bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid-Resistant Nephrotic Syndrome Associated with Kimura’s Disease
Authors: Chartapisak Wattana , Opastirakul Sauwalak
Published: April 2003

Kimura’s disease is a chronic inflammatory disease characterized by tumor-like lesions in the soft tissue and lymph nodes of head and neck area or parotid gland. It has a high frequency of an association with nephrotic syndrome. Reported cases of nephrotic syndrome and Kimura’s disease were mostly from adult patients with only 5 children mentioned. This study reports the case of a 15-year-old-boy who manifested with steroid-resistant nephrotic syndrome for 4 years. Pathological examination of the kidney revealed mild mesangial proliferation. Subsequently, he developed a soft-tissue mass in the parotid gland area. Histopathological investigation of the mass revealed eosinophilic infiltration together with plasma cells and mast cells which is a main characteristic of Kimura’s disease. The patient, however, continued to have nephrotic-range proteinuria after removing the subcutaneous mass.
Effect of Intrauterine Growth Retardation on the Progression of Nephrotic Syndrome
Authors: Na Yo Won , Yang Hae Joung , Choi Jeong Hoon , Yoo Kee Hwan , Hong Young Sook , Lee Joo Won , Kim Soon Kyum
Published: April 2003

Background/Aim: Neonates with intrauterine growth retardation (IUGR) experience higher morbidity and mortality rates than appropriate-for-gestational-age (AGA) neonates. The purpose of our study was to clarify whether IUGR has any influences on the progression of nephrotic syndrome in children. Methods: We performed a retrospective review of 56 children with nephrotic syndrome. IUGR was defined as a birth weight less than the tenth percentile for gestational age. Among 56 patients having nephrotic syndrome, 8 had IUGR, and 48 were AGA. Results: The 24-hour urinary protein level in children with IUGR was significantly higher than that in children who were AGA (7.61 ± 6.75 vs. 3.92 ± 3.70 g/day, p < 0.05). There was a statistically significant difference in the incidence of steroid resistance (62.5 vs. 10.4%, p < 0.05) and in the time to remission (median 60 vs. 13 days, p < 0.05) between the children with IUGR and those being AGA. Also, there was a significant difference in the incidences of treatment with cytotoxic agents (75 vs. 29.2%, p < 0.05) and complications such as hypertension. Conclusions: Our report indicates that IUGR predicts an unfavorable progression of nephrotic syndrome. So, it is important for nephrologists to pay attention to the clinical course of nephrotic syndrome in neonates with IUGR.
Apoptotic Cell Loss following Cell Proliferation in Renal Glomeruli of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes
Authors: Murata Ichijiro , Takemura Genzou , Asano Kiyoji , Sano Hirotake , Fujisawa Koh , Kagawa Tomoyo , Baba Kaoru , Maruyama Rumi , Minatoguchi Shinya , Fujiwara Takako , Fujiwara Hisayoshi
Published: April 2003

Background: The mechanism of glomerular cell loss during the late stage of diabetic nephropathy is unknown. Methods: We examined cell population, proliferation, apoptosis, and immunohistochemical expression of apoptosis-related proteins, Bcl-2 and Bax, in renal glomeruli of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of human type 2 diabetes. 10-, 30-, 50-, and 70-week-old rats were used (n = 5–8). Control was the Long-Evans Tokushima Otsuka (LETO) rat. Results: The cell population in renal glomeruli of OLETF rats progressively increased with age, but decreased at 70 weeks old. High cell proliferative activity based on proliferating cell nuclear antigen (PCNA) expression was limited during the early stage, whereas by in situ nick end-labeling (TUNEL), Taq polymerase based in situ ligation, and electron microscopy, apoptosis was detected during the late stage (50 and 70 weeks old). Augmented expression of Bax, but not of Bcl-2, was evident in glomeruli of OLETF rats during the late stage, which contributed to an increased Bax/Bcl-2 ratio. Conclusion: It appears that high cell proliferative activity and the subsequent cell loss via apoptosis counterbalance each other and determine glomerular cell population of OLETF rats. Augmented Bax expression may be one of the important regulators of this apoptosis.
Altered Renin Synthesis and Secretion in the Kidneys of Heterozygous Mice with a Null Mutation in the TGF-β2 Gene
Authors: Pietri Laurence , Bloch-Faure May , Belair Marie-France , Sanford L. Philip , Doetschman Tom , Ménard Joël , Bruneval Patrick , Meneton Pierre
Published: April 2003

Transforming growth factors β (TGF-βs) are peptides involved in autocrine and paracrine control of cell growth and differentiation. In the kidneys, TGF-β2 has been shown to localize specifically in renin-producing cells in various conditions stimulating the renin response. To test in vivo the functional role of TGF-β2, the renin response was investigated in mice heterozygous for a null mutation of the TGF-β2 gene, which had a twofold reduction in the amount of TGF-β2 mRNA. Although the increase in plasma renin concentration triggered by dehydration was not different from wild-type mice, renal renin mRNA and protein levels were higher in mutant mice under hydrated or dehydrated conditions. These data suggest that TGF-β2 exerts an inhibitory effect on renin synthesis and release from the juxtaglomerular apparatuses.
Activation of Peroxisome Proliferator-Activated Receptor-g Inhibits Apoptosis Induced by Serum Deprivation in LLC-PK1 Cells
Authors: Haraguchi Kazutaka , Shimura Hiroki , Onaya Toshimasa
Published: April 2003

Peroxisome proliferator-activated receptor-γ (PPARγ) belongs to a superfamily of nuclear receptors, which plays important roles in lipid and glucose metabolism. However, expression of PPARγ in extra-adipose tissues and stimulation of apoptosis by PPARγ activators has been previously reported. We investigated the functions of PPARγ using a clonal kidney cell line (LLC-PK1). RT-PCR revealed the expression of PPARγ in LLC-PK1 cells. The cells accumulated fat droplets and increased β-oxidation of free fatty acids in response to troglitazone, a ligand for PPARγ. At physiological concentrations, ligands for PPARγ including troglitazone, BRL49653, and 15-deoxy-δ-12,14-prostaglandin J2 inhibited serum-deprivation-induced apoptosis of the cells. On the other hand, PPARα activators did not inhibit the apoptosis. Apoptosis of LLC-PK1 cells was determined by a cell viability assay, condensation of the nucleus on fluorescent and electron microscopy, and DNA fragmentation as indicated by the appearance of nucleosomal ladders on an agarose gel. Troglitazone also suppressed serum-deprivation-induced activation of Caspase 3. However, troglitazone did not suppress apoptosis induced by ATP deprivation. Anti-apoptotic effects of troglitazone were partially blocked by a phosphatidylinositol-3-kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors such as PD98059 and AG490. These results suggest that PPARγ is functionally expressed in LLC-PK1 cells, and its activation inhibits apoptosis induced by serum deprivation, at least in part, through the PI3K pathway.
First Trimester Twin-to-Twin Transfusion Syndrome in a Trichorionic Quadruplet Pregnancy – A Diagnostic Challenge
Authors: Berg C. , Baschat A.A. , Geipel A. , Germer U. , Smrcek J. , Krapp M. , Gembruch U.
Published: April 2003

We report the prenatal diagnosis of twin-to-twin transfusion syndrome (TTS) at 11 weeks’ gestation. The diagnosis was made in a trichorionic quadruplet pregnancy which was conceived after in vitro fertilization and intracytoplasmic sperm injection for male subfertility and transfer of 3 embryos. Growth discordance, oligo/polyhydramnios and abnormal arterial and venous Doppler flows were demonstrated in 2 monochorionic fetuses, while the remaining 2 dichorionic fetuses were unremarkable. Selective fetocide of the donor by intracardiac injection of potassium chloride was followed by the spontaneous demise of the recipient. The pregnancy course remained uneventful until 32 weeks of gestation when the patient developed preterm labor. Two healthy preterm babies were delivered by cesarean section. The diagnostic problems of this early manifestation of TTS are discussed.
A Different Technique to Create a ‘Myelomeningocele-Like’ Defect in the Fetal Rabbit
Authors: Pedreira Denise A.L. , Valente Paulo R. , Abou-Jamra Rogério C. , Pelarigo Cláudio L. , Silva Lilian M. , Goldenberg Saul
Published: April 2003

Objective: To evaluate the fetal survival rate using a modified technique to surgically create a ‘myelomeningocele-like’ defect in a rabbit model. Methods: Six white New Zealand rabbits had a spinal defect created in their fetuses at 23 days of gestation. At 30 days of gestation, the fetuses were harvested for anatomo-pathologic evaluation. Results: The defect was created in 19 fetuses and an attempt to correct it was made in 15 cases (group I), and 4 fetuses where left without correction (group II). At 30 days, a ‘myelomeningocele-like’ defect was present in all surviving fetuses. The total survival rate was 73.68% (14/19); 11 fetus survived in group I and 3 in group II. Conclusion: The technical modifications, including fetal positioning and exposure of its back prior to the incision of the lamina, associated with a different technique for myometrium closure, offer an alternative and probably safer method to surgically create a spinal defect in the fetal rabbit.
Changes of P300 Elicited during a Working Memory Test in Individuals with Depersonalization-Derealization Experiences
Authors: Papageorgiou Charalabos , Ventouras Erricos , Uzunoglu Nikolaos , Rabavilas Andreas , Stefanis Costas
Published: April 2003

Background/Aim: The P300 component of Event-Related Potentials (ERPs) is related to fundamental aspects of cognitive functions, such as Working Memory (WM) and attention allocation. Deficits in these domains have been implicated in the pathophysiology of depersonalization-derealization (DD). The present study focused on the P300 elicited during a WM test in transient DD experiences. Methods: Fifteen subjects with transient DD experiences were matched for age, sex and educational level to an equal number of healthy controls. Both groups were submitted to a computerized version of the digit span Wechsler batteries. P300 was measured during the anticipatory period of this test. All participants completed the Dixon self-rating questionnaire. Results: In relation to the control group, the subjects with transient DD experiences showed significantly decreased amplitudes of P300 at central posterior brain areas. Concerning memory performance, the groups did not differ significantly. Conclusions: These findings may indicate that subjects with transient DD experiences manifest altered aspects of information processing, as reflected by P300 amplitudes elicited during a WM test. Additionally, P300 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of DD.
Prognostic Value of Urinary Interleukin 6 in Patients with IgA Nephropathy: An 8-Year Follow-Up Study
Authors: Harada Koji , Akai Yasuhiro , Kurumatani Norio , Iwano Masayuki , Saito Yoshihiko
Published: April 2003

We evaluated the significance of urinary IL-6 levels in the prediction of long-term renal outcome in patients with IgA nephropathy (IgAN). Fifty-nine patients with biopsy-proven IgAN were enrolled in this study. All patients had a creatinine clearance (Ccr) greater than 80 ml/min and normal serum creatinine concentration (Scr) on enrollment and were followed for 8.07 ± 1.72 years. Twenty- four-hour urine samples were obtained and urinary IL-6 was measured by ELISA. Fifteen patients exhibited a worsening of renal function (progressor). Renal function of the remaining 44 patients was stable during follow-up (non-progressor). The urinary IL-6 levels of progressors on enrollment were significantly higher than those of non-progressors (3.8 ± 3.8 and 1.8 ± 1.5 ng/day, respectively, p = 0.0138). We calculated the risk ratio for the progression to renal failure. Patients with a urinary IL-6 level greater than 2.5 ng/day at diagnosis had a 7.8-fold higher risk for the progression of the disease (95% CI 1.31–46.47, p = 0.024) compared with those whose urinary IL-6 level was less than 1.0 ng/day. In conclusion, urinary IL-6 levels could be used as a predictor of long-term renal outcome in patients with IgAN. Patients with a urinary IL-6 level greater than 2.5 ng/day at diagnosis may have a worse prognosis.
Ageing and Longevity Are Related to Growth Hormone/Insulin-Like Growth Factor-1 Secretion
Authors: Ruiz-Torres Antonio , Soares de Melo Kirzner Marcia
Published: April 2003

Background: It is known that the growth process is related to an individual’s life-span, but the role of growth hormone (GH) secretion in human ageing remains unknown. Objectives: This study has focussed on the influence of GH on ageing parameters and on its relationship with human longevity. Methods: To deal with the first issue, we compared ageing parameters of young (up to 39) and old (over 70) individuals having similar insulin-like growth factor-1 (IGF-1) blood levels. For the second one, the decline in IGF-1 levels was studied comparing its behaviour in the first half with that in the second half of adult life. The latter represents the period of life in which mortality progressively increases. Two hundred and five healthy individuals were chosen as subjects, well distributed by gender and age (between 19 and 93 years). Results: Old males with IGF-1 levels similar to young ones do not show the age-dependent decrease in serum testosterone and lean body mass, nor the increase in fat body mass. Other hormone-metabolic and nutritional parameters do not reveal any change compared with the results of all individuals. In females, the results do not allow to assume any IGF-1 influence. The behaviour of the linear regression in the second half of adult life of males, which becomes flat because old men having low IGF-1 blood levels die earlier, is consistent with these results. This effect, which is supported by predictive analysis, is not observed in females, i.e. the IGF-1 level declines in the second half of the women’s adult life are only a little flatter than in the first half. Finally, extrapolating the regressions obtained in the first half of adulthood, the age at which the curve crosses the x-axis is 110 years for males and 132 for females. Conclusion: The presented study of IGF-1 levels suggests that the GH secretion in adulthood plays a determinant role not only for some regressive manifestations, but also for life potential.
Visual and Spectral Analysis of Sleep EEG in Acute Hemispheric Stroke
Authors: Müller Caroline , Achermann Peter , Bischof Matthias , Nirkko Arto C. , Roth Corinne , Bassetti Claudio L.
Published: April 2003

Background: Reports on the effects of focal hemispheric damage on sleep EEG are rare and contradictory. Patients and Methods: Twenty patients (mean age ± SD 53 ± 14 years) with a first acute hemispheric stroke and no sleep apnea were studied. Stroke severity [National Institute of Health Stroke Scale (NIHSS)], volume (diffusion-weighted brain MRI), and short-term outcome (Rankin score) were assessed. Within the first 8 days after stroke onset, 1–3 sleep EEG recordings per patient were performed. Sleep scoring and spectral analysis were based on the central derivation of the healthy hemisphere. Data were compared with those of 10 age-matched and gender-matched hospitalized controls with no brain damage and no sleep apnea. Results: Stroke patients had higher amounts of wakefulness after sleep onset (112 ± 53 min vs. 60 ± 38 min, p < 0.05) and a lower sleep efficiency (76 ± 10% vs. 86 ± 8%, p < 0.05) than controls. Time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep and total sleep time were lower in stroke patients, but differences were not significant. A positive correlation was found between the amount of SWS and stroke volume (r = 0.79). The slow-wave activity (SWA) ratio NREM sleep/wakefulness was lower in patients than in controls (p < 0.05), and correlated with NIHSS (r = –0.47). Conclusion: Acute hemispheric stroke is accompanied by alterations of sleep EEG over the healthy hemisphere that correlate with stroke volume and outcome. The increased SWA during wakefulness and SWS over the healthy hemisphere contralaterally to large strokes may reflect neuronal hypometabolism induced transhemispherically (diaschisis).
Therapy of Sneddon Syndrome
Authors: Flöel Agnes , Imai Tanya , Lohmann Hubertus , Bethke Florian , Sunderkötter Cord , Droste Dirk W.
Published: April 2003

We report the case of a young woman with progressive cognitive decline and epilepsy. She showed ischemic cerebrovascular disease and proximal livedo racemosa. Antiphospholipid antibody (aPL) could not be detected and there were no microemboli on continuous transcranial Doppler ultrasonography monitoring. Histology of cerebral vessels showed intimal hyperplasia in small leptomeningeal venous vessels and micronecrosis of grey and white matter. We subsequently made the diagnosis of aPL-negative Sneddon Syndrome (SNS). Anticoagulation with warfarin could not be initiated because of a drug-resistant epilepsy with the risk of falls and subsequent bleeding; immunosuppression with steroids and azathioprine was ineffective, as was initial antiplatelet therapy with clopidogrel alone. However, when we intensified antiplatelet therapy by combining clopidogrel and ASS, a slowing of disease progression, as assessed by neuropsychological testing and magnetic resonance imaging, was noted on a follow-up after 6 months. Therapeutic options in SNS in both aPL-positive and aPL-negative patients with SNS are discussed.
Pre-Attentive Cognitive Processing in Epilepsy
Authors: Rahmann Alexandra , Stodieck Stefan , Husstedt Ingo-W. , Evers Stefan
Published: April 2003

Patients suffering from epilepsy often complain of deficits in attentive cognition affecting, for instance, concentration, reaction time, memory and psychomotor speed. We were interested in the impact of epilepsy and its treatment on pre-attentive cognitive functions and enrolled 107 subjects (50 male, 57 female; mean age 26 years): 50 patients with partial epilepsy, 15 with primary generalised epilepsy and 42 healthy controls. We used a new computer-adapted neuropsychological test (called textest), measuring the pre-attentive visual processing speed. The subjects had to discriminate 5 different stimuli presented on a computer screen. As a primary result, we calculated the time the subject needed to detect 50% of the demonstrated stimuli correctly (t-50 time). We also applied the d2 test. For the textest results, no significant group differences between the different patient and healthy groups could be revealed, except for a significantly increased t-50 time in patients with polytherapy compared with the control group. Compared with healthy controls, significantly worse d2 test results were found in patients with epilepsy in general, a duration of disease >1 year, anti-epileptic drug therapy in general and in patients receiving polytherapy in particular (all p < 0.001). Our data suggest that polytherapy, but not monotherapy or the subtype of epilepsy, might have a slowing impact on pre-attentive cognitive processing.
Proton Magnetic Resonance Spectroscopy in Dementia with Lewy Bodies
Authors: Molina J.A. , García-Segura J.M. , Benito-León J. , Gómez-Escalonilla C. , del Ser T. , Martínez V. , Viaño J.
Published: April 2003

Proton magnetic resonance spectroscopy (1H-MRS) provides a non-invasive, in vivo insight into the brain metabolism, and has been successfully used in several neurological conditions. Our objective was to characterise the cerebral metabolic changes in dementia with Lewy bodies (DLB) patients using 1H-MRS. Single Voxel 1H-MRS was performed in 12 DLB patients with mild to moderate symptoms and 11 age-matched healthy controls. Volumes of interest (VOI) were selected, including white matter (WM) in the centrum semiovale and grey matter (GM) in the parasagittal parietal cortex. Main metabolic peaks corresponding to N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were identified. These areas were measured and referred to that of the water. Metabolic ratios among the different peak areas were also calculated. In comparison with the control group, DLB patients showed significantly lower mean NAA/Cr, Glx1/Cr and Cho/Cr ratios in the WM, while their Ins/Cr and Ins/NAA ratios did not differ from those of the control group. In the GM, no significant differences were found between both groups. Correlations between age at onset, disease duration, Mini-Mental State Examination, the motor section of the Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr staging and metabolic ratios, both for WM and GM, were not significant in DLB patients. Our spectroscopy data show WM involvement, along with GM preservation, in DLB patients with early or intermediate stages. Hence, 1H-MRS may provide adjunctive information in the ante-mortem diagnosis of DLB.
Pancreatic Protease Inhibition during Shock Attenuates Cell Activation and Peripheral Inflammation
Authors: Fitzal Florian , DeLano Frank A. , Young Corey , Rosario Henrique S. , Schmid-Schönbein Geert W.
Published: April 2003

Intestinal ischemia contributes to shock-induced multiple organ failure. Our recent evidence suggests that pancreatic proteases may be involved in the formation of inflammatory activators within an ischemic intestine. These inflammatory mediators are released early into the circulation and may contribute to the severe systemic inflammatory response syndrome (SIRS) during shock. We examined the impact of intra-intestinal pancreatic protease inhibition on acute intestinal ischemia-induced hypotension, the formation of activating factors for cardiovascular cells, as well as cremaster muscle cell death and intestinal injury by intravital microscopy. Male Wistar rats were divided into four groups: (1) a sham group; and experimental groups with 100 min of superior mesenteric artery occlusion (2) without (SMAO group), and (3) with intestinal lavage using Krebs-Henseleit solution (LAV group), or (4) lavage using the protease inhibitor gabexate mesilate in Krebs-Henseleit solution (FOY group, 0.37 mM). Intestinal ischemia and reperfusion-induced hypotension upon reperfusion was accompanied by a significant increase in the level of neutrophil-activating factors in the intestine and plasma. During reperfusion, a significant increase in leukocyte-endothelium interactions in postcapillary venules and parenchymal cell death were observed in the cremaster muscle in LAV and SMAO animals suggesting peripheral neutrophil cell activation. Intra-intestinal pancreatic protease inhibition resulted in a stable blood pressure throughout the experiment. Cell activation, leukocyte-endothelial interactions and cell death in the cremaster muscle were almost completely abolished in the FOY group. In addition, ischemia-induced intestinal mucosal injury was attenuated with intestinal pancreatic protease inhibition. These results indicate that intestinal pancreatic protease inhibition significantly attenuates intestinal ischemia-induced shock by reducing SIRS and gut injury.
Platelet Kinetics in the Pulmonary Microcirculation in vivo Assessed by Intravital Microscopy
Authors: Eichhorn M.E. , Ney L. , Massberg S. , Goetz A.E.
Published: April 2003

Growing evidence supports the substantial pathophysiological impact of platelets on the development of acute lung injury. Methods for studying these cellular mechanisms in vivo are not present yet. The aim of this study was to develop a model enabling the quantitative analysis of platelet kinetics and platelet-endothelium interaction within consecutive segments of the pulmonary microcirculation in vivo. New Zealand White rabbits were anesthetized and ventilated. Autologous platelets were separated from blood and labeled ex vivo with rhodamine 6G. After implantation of a thoracic window, microhemodynamics and kinetics of platelets were investigated by intravital microscopy. Velocities of red blood cells (RBCs) and platelets were measured in arterioles, capillaries and venules, and the number of platelets adhering to the microvascular endothelium was counted. Kinetics of unstimulated platelets was compared with kinetics of thrombin-activated platelets. Velocity of unstimulated platelets was comparable to RBC velocity in all vessel segments. Unstimulated platelets passed the pulmonary microcirculation without substantial platelet-endothelial interaction. In contrast, velocity of activated platelets was decreased in all vascular segments indicating platelet margination and temporal platelet-endothelium interaction. Thrombin-activated platelets adhered to arteriolar endothelium; in capillaries and venules adherence of platelets was increased 8-fold and 13-fold, respectively. In conclusion, using intravital microscopy platelet kinetics were directly analyzed in the pulmonary microcirculation in vivo for the first time. In contrast to leukocytes, no substantial platelet-endothelium interaction occurs in the pulmonary microcirculation without any further stimulus. In response to platelet activation, molecular mechanisms enable adhesion of platelets in arterioles and venules as well as retention of platelets within capillaries.
Characterization of Differential Gene Expression in Quiescent and Invasive Human Arterial Smooth Muscle Cells
Authors: Blindt Rüdiger , Vogt Felix , Lamby Daniel , Zeiffer Ute , Krott Nicole , Hilger-Eversheim Kristina , Hanrath Peter , vom Dahl Jürgen , Bosserhoff Anja-Katrin
Published: April 2003

Proliferation, migration and invasion of smooth muscle cells (SMCs) are essential pathogenic processes in the development of a broad spectrum of cardiovascular disorders, like arteriosclerosis, restenosis after percutaneous transluminal angioplasty and stent implantation as well as transplant vessel disease. As an in vitro model mimicking these processes, the Boyden chamber was employed to characterize the diverging migratory and invasive potentials of proliferating and nonproliferating human arterial SMCs (haSMCs). Using this model, differential gene expression of both phenotypes was analyzed by a cDNA array system (Clontech human cardiovascular array). With these arrays, 558 cardiovascular-associated genes could be compared. Further, gene expression was exactly quantified by real-time RT-PCR. Protein expression was analyzed by ELISA and Western blotting. In total, 47 genes were differentially expressed more than 1.5 times. Most of the differentially regulated genes in this study were associated with the extracellular matrix (ECM) and cell motility. In detail, the respective groups were matrix-organizing proteins, ECM proteins, cell adhesion proteins, extracellular communication and cytoskeleton motility proteins. Genes known to be differentially regulated during haSMC migration and invasion, like TIMP 2, TIMP 3, and MMP 3, were confirmed by the array data. Reduced expression of several cytoskeletal proteins, like vimentin, fibronectin, cytokeratins and β1 integrin, was shown in the invasive phenotype. Further, angio-associated protein, alpha E-catenin and atrial brain natriuretic peptide receptor were downregulated whereas TFPI 2 was strongly upregulated in invasive haSMCs. In conclusion, several relevant potential candidate genes for the quiescent and the invasive SMC phenotype were identified and genes already known to be differentially regulated by previous analysis were confirmed.
Major Complex Pelvic Arteriovenous Malformation in a Patient with Down Syndrome
Authors: Kassardjian Zareh , Lebret Thierry , Mellot François , Hervé Jean-Marie , Barré Philippe , Lugagne Pierre-Marie , Scherrer Antoine , Botto Henry
Published: April 2003

Pelvic arteriovenous malformations (AVM) are rare, and the treatment of this condition presents an interesting challenge. We report the first case of a major AVM in a patient with Down syndrome which was revealed by a massive hematuria. Arteriography showed a bilateral complex iliac artery malformation. The first proximal embolization (unilateral) did not prevent bladder hemorrhage, and the second distal (bilateral) immobilization produced bladder necrosis. However, the patient died despite an emergency cystectomy.
Intestinal Resection- and Steroid-Associated Alterations in Gene Expression Were Not Accompanied by Changes in Lipid Uptake
Authors: Thiesen A. , Wild G.E. , Tappenden K.A. , Agellon L.B. , Drozdowski L. , Keelan M. , Thomson B.K.A. , McBurney M.I. , Clandinin M.T. , Thomson A.B.R.
Published: April 2003

Background/Aims: Glucocorticosteroids alter the morphology and transport function of the intestine of adult rats. This study was undertaken to assess the possible effect on intestinal lipid uptake of the locally acting steroid budesonide, or the systemically active prednisone or dexamethasone. Methods: Sprague-Dawley rats underwent intestinal transection or 50% intestinal resection. Budesonide, prednisone, dexamethasone, or control vehicle was given for 2 weeks from the time of surgery. Uptake was measured using ring uptake technique. Results: Resection had no effect on the mRNA expression for the early response genes, for proglucagon, or for the ileal lipid binding protein (ILBP), but was associated with reduced jejunal ornithine decarboxylase (ODC) mRNA and with reduced jejunal mRNA for the liver fatty acid binding protein (L-FABP). All three steroids reduced jejunal mRNA for proglucagon and c-jun, and did not affect the mRNA for L-FABP or for ILBP. These resection- and steroid-associated changes in gene expression were not associated with alterations in the intestinal uptake of long chain fatty acids or cholesterol. Conclusions: The resection-associated alterations in the RNA expression of ODC and L-FABP and the steroid-associated changes in mRNA expression of c-jun and proglucagon were not accompanied by variations in lipid uptake.
Candidate Genes Colocalized to Linkage Regions in Inflammatory Bowel Disease
Authors: Martin K. , Radlmayr M. , Borchers R. , Heinzlmann M. , Folwaczny C.
Published: April 2003

Background and Aims: The genes encoding for tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and the vitamin D receptor (VDR) are colocalized to inflammatory bowel disease-associated linkage regions on chromosomes 6, 7 and 12. An association study of these gene polymorphisms with ulcerative colitis or Crohn’s disease and a stratification according to disease phenotypes was performed in order to identify gentically homogenous subgroups. Patients and Methods: 119 healthy, unrelated controls, 95 patients with Crohn’s disease and 93 patients with ulcerative colitis were genotyped for the (G to A) –308 TNF-α promoter polymorphism on chromosome 6, the codon 497 EGFR polymorphism on chromosome 7 and the TaqI polymorphism of the VDR gene on chromosome 12. After genotyping, patients were stratified according to the respective disease phenotype. Results: A disequilibrium in the distribution of the VDR genotypes was found in patients with ulcerative colitis compared to controls (p = 0.024). In fistulizing and fibrostenotic Crohn’s disease the ‘TT’ genotype was significantly reduced compared with other phenotypes (p = 0.006), whereas the ‘tt’ genotype was found more frequently (p = 0.04). The frequency of the WT allele of the EGFR gene was significantly higher in ulcerative colitis (p = 0.04) than in controls. Further significant differences, concerning the associations of the different polymorphisms and disease susceptibility or clinical phenotypes, were not observed. Conclusions: Regardless of the disease phenotype, the associations between the polymorphisms and inflammatory bowel disease investigated herein are modest, even after stratification for the disease phenotypes. Hence, these polymorphisms are unlikely to confer the reported linkage between inflammatory bowel disease and chromosomes 6, 7 and 12.
Helicobacter Species Are Not Detectable by16S rDNA PCR in Bile from Dutch Patients with Common Bile Duct Stones
Authors: Roosendaal Robert , Kuipers Ernst J. , Vandenbroucke-Grauls Christina M.J.E. , Kusters Johannes G.
Published: April 2003

Background: Some Helicobacter species colonize the intestinal tract. To explore the possible relation between Helicobacter spp. and gallbladder disorders, we have investigated their presence in bile of patients with biliary obstruction and dilatation of the bile ducts. Methods: Bile was sampled from 31 Dutch patients with biliary obstruction identified by jaundice and dilatation of the bile ducts on ultrasound. Samples (n = 31) were obtained immediately following cannulation of the common bile duct (CBD) by endoscopic retrograde cholangiopancreatography (ERCP) (n = 29) or by peri-operative puncture of the galbladder (n = 2). DNA was isolated from bile by binding to diatoms. Helicobacter spp. were detected by a sensitive (detection limit 1 CFU per reaction tube) 16S rDNA PCR with genus-specific primers. Duplicate samples were spiked with Helicobacter pylori DNA and subjected to PCR in order to check for inhibition. Results: 28 patients had CBD stones (bile collected by ERCP (n = 26) or operatively (n = 2)), 2 had a pancreatic head tumor, and in 1 no abnormalities were found. In 1 of 21 amplifiable bile samples (10/31 inhibited) from Dutch patients with CBD stones, H. pylori 16S rDNA was found. Conclusion: Our data indicate that CBD stones in Dutch patients are not associated with the presence of Helicobacter spp. in bile.
Distribution of Ferroportin1 Protein in Different Regions of Developing Rat Brain
Authors: Jiang Dai He , Ke Ya , Cheng Yan Zhong , Ho Kwok Pin , Qian Zhong Ming
Published: April 2003

Ferroportin1 is a newly discovered transmembrane iron export protein. It plays a key role in Fe2+ transport across the basal membrane of enterocytes in the gut. It has been suggested that this protein might have the same role in Fe2+ transport across the abluminal membrane of the blood-brain barrier as it works in enterocytes. However, the presence of ferroportin1 in the brain has not been well determined. In the present study, we investigated expression of ferroportin1 protein in different brain regions, including cortex, hippocampus, striatum and substantia nigra, in developing male Sprague-Dawley rats. The results provided direct evidence for the existence of ferroportin1 protein in the rat brain. All brain areas examined have the ability to synthesize ferroportin1 protein. The findings also showed that age has a significant effect on the expression of ferroportin1 protein in the cortex, hippocampus, striatum and substantia nigra of the rat brain.
Extracorporeal Circulation Induced Microvascular Perfusion Injury of the Small Bowel
Authors: Sack F.-U. , Dollner R. , Reidenbach Bettina , Schledt A. , Taylor Sarah , Gebhard Martha Maria , Hagl S.
Published: April 2003

Gastrointestinal complications following cardiopulmonary bypass (CPB) are relatively uncommon, but are associated with a high mortality rate. Impairment of bowel perfusion during and following CPB may serve as a trigger for the development of multiorgan failure. The aim of our study was the development of a new animal model allowing quantitative analysis of small bowel microcirculation during and after CPB. Twelve Landrace pigs served as laboratory animals. A 15-cm loop of the terminal ileum was exteriorized for microscopic observation. In 6 animals, a normothermic, partial left heart bypass (pLHB) was established for 2 h with a flow rate of 2,000 ml/min. Arterioles, collecting venules and the capillaries of the small bowel were recorded for the analysis of the microcirculation. All parameters were recorded prior to, during pLHB and up to 2 h after weaning off the bypass. Six sham operated animals served as controls. Despite unchanged hemodynamics, pLHB leads to microvascular perfusion disturbances of the small bowel. In pLHB animals, blood cell velocity in postcapillary venules (30–70 µm) was significantly decreased during and following bypass. Capillary density was also reduced during bypass and decreased even further after pLHB to only 30% of the control values. With this new large animal model for quantitative assessment of microvascular perfusion of the small bowel during CPB, it could be clearly demonstrated that partial normothermic left heart bypass leads to a significant disturbance of the small bowel microcirculation even under stable hemodynamic conditions.
Prognostic Significance of p21 and p27 Protein, Apoptosis, Clinical and Histologic Factors in Rectal Cancer without Lymph Node Metastases
Authors: Schwandner O. , Bruch H.-P. , Broll R.
Published: April 2003

The aim of this study was to evaluate the prognostic role of clinical and histopathologic factors, cell-cycle regulator proteins (p21Waf1/Cip1, p27Kip1), and apoptotic index in lymph node-negative rectal cancer. Formalin-fixed, paraffin-embedded tissue samples of 97 rectal carcinomas (UICC stages I and II) resected curatively within five years were used. Immunohistochemical analysis of protein expression was performed by monoclonal antibodies: p21 (clone SX118), p27 (clone SX53G8). Apoptosis was assessed by the TUNEL method. Clinical, surgical, histopathologic, and follow-up data were prospectively recorded in a computerized registry. To assess prognostic significance (end points: metachronous distant metastases, 5-year disease-free and overall survival), statistics included univariate and multivariate analysis (p < 0.05 statistically significant). Of the 97 rectal carcinomas without lymph node metastases, 46.4% (45/97) were p21-positive, 49.5% were p27-positive (48/97), whereas 27.8% (27/97) showed a high apoptotic index. Within a median follow-up of 54 months, 4 patients developed local recurrence (4.1%). Distant metastases occurred in 12 patients (12.4%). Univariate analysis showed that gender, UICC stage, p21 and p27 were significantly associated with the incidence of distant metastases (p < 0.05). UICC stage and p21 were the only factors to be significantly related to 5-year disease-free survival by univariate analysis (p < 0.05). Only UICC stage was significantly related to 5-year overall survival (p < 0.05). The apoptotic index was correlated neither to recurrence nor to survival (p > 0.05). Multivariate analysis demonstrated that gender, UICC stage and p21 were independently related to the incidence of distant metastases; however, UICC stage was the only independent factor predictive of 5-year disease-free survival and overall survival (p < 0.05).
Portal Venous Air in an Adult Patient with Obstructive Small Bowel Volvulus
Authors: Tan Edward C.T.H. , Jager Gerit J. , Bleeker Wim A. , van Goor Harry
Published: April 2003

Background: Diagnosis of small bowel volvulus is frequently delayed often resulting in bowel ischaemia and infarction and impairing clinical outcome. Instant and correct diagnosis and subsequent adequate surgery may improve the outcome. Methods: We describe a 19-year-old female with small bowel obstruction due to volvulus in whom the diagnosis was suspected based on the finding of air in the bowel wall and in the portal vein on a plain abdominal radiograph. Conclusions: Air, present in the portal vein and bowel wall on a plain abdominal X-ray, suggests bowel ischaemia or necrosis and that the need for laparotomy is urgent.
Caudate Lobectomy Combined with Resection of the Inferior Vena cava and Its Reconstruction by a Pericardial Autograft Patch
Authors: Togo Shinji , Tanaka Kuniya , Endo Itaru , Morioka Daisuke , Miura Yasuhiko , Masunari Hideki , Kubota Toru , Nagano Yasuhiko , Masui Hidenobu , Sekido Hitoshi , Shimada Hiroshi
Published: April 2003

A 53-year-old woman with remnant liver metastasis originating from colon cancer was referred to our department. She underwent successful caudate lobectomy combined with resection of the inferior vena cava (IVC), including reconstruction with a pericardial autograft patch. IVC clamping was performed between the IVC below the confluence of the left hepatic vein and the infrahepatic IVC in order to preserve the hepatic circulation. After 18 months, the graft was patent and there was no sign of recurrence. A part of the pericardium used as an autograft for patch repair of the defect of the IVC was very useful because it was easily available, required only division of the diaphragm, and was of sufficient length and width.
Hepatocellular Carcinoma in a Low-Incidence Region
Authors: Mala Tom , Mathisen Øystein , Bergan Anstein , Søreide Odd
Published: April 2003

Background/Aims: To study the characteristics and outcome of patients with hepatocellular carcinoma in a low-incidence region. Methods: 98 patients with hepatocellular carcinoma who had been referred to the Surgical Department, National Hospital, Oslo, between 1981 and 1999 were studied retrospectively. Tumour size, prevalence of cirrhosis, serum α-fetoprotein concentration, rate of resection, type of resection and survival were analysed. Results: 19% (19/98) of the patients had cirrhosis of varying aetiology. Median tumour size was 10 cm. α-Fetoprotein was normal in 46% of the patients. Hepatic resection was performed in 30 (31%) patients and 77% of the resections were major (more than 2 segments). Abdominal exploration was done in 33 patients and liver transplantation in 6 patients. No surgical intervention was made in 31 patients. Five-year actuarial survival in resected patients was 24%. Median survival of non-resected patients was 3.3 months. Conclusion: The patient characteristics in this study differ from patient cohorts with hepatocellular carcinoma in other geographical areas. The main differences are large tumour size, low prevalence of the disease, and diverse aetiology of cirrhosis.
A Comparative Study of 20% Azelaic Acid Cream Monotherapy versus a Sequential Therapy in the Treatment of Melasma in Dark-Skinned Patients
Authors: Sarkar Rashmi , Bhalla Mala , Kanwar Amrinder J.
Published: April 2003

Background: Melasma is a commonly found hyperpigmentary disorder in dark-complexioned persons, which is rather difficult to treat. Azelaic acid (AZA) 20% is considered efficacious in the treatment of melasma, although the response is rather slow. It has also been combined synergistically with topical retinoic acid, where the results were satisfactory. Objective: The study was done to evaluate the usefulness of a sequential therapy of potent topical steroids +20% AZA cream versus only 20% AZA cream in the treatment of melasma. Methods: This was a prospective, single-blind, right-left comparison pilot study with (1) twice daily application of 20% AZA to one half of the face for 24 weeks and (2) a potent topical steroid, 0.05% clobetasol propionate cream, to be applied for 8 weeks only and then to be followed by 20% AZA cream only for the next 16 weeks on the other half. Concomitant use of a broad-spectrum sunscreen was also mandatory. Thirty Indian patients (25 females, 5 males), whose ages ranged from 21 to 45 years and who were not pregnant, nursing or on any concurrent therapy, completed the study. Clinical evaluation, photography and the overall response were assessed at 4, 8, 16 and 24 weeks. Results: At 4, 8 and 16 weeks, the lightening of melasma was significantly more marked on the side receiving the sequential therapy rather than the side receiving only 20% AZA cream (p < 0.001). However, at 24 weeks, although the difference was still significant (p = 0.0052), as many as 96.7 and 90% of patients of each group (sequential therapy and AZA) had good to excellent responses to treatment. The side-effects noted were mostly mild and transient and mainly local irritant effects. Conclusions: A sequential therapy of topical potent steroids +20% AZA cream can be considered as another alternative treatment for melasma, which combines the beneficial effects of both besides perhaps increasing the compliance of the patients. 20% AZA monotherapy itself is also an effective and well-tolerated therapy for melasma in dark-skinned races.
Inhibition of Lipase Activity in Antibiotic-Resistant Propionibacterium acnes Strains
Authors: Gloor Max , Wasik Barbara , Becker Andrea , Höffler Ulrich
Published: April 2003

Background and Objective: Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC). The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P. acnes strains resistant to these antibiotics. Methods: Of 42 P. acnes strains, 10 showed an MIC >256 µg/ml for erythromycin. Two strains showed MICs of 0.19 and 0.25 µg/ml, while the MIC of the remaining strains was ≤0.016 µg/ml. Lipase activity was determined up to a concentration of 192 µg/ml by cultivation on spirit blue agar + lipase reagent. The 10 strains whose erythromycin MIC was >256 µg/ml were also tested for lipase inhibition by clindamycin. While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production. Results: Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P. acnes strains. However, lipase inhibition was seen only at the dilution level immediately below the MIC. Conclusions: Resistant P. acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC.
Renal Effects of Cyclooxygenase-2 Inhibition in Fetal Lambs
Authors: Kajino Hiroki , Roman Christine , Clyman Ronald I.
Published: April 2003

We used late gestation fetal lambs to examine the effects of a selective COX-2 inhibitor (celecoxib) on fetal renal function. After a 2-hour baseline period, each fetus was exposed to either saline (control, n = 10), ‘low-dose’ celecoxib (plasma concentration 0.47 µg/ml, n = 4), or ‘high-dose’ celecoxib (1.4 µg/ml, n = 8) during a 5-hour study period. High-dose celecoxib (but not low-dose celecoxib) caused a significant decrease in urine volume, free water clearance, arterial pH, and an increase in blood lactate compared with the control group. There were no significant differences in creatinine clearance, fractional excretion of sodium and potassium, or in renal blood flow between the 3 groups. These effects are similar to those reported for the nonselective COX-1/-2 inhibitor, indomethacin. COX-2 appears to play an important role in promoting free water excretion in the fetal lamb.
Estrogen Modulation of Mu-Opioid Receptor-Stimulated [35S]-GTP-Gamma-S Binding in Female Rat Brain Visualized by in vitro Autoradiography
Authors: Acosta-Martinez Maricedes , Etgen Anne M.
Published: April 2003

The µ-opioid receptor (OR) is involved in several aspects of female reproductive neuroendocrinology, such as the control of gonadotropin release and the display of lordosis behavior. Even though the neuroendocrine events modulated by µ-ORs are steroid hormone-dependent, few studies have shown how steroid hormones such as estrogen and/or progesterone can affect µ-OR function. Therefore, the present study investigated if in vivo estrogen or estrogen plus progesterone treatment of ovariectomized (OVX) rats affects µ-OR coupling to its G proteins. We used autoradiographic analysis of agonist-stimulated [35S]-GTPγS binding, in which brain sections were incubated in the presence or absence of the µ-OR agonist [D-Ala2, N-Me-Phe4, Gly2ol]-enkephalin (DAMGO). Film images were quantified using calibrated [14C] standards. Analysis was performed in steroid-responsive hypothalamic regions such as the medial preoptic area (mPOA) and the ventromedial nucleus of the hypothalamus, as well as in non-hypothalamic brain regions. Treatment with estrogen, alone or with progesterone, significantly increased DAMGO-stimulated [35S]-GTPγS binding in the mPOA when compared to control OVX animals. In addition, estrogen increased µ-OR coupling in the caudate putamen. Steroid treatment had no effect on either basal or DAMGO-stimulated binding in the other brain regions examined. These findings suggest that estrogen modulates µ-OR function in a brain region-specific fashion. This could have important implications in terms of how these hormones synchronize reproductive behavior and gonadotropin release.