bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin Modulates the Inflammatory Response in Acute Pancreatitis
Authors: Konturek P.C. , Jaworek J. , Maniatoglou A. , Bonior J. , Meixner H. , Konturek S.J. , Hahn E.G.
Published: April 2003

Background: Leptin is a pleiotropic hormone that is involved in the regulation of food intake and body weight. Recent findings demonstrated that leptin receptors are present in the pancreas but the involvement of leptin in pancreatitis remains unknown. The aim of the present study was: (1) to assess plasma leptin levels in rats with caerulein-induced pancreatitis (CIP) and humans with acute pancreatitis; and (2) to determine the effects of exogenous leptin on the course of acute CIP in rats Methods: CIP was produced in Wistar rats by s.c. infusion of 5 µg of caerulein for 5 h. Plasma leptin was measured by specific RIA and leptin expression in the pancreas was determined at the transcriptional and protein levels. In addition, the effects of exogenous leptin at the doses of 1 or 10 µg/kg i.p. on the course of CIP and the plasma levels and mRNA expression in pancreas of cytokines TNFα and IL-4 were studied. Furthermore, pancreatic cNOS and iNOS expression at mRNA level were measured in rats with CIP and pretreated with leptin. Parallel to these studies, the plasma levels of leptin were measured in 15 patients with acute edematous pancreatitis and in 30 healthy controls of comparable age and body mass index. Results: In rats, plasma leptin rose significantly from the median of 0.14 (0.03–0.3 ng/ml) in the control group to 0.56 (0.2–3.2 ng/ml) in rats with CIP. The CIP was associated with an upregulation of mRNA and protein for leptin in the pancreas. The administration of exogenous leptin significantly reduced the weight of pancreas, histological manifestations of pancreatitis, plasma TNFα and mRNA expression for iNOS in the pancreatic tissue. The assessment of leptin plasma level in humans demonstrated significantly higher median values of plasma leptin in patients with acute pancreatitis [7.5 (4.3–18.4 ng/ml)] than in healthy controls [2.1 (1.0–11.8 ng/ml)]. Conclusions: (1) Acute pancreatitis in rats and in humans is associated with a marked increase in the plasma level of leptin. (2) The transcriptional upregulation of leptin in the pancreas after induction of pancreatitis indicates that the inflammed pancreas could be the source of local production of leptin. (3) Exogenous leptin protects the pancreas against development of acute CIP in rats and one possible mechanism of action of leptin might be attributed to the activation of nitric oxide pathway.
Vagal Tone and Meal-Induced Abdominal Symptoms in Healthy Subjects
Authors: Hjelland I.E. , Hausken T. , Svebak S. , Olafsson S. , Berstad A.
Published: April 2003

Background/Aims: Patients with functional dyspepsia often have meal-induced dyspeptic symptoms and low vagal tone. We examined whether these variables are related in healthy subjects. Methodology: In 40 healthy subjects vagal tone and abdominal symptoms were recorded before and after a 500-ml soup meal ingested in 1 and 4 min on separate visits. Vagal tone was indexed by respiratory sinus arrhythmia (RSA). Results: Scores for nausea and discomfort were higher when the soup was ingested in 1 min as compared with 4 min (nausea: p = 0.02; discomfort: p = 0.04). There was no difference in fullness or abdominal pain. RSA was unrelated to meal-induced symptom scores. RSA varied with respiration and body position: It was highest while breathing deeply in the sitting position (24.0 beats/min). With normal breathing RSA was highest in the supine position (9.0 beats/min), lower while sitting (7.0 beats/min) and lowest while standing (6.2 beats/min). Conclusions: Epigastric discomfort in response to rapid ingestion of a test meal in healthy subjects was not related to vagal tone as indexed by RSA. Vagal tone varied with breathing pattern and body position. It is possible that increasing vagal tone by such measures can be beneficial in the treatment of patients with functional dyspepsia.
Cardiac Positron Emission Tomography
Authors: Kumar Sanjay , Khan Masood A. , Camici Paolo G.
Published: April 2003

Positron emission tomography (PET) is a non-invasive radionuclide imaging technique that, when used with appropriate radiotracers and kinetic models, permits absolute quantitative measurements of myocardial perfusion, metabolism and receptor densityin vivo. Assessment of the coronary vasodilator reserve (ratio of hyperaemic to baseline myocardial blood flow) has provided insights into both the functional significance of coronary artery stenoses in patients with coronary artery disease and abnormalities of the coronary microcirculation in patients with different cardiomyopathies. The use of PET to identify myocardial viability (by preserved uptake of 18F-fluoro-deoxy-glucose) allows the localisation of hibernating myocardium and the quantification of infarct size in patients with coronary artery disease. Measurements of myocardial oxygen consumption using PET with oxygen-15 and 11C-acetate have provided information on myocardial metabolism during ischaemia and myocardial stunning. Tracers and kinetic models have also been developed permitting investigation of the role of the cardiac autonomic nervous system in the pathophysiology of heart failure and arrhythmogenesis. The high spatial resolution of modern PET cameras and the validation of new tracers may provide further insights into cardiac pathophysiology, e.g. to assess the transmural distribution of myocardial blood flow and metabolism across the left ventricular wall.
Toward a Multiculture, Multiage, Multimethod Science
Authors: Bornstein Marc H.
Published: April 2003

Historically, developmental investigators have tended to assess phenomena of interest in one way at one age in one culture. In this essay, I explore some rationales and advantages for a multiculture, multiage, multimethod science.
Some Cases for Culture
Authors: Brenneis Don
Published: April 2003

This article briefly explores the underlying analogy between culture and language common in American anthropology and related fields. Certain key assumptions about culture – among them systematicity, homogeneity, sharedness, and boundedness – derive in part from this analogy. Three points are central: first, that these operating assumptions are interpretively and rhetorically powerful but can lead to particularly static models; second, that these are not necessarily inherent features of language itself, i.e., that the language end of the analogy may be misunderstood; and, third, that the use of a case approach, one tracking the making and transformation of cultural practice over time, can help us better account for the complex relationships among culture, social life, and socialization.
Glomerular Remodelling: Novel Therapeutic Approaches Derived from the Apparently Chaotic Growth Factor Network
Authors: Floege Jürgen
Published: April 2003

Glomerular remodelling, i.e. cell and matrix turnover, is a permanent process even in the normal kidney. Within the glomerulus, two cell types, namely the endothelial and mesangial cell, exhibit relatively high turnover and thus high capacity to regenerate following injury, whereas podocytes appear to be in a state of growth arrest with very limited potential for mitosis and apparently even lesser potential for complete cell division. An understanding of how these processes are regulated by growth factors may allow novel therapeutic approaches aimed at deviating the response to injury from the scaring pathway to reconstitution of normal glomerular morphology. Out of the apparently chaotic network of cytokines and growth factors some factors have evolved, which exhibit well-defined actions in the glomerulus that renders them attractive targets for interventions. These include platelet-derived growth factor (PDGF), a central mediator of mesangial cell proliferation and matrix synthesis, vascular endothelial growth factor (VEGF), a central angiogenic mediator regulating endothelial cell proliferation and survival and finally hepatocyte growth factor (HGF), an angiogenic growth factor with additional pronounced activity at the tubulointerstitial level.
Ameliorative Effect of Hepatocyte Growth Factor on Glycerol-Induced Acute Renal Failure with Acute Tubular Necrosis
Authors: Nagano Tomokazu , Mori-Kudo Ikue , Tsuchida Atsushi , Kawamura Takao , Taiji Mutsuo , Noguchi Hiroshi
Published: April 2003

Background/Aims: Hepatocyte growth factor (HGF), a multi-potent growth factor, is known to promote regeneration of damaged renal epithelial cells. Glycerol injection into rats induces severe acute renal failure (ARF) with ischemia and tubular necrosis, a model which shares many features with human ARF or rhabdomyolysis. We investigated the efficacy of HGF in this glycerol-induced ARF rat model. Methods: ARF was induced by intramuscular injection of glycerol into the hind limbs of male Wistar rats. HGF (0.25 mg/kg/shot) or vehicle was administered intravenously 1 h before and 1, 3, 5, 8, 24 and 36 h after glycerol injection. Biochemical parameters for serum and urine were measured and histological analyses of the kidneys were performed. We also analyzed endogenous HGF expression and phosphorylation of c-Met/HGF receptor in the kidneys of glycerol-induced ARF rats. Results: Glycerol treatment caused severe ARF which invariably led to death of the rats. Repeated administration of HGF protected rats from death caused by severe ARF. Histological analyses revealed that HGF treatment reduced necrosis of tubular cells in the renal cortex. Serum/urine biochemical parameters also showed that renal dysfunction was improved by HGF administration. Intravenous administration of HGF enhanced phosphorylation of the c-Met/HGF receptor and mitogen-activated protein kinase in the kidney. In the vehicle-treated group the renal endogenous HGF concentration decreased and there was no change in c-Met/HGF receptor phosphorylation. Conclusion: These results indicate that HGF effectively accelerated the recovery of renal function and improved survival in glycerol-induced ARF rats.
Serum IgA/C3 Ratio May Predict Diagnosis and Prognostic Grading in Patients with IgA Nephropathy
Authors: Ishiguro Chizuru , Yaguchi Yutaka , Funabiki Kazuhiko , Horikoshi Satoshi , Shirato Isao , Tomino Yasuhiko
Published: April 2003

Recently, the authors reported that the ratio of serum IgA to C3 (serum IgA/C3 ratio) is a good marker to distinguish patients with IgA nephropathy from non-IgA nephropathy patients together with serum IgA levels using an international reference preparation (IFCC/CRM470). In this study, the authors investigated whether the serum IgA/C3 ratio might be an indicator of prognostic grading in patients with IgA nephropathy. Two hundred and thirteen patients with IgA nephropathy and 96 other glomerular diseases including diffuse or focal mesangial proliferative glomerulonephritis without mesangial IgA deposition (non-IgA PGN), membranous nephropathy and thin basement membrane syndrome were examined. The levels of serum IgA and C3 in these patients were adjusted by the specified formula to those using international standard serum (IFCC/CRM470) in this study. The results of this study showed the highest levels of IgA/C3 ratio in patients with IgA nephropathy. The serum IgA/C3 ratio appears to gradually increase according to the prognostic grading of this disease. Therefore, measurement of the serum IgA/C3 ratio may be useful for prediction of diagnosis and prognostic grading in patients with IgA nephropathy.
Expression of Angiopoietin-1, Angiopoietin-2, and Tie2 Genes in Normal Ovary with Corpus luteum and in Ovarian Cancer
Authors: Hata Kohkichi , Udagawa Jun , Fujiwaki Ritsuto , Nakayama Kentaro , Otani Hiroki , Miyazaki Kohji
Published: April 2003

Objective: The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation. Ang1 and Ang2 bind with similar affinity to the endothelial cell tyrosine kinase receptor Tie2. Our purpose was to assess the potential role of the Ang/Tie2 system in physiological and pathological angiogenesis in the ovary. Methods:Ang1, Ang2, and Tie2 gene expression in 14 normal ovaries with corpus luteum (CL) and in 19 cases of ovarian cancer were analyzed by polymerase chain reaction of RNA after reverse transcription. The level of each gene expression was presented by the relative yield of each gene to the β2-microglobulin gene, respectively. Furthermore, cellular distribution of Ang1 and Ang2 mRNA was examined by in situ hybridization, and localization of Tie2 was studied by immunochemistry. Results: The Ang1, Ang2, and Tie2 gene expression in normal ovary with CL ranged from 0.18 to 1.06 (median 0.54), 0.31–2.64 (median 1.01), and 0.10–0.47 (median 0.20), respectively. The expression of these same genes in ovarian cancer ranged from 0.06 to 0.75 (median 0.14), 0.69–1.59 (median 1.12), and 0.04–0.35 (median 0.15), respectively. Ang1 gene expression in normal ovary with CL was significantly higher than that in ovarian cancer (p = 0.0004). The gene expression levels of Ang2 and Tie2 were statistically the same in both groups. There was a significant correlation between Ang1 gene expression and Tie2 gene expression in normal ovary with CL (r = 0.619, p = 0.018). No such significant correlation was found in ovarian cancer. Moreover, Ang2 gene expression showed no significant correlation with the Tie2 gene expression either in normal ovary with CL or in ovarian cancer. Transcripts for Ang1 were observed in CL cells and endothelial cells around CL, and in tumor cells and endothelial cells at the periphery of tumor invasion. Ang2 transcripts were expressed in the same patterns. Tie2 expression was positive primarily in the endothelial cells around CL and in those at the periphery of tumor invasion. Conclusion: Our results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. This finding may aid in the development of new therapeutic interventions for ovarian cancer.
Proliferation of Myofibroblasts in the Stroma of Epithelial Hyperplastic Lesions and Squamous Carcinoma of the Larynx
Authors: Zidar Nina , Gale Nina , Kambič Vinko , Fischinger Janez
Published: April 2003

Objectives: The immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts in laryngeal epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) were analyzed. Methods: Samples of 42 resected larynxes and 40 laryngeal biopsies of EHL and SC were included. Immunohistochemistry was performed using antibodies against vimentin, α-smooth muscle actin (SMA), desmin and leukocyte common antigen. Results: Myofibroblasts were vimentin- and SMA-positive, and were found exclusively in SC, indicating that invasion beyond the basement membrane is necessary to evoke a myofibroblastic stromal reaction. We observed two patterns of stromal reaction in SC: one was characterized by a marked proliferation of myofibroblasts and desmoplasia, with scarce lymphocytic infiltration; this pattern tended to be associated with well- or moderately differentiated SC. The other was characterized by few myofibroblasts, weak desmoplasia, and dense lymphocytic infiltration; the latter pattern tended to be associated with moderately or poorly differentiated SC. The degree of myofibroblast proliferation was inversely related to the density of lymphocytic infiltration. Antibodies against SMA also stained stromal blood vessels, demonstrating a gradual increase of vessel density as the grade of EHL increased. Conclusions: Immunohistochemical analysis of myofibroblasts provides useful information on the phenotypic characteristics of the stroma in laryngeal EHL and SC, and can serve as an additional marker of invasion.
Home Treatment of Deep Vein Thrombosis
Authors: Lapidus Leif , Börretzen Jens , Fahlén Martin , Thomsen Hans Grönlund , Hasselblom Sverker , Larson Lars , Nordström Henrik , Stigendal Lennart , Waller Lotte
Published: April 2003

During a 22-month period, 555 consecutive patients at seven hospitals in the western part of Sweden with an acute deep vein thrombosis (DVT) not involving the iliac vein and not having pulmonary embolism were included in a study testing the efficacy of implementing out-patient treatment. For all patients with a confirmed diagnosis of acute DVT, a folder was used that contained two checklists with detailed instructions for further treatment, one for the doctor and one for the nurse, an information pamphlet for the patient and prepared prescriptions for low-molecular-weight heparin (LMWH) tinzaparin (Innohep®) of 175 anti-Xa IU/kg body weight subcutaneously once daily and warfarin. Patients not requiring hospitalisation, according to strict guidelines, were then eligible for treatment as out-patients. Prior to release from the emergency department for home treatment, a nurse provided detailed information to the patient and administered the first tinzaparin injection. In 194 (35.0%) out of 555 patients, the DVT was localised only in the lower leg not reaching the popliteal vein. Factors predisposing to venous thromboembolism were identified in 35.0% of the patients. 332 (59.8%) out of the 555 patients studied did not require hospitalisation and were therefore treated as out-patients. 140 of these patients (42.2%) injected themselves, the injection was given by a relative in 63 (19.0%) patients and by the community nurse in 129 (38.9%). Six (1.8%) patients reported a worsening of the DVT condition during the LMWH treatment period. No major bleedings were observed during the injection treatment period. Except for local minor skin bleedings at the injection site, only 3 (0.9%) patients reported minor bleedings during the injection treatment period. Recurrences of venous thromboembolism during the first 2 months were reported in 9 patients (2.7%) out of 332 patients who were sent home from the emergency department. Five (2.2%) patients out of the 223 who were admitted to the hospital had an increased tendency to bleeding. Twelve patients (5.4%) were hospitalised because of a pronounced local status, 26 (11.7%) were senile, social factors were the reason for hospitalisation in 76 (34.1%) and lack of time of the physician in 39 (17.5%) of the patients. A pharmacoeconomic analysis found a cost reduction of 69% with the present model for home treatment compared with traditional in-hospital treatment of DVT patients. We conclude that tinzaparin can be safely used at home by patients with DVT below the inguinal region and that the model used in the present study is cost-effective.
Medulloblastoma in a Child with the Metabolic Disease L-2-Hydroxyglutaric Aciduria
Authors: Özışık Pınar Akdemir , Akalan Nejat , Palaoğlu Selçuk , Topçu Meral
Published: April 2003

L-2-Hydroxyglutaric aciduria (LHGA) is a rare autosomal recessively inherited neurodegenerative disorder. It is characterized by psychomotor retardation, progressive ataxia and typical magnetic resonance imaging findings, and presents in early infancy. On the other hand, medulloblastomas are very common solid tumors of childhood and infancy. We present a 3-year-old boy with LHGA who developed a medulloblastoma during the course of the disease. There has been no previous report of the coexistence of medulloblastomas with LHGA. Central nervous system tumors are encountered in children with other metabolic neurodegenerative disorders. The aim of this paper is to focus on the difficulties in the diagnosis and treatment of an intracranial tumor in a child already neurologically impaired due to metabolic neurodegenerative disease.
Posterior Fossa Ependymoma with Intense but Transient Disseminated Enhancement but Not Metastasis
Authors: Butler William E. , Khan Asad , Khan Saad A.
Published: April 2003

We report a pediatric patient with a posterior fossa ependymoma in whom the second of two magnetic resonance imaging (MRI) scans obtained preoperatively within a 10-day span showed intense but transient disseminated enhancement. However, following posterior fossa craniotomy for near total tumor resection, neither three MRI exams nor two craniospinal fluid samplings revealed evidence of disseminated disease. Concerned that the one MRI with disseminated enhancement indicated an elevated risk of leptomeningeal metastasis, we initiated craniospinal irradiation. However, we terminated this treatment after realizing that the bulk of the clinical evidence refuted the diagnosis of metastatic disease.
Carpal Tunnel Syndrome in a 28-Month-Old Child
Authors: Musharbash Awni
Published: April 2003

We report a 28-month-old male child, known to have Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI), who presented with inconsistent right hand discomfort. Clinical suspicion of right carpal tunnel syndrome was confirmed by nerve conduction and electromyographic studies, and a decompressive procedure was done with uneventful recovery. Carpal tunnel syndrome in mucopolysaccharidosis patients should be suspected, diagnosed and treated early for better outcome.
Endoscopically Assisted Retrieval of an Intracranial Air Gun Pellet
Authors: Mohanty Aaron , Manwaring Kim
Published: April 2003

Intracranial missile injuries often lodge in deep and inaccessible areas of the brain and are sometimes difficult to remove. Many such missiles are left behind for the fear of surgical morbidity. The authors report the successful removal of a deep-seated intracranial air gun pellet with the aid of an endoscope. A 4-year-old child was admitted after being injured by an air gun pellet in the left forehead. He had no neurological deficits. Cranial CT scan revealed evidence of a pellet lodged in the left frontal region with small bone fragments driven into the adjacent parenchyma. The patient underwent a left frontal craniotomy around the entry wound and debridement of the bone fragments. The track was explored carefully with the aid of a rigid fiberscope and the pellet was identified and removed easily. Postoperatively, the patient had an uneventful recovery. Endoscopic retrieval of the projectile by following the track may be considered a reasonable alternative in suitable cases. This might be useful in retrieving deep-seated missiles.
WHO Perspectives on International Classification
Authors: Üstün T. Bedirhan
Published: April 2003

The classification of mental disorders improved greatly in the last decade of the 20th century and now provides a reliable operational tool. Both the ICD and DSM classifications have greatly facilitated practice, teaching and research by providing better delineation of ‘syndromes’ (i.e. clustering commonly seen symptoms together). The absence of aetiological information linked to brain physiology that could serve as the basis of independent definitional variables has limited understanding of mental illness and has been a stumbling block to the development of better classifications. The use of a universal classification for differing cultures has also raised concerns about a lack of sensitivity to local diversity, especially as human behaviour is not always context free. Given these limitations and the expectations of scientific advances in the field of genetics, neurobiology and cultural studies, we should be able to build better classifications based on an international consensus informed by evidence-based research.
Diagnosis and Classification in Child and Adolescent Psychiatry: The Case of Unipolar Affective Disorder
Authors: Kolvin Israel , Trowell Judith
Published: April 2003

Child and adolescent psychiatric classification is a broad domain in which the consideration of a developmental and longitudinal approach is essential. Some of the key issues involved are reviewed in this paper by focusing attention on childhood affective disorders, which are important both clinically and epidemiologically. It has been argued and demonstrated by Kovacs that in contrast to adults, children may not be capable of experiencing or reporting the symptoms thought to be representative of major depressive disorder. Nor may they be able to give an account of their duration. Hence, the pattern of manifested depressive symptoms is likely to vary according to age and stage of development of the child and young adolescent, and this is probably related to concept and language development. Further, distress and negative affect may be expressed by externalising symptomatology, especially in the pre-school years. The complexity of multiple depressive disorders, their coexistence and comorbidity with anxiety disorders needs to be studied further, employing whenever possible a developmental perspective and a longitudinal design.
Experience with Current Multiaxial Diagnostic Systems: A Critical Review
Authors: Kastrup Marianne
Published: April 2003

It is difficult to capture the complexity of the psychiatric condition with a single diagnostic category, and a multiaxial approach provides a more comprehensive picture of the current disorder. The WPA section on classification has developed a multiaxial schema based on the ICD-10 family of classifications. Four axes are proposed. Axis I: on clinical disorders; axis II: on disabilities; axis III: on contextual factors, and axis IV: on quality of life. Even though the multiaxial approach has been widely taught and surveys report on its international acceptability, daily use by clinicians of the ‘non-diagnostic’ axes have till now been limited, despite expressed interest by the very same clinicians. The multiaxial formulation is still developing and transcultural experiences need to be gained.
Psychological Perspectives for the Development of Future Diagnostic Systems
Authors: Mundt Christoph
Published: April 2003

Psychological aspects of classification broadly refer to mental functions and dysfunctions and are important to consider both in terms of clinical use and the elucidation of pertinent theories. There are a number of concepts crucial to consider for psychologically informed classification, including personality structure, temperament, psychodynamic psychiatry, functional psychopathology, basic symptoms, anthropological phenomenology and health psychology. In future diagnostic systems, one must critically consider objective measurement and subjective experience, as well as categorical and dimensional measurement. It would also be important to articulate the clinical mental phenomenon, its interpretation and experimental findings as well as to consider the influence of a classification system on the public image of a disorder and a person.
Chinese Classification of Mental Disorders (CCMD-3): Towards Integration in International Classification
Authors: Chen Yan-Fang
Published: April 2003

The CCMD-3 Task Force has prepared and completed field trials for the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It has also worked on the Treatment and Nursing of Mental Disorders Relevant to CCMD-3, and the Rating Test for Health Problems and Diseases as a set of relevant diagnostic scales and software. From 1996 to 2000, the CCMD-3 Task Force has been actively engaged in prospective follow-up field trials aimed at improving the classification and diagnostic criteria of mental disorders in China. A total of 114 psychiatrists from 41 mental health centers and psychiatric hospitals carried out the trials, considering for the 17 adult mental disorders, and 7 mental disorders with onset usually occurring in childhood and adolescence. Based on the results of the field trials, the Task Force has finalized the CCMD-3. Throughout the phase of initial drafting, each item in CCMD-3 was compared with the corresponding item in the CCMD-2R, and the descriptive definitions were based on the Clinical descriptions and diagnostic guidelines of ICD-10. The diagnostic criteria also refer to the Research Criteria of ICD-10, and the DSM-IV. Following the decision made by the Chinese Psychiatric Association, CCMD-3 has been published as diagnostic guidelines to be used by all psychiatrists across the country.
Mammadiagnostik: Neue Erkenntnisse und Entwicklungen
Authors: Haller U. , Hepp H. , Winter R.
Published: April 2003

Die Entwicklung und Verfeinerung der Mammadiagnostik hat dazu geführt, dass die Mammasonographie an Bedeutung gewonnen hat, dass die mammographischen Klassifikationskriterien (BI-RADS) entwickelt wurden und die Terminologie für die Befundung vereinheitlicht und codierbar wurde. Gezielte stereotaktische Mammabiopsien (Stanz- und Schneiderohrbiopsie) nehmen heute einen festen Platz in der prätherapeutischen Diagnostik ein.
General Practitioners and Predictive Genetic Testing for Late-Onset Diseases in Flanders: What Are Their Opinions and Do They Want to Be Involved?
Authors: Welkenhuysen M. , Evers-Kiebooms G.
Published: April 2003

Objective: Investigate the attitudes of general practitioners (GPs) concerning predictive testing for late-onset diseases, as well as the perception of their own role in this context. Methods: 356 GPs received mail questionnaires with telephone pre-notifications and reminders. Results: The questionnaire was returned by 60% (n = 215). The GPs’ attitudes toward predictive testing for breast cancer, thyroid cancer, Alzheimer disease and Huntington’s disease were influenced by the availability and the type of preventive and therapeutic options, the age of onset of the disease as well as by ethical concerns. Regarding a possible task for GPs, most of the GPs focussed on gate-keeping aspects, such as providing information and making referrals. Conclusion: The GPs were supportive of a limited role for general practice in predictive testing. Genetic education for GPs is needed, with attention to non-directiveness and the characteristic psychosocial and ethical implications of this particular type of genetic testing.
A Functional Study on CysLT1 Receptors in Human Eosinophils
Authors: Ohshima Nobuharu , Nagase Hiroyuki , Koshino Takeshi , Miyamasu Misato , Yamaguchi Masao , Hirai Koichi , Yamamoto Kazuhiko , Fujisawa Takao , Nakagawa Naoki , Kishikawa Katsuya , Morita Yutaka
Published: April 2003

Background: The cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors: CysLT1 receptor and CysLT2 receptor. Objective: This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT1. Methods: Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity >99%). They were subjected to reverse transcription-PCR analysis and flow-cytometric analysis for CysLT1. Binding assays were performed with [3H]LTD4. Purified eosinophils loaded with Fura-2 acetoxymethyl ester were stimulated with CysLTs, and Ca2+ influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD4 at 10–6M for 60 min followed by incubation for 4 h at 37°C in the presence or absence of IL-5 and eosinophil-derived neurotoxin (EDN) release was evaluated. Results: The expression of the mRNA and protein of CysLT1 on eosinophils and [3H]LTD4-specific binding to eosinophils were observed. Neither Th1 cytokine (IFN-γ) nor Th2 cytokines (IL-4 or IL-5) affected CysLT1 expression in eosinophils. CysLTs induced an increase in intracellular free Ca2+ in eosinophils via CysLT1, as suggested by the efficient inhibition by a CysLT1 antagonist, pranlukast, in addition to the rank order of potency being LTD4, LTC4 and LTE4. LTD4 stimulated eosinophils to migrate at 10–6M via CysLT1. LTE4 also induced significant eosinophil migration at 10–6M. LTD4 enhanced EDN release induced by IL-5 via CysLT1. Conclusion: CysLTs induce migration and enhance degranulation in eosinophils via CysLT1. Accordingly, interaction of CysLTs and CysLT1 on eosinophils has the potential to play a prominent role in the pathophysiology of asthma.
Alteration of Locus coeruleus Neuronal Activity by Interleukin-1 and the Involvement of Endogenous Corticotropin-Releasing Hormone
Authors: Borsody Mark K. , Weiss Jay M.
Published: April 2003

Activity of the locus coeruleus (LC), which is the source of most of the norepinephrine in the brain, may participate in effects of the cytokine interleukin (IL)-1. This report describes the influence of IL-1β on the electrophysiological single-unit activity of LC neurons. When microinjected into the LC, human recombinant IL-1β (50 pg to 5 ng) increased the activity of LC neurons, predominantly by increasing ‘burst’ firing, which occurs in response to a sensory stimulus. At the higher doses and/or with longer time delays after injection, the spontaneous depolarization rate was also increased. This excitation (1) did not occur if IL-1β was microinjected nearby but outside of the LC and (2) could be reversed by administration of IL-1 receptor antagonist (IL-1RA). In contrast to excitatory effects, microinjection of a very low dose of IL-1β (5 pg) into the LC inhibited LC activity, and this change could also be blocked by IL-1RA. In view of earlier findings that (1) LC electrophysiological activity could be inhibited by microinjection of corticotropin-releasing hormone (CRH) into the LC region and (2) IL-1β in the brain stimulates the release of CRH, the hypothesis was tested that the inhibition of LC activity produced by the low dose of IL-1 was mediated by CRH. Microinfusion of the CRH receptor antagonist α-helical CRH(9–41) blocked the inhibition of LC activity otherwise produced by 5 pg of IL-1β, thus indicating that IL-1β also influences the activity of LC neurons via CRH. Finally, microinjection of IL-1RA alone was found to decrease LC activity, raising the possibility that LC neurons are under the influence of tonic excitation by IL-1 in the brain. In summary, the findings described here show that the activity of LC neurons can be influenced by IL-1β through stimulation of IL-1β receptors. The potential involvement of IL-1β in stress responses by means of this cytokine influencing the activity of LC neurons is discussed.
Thermal Response to Zymosan: The Differential Role of Complement
Authors: Li Shuxin , Llanos-Q Jose , Blatteis Clark M.
Published: April 2003

Objectives: This study was designed to determine whether the complement (C) system may be involved in the febrile response to zymosan (Zym), a glycan derived from yeast cell walls. Methods: Cobra venom factor (CVF) at 100 U/animal or its vehicle, pyrogen-free saline (PFS), was injected intravenously (i.v.) into guinea pigs to deplete serum C. Eighteen hours later, a low or high dose of Zym or its vehicle, PFS, was administered i.v. or intraperitoneally (i.p.) to these animals. The core temperature (Tc) was measured continuously by thermocouples. Serum C levels were determined by sheep erythrocyte hemolytic assay. Results: Zym at 1 mg/kg caused a 1°C Tc rise that was not significantly affected by CVF pretreatment. However, CVF-induced hypocomplementation converted the Tc fall (∼1.2°C) produced by 100 mg/kg of Zym i.p. into a 1°C Tc rise. Similarly, CVF pretreatment did not affect the Tc rise caused by 0.5 mg/kg of Zym i.v., but converted the Tc fall induced by 25 mg/kg i.v. into a 1°C Tc rise. A separate experiment showed that 25, but not 0.5 mg/kg of Zym i.v., decreased serum C by 34% in 15 min; C did not recover over the next 6 h. A second i.v. injection of 25 mg Zym/kg 210 min later, when the Tc had recovered but the serum C had not, yielded a smaller and briefer Tc fall. Conclusion: These results suggest that Zym is inherently pyrogenic, but this effect is manifested only when the dose of zymosan is too small to activate C or when C has been reduced by prior activation.
Estimation of Creatinine Clearance in Patients with Unstable Renal Function, without a Urine Specimen
Authors: Jelliffe Roger
Published: April 2003

Background: There is a significant need to estimate creatinine clearance easily in acutely ill patients with unstable renal function, who have rapidly changing serum creatinine values and who need careful individualization of drug dosage, all without the problems associated with having to collect the traditional carefully timed urine specimen. Method: The daily change in the total amount of creatinine is the difference between its production and excretion. Production is estimated based on studies by others, using many carefully timed urine specimens. Daily creatinine production is related both to age and to the serum creatinine concentration. Urinary excretion of creatinine is equal to creatinine clearance times the average of a pair of timed serum creatinine concentrations, times the duration of the collection (usually 24 h). Results: Good correlation was found between conventional measured creatinine clearances and the estimated values. The estimates had a precision essentially equal to that of the traditional method. Conclusions: One can now estimate the creatinine clearance which makes serum creatinine change from an initial concentration at one stated time to another concentration at another stated time, for a patient of a stated age, gender, height and weight, without requiring a urine specimen. This method has been incorporated into software to perform the calculations easily and rapidly, and has been integrated into the USC*PACK PC programs for planning, monitoring and adjusting individualized dosage regimens of drugs.
Sex Difference of Urinary Osmolality in German Children
Authors: Ebner Arno , Manz Friedrich
Published: April 2003

Background/Aims: Origin of sex difference in urinary osmolality. Methods: In 495 healthy children aged 4.0–14.9 years participating in the DONALD (Dortmund Nutritional and Anthropometric Longitudinally Designed) study (247 boys, 248 girls), the water intake recorded in 24-hour weighed dietary records along with urinary volume, osmolality and free water reserve in 24-hour urine samples from the same day as the dietary record were determined. Results: Boys showed a significantly higher energy intake, total water intake, urinary osmolality and osmolar load than girls but no increase in urinary volume. When referred to energy intake, mean urinary volume and mean free water reserve were significantly higher in girls than boys. Girls could have a preference for food with a higher water density and lower non-renal water losses. Conclusion: German girls of the DONALD study displayed a lower urinary osmolality than German boys due to a relatively higher urinary volume. The sex difference could be caused by a higher water density of the ingested food (ml/kcal) and a lower insensible water loss (ml/kcal) in girls than boys.
Dermatomyositis Associated with Membranous Nephropathy in a 43-Year-Old Female
Authors: Akashi Yoshihiro , Inoh Masayuki , Gamo Naoyuki , Kinashi Makoto , Ohbayashi Seiichi , Miyake Hayashi , Kurata Noriyuki
Published: April 2003

A 43-year-old woman was admitted to our hospital for myalgic pain and erythema of the face and thighs. She had been diagnosed with dermatomyositis at another hospital 8 years earlier and proteinuria had developed suddenly. Renal histological examination revealed membranous nephropathy. Membranous nephropathy associated with dermatomyositis is very rare. To date, malignant disease has not been detected in our patient, but the serum level of CA125, a tumor marker, has been elevated to 1,097 U/ml. The increased CA125 level is related to the degree of proteinuria and after prednisolone and cyclosporine therapy, proteinuria and the CA125 level gradually decreased.
Cytokine Release Pathway in Mononuclear Cells Stimulated in vitro by Dialysis Membranes
Authors: Menegatti Elisa , Rossi Daniela , Chiara Marica , Alpa Mirella , Sena Luigi M. , Roccatello Dario
Published: April 2003

Background: Among the possible variables associated with cytokine activation in hemodialysis, filter membrane has been reported to be a major factor and monocytes adherent to the membrane have been suggested as a possible source for cytokine synthesis. Methods: In order to exclude variables other than the direct cell-to-membrane interaction, suspensions of peripheral blood monocytes isolated from donors’ blood were incubated for 180 min at 37°C in Petri dishes coated with cuprophan (Cu) or polyacrylonitrile (AN69S) or polysulfone (PS). Total RNA was purified, reverse transcribed in cDNA and amplified by polymerase chain reaction (PCR) primed with specific oligomers for determining IL-1β and TNF-α gene expression. For Western blot analysis, cell homogenates and supernatants were electrophoresed and transferred to a polyvinylidene difluoride membrane and the membrane was then incubated with polyclonal antibodies specific for the detection of IL-1β and TNF-α. Results: Semi-quantitation of targets for PCR (using the technique of limiting dilutions and referring to actin and glyceraldehyde-3-phosphate dehydrogenase as noninducible molecule) revealed a comparable increase at 180 min (p < 0.05) in IL-1β and TNF-α mRNA in monocytes incubated with polyacrylonitrile, PS and Cu membranes. In 2 of 10 experiments pro-IL-1β was detected in monocytes interacting with Cu, PS and AN69S membrane. However, the extent of extracellular release of mature protein was greater for Cu. Conclusion: Some dissociation between transcriptional and translational events was detected in experiments using donors’ blood in vitro. More specifically, synthetic membranes (both polyacrylonitrile and PS) were found to be as active as Cu in inducing IL-1β and TNF-α mRNA expression, but less effective in promoting the extracellular release of proinflammatory cytokine products.
Friedrich Theodor von Frerichs (1819–1885) and Bright’s Disease
Authors: Wolf Gunter
Published: April 2003

Background: Richard Bright (1789–1858) discovered that edema and proteinuria are linked with renal disease. Friedrich Theodor von Frerichs (1819–1885) performed microscopic studies on Bright’s disease and wrote the first German textbook of nephrology. The present contribution analyzes Frerichs’ work. Methods: Frerichs’ career and his book Die Bright`sche Nierenkrankheit und deren Behandlung are examined in terms of contemporary medical knowledge. Results: Frerichs conducted clinical and microscopic studies that led him to conclude that Bright’s disease is a single pathological entity with many possible causes. Frerichs identified three stages through which the condition progresses. Although an oversimplification, Frerichs’ various stages are reflected in the current notion that chronic renal disease, irrespectively of its etiology, relentlessly progresses to end-stage renal failure with common features of tubulointerstitial fibrosis and tubular atrophy. After writing his monograph, Frerichs never touched on renal disease again and is actually better known for his contributions to hepatology. Frerichs was a volatile and difficult person who was not always fair to his students and colleagues. Conclusion: Frerichs put the study of renal diseases on the map in Germany and made the novel observation that chronic renal diseases follow similar morphological patterns despite multiple origins.
Torsion of a Lumbar Nerve Root Schwannoma
Authors: Khoshyomn Sami , Barth Konrad N.M. , Christman Robert A. , Braff Steven P. , Wilson James T.
Published: April 2003

We report a very rare case of a lumbar nerve root schwannoma presenting with torsion and infarction. The patient was a 16-year-old male presenting with severe low back pain and urinary retention following an aggressive game of hockey. Subsequent MRI of the lumbar spine revealed a nonenhancing lumbar intradural lesion at the level of L3. The patient was taken to the operating room where he underwent a bilateral L2 and L3 laminectomy and gross total resection of an intradural nerve root tumor, which appeared to have undergone torsion and infarction. Subsequent histopathological examination of the surgical specimen verified the diagnosis of infarcted schwannoma. This is a unique case of lumbar nerve root schwannoma, with atypical MRI findings, presenting with infarction due to torsion of the involved nerve root.
Social Thermoregulation in Redfronted Lemurs (Eulemur fulvus rufus)
Authors: Ostner Julia
Published: April 2003

Pronounced seasonality, with temperatures dropping as low as 5°C during the dry season, has led to the hypothesis that Malagasy lemurs face cold stress and respond to this by inactivity and social thermoregulation, i.e. resting in tight body contact with conspecifics. Compared to anthropoids, lemur groups are comprised of an unusually high number of males, leading to an even or slightly male-biased adult sex ratio. According to one hypothesis, females may benefit from these surplus males in their groups if males huddle with females. The results of this study on redfronted lemurs (Eulemur fulvus rufus) in Kirindy Forest, Madagascar revealed that the animals indeed responded to cold ambient temperatures by increased inactivity and the formation of huddling groups. However, surplus males did not participate more frequently than expected in huddling groups with females and females do not, therefore, benefit from the high number of males in their groups by increased social thermoregulation.
Social Behaviour of the Slender Loris (Loris tardigradus lydekkerianus)
Authors: Radhakrishna Sindhu , Singh Mewa
Published: April 2003

The social behaviour of the nocturnal prosimian Loris tardigradus lydekkerianus in its natural habitat was studied for 21 months in a scrub jungle in Dindigul, southern India. A total of 22,834 scans were collected during 2,656 hours of observation on identified and unidentified lorises. Social interactions were observed between individuals of all age-sex classes, both during the night and at dawn, when the animals met to sleep together. The majority of aggressive encounters between individuals occurred in territorial and mating contexts. Individuals also communicated with each other through chemical and vocal signals. Adults and sub-adults of both sexes were observed to immigrate into the study area, leading to social interactions with resident individuals.
A Biomechanical Analysis of Skull Form in Gum-Harvesting Galagids
Authors: Williams Susan H. , Wall Christine E. , Vinyard Christopher J. , Hylander William L.
Published: April 2003

Among primates, some highly gummivorous species habitually gouge trees to elicit exudate flow whereas others scrape the hardened gums from trees. These foraging behaviors are thought to require high external forces at the anterior dentition. In this study, we test whether skull form in gouging and scraping galagids corresponds to this suggested need to produce these higher external forces and to resist increased internal loads in the jaws. We find few consistent morphological patterns linking skull form and the generation of high forces during gouging. However, there is some tendency for gougers and scrapers to show increased load resistance capabilities in their mandibles. Future research on the mechanical properties of trees exploited by these species and on jaw function during gouging and scraping will improve our understanding of the mechanical demands of gum feeding on the galagid skull form.