, a little‐known but well‐established CNS method was chosen: trans‐synaptic pseudorabies virus (PRV) tracing. Sheets of E19 rat retina with or without retinal pigment epithelium (RPE) were transplanted to the subretinal space in 33 Royal College of Surgeons (RCS) and transgenic s334ter‐5 rats with retinal degeneration. Several months later, PRV‐BaBlu (expressing E. coliβ‐galactosidase) or PRV‐Bartha was injected into an area of the exposed superior colliculus (SC), topographically corresponding to the transplant placement in the retina. Twenty normal rats served as controls. After survival times of 1–5 days, retinas were examined for virus by X‐gal histochemistry, immunohistochemistry and electron microscopy. In normal controls, virus was first seen in retinal ganglion cells and Müller glia after 1–1.5 days, and had spread to all retinal layers after 2–3 days. Virus‐labeled cells were found in 16 of 19 transplants where the virus injection had retrogradely labeled the topographically correct transplant area of the host retina. Electron microscopically, enveloped and nonenveloped virus could clearly be detected in infected cells. Enveloped virus was found only in neurons. Infected glial cells contained only nonenveloped virus. Neurons in retinal transplants are labeled after PRV injection into the host brain, indicating synaptic connectivity between transplants and degenerated host retinas. This study provides evidence that PRV spreads in the retina as in other parts of the CNS and is useful to outline transplant–host circuitry.
Antioxidant metabolite profiles in tomato fruit constitutively expressing the grapevine stilbene synthase gene
Authors: Giovinazzo Giovanna , D’Amico Leone , Paradiso Annalisa , Bollini Roberto , Sparvoli Francesca , DeGara Laura
Published: January 2005

Tomato (Lycopersicon esculentum Mill.) tissues were transformed with a grape (Vitis vinifera L.) stilbene synthase cDNA, transcriptionally regulated by the cauliflower mosaic virus (CaMV) 35S promoter. Transgenic plants accumulated new compounds, not present in either wild‐type or vector‐transformed plants. These were identified, by high‐pressure liquid chromatography, as trans‐resveratrol and trans‐resveratrol‐glucopyranoside. The amounts of trans‐resveratrol and its piceid form were evaluated in the transgenic fruit. It was found that the content of the metabolite varied during fruit maturation to up to 53 µg/g fresh weight of total trans‐resveratrol at the red stage of ripening. This metabolite accumulation was possibly dependent on a combination of sufficiently high levels of stilbene synthase and the availability of substrates. With the aim of verifing the metabolic impairment, the amounts of chlorogenic acid and naringenin in both transgenic and wild‐type ripening fruit were compared and no dramatic variation in the synthesis profile of the two metabolites was noted. To our knowledge, no data are available on the assessment of the effects of the expression of the StSy gene on other antioxidant compounds present in tomato fruit. To establish whether the presence of a novel antioxidant molecule affected the redox regulation in transgenic tomato fruit cells, the effect of resveratrol accumulation on the naturally present antioxidant pool was analysed. We showed that, in transgenic fruit which accumulate trans‐resveratrol, there is an increase in the levels of ascorbate and glutathione, the soluble antioxidants of primary metabolism, as well as in the total antioxidant activity. Conversely, the content of tocopherol and lycopene, which are membrane‐located antioxidants, is not affected. Consistent with the increased antioxidant properties, the lipid peroxidation was lower in transformed than in wild‐type fruit.
Experiences from Teaching Statistics Using Directed Projects in Greek Elementary School
Authors: Ghinis D. , Chadjipantelis Th. , Bersimis S.
Published: January 2005

In this article, we present the main findings of an experiment which involves teaching statistics in the 5th and 6th grade classes of Greek elementary schools. This experiment focused on the evaluation of the potentials of teaching statistical concepts and methods using directed projects.
A ‘Striking’ Demonstration of the Poisson Distribution
Authors: Buonaccorsi Vincent , Skibiel Amy
Published: January 2005

This article describes a simple classroom activity that helps students immediately visualize and understand the meaning and mathematical properties of the Poisson distribution.
The influence of perinatal complications and environmental adversity on boys’ antisocial behavior
Authors: Beck Joy E. , Shaw Daniel S.
Published: January 2005

Background:  The purpose of the present study was to test components of biosocial model, specifically the interactive effects of perinatal complications, rejecting parenting, and family adversity on the development of early‐onset antisocial behavior (ASB). Boys’ internalizing problems were also tested to investigate the specificity of the model.

Methods:  Birth records in addition to longitudinal data were collected on 310 low‐income boys followed from birth until 10 years of age.

Results:  Findings demonstrated support for a biosocial framework in predicting ASB but not internalizing problems. Family adversity, and to some extent rejecting parenting, consistently predicted youth outcome. Perinatal complications emerged as a predictor of ASB but only in the context of other family risk factors. According to maternal report, boys experiencing high levels of perinatal complications, rejecting parenting, and family adversity showed significantly higher levels of ASB than boys with lower levels of these risk factors. This finding was partially corroborated by youth self‐report, such that boys experiencing high levels of perinatal complications and family adversity reported more antisocial activity than boys experiencing no risk or risk in only one domain.

Conclusions:  This study supports the specific prediction of ASB in middle childhood from a biosocial model. Findings also highlight the salience of a negative psychosocial environment on childhood maladjustment. Intervention efforts including parenting skills and coping strategies for mothers of children from multiple risk environments are advocated.
Time‐course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging
Authors: Manczak Maria , Jung Youngsin , Park Byung S. , Partovi Dara , Reddy P. Hemachandra
Published: January 2005

The study of aging is critical for a better understanding of many age‐related diseases. The free radical theory of aging, one of the prominent aging hypotheses, holds that during aging, increasing reactive oxygen species in mitochondria causes mutations in the mitochondrial DNA and damages mitochondrial components, resulting in senescence. Understanding a mitochondrial gene expression profile and its relationship to mitochondrial function becomes an important step in understanding aging. The objective of the present study was to determine mRNA expression of mitochondrial‐encoded genes in brain slices from C57BL6 mice at four ages (2, 12, 18, and 24 months) and to determine how these altered mitochondrial genes influence age‐related changes, including oxidative damage and cytochrome c in apoptosis. Using northern blot analysis, in situ hybridization, and immunofluorescence analyses, we analyzed changes in the expression of mitochondrial RNA encoding the mitochondrial genes, oxidative damage marker, 8‐hydroxyguanosine (8‐OHG), and cytochrome c in brain slices from the cortex of C57BL6 mice at each of the four ages. Our northern blot analysis revealed an increased expression of mitochondrial‐encoded genes in complexes I, III, IV, and V of the respiratory chain in 12‐ and 18‐month‐old C57BL6 mice compared to 2‐month‐old mice, suggesting a compensatory mechanism that allows the production of proteins involved in the electron transport chain. In contrast to the up‐regulation of mitochondrial genes in 12‐ and 18‐month‐old C57BL6 mice, mRNA expression in 24‐month‐old C57BL6 mice was decreased, suggesting that compensation maintained by the up‐regulated genes cannot be sustained and that the down‐regulation of expression results in the later stage of aging. Our in situ hybridization analyses of mitochondrial genes from the hippocampus and the cortex revealed that mitochondrial genes were over‐expressed, suggesting that these brain areas are critical for mitochondrial functions. Our immunofluorescence analysis of 8‐OHG and cytochrome c revealed increased 8‐OHG and cytochrome c in 12‐month‐old C57BL6 mice, suggesting that age‐related mitochondrial oxidative damage and apoptosis are associated with mitochondrial dysfunction. Our double‐labeling analysis of in situ hybridization of ATPase 6 and our immunofluorescence analysis of 8‐OHG suggest that specific neuronal populations undergo oxidative damage. Further, double‐labeling analysis of in situ hybridization of ATPase 6 and immunofluorescence analysis of cytochrome c suggest cytochrome c release is related to mitochondrial dysfunction in the aging C57BL6 mouse brain. This study also suggests that these mitochondrial gene expression changes may relate to the role of mitochondrial dysfunction, oxidative damage, and cytochrome c in aging and in age‐related diseases such as Alzheimer's disease and Parkinson's disease.
Protective effects of insulin‐like growth factor‐I on the somatostatinergic system in the temporal cortex of β‐amyloid‐treated rats
Authors: Aguado‐Llera D. , Arilla‐Ferreiro E. , Campos‐Barros A. , Puebla‐Jiménez L. , Barrios V.
Published: January 2005

Insulin‐like growth factor‐I (IGF‐I) has protective effects against β‐amyloid (Aβ)‐induced neuronal cell death. Because alterations of the somatostatinergic system have been described in Alzheimer's disease, we investigated the effects of the Aβ peptide and the possible protective role of IGF‐I on the somatostatinergic system of the rat temporal cortex and on cell death and phosphorylated (p)‐Akt levels in this area. Aβ25–35 was administered intracerebroventricularly to male rats via an osmotic minipump over 14 days (300 pmol/day). Another group received a subcutaneous IGF‐I infusion (50 μg/kg/day), concomitant with Aβ25–35 administration, whereas a third group received IGF‐I alone. Aβ25–35 significantly decreased the somatostatin (SRIF)‐like immunoreactive content and the SRIF receptor density, as a result of a decrease in the levels of the SRIF receptor subtype 2. The inhibitory effect of SRIF on adenylyl cyclase activity was significantly lower after Aβ25–35 infusion, whereas the levels of the inhibitory G protein subunit Giα1, Giα2 or Giα3 were unaltered. Cell death was increased and p‐Akt levels decreased in Aβ25–35‐treated animals. IGF‐I administration increased immunoreactive IGF‐I levels in the temporal cortex and restored all parameters affected by Aβ25–35 to baseline values. These findings suggest that IGF‐I prevents the deleterious effect of Aβ25–35 on the somatostatinergic system.
Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain
Authors: Groffen Alexander J. A. , Jacobsen Linda , Schut Désireé , Verhage Matthijs
Published: January 2005

Tomosyn was previously identified as a syntaxin‐binding protein that inhibits soluble NSF (n‐ethylmaleimide‐sensitive fusion protein) attachment protein receptor (SNARE)‐mediated secretion. We set out to investigate the distribution of tomosyn mRNA in the mammalian brain and found evidence for the presence of two paralogous genes designated tomosyn‐1 and ‐2. In a collection of tomosyn‐2 cDNA clones, we observed four splice variants (named xb‐, b‐, m‐ and s‐tomosyn‐2) derived from the skipping of exons 19 and 21. This feature is conserved with tomosyn‐1 that encodes three splice variants. To compare the expression pattern of tomosyn‐1 and ‐2, we performed in situ hybridization experiments with gene‐specific probes. Both genes were expressed in the nervous system, clearly following distinct spatial and developmental expression patterns. Real‐time quantitative PCR experiments indicated that tomosyn‐1 expression was up‐regulated less than threefold between developmental stages E10 and P12, whereas tomosyn‐2 expression increased 31‐fold. Not only the transcription level, but also the splice composition of tomosyn‐2 mRNA shifted during development. We conclude that two distinct genes drive expression of seven tomosyn isoforms. Their expression patterns support a role in regulating neuronal secretion. All isoforms share conserved WD40 and SNARE domains separated by a hypervariable module, the function of which remains to be clarified.
Differential effects of melanin concentrating hormone on the central dopaminergic neurons induced by the cocaine‐ and amphetamine‐regulated transcript peptide
Authors: Yang Shu‐Chuan , Shieh Kun‐Ruey
Published: January 2005

Stimulatory effects of cocaine‐ and amphetamine‐regulated transcript (CART) peptide on central mesolimbic, nigrostriatal and mesocortical dopaminergic (DA) neurons were examined in female Sprague–Dawley rats. We also determined the different blocking effects of melanin concentrating hormone (MCH) on the stimulation by CART peptide in central DA systems. Intracerebroventricular administration of 1 µg CART peptide (55–102) produced increases in 3,4‐dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens (NA) at 15 and 45 min, and in the striatum (ST) at 15 min, but not in the medial prefrontal cortex (MPFC). We found that the agonist of α‐melanocyte stimulating hormone (α‐MSH), MT II, at 10 µg had a stimulatory effect on the NA and ST DOPAC levels similar to the CART peptide. In contrast, 1 µg MCH and the antagonist of α‐MSH, HS014, significantly decreased NA and ST DOPAC levels. However, only MCH prevented the stimulatory effect of CART peptide on DOPAC levels in the NA, but not in the ST. These results indicate that the stimulation of CART peptide on central DA neurons is region‐specific, and that this effect can be blocked by MCH but not by the antagonist of α‐MSH.
Neuronal calcium sensor‐1 facilitates neuronal exocytosis through phosphatidylinositol 4‐kinase
Authors: Zheng Qian , Bobich Joseph A. , Vidugiriene Jolanta , McFadden Susanne C. , Thomas Fairwell , Roder John , Jeromin Andreas
Published: January 2005

This work tested the theory that neuronal calcium sensor‐1 (NCS‐1) has effects on neurotransmitter release beyond its actions on membrane channels. We used nerve‐ending preparations where membrane channels are bypassed through membrane permeabilization made by mechanical disruption or streptolysin‐O. Nerve ending NCS‐1 and phosphatidylinositol 4‐kinase (PI4K) are largely or entirely particulate, so their concentrations in nerve endings remain constant after breaching the membrane. Exogenous, myristoylated NCS‐1 stimulated nerve ending phosphatidylinositol 4‐phosphate [PI(4)P] synthesis, but non‐myristoylated‐NCS‐1 did not. The N‐terminal peptide of NCS‐1 interfered with PI(4)P synthesis, and with spontaneous and Ca2+‐evoked release of both [3H]‐norepinephrine (NA) and [14C]‐glutamate (glu) in a concentration‐dependent manner. An antibody raised against the N‐terminal of NCS‐1 inhibited perforated nerve ending PI(4)P synthesis, but the C‐terminal antibody had no effects. Antibodies against the N‐ and C‐termini of NCS‐1 caused significant increases in mini/spontaneous/stimulation‐independent release of [3H]‐NA from perforated nerve endings, but had no effect on [14C]‐glu release. These results support the idea that NCS‐1 facilitates nerve ending neurotransmitter release and phosphoinositide production via PI4K and localizes these effects to the N‐terminal of NCS‐1. Combined with previous work on the regulation of channels by NCS‐1, the data are consistent with the hypothesis that a NCS‐1–PI4K (NP, neuropotentiator) complex may serve as an essential linker between lipid and protein metabolism to regulate membrane traffic and co‐ordinate it with ion fluxes and plasticity in the nerve ending.
Ampakine™ CX546 bolsters energetic response of astrocytes: a novel target for cognitive‐enhancing drugs acting as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor modulators
Authors: Pellerin Luc , Magistretti Pierre J.
Published: January 2005

Glutamate was previously shown to enhance aerobic glycolysis i.e. increase glucose utilization and lactate production with no change in oxygen levels, in mouse cortical astrocytes by a mechanism involving glutamate uptake. It is reported here that a similar response is produced in both hippocampal and cerebellar astrocytes. Application of the cognitive‐enhancing drug CX546 promoted further enhancement of glucose utilization by astrocytes from each brain area following glutamate exposure. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors represent the purported molecular target of cognitive‐enhancing drugs such as CX546, and the presence of AMPA receptor subunits GluR1–4 was evidenced in astrocytes from all three regions by immunocytochemistry. AMPA itself did not stimulate aerobic glycolysis, but in the presence of CX546, a strong enhancement of glucose utilization and lactate production was obtained in cortical, hippocampal and cerebellar astrocytes. The effect of CX546 was concentration‐dependent, with an EC50 of 93.2 µm in cortical astrocytes. AMPA‐induced glucose utilization in the presence of CX546 was prevented by the AMPA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and the negative modulator GYKI 52466. In addition, the metabolic effect of CX546 in the presence of AMPA was mimicked by the AMPA receptor modulator cyclothiazide. Our data suggest that astrocyte energetics represents a novel target for cognitive‐enhancing drugs acting as AMPA receptor modulators.
C‐terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
Authors: Boeckers Tobias M. , Liedtke Thomas , Spilker Christina , Dresbach Thomas , Bockmann Jürgen , Kreutz Michael R. , Gundelfinger Eckart D.
Published: January 2005

Synapses are specialized contact sites mediating communication between neurons. Synaptogenesis requires the specific assembly of protein clusters at both sides of the synaptic contact by mechanisms that are barely understood. We studied the synaptic targeting of multi‐domain proteins of the ProSAP/Shank family thought to serve as master scaffolding molecules of the postsynaptic density. In contrast to Shank1, expression of green‐fluorescent protein (GFP)‐tagged ProSAP1/Shank2 and ProSAP2/Shank3 deletion constructs in hippocampal neurons revealed that their postsynaptic localization relies on the integrity of the C‐termini. The shortest construct that was perfectly targeted to synaptic sites included the last 417 amino acids of ProSAP1/Shank2 and included the C‐terminal sterile alpha motif (SAM) domain. Removal of 54 residues from the N‐terminus of this construct resulted in a diffuse distribution in the cytoplasm. Altogether, our data delineate a hitherto unknown targeting signal in both ProSAP1/Shank2 and ProSAP2/Shank3 and provide evidence for an implication of these proteins and their close homologue, Shank1, in distinct molecular pathways.
Tournefolic acid B methyl ester attenuates glutamate‐induced toxicity by blockade of ROS accumulation and abrogating the activation of caspases and JNK in rat cortical neurons
Authors: Chi Chih‐Wen , Wang Chuen‐Neu , Lin Yun‐Lian , Chen Chieh‐Fu , Shiao Young‐Ji
Published: January 2005

The effects of nine polyphenolic compounds on glutamate‐mediated toxicity were investigated. The underlying mechanisms by which a polyphenolic compound confers its effect were also elucidated. Treatment of cortical neurons with 50 µm glutamate for 24 h decreased cell viability by 45.8 ± 7.9%, and 50 µm of tournefolic acid B methyl ester attenuated glutamate‐induced cell death by 46.8 ± 17.8%. Glutamate increased the activity of caspase 35.2‐fold, and to a similar extent for caspase 2, 6, 8 and 9. Tournefolic acid B methyl ester abrogated glutamate‐induced activation of caspase 2, 3, 6 and 9 by about 70%, and to a lesser extent for caspase 8. Treatment with glutamate for 1 h elevated reactive oxygen species (ROS) by 208.3 ± 21.3%. Tournefolic acid B methyl ester eliminated the glutamate‐induced accumulation of ROS. Glutamate increased the phosphorylation of p54‐c‐jun N‐terminal kinase (JNK) concomitantly with activation of the endogenous antioxidant defense system. Tournefolic acid B methyl ester at 50 µm diminished the activity of p54‐JNK in control and glutamate‐treated cells, coinciding with the abolishment of the glutamate‐triggered antioxidant defense system. Therefore, tournefolic acid B methyl ester blocked the activation of the caspase cascade, eliminated ROS accumulation and abrogated the activation of JNK, thereby conferring a neuroprotective effect on glutamate‐mediated neurotoxicity.
Musical hallucinations induced by bromocriptine
Authors: KOBAYASHI Toshiyuki , MIYATA Yoshifumi , OKAMOTO Sohei , KATO Satoshi
Published: January 2005

A case of bromocriptine‐induced musical hallucinations in a 67‐year‐old patient with probable Lewy body dementia is reported. The patient was given bromocriptine for the treatment of parkinsonism. At a bromocriptine dosage of  7.5 mg,  the  patient  complained,  ‘I  hear  karaoke  songs  in  the  inner  part of my head.’ The musical hallucinations gradually decreased after administration of the drug was discontinued. Bromocriptine is known to cause hallucinations, but not musical hallucinations. The dopaminergic effect of bromocriptine and the patient's cognitive impairment might have acted together to generate the musical hallucinations.
Early diagnosis of Alzheimer's type dementia with special reference to the clinicopathology of mild cognitive impairment
Authors: IKEDA Kenji , MIZUNO Yutaka , AKIYAMA Haruhiko , IRITANI Shuji , MATSUSHITA Masaaki
Published: January 2005

A considerable number of patients with Alzheimer‐type pathology begin with various types of psychiatric symptoms. In discussing mild cognitive impairment (MCI) and Alzheimer‐type dementia (ATD), psychiatric symptoms other than memory impairment must be considered. There is no obvious neuropathological boundary that distinguishes dementia from non‐dementia. In fact, although Alzheimer‐type pathology of MCI corresponds mainly to Braak's stage I or II, it has a wide range extending from Braak's stage I to V or VI. Difference in compensatory ability and environmental factors among individuals seem to affect the mental state more extensively than previously thought. MCI manifests most frequently in Braak's stage I and II (transentorhinal stage) and its Alzheimer‐type pathology is almost confined to the hippocampal region. Although the degree and distribution of senile plaques vary in each patient, the cerebral isocortex is virtually free from degeneration. There is discrepancy between the corresponding neuropathology and hypo‐metabolism in the posterior cingulated cortex (PCC), which is regarded as an important finding for the early diagnosis of ATD. In PCC, hypo‐metabolism seems to precede that morphological change especially in its premorbid or early period of ATD. The state of MCI could also occur in other diseases causing dementia, among which tangle‐only dementia is particularly notable. The characteristic of tangle‐only dementia is the gradually progressive, persistent pathological memory impairment with relative preservation of personality and cognitive function. These characteristics meet the criteria for MCI. Thus, tangle‐only dementia should be taken into account in patients who exhibit MCI but do not progress to the development of dementia over a prolonged period.
Parathyroid hormone and biochemical profile in chronic kidney disease patients in South India
Authors: Sankarasubbaiyan Suresh , Abraham Georgi , Soundararajan P , Chandrasekaran V , Padma G
Published: January 2005

Renal osteodystrophy is an important complication of chronic kidney disease characterized by abnormal bone turnover with varied bone histologic changes. Etiology is multifactorial including abnormalities of serum calcium, phosphorus, and 1,25(OH)2‐vitamin D deficiency; secondary hyperparathyroidism; age; cause of kidney disease; diet; renal replacement therapy; and drug therapy. In addition, there is evidence that there may be ethnic differences. Our study is a description of a case series of hormonal and biochemical abnormalities of bone disease in end‐stage renal disease patients in South India. A total of 115 patients were studied; 86% were on hemodialysis and 14% were on peritoneal dialysis (age, 47.31 ± 14.66 years). Sixty‐eight% were men. Diabetes was the cause of end‐stage renal disease in 29.5%. Intact parathyroid hormone (PTH) level was 124.6 ± 174.9 pg/mL and less than twice normal in 69.5% of patients. Hypocalcemia was present in 16.5% and hyperphosphatemia in 35.7% of patients. Empirical vitamin D was prescribed in 40% of patients. Age, sex, diabetic status, and vitamin D use were similar in patients with high PTH (130 pg/mL) and low PTH levels (< 130 pg/mL). Bone histologic studies were not performed owing to economic limitation. But the biochemical and hormonal results are suggestive of a mild form of osteodystrophy in Indian patients. Etiology remains uncertain but differences in dietary intake, tropical climate, vitamin D activation, vitamin D receptor polymorphism, parathyroid gland sensitivity, and PTH target organ sensitivity may account for the difference in pattern in bone disease.
Clearance of small molecules in different dialyzer flow configurations
Authors: Eloot S. , De Vos J.Y. , Hombrouckx R. , Verdonck P.
Published: January 2005

To overcome problems of insufficient clearance, multiple dialyzers may be placed in series or in parallel. The present study aimed to investigate in vitro the overall clearance of small molecules in different dialyzer configurations in which mutual flow directions were changed.

Single pass tests were performed with low flux Fresenius F6HPS dialyzers placed in series (12 tests), in parallel (6) and in single use (2). As blood substitute, either high concentrated (45 mS) bicarbonate dialysate (AB solution – MW20‐180) or a trisodiumphosphate (Na3PO4– MW395) concentration (30 mS) was used. Standard blood and dialysate flows of 250 and 500 mL/min, respectively, were applied. Furthermore, clearance was derived from conductivity measurements in the inlet and outlet bloodline, correcting for the overall ultrafiltration rate of 0.5 L/h (AB) and 0.1 L/h (Na3PO4).

Compared to the standard setup using a single dialyzer with counter current flows, clearance increases by 3 to 8%(AB) and by 15 to 18%(Na3PO4) using two dialyzers in parallel and in series, respectively. With co‐current flows in a serial dialyzer set up, clearance increases by 16%(AB) and 22%(Na3PO4) compared to the single dialyzer use. Changing subsequently the counter current flows to co‐current in one and both dialyzers in series, the overall clearance decreases by 2 to 9%, respectively, for the AB solution, and by 8 to 15% for the Na3PO4 concentration. With respect to the parallel dialyzer setup, a split dialysate flow (250 mL/min in each dialyzer) counter current to the blood flow, increases the clearance by 4 and 12%, respectively.

In conclusion, overall clearance is most ameliorated using two dialyzers in series with counter current flows.
Extrapulmonary tuberculosis with multiple localizations in a patient with end‐stage renal disease
Authors: Sav T. , Tokgoz B , Sipahioglu M.H , Mavili E , Oymak O , Utas C.
Published: January 2005

The incidence of active tuberculosis among patients on long‐ term dialysis is higher than the rate in the general population. Case: 39‐year‐old male patient with ESRD was admitted to hospital with dyspnea, weight loss, cough without sputum and hemoptysis, and a palpable painless mass under the right areola. He was on maintenance hemodialysis three times a week for the last six months. PPD was negative. Chest X‐ray examination revealed a hyperdense lesion. On the computerized tomography a cystic mass at the inferior lobe superior segment near the thorasic vertebra was detected. Fine needle aspiration from each of the mass lesions revealed granulomas and acido‐resistant bacteria. Anti‐tuberculous therapy was initiated. After eight months he came back with paraplegia. Magnetic resonance imaging (MRI) revealed that the lesion which previously has been described by CT was extending to the spinal duct and pressing on the spinal cord. After a biopsy, granuloma was seen; however, mycobacterium tuberculosis did not grow in the culture. Discussion: Extrapulmonary tuberculosis is common in patients with ESRD. In the present case we established that the patient who presented a mass on the chest wall without pulmonary tuberculosis findings had indeed a tuberculous cavity mass. It is interesting to note that in this case this mass had no relationship to the tuberculous cavity in the lung tissue. Moreover, it is also interesting that paraspinal lesion occured during the period in which the patient was under treatment and it quickly progressed and led to paraplegia. Tissue biopsy with invasive procedures may be necessary. Thus, in areas with a high prevalence of tuberculosis, renal patients in high‐risk group (renal transplant recipients, hemodialysis and CAPD patients) should be examined periodically to exclude silent infection and reduce morbidity and mortality.
Effectiveness of catheter hub sanitation prior to dialysis
Authors: Bousquet G
Published: January 2005

Purpose: 
Contamination of catheter hub connectors is known to cause catheter‐related blood stream infections in patients undergoing hemodialysis via central venous catheters (CVC). The effectiveness of cleansing the hub with an antimicrobial agent was assessed by culturing the surface of the hub following sanitation. Methods: The CVC hub connectors of 24 patients were sanitized using the standard hospital protocol of aseptically swabbing the connectors with a solution of bleach or Betadine, and then bathing the hub in sterile gauze soaked with the antimicrobial solution for 5 minutes. The exterior surface of the hub was then cultured for a broad spectrum of microorganisms. Patients were monitored for exit site infection, tunnel infection, and septicemia. In the laboratory, sterile hubs were inoculated with E. coli, staph. aureus neg., and yeast. Hubs were then immersed in Betadine for 5, 10, or 30 min. and cultures were taken. Results: Positive cultures were obtained from the hubs of 17 of the 24 patients. Seven (7) of the patients with positive results developed bacteremia from the cultured organism within 7 weeks. Positive cultures were obtained from 50% of inoculated lab samples after 5 min, 10% after 15 min, and 0% after 30 min. of immersion sanitation. Conclusions: The techniques for cleansing CVC hubs should be revisited.
Clinical Experiences  High‐flux hemodialysis in the treatment of severe valproic acid overdose: A case report
Authors: Chebrolu S.B. , Hou S.H. , Kjellstrand C.M. , Ing T.S. , Hines VA
Published: January 2005

Introduction: 
Hemoperfusion, with or without hemodialysis, has been used to treat patients suffering from severe valproic acid poisoning. We report a patient suffering from severe valproic acid intoxication who was treated effectively with high‐flux hemodialysis alone. Case: A 20‐year‐old man with a history of bipolar disorder was admitted after having ingested unknown amounts of valproic acid (Depakote®), prednisone, and erythromycin. He was agitated and obtunded but hemodynamically stable initially. Serum valproic acid level was 1,028 μg/mL. Urine toxicology screen as well as serum levels of ethanol, acetaminophen, and acetylsalicylic acid levels were negative. A gastric lavage was followed by activated charcoal instillation. Subsequent myoclonic twitchings that progressed to continuous seizure activity were managed with intravenous lorazepam therapy and endotracheal intubation. Serum valproic acid value measured two hours after admission remained elevated at 1,046 μg/mL. Hemodialysis was performed continuously for 10.5 hours using a high‐flux, polysulfone dialyzer (Polyflux 21S, Fresenius Medical Care, Lexington, MA), a dialyzer blood flow of 200–300 mL/min, and a dialysate flow of 500 mL/min. The therapy brought about a fall in serum valproic acid level to 110 μg/mL and a complete recovery of the patient. Discussion: Valproic acid (144 Dalton) is 90–95% protein‐bound at therapeutic serum values. However, in the face of an overdose, the unbound fraction rises because of saturation of protein‐binding sites. This unbound fraction is readily dialyzable. We suggest that high‐flux hemodialysis is effective in the treatment of severe valproic acid poisoning.
Hemodialysis‐induced acute pancreatitis secondary to kinked hemodialysis blood lines
Authors: Abtahi M. , Uzan M. , Souid M.
Published: January 2005

Introduction: 
Hemolytic reactions developing during hemodialysis usually are caused by oxidant damage, reduction injury, and osmolar, thermal, and mechanical injury to the red blood cells. Mechanical injury due to maloccluded blood pumps, arterial line collapse, and use of subclavian hemodialysis catheters has been reported. We report one episode of acute hemolysis due to kinked hemodialysis blood lines complicated with pancreatitis. Case Report: An 18‐year‐old man with end‐stage renal failure of unknown origin had been on hemodialysis since 2002. His past medical history included asthma and hypertension. He was admitted to the hospital because of severe abdominal pain, nausea, and vomiting during the dialysis session. Laboratory examination showed hematocrit −30 %, platelet count of 131,000 per cubic mL, LDH −5151 U/L, haptoglobin −0.09 g/L, lipase −919 U/L, CPK‐ 260, ASAT −584 U/L, ALAT‐ 316 U/L, bilirubin −36 μmol/L, and visible schistocytes on smear. Examination of the abdomen revealed diffuse discomfort and tenderness in epigastrium. The patient was diagnosed as having hemolysis‐induced acute pancreatitis. He was treated symptomatically and recovered within a few days. We found the arterial blood line tightly kinked at the dialyser inlet port, and we excluded other reported causes of intravascular hemolysis during hemodialysis. Discussion: Until a critical pressure is exceeded, despite a kink in the post pump predialyser blood tubing, the blood pump can maintain sufficient blood flow to prevent an increase in the arterial pressure with a triggering of the arterial alarm and a decrease in the venous pressure with a triggering of the venous alarm. Thus, an excessively high pressure can be maintained in this silent segment of the dialyser tubing without activating the pressure alarms, exposing the red blood cells to high sheer stresses and resulting in clinically significant hemolysis. Acute hemolysis can cause a life‐threatening acute pancreatitis. The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. The important role of inflammatory cytokines in the pathogenesis of acute pancreatitis is well known. Heme released from hemoglobin after episodes of vascular hemolysis has the potential to act as a signalling molecule involved in the triggering of the inflammatory processes associated with massive hemolysis. Hemolysis itself may induce acute pancreatitis by all or some pathways of neutrophil activation and chemoattraction, such as oxidative burst, direct proinflammatory effect, microcirculatory disturbance, and increased expression of proinflammatory and immunoregulatory cytokines.
Cutting balloon angioplasty for resistant venous stenoses in hemodialysis patients
Authors: Jung H.W. , Kim Y.O. , Song H.H. , Park J.A. , Kim Y.S. , Kim S.Y. , Choi E.J. , Chang Y.S. , Bang B.K.
Published: January 2005

Purpose: 
To report our initial experience of using cutting balloons angioplasty in the treatment of resistant venous stenoses of Brescia‐Cimino fistulas. Materials and Methods: Forty‐eight patients with Brescia‐Cimino fistulas underwent percutaneous transluminal angioplasty (PTA) of 62 venous stenoses. Of these 48 patients, we encountered 8 venous stenoses (8/62, 12.9%) in 7 patients that were not successfully dilated with 6–8 mm high‐pressure balloons inflated up to 24 atm. In each of 8 stenoses, peripheral cutting balloons with diameters of 5–8 mm were employed to dilate resistant stenoses. Results: The locations of stenoses were 3 at the surgical vein mobilization site (“swing point”), 4 at the cephalic vein downstream from the anastomosis, and 1 at the cephalic arch. The grade of stenosis after high‐pressure balloon angioplasty ranged from 57% to 87%(mean, 76%). Cutting balloons expanded completely in all stenoses and the residual stenosis after cutting balloon PTA ranged from 0% to 24%(mean, 7%). Residual stenosis was virtually nonexisistent at the 3 stenoses of “swing point.” A focal rupture with a large hematoma occurred at the cephalic arch stenosis, which was treated by a stent placement. One minimal rupture that did not require any treatment occurred at the stenosis of downstream cephalic vein. No repeat angioplasty has been needed during follow‐up period (range, 74–249 days). Conclusion: Our early experience demonstrated that when high‐pressure balloons fail to dilate stenoses of Brescia‐Cimino fistulas, peripheral cutting balloons with diameters of 5–8 mm can be effectively used to overcome the resistance of stenoses.
Role of bicarbonate dialysis in prevention of serious arrhythmias in high‐risk cardiac patients undergoing regular hemodialysis
Authors: El Sharkawy M.M. , Shaalan H.S. , Okasha N. , El Gendy M.F.
Published: January 2005

Background: 
Cardiac arrhythmias are considered as one of the most important causes of mortality in patients on hemodialysis. Arrhythmias frequently occur in patients with chronic renal failure on regular hemodialysis with reported incidences varying from 30–48% of patients. These abnormalities can span from supraventricular to severe ventricular arrhythmia. There is an increased frequency of occurrence and clustering of arrhythmias around the dialysis time. Aim of the study: To detect the difference between acetate and bicarbonate dialysis as regard to the type and frequency of arrhythmia in those patients. Study design: This study was done on 20 male patients age 51–73, all have history of heart disease. Patients were divided into 2 equal groups using acetate in group 1 and bicarbonate in group 2. All patients were on regular hemodialysis (4 hours, thrice weekly). Careful history and clinical examination were done. Pre‐dialysis investigations included serum creatinine, blood urea nitrogen, serum sodium, potassium, calcium and phosphorus, serum albumin, hemoglobin, and arterial blood gases. Post‐dialysis serum potassium and arterial blood gases were measured. ECG and forty‐eight hours ambulatory monitor (Holter monitor)(before, during, and after hemodialysis, till the end of the dialysis day and throughout the following day) were performed. Results: Group 1 showed significantly less post‐dialysis supraventricular arrhythmias than in dialysis day (210.9 ± 236 and 62.3 ± 14.4), respectively. Significantly less ventricular arrhythmias in post‐dialysis than in dialysis day (30.7 ± 50.4, and 106.2 ± 128.4), respectively. While in Group 2 there were insignificant differences regarding supraventricular arrhythmias (21.9 ± 28.9 and 16.6 ± 36.3) and ventricular arrhythmias (22.9 + 7.8 and 29.6 + 12.8) in dialysis day than in post‐dialysis day. There was significantly higher frequency of supraventricular and ventricular arrhythmias in the dialysis day in acetate hemodialysis in comparison to bicarbonate hemodialysis. Conclusion: Bicarbonate hemodialysis is less arrhythmogenic in comparison to acetate hemodialysis and has better effect on the blood pH and greater degree of base repletion. Continuous ambulatory ECG recording (Holter) is a useful tool in detecting arrhythmias in dialysis patients.
Compliance, quality of life, and contributing factors in renal transplantation waiting list patients
Authors: Akman B. , Colak T. , Ibis A. , Arat Z. , Ozdemir F.N , Haberal M.
Published: January 2005

Poor patient compliance is common during dialysis therapy. We aimed to study incidence of noncompliance, contributing factors, and effects on quality of life (QOL) among cadaveric renal transplantation waiting list patients. We included 86 renal transplantation waiting list patients (56M/30F). Dialysis duration, previous renal transplantation history, comorbid conditions, interdialytic weight gain, predialysis BUN, creatinine, potassium, and phosphate were recorded. Noncompliance criteria were skipping >1 dialysis session or shortening a dialysis session>10 min in 1 month, interdialytic weight gain>5.7% of body weight, predialysis serum potassium >6 mEq/L, and phosphate level >7.5 mg/dl. There were 49 noncompliant (age: 46.8 ± 21.8 years, HD duration: 83.9 ± 48.7 months) and 37 compliant (age: 42.8 ± 12.1 years, HD duration: 96.5 ± 45.2 months) patients. QOL was evaluated by short form 36 and depression levels by Beck Depression Inventory. Previous renal transplantation was present in 24.4% and comorbid diseases in 31.3% of all patients. In depressed patients, 77.8% had comorbid diseases. No difference was found between the groups considering age, gender, dialysis duration, previous transplantation history, and comorbid diseases (p > 0.05). Noncompliant patients had lower QOL (p < 0.04). Noncompliant patients had higher degree of depression (p = 0.01). QOL and Beck scores were negatively correlated (p = 0.001, r = −0.561). Noncompliance to diet and dialysis therapy is associated with depression, which further decreases QOL in renal transplantation waiting list patients. Early diagnosis of depression, is possible by monitoring noncompliance, and therapeutic intervention may benefit during the transplantation‐waiting period.
Kinetics, Dialysis Systems, and Adequacy  Copper deficiency: A common cause of erythropoietin (rHuEPO) resistant anemia in children on hemodialysis (HD)?
Authors: Warady B.A. , Nelms C. , Jennings J. , Johnson S.
Published: January 2005

Copper (CU) deficiency, as reflected by a low serum CU and ceruloplasmin (CER) level, is a rare complication of chronic HD. When present, common clinical manifestations include anemia and neutropenia. Anecdotally, CU deficiency has been linked to the use of sevelamer hydrochloride (SH), a recently introduced phosphate binding agent. The finding of severe CU deficiency and rHuEPO‐resistant anemia in 3 of our patients (pts) prompted a review of our entire pediatric HD population for the frequency of CU deficiency and its possible relationship to SH. An assessment of serum CU was conducted in 17 pts (male‐11; mean age 169.4 + 49.6 mo) who had received HD for 21.5 + 33.9 months. All pts received three 4‐hour HD sessions weekly with mean single‐pool and equilibrated Kt/V values of 2.29 + 2.5 and 1.56 + 0.37, respectively. 14 of 17 (82%) pts had low serum CU levels with a mean value of 69.1 + 38.3 mcG/DL (normal = 85–150 mcG/DL). 9 of 17 (53%) pts had values <60 mcG/DL and 3 pts had values <25 mcG/DL with CER values of 1.2 mg/dL, 0.6 mg/dL, and 1.8 mg/dL, respectively (normal = 24–40 mg/dL). In the latter 3 pts, hemoglobin values fell to 5.4 gm/dL, 5.2 gm/dL, and 9.2 gm/dL despite regular rHuEPO dosing and adequate iron stores and all pts responded to supplemental CU therapy. The mean hemoglobin of the remaining 14 pts was 11.7 + 1.3 gm/dL. Whereas 13 of 14 (93%) CU deficient pts were receiving SH (142.1 + 112.3 mg/kg/d) for 331.0 + 293.6 days at the time of the CU assessment, there was no significant relationship demonstrated between the dose of SH or the duration of SH therapy and the serum CU level. In conclusion, CU deficiency appears to commonly occur in pediatric HD pts with extremely low values associated with profound anemia responsive to CU therapy. While the chronology of CU deficiency and the introduction of SH suggests an association, additional research is necessary to address this issue in a more definitive manner.