bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Chinese Patients with Symptomatic Brugada Syndrome in Taiwan
Authors: Juang Jyh-Ming , Huang Shoei K. Stephen , Tsai Chia-Ti , Chiang Fu-Tien , Lin Jiunn-Lee , Lai Ling-Ping , Wang Chun-Chieh , Kuo Chi-Tai , Ueng Kwo-Chang , Kong Chi-Woon , Ko Wen-Chin , Lei Meng-Huan , Tsao Hsuan-Ming
Published: July 2003

Since 1992, the Brugada syndrome has been increasingly recognized worldwide, although its incidence and distribution remain unclear. In Asia, several cases have been reported in Japan, Thailand, Singapore, and Vietnam. However, little information is available from the Chinese population. Since June 1997, we have identified 10 patients with the diagnosis of the Brugada syndrome from six hospitals in Taiwan. All patients were male with the mean age of 46 ± 7 years (range 36–61). They all had a normal chemistry profile, coronary angiography and echocardiography. Clinical presentations varied from seizure and syncope to sudden cardiac death. MRI and ultrafast CT of the heart did not show any abnormalities. Sustained ventricular tachycardia/ventricular fibrillation (VF) was induced in 7 of 8 patients who underwent an electrophysiologic study. The pharmacological provocation test was positive in 4 of 5 patients. One of the 4 patients who had a genetic study showed SCN5A gene mutation. An implantable cardioverter defibrillator (ICD) was implanted in 8 patients. During a mean follow-up of 29 ± 17 months (range 2–54), 3 of 8 patients who had an ICD received appropriate ICD discharges after implantation. These 3 patients who were subsequently treated with antiarrhythmic agents have had no further recurrent ICD discharges. Two patients who refused ICD implantation are alive and well without taking antiarrhythmic agents. Our study showed that the clinical characteristics of our patients are similar to those described in the literature and that ICD is an effective treatment modality for patients with recurrent VF. However, antiarrhythmic agents may be beneficial for suppressing arrhythmia recurrences in selected patients.
Electrocardiographic Gated 99mTc-Sestamibi SPECT Immediately after Primary Percutaneous Coronary Intervention Characterizes Reperfusion Success
Authors: Kaltoft Anne , Bøttcher Morten , Sand Niels Peter Rønnow , Nielsen Torsten Toftegaard , Rehling Michael
Published: July 2003

Following an acute myocardial infarction, the size of the infarct and the resulting left ventricular volume and function are important predictors of mortality. Identifying patients with impaired tissue level perfusion after percutaneous coronary intervention (PCI) for myocardial infarction therefore could have prognostic implications. To obtain combined measures of left ventricular perfusion, volumes and function we applied a gated myocardial perfusion imaging by 99mTc-sestamibi single photon emission computerized tomography to 19 patients immediately after revascularization by PCI and repeated this after 3 months. The results of the acute myocardial perfusion imaging significantly correlated to final infarct size, left ventricular volumes and function 3 months later. It is concluded that the method holds the potential for risk stratifying patients immediately after revascularization for acute myocardial infarction.
Auditory Verbal Hallucinations – Breaking the Silence of Inner Dialogue
Authors: Stanghellini Giovanni , Cutting John
Published: July 2003

Auditory verbal hallucinations (AVHs) are usually defined as perceptions of speech that occur in the absence of any appropriate external stimulus. This definition, we argue, is false. We maintain that AVHs are disorders of self-consciousness that are best understood as the becoming conscious of inner dialogue. Normally, subconscious interior conversations are experienced as a sense of partnership between distinct parts: we feel these parts as distinct, but also integrated and collaborating with each other in decision-making and in self-representation. AVHs attest to a breakdown in this process of interior conversation: the feeling of unity in duality falls apart, and the dialectic partnership on which self-representation is grounded shatters into a mere dichotomy. There is a fracture in self-consciousness. If ipseity (i.e. the prereflective modality of self-awareness, the self-feeling of one’s own self in which the one who feels and what is felt is but one thing) is lacking, the sense of unity weakens, and the sense of duality increases. This crisis of ipseity is accompanied by an increase of reflexivity (i.e. the process through which I take a part of myself as a focal object of awareness). Hyperreflexivity contributes to the objectification of the sense of duality and to the loss of the sense of ‘myness’ of inner speech. In schizophrenics, inner dialogue becomes anomalously manifest. Whereas in normal conditions, inner dialogue is the medium for self-representation, AVHs arise through its morbid objectification: inner speech comes to the foreground in the concrete fashion of alien ‘voices’.
Conscious Compensations for Thought Insertion
Authors: Area R. , Garcia-Caballero A. , Gómez I. , Somoza M.J. , Garcia-Lado I. , Recimil M.J. , Vila L.
Published: July 2003

Thought insertion and other experiences of alien control have been explained as a source monitoring deficit, that results from a disconnection between a cognitive system for willed actions and a different system that monitors them. The case we present is a schizophrenic patient that in order to consciously avoid feeling his thoughts as not belonging to himself performs them as a motor act of speech. We suggest an interpretation for this conscious compensation following C. Frith’s neuropsychological model of schizophrenia.
Factor Structure of Paranoid Schizophrenia: A Prospective Study
Authors: Loza Bartosz , Kucharska-Pietura Katarzyna , Kopacz Grzegorz , Debowska Grazyna
Published: July 2003

Paranoid schizophrenics were scored and analyzed using PANSS and principal component method on admission (T1, 480 patients), after 4 weeks (T2, 223 patients), after 8 weeks (T3, 146 patients) and after 6 months of treatment (T4, 104 patients). Seven factor models accounted for 68–74% of the variances (including models of 104 patients present at all four stages). T1 and T2 models comprised 6–7 factors and were dominated by positive and excitement symptoms. The grandiosity factor could only be identified in T1. T3 and T4 models were reduced to 5 factors and incorporated a greater expression of depressive disorders and a relatively greater expression of negative and cognitive symptoms. Negative and cognitive dimensions were the most stable elements of all the models. The concept of the depressive factor appeared to be too restrictive to describe a whole variety of the affective dimension.
Depression in the Mother and Maternal Attachment – Results from a Follow-Up Study at 1 Year Postpartum
Authors: Nagata Masako , Nagai Yukiyo , Sobajima Hisanori , Ando Tsunesaburo , Honjo Shuji
Published: July 2003

Although evidence exists pointing to the impact of maternal depression in puerperium upon mother-child interaction, longitudinal studies on this perspective are rare. Hence, this study was designed to examine the association between maternity blues and maternal attachment in the puerperium with depression in the mother and attachment after 1 year together with the factors involved. A questionnaire survey consisting of Zung’s Self-Rating Depression Scale (ZSDS) and a ‘maternal attachment’ scale, comprised of subscales on ‘core maternal attachment’ and ‘anxiety regarding children’, was conducted on mothers who had participated in a previous puerperium survey. The mean ZSDS score of 42.1 ± 7.45 after 1 year did not differ significantly from puerperium results. ‘Maternity blues’ was found to influence the maternal depression after 1 year, which was in turn associated with ‘core maternal attachment’ and ‘anxiety regarding children’, supporting the need for early intervention in maternity blues starting in the perinatal period for the mental health of mother and child.
On the Descriptive Validity of ICD-10 Schizophrenia: Empirical Analyses in the Spectrum of Non-Affective Functional Psychoses
Authors: Jäger Markus , Bottlender Ronald , Strauss Anton , Möller Hans-Jürgen
Published: July 2003

In order to examine the descriptive validity of ICD-10 schizophrenia, 1,476 consecutively admitted in-patients were included in the present study. ICD-10 schizophrenia (n = 951) was compared with other non-affective psychotic disorders [persistent delusional disorders (n = 51), acute and transient psychotic disorders (n = 116) and schizoaffective disorders (n = 354)] with respect to sociodemographic, symptomatological and other clinical parameters. Analyses revealed that it is possible to distinguish schizophrenia from other non-affective psychotic disorders according to ICD-10 criteria: schizophrenic patients were characterised by more pronounced negative symptoms and a lower global functioning. They were younger than patients with persistent delusional disorders and schizoaffective disorders but older than patients with acute and transient psychotic disorders. The results are in line with a high descriptive validity of ICD-10 schizophrenia and highlight the importance of negative symptoms for this diagnosis.
A Case of Bipolar Psychosis and Transsexualism
Authors: Habermeyer Elmar , Kamps Ingrid , Kawohl Wolfram
Published: July 2003

A case of bipolar disorder and transsexualism is reported and discussed. The case report shows the problematic nature of the distinction between transsexualism and psychosis-induced transsexual desires. If there is a true comorbidity of these disorders, a subtly differentiated process to guide medical expert opinion and therapy is necessary.
Selective Alterations in Mast Cell Subsets and Eosinophil Infiltration in Two Complementary Types of Intestinal Inflammation: Ascariasis and Crohn’s Disease
Authors: Beil Waltraud J. , McEuen Alan R. , Schulz Matthias , Wefelmeyer Udo , Kraml Georg , Walls Andrew F. , Jensen-Jarolim Erika , Pabst Reinhard , Pammer Johannes
Published: July 2003

Objective: Numbers of mast cells (MCs) of different subpopulations and the extent of eosinophil infiltration were compared in Crohn’s disease and ascariasis. These two types of intestinal inflammation are complementary with regard to T cell response (TH1 versus TH2), prevalence and environmental factors. Methods: Histochemical, immunohistochemical and ultrastructural tools were applied to biopsies of morphologically uninvolved colon, ileum and duodenum from Crohn’s and ascariasis patients, as well as resection margins and tissues from an experimental porcine ascariasis model. MC subsets were defined by their dye-binding properties, and their chymase content was analysed using biochemical tools. Results: The TH2 (IgE-mediated) response in ascariasis was characterised by a dramatic increase in mucosal- type MCs (MMCs) and eosinophils in both the mucosa and the deeper layers of the intestinal wall and a simultaneous decrease of connective tissue-type MCs (CTMCs). Uninvolved intestine of Crohn’s patients showed moderate proliferation of CTMCs in the deeper layers of the intestinal wall, but a significant decrease of the MMCs, associated with moderate eosinophilia in all layers of the gut. Similar changes were present in the uninvolved duodenum of Crohn’s patients. Comparable amounts of chymase could be extracted from mucosal and submucosal duodenum, with similar proportions of its two principal isoforms in each. Conclusions: Our results indicate that T cell responses (TH1 or TH2) are associated with different MC subsets in intestinal inflammation. Changes remote from the focus of inflammation point to the systemic nature of the different MC responses.
Tumor Antigens and Antigen-Presenting Capacity in Breast Cancer
Authors: McDermott Raymond S. , Beuvon Frédéric , Pauly Marc , Pallud Claude , Vincent-Salomon Anne , Mosseri Veronique , Pouillart Pierre , Scholl Susy M.
Published: July 2003

Aims: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens. Methods: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO. Results: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates. Conclusions: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.
Giant Cell Tumor of Bone
Authors: Robinson Dror , Segal Michael , Nevo Zvi
Published: July 2003

Objectives: Giant cell tumor of bone is typified by massive infiltration of a bland neoplastic stroma by osteoclasts and monocyte progenitors. The current study aimed at evaluating the nature of the neoplastic cells and the mechanisms underlying the massive giant cell recruitment. Methods: Five different giant cell tumors were evaluated by immunohistochemistry, and explant cell cultures were established from the same tumors. Antigen expression profiles of both the tumors and the derived cultures were assessed. In order to determine if the mesenchymal cells are capable of differentiating into mature osteoblasts, retinoic acid was added to cell cultures and osteocalcin and alkaline phosphatase levels were measured. The proliferative effects of the mesenchymal cells on histiocyte-like cells were evaluated using the U-937 cell line. Results: A large stromal subpopulation expresses fibroblast growth factor receptor 3 (FGF-R3), indicating a mesenchymal origin of these cells. Few cells express bone- or cartilage-specific markers. Cell cultures are predominated by mesenchymal cells, as indicated by a strong staining by FGF R3. Retinoic acid induces osteoblastic differentiation, i.e. osteocalcin expression and alkaline phosphatase production. Conditioned medium of giant-cell-tumor-derived stromal cell cultures induces proliferation of U-937 cells, derived from histiocytic lymphoma. Papain digestion and dialysis of the conditioned media indicates the effector molecule to be a protein over 40 kD in size. The giant cell tumors as well as stromal cell cultures derived from giant cell tumors express osteoprotegerin ligand, the osteoclast activator. Conclusions: The neoplastic stromal spindle-shaped subpopulation of cells in giant cell tumors are mesenchymal stem cells capable of inducing histiocyte proliferation. Retinoid acid is capable of inducing differentiation of the cells into mature osteoblasts. This should be further investigated in an in vivo model to ascertain whether induction of differentiation will prevent bone loss and retard tumor progression.
Expression of Das-1 in Primary Lung Adenocarcinomas Represents Reactivation of an Oncofetal Pulmonary Antigen
Authors: Deshpande C.G. , Shah R.N. , Yeldandi A. , Papreddy K. , Badve S.
Published: July 2003

Objective: The monoclonal antibody (mAb) designated as mAb Das-1 was generated against a colonic epithelial protein. It reacts with bronchiolar epithelium and submucosal glands and weakly with alveolar lining cells of fetal lung. Adult alveolar epithelium is, however, nonreactive for mAb Das-1. The present study was designed to evaluate the immunoexpression of Das-1 and to correlate it with the histomorphology of primary lung adenocarcinomas and intestinal metaplasia. Methods: Eighty-four cases of primary lung adenocarcinomas were reviewed and categorized according to histologic grade and subtype. Immunohistochemical staining with mAb Das-1 was performed with normal colon as control. Results: Expression of Das-1 in the submucosal bronchial glands also served as internal control. Strong and diffuse staining was seen in 33 of the 84 cases of adenocarcinomas (39%). Conclusions: Expression of Das-1 was seen in primary lung adenocarcinomas even though adult alveolar epithelium is negative. Staining with mAb Das-1 was seen regardless of the grade or histological subtype of the lung adenocarcinomas. As most primary lung adenocarcinomas are not of bronchial gland origin, expression of Das-1 represents activation of oncofetal antigens.
Manganese Superoxide Dismutase Expression Correlates with a Poor Prognosis in Gastric Cancer
Authors: Kim Jeong Jin , Chae Seoung Wan , Hur Gwong Cheung , Cho Sung Jin , Kim Min Kyu , Choi Jimi , Nam Seon Young , Kim Woo Ho , Yang Han-Kwang , Lee Byung Lan
Published: July 2003

Objective: The biologic significance of superoxide dismutase (SOD) in transformed gastric carcinoma cells is unclear. The aim of this study was to examine the role of SOD as a prognostic indicator of gastric carcinomas and its association with other clinicopathological factors. Methods: Expression of MnSOD and Cu/ZnSOD was evaluated immunohistochemically in gastric carcinomas and adenomas using tissue-array methods. The correlation between SOD immunoreactivity and clinical outcome or clinicopathological factors was investigated. Results: MnSOD expression was associated with a poor patient prognosis and was strong in advanced gastric cancer, in the well-differentiated type and in the presence of lymphoid stroma (p < 0.05). On the other hand, there was no association between Cu/ZnSOD expression and patient survival. Cu/ZnSOD immunoreactivity was strong in advanced gastric cancer and in the presence of lymphoid stroma (p < 0.05) and was weak in signet ring cell type. Conclusion: MnSOD immunoreactivity is significantly associated with poor outcome in gastric carcinoma patients although both MnSOD and Cu/ZnSOD have a connection with several clinicopathological parameters with some overlap.
Resistance of Epiphyseal Cartilage to Invasion by Osteosarcoma Is Likely to Be Due to Expression of Antiangiogenic Factors
Authors: Quan Gerald M.Y. , Ojaimi Joseline , Nadesapillai A.P. Wijayanthi , Zhou Hong , Choong Peter F.M.
Published: July 2003

Objectives: Epiphyseal cartilage is a barrier to osteosarcoma invasion, however the mechanisms behind this resistance remain unclear. The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage. Methods: We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression. We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis; proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium-derived factor (PEDF). Results: Epiphyseal cartilage remained intact across its entire length in all sections examined, despite increasing tumor size as well as intra- and extraosseous destruction. In the most advanced cases, only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded. This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF. In contrast, the resting, proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases. This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF. Conclusion: Epiphyseal cartilage is resistant to local invasion by osteosarcoma. The balance of angiogenesis, influenced by pro- and antiangiogenic factors, is likely to play an important role in this resistance.
Hemoperfusion with Polymyxin B-Immobilized Fiber in Septic Patients with Methicillin-Resistant Staphylococcus aureus-Associated Glomerulonephritis
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Suzuki Yoshimasa , Osada Shiwori , Inoue Teruo , Shoji Hisataka , Hara Masanori , Shimada Noriaki , Koide Hikaru
Published: July 2003

Background/Aims: We investigated whether urinary podocytes are present in septic patients with methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis and whether polymyxin B-immobilized fiber (PMX-F) treatment affects proteinuria and urinary podocyte excretion in these patients. Methods: Twenty septic patients with MRSA-associated glomerulonephritis (mean age: 63.7 years) and 80 septic patients whose MRSA infection was not followed by glomerulonephritis (mean age: 60.5 years) were included in this study. All septic patients were treated with fosfomycin sodium, β-lactams, arbekacin sulfate, and teicoplanin, or a combination of these. Twenty septic patients with MRSA-associated glomerulonephritis were randomly assigned to one of two treatments: PMX-F treatment (group A, n = 10) and conventional treatment (group B, n = 10). PMX-F treatment was repeated twice. Results: Urinary podocytes and urinary protein excretion were not detected in MRSA septic patients without glomerulonephritis. However, urinary podocytes (1.7 ± 0.6 cells/ml) and proteinuria (2.6 ± 0.6 g/d) were detected in the 20 septic patients with MRSA-associated glomerulonephritis. Plasma endotoxin levels were decreased from 13.6 ± 4.6 pg/ml to 6.6 ± 2.2 pg/ml (p < 0.05) in group A. Levels in group B, however, showed little difference after treatment. Urinary podocytes were reduced in group A (from 1.8 ± 0.6 cells/ml to 0.4 ± 0.2 cells/ml, p < 0.01) as was urinary protein excretion (from 3.0 ± 0.5 g/d to 0.8 ± 0.4 g/d, p < 0.01) but urinary podocytes and protein excretion levels showed little difference after treatment in group B. Conclusion: PMX-F treatment may be effective in reducing urinary protein and urinary podocyte excretion in septic patients with MRSA-associated glomerulonephritis.
Hepatocyte Growth Factor-Stimulating Endothelial Cell Growth and Accelerating Glomerular Capillary Repair in Experimental Progressive Glomerulonephritis
Authors: Mori Takahiro , Shimizu Akira , Masuda Yukinari , Fukuda Yuh , Yamanaka Nobuaki
Published: July 2003

Hepatocyte growth factor (HGF) is one of the major growth factors that stimulate the growth and the migration of vascular endothelial cells. In this study, we examined the beneficial effects of HGF for glomerular repair in an experimental progressive glomerulonephritis (GN) model prepared by injecting both anti-Thy-1.1 antibody (day 0) and habu-snake venom (day 1) in rats. The rats received continuous intraperitoneal administration of recombinant human HGF (80 µg/100 g/day) or vehicle control at an early stage (day 2 to day 9), after severe glomerular injury. The vehicle-infused control rats initially showed severe mesangiolysis with large ballooning (day 2), followed by the prominent proliferation of mesangial cells with minimal capillary regeneration (day 5 to week 2), and global sclerosis with chronic renal failure (week 4 to week 8). Although mesangiolysis with large ballooning and mesangial cell proliferation were also observed in the HGF-infused rats, glomerular capillary regeneration with marked endothelial cell proliferation occurred during HGF administration from day 2 to day 9. Subsequently, the glomerulus was repaired with the development of the capillary network and the reduction of mesangial hypercellularity from week 2 to week 4, and almost all of the glomeruli showed a normal structure by week 8. The HGF-treated rats showed significantly better renal functions (Cr: 0.3 ± 0.1 vs. 3.5 ± 1.1 mg/dl in control, p < 0.001), less proteinuria (21.2 ± 8.0 mg/day vs. 421.4 ± 45.1 mg/day in control, p < 0.001) and less glomerular sclerosis at week 8 than the vehicle-infused rats. We conclude that HGF accelerated glomerular repair through the growth of capillary endothelial cells and capillary regeneration in experimental progressive GN. Administering HGF is a logical and efficient strategy for treating progressive GN with severe capillary destruction.
Increased Expression of CD54, CD18, MHC Class II Molecules, and Proliferating Cell Nuclear Antigen in Acute Puromycin Aminonucleoside Nephrosis
Authors: Fernandez Lucas , Romero Maritza , Rincón Jaimar , Mosquera Jesús
Published: July 2003

Cellular infiltration to renal tissues is an important feature during acute puromycin aminonucleoside nephrosis (PAN) in rats. The mechanisms responsible for this infiltration are poorly understood. To elucidate the participation of adhesion molecules in PAN, nephrosis was induced in rats by intraperitoneal puromycin aminonucleoside injection. Controls represent animals injected with a 0.9% saline solution. ICAM-1 (intercellular adhesion molecule 1), CD18 (beta chain of lymphocyte-function-associated antigen), LCA (leukocyte common antigen), ED1 (monocyte/macrophage marker), and proliferating cell nuclear antigen expressions were evaluated in renal tissues 1, 2, and 7 weeks after injection. Frozen sections from PAN rat kidneys showed increased expressions of ICAM-1 and its ligand, and these findings were associated with increased levels of LCA+ and ED1+ cells in glomerulus and interstitium. The kinetics of leukocyte infiltration was similar to the kinetics of ICAM-1 expression: high values at week 2 which returned to normal values at week 7. Increased glomerular and interstitial proliferative activities (proliferating cell nulear antigen positive cells) were also found at week 2 of nephrosis. There was a correlation between ICAM-1 expression and numbers of LCA+ and ED1+ cells and between numbers of LCA+ cells and proliferating cells in glomerulus and interstitium. Correlations between glomerular and tubular ICAM-1 expression, interstitial leukocyte infiltration, and glomerular, interstitial, and tubular proliferative activities with the proteinuria were also observed during the nephrotic phase. In addition, increased lymphocyte binding to PAN renal tissues was observed, and this binding was diminished by anti-LFA-1β monoclonal antibody pretreatment of lymphocytes. A similar result was found with anti-ICAM-1 monoclonal antibody pretreatment of renal tissues. Our results suggest that increased expression of ICAM-1 and proliferative activity could be important determinants in the renal hypercellularity found in this experimental model.
Serum Cystatin C Is a More Sensitive and More Accurate Marker of Glomerular Filtration Rate than Enzymatic Measurements of Creatinine in Renal Transplantation
Authors: Christensson Anders , Ekberg Jana , Grubb Anders , Ekberg Henrik , Lindström Veronica , Lilja Hans
Published: July 2003

Background/Aims: Serum creatinine has several drawbacks as marker of glomerular filtration rate (GFR), and therefore serum cystatin C has been proposed as a more optimal GFR marker. Previous reports have suggested benefits of serum cystatin C measurements in patients with renal transplants. The purpose of the present study was to evaluate the diagnostic accuracy of cystatin C measurements compared with enzymatic creatinine measurements as serum markers of GFR (established from plasma clearance of iohexol) in a large cohort of stable renal transplant recipients and in the early postoperative phase. Methods: Renal transplant patients (n = 125) with stable graft function were evaluated from reciprocals of serum creatinine and cystatin C compared with iohexol clearance. Fourteen patients were examined immediately after the onset of renal function. Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Results: In stable renal transplant recipients, serum cystatin C showed a significantly (p = 0.033) closer correlation (r = 0.89 or 79% co-variance) with iohexol clearance than did serum creatinine (r = 0.81 or 66% co-variance). Using the χ2 test and a cut-off at 60 ml/min/1.73 m2, serum cystatin C levels demonstrated significantly higher sensitivity for early GFR impairment (p = 0.0045) compared with serum creatinine measurements. On the first day after transplantation, serum cystatin C fell more rapidly than serum creatinine. Conclusion: Serum cystatin C levels correlate significantly closer to accurate measurements of GFR and are significantly more sensitive to detect early GFR impairment than enzymatic measurements of creatinine in serum.
Insights into Mechanisms Responsible for Mesangial Alterations Associated with Fibrogenic Glomerulopathic Light Chains
Authors: Teng Jiamin , Zhang Ping L. , Russell William J. , Zheng Lu P. , Jones M. Lamar , Herrera Guillermo A.
Published: July 2003

Our previous studies have shown that human mesangial cells (HMCs) incubated with fibrogenic glomerulopathic monoclonal light chains (G-LCs) obtained from the urine of patients with light chain deposition disease produce increased extracellular matrix (ECM) when compared with HMCs not exposed to fibrogenic LCs. This overproduction of ECM proteins is regulated by transforming growth factor-β (TGF-β); blocking TGF-β normalizes the production of ECM proteins. All ECM proteins, after synthesis, have to go through the secretory pathway in the endoplasmic reticulum (ER) and Golgi complex for final maturation and secretion. Blocking the secretory pathway may reduce the accumulation of ECM proteins. We tested the effect of tunicamycin, a specific inhibitor of N-linked glycosylation in the ER which inhibited glycosylation and brefeldin A, an inhibitor of vesicle transport between the endoplasmic reticulum and the Golgi complex, on ECM protein production, both resulting in subsequent upregulation of glucose-regulated protein 78. Overproduction of fibronectin and tenascin by HMCs was normalized by tunicamycin and brefeldin A. Similarly, when HMCs were exposed to exogenous TGF-β, the increase in fibronectin was reversed by tunicamycin and brefeldin A. Exogenous platelet-derived growth factor-β (PDGF-β) did not induce fibronectin overproduction but significantly stimulated proliferation of HMCs. In summary, this study further supports the notion that fibrogenic G-LCs promote the accumulation of ECM proteins, through the actions of TGF-β. Importantly, the data indicate that altering protein trafficking in the ER results in impairment of secretion of proteins into the ECM. Furthermore, the data also reveal that PDGF-β and TGF-β act independently and that PDGF-β activation by itself cannot increase ECM proteins directly, but only by increasing the number of HMCs.
Angiotensin II Blockade Augments Renal Cortical Microvascular pO2 Indicating a Novel, Potentially Renoprotective Action
Authors: Norman Jill T. , Stidwill Ray , Singer Mervyn , Fine Leon G.
Published: July 2003

Background: The existence of tubulointerstitial damage in most cases of progressive human glomerular disease suggests that this compartment of the kidney is likely to be targeted by renoprotective agents which slow the progression of disease. Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of renal protection. Since we have proposed that perturbation of the interstitial capillary circulation with consequent chronic hypoxia could be critical to the progressive nature of many renal diseases, we developed a dynamic method of measuring renal cortical pO2 and sought to determine whether agents which block the renal effects of angiotensin II (AII) could affect interstitial microvascular oxygenation in the normal rat kidney. Methods: Instrumented, anaesthetised adult male Sprague-Dawley rats were studied. Cortical microvascular pO2 was measured on the surface of the exposed kidney using protoporphyrin phosphorescence. Blood pressure and renal artery blood flow (Doppler flowmetry) were measured concurrently over a 180-min experimental period. Animals received non-hypotensive doses of enalaprilat (100 µg/kg i.v.) or candesartan (40 µg/kg i.v.) either at the beginning of the experimental period or after an initial decline in cortical microvascular pO2. Results: After a 30-min stabilisation period there was a slow decline in pO2 from 48.6 ± 4.1 to 38.5 ± 6.9 mm Hg in control animals over the 180-min experimental period. Administration of the ACE inhibitor, enalaprilat at the beginning of the experimental period, completely abrogated this decline and protected pO2 levels throughout this period with no effect on blood pressure or renal blood flow. In separate experiments, administration of enalaprilat after microvascular pO2 had fallen by 5 mm Hg, resulted in a rise in RBF and pO2 within 15 min with pO2 remaining elevated for up to 60 min post-injection. The angiotensin II AT1 receptor antagonist, candesartan, had a similar effect to enalaprilat, inducing a rapid and sustained elevation in cortical pO2. Conclusions: These studies indicate that blockade of AII raises pO2 in the interstitial microvascular compartment of the normal rat kidney. This effect may contribute to the renoprotective action of ACE inhibitors and AII receptor antagonists in slowing the progression of chronic renal diseases.
GERD 2003 – A Consensus on the Way Ahead
Authors: Moss Steven F. , Armstrong David , Arnold Rudi , Ferenci Peter , Fock Kwong M. , Holtmann Gerald , McCarthy Denis M. , Moraes-Filho Joaquim P. , Mutschler Ernst , Playford Raymond , Spechler Stuart J. , Stanghellini Vincenzo , Modlin Irvin M.
Published: July 2003

Gastroesophageal reflux disease (GERD) has in recent times become an important public health issue owing to the considerable health care resources utilized in its management, its deleterious effect on quality of life and the increasing prevalence of a relatively rare complication of reflux disease – esophageal adenocarcinoma. We review here the major current challenges in the field of reflux disease and its complications, and provide some approaches that may be useful in management. The issues to be faced include the very limited comprehension of the reasons behind the increasing prevalence of the disease, difficulties in correlating symptoms with objective data of pathological gastroesophageal reflux and the relatively unsophisticated tools we are employing to investigate the underlying pathophysiology. It is certain that the lack of well-defined and characterized methodologies to compare the effects of therapy require the development of more effective questionnaire-type analytic tools. In regard to treatment, there is little doubt that the widely prescribed proton pump inhibitors have dose-equivalent efficacy and are the most highly effective agents capable of suppressing acid, controlling many of the symptoms of GERD and healing erosions. Nevertheless, many patients continue to experience symptoms on withdrawal or at night. Pharmacological agents that can effectively increase lower esophageal sphincter pressure or promote motility are as yet unavailable. Although the introduction of laparoscopic techniques has resulted in a modest revival in surgical intervention using a variety of ‘wrap-type’ operations, the indications are few and the procedure is associated with a significant morbidity and even mortality especially if the expertise of the surgeon is an issue. Endoscopic techniques of regulating reflux are at this time experimental and not applicable to the general population. Intestinal metaplasia in the lower esophagus is probably very common. Whether and how to, first, screen for, and then, perform surveillance in Barrett’s esophagus remains highly problematic and contentious.
Interaction of Hepatocyte Growth Factor and Non-Steroidal Anti-Inflammatory Drugs during Gastric Epithelial Wound Healing
Authors: Netzer Peter , Halter Fred , Ma Thomas Y. , Hoa Neil , Nguyen Nathan , Nakamura Toshikazu , Tarnawski Andrzej S.
Published: July 2003

Background/Aims: Expression of the hepatocyte growth factor (HGF) and cyclooxygenase-2 (COX-2) is upregulated at the margins of healing gastric ulcers. We investigated in vitrothe interference of HGF, the selective COX-2 inhibitor NS-398 and the nonselective COX inhibitor indomethacin with gastric epithelial wound healing and actin microfilament (actin-MF) formation. Methods: Standardized gastric epithelial wounds, created in confluent RGM1 rat cell monolayers were treated with: HGF (10 ng/ml), NS-398 (1–100 µM) or indomethacin (0.01– 0.5 mM). The areas of re-epithelialization and cell proliferation were measured 24 h after wounding. Actin-MFs were labeled with fluorescein-conjugated phalloidin and their distribution was examined using a Nikon epifluorescence microscope. Results: HGF caused a significant increase in gastric monolayer wound re-epithelialization and this was not affected by mitomycin C. Both indomethacin and NS-398 inhibited HGF-stimulated re-epithelialization, but the basal wound re-epithelialization rate and cell proliferation was only significantly inhibited by indomethacin. HGF triggered actin stress fiber formation which was inhibited by both indomethacin and NS-398, but only indomethacin interfered with actin-MF formation at the baseline condition. Conclusions: HGF significantly increased gastric wound re-epithelialization by activating cell migration which may be mediated by the COX-2 pathway.
Patients with Chronic Renal Failure Have Abnormal Small Intestinal Motility and a High Prevalence of Small Intestinal Bacterial Overgrowth
Authors: Strid Hans , Simrén Magnus , Stotzer Per-Ove , Ringström Gisela , Abrahamsson Hasse , Björnsson Einar S.
Published: July 2003

Background/Aims: Gastrointestinal (GI) symptoms are common among patients with chronic renal failure (CRF). The pathogenesis of these symptoms is probably multifactorial. Our aims were to assess gastric and small intestinal motility and the prevalence of small intestinal bacterial overgrowth (SIBO) in order to clarify possible pathophysiological mechanisms behind these symptoms in CRF patients. Methods: Twenty-two patients with CRF, 12 with GI symptoms and 10 without GI symptoms underwent antroduodenojejunal manometry. All patients with GI symptoms had diarrhea and half of them had abdominal pain, nausea and/or early satiety. Symptoms were unexplained by conventional investigations. Interdigestive motility was recorded for 5 h and postprandially for 1 h. Samples for culture from the small intestine were obtained through the manometry catheter. Results were compared with 34 healthy controls. Results: On manometry, 11 CRF patients demonstrated neuropathic-like abnormalities, with no significant difference between the patients with (7/12) and without (4/10) GI symptoms. SIBO was seen in 8 CRF patients (36%), 3 with and 5 without GI symptoms (p = 0.15). Six of eleven (55%) of the CRF patients with neuropathic-like abnormalities had SIBO, compared to 2/11 (18%) in those without abnormalities on conventional analysis (p = 0.07). The propagation velocity of phase III was significantly faster in CRF patients with GI symptoms compared to CRF patients without symptoms and healthy controls (21.4 (16.4–54.7) vs. 8.1 (4.6–9.6) and 10.8 (7.2–21.6) cm/min, p = 0.007 and p = 0.019, respectively). We found a higher proportion of retrograde pressure waves in late phase II in the proximal duodenum in patients with and without GI symptoms, than in healthy controls (29 (17–38) and 16 (14–42) vs. 8 (0–24)%, p < 0.0001 and p = 0.0005, respectively). The number of long clusters during the fasting recording was higher in both patient groups than in controls (9 (5–21) and 11 (7–15) vs. 4 (2–9)/5, p = 0.046 and p = 0.002, respectively). Conclusion: In the small intestine, abnormal motility and bacterial overgrowth are common in patients with chronic renal failure. These alterations correlate poorly with GI symptoms, but disturbed intestinal motility might explain diarrhea in some of these patients.
Bleeding Complications after Percutaneous Liver Biopsy
Authors: Terjung Birgit , Lemnitzer Isabelle , Dumoulin Franz Ludwig , Effenberger Wolfgang , Brackmann Hans Hermann , Sauerbruch Tilman , Spengler Ulrich
Published: July 2003

Background and Aims: To assess the risk of bleeding after percutaneous liver biopsy, we retrospectively analyzed 629 procedures with particular respect to patients with an increased a priori bleeding risk. Methods: Factors possibly related to the risk of bleeding were analyzed by univariate analysis. Those variables which were significant in the univariate analysis were then entered into a forward conditional logistic regression model. Results: Biopsy-related bleeding events defined as clinically overt complication (n = 10; 1.6%), an otherwise unexplained drop in serum hemogloblin concentration of greater than 2 g/dl (n = 45; 7.1%) or intra- or extrahepatic hematoma assessed by ultrasound (n = 17; 2.7%) were identified in 72 patients. 58% of the bleeding events occurred in patients with particular risk factors for bleeding. Biopsy-related mortality in the study cohort was 0.48%. Logistic regression analysis indicated mycobacterial infection [odds ratio (OR) 24.0], pre-biopsy prophylactic platelet substitution (OR 9.9), acute liver failure (OR 9.1), heparin administration on the day of biopsy (OR 8.7), advanced liver cirrhosis (OR 5.1), therapy with corticosteroids (OR 3.5) or metamizole (OR 2.8) and leukemia or lymphoma (OR 2.8) as significant (p ≤ 0.05) independent risk factors. Delayed bleeding (>24 h after biopsy) was identified in 70% of the bleeding events. Conclusions: In our study cohort which comprised a high proportion of patients with particular risk factors for bleeding, biopsy-related bleeding occurred more frequently and later than commonly observed and was associated with only a few prognostic factors. Considering these predictors before liver biopsy will aid to reduce the rate of bleeding complications.
Mucosal Villus Microcirculatory Disturbances Associated with Rat Intestinal Ischaemia-Reperfusion Injury Are Not Prevented by Tacrolimus
Authors: Kalia Neena , Wood Richard F.M. , Pockley A. Graham , Brown Nicola J.
Published: July 2003

Background/Aims: Microcirculatory disturbances following small intestinal ischaemia-reperfusion (I/R) injury lead to tissue damage that may affect short- and long-term outcome after transplantation. The immunosuppressive drug Tacrolimus (FK506) attenuates I/R injury in a number of organs, raising the possibility that it might be able to control both I/R injury and rejection after small bowel transplantation. However, its effects on intestinal I/R injury have not been evaluated. Methods: PVG rats were subjected to 30 min intestinal ischaemia. Animals received Tacrolimus (1 mg/kg i.p.) 4 and 1 h prior to ischaemia. The mucosa was visualised in an exteriorised ileal segment using in vivo microscopy. FITC-BSA or Acridine orange was used to quantitate macromolecular leak (MML) and leucocyte adhesion respectively every 15 min for 2 h during reperfusion. Heart rate and mean blood pressure (mBP) were monitored throughout the experiment. Results: Ten of 12 untreated animals subjected to intestinal I/R injury failed to survive the 2-hour reperfusion period. MML and leucocyte adhesion were increased in untreated animals (p < 0.001) and blood flow stasis eventually ensued. Similar results were obtained for Tacrolimus pre-treated I/R animals, with 10 of 12 animals again failing to survive reperfusion. Conclusions: Despite previous evidence that Tacrolimus reduces I/R injury in other organs, it did not improve survival rates or prevent villus microcirculatory disturbances following intestinal I/R injury. The severity of microcirculatory damage suffered by the small intestine highlights the importance of alternative therapies to combat I/R in this organ.
Bacterial Load in Animal Models of Acute and Chronic ‘Reactivated’ Colitis
Authors: Hernández Gerardo A. , Appleyard Caroline B.
Published: July 2003

Background: The involvement of enteropathogenic microorganisms in the pathogenesis of inflammatory bowel disease (IBD) and their importance in the different phases of inflammation are still unknown. Aim: To quantify the aerobic bacterial load in models of acute and chronic ‘reactivated’ colitis, and correlate this with damage. Methods: Acute colitis was induced in rats by administration of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS). Colitis was ‘reactivated’ 6 weeks later by intravenous administration of TNBS. The distal colon was removed and scored macroscopically before inoculating samples. Results: Bacterial load in rats with acute colitis (72 h) and chronic ‘reactivated’ colitis or their controls was significantly higher than untreated (p < 0.05); however, there were significantly more bacteria in acute colitis than in chronic ‘reactivated’ or their controls (p < 0.05). Both acute and chronic ‘reactivated’ colitis had significantly higher damage scores than untreated animals (p < 0.05). Bacterial load and damage score were significantly correlated only with acute colitis. Conclusions: The role of enteric microflora in the pathogenesis of IBD is greater during the acute phase of colitis. The correlation between bacterial load and tissue damage suggests that damage contributes to bacterial multiplication and exacerbation of colitis. Normal colonic flora may contribute to the relapse of the disease.
Analysis of the T Cell Receptor Vβ Repertoire in 2,4,6-Trinitrobenzenesulfonic Acid Induced Colitis in Mice
Authors: Kanetake Kazuto , Iwata Hisashi , Mori Yoshio , Takagi Hisato , Hirota Toshio , Nitta Toyoo , Hayashi Masatomo , Onitsuka Atsuyoshi , Hirose Hajime
Published: July 2003

The aim of this study was to analyze which types of T cells are at work and the specific nature of their response, using a mouse 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model. The response of T cells to TNBS was analyzed by anti-TNBS mixed-lymphocyte reaction. T cell clones were established by limiting dilution. Phenotypes and T cell receptor (TCR) Vβ of T cells were analyzed by flow cytometry. Colitis was induced by administration of TNBS enemas, and lamina propria lymphocytes were isolated and analyzed. The proliferative responses to TNBS of spleen T cells were partially inhibited by the addition of antimouse CD4 or CD8 antibodies to the mixed-lymphocyte culture. Conversely, these were inhibited by the addition of both antibodies. Flow cytometric analysis showed that TCR Vβ14 T cells specifically increased in the CD8+ T cell population. We established CD8+ TCR Vβ14 T cell clones which were TNBS reactive and self-restricted. Investigation using lamina propria lymphocytes in TNBS-induced colitis revealed that the rate of CD8+ TCR Vβ14 T cells changed with histological inflammatory activity which also attained a peak on day 5 following enema administration. Both CD4+ and CD8+ T cell subsets responded to TNBS, and the rate of CD8+ TCR Vβ14 T cells changed with histological inflammatory activity in TNBS-induced colitis.