bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Evaluation of Preoperative Screening Laboratory Tests in General Surgery Patients
Authors: Alsumait Basel M. , Alhumood Salah A. , Ivanova Titiana , Mores Maher , Edeia Magdi
Published: April 2003

Objective: To assess the value of routine biochemical and hematological screening of otherwise healthy patients prior to elective general surgery. Materials and Methods: Prospective laboratory screening tests were done for 1,000 consecutive patients undergoing elective general surgery at Mubarak Al-Kabeer Hospital, Kuwait, from January to August 1999. Patients with abnormal laboratory results were interviewed and examined preoperatively as part of the present study protocol, to identify a possible cause for the abnormal laboratory result. The perioperative course of these patients was also monitored. Results: Approximately 14% of the preoperative tests were abnormal, 9.2% of which was expected while 4.9% was unexpected; there was no change in the preoperative care of patients with unexpected abnormalities, nor was there surgical delay or related postoperative complication. Conclusion: The results indicate that laboratory tests should be selectively used when the patient has appropriate risk factors. Instead, greater emphasis should be placed on history and physical examination. Application of such policy will result in substantial financial savings that could be utilized to improve the health care system.
Unexpected Prolonged Neuromuscular Block after Mivacurium: A Case Report
Authors: Hemadri Makani , Purva Makani , Traykova Vesselka
Published: April 2003

Objective: To present a case of unexpected prolonged apnoea following the administration of mivacurium, a short-acting muscle relaxant and to identify the factors for early diagnosis and management. Clinical Presentation and Intervention: A 19-year-old physically fit lady without personal or family history suggestive of anaesthetic problems had an excision of fibro-adenoma from the breast. She did not recover as quickly as was expected from the anaesthetic, which included the administration of mivacurium. She had prolonged neuromuscular blockade. She was kept ventilated and sedated. Five hours after the last dose of mivacurium, she showed signs of spontaneous respiration and at 6 h she was extubated and fully recovered. It was shown later that the patient had a pseudocholinesterase deficiency. Conclusion: Pseudocholinesterase deficiency is an uncommon occurrence but should be highly suspected in cases of prolonged paralysis following the administration of a short-acting muscle relaxant. The use of a nerve stimulator is recommended whenever muscle relaxants are used. Muscle relaxants should be used only when facilities for prolonged ventilation are available.
Successful Implantation of a Permanent Pacemaker through a Persistent Left Superior Vena cava
Authors: Al-Sayegh Ali H. , Al-Kandari Fawziah
Published: April 2003

We present a case of successful implantation of a permanent pacemaker through an unusual course of a persistent left superior vena cava (PLSVC). A young male patient presented with symptomatic bradycardia and a heart rate of 35 beats per minute. The pacing lead was introduced through the standard left subclavian vein approach and was found to pass through an unusual course that was suspected to be a PLSVC. The lead was further advanced to the right atrium and positioned successfully in the right atrial appendage with excellent short-term and long-term pacing parameters. PLSVC should be suspected whenever the catheter takes an unusual position during central venous catheterization. Most right heart catheterization procedures, including permanent pacemaker implantation, can be safely completed in spite of this anomaly.
Effect of Chronic Repetitive Transcranial Magnetic Stimulation on Regional Cerebral Blood Flow and Regional Cerebral Glucose Uptake in Drug Treatment-Resistant Depressives
Authors: Conca Andreas , Peschina William , König Peter , Fritzsche Heinz , Hausmann Armand
Published: April 2003

Brain imaging studies have shown that repetitive transcranial magnetic stimulation (rTMS) is biologically active. The aim of the present study was to investigate the patterns of the regional cerebral glucose uptake rate (rCMRGlu) and regional 99mTc HMPAO uptake rate (regional cerebral blood flow; rCBF) during a series of therapeutic rTMS sessions at low frequency. Four drug-resistant depressed patients underwent 10 rTMS sessions as an add-on measure over 14 days. One day before and 1 day after the TMS series, 511-keV SPECT with simultaneous 18F-fluorodeoxyglucose and 99mTc HMPAO measurements were carried out. All patients showed a good clinical outcome. Statistically significant common changes in rCBF and rCMRGlu patterns were found in the upper frontal regions bilaterally in terms of increased uptake rates and in the left orbitofrontal cortex in terms of decreased uptake rates of both isotopes compared to controls. However, the lateralization patterns of rCBF and rCMRGlu after rTMS treatment revealed marked differences. Thus, although no relevant changes in lateralization of the glucose uptake were observed, a clear right-sided preponderance of rCBF also in areas remote from the stimulation site was described. Therapeutic rTMS seems to influence distinct cortical regions, affecting rCBF and rCMRGlu in a homogeneous manner as well as in different ways, which are probably region dependent and illness related. The role of the stimulation coil placement site should be taken into account.
Metabotropic Glutamate Receptors mGluR1α and mGluR2/3 Display Dynamic Expression Patterns in Developing Rat Striatum
Authors: Jokel E.S. , Garduno E.R. , Ariano M.A. , Levine M.S.
Published: April 2003

The developmental expression of two metabotropic glutamate receptors (mGluR), mGluR1α and mGluR2/3 was evaluated in the rat striatum from birth to adulthood. The mGluR1α receptor subtype displayed a patchy organization perinatally that became more homogeneous after the first postnatal week. The adult pattern of receptor expression consisted of homogeneous punctate profiles spread throughout the striatum. The mGluR2/3 receptor subtype exhibited a unique pattern of ontogenic expression, being associated exclusively with fibers of the internal capsule that penetrate the striatum, during the perinatal period. The protein localization for this subtype spread into the striatal neuropil after the first postnatal week, in parallel to the development of afferent terminations and arborizations to the nucleus. Unlike the ionotropic GluR subunits that are associated with somata and dendrites, neither subtype of metabotropic receptor was associated with neuronal cell bodies within the striatum.
The Orphan Nuclear Receptor NOR-1 Interacts with the Homeobox Containing Protein Six31
Authors: Ohkura Naganari , Ohkubo Takao , Maruyama Kouji , Tsukada Toshihiko , Yamaguchi Ken
Published: April 2003

Neuron-derived orphan receptor 1 (NOR-1) is a member of the NGFI-B subfamily within the nuclear receptor superfamily. In order to identify cofactors that associate with NOR-1 in the fetal forebrain, we tested a yeast two-hybrid system with the NOR-1 cDNA fragment lacking a transactivating domain as a bait. By screening of the rat fetal brain embryonic day 17 library, a rat homologue of Six3 was identified as an associated protein. We demonstrated that NOR-1 interacted with Six3 in yeast and in vitro, and the association was required for the DNA binding and AF2 domains of NOR-1. Regarding the other members of the family (NGFI-B and RNR-1), association with Six3 was not observed in yeast. In addition, cotransfection experiments with Six3 and NOR-1 indicated that Six3 had a negative activity against the transactivation by NOR-1 through the NBRE response element in a dose- dependent manner. The overlap in expression of NOR-1 and Six3 was mainly detected in the rat fetal forebrain on embryonic day 18. Thereafter, the expression of both genes diminished rapidly. These results suggest that a dimer consisting of a homeobox containing protein Six3 and transcriptional factor NOR-1 might regulate gene expression during the late stage of the fetal forebrain development. This study provides, after the association of Ftz and Ftz-F1 in Drosophila, another example of a dimer formation of a homeobox protein and an orphan nuclear receptor.
Are Hypothyroidism and Iron Deficiency Precursor Cell Diseases?
Authors: Mayer-Pröschel Margot , Morath Dan , Noble Mark
Published: April 2003

It is neither known why hormonal and nutritional deficiencies only cause neurological abnormalities at particular periods of development, nor is it known why repair only occurs if normal metabolic status is restored within a particular temporal window. We propose that these maladies are precursor cell diseases, in which the normal balance between self-renewal and differentiation is compromised in dividing precursor cells. According to this hypothesis, the windows of vulnerability in these disorders correspond to the timing of particular transitions in CNS precursor cells, as seen in our studies on the effects of thyroid hormone and iron on the generation of oligodendrocytes and their immediate ancestor, the O-2A progenitor cell.
Influence of Non-Neuronal Cells on Establishment of Neuropeptide Y Expression by Sympathetic Neurons in vitro
Authors: MacPhedran Sally E. , Hall Alison K.
Published: April 2003

Sympathetic ganglion precursors were used to test the role of non-neuronal cell-derived factors in the establishment of mature neuronal phenotypes. In control conditions, characteristic neuronal populations with and without neuropeptide Y (NPY) expression developed after 1 week, but following removal of non-neuronal cells, virtually all neurons expressed NPY. Thus, ganglionic non-neuronal cells downregulated NPY expression in some but not all neurons in vitro. Conditioned medium from non-neuronal cells restored heterogeneous NPY expression, a finding that suggests the factors are soluble. A non-neuronal cell-derived cytokine, leukemia inhibitory factor, dramatically reduced NPY expression in all neurons, but no concentration tested could recapitulate heterogeneous neuronal NPY expression. Sympathetic precursors that incorporated BrdU early in the culture were more likely to develop NPY expression than neurons that became postmitotic later in vitro. Together, these findings support the notion that the environment in which neurons become postmitotic contributes to neuronal phenotype.
The Early Steps of Oligodendrogenesis: Insights from the Study of the plp Lineage in the Brain of Chicks and Rodents
Authors: Spassky Nathalie , Olivier Christelle , Cobos Immaculada , LeBras Barbara , Goujet-Zalc Cécile , Martínez Salvador , Zalc Bernard , Thomas Jean-Léon
Published: April 2003

Oligodendrocytes are the myelin-forming cells of the central nervous system. Over the last decade, their development in the embryonic brain and spinal cord has been documented following the discovery of early oligodendroglial markers. These early expressed oligodendroglial genes nevertheless show differences in their spatiotemporal pattern of expression and it is not yet clear if their expression is linked in a linear way. This review highlights the common themes underlying the spatiotemporal aspects of oligodendrogenesis in chick and rodent brain and discusses some recent advances in the knowledge of the cell lineage expressing plp, one of the early oligodendroglial genes. We suggest a model of oligodendroglial commitment whereby definitive oligodendroglial progenitor formation is preceded by a primitive neuroglial progenitor stage and whereby different oligodendrocyte lineages might segregate from either plp-positive or plp-negative primitive progenitor cells.
Morphological Changes and Cellular Dynamics of Oligodendrocyte Lineage Cells in the Developing Vertebrate Central Nervous System
Authors: Ono Katsuhiko , Kagawa Tetsushi , Tsumori Toshiko , Yokota Shigefumi , Yasui Yukihiko
Published: April 2003

Oligodendrocyte precursor cells (OPCs) originate in multiple restricted regions of the developing central nervous system (CNS). Here, we focus on morphological changes of oligodendrocyte lineage cells and their cellular dynamics including cell motility and proliferation. Morphological studies with molecular markers for OPCs suggest distinct spatiotemporal patterns of OPC migration in vivo, which are directly demonstrated by application of exogenous fluorescent markers to OPCs. Extensive proliferation of OPCs in the CNS parenchyma is also demonstrated by pulse labeling of the cells with bromodeoxyuridine. The results strongly suggest that oligodendrocyte lineage cells are highly motile and actively proliferate with an elongated morphology. These data provide insights into the potential molecular mechanisms of OPC dispersal throughout the CNS.
Greater Resistance and Lower Contribution of Free Radicals to Hypoxic Neurotoxicity in Immature Rat Brain Compared to Adult Brain as Revealed by Dynamic Changes in Glucose Metabolism
Authors: Maruoka Nobuyuki , Murata Tetsuhito , Omata Naoto , Fujibayashi Yasuhisa , Waki Atsuo , Yoshimoto Mitsuyoshi , Yano Ryoichi , Yonekura Yoshiharu , Wada Yuji
Published: April 2003

Seven-day-old rat brain slices were incubated at 36°C in oxygenated Krebs-Ringer solution containing [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), and serial two-dimensional time-resolved images of [18F]FDG uptake by the slices were obtained. The Gjedde-Patlak graphical method was applied to the image data, and the duration limit of hypoxia loading that allowed recovery of the fractional rate constant (k3*) of [18F]FDG (proportional to the cerebral glucose metabolic rate) after hypoxia loading to the unloaded control level was 50 min, and MK-801 as an N-methyl-D-aspartate antagonist had neuroprotective effects, but PBN as a free radical scavenger was ineffective. In our previous study in adult (7-week-old) rat brains [Murata et al., Exp Neurol 2000, 164:269–279], the limit of the hypoxia loading time was 20 min, and both MK-801 and PBN were effective. In the immature rat brains, the ratio of aerobic glucose metabolism to the total glucose metabolism was low compared with the adult rat brains, suggesting only a slight involvement of free radicals in hypoxic neurotoxicity. These data suggest that the higher resistance of immature brains to hypoxia compared to that of adult brains is attributable to a lower involvement of free radicals due to a lower aerobic glucose metabolic rate.
Gap Junction-Mediated Bidirectional Signaling between Human Fetal Hippocampal Neurons and Astrocytes
Authors: Rozental Renato , Andrade-Rozental Adriana F. , Zheng Xin , Urban Marcia , Spray David C. , Chiu Fung-Chow
Published: April 2003

Gap junctions are clusters of intercellular channels that connect the interiors of coupled cells. In the brain, gap junctions function as electrotonic synapses between neurons and as pathways for the exchange of metabolites and second-messenger molecules between glial cells. Astrocytes, the most abundant glial cell type coupled by gap junctions, are intimately involved in the active control of neuronal activity including synaptic transmission and plasticity. Previous studies have suggested that astrocytic-neuronal signaling may involve gap junction-mediated intercellular connections; this issue remains unresolved. In this study, we demonstrate that second-trimester human fetal hippocampal neurons and astrocytes in culture are coupled by gap junctions bidirectionally; we show that human fetal neurons and astrocytes express both the same and different connexin subtypes. The formation of functional homotypic and heterotypic gap junction channels between neurons and astrocytes may add versatility to the signaling between these cell types during human hippocampal ontogeny; disruption of such signaling may contribute to CNS dysfunction during pregnancy.
Interleukin-15 Expression Is Associated with Malignant Potential in Colon Cancer Cells
Authors: Kuniyasu Hiroki , Oue Naohide , Nakae Dai , Tsutsumi Masahiro , Denda Ayumi , Tsujiuchi Toshifumi , Yokozaki Hiroshi , Yasui Wataru
Published: April 2003

Interleukin 15 (IL-15 mRNA expression was detected in human colorectal cancer cells (Colo320, WiDr, TCO and DLD1) by the reverse transcriptase-polymerase chain reaction (RT-PCR). Only Colo320 and WiDr cells secreted IL-15 culture medium. With IL-15 treatment, all cell lines grew at a rate of 120–180% of that of nontreated cells. A binding assay with 125I-labeled IL-15 showed binding activity to IL-15 in Colo320 (Kd: 0.098 nM) cells. IL-15 also reversed the growth inhibition caused by serum starvation in Colo320 cells. IL-15-induced cell growth in regular and serum-free media was abrogated by anti-IL-15 antibody treatment in Colo320 cells. Moreover, IL-15 treatment reduced doxorubicin-induced cytostasis and cytolysis in Colo320 cells by 50%. The invasion capacity of IL-15-treated Colo320 cells was 5.3 times that of untreated cells. Immunoblotting showed that IL-15-treated Colo320 cells exhibited downregulation of p21Waf1 and Bax, and upregulation of Bcl-2, phospho-AKT, MMP9/MMP2, and VEGF. Finally, immunostaining of human colon cancer revealed that 33 (70%) of 47 Dukes’ C cases showed IL-15 expression in cancer cells, whereas only 16% of Dukes’ B cases did (p < 0.0001). IL-15 may play important roles in cell proliferation, invasion, and metastasis of human colorectal cancer.
Effects of Z-100, a Mycobacterium-tuberculosis-Derived Arabinomannan, on the LP-BM5 Murine Leukemia Virus Infection in Mice
Authors: Sasaki Hidetaka , Kobayashi Makiko , Pollard Richard B. , Suzuki Fujio
Published: April 2003

Objective: To investigate the effects of Z-100, an arabinomannan extracted from Mycobacterium tuberculosis, on the LP-BM5 murine leukemia virus (LP-BM5 MuLV) infection in mice. Methods: C57BL/6 mice infected intraperitoneally with 4.5 × 102 PFU/mouse of LP-BM5 MuLV (MAIDS mice) were treated intraperitoneally with a 10-mg/kg dose of Z-100 every other day beginning 1 day after the viral infection. MAIDS mice treated with Z-100 were compared with control mice (MAIDS mice treated with saline) for their survival and splenomegaly after LP-BM5 infection. Cytokine-producing profiles of splenic T cells from these two groups of mice were also compared. Results: When MAIDS mice treated with Z-100 were compared with those of control mice, a decrease in splenomegaly and lymphadenopathy was observed. Splenomegaly was markedly enhanced in MAIDS mice treated intraperitoneally with IL-4 or IL-10. When MAIDS mice were treated with Z-100, their survival rates were significantly increased compared to those of controls. Splenic T cells from control mice produced type-2 cytokines (IL-4 and IL-10). However, a decreased production of type-2 cytokines by splenic T cells from MAIDS mice treated with Z-100 was demonstrated. Conclusion: Z-100 could decrease the severity of the LP-BM5 MuLV infection through the regulation of MAIDS-associated type-2 T-cell responses.
Antigen Presentation by Murine Peritoneal Cavity Macrophage-Derived Dendritic Cells
Authors: Makala L.H.C. , Nishikawa Y. , Kamada T. , Xuan X. , Nagasawa H.
Published: April 2003

Murine peritoneal cavity macrophage derived dendritic cells (PEC-DC) generated using early growth factors, interleukin 4 and granulocyte-macrophage colony-stimulating factor followed by maturation in interferon-gamma plus either, Toxoplasma lysate antigen (TLA) or lipopolysaccharide, bind TLA by a nonspecific mechanism and continue to express major histocompatibility complex class II antigens after 24 h of culture in vitro. Moreover, the proliferation of CD3+ spleen T cells from mice immunized with Toxoplasma gondii homogenate, induced by PEC-DC-mediated antigen presentation was statistically significant and of consistent amplitude. This accessory function of PEC-DC is antigen specific.
Overexpression of Sialyl Lewis x Antigen Is Associated with Formation of Extratumoral Venous Invasion and Predicts Postoperative Development of Massive Hepatic Metastasis in Cases with Pancreatic Ductal Adenocarcinoma
Authors: Takahashi Shinichiro , Oda Tatsuya , Hasebe Takahiro , Sasaki Satoshi , Kinoshita Taira , Konishi Masaru , Ueda Takanori , Nakahashi Chigusa , Ochiai Takenori , Ochiai Atsushi
Published: April 2003

The clinicopathological factors and expression of sialyl Lewis antigens which are the cell adhesion molecules to endothelial cells were compared in relation to the extent of the postoperative hepatic metastasis in 23 consecutive patients with pancreatic ductal adenocarcinoma whose clinical courses were carefully monitored and documented. The overall survival of cases with massive hepatic metastasis (MHM) was significantly poorer than that of those with local or no hepatic metastasis (p = 0.0453). Postoperative MHM was significantly correlated with the presence of duodenal invasion (p = 0.0418), the presence of portal vein invasion (p = 0.0435), the presence of extratumoral venous invasion (p = 0.0052) and high expression of sialyl Lewis x antigen (p = 0.0022). Multivariate analysis confined significant correlation between the high expression of sialyl Lewis x antigen and the development of MHM (p = 0.0402). Kaplan-Meier analysis revealed that the overall survival of patients with a high expression of sialyl Lewis x antigen was significantly poorer than that of patients with a low expression of the antigen (p = 0.0216). These results indicate that the overexpression of sialyl Lewis x antigen plays an important role in the development of MHM, and also predicts a poorer overall survival of these patients. Further studies with more cases are warranted to confirm these results.
An integrated genetic and physical map of the 650-kb region containing the congenital polycystic kidney (cpk) locus on mouse Chromosome 12
Authors: Mrug M. , Green W.J. , DasGupta S. , Beier D.R. , Lu W. , D’Eustachio P. , Guay-Woodford L.M.
Published: April 2003

Mice homozygous for the congenital polycystic kidney (cpk) mutation develop a rapidly progressive form of polycystic kidney disease. We report an integrated genetic and physical map of the 650-kb region containing the cpk locus and the exclusion of Rrm2 and Idb2 as candidate cpk genes. Our study establishes the requisite foundation for positional cloning of the cpk gene.
Insertion of a loxP site in a size-reduced human accessory chromosome
Authors: Moralli D. , Vagnarelli P. , Bensi M. , De Carli L. , Raimondi E.
Published: April 2003

The generation in vitro of mammalian artificial chromosomes, in view of the possibility of developing new technologies for gene therapy, is still an ambitious goal. Mammalian artificial chromosomes, to be used as cloning and expression vectors, have been constructed either by de novo synthesis or by reduction of pre-existing chromosomes. In the work here reported, we introduced a loxP sequence into the pericentromeric region of a chromosome 9-derived X-ray-reduced minichromosome, with the purpose of generating a human chromosome vector (HCV). The modified accessory chromosome is linear and mitotically stable, has lost at least 1400 kb of alpha satellite DNA and normally binds CENP-B, CENP-C and CENP-E. The efficiency of gene targeting via loxP mediated homologous recombination was tested using the histone H2B-Green Fluorescent Protein chimaeric gene as a reporter. The frequency of site-specific insertion of the exogenous sequence was found to be about 50% and to occur in a controlled way with regard to the number of copies. The expression level of the fusion protein was stable over prolonged time in culture.
Assignment to chromosome 12q24.33, gene organization and splicing of the human KRAB/FPB containing zinc finger gene ZNF84
Authors: Rosati M. , Rocchi M. , Storlazzi C.T. , Grimaldi G.
Published: April 2003

FISH analysis was used to assign the human ZNF84 gene to chromosome 12q24.33, a region associated with recurrent breakpoints and allelic loss in several human cancers. In this report we show that the ZNF84 coding region is organized in four exons; two are dedicated to encoding the KRAB/FPB-A and KRAB/FPB-B modules, the remaining exons encode the N-terminal amino acids and C-terminal array of zinc finger units, respectively.
Characterization and chromosome assignment of the canine gamma-sarcoglycan gene (SGCG) to CFA 25q21→q23
Authors: Conrad K. , Deppe A. , Neumann S. , Breen M. , Quignon P. , André C. , Brenig B. , Leeb T.
Published: April 2003

Mutations in the gene for gamma-sarcoglycan (SGCG) located on HSA 13q12 are responsible for limb girdle muscular dystrophy (LGMD2C) in human. Here we report the cloning of the canine SGCG gene together with its genomic structure and several intragenic polymorphisms. The coding part of the canine SGCG contains seven exons spanning at least 70 kb of genomic DNA. The chromosome assignment of the canine SGCG gene to CFA 25q21→q23 confirms that the canine syntenic group 10 corresponds to CFA 25 and also supports the findings of human-canine reciprocal chromosome painting.
A pericentric inversion in the cattle Y chromosome
Authors: Iannuzzi L. , Di Meo G.P. , Perucatti A. , Eggen A. , Incarnato D. , Sarubbi F. , Cribiu E.
Published: April 2003

Sixteen male Podolian cattle, two sires and their 14 male offspring, were investigated cytogenetically on the basis of a female-like phenotype found in one of them. Eleven male offspring, including the one with female traits, and one of the two sires were found to carry an abnormal Y chromosome which originated from a pericentric inversion of the proximal half of the Yq arm (Yq11→q12.2), as demonstrated by both banding and FISH mapping techniques with Y-specific molecular markers.
Healing of Active, Non-Atrophic Autoimmune Gastritis by H. pylori Eradication
Authors: Müller H. , Rappel S. , Wündisch T. , Bayerdörffer E. , Stolte M.
Published: April 2003

Background and Aims: The antigastric antibodies present in Helicobacter pylori infection act as a marker for an ongoing antigastric autoimmune process in the gastric mucosa, which can already be diagnosed in the non-atrophic stage. In a retrospective, uncontrolled study, therefore, we investigated the question as to whether this type of gastritis can be healed by the eradication of H. pylori. Patients and Methods: In 80 patients with an active, not yet atrophic autoimmune gastritis, we analysed a maximum of four investigations per patient over a period of up to 39.5 months. The following parameters were graded in the antral and corpus mucosa prior to and after H. pylori eradication treatment: grade and activity of the gastritis, H. pylori colonization, atrophy, parietal cell hypertrophy, and incidence of intestinal metaplasia. In addition, the typical parameters for this type of gastritis, such as grade of the periglandular lymphocytic infiltration, grade of glandular destruction and incidence of nodular ECL cell proliferates in the corpus mucosa were determined. Results: In 64 patients (80%), H. pylori eradication treatment was followed by healing of the active autoimmune corpus gastritis, that is, the activity of the gastritis disappeared, and lymphocytic infiltration of the glands, glandular destruction and parietal cell hypertrophy was found to be significantly reduced. Conclusions: Our uncontrolled, retrospective study confirms the existence of an active, not yet atrophic autoimmune gastritis as a sequela of H. pylori infection.
Transient Loss of T-Cell Reactivity in a Patient with Hepatitis C Virus Reinfection
Authors: Düesberg Uta , Geulen Oliver , Schneiders Angelika M. , Kaiser Rolf , Brackmann Hans H. , Matz Bertfried , Sauerbruch Tilman , Spengler Ulrich
Published: April 2003

Background/Aims: Self-limited acute hepatitis C virus (HCV) infection with spontaneous recovery is only rarely observed in clinical practice. All existing studies correlate strong cellular immune responses to the recovery from HCV infection. Case Report: Here, we present a 49-year-old haemophiliac, who had successfully recovered from an acute hepatitis, which was classified retrospectively as HCV infection based on his antibody profiles. This patient was reinfected with HCV 18 years later from an exogenous source, and successfully recovered from this reinfection within 2 months. After his first hepatitis the patient displayed strong cellular responses against recombinant HCV proteins. During reinfection, T-cell proliferation was markedly reduced, while HCV antibody titres increased. However, E2 antibodies were consistently not detectable. T-cell proliferation returned to the pre-reinfection level only several months after loss of viraemia. Discussion: Our observations resulted in the unexpected finding that our patient cleared HCV reinfection despite an apparent loss of his pre-existing T-cell reactivity in the peripheral blood.
Hypergastrinemia as a Cause of Chromogranin A Increase in Blood in Patients Suspected to Have Neuroendocrine Tumor
Authors: Kleveland Ola , Syversen Unni , Slørdahl Kari , Waldum Helge L.
Published: April 2003

Background: Chromogranin A (CgA) is a sensitive marker for neuroendocrine neoplasia. Enterochromaffin-like cell hyperplasia secondary to hypergastrinemia also leads to CgA increase in blood. Treatment with inhibitors of acid secretion, atrophic gastritis and infection with Helicobacter pylori are prevalent conditions leading to hypergastrinemia. We therefore wanted to study whether concomitant determination of gastrin could increase the utility of CgA as a marker of neuroendocrine neoplasia. Methods: CgA and gastrin concentrations were determined by radioimmunoassay methods, while pepsinogen I (used to diagnose severe atrophic gastritis) was determined by a commercial immunoenzymatic assay. Results: Among 100 patients with elevated CgA, we found that 29% had hypergastrinemia. Vice versa, CgA was elevated in 23 out of 26 (88.5%) in a population of patients with hypergastrinemia. By determining pepsinogen I in blood in patients with hypergastrinemia, a proportion of them was diagnosed as having severe atrophic gastritis. Conclusion: We conclude that determination of gastrin in blood in patients with CgA elevation will increase the utility of CgA in the diagnosis of neuroendocrine tumors.
Ischemic Colitis during Pregnancy and Contraceptive Medication
Authors: Frossard Jean Louis , Spahr Laurent , Queneau Pierre Edouard , Armenian Berj , Bründler Marie-Anne , Hadengue Antoine
Published: April 2003

Ischemic bowel disease is generally considered a disease of the elderly and usually consists of reversible colopathy. Nonocclusive causes of ischemic colitis include low-flow states due to cardiac dysfunction and hypovolemia and use of certain medications including progestational medication. We report 2 cases of ischemic colitis in young women. The first one occurred in a young patient who developed three consecutive episodes of ischemic colitis during her pregnancy, whereas the second woman presented with ischemic colitis in relation with the estrogen use. Each episode had a favorable outcome. Having ruled out an infectious cause, or a low blood flow state and in the absence of known thrombogenic disease, we hypothesized the etiology of these ischemic episodes to a high level of circulating estrogens due to pregnancy in the first case and oral contraceptive medication in the second. Physicians treating hemorrhagic colitis in young women should consider the use of contraceptive medication containing estrogens or pregnancy as possible causes.
Massive Gastrointestinal Bleeding Caused by Ectopic Pancreas Mimicking Jejunal Tumor
Authors: Joo Young-Eun , Kim Hyun-Soo , Choi Sung-Kyu , Rew Jong-Sun , Park Chang-Soo , Kim Young-Jin , Kim Sei-Jong
Published: April 2003

Background: Ectopic pancreas is usually an incidental finding at surgery or autopsy and rarely produces clinical symptoms. But it is capable of producing symptoms, depending on its location, size and involvement of the overlying mucosa. Case Report: We report a case with massive gastrointestinal bleeding from ectopic pancreas mimicking jejunal tumor, confirmed by emergency operation. A 40-year-old male was admitted to Chonnam National University Hospital with a 2-day history of melena. A technetium-99m-labeled RBC scan showed massive radioactivity in loops of small bowel due to active bleeding. Superior mesenteric angiography revealed a hypervascular stained mass supplied by proximal jejunal branch. A computed tomographic scan of abdomen revealed an enhancing mass in the proximal jejunum. At emergency operation, bleeding from the center of the mass was found situated approximately 30 cm from the Treitz ligament. Segmental resection of the involved jejunum and end-to-end anastomosis were performed. Histologic examination of resected specimen revealed an ectopic pancreas. Conclusion: So far, there have been no case reports of massive gastrointestinal bleeding from ectopic pancreas mimicking jejunal tumor as described in our case. In every patient in whom ectopic pancreas can definitely be seen to cause clinical symptoms including gastrointestinal bleeding, the lesion should be excised.
Young Patients with Barrett’s Oesophagus Experience Less Reflux Complaints
Authors: Loffeld R.J.L.F.
Published: April 2003

Background/Aim: Barrett’s oesophagus can be expected to be more resistant to the effects of acidic refluxate, and, hence, it can be postulated that patients with Barrett’s oesophagus experience less reflux complaints. A cross-sectional study in consecutive patients presenting with Barrett’s oesophagus and reflux oesophagitis was done in order to test this hypothesis. Methods: Patients received a standardized questionnaire, and overall and specific symptom scores were assessed on a five-point Likert scale. Results: Reflux oesophagitis was diagnosed in 128 patients and Barrett’s oesophagus in 42. Patients with reflux oesophagitis had statistically significantly higher symptom scores than patients with Barrett’s oesophagus (mean ± SD): 9.1 ± 6.3 vs. 6.2 ± 5.4 (p = 0.01). The scores for heartburn and acid regurgitation were significantly higher in reflux oesophagitis, while there was a trend for epigastric pain, retrosternal pain, and vomitus. The symptom scores of patients with Barrett’s oesophagus older than 60 years were not different from patients with reflux oesophagitis older than 60 years: 5.2 ± 4.8 vs. 7.4 ± 6.4. However, the symptom scores of patients younger than 60 years were significantly higher in those with reflux oesophagitis: 10.2 ± 5.7 vs. 7.2 ± 5.7 (p = 0.04). Odynophagia, heartburn, and acid regurgitation scored significantly higher in patients with reflux oesophagitis younger than 60 years as compared with Barrett patients younger than 60 years. Conclusions: Patients with Barrett’s oesophagus indeed suffer less from reflux complaints. However, this is only true for those younger than 60 years.
Effects of Berberine on Intracellular Free Calcium in Smooth Muscle Cells of Guinea Pig Colon
Authors: Cao Ji-Wang , Luo He-Sheng , Yu Bao-Ping , Huang Xiao-Dong , Sheng Zhi-Xiang , Yu Jie-Ping
Published: April 2003

Aim: To investigate the effects and mechanism of berberine (Ber) on the intracellular free calcium concentration ([Ca2+]i) in the smooth muscle cells of guinea pig colon. Methods: The changes of [Ca2+]i were assayed by the biwavelength spectrophotometry with Fura 2-AM in the cell suspension of the smooth muscle cells, which were freshly isolated from guinea pig colon. Results: In the resting state, [Ca2+]i in the HEPES-Ringer solution (CaCl2 1.5 mmol·l–1) was (108 ± 9.4) nmol·l–1 (n = 7). Ber had no significant effects on the resting [Ca2+]i, but markedly inhibited the increase in [Ca2+]i induced by 60 mmol·l–1 KCl in a concentration-dependent manner. The value of IC50 was 34.09 µmol·l–1. 30 and 100 µmol·l–1 Ber also inhibited the elevation of [Ca2+]i evoked by 10 µmol·l–1 Ach in a dose-dependent fashion in the presence or absence of extracellular Ca2+. In addition, Ber inhibited the elevation of [Ca2+]i stimulated by cyclopiazonic acid (CPA) in a dose-dependent manner. This effect was more potent in the HEPES-Ringer solution (IC50 = 37.79 µmol·l–1) than Ca2+-free medium (IC50 = 49.70 µmol·l–1). Conclusions: Ber possessed an inhibitory effect on the influx of extracellular Ca2+ and Ca2+-release from intracellular stores in the smooth muscle cells of colon. That is to say Ber may be a blocker of Ca2+ channels.
Pancreatitis-Associated Protein (HIP/PAP) Gene Expression Is Upregulated in NOD Mice Pancreas and Localized in Exocrine Tissue during Diabetes
Authors: Baeza N. , Sanchez D. , Christa L. , Guy-Crotte O. , Vialettes B. , Figarella C.
Published: April 2003

We have previously shown a specific significant overexpression in the exocrine pancreatic tissue of two members of the regenerating gene multifamily: reg I and reg II in the non-obese diabetic (NOD) mouse during active diabetogenesis. To strengthen the hypothesis that the overexpression of these genes may represent a defence of the acinar cell against pancreatic endocrine agression, we studied the pancreatic expression and the localization of another member of this family: the pancreatitis-associated protein (PAP) in NOD mice under the same conditions. We found that NOD mice present significantly higher PAP mRNA levels than control IOPS-OF1 mice. There is no difference between female NOD mice which progressively develop type I diabetes between 100 and 200 days and male NOD mice which are protected. The only difference observed was in function of the age of onset of diabetes. Before 180 days, the PAP mRNA levels were similar to those found in NOD males and nondiabetic females, but above 180 days the levels of PAP mRNA increased significantly. More importantly immunohistological studies demonstrate a striking difference in the protein localization between normal or nondiabetic NOD mice and diabetic NOD mice. If the protein is mainly detected in the islet cells in the absence of diabetes, a specific and intense expression of PAP was observed in the acinar cells of diabetic NOD mice. In conclusion, our data demonstrates that the acinar cells may react to a long-lasting pancreatic endocrine aggression by an induction of PAP and underlines the existence of a symbiotic relationship between endocrine and exocrine tissue.
Function of BID – a Molecule of the bcl-2 Family – in Ischemic Cell Death in the Brain
Authors: Plesnila Nikolaus , Zinkel Sandra , Amin-Hanjani Sepideh , Qiu Jianhua , Korsmeyer Stanley J. , Moskowitz Michael A.
Published: April 2003

Mitochondrial mechanisms, particularly the release of cytochrome c, play a role in the death of nerve and glial cells in cerebral ischemia. We have currently investigated whether BID, a proapoptotic molecule of the bcl-2 family and promoter of the release of cytochrome c is expressed in the brain, activated by cerebral ischemia in vivo, and contributes to ischemic cell death. We found BID in the cytosol of mouse brain and of primary cultured mouse neurons and showed that neuronal BID is a substrate for caspase 8. BID was cleaved in vivo 4 h after transitory occlusion of the middle cerebral artery. Further, BID–/– mice had a significant attenuation of infarction (–67%) and significantly lower release of cytochrome c (–41%). The findings indicate that the proapoptotic molecule BID may contribute to the demise of nerve cells from cerebral ischemia by release of cytochrome c and activation of caspase.
Improvement of Lung Preservation – From Experiment to Clinical Practice
Authors: Müller C. , Bittmann I. , Hatz R. , Kellner B. , Schelling G. , Fürst H. , Reichart B. , Schildberg F.W.
Published: April 2003

Background: Reperfusion injury represents a severe early complication following lung transplantation. Among the pathogenetic factors, the high potassium content of Euro-Collins® solution is discussed. Material and Methods: In a pig model of orthotopic left-sided lung transplantation we investigated the effect of Euro-Collins solution (EC: n = 6) versus low potassium dextran (LPD: Perfadex®: n = 6). Sham-operated (n = 6) animals served as control. Transplant function, cellular energy metabolism and endothelial morphology served as parameters. In a clinical investigation, 124 patients were evaluated following single (EC: n = 31; LPD n = 37) or double (EC: n = 17; LPD n = 39) lung transplantation, whose organs where preserved with EC (n = 48) or LPD (n = 76). Duration of ischemia, duration of ventilation and stay on ICU were registered. Primary transplant function was evaluated according to AaDO2 values. Cause of early death (30 days) was declared. Results:Experimental results: After flush with EC and 18 h ischemia, a reduction of tissue ATP content (p < 0.01 vs inital value and LPD) was noted. Endothelial damage after ischemia was severe (p < 0.05 vs control), paO2 was significantly decreased. Clinical results: In the LPD group, duration of ischemia was longer for the grafts transplanted first (SLTx and DLTx: p = 0.0009) as well as second (2. organ DLTx: p = 0.045). Primary transplant function was improved (day 0: SLTx: p = 0.0015; DLTx: p = 0.0095, both vs EC). Duration of ventilation and stay on ICU were shorter (n.s.). Reperfusion injury-associated death was reduced from 8% (EC) to 0 (LPD). Conclusion: In experimental lung preservation, LPD lead to an improved graft function. These results were confirmed in clinical lung transplantation. Clinical lung preservation, therefore, should be carried out by use of LPD.
Risk/Benefit Evaluation of Drugs: The Role of the Pharmaceutical Industry in Germany
Authors: Schosser R.
Published: April 2003

Drugs that are efficacious have usually also undesired side effects. When applying for marketing authorization of a drug, demonstration of a positive risk/benefit ratio is a prerequisite for approval by the competent authorities. Once on the market, risk/benefit evaluation has to be continued in order to determine whether the risk/benefit ratio is still positive or not. The German Drug Law, by means of article 5, poses this responsibility on the pharmaceutical entrepreneur. Specific instructions on how to perform the risk/benefit evaluation can be derived from article 5, and a decision matrix was developed to support taking action if the risk/benefit ratio has changed. Historical and current examples are presented to illustrate changes of the risk/benefit ratio, problems associated with detecting risk signals, and the resulting regulatory actions.
The Danish Multicenter Randomized Study on Atrial Inhibited versus Dual-Chamber Pacing in Sick Sinus Syndrome (The DANPACE Study)
Authors: Andersen Henning Rud , Svendsen Jesper Hastrup
Published: April 2003

The DANPACE study is a Danish multicenter study which will evaluate the potential benefit of dual-chamber pacing as compared to atrial inhibited (AAI) pacing in patients with sick sinus syndrome requiring a permanent pacemaker. A previous small-scale Danish pacemaker study compared AAI with ventricular inhibited (VVI) pacing in this patient population and found reduced mortality, reduced occurrence of atrial fibrillation and reduced risk of thromboembolic complications in patients randomized to physiologic pacing (AAI mode) compared with VVI pacing. The DANPACE study plans to include a total of 1,900 patients and have a mean follow-up of 5.5 years. At present (February 2001), all 11 pacemaker-implanting centers in Denmark are actively recruiting patients for the study and about 350 patients have been randomized. The recruitment period is expected to be 6 years. The primary end point of the study is total mortality.
Observations on the Use of Low-Dose Hydrochlorothiazide in the Treatment of Hypertension in Diabetic Nigerians
Authors: Okoro E.O. , Jolayemi E.T. , Oyejola B.A.
Published: April 2003

Objective: The effects of low doses of hydrochlorothiazide (HCTZ) and amiloride in a fixed-combination formulation on blood pressure (BP), serum K+ and diabetic control were assessed in 11 adult Nigerians with hypertension and type 2 diabetes for 12 weeks. Methods: The study included concurrent exposure to 75 mg of aspirin daily by mouth and dietary advice not to add table salt to regular meals, initiated 4 weeks prior to HCTZ therapy. Results: The addition of 12.5 mg of HCTZ resulted in a significantly lower BP, which was evident within 4 weeks. There was no significant variation in serum K+, Na+, creatinine or body weight or the need to alter the dose of hypoglycaemic agents. An initial rise in fasting blood sugar (FBS) after 4 weeks of HCTZ therapy was evident but subsequent rises were not significantly different to the initial rise in FBS observed at week 4. Conclusions: These observations are preliminary and would need longer-term follow-up and treatment of a larger number of patients for confirmation, but they do have the potential to lead to a cheaper and safer therapeutic approach to effective control of BP in diabetic Nigerians with hypertension.
Glycoprotein IIb/IIIa Inhibitors in Acute Coronary Syndromes
Authors: Spence M.S. , Mathew T.P. , Manoharan G. , Riddell J.W. , Adgey A.A.J.
Published: April 2003

Platelet activation following the erosion or rupture of an atherosclerotic plaque is central to the development of acute coronary syndromes (ACS). Inhibition of the final common pathway of platelet aggregation using glycoprotein (GP) IIb/IIIa inhibitors has been evaluated in large-scale trials of patients with ACS. There is now consistent evidence across several trials using different parenteral GP IIb/IIIa inhibitors of improved outcomes for ACS patients treated with these agents both as primary treatment and as an adjunct to coronary intervention. The benefits particularly relate to high-risk patients. In contrast oral GP IIb/IIIa inhibitors have not been shown to improve outcomes in ACS patients.
Aspirin and ACE Inhibitors in Patients with Heart Failure: WATCHing for a Potential Interaction
Authors: Moore Scott A. , Steinhubl Steven R.
Published: April 2003

Coronary artery disease is the leading cause of chronic heart failure and consequently a large proportion of patients with left ventricular (LV) dysfunction are treated with aspirin. Angiotensin-converting enzyme (ACE) inhibitors have emerged as the standard therapy for patients with both symptomatic and asymptomatic LV dysfunction. When the respective actions of these two agents with regard to prostaglandin synthesis are considered, the potential for an antagonistic interaction is evident. In a bradykinin-dependent mechanism, ACE inhibitors stimulate the synthesis of the vasodilator prostacyclin. Aspirin, a cyclooxygenase inhibitor, inhibits the production of prostaglandins. There is evidence that in patients with LV dysfunction, the favorable effects of ACE inhibitors on hemodynamic measures of systemic vascular resistance, cardiac output and LV filling pressures are significantly attenuated by the coadministration of aspirin. There is an accumulating body of retrospective clinical trial data suggesting that these hemodynamic influences translate into a reduction in the mortali- ty benefit seen in ACE inhibitor-treated patients not receiving aspirin. This review will address the mechanism of this potential interaction, as well as the hemodynamic and clinical trial data suggesting the relevance of this interaction. The Warfarin Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial, an ongoing study designed to address the issue of the appropriate antithrombotic therapy for patients with chronic heart failure will be discussed.