bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative approaches for regional ulnar nerve blockade: A cadaveric study
Authors: Lizamore N. , Venter E. , Boon J.M.
Published: May 2004

Wrist blockade is a safe and effective alternative to general anesthesia in surgery of hand injuries. With regard to the ulnar nerve, the volar approach is used, where the needle passes through or medial to the flexor carpi ulnaris tendon; however, the ulnar artery is at risk because the needle may accidentally penetrate it, causing profuse bleeding. Alternatively, the wrist may be approached medially, the ulnar approach, and the needle tip placed posterior to the flexor carpi ulnaris tendon. To determine which of these methods may be preferable for avoiding ulnar artery injury, needles were inserted into the wrist area of cadaver hands (n = 57) using the volar and ulnar approaches; detailed dissection of the region around the inserted needles was subsequently carried out. The position of the ulnar nerve relative to the ulnar artery and injury to the artery was documented. Damage to the ulnar artery using the volar approach was 36.8% (21/57 cases) compared to no (0%) injury observed using the ulnar approach. At the level of the wrist crease just proximal to the pisiform bone, the ulnar nerve was medial to the artery in 92.9% (53/57) of cases, medial and posterior in 5.3% (3/57), and anterior to the artery in 1.8% (1/57) of cases. This study suggests that in cases where ulnar artery pulsation is not reliable, the ulnar approach may be preferable for ulnar nerve blockade due to an increased incidence of ulnar artery penetration with the volar approach. Clin. Anat. 17:373–377, 2004. © 2004 Wiley‐Liss, Inc.
Great cardiac vein variations
Authors: Bales Gerald S.
Published: May 2004

A novel variation in the relationship of the great cardiac vein to the circumflex artery was observed in an otherwise normal cadaver heart. Vessels originated and terminated normally, but in their midcourse they were twisted around each other such that each made one complete loop around the other. This variation did not seem to be involved in any pathologies. Variations in the course of the great cardiac vein have been little studied until recently, but their simplicity emphasizes the uniqueness of our intertwined case. Commonly, the great cardiac vein varies with respect to presence, location, and the superficial or deep relationship of single crossings of the anterior interventricular and circumflex arteries. Although rare, the intertwined variation described in the present case may have important basic science implications for understanding mechanisms of vasculo‐angiogenesis, and clinical implications for catheter‐based procedures and surgeries in the region of the coronary sulcus. Also, a review of great cardiac vein variations is presented herein. Clin. Anat. 17:436–443, 2004. © 2004 Wiley‐Liss, Inc.
Unusual variation of the inferior attachment of the pectoralis minor muscle
Authors: Turan‐Ozdemir S. , Cankur N.S.
Published: May 2004

An unusual inferior attachment of pectoralis minor muscle was found on the right side of a male cadaver. The tendinous attachment, originating only from the 5th rib, was detected during the routine practical dissections. There were no other associated features in the thoracic region of this cadaver. We believe that this variation that has not been reported previously in the literature, should be taken into consideration by the surgeons. Clin. Anat. 17:416–417, 2004. © 2004 Wiley‐Liss, Inc.
Yttrium and Lanthanide Diphosphanylamides: Syntheses and Structures of Complexes with one {(Ph2P)2N}− ligand in the Coordination Sphere
Authors: Roesky Peter W. , Gamer Michael T. , Marinos Nicolas
Published: May 2004

Treatment of the recently reported potassium salt [K(thf)n][N(PPh2)2] (n=1.25, 1.5) with anhydrous yttrium or lanthanide trichlorides in THF leads after crystallization from THF/n‐pentane (1:2) to the monosubstituted diphosphanylamide complexes [LnCl2{(Ph2P)2N}(thf)3] (Ln=Y, Sm, Er, Yb). The single‐crystal X‐ray structures of these complexes show that the metal atoms are surrounded by seven ligands in a distorted pentagonal bipyramidal arrangement, in which the chlorine atoms are located in the apical positions. The diphosphanylamide ligand is always η2‐coordinated through the nitrogen atom and one phosphorus atom. Further reaction of [SmCl2{(Ph2P)2N}(thf)3] with K2C8H8 or reaction of [LnI(η8‐C8H8)(thf)3] with [K(thf)n][N(PPh2)2] in THF gives the corresponding cyclooctatetraene complexes [Ln{(Ph2P)2N}(η8‐C8H8)(thf)2] (Ln=La, Sm). The single crystals of these compounds contain enantiomerically pure complexes. Both compounds adopt a four‐legged piano‐stool conformation in the solid state. The structures of the A and the C enantiomers were established by single‐crystal X‐ray diffraction. The more soluble bistrimethylsilyl cyclooctatetraene complex [Y{(Ph2P)2N}(η8‐1,4‐(Me3Si)2C8H6)(thf)2] was obtained by transmetallation of Li2[1,4‐(Me3Si)2C8H6] with anhydrous yttrium trichloride in THF followed by the addition of one equivalent of [K(thf)n][N(PPh2)2]. The 89Y NMR signal of the complex is split up into a triplet, supporting other observations that the phosphorus atoms are chemically equivalent in solution and, thus, dynamic behavior of the ligand in solution can be anticipated.
Molecular Evolution Using Intramolecular Acyl Migration on myo‐Inositol Benzoates with Thermodynamic and Kinetic Selectors
Authors: Ahn Young‐Hoon , Chang Young‐Tae
Published: May 2004

A molecular evolution model was successfully demonstrated by combining the intramolecular acyl migration on inositol tribenzoates and boron selectors. The addition of boric acid to 12 members of DCL (dynamic combinatorial library) induced the dramatic amplification of myo‐I(2,4,6)Bz3 (1) with up to 94 % under thermodynamic (see Figure 1 c) control while a portion of phenyl boronic acid caused two significant different distributions: under kinetic control, the pre‐equilibrium of DCL shifted to induce the exclusive amplification of 1,4,6‐tribenzoyl myo‐inositol (7) with decrease of other members up to 82 % from the mixture (see Figure 2 b), and changed gradually to form 2,4,6‐tribenzoyl myo‐inositol (1) with up to 96 % under thermodynamic control (Figure 2 c).
Phasenverhalten von hochselektiven nichtflüchtigen Flüssigkeiten mit designbarem Eigenschaftsprofil und neue Anwendungen in der thermischen Verfahrenstechnik
Authors: Seiler M. , Jork C. , Arlt W.
Published: May 2004

No abstracts.
Messung der Scherfestigkeit von Belebtschlamm während des Separationsvorgangs
Authors: Meisl C. , Divjak S. , Staudinger G.
Published: May 2004

No abstracts.
Produktionsintegrierter Einsatz der katalytischen Elektrolyse zur Reduzierung des Wasserbedarfs in der Prozessindustrie
Authors: Forstmeier M. , Wozny G. , Buss K. , Tölle J.
Published: May 2004

No abstracts.
Thermochemische Vergasung zur energetischen Nutzung von Biomasse
Authors: Wiese L. , Kather A.
Published: May 2004

No abstracts.
Beeinflussung der Verbrennungsluftzusammensetzung zur Minderung der Schadstoffemission aus Verbrennungsmotoren
Authors: Hofmann U. , Velji A.
Published: May 2004

No abstracts.
Einfluss der Gasdüsenanordnung auf den Desintegrationsvorgang und das Zerstäubungsergebnis bei der Zweistoffzerstäubung
Authors: Czisch C. , Lohner H. , Fritsching U.
Published: May 2004

No abstracts.
Nicht‐isokratische SMB‐Trennung von Proteinen mittels Ionenaustauschchromatographie
Authors: Wenkenborg K. , Susanto A. , Frederiksen S. , Schmidt‐Traub H.
Published: May 2004

No abstracts.
Blindreaktionen heterogen‐ gaskatalytischer Reaktionen in Differenzial‐Kreislaufreaktoren
Authors: Hesselbarth B. , Adler R.
Published: May 2004

No abstracts.
Partikeltemperaturmessung bei der Zerstäubung von Metallschmelzen
Authors: Krauss M. , Fritsching U.
Published: May 2004

No abstracts.
Untersuchungen zum Coating von submikronen Partikeln mit dem CORESS‐Verfahren
Authors: Türk M.
Published: May 2004

No abstracts.
Modellierung differenzierter mikro‐struktureller Polymereigenschaften
Authors: Busch M.
Published: May 2004

No abstracts.
Fließschema‐Simulation von Feststoffprozessen
Authors: Werther J. , Hartge E.‐U. , Gruhn G.
Published: May 2004

No abstracts.
Gekoppelte Fließbildsimulation von Partikelprozessen durch Integration verschiedener Simulationswerkzeuge
Authors: Briesen H. , Grosch R. , Kulikov V. , von Wedel L. , Yang A. , Marquardt W.
Published: May 2004

No abstracts.
Vergleich chromatographischer Reaktorkonzepte
Authors: Borren T. , Schmidt‐Traub H.
Published: May 2004

Durch die Integration einer chemischen oder biochemischen Reaktion und einer chromatographischen Trennung in einem gemeinsamen Apparat ist es möglich, die Gleichgewichtslimitierung der Reaktion zu überwinden und die Trenneffektivität zu erhöhen. Verschiedene prozesstechnische Varianten des chromatographischen Reaktors werden vorgestellt. Aufgrund der komplexen Zusammenhänge sind Modellierung und Simulation wichtige Werkzeuge bei der Entwicklung und Gestaltung der Prozesse. Eine Übersicht über die zur Verfügung stehenden Modellansätze wird gegeben. Ein Vergleich der verschiedenen chromatographischen Simulated Moving Bed (SMB)‐Reaktoren erfolgt am Beispiel der Glucose‐Isomerisierung. In Abhängigkeit von der jeweiligen Reinheitsanforderung an den gewonnenen Fructose‐Sirup bieten unterschiedliche Integrationsgrade von Reaktion und Trennung Vorteile.
Innovative Katalysatoren zur oxidativen Dehydrierung in der Gasphase – Metallische Kurzfasern
Authors: Brüning R. , Scholz P. , Morgenthal I. , Andersen O. , Ondruschka B.
Published: May 2004

Metallische Kurzfasern in ausgesuchter Legierungszusammensetzung und Gefügestruktur wurden auf ihre katalytische Aktivität bei der oxidativen Dehydrierung (ODH) von Propan zu Propen und von Isopropanol zu Aceton untersucht. Die über das Schmelzextraktions‐Verfahren hergestellten Kurzfasern wurden einer intensiven Charakterisierung ihrer werkstoffseitigen Eigenschaften unterworfen. Dabei kamen lichtmikroskopische, DSC‐, XRD‐, REM‐ und EDX‐Untersuchungen zum Einsatz, um Zusammenhänge zwischen der Werkstoffzusammensetzung, dem Gefüge und den katalytischen Eigenschaften zu ermitteln. Es werden ausgewählte Ergebnisse zur Temperaturabhängigkeit des Propan‐Umsatzes bzw. der Propen‐Selektivität präsentiert. So wurde Propen bei einem Propan‐Umsatz von mehr als 50 % mit einer Ausbeute von 35 % gebildet. Auch die Selektivoxidation von Isopropanol zu Aceton erfolgte mit attraktiven Ausbeuten von über 80 %. Die Ergebnisse insgesamt belegen das hohe Innovationspotenzial der Metallfaserwerkstoffe.
Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129X1/SvJ) with a diminished inflammatory response
Authors: Ma Manhong , Wei Ping , Wei Tao , Ransohoff Richard M. , Jakeman Lyn B.
Published: May 2004

After injury in the adult central nervous system, invading and intrinsic cells contribute to the formation of a lesion site that is refractory to axonal growth. To test the hypothesis that the inflammatory response to trauma dictates the extent of axonal growth after spinal cord injury, the time course of lesion evolution was compared in two mouse strains with contrasting cellular responses to peripheral inflammatory challenge. Adult C57Bl/6 and 129X1/SvJ mice received identical contusion injuries to the mid‐thoracic spinal cord and were allowed to recover for 6 hours to 9 weeks. Both strains responded with a rapid, transient increase in chemokine expression, but the magnitude of this early response was slightly reduced in the 129X1/SvJ mice. Morphological indicators of inflammation were similar during the first week postinjury. After 7 days postinjury, however, the cellular responses differed between strains. The C57Bl/6 lesion core was chronically occupied by macrophages, devoid of astrocytes, and contained few axonal profiles. In contrast, as the macrophage density decreased a network of astrocytic processes and axons of central and peripheral origin invaded the center of the lesion site in 129X1Sv/J mice. Growth of axons in the 129X1Sv/J mice was accompanied by increased extravascular laminin in the lesion core and a reduced expression of chondroitin sulfate proteoglycan glycosaminoglycan sidechains in the periphery of the lesion. These results demonstrate that the diminished chronic inflammatory response in 129X1/SvJ mice is associated with enhanced cellular repair and increased axonal growth after spinal cord injury. J. Comp. Neurol. 474:469–486, 2004. © 2004 Wiley‐Liss, Inc.
Expression of the genes Emx1, Tbr1, and Eomes (Tbr2) in the telencephalon of Xenopus laevis confirms the existence of a ventral pallial division in all tetrapods
Authors: Brox Aurora , Puelles Luis , Ferreiro Beatriz , Medina Loreta
Published: May 2004

To investigate the pallial organization and the exact location and extension of the ventral pallium in amphibians, we cloned a fragment of the homeobox XenopusTbr1 (xTbr1) gene and analyzed its expression compared with that of the genes xEomes (Tbr2) and xEmx1 in the telencephalon of the frog Xenopus laevis during embryonic and larval development. The expression of xEmx1 was also analyzed in the adult frog. We compared the expression patterns of these pallial marker genes with that of the subpallial gene xDistal‐less‐4 (xDll4). Our results indicate that the whole pallium of Xenopus expresses the T‐box genes xTbr1 and xEomes (in proliferating cells and/or mantle) during embryonic and larval development, and the expression of these genes is topographically complementary to that of xDll4 in the subpallium. In addition to their massive expression in the pallium, both xTbr1 and xEomes are expressed in a few dispersed cells in the subpallium, which may represent immigrant cells of pallial origin, because these genes are not found in the subpallial proliferating cells. On the other hand, during development xEmx1 is expressed in a large part of the pallium (proliferating and postmitotic cells) except for an area adjacent to the pallio‐subpallial boundary, where xEmx1 is observed only in some mantle cells. This pallial area poor in xEmx1 expression and poor in expression of the subpallial gene xDll4, but expressing the pallial marker genes xTbr1 and xEomes, appears to represent the amphibian ventral pallium, comparable to that described in other vertebrates (Puelles et al. [2000] J. Comp. Neurol. 424:409–438). In the adult frog, the ventral pallium appears to include the rostral part of the lateral amygdalar nucleus as well as a large part of the medial amygdalar nucleus (as defined by Marín et al. [1998] J. Comp. Neurol. 392:285–312). In contrast, the caudal part of the previously termed lateral amygdalar nucleus shows strong xEmx1 expression and may be a lateral pallial derivative. The possible homology of these amphibian amygdalar nuclei is discussed. Finally, expression of xTbr1, xEomes, and xEmx1 is observed in the mitral cell layer of the olfactory bulb from early developmental stages, further supporting that this structure is a pallial derivative. J. Comp. Neurol. 474:562–577, 2004. © 2004 Wiley‐Liss, Inc.
The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers
Authors: Roux Kyle J. , Amici Stephanie A. , Notterpek Lucia
Published: May 2004

Peripheral myelin protein 22 (PMP22), also known as growth arrest‐specific gene 3 (gas3), is a tetraspan membrane protein whose misexpression is associated with demyelinating peripheral neuropathies. Although the function of PMP22 in Schwann cells is unknown, the protein is found at intercellular junctions of various epithelia and endothelia. To begin to elucidate the role of PMP22 at cell junctions, we examined the temporal expression and protein localization during development and maturation of the rat blood‐nerve barrier (BNB) and blood‐brain barrier (BBB). Developing and adult rat sciatic nerves and brains were coimmunostained for PMP22 and known junctional proteins including zonula occludens‐1 (ZO‐1), occludin, and claudin‐5. Prior to the maturation of the BNB and BBB and detection of the tight junction protein occludin, PMP22 is present at ZO‐1 positive endothelial junctions of the sciatic nerve and brain cortex. The subcellular localization of PMP22 in cultured brain endothelia was confirmed by internalization with ZO‐1 after EGTA‐induced disruption of cell junctions. In choroid epithelia, PMP22 is detected along with occludin and ZO‐1 as early as embryonic day 15 (E15). In agreement, PMP22 message is elevated in P1 rat brain microvasculature and choroid epithelia, compared with total cortex. Additionally, neuroepithelial cell junctions in the embryonic rat brain are immunoreactive for PMP22, ZO‐1, and β‐catenin but not occludin. Together, these studies identify PMP22 as an early constituent of intercellular junctions in the developing and mature rat BNB and BBB. J. Comp. Neurol. 474:578–588, 2004. © 2004 Wiley‐Liss, Inc.
Localization of the GABAB receptor 1a/b subunit relative to glutamatergic synapses in the dorsal cochlear nucleus of the rat
Authors: Luján Rafael , Shigemoto Ryuichi , Kulik Akos , Juiz José M.
Published: May 2004

Metabotropic γ‐aminobutyric acid receptors (GABAB) are involved in pre‐ and postsynaptic inhibitory effects upon auditory neurons and have been implicated in different aspects of acoustic information processing. To understand better the mechanisms by which GABAB receptors mediate their inhibitory effects, we used pre‐embedding immunocytochemical techniques combined with quantification of immunogold particles to reveal the precise subcellular distribution of the GABAB1 subunit in the rat dorsal cochlear nucleus. At the light microscopic level, GABAB1 was detected in all divisions of the cochlear complex. The most intense immunoreactivity for GABAB1 was found in the dorsal cochlear nucleus, whereas immunoreactivity in the anteroventral and posteroventral cochlear nuclei was very low. In the dorsal cochlear nucleus, a punctate labeling was observed in the superficial (molecular and fusiform cell) layers. At the electron microscopic level, GABAB1 was found at both post‐ and presynaptic locations. Postsynaptically, GABAB1 was localized mainly in the dendritic spines of presumed fusiform cells. Quantitative immunogold immunocytochemistry revealed that the highest concentration of GABAB1 in the plasma membrane was in dendritic spines, followed by dendritic shafts and somata. Thus, the most intense immunoreactivity for GABAB1 was observed in dendritic spines with a high density of immunogold particles at extrasynaptic sites, peaking around 300 nm from glutamatergic synapses. This is in contrast to GABAergic synapses, in which GABAB1 was only occasionally found. Presynaptically, receptor immunoreactivity was detected primarily in axospinous endings, probably from granule cells, in both the active zone and extrasynaptic sites. The localization of GABAB1 relative to synaptic sites in the DCN suggests a role for the receptor in the regulation of dendritic excitability and excitatory inputs. J. Comp. Neurol. 475:36–46, 2004. © 2004 Wiley‐Liss, Inc.
Voltammetric Oxidation of Drugs of Abuse III. Heroin and Metabolites
Authors: Garrido J. M. P. J. , Delerue‐Matos C. , Borges F. , Macedo T. R. A. , Oliveira‐Brett A. M.
Published: May 2004

The oxidative behavior of heroin in aqueous solution is reported. In order to identify its oxidation peaks, several metabolites, 6‐monoacetylmorphine, 3‐monoacetylmorphine and norheroin, were synthesized and their electrochemical behavior studied using differential pulse voltammetry. The anodic waves observed for heroin correspond to the oxidation of the tertiary amine group and its follow‐up product (secondary amine), and to the oxidation of the phenolic group obtained from hydrolysis, at alkaline pHs, of the 3‐acetyl group. The results enabled a new oxidative mechanism for heroin to be proposed in which a secondary amine, norheroin, and an aldehyde are obtained. The voltammetric behavior of 6‐monoacetylmorphine and morphine was found to be similar demonstrating that the presence of an acetyl substituent on the 6‐hydroxy group does not have a relevant influence on the peak potential of the wave resulting from oxidation of the 3‐phenolic group.
Synthesis and properties of novel pyrazolopyrimidine derivatives containing sulfur atom
Authors: Wang Hong‐Qing , Ding Ming‐Wu , Liu Zhao‐Jie
Published: May 2004

A series of new pyrazolopyrimidine derivatives containing sulfur atom 5 has been designed and synthesized by treatment of carbodiimide 3, which came from iminophosphorane 2 undergoing a aza‐Wittig reaction with phenyl ioscyanate, with alkylamine. The structures of compounds 5 were confirmed by 1H NMR, IR, EI‐mass spectroscopy, and elemental analysis. The results of preliminary bioassay indicate that most compounds 5 exhibit an inhibition effect against Cercospora beticola, Botryosphaeria berengeriana, and Pellicularia sasakii, and compound 5g shows 91.2% inhibitory rate to root of rape and the other less than 50% at 100 mg/l. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:333–337, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20024
Effect of murine liver cell proliferation on herpes viral behavior: Implications for oncolytic viral therapy
Authors: Delman Keith A. , Zager Jonathan S. , Bhargava Amit , Petrowsky Henrik , Malhotra Sandeep , Ebright Michael I. , Bennett Joseph J. , Gusani Niraj J. , Kooby David A. , Roberts Gretchen D. , Fong Yuman
Published: May 2004

Replication-competent herpes simplex oncolytic viruses are promising anticancer agents that partly target increased DNA synthesis in tumor cells. Investigators have proposed that these DNA viruses may be combined with liver resection to enhance killing of liver malignancies. Whether or not the cellular alterations associated with hepatic regeneration affect the efficacy and toxicity of these promising anticancer agents is unknown. This study examined the behavior of two oncolytic viruses, NV1020 and G207, during liver regeneration. When delivered during the peak of liver regeneration, replication and appearance of both G207 and NV1020 in hepatic tissue are enhanced as demonstrated by histochemical staining for the marker gene lac Z, immunohistochemical staining, and quantitative polymerase chain reaction. This increased appearance of virus in liver tissue correlates with increases in cellular ribonucleotide reductase activity and DNA synthesis and is also associated with increased viral binding. However, increased viral presence is transient, and viral detection declines to baseline within 7 days. When these viruses were delivered to animals even as early as 7 days after hepatectomy, there proved to be no measurable viral replication in any organ and no increased morbidity or mortality. In conclusion, the early stages of hepatic regeneration after resection provide an environment suitable for viral replication. Administration of replication-competent herpes simplex virus during the peak of hepatocyte regeneration (24-48 hours) permits viral productivity in tissue that otherwise does not support viral growth. The increase in hepatotoxicity after hepatectomy is short-lived and can be predicted by peak hepatocyte DNA synthesis. (Hepatology 2004;39:1525-1532.)
Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1
Authors: Jeffers Lennox J. , Cassidy William , Howell Charles D. , Hu Sylvia , Reddy Rajender K.
Published: May 2004

Black Americans (blacks) have a high prevalence of chronic hepatitis C virus (HCV) infection and respond poorly to therapy with interferon alfa-based regimens, but they have been underrepresented in clinical trials. The aim of this study was to assess the rate of sustained virological response (SVR) to peginterferon alfa-2a (40 kd) in combination with ribavirin in black patients chronically infected with HCV genotype 1. In a prospective, multicenter, open-label trial, 78 black and 28 white American interferon-naïve patients were enrolled to receive once weekly subcutaneous injections of 180 μg peginterferon alfa-2a plus oral ribavirin (1000 mg/d for patients weighing less than 75 kg and 1200 mg/d for patients weighing 75 kg or more) for 48 weeks. Pre- and post-treatment liver biopsies were evaluated for necroinflammation and fibrosis. SVR, defined as undetectable (<50 IU/mL) HCV RNA, was 26% in the black group and 39% in the white group. Although the SVR rate was lower in blacks than in whites, the SVR of 26% represents an improvement over previously reported SVR rates from smaller, retrospective studies of black patients. We also observed improvement in fibrosis in 25% of the black patients. No unexpected adverse events occurred. In conclusion, this prospective study evaluating responses of black patients with chronic hepatitis C to peginterferon alfa-2a/ribavirin has demonstrated that treatment can be safely offered to such individuals with reasonable antiviral and histological benefit. (Hepatology 2004;39:1702-1708.)
Plasticity in the adult rat pancreas: Transdifferentiation of exocrine to hepatocyte-like cells in primary culture
Authors: Lardon Jessy , De Breuck Saskia , Rooman Ilse , Van Lommel Leentje , Kruhøffer Mogens , Orntoft Torben , Schuit Frans , Bouwens Luc
Published: May 2004

Under certain experimental conditions, hepatocytes can arise in the pancreas. It has been suggested that the pancreas retains a source of hepatocyte progenitor cells. However, such cells have not been yet identified in the adult pancreas. We describe here the transdifferentiation of primary rat pancreatic exocrine cells into hepatocyte-like cells during 5 days of tissue culture in the presence of dexamethasone (DX). Using reverse-transcription polymerase chain reaction and immunocytochemistry, it was observed that DX treatment induced albumin RNA and protein expression in the cells. Coexpression of albumin and amylase, and the absence of cell proliferation, demonstrated a direct transdifferentiation of acinar cells to hepatocytic cells. CCAAT enhancer-binding protein-β protein, a liver-enriched transcription factor that is considered to be the master switch in pancreatohepatic transdifferentiation, and α-fetoprotein were markedly upregulated in the cells after treatment with DX. We compared transcriptional profiles of freshly isolated exocrine cells and DX-treated cells using oligonucleotide microarrays and found that multiple liver-specific genes are induced along with albumin, and that certain pancreatic genes are downregulated in the DX-treated cells. In conclusion, these observations support the notion of plasticity in the adult pancreas and that exocrine cells can be reprogrammed to transdifferentiate into other cell types such as hepatocytes. (Hepatology 2004;39:1499-1507.)
HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease
Authors: Andrade Raúl J. , Lucena Isabel M. , Alonso Anabel , García-Cort'es Miren , García-Ruiz Elena , Benitez Rafael , Fernández Carmen M. , Pelaez Gloria , Romero Manuel , Corpas Raquel , Durán José Antonio , Jiménez Manuel , Rodrigo Luis , Nogueras Flor , Martín-Vivaldi Rafael , Navarro José María , Salmerón Javier , de la Cuesta Felipe Sánchez , Hidalgo Ramón
Published: May 2004

Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P = .002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P = .001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P = .003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P = .0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage. (Hepatology 2004;39:1603-1612.)
Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis
Authors: Avgerinos Alec , Armonis Anastasios , Stefanidis Gerasimos , Mathou Nikoleta , Vlachogiannakos Jiannis , Kougioumtzian Anastasios , Triantos Christos , Papaxoinis Costas , Manolakopoulos Spilios , Panani Anna , Raptis Sotiris A.
Published: May 2004

During variceal bleeding, several factors may increase portal pressure, which in turn may precipitate further bleeding. This study investigates the early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on hepatic venous pressure gradient (HVPG) during acute bleeding and the possible influence in outcome. In 50 cirrhotic patients with bleeding esophageal varices treated with EIS (n = 25) or EBL (n = 25), we performed repeated HVPG measurements before and immediately after endoscopic treatment (time 0) and every 24 hours for a 5-day period. Endotherapy was continued until the varices were too small for further treatment. Both groups were comparable with regard to age, gender, Child-Turcotte-Pugh grade, and HVPG. In the EBL and EIS groups, a significant (P < .0001) increase was observed in mean portal pressure (20.7 mm Hg ± 4.4 SD and 21.5 mm Hg ± 4.5 SD, respectively) immediately after treatment (time 0) as compared with pretreatment (18.1 ± 4.5 and 18.1 ± 4.0). However, HVPG in the EBL group returned to baseline values within 48 hours after treatment, while in the EIS group it remained high during the 120-hour study period (P < .0001). Bleeding stopped in all patients after endotherapy. During the 42-day follow-up period, the rebleeding rate over time was lower in the EBL group compared with the EIS group (P = .024). Patients with an initial HVPG greater than 16 mm Hg had, despite endoscopic treatment, a significantly higher likelihood of rebleeding (P = .05) and death (P = .024) and overall failure (P = .037). In conclusion, during acute variceal bleeding EIS, but not EBL, causes a sustained increase in HVPG, which is followed by a higher rebleeding rate. (Hepatology 2004;39:1623-1630.)
Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis
Authors: Smith Jeffery L. , Lewindon Peter J. , Hoskins Anita C. , Pereira Tamara N. , Setchell Kenneth D. R. , O'Connell Nancy C. , Shepherd Ross W. , Ramm Grant A.
Published: May 2004

Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas-liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD. (Hepatology 2004;39:1673-1682.)
HBsAg seroclearance in chronic hepatitis B in the Chinese: Virological, histological, and clinical aspects
Authors: Yuen Man-Fung , Wong Danny Ka-Ho , Sablon Erwin , Tse Eric , Ng Irene Oi-Lin , Yuan He-Jun , Siu Chung-Wah , Sander Tamara J. , Bourne Eric J. , Hall Jeff G. , Condreay Lynn D. , Lai Ching-Lung
Published: May 2004

Few studies have examined Chinese patients with chronic hepatitis B who exhibit hepatitis B surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 patients with HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, and duration of follow-up were also recruited. Liver biochemistry, serum hepatitis B virus (HBV) DNA levels, and development of clinical complications were monitored. Intrahepatic total and covalently closed circular (ccc) HBV DNA were measured quantitatively in 16 patients. HBV genotype was determined in 30 patients. The mean age at HBsAg seroclearance was 48.8 (+ 13.81) years. There was a significant improvement in serum alanine aminotransferase levels after HBsAg seroclearance (p<0.0001). Patients with genotype B had a higher chance of HBsAg seroclearance than those with genotype C (P = .014). Ninety-eight percent of patients had undetectable serum HBV DNA. Thirty-seven percent of patients had low titer of intrahepatic HBV DNA, mainly in the form of cccDNA (71%-100%). All 14 patients with liver biopsies had near normal histology. There was no difference in the risk of development of hepatocellular carcinoma (HCC) between patients with and without HBsAg seroclearance. However, the mean age of HBsAg seroclearance was significantly older in patients with HCC than in patients without HCC (P = .016). In conclusion, patients with HBsAg seroclearance had favorable biochemical, virological, and histological parameters. Intrahepatic HBV DNA level was low and predominantly in the form of cccDNA. However, HCC could still develop, particularly in patients with cirrhosis who had HBsAg seroclearance at an older age. (Hepatology 2004;39:1694-1701.)
The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat
Authors: Ling Yiqun , Zhang Junlan , Luo Bao , Song Daisheng , Liu Lichuan , Tang Liping , Stockard Cecil R. , Grizzle William E. , Ku David D. , Fallon Michael B.
Published: May 2004

Endothelin-1 (ET-1) stimulation of endothelial nitric oxide synthase (eNOS) via pulmonary endothelial endothelin B (ETB) receptors and pulmonary intravascular macrophage accumulation with expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are implicated in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Our aim was to evaluate the role of ET-1 in the development of experimental HPS. The time course of molecular and physiological changes of HPS and the effects of selective endothelin receptor antagonists in vivo were assessed after CBDL. Effects of ET-1 on intralobar pulmonary vascular segment reactivity and on eNOS expression and activity in rat pulmonary microvascular endothelial cells (RPMVECs) were also evaluated. Hepatic and plasma ET-1 levels increased 1 week after CBDL in association with a subsequent increase in pulmonary microvascular eNOS and ETB receptor levels and the onset of HPS. Selective ETB receptor inhibition in vivo significantly decreased pulmonary eNOS and ETB receptor levels and ameliorated HPS. CBDL pulmonary artery segments had markedly increased ETB receptor mediated, nitric oxide dependent vasodilatory responses to ET-1 compared with controls and ET-1 triggered an ETB receptor dependent stimulation of eNOS in RPMVECs. Pulmonary intravascular macrophages also accumulated after CBDL and expressed HO-1 and iNOS at 3 weeks. Selective ETB receptor blockade also decreased macrophage accumulation and iNOS production. In conclusion, ET-1 plays a central role in modulating pulmonary micovascular tone in experimental HPS. (Hepatology 2004;39:1593-1602.)
Covalent modification as a mechanism for the breakdown of immune tolerance to pyruvate dehydrogenase complex in the mouse
Authors: Palmer Jeremy M. , Robe Amanda J. , Burt Alastair D. , Kirby John A. , Jones David E. J.
Published: May 2004

The autoimmune liver disease primary biliary cirrhosis (PBC) is characterized by the breakdown of normal immune self tolerance to pyruvate dehydrogenase complex (PDC). How tolerance is broken to such a central and highly conserved self antigen in the initiation of autoimmunity remains unclear. One postulated mechanism is that reactivity arises to an altered form of self antigen with subsequent cross-reactivity to native self. In this murine study, we set out to examine whether sensitization with a covalently modified form of self PDC can give rise to the pattern of breakdown of B-cell and T-cell tolerance to self PDC seen in PBC patients. The notion that altered self can lead to tolerance breakdown was studied by sensitizing SJL/J mice with a covalently modified (biotinylated) preparation of self murine PDC (mP/O-B). Subsequently, antibody and T-cell reactivities to unmodified self mP/O were studied. Sensitization with mP/O-B elicited high-titre, high-affinity antibody responses reactive with both the mP/O-B immunogen and, importantly, native mP/O. In addition, significant MHC class II restricted splenic T-cell responses to native mP/O (i.e., true autoimmune responses) were seen in mP/O-B sensitized animals. The breakdown of T-cell self tolerance to mP/O was not seen in animals sensitized with irrelevant biotinylated antigens. In conclusion, this study provides evidence to support the concept that exposure to covalently modified self PDC can, in the correct proimmune environment, replicate the full breakdown of B-cell and T-cell immune tolerance to PDC seen in PBC. One potential etiological pathway in PBC therefore could be the breakdown of tolerance to self PDC occurring after exposure to self antigen covalently modified in the metabolically active environment of the liver. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;39:1583-1592.)
Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss
Authors: Dixon John B. , Bhathal Prithi S. , Hughes Norman R. , O'Brien Paul E.
Published: May 2004

The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable gastric band placement and the second after weight loss. Second biopsies were obtained from two groups: those requiring a subsequent laparoscopic procedure (n = 19) and those with index biopsy score of 2 or greater for zone 3-centric hepatic fibrosis (n = 17). All biopsies were scored, blinded to the patient's identity and clinical condition, for individual histological features and for NASH stage and grade. Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients. Repeat biopsies were taken at 25.6 ± 10 months (range, 9-51 months) after band placement. Mean weight loss was 34.0 ± 17 kg, and percentage of excess weight loss was 52 ± 17%. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis at the second biopsy (P < .001 for all). Portal abnormalities remained unchanged. Only four of the repeat biopsies fulfilled the criteria for NASH. There were 18 patients with an initial fibrosis score of 2 or more compared with 3 patients at follow-up (P < .001). Those with the metabolic syndrome (n = 23) had more extensive changes before surgery and greater improvement with weight loss. In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome-associated abnormal liver histological features in severely obese subjects. (Hepatology 2004;39:1647-1654.)
Pegylated interferon α therapy in acute hepatitis C: Relation to hepatitis C virus-specific T cell response kinetics
Authors: Kamal Sanaa M. , Ismail Alaa , Graham Camilla S. , He Qi , Rasenack Jens W. , Peters Thomas , Tawil Ahmed A. , Fehr Jutta J. , Khalifa Khalifa El Sayed , Madwar Mahmoud M. , Koziel Margaret James
Published: May 2004

Pegylated interferon α (PEG IFN-α) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined. This prospective study assessed the efficacy of PEG IFN-α treatment in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-specific CD4+ T cell responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who received either PEG IFN-α plus ribavirin (n = 20) or PEG IFN-α monotherapy (n = 20) for 24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively followed. Serum HCV RNA, HCV-specific CD4+ T cell responses, and cytokine production were measured before and during therapy and at follow-up and correlated to the outcome. The sustained virological response rate was 85% with PEG IFN-α/ribavirin combination and 80% with PEG IFN-α monotherapy. Five untreated subjects had spontaneous recovery. The frequency, magnitude, and breadth of HCV-specific CD4+ T helper 1 responses were significantly higher in treated subjects compared with untreated subjects with self-limited disease or subjects with chronic evolution. The CD4+ T cell responses were maintained in subjects with sustained virological responses and self-limited disease but fluctuated in those who developed chronic infection. In conclusion, PEG IFN-α therapy in acute hepatitis induces high rates of sustained virological response and prevents choronicity, probably through efficient early stimulation of multispecific HCV-specific CD4+ T helper 1 responses. (Hepatology 2004;39:1721-1731.)
A critical role for the chimpanzee model in the study of hepatitis C†
Authors: Bukh Jens
Published: May 2004

Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses—particularly the intrahepatic responses—following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. The RNA inoculated into chimpanzees originated from a single sequence, and the animals therefore had a monoclonal HCV infection. Monoclonal infection simplifies studies of HCV, because virus interaction with the host is not confounded by the quasispecies invariably present in a natural infection. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity. (Hepatology 2004;39:1469-1475.)
The role of Taiwan's national health insurance program in influencing adequate prenatal care
Authors: Liu Tsai‐Ching , Chen Chin‐Shyan
Published: May 2004

This paper reviews achievements in the utilization of prenatal care by pregnant women in Taiwan by analysing the 1989 and 1996 National Maternal and Infant Health Survey data. More precisely, it identifies and examines the programmatic and non‐programmatic factors that influence prenatal care utilization, thus determining the areas that require further attention from the programe. Logistic regression results show that the adequacy of prenatal care use was significantly associated with the implementation of the National Health Insurance (NHI). A higher likelihood of adequate care utilization was found among women who were married or employed, had a higher level of education, had more experience with regard to pregnancy and were at higher risk in terms of obstetrics. The effect of facility choice showed variations after the implementation of the NHI programme. Prior to NHI, no differences were noted between the use of clinics and hospitals. After the implementation of NHI, on the other hand, women who received most of their care from clinics had a higher likelihood of receiving more adequate prenatal care than those who received care from hospitals. Regional differences in seeking adequate prenatal care were also evident. Mothers who were living in southern areas were less likely to receive adequate prenatal care despite the implementation of NHI. The Bureau of NHI, therefore, still needs to work on mechanisms to ensure that more attention is given to the distribution of its medical resources and that additional health care accessibility is provided to pregnant women in these areas. Copyright © 2004 John Wiley & Sons, Ltd.
Popular participation and the State: democratizing the health sector in rural Peru
Authors: Bowyer Tim
Published: May 2004

Popular participation has been an important component of most primary health care strategies since the Alma Ata Declaration, 1978. This article examines the use of state‐sponsored participation in the health sector in Peru and some of the experiences that have accompanied its implementation. Taking the Local Health Administration Committees (CLAS) from the second Fujimori government (1995–2000) as an example, it is shown that for self‐motivated rural communities to work in harmony with the state, there must be willingness to adapt to the varying levels of intra‐community differences, social integration and social support. Copyright © 2004 John Wiley & Sons, Ltd.
Paroxetine treatment of delusional disorder, somatic type
Authors: Hayashi Hiroshi , Oshino Shingo , Ishikawa Junichi , Kawakatsu Shinobu , Otani Koichi
Published: May 2004

A 77‐year‐old female showed delusion of infestation in the oral cavity. She was treated by paroxetine 20 mg/day, and the hypochondriacal delusion disappeared after 8 weeks. Hypoperfusion in the left temporal and parietal lobes which was observed when she had the delusion was normalized after resolution of the delusion. This report suggests that paroxetine may be effective for delusional disorder, somatic type. It also supports the previous views that this disorder is associated with serotonergic dysfunction and hypoperfusion in the temporal and parietal lobes. Copyright © 2004 John Wiley & Sons, Ltd.