bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the radiological relationship between iliac crests, conus medullaris and vertebral level in children
Authors: Tame Simon J. , Burstal Richard
Published: October 2003

Background: The inability of anaesthetists to accurately identify vertebral spaces has been documented. The aim of our magnetic resonance imaging (MRI) study was to find the relationship of vertebral body level with Tuffier's line and the conus medullaris in children.

Methods: Forty‐nine children aged 10 years or less who had MRI scanning in the region of the lumbar spine were identified. If either the conus medullaris or iliac crests were visible, the corresponding vertebral body level was recorded.

Results: The level of the conus could be identified in 43 patients. The median conus level was at L1 with an interquartile range (IQR) of 0.5 vertebral levels. The level of the crests could be identified in 35 patients. The median crest height was L5 with an IQR of 0.5 vertebral levels. The difference between conus and crest levels could only be calculated in 29 patients. In the remainder of the children one of the two pieces of the data was not available. The median difference was 4 vertebral levels with an interquartile range (IQR) of 1. Two of 49 children, both of whom had tethered cords, had differences of <2 vertebral levels.

Conclusions: Our data confirmed that the iliac crests and conus medullaris were consistently related to the predicted vertebral levels in children. In the absence of a tethered spinal cord, subarachnoid puncture at L4–5 or below should present little risk of conus damage. Tuffier's line corresponded with a radiological level of L4–L5 in our study population.
Anaesthetic implications of Robinow syndrome
Authors: Lirk Philipp , Rieder Josef , Schuerholz Andreas , Keller Christian
Published: October 2003

Summary Robinow (fetal face) syndrome is a rare inherited multisystem disorder featuring mesomelic or acromesomelic limb shortening, facial and spinal deformities, hypoplastic genitalia, kidney disease and congenital heart defects. We report the anaesthetic management of a patient with Robinow syndrome presenting for elective surgery and review specific issues of interest in the perioperative workup.
A long‐term continuous infusion via a sciatic catheter in a 3‐year‐old boy
Authors: Ivani Giorgio , Codipietro Luigi , Gagliardi Ferdinando , Rosso Franca , Mossetti Valeria , Vitale Pasquale
Published: October 2003

We describe the case of a 3‐year‐old boy with a subtotal amputation of the right foot who received treatment for pain via a peripheral catheter positioned at the level of the sciatic nerve (lateral approach).We administered a continuous infusion of 0.2% ropivacaine, 0.4 mg·kg−1·h−1 plus clonidine 0.12 μg·kg−1·h−1 for 21 days.

Pain relief was complete and the patient did not require any further rescue analgesia throughout the period even during medications and surgical treatment in our intensive care unit.

We discuss the safety and efficacy of the use of a peripheral continuous infusion in children compared with other techniques of analgesia.
Validation of a six‐graded faces scale for evaluation of postoperative pain in children
Authors: Bosenberg A. , Thomas J. , Lopez T. , Kokinsky E. , Larsson L.E.
Published: October 2003

Background: The faces pain scales are often used for self‐report assessment of paediatric pain. The aim of this study was to evaluate the validity of a six‐graded faces pain scale after surgery by comparing the level of agreement between the children's report of faces pain scores and experienced nurses’ assessment of pain by observation of behaviour. The faces pain scores before, at and after administration of analgesics were analysed. The study was performed in two South African hospitals, one with a mainly rural population and the other with an urban population.

Methods: A total of 110 children aged 4–12 years, scheduled for inguinal surgery in the two South African hospitals, were included in the study. The anaesthetic technique was standardized. All patients received a caudal block preoperatively. Postoperative pain assessments were made every hour for 8 h after the caudal block was performed. A designated nurse assessed pain by using a four‐graded descriptive scale (no, mild, moderate or severe pain) and thereafter the child reported pain by using the six‐graded faces pain scale.

Results: A high correlation was found between the two methods of assessment (τ = 0.76, P < 0.0001). The correlation between methods was high in both hospital populations and in all age groups. The weakest correlation was found in children aged 8–12 years (τ = 0.56, P < 0.01). Significantly lower faces pain scores were found after administration of analgesics compared with pain rating before analgesics (P < 0.0001). The proportion of patients with pain scores above 2 decreased from 86% to 31% (P < 0.001).

Conclusions: The findings support this six‐graded faces pain scale as a useful and valid instrument for measuring pain in the postoperative period in children aged 4–12 years.
Detection of epidural catheters with ultrasound in children
Authors: Chawathe M.S. , Jones R.M. , Gildersleve C.D. , Harrison S.K. , Morris S.J. , Eickmann C.
Published: October 2003

Background:  The aim of this study was to assess whether a noninvasive imaging technique such as ultrasound could visualize an epidural catheter in the epidural space in children.

Methods:  Following local ethics committee approval and informed parental consent a pilot study of 12 cases was performed. Children undergoing major surgery requiring epidural analgesia were recruited. All catheters were introduced via the lumbar region. All children were scanned within 24 h of epidural insertion by consultant paediatric radiologists. If the catheter was identified in the epidural space then an attempt was made to visualize the entire length of the catheter.

Results:  The epidural catheter was detected in nine of 12 patients. All of these were less than 6 months old. The entire length of the catheter was visualized in five of the nine patients. It was possible to estimate the most cephalad level of the catheter in seven of the nine patients. This was in the thoracic region in all cases and an appropriate level for the intended surgical procedure. It was not possible to precisely identify the tip of the catheter as a distinct entity using ultrasound.

Conclusion:  This study shows that it is possible to visualize an epidural catheter in the epidural space in children under 6 months of age using ultrasound.
4D study of fluid effects on seismic data in the Gullfaks Field, North Sea
Authors: Landrø M. , Strønen L. K.
Published: October 2003

The use of seismic data as a fluid indicator has been investigated on data from a typical North Sea Field (Gullfaks). Examples of qualitative seismic analysis on one single dataset as well as on repeated datasets are shown, clearly demonstrating the usefulness for reservoir description and reservoir management for this field. Quantitative comparisons between expected and measured changes between water‐ and oil‐saturated reservoir rocks are presented. On a single dataset, we found a seismic amplitude increase of 26% between the water zone and the oil zone for the dipping top reservoir horizon. This value was significantly lower than the expected value based on rock physics and simple two‐layer seismic modelling, which was 80%. The discrepancy is attributed to initial oil saturations of probably less than 100%, the relatively high‐noise level in the seismic data, and interference effects with reflectivity from the oil–water contact. For a horizon between a low‐permeable layer (Ness) and a high‐permeable layer (Etive) we find a good quantitative agreement between the observed amplitude increase on the time lapse seismic data (41%) and the predicted amplitude increase from fluid substitution of well logs (40%). The general observation made in this study is that the seismic amplitudes are in good correspondence with the rock physics theory. Furthermore, the seismic fluid effects are visible in good reservoir sands, while heterogeneous sands with higher clay content show a weaker fluid signal on the seismic data.
Seismic constraints on the effects of gas hydrate on sediment physical properties and fluid flow: a review
Authors: Chand S. , Minshull T. A.
Published: October 2003

The formation of gas hydrates in marine sediments changes their physical properties and hence influences fluid flow. Here, we review seismic indicators of gas hydrates and relate these indicators to gas hydrate formation and fluid migration. Analyses of seismic data from sediments containing gas and gas hydrates in a variety of locations have shown that the characteristic bottom‐simulating reflector (BSR), which commonly marks the hydrate phase boundary is caused mainly by the presence of gas beneath the gas hydrate stability zone (GHSZ). The amplitude of the BSR is also dependent on the hydrate concentration and on the porosity of the sediment. The presence of gas hydrate alters the elastic properties of sediments, particularly if it cements sediment grains. However, multifrequency studies in various geological provinces show that any loss of reflectivity or blanking observed within the GHSZ is dependent on both the nature of the sediments and concentration of hydrate present. Gas beneath the BSR may cause amplitude anomalies and may result in bright spots and enhanced reflections. The presence of gas beneath the BSR is the primary cause of observed amplitude versus offset (AVO) anomalies, but the amplitude of these anomalies is also dependent on the amount of cementation brought by the gas hydrates within the GHSZ.

Fluid migration appears to play an important role in the formation and dissociation of gas hydrates in both active and passive margin settings. Fluid migration in accretionary prisms influences hydrate accumulation and may therefore control the spatial distribution of BSRs. Fluid migration may influence also the type of hydrate formed by bringing thermogenic gas containing higher order hydrocarbons to the GHSZ from below. Fluid advection may cause local dissociation of gas hydrates by bringing heat from below, thus shifting the gas hydrate phase boundary. Fluid flow within the GHSZ is limited by the formation of hydrate in the pore space, which reduces the permeability of the sediment. Features such as pockmarks, acoustic masking and acoustic turbidity are indirect indicators of fluid flow and identification of these features in seismic sections within and beneath the GHSZ may also suggest the formation of gas hydrate.
Unravelling the petroleum system by enhancing fluid migration paths in seismic data using a neural network based pattern recognition technique
Authors: Ligtenberg J. H.
Published: October 2003

Understanding the hydrocarbon migration system in the sub‐surface is a key aspect of oil and gas exploration. It is well known that conventional 3D seismic data contains information about hydrocarbon accumulations. Less known is the fact that 3D seismic data also contains information about hydrocarbon migration paths in the form of vertical noise trails. A method has been developed to highlight vertical noise trails in seismic data semi‐automatically, using assemblies of directive multi‐trace seismic attributes and neural network technology. The results of this detection method yield valuable information about the origin of hydrocarbons, about migration paths from source to prospect and about leakage or spillage from these prospects to shallow gas pockets or to the sea bed. Besides, the results reveal the sealing quality of faults, provide information on overpressure and whether prospects are charged or not. All these aspects are useful information for basin modelling studies and for an increased understanding of the petroleum system.
Fe(II)‐induced DNA damage in α‐synuclein‐transfected human dopaminergic BE(2)‐M17 neuroblastoma cells: detection by the Comet assay
Authors: Martin Francis L. , Williamson Sally J. M. , Paleologou Katerina E. , Hewitt Rebecca , El‐Agnaf Omar M. A. , Allsop David
Published: October 2003

Lewy bodies in the brains of patients with Parkinson's disease (PD) contain aggregates of α‐synuclein (α‐syn). Missense mutations (A53T or A30P) in the gene encoding α‐syn are responsible for rare, inherited forms of PD. In this study, we explored the susceptibility of untransfected human dopaminergic BE(2)‐M17 neuroblastoma cells, cells transfected with vector only, or cells transfected with wild‐type α‐syn, A30P α‐syn or A53T α‐syn to Fe(II)‐induced DNA damage in the form of single‐strand breaks (SSBs). DNA SSBs were detected following 2‐h treatments with various concentrations of Fe(II) (0.01–100.0 μm), using the alkaline single cell‐gel electrophoresis (‘Comet’) assay and quantified by measuring comet tail length (CTL) (μm). Fe(II) treatment induced significant increases in CTL in cells transfected with A30P α‐syn or A53T α‐syn, even at the lowest concentrations of Fe(II) tested. In comparison, untransfected cells, vector control cells or cells transfected with wild‐type α‐syn exhibited increases in SSBs only when exposed to concentrations of 1.0 μm Fe(II) and above. Even when exposed to higher concentrations (10.0–100.0 μm) of Fe(II), untransfected cells, vector control cells or cells transfected with wild‐type α‐syn were less susceptible to DNA‐damage induction than cells transfected with A30P α‐syn or A53T α‐syn. Incorporation of DNA‐repair inhibitors, hydroxyurea and cytosine arabinoside, enhanced the sensitivity of DNA damage detection. Susceptibility to Fe(II)‐induced DNA damage appeared to be dependent on α‐syn status because cells transfected with wild‐type α‐syn or A53T α‐syn were equally susceptible to the damaging effects of the mitochondrial respiratory chain inhibitor rotenone. Overall, our data are suggestive of an enhanced susceptibility to the toxic effects of Fe(II) in neuroblastoma cells transfected with mutant α‐syn associated with inherited forms of PD.
Stroke‐induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: effect of exogenous IGF‐1 and GDNF
Authors: Dempsey Robert J. , Sailor Kurt A. , Bowen Kellie K. , Türeyen Kudret , Vemuganti Raghu
Published: October 2003

Progenitor cells in the dentate gyrus of hippocampus (DG) and the subventricular zone of lateral ventricles (SVZ) generate new neurons throughout the life of mammals. Cerebral ischemia increases this basal progenitor cell proliferation. The present study evaluated the time frame of proliferation, length of survival and the phenotypes of the new cells formed after transient middle cerebral artery occlusion (MCAO) in adult spontaneously hypertensive rats. Compared to sham controls, ischemic rats showed a significantly higher number of newly proliferated cells (as defined by BrdU immunostaining) in both the DG (by fourfold, p < 0.05) and the SVZ (by twofold, p < 0.05). DG showed increased proliferation only in the first week of reperfusion and 49% of the cells formed in this period survived to the end of third week. Whereas, SVZ showed a continuous proliferation up to 3 weeks after MCAO, but the cells formed survived for less than a week. In both DG and SVZ, at the end of the first week of reperfusion, majority of the BrdU‐positive (BrdU+) cells were immature neurons (DCX positive). In the DG, 28% of the cells formed in the first week after MCAO mature into neurons (NeuN positive). The ischemic cortex and striatum showed several BrdU+ cells which were ED‐1 positive microglia/macrophages. At 1 week of reperfusion, MCAO‐induced progenitor cell proliferation in the ipsilateral DG was significantly increased by i.c.v. infusion of IGF‐1 (by 127 ± 14%, p < 0.05) and GDNF (by 91 ± 5%, p < 0.05), compared to vehicle. In the growth factor treated rats subjected to transient MCAO, several BrdU+ cells formed in the first week survived up to the third week.
Mass spectrometric investigation of the neuropeptide complement and release in the pericardial organs of the crab, Cancer borealis
Authors: Li Lingjun , Kelley Wayne P. , Billimoria Cyrus P. , Christie Andrew E. , Pulver Stefan R. , Sweedler Jonathan V. , Marder Eve
Published: October 2003

The crustacean stomatogastric ganglion (STG) is modulated by both locally released neuroactive compounds and circulating hormones. This study presents mass spectrometric characterization of the complement of peptide hormones present in one of the major neurosecretory structures, the pericardial organs (POs), and the detection of neurohormones released from the POs. Direct peptide profiling of Cancer borealis PO tissues using matrix‐assisted laser desorption/ionization (MALDI) time‐of‐flight (TOF) mass spectrometry (MS) revealed many previously identified peptides, including proctolin, red pigment concentrating hormone (RPCH), crustacean cardioactive peptide (CCAP), several orcokinins, and SDRNFLRFamide. This technique also detected corazonin, a well‐known insect hormone, in the POs for the first time. However, most mass spectral peaks did not correspond to previously known peptides. To characterize and identify these novel peptides, we performed MALDI postsource decay (PSD) and electrospray ionization (ESI) MS/MS de novo sequencing of peptides fractionated from PO extracts. We characterized a truncated form of previously identified TNRNFLRFamide, NRNFLRFamide. In addition, we sequenced five other novel peptides sharing a common C‐terminus of RYamide from the PO tissue extracts. High K+ depolarization of isolated POs released many peptides present in this tissue, including several of the novel peptides sequenced in the current study.
Selective γ‐hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ‐hydroxybutyric acid
Authors: Castelli M. Paola , Ferraro Luca , Mocci Ignazia , Carta Francesca , Carai Mauro A. M. , Antonelli Tiziana , Tanganelli Sergio , Cignarella Giorgio , Gessa Gian Luigi
Published: October 2003

Two γ‐hydroxybutyric acid (GHB) analogues, trans‐γ‐hydroxycrotonic acid (t‐HCA) and γ‐(p‐methoxybenzyl)‐γ‐hydroxybutyric acid (NCS‐435) displaced [3H]GHB from GHB receptors with the same affinity as GHB but, unlike GHB, failed to displace [3H]baclofen from GABAB receptors. The effect of the GHB analogues, GHB and baclofen, on G protein activity and hippocampal extracellular glutamate levels was compared. While GHB and baclofen stimulated 5′‐O‐(3‐[35S]thiotriphospate) [35S]GTPγS binding both in cortex homogenate and cortical slices, t‐HCA and NCS‐435 were ineffective up to 1 mm concentration. GHB and baclofen effect was suppressed by the GABAB antagonist CGP 35348 but not by the GHB receptor antagonist NCS‐382. Perfused into rat hippocampus, 500 nm and 1 mm GHB increased and decreased extracellular glutamate levels, respectively. GHB stimulation was suppressed by NCS‐382, while GHB inhibition by CGP 35348. t‐HCA and NCS‐435 (0.1–1000 µm) locally perfused into hippocampus increased extracellular glutamate; this effect was inhibited by NCS‐382 (10 µm) but not by CGP 35348 (500 µm). The results indicate that GHB‐induced G protein activation and reduction of glutamate levels are GABAB‐mediated effects, while the increase of glutamate levels is a GHB‐mediated effect. Neither t‐HCA nor NCS‐435 reproduced GHB sedative/hypnotic effect in mice, confirming that this effect is GABAB‐mediated. The GHB analogues constitute important tools for understanding the physiological role of endogenous GHB and its receptor.
Membrane receptors for oestrogen in the brain
Authors: Beyer Cordian , Pawlak Justyna , Karolczak Magdalena
Published: October 2003

Oestrogen is important for the development of neuroendocrine centres and other neural networks including limbic and motor systems. Later in adulthood, oestrogen regulates the functional performance of different neural systems and is presumably implicated in the modulation of cognitive efficiency. Although still a matter of controversial discussion, clinical and experimental studies point at a potential neuroprotective role of oestrogen. Concerning the concept of cellular oestrogen action, it is undisputed that it comprises the binding and activation of nuclear receptors. The last decades have, however, immensely broadened the spectrum of steroid signalling within a cell. Novel steroid‐activated intracellular signalling mechanisms were described which are usually termed ‘non‐classical’ or ‘non‐genomic’. The brain appears to be a rich source of this new mode of oestrogen action. Studies from the past years have pinpointed non‐classical oestrogen effects in many CNS regions. All available data support the view that non‐classical oestrogen action requires interactions with putative membrane binding sites/receptors. In this article, we aim at compiling the most recent findings on the nature and identity of membrane oestrogen receptors with respect to the brain. We also attempt to turn readers attention to the coupling of these ‘novel’ receptors to distinct intracellular signalling pathways.
15‐Deoxy‐Δ12,14‐prostaglandin J2regulates the functional state and the survival of microglial cells through multiple molecular mechanisms
Authors: Bernardo Antonietta , Ajmone‐Cat Maria Antonietta , Levi Giulio , Minghetti Luisa
Published: October 2003

We have previously reported that rat primary microglial cultures express the nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and that several functions associated with the activation of these cells, including nitric oxide (NO) and tumor necrosis factor‐α synthesis, are down‐regulated by 15‐deoxy‐Δ12,14‐prostaglandin J2(15d‐PGJ2) and ciglitazone, two specific PPAR‐γ agonists. Here we demonstrate that microglial cells not only express a functionally active PPAR‐γ, but also synthesize large amounts of 15d‐PGJ2upon stimulation with lipopolysaccharide (LPS). In addition, we show that, although 15d‐PGJ2and ciglitazone were equally effective in reducing microglial activation when used at 1–5 µmconcentrations, 15d‐PGJ2, but not of ciglitazone, reduced PGE2production at low concentration (0.1 µm) and induced a time‐dependent microglial impairment and apoptosis at high concentration (10 µm). Interestingly, the inhibition of PGE2production was achieved mainly through the inhibition of cycloxygenase‐2 enzymatic activity, as the expression of this enzyme and that of the microsomal isoform of PGE synthase remained unaltered. These findings suggest that 15d‐PGJ2affects the functional state and the survival of activated microglia through mechanisms only in part dependent on PPAR‐γ and that the concentration of 15d‐PGJ2is crucial in determining the particular microglial function affected.
Primary cortical neuronal cultures reduce cellular energy utilization during anoxic energy deprivation
Authors: Munns Shane E. , Meloni Bruno P. , Knuckey Neville W. , Arthur Peter G.
Published: October 2003

It has been widely hypothesized that neurons reduce cellular energy use in response to periods of energy deprivation. To test this hypothesis, we measured rates of energy use under normoxia and anoxia in immature (6 days in vitro) and mature (13 days in vitro) neuronal cultures. During anoxic incubation immature and mature cultures reduced cellular energy use by 80% and 45%, respectively. Reduced cellular energy use dramatically affected ATP depletion in neuronal cultures under anoxia. Intracellular ATP stores were expected to deplete within 3 min of anoxia. However, ATP was maintained at decreased but stabilized concentrations for at least 3 h. The capacity of neuronal cultures to reduce cellular energy use during anoxia correlated with their sensitivity towards simulated ischemia. Immature cultures, with the largest capacity to reduce cellular energy use, survived simulated ischemia 2.5 times longer than mature cultures. The addition of glutamate receptor antagonists to mature cultures further decreased cellular energy use during anoxia and significantly extended their survival time under simulated ischemia. This study verifies that primary cortical neuronal cultures reduce cellular energy use during energy deprivation. Additionally, we show that maturation of glutamate receptor activity increases non‐depressible energy demand in neuronal cultures.
Identification of Tau and MAP2 as novel substrates of Rho‐kinase and myosin phosphatase
Authors: Amano Mutsuki , Kaneko Takako , Maeda Akio , Nakayama Masanori , Ito Masaaki , Yamauchi Takashi , Goto Hideyuki , Fukata Yuko , Oshiro Noriko , Shinohara Azusa , Iwamatsu Akihiro , Kaibuchi Kozo
Published: October 2003

Rho‐kinase and myosin phosphatase are implicated in the phosphorylation‐state of myosin light chain downstream of Rho, which is thought to induce smooth muscle contraction and stress fibre formation in non‐muscle cells. Here, we found that microtubule‐associated proteins, Tau and MAP2, interacted with the myosin‐binding subunit (MBS) of myosin phosphatase, and were the possible substrates of both Rho‐kinase and myosin phosphatase. We determined the phosphorylation sites of Tau (Thr245, Thr377, Ser409) and MAP2 (Ser1796) by Rho‐kinase. We also found that Rho‐kinase phosphorylated Tau at Ser262 to some extent. Phosphorylation by Rho‐kinase decreased the activity of Tau to promote microtubule assembly in vitro. Substitutions of Ala for Ser/Thr at the phosphorylation sites of Tau (Tau‐AAA) did not affect the activity to promote microtubule assembly, while substitutions of Asp for Ser/Thr (Tau‐DDD), which are expected to mimic the phosphorylation‐state of Tau, slightly reduced the activity. When Tau, or mutated forms of Tau, were expressed in PC12 cells, followed by treatment with cytochalasin D, they promoted extension of the cell process in a cytochalasin‐dependent manner. However, Tau‐DDD showed the weaker activity in this capacity than wild‐type Tau or Tau‐AAA. These results suggest that the phosphorylation‐state of these residues of Tau affects its activity both in vitro and in vivo. Thus, it is likely that the Rho‐kinase/MBS pathway regulates not only the actin‐myosin system but also microtubule dynamics.
Polarized actin bundles formed by human fascin‐1: their sliding and disassembly on myosin II and myosin V in vitro
Authors: Ishikawa Ryoki , Sakamoto Takeshi , Ando Toshio , Higashi‐Fujime Sugie , Kohama Kazuhiro
Published: October 2003

Fascin‐1 is a putative bundling factor of actin filaments in the filopodia of neuronal growth cones. Here, we examined the structure of the actin bundle formed by human fascin‐1 (actin/fascin bundle), and its mode of interaction with myosin in vitro. The distance between cross‐linked filaments in the actin/bundle was 8–9 nm, and the bundle showed the transverse periodicity of 36 nm perpendicular to the bundle axis, which was confirmed by electron microscopy. Decoration of the actin/fascin bundle with heavy meromyosin revealed that the arrowheads of filaments in the bundle pointed in the same direction, indicating that the bundle has polarity. This result suggested that fascin‐1 plays an essential role in polarity of actin bundles in filopodia. In the in vitro motility assay, actin/fascin bundles slid as fast as single actin filaments on myosin II and myosin V. When myosin was attached to the surface at high density, the actin/fascin bundle disassembled to single filaments at the pointed end of the bundle during sliding. These results suggest that myosins may drive filopodial actin bundles backward by interacting with actin filaments on the surface, and may induce disassembly of the bundle at the basal region of filopodia.
GABAC receptor agonist suppressed ammonia‐induced apoptosis in cultured rat hippocampal neurons by restoring phosphorylated BAD level
Authors: Yang Li , Omori Kyoko , Omori Koichiro , Otani Hitomi , Suzukawa Junko , Inagaki Chiyoko
Published: October 2003

Ammonia‐induced apoptosis and its prevention by GABAC receptor stimulation were examined using primary cultured rat hippocampal neurons. Ammonia (0.5–5 mm NH4Cl) dose‐dependently induced apoptosis in pyramidal cell‐like neurons as assayed by double staining with Hoechst 33258 and anti‐neurofilament antibody. A GABAC receptor agonist, cis‐4‐aminocrotonic acid (CACA, 200 µm), but not GABAA and GABAB receptor agonists, muscimol (10 µm) and baclofen (50 µm), respectively, inhibited the ammonia (2 mm)‐induced apoptosis, and this inhibition was abolished by a GABAC receptor antagonist (1,2,5,6‐tetrahydropyridin‐4‐yl)methylphosphinic acid (TPMPA, 15 µm). Expression of all three GABAC receptor subunits was demonstrated in the cultured neurons by RT‐PCR. The ammonia‐treatment also activated caspases‐3 and ‐9 as observed in immunocytochemistry for PARP p85 and western blot. Such activation of the caspases was again inhibited by CACA in a TPMPA‐sensitive manner. The anti‐apoptotic effect of CACA was blocked by inhibitors for MAP kinase kinase and cAMP‐dependent protein kinase, PD98059 (20 µm) and KT5720 (1 µm), suggesting possible involvement of an upstream pro‐apoptotic protein, BAD. Levels of phospho‐BAD (Ser112 and Ser155) were decreased by the ammonia‐treatment and restored by coadministration of CACA. These findings suggest that GABAC receptor stimulation protects hippocampal pyramidal neurons from ammonia‐induced apoptosis by restoring Ser112‐ and Ser155‐phospho‐BAD levels.
Nocturnal Hemodialysis in Australia
Authors: Agar John W.M. , Somerville Christine A. , Dwyer Karen M. , Simmonds Rosemary E. , Boddington Janeane M. , Waldron Claire M.
Published: October 2003

Background:  Because home hemodialysis has long been a common Australian support modality, the advent of home‐based nocturnal hemodialysis (NHD) in Canada stimulated the extension of our existing home‐ and satellite‐based conventional hemodialysis (CHD) programs to NHD. As a result, the first government‐funded, home‐based, 6‐nights‐per‐week NHD program in Australia began in July 2001.

Methods:  Sixteen patients have been trained for NHD; 13 dialyzed at home 8 to 9 hr per night for 6 nights per week, whereas 3 preferred to train for NHD at home using an 8‐ to 9‐hr alternate‐night regime.

Results:  The program experience to March 1, 2003, was 655 patient‐weeks. Two patients had withdrawn for transplantation and 2 for social reasons, although 1 continues on alternate‐night NHD. There hade been no deaths. Ten patients had dialyzed without partners. All patients ceased phosphate binders at entry. Thirteen of 16 discontinued all antihypertensive drugs. There were no fluid or dietary restrictions. Phosphate was added to the dialysate to prevent hypophosphatemia. Pre‐ and postdialysis urea and phosphate levels were broadly within the normal ranges. All patients reported restorative sleep; similarly partners reported stable sleep patterns and noted improved mood, cognitive function, and marital relationships in their NHD partners. Preliminary cost analyses show that whereas consumables had doubled, and epoetin and iron expenditures had risen by 28.9%, other pharmaceutical costs had fallen by 47%, and nursing wage costs were 48% of the notional cost had these patients remained on CHD. Three patients on NHD were retired, 7 worked full‐time, 3 worked part‐time, and 3 drew disability support, whereas previously on CHD, 3 were retired, 3 had worked full‐time, 3 had worked part‐time, and 7 had drawn disability support.

Conclusion:  We believe that NHD is viable, safe, effective, and well accepted with significant lifestyle benefits and reemployment outcomes. Although initial setup costs are significant, NHD cost advantage over CHD progressively accrues as program numbers exceed 12 to 15 patients.
Psychological Symptoms Are Greater in Caregivers of Patients on Hemodialysis Than Those of Peritoneal Dialysis
Authors: Sezer M. Tugrul , Eren Ibrahim , Ozcankaya Ramazan , Civi Ikbal , Erturk Jale , Ozturk Mustafa
Published: October 2003

Background:  The purpose of this study was to evaluate and compare psychosocial characteristics in caregiving relatives (caregivers) of hemodialysis (HD) and peritoneal dialysis (PD) patients.

Methods:  Thirty‐three caregivers (17 women, 16 men) of HD patients, 27 caregivers (11 women, 16 men) of PD patients, and a control group of 49 subjects who do not care for family members with chronic illness (23 women, 26 men) are included in this study. The brief symptom inventory (BSI), social disability schedule (SDS), and brief disability questionnaire (BDQ) were used for the psychosocial evaluation.

Results:  The mean age, men‐to‐women ratios, duration of education, and distribution of marital status did not differ significantly among the three groups. In addition, dialysis duration and distribution of caregiver type were not different between the HD and PD groups. Although the mean global severity index scores of the three groups were similar, somatization and depression scores from BSI subitems were greater in the HD group than the scores of the PD and control groups. Although the mean SDS and BDQ scores were higher in the HD group, the differences did not achieve statistical significance. BSI subitems such as somatization, obsession–compulsion, interpersonal sensitivity, depression, and anxiety were positively correlated among themselves. Hostility and somatization were negatively correlated with age and education, respectively. Nevertheless, somatization was positively correlated with age. Social disability was negatively correlated with duration of education.

Conclusion:  Somatization and depression are greater in the caregivers of center HD patients compared to PD and control groups. According to the findings of this study, we suggest that caregiving family members of dialysis patients especially on HD also should be evaluated for psychosocial problems and supported as needed. Further studies are needed to explore whether psychosocial parameters of caregivers predict outcomes for caregivers and patients.
The Neglect of Sodium Restriction in Dialysis Patients: A Short Review
Authors: Charra Bernard , Chazot Charles
Published: October 2003

In end‐stage renal failure, natriuresis decreases, sodium accumulates, and extracellular volume (ECV) excess develops. In 1962, Scribner, reporting about the first maintenance hemodialysis (HD) patient, observed that ECV control using a low‐salt diet and ultrafiltration led to blood pressure (BP) normalization. Thus, the concept of dry weight, the ideal postdialysis weight allowing for a stable normal BP, was born. Achieving dry weight requires a combination of negative diffusive sodium balance, adequate ultrafiltration, and a low‐salt diet. Unfortunately, the low‐salt diet is very often neglected today. In the late 1960s, BP control was achieved in 90% of HD patients using low‐sodium dialysis and a low‐salt diet. As time passed and HD duration was reduced, there was a worsening BP control and subsequent increasing in morbidity and mortality.

In recent years, interventional studies have examined the effects of reducing sodium in dialysate, in diet, or in both. All of them show that low‐salt diet is essential for BP control in HD. While the healthy population is advised to eat a reasonably low‐salt diet (5 g of NaCl), the K/DOQI Guidelines and the European Best Practice Guidelines surprisingly do not even mention salt restriction.

To achieve dry weight under the present conditions, with short HD duration and a frail population, it is mandatory to reduce the interdialytic weight gain. A low‐salt diet is, more than ever, a necessity.
Continuous Renal Replacement Therapy for Liver Disease
Authors: Davenport Andrew
Published: October 2003

Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for critically ill patients with acute renal failure around the world. In particular, CRRT is used for patients with combined liver and acute renal failure, because they are often hemodynamically unstable. The question arises as to whether the use of CRRT should be extended to those patients with acute and chronic liver failure who do not have dialysis‐dependent renal failure. CRRT could potentially allow some detoxification by removing water‐soluble toxins and also allow regulation of intravascular volume and correction of sodium and other electrolyte and acid–base imbalances. By providing homeostatic control, CCRT could potentially help support patients by bridging to liver transplantation and managing those who eventually recover with hepatic regeneration.
Unusual Marine Pathogens Causing Cellulitis and Bacteremia in Hemodialysis Patients: Report of Two Cases and Review of the Literature
Authors: Ruiz Claudia C. , Agraharkar Mahendra
Published: October 2003

Cellulitis in immunocompetent hosts is usually caused by skin organisms and responds to oral antibiotics. In immunocompromised hosts, such as end‐stage renal disease (ESRD) patients, unusual organisms with unpredictable pathogenicity can cause infections. We present two cases with isolates that are usually encountered in coastal waters. The first case describes a 71‐year‐old African‐American ESRD patient who presented with bacteremia secondary to a wound infection after exposure to flood waters in a tropical storm. The second case describes a 70‐year‐old Caucasian male ESRD patient who developed septic shock after a trivial wound inflicted while on a shrimp boat. Both patients were successfully treated with appropriate antibiotics and supportive measures.

The infective agents in both cases belong to the halophilic Vibrio species. The causative agent of cellulitis and bacteremia in the first hemodialysis patient was identified as Vibrio alginolyticus, a non‐lactose‐fermenting gram‐negative bacillus that is rarely isolated from blood. The second patient presented with septic shock owing to Vibrio vulnificus, which is a lactose‐fermenting bacillus known to produce severe localized or systemic illness. In both cases, the common features were ESRD‐related immunocompromised state and exposure to marine environments. These two cases of life‐threatening cellulitis and bacteremia are presented as examples of environmental pathogens common to a marine environment in coastal areas and the imperative need of rapid identification and prompt initiation of treatment in immunocompromised hosts.
Induction of Cyclooxygenase 2 by Escherichia coli but not Helicobacter pylori lipopolysaccharide in gastric epithelial cells in vitro
Authors: Smith Geoff V. , Moran Anthony P. , Bajaj‐Elliott Mona , Farthing Michael J.G.
Published: October 2003

Background.  Cyclooxygenase 2 (COX‐2) is an inducible enzyme that plays a key role in the synthesis of prostaglandins in response to inflammatory stimuli. It is expressed in the gastric mucosa as part of the response to infection with Helicobacter pylori. The specific interaction between H. pylori and the gastric epithelium that results in COX‐2 expression has not been identified.

Methods.  In order to investigate the hypothesis that lipopolysaccharide (LPS) from H. pylori plays a role in the induction of cyclooxygenase 2 in the stomach, gastric cell lines MKN‐7 and MKN‐45 were incubated with LPS from either H. pylori NCTC 11637 or Escherichia coli 055:B5. Incubation of cells with live H. pylori NCTC 11637 was also carried out as a positive control. Cells were then analysed for COX‐2 protein and mRNA and prostaglandin E2 synthesis.

Results.  Cyclooxygenase 2 protein and mRNA expression was induced by E. coli LPS and live H. pylori, but not by H. pylori LPS. Prostaglandin E2 synthesis increased in a dose‐dependent manner in both cell lines with E. coli but not H. pylori LPS.

Conclusions.  H. pylori LPS is of low biological activity when compared with E. coli LPS in its ability to induce the expression of cyclooxygenase 2 and synthesis of prostaglandin E2. This may provide one mechanism by which H. pylori minimizes the inflammatory response in the gastric mucosa, allowing chronic infection.
Interactions between Inducible Nitric Oxide and Other Inflammatory Mediators during Helicobacter pylori Infection
Authors: Obonyo Marygorret , Guiney Donald G. , Fierer Joshua , Cole Sheri P.
Published: October 2003

Background.  Recent studies in both humans and animal models strongly suggest the contribution of the host immune response to Helicobacter pylori‐related disease. Inducible nitric oxide synthase has been shown to be up‐regulated in the gastric epithelium during H. pylori gastritis, suggesting a role in inflammation.

Materials and Methods.  C57BL/6 wild‐type and inducible nitric oxide synthase gene knockout mice were infected with H. pylori strain SS1. Expression of macrophage inflammatory protein‐2 (MIP‐2), interleukin‐1 beta (IL‐1β), Th1 (IL‐2 and gamma interferon) and Th2 (IL‐4 and IL‐10) cytokines, and inducible cyclooxygenase mRNA in mice was determined in mouse gastric tissues and quantified using either competitive reverse transcription–polymerase chain reaction or competitive polymerase chain reaction following reverse transcription.

Results.  The Th1 cytokine gamma interferon was only detected in wild‐type and inducible nitric oxide synthase gene knockout infected mice, while a Th2 (IL‐4) response was not detected. H. pylori induced MIP‐2 and IL‐1β mRNA in mice.

Conclusions.  Because similar levels of inflammatory mediators were noted in both wild‐type and nitric oxide synthase gene knockout infected mice, our data suggest that inducible nitric oxide synthase does not influence expression of these inflammatory mediators in the early stages of H. pylori infection in mice.
Oxidative Damage of the Gastric Mucosa in Helicobacter pylori Positive Chronic Atrophic and Nonatrophic Gastritis, Before and After Eradication
Authors: Iacopini Federico , Consolazio Adriana , Bosco Daniela , Marcheggiano Adriana , Bella Antonino , Pica Roberta , Paoluzi Omero A. , Crispino Pietro , Rivera Margherita , Mottolese Marcella , Nardi Francesco , Paoluzi Paolo
Published: October 2003

Background.  Helicobacter pylori is the main cause of gastritis and a primary carcinogen. The aim of this study was to assess oxidative damage in mucosal compartments of gastric mucosa in H. pylori positive and negative atrophic and nonatrophic gastritis.

Materials and methods.  Five groups of 10 patients each were identified according to H. pylori positive or negative chronic atrophic (Hp‐CAG and CAG, respectively) and nonatrophic gastritis (Hp‐CG and CG, respectively), and H. pylori negative normal mucosa (controls). Oxidative damage was evaluated by nitrotyrosine immunohistochemistry in the whole mucosa and in each compartment at baseline and at 2 and 12 months after eradication. Types of intestinal metaplasia were classified by histochemistry.

Results.  Total nitrotyrosine levels appeared significantly higher in H. pylori positive than in negative patients, and in Hp‐CAG than in Hp‐CG (p < .001); no differences were found between H. pylori negative gastritis and normal mucosa. Nitrotyrosine were found in foveolae and intestinal metaplasia only in Hp‐CAG. At 12 months after H. pylori eradication, total nitrotyrosine levels showed a trend toward a decrease in Hp‐CG and decreased significantly in Hp‐CAG (p = .002), disappearing from the foveolae (p = .002), but remaining unchanged in intestinal metaplasia. Type I and II of intestinal metaplasia were present with the same prevalence in Hp‐CAG and CAG, and did not change after H. pylori eradication.

Conclusions.  Oxidative damage of the gastric mucosa increases from Hp‐CG to Hp‐CAG, involving the foveolae and intestinal metaplasia. H. pylori eradication induces a complete healing of foveolae but not of intestinal metaplasia, reducing the overall oxidative damage in the mucosa.
The MUC5AC Glycoprotein is the Primary Receptor for Helicobacter pylori in the Human Stomach
Authors: Van de Bovenkamp Jeroen H. B. , Mahdavi Jafar , Korteland‐Van Male Anita M. , Büller Hans A. , Einerhand Alexandra W. C. , Borén Thomas , Dekker Jan
Published: October 2003

Background and objectives.  Helicobacter pylori shows a characteristic tropism for the mucus‐producing gastric epithelium. In infected patients, H. pylori colocalizes in situ with the gastric secretory mucin MUC5AC. The carbohydrate blood‐group antigen Lewis B (LeB) was deemed responsible for the adherence of H. pylori to the gastric surface epithelium. We sought to determine if MUC5AC is the carrier of LeB, and thus if MUC5AC is the underlying gene product functioning as the main receptor for H. pylori in the stomach.

Methods.  We studied three types of human tissue producing MUC5AC: Barrett's esophagus (BE), normal gastric tissue, and gastric metaplasia of the duodenum (GMD). Tissue sections were immuno‐fluorescently stained for MUC5AC or LeB, and subsequently incubated with one of three strains of Texas red‐labeled H. pylori, one of which was unable to bind to LeB. We determined the colocalization of MUC5AC or LeB with adherent H. pylori.

Results.  The binding patterns for the two LeB‐binding strains to all tissues were similar, whereas the strain unable to bind to LeB did not bind to any of the tissues. In normal gastric tissue, the LeB‐binding strains always bound to MUC5AC‐ and LeB‐positive epithelial cells. In four nonsecretor patients, colocalization of the LeB‐binding strains was found to MUC5AC‐positive gastric epithelial cells. In BE, the LeB‐binding H. pylori strains colocalized very specifically to MUC5AC‐positive cells. MUC5AC‐producing cells in GMD contained LeB. Yet, LeB‐binding H. pylori not only colocalized to MUC5AC or LeB present in GMD, but also bound to the LeB‐positive brush border of normal duodenal epithelium.

Conclusions.  Mucin MUC5AC is the most important carrier of the LeB carbohydrate structure in normal gastric tissue and forms the major receptor for H. pylori.
Intensity of Inflammation, Density of Colonization and Interleukin‐8 Response in the Gastric Mucosa of Children Infected with Helicobacter pylori
Authors: Camorlinga‐Ponce Margarita , Aviles‐Jimenez Francisco , Cabrera Lourdes , Hernández‐Pando Rogelio , Muñoz Onofre , Soza Jorge , Torres Javier
Published: October 2003

Background.  Few reports exist on inflammation and interleukin (IL)‐8 response in H. pylori‐infected children. The aim of this study was to determine the intensity of inflammation, density of colonization and magnitude of IL‐8 response in children with and without H. pylori infection.

Materials and Methods.  We studied 45 children with dyspeptic symptoms, 21 infected with H. pylori and 24 without infection. Antrum and corpus gastric biopsies were obtained and studied for H. pylori infection with an immunofluorescence technique and for IL‐8 with an immunohistochemical assay. Biopsy specimens were stained with hematoxilin and eosin and gastritis was graded according to the Sydney system. The magnitudes of the IL‐8 response and H. pylori colonization were estimated microscopically with image analyzer software.

Results.  In H. pylori‐infected children, mild mono‐nuclear cell infiltration was found in 50%, and no neutrophils in 40% of cases. In the antrum but not in the corpus, the intensity of colonization correlated with neutrophil and mononuclear cell infiltration. The IL‐8 response was significantly higher in the antrum (p < .05) and corpus (p < .02) of infected children, and was localized mainly in the surface and crypts of the epithelium. No correlation was found between the magnitude of the IL‐8 response and the infiltration of either neutrophil or mononuclear cells.

Conclusions.  In H. pylori‐infected children, poor mononuclear and neutrophil infiltration was observed. Infection was associated with a higher IL‐8 response by gastric epithelial cells. The density of colonization but not the IL‐8 response correlated with neutrophil cell infiltration.