bluuebunny/crossref_metadata_2025 huggingface dataset:
Endarterectomy for Carotid Stenosis: New Approaches in Patient Selection
Authors: Barnett H.J.M. , Meldrum H.E.
Published: April 2003

Results of randomized trials on carotid endarterectomy make it mandatory that therapeutic decisions for patients with carotid stenosis consider the degree of stenosis, presence of symptoms, skill of surgeon and time since the last ischemic event. Patients with severe (>70% by angiogram) stenosis should receive carotid endarterectomy, provided the operative risk is <6% and symptoms have recurred within 6 months. With moderate stenosis (50–69% by angiogram), and with similar low operative risk and time limit, males with hemispheric, nondisabling stroke and appropriate CT lesion will benefit from carotid endarterectomy. Patients with TIA only, retinal symptoms alone and who are women are not going to benefit in this range of stenosis. Particularly at risk with medical care alone are symptomatic patients with coexistent intracranial stenosis, widespread white-matter lesions, intraluminal thrombi, contralateral occlusion and absence of good collateral circulation. The same high-risk patients, enjoy good long-term results from endarterectomy. Lacunar syndromes at presentation respond to endarterectomy, but with less benefit. Symptomatic patients do as well, regardless of age, provided patients with serious cardiac disorders and with organ failure are avoided. Serious doubt exists about indications for endarterectomy in asymptomatic subjects. Even if the upper limit of 3% perioperative risk is exceeded (and in large institutional databases and other studies, it usually is), the risk of large-artery strokes from the asymptomatic lesion is only slightly above the risk facing these subjects from lacunar and cardioembolic stroke. To prevent 1 large-artery stroke in 5 years in asymptomatic subjects requires that 111 subjects be submitted to endarterectomy.
Atherothrombosis: A Major Health Burden
Authors: Leys Didier
Published: April 2003

Atherosclerosis involves structural change to the intima and media of medium- and large-sized arteries. Although an atherosclerotic plaque may remain clinically silent, it is prone to disruption, leading to local platelet activation and aggregation. Therefore, the major complication of atherosclerosis is thrombosis, with local occlusion or distal embolism – a generalized disease process known as atherothrombosis. The three main clinical manifestations of atherothrombosis are coronary heart disease (myocardial infarction and angina), peripheral arterial disease and cerebral ischaemia. Atherothrombosis is a leading cause of mortality, and stroke is the leading cause of disability in adults, the second most important cause of dementia and the third most common cause of death in Western countries. Ischaemic stroke accounts for 80% of strokes and atherothrombosis accounts for approximately 20% of all strokes. Criteria for atherothrombotic stroke are evidence of a 50% (or greater) stenosis of a cervical artery and exclusion of other potential causes. The incidence of cerebrovascular events is 2,900 per million inhabitants per year, consisting of 500 transient ischaemic attacks and 2,400 strokes, of which 75% are first-ever stroke. The prevalence of stroke in the same population is 12,000, of which 800 patients (7%) per year have recurrences. The risk of ipsilateral stroke is 5% per year and the risk of a cardiac event is higher at 7%. Besides optimal management of risk factors for atherothrombosis and carotid surgery, antiplatelet therapy is the cornerstone of vascular prevention. In secondary prevention, antiplatelet agents are effective in reducing the risk of further ischaemic events in patients with atherothrombosis. Clopidogrel, a newly licensed ADP receptor antagonist, is the only antiplatelet agent to have demonstrated its superiority versus aspirin for the reduction of major ischaemic events (myocardial infarction, ischaemic stroke, vascular death) in patients whose initial manifestation of atherothrombosis was one of the three main clinical manifestations of the disease (recent ischaemic stroke, myocardial infarction, established peripheral arterial disease).
Established Clinical Use of Octreotide and Lanreotide in Oncology
Authors: Öberg Kjell
Published: April 2003

The diagnosis and treatment of neuroendocrine tumors have been significantly improved during the last decades. Localization and staging of the disease by somatostatin receptor scintigraphy (Octreoscan) are now the ‘gold standard’ for the management of these tumors. Treatment with somatostatin analogs has improved quality of life and possibly also survival for patients with neuroendocrine tumors. New long-acting formulations of the somatostatin analogs are as effective as the old regular formulations but will further improve quality of life for the patients. Tumor-targeted therapy with 111In and 90Y coupled to somatostatin analogs show promising results but await further studies.
IGHV3-Associated Restriction Fragment Length Polymorphisms Confer Susceptibility to Bullous Pemphigoid
Authors: Raux Grégory , Gilbert Danièle , Joly Pascal , Martel Philippe , Roujeau Jean-Claude , Prost Catherine , Lefranc Marie-Paule , Tron François
Published: April 2003

Objective: To determine whether the immunoglobulin heavy chain genes contribute to the occurrence of bullous pemphigoid (BP), polymorphisms of both the immunoglobulin constant IGHC and variable IGHV groups were studied in 100 Caucasian BP patients and 143 ethnically matched healthy individuals. Methods: To analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3 probe to EcoRI-digested DNA. Results: No difference in the frequencies of the genotypes defined by the constant probe was observed between patients and controls. Analysis of the RFLP obtained with the VH3 probe showed that within the range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different restriction patterns. One pattern was shown to be significantly less frequent in patients than in controls. Conclusion: IGHV3 polymorphism might be a factor conferring susceptibility to BP.
Gab2 Is Phosphorylated on Tyrosine upon Interleukin-2/Interleukin-15 Stimulation in Mycosis-fungoides-Derived Tumor T Cells and Associates Inducibly with SHP-2 and Stat5a
Authors: Brockdorff Johannes Lundin , Gu Haihua , Mustelin Tomas , Kaltoft Keld , Geisler Carsten , Röpke Carsten , Ødum Niels
Published: April 2003

Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.
Development of Single-Chain Fv Fragments from a Human Anti-Double-Stranded DNA Antibody to Study the Influence of Somatic Mutations on Antigen Binding
Authors: Kersten B. , Niemann B. , Jahn S.
Published: April 2003

Objective: The monoclonal IgG anti-double-stranded (ds) DNA antibody 32B9, obtained from a patient with systemic lupus erythematosus, was found to be encoded by somatically mutated immunoglobulin genes. We examined the input of several somatic mutations into antibody specificity and affinity. Methods: Five single-chain (sc) Fv fragments [variable domain of the heavy chain (VH)-linker-variable domain of the light chain (VL)] derived from 32B9 were constructed and expressed in Escherichia coli. These scFv fragments contained VH or VL fragments, differing in the somatic mutation pattern. The antigen binding features of the 32B9 IgG were compared with the corresponding scFv fragments, and the binding to DNA of all fragments was analyzed by ELISA. Binding constants to dsDNA were determined by surface plasmon resonance and ELISA. Results: The scFv 32B9 reflected the binding features of the 32B9 IgG. Independently of the somatic mutations, all scFv fragments bound to dsDNA in ELISA. The affinity data indicated that the mutations studied had only a marginal effect on affinity maturation of the 32B9. Discussion: We discuss the approach to constructing scFv fragments as a tool to study autoantibody maturation.
Oligonucleotide Fishing for STAT6: Cross-Talk between IL-4 and Chemokines
Authors: Eriksen K.W. , Nielsen M. , Kaltoft K. , Svejgaard A. , Nissen M.H. , Röpke C. , Ødum N.
Published: April 2003

Signal transducer and activator of transcription 6 (STAT6) is essential for the biological activities of interleukin-4 (IL-4) and the development of allergic responses in mice. Here we report on a sensitive and specific assay for STAT6 activation in response to IL-4. We took advantage of double-stranded oligonucleotide probes containing a STAT6-binding gene-sequence from the promotor of the immunoglobulin heavy chain germline Ε transcript to study the IL-4-induced DNA binding of STAT6. Using these probes, we show that repeated adjacent STAT6-binding sites result in enhanced STAT6-DNA binding. Moreover, the distance between the binding sites is critical for STAT-DNA binding, i.e. STAT6 binding is decreased at distances above 20 nucleotides between neighbouring binding sites. Using this assay to study cross-talk between IL-4 and chemokines, we provide evidence that MIP-1β and MIG inhibit IL-4-induced STAT6 activation, whereas other chemokines and cytokines do not. In conclusion, our data show that oligonucleotide fishing is a supplementary tool for studying cytokine cross-talk at a genomic level.
Duration of Untreated Psychosis: Are We Ignoring the Mode of Initial Development?
Authors: Møller P.
Published: April 2003

Duration of untreated psychosis (DUP) might affect the course and treatment outcome in schizophrenia significantly. Looking for potential determinants of DUP, researchers have mostly assessed the initial untreated psychosis in terms of plain duration, not developmental content. The present study provides empirical contributions to the discussion of phenomenal continuity throughout the entire untreated illness by pointing out continuous trajectories from prodrome to psychosis. In a series of 19 first-episode DSM-IV schizophrenia patients, we explore prodromal and untreated psychotic phenomena, and the data indicate that symptoms considered intrinsic to core psychosis phenomenology had attenuated antecedents in the prodromes, increasing continuously until treatment, whereas symptoms considered not intrinsic to core psychosis were characterized by fluctuations. Mode of initial psychosis development is proposed as a tentatively informative concept, comprising duration and content aspects of the initial prodrome and untreated psychosis.
Basic Symptoms and Their Contribution to the Differential Typology of Acute Schizophrenic and Schizoaffective Disorders
Authors: Fabisch K. , Fabisch H. , Langs G. , Macheiner H. , Fitz W. , Hönigl D.
Published: April 2003

One hundred and fifty male inpatients – 128 patients with DSM-IV schizophrenia and 22 patients with DSM-IV schizoaffective disorder – were investigated, over the course of their acute psychosis, on whether there were differences in the extent of basic symptoms (measured by the Bonn Scale for the Assessment of Basic Symptoms) according to their diagnostic subtype. Another aim was to find out if the diagnostic subtypes could be discriminated by means of basic symptoms and if clusters gained from basic symptoms were in accordance with the diagnostic subtypes. Differences in basic symptoms were found between the subtypes, but a clear discrimination of diagnostic subtypes by means of basic symptoms could not be achieved. There was indication that patients with prominent delusions or auditory hallucinations reported more basic symptoms than patients with exclusively prominent disorganization.
Evaluation of the Multiaxial System of ICD-10 (Preliminary Draft): Correlations between Multiaxial Assessment and Clinical Judgements of Aetiology, Treatment Indication and Prognosis
Authors: Michels Rolf , Siebel Ute , Freyberger Harald J. , Schönell Helmut , Dilling Horst
Published: April 2003

Forty-five raters in 7 German centres took part in a multicentric field trial of the multiaxial system of ICD-10, delivering a total of 488 multiaxial assessments of 12 written case summaries. In addition to the multi-axial ratings (including main and subsidiary psychiatry diagnoses, level of social dysfunctioning and psychosocial stressors), assessments were made by the raters of the aetiology, treatment indications and prognosis of the main psychiatric disorder. There were significant correlations between these judgements and the measures of the multiaxial ratings: 62% of the cases diagnosed as endogenous were assessed as having a high level of social dysfunctioning (the proportion for all cases being 50.4%) and 63.4% as having a low number of stressors (vs. 52.8% in all cases). In contrast, cases diagnosed as reactive were assessed as having a lower level of social dysfunctioning and more social stressors. Cases whose prognosis was poor showed a higher rate of comorbidity and a high level of social dysfunctioning. The results demonstrate that the multiaxial approach reflects factors important to the process of clinical treatment and decision making and delivers preliminary evidence of this system’s treatment and prognostic validity.
Lateralized Direct and Indirect Semantic Priming Effects in Subjects with Paranormal Experiences and Beliefs
Authors: Pizzagalli D. , Lehmann D. , Brugger P.
Published: April 2003

The present investigation tested the hypothesis that, as an aspect of schizotypal thinking, the formation of paranormal beliefs was related to spreading activation characteristics within semantic networks. From a larger student population (n = 117) prescreened for paranormal belief, 12 strong believers and 12 strong disbelievers (all women) were invited for a lateralized semantic priming task with directly and indirectly related prime-target pairs. Believers showed stronger indirect (but not direct) semantic priming effects than disbelievers after left (but not right) visual field stimulation, indicating faster appreciation of distant semantic relations specifically by the right hemisphere, reportedly specialized in coarse rather than focused semantic processing. These results are discussed in the light of recent findings in schizophrenic patients with thought disorders. They suggest that a disinhibition with semantic networks may underlie the formation of paranormal belief. The potential usefulness of work with healthy subjects for neuropsychiatric research is stressed.
Panic Attack as a Marker of Core Psychopathological Processes
Authors: Goodwin Renee D. , Hamilton Steven P.
Published: April 2003

Objective: The goal of this study is to test the hypothesis that panic attacks are a marker of core psychopathological processes across mental disorders and that there are distinct syndromal patterns of psychopathology associated with specific subtypes of panic attack that can be distinguished by age and associated fear at onset. Methods: Data were drawn from the National Comorbidity Survey, a community-based household sample (n = 8,098) representative of the United States adult population. Four panic subtypes were identified based on findings from clinical studies and on our hypothesis. Multivariate logistic regression models were used to identify sociodemographic characteristics, panic symptoms and mental disorder correlates of each subtype. Results: Results of multivariate logistic regression analyses identified distinct sociodemographic characteristics, panic symptoms, psychiatric comorbidity, suicidal behavior and use of services associated with early-onset and late-onset panic with and without fear/anticipatory anxiety at the first attack. Conclusions: These findings provide support for the hypothesis that panic attacks are a marker of core underlying psychopathological processes and introduce new, preliminary evidence to support the possible existence of different panic subtypes in the general population. While these results need replication, these findings suggest that the specific type of comorbidity among those with panic attacks can be predicted to a large degree by the age and associated fear/anticipatory anxiety at the onset of the panic attacks.
Quality of Early Working Alliance in Psychotherapy: Diagnoses, Relationship and Intrapsychic Variables as Predictors
Authors: Hersoug Anne Grete , Monsen Jon T. , Havik Odd E. , Høglend Per
Published: April 2003

Background: The aim of the study was the prediction of the quality of early working alliance, using possible predictors among patient pretreatment variables: diagnoses, current and past relationships and intrapsychic ones. Data arefrom the ongoing, naturalistic Norwegian Multisite Project on Process and Outcome of Psychotherapy (NMSPOP). Methods: The sample, n = 270, is recruited from 15 outpatient clinics; 61.1% of the patients have personality disorders. Alliance was assessed with the Working Alliance Inventory (WAI), and predictors include independent clinicians’ evaluations of diagnostic/interpersonal/intrapsychic characteristics and the patients’ self-reports on similar and additional variables. Results: Four of 6 hypotheses were supported: Quality of working alliance is difficult to predict, early alliance is better predicted than later, diagnostic variables do not predict quality of working alliance, but quality of both current and past relationships is associated with working alliance. In a hierarchical multiple-regression analysis, 7% variance of working alliance in the 3rd session was explained from current relationship variables, whereas alliance in the 12th session was not predicted by the same model. Intrapsychic variables predicted the therapists’ ratings of alliance, but not the patients’ ratings. Conclusion: The results are in line with previous research, and also with the theoretical model for working alliance.
An Elderly Patient with Hemophagocytic Syndrome due to Severe Mycoplasma Pneumonia with Marked Hypercytokinemia
Authors: Mizukane Ryusuke , Kadota Jun-ichi , Yamaguchi Toshiyuki , Kiya Takakazu , Fukushima Hiromichi , Nakatomi Masao , Kohno Shigeru
Published: April 2003

We present an extremely rare case of hemophagocytic syndrome (HPS) induced by fulminant Mycoplasma pneumoniae(Mp) pneumonia in an elderly adult. Erythrocytopenia and thrombocytopenia were observed in a patient with acute respiratory failure, liver dysfunction and renal failure. Mp-associated HPS was diagnosed in this case by clinical and laboratory findings, including a bone marrow aspiration specimen and serum Mp antibody titer. High serum levels of soluble interleukin-2 receptor, interleukin-6, human interleukin-10 and macrophage-colony stimulating factor were observed. Hypercytokinemia is a useful marker of disease activity and prognosis. Combined treatment with methylprednisolone and erythromycin was successful and led to a favorable outcome. Physicians should be aware of HPS as a complication in Mp infection.
The Clinical Usefulness of Salivary Progesterone Measurement for the Evaluation of the Corpus luteum Function
Authors: Ishikawa Mutsuo , Sengoku Kazuo , Tamate Kenichi , Takaoka Yasuo , Kane Marian , Fottrell Patrick F.
Published: April 2003

The present study was designed to construct reliable daily salivary progesterone profiles throughout the luteal phase to accurately evaluate the corpus luteum function. Furthermore, we investigated the clinical relevance of a simple midluteal salivary progesterone estimation for the diagnosis of luteal phase insufficiency by determining the diagnostic efficiency and cutoff values. A total of 121 women were divided into 3 groups; normal luteal function, luteal phase insufficiency and unclassified group, based on basal body temperature recordings and serum progesterone levels at 3 sampling points during the midluteal phase. Salivary progesterone values across the luteal phase of the normal luteal function group were significantly increased from day 1 to day 4, remained constant from day 5 to day 9 (mean ± SD, 318 ± 170 pmol/l on day 5, 287 ± 169 pmol/l on day 9; urinary LH surge = day 0) and decreased thereafter. Salivary progesterone concentrations in the luteal phase insufficiency group showed significantly lower values compared with those in the normal group between days 3 and 10. The cutoff values of 189 pmol/l in the midluteal phase yielded a sensitivity of 78.0% and a specificity of 76.5%. Our results suggest that daily salivary progesterone profiles during the luteal phase and a simple estimation of midluteal salivary progesterone appeared to be useful for the diagnosis of luteal phase defects.
Identification of the White Blood Cell Populations Responsible for Th1 Immunity to Trophoblast and the Timing of the Response in Women with Recurrent Pregnancy Loss
Authors: Polgar K. , Hill J.A.
Published: April 2003

Aim: The purpose of this study was to identify the white blood cell populations responsible for Th1 immunity to trophoblast as evidenced in our in vitro assays following trophoblast activation and the timing of this response. Study Design: Peripheral blood mononuclear cells (PBMC) were isolated from 32 nonpregnant women with a history of at least three prior first trimester spontaneous abortions of unknown etiology except their PBMC secreted Th1 embryotoxic cytokines in response to trophoblast stimulation. White blood cell populations were separated from PBMC by magnetic immunobeads and cultured with and without a trophoblast antigen extract. Supernatants from these cultures were added to two cell mouse embryos and after four days of culture assessment of blastocyst development was made to determine the white blood cell population responsible for embryotoxicity. In separate experiments trophoblast-activated PBMC culture supernatants were prepared over seven time points and individual Th1 cytokines (IL-2, INF-γ, TNF-α) were measured by ELISA to determine the timing of the response to trophoblast stimulation. Results: The white blood cell (CD45) populations responsible for embryotoxicity in response to trophoblast were T cells (CD3) and NK (CD56) cells. Levels of IL-2 peaked in the first 24 h of culture followed by TNF-α and IFN-γ levels which peaked at 96 h of culture. Conclusions: Our data demonstrated that the white blood cell populations responsible for embryotoxicity in our in vitro assays, were both T and NK cells. The kinetics of the cytokine response to trophoblast found in our study parallels the time course of a typical Th1 cytokine response. The profile of secreted cytokines support our hypothesis that trophoblast can produce Th1 immunity in some women with recurrent pregnancy loss that have embryotoxic effects in vitro.
Serial Assessment in Eclampsia of Cerebrohemodynamics by Combined Transcranial Doppler and Magnetic Resonance Angiography
Authors: Ikeda Tomoaki , Urabe Hirotoshi , Matsukage Syoichi , Sameshima Hiroshi , Ikenoue Tsuyomu
Published: April 2003

We used two different noninvasive methods, i.e., transcranial Doppler velocimetry and magnetic resonance angiography to serially assess cerebrohemodynamics in a patient with postpartum eclampsia. Five hours after an eclamptic seizure, a decrease in mean velocity in both middle cerebral arteries and slight angiographical spasms indicated cerebral hypoperfusion. On hospital day 8, the patient showed an increase in the mean velocity of the middle cerebral artery, accompanied by significant vasospasms. Abnormal findings were not observed on hospital day 20. These combined methods are useful in assessing cerebrohemodynamics in eclampsia.
Prediction of Pregnancy in Infertile Women with Endometriosis
Authors: Murakami Takashi , Okamura Chikako , Matsuzaki Sachiko , Terada Yukihiro , Yokomizo Rei , Noda Takahiro , Yaegashi Nobuo , Okamura Kunihiro
Published: April 2003

To estimate the probability of pregnancy in infertile women with endometriosis, two series of multivariate analyses were performed in Tohoku University Hospital. In the first series, from 1993 to 1997, 103 patients participated. The Cox proportional hazard regression model revealed a hazard ratio of 2.43 in patients with high ovarian adhesion scores. Bilateral ovarian adhesion was an important variable in anatomical factors, probably second only to bilateral tubal adhesion. In the next series, from 1998 to 1999, 23 patients were included, and the preoperative serum concentrations of cytokines, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were analyzed. Only TNF-α was selected with a forward stepwise analysis after forcing age and infertile duration. In the logistic regression model, the serum TNF-α level had a significant and negative impact on the likelihood of pregnancy.
Endometriosis and Oocyte Quality
Authors: Saito Hidekazu , Seino Tomofumi , Kaneko Tomoko , Nakahara Kenji , Toya Mayumi , Kurachi Hirohisa
Published: April 2003

Endometriosis is associated with marked subfertility and various causes for this subfertility have been previously studied. The poor quality of oocytes has been suggested as one possible cause. In this study, we evaluated the quality of oocytes by examining the status of granulosa cells surrounding the oocyte. For this purpose, we analysed the incidence of apoptosis, changes in cell cycle, and oxidative stress in the granulosa cells. Endometriosis patients had a higher apoptotic incidence, more alterations of the cell cycle, and a higher incidence of oxidative stress than patients with any of the other infertility causes (tube, male, and idiopathic factors). These changes might affect oocyte quality, and thus fertility in endometriosis patients.
Renal Effects of Essential Fatty Acid Deficiency in Hydropenic and Volume-Expanded Rats
Authors: Paixão Ana D.O. , Nunes Flávia A. , Léger Claude , Aléssio Maria L.M.
Published: April 2003

The aim of this paper was to study the effects of essential fatty acid (EFA) on fractional sodium excretion (FENa+) and renal hemodynamics in rats during hydropenia (H) and acute volume expansion (VE), successively. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured using a blood pressure transducer and a flow probe, respectively, both connected to a flowmeter. Glomerular filtration rate (GFR) was estimated by inulin clearance. The rats receiving coconut oil as only source of dietary lipids (the EFA-deficient group) presented lower levels of linoleic acid in cortex and medulla and lower body weight than the rats receiving soy oil in place of coconut oil (the control non-EFA-deficient group). During H, the EFA-deficient rats exhibited a lower level of renal vascular resistance resulting in a higher level of RBF and a higher urinary flow (V’) and FENa+, although GFR was lower than in the control group. During VE, the rats of the control group responded with increased MAP, RBF, V’ and FENa+, which were not found in the EFA-deficient group, suggesting an impaired hemodynamic adjustment in EFA deficiency. In conclusion, both experimental conditions revealed that EFA deficiency affects the renal hemodynamics.
Effect of Dilazep Dihydrochloride on Serum Cardiac Troponin T Levels in Hemodialysis Patients
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Osada Shiwori , Ugai Kazuya , Takahashi Yutaka , Tanaka Araki , Shimada Noriaki , Ebihara Isao , Koide Hikaru
Published: April 2003

Background/Aim: Cardiac troponin T is a highly sensitive marker for the detection of myocardial injury. We studied whether dilazep dihydrochloride affects cardiac troponin T levels in hemodialysis patients. Methods: Our study included 60 hemodialysis patients without symptoms of acute myocardial ischemia. We measured serum cardiac troponin T levels by the Elecsys® troponin T assay and randomized 40 hemodialysis patients with left ventricular hypertrophy (LVH) into two treatment groups: a dilazep dihydrochloride group (300 mg/day, n = 20) and a placebo group (n = 20). Treatment was continued for 12 months. Results:There were no significant differences between pre- and postdialysis cardiac troponin T levels before treatment. LVH was noted in 40 patients out of 60 hemodialysis patients (67%). Cardiac troponin T levels were significantly higher in these patients (0.23 ± 0.08 µg/l) than in hemodialysis patients without LVH (0.09 ± 0.03 µg/l). Cardiac troponin T levels were reduced from 0.24 ± 0.08 to 0.12 ± 0.06 µg/l (p < 0.01) in patients treated with dilazep dihydrochloride. There were no change in cardiac troponin T levels in patients receiving placebo (from 0.21 ± 0.08 at baseline to 0.20 ± 0.07 µg/l). Conclusion: Dilazep dihydrochloride may be effective in ameliorating myocardial damage in hemodialysis patients.
Bumm, Zweifel, Kubli und andere – Beispiele der akademischen Verflechtung zwischen der Schweiz und Deutschland
Authors: Ludwig H.
Published: April 2003

Die akademischen Verflechtungen der Frauenheilkunde in den deutschsprachigen Ländern waren vielfältig; sie reichen in die Gründungsjahre zurück und haben sich in die Gegenwart hinein fortgesetzt. Mit Deutschen auf den Lehrstühlen in Zürich, Bern und Basel oder mit Schweizern auf denen in Erlangen, Leipzig, Dresden und Frankfurt kann man belegen, dass im akademischen Bereich auf beiden Seiten kaum Vorbehalte bestanden. Die Bilanz hat sich zwar gegenwärtig wieder mehr auf die Seite der deutschen Professoren geneigt, aber die nachgezeichnete historische Linie widerspricht dem Eindruck der Einseitigkeit. Der akademische Austausch und die sich daraus ergebenden Verflechtungen werden, davon bin ich überzeugt, zu beider Nutzen fortgesetzt werden, zumal in einem Europa, das mehr und mehr zusammenwächst. Die jüngere Generation ist längst davon überzeugt. Was sie braucht, sind Vorbilder. Die genannten Hochschullehrer, insbesondere aber auch Fred Kubli, waren solche. An ihn und an die anderen, die ihm vorausgingen, wird man sich erinnern müssen, wenn immer man in unserem Fach darauf stösst, dass die Wissenschaften international sind und global vernetzt bleiben müssen. Auch der zuletzt genannte Fred Kubli wird seinerseits Nachfolger haben. Mögen sie so gut sein, wie die Vorgänger es waren.
How to Deal with Polarized Th2 Cells: Exploring the Achilles’ Heel
Authors: Smits Hermelijn H. , Hilkens Catharien M.U. , Kalinski Pawel , Kapsenberg Martien L. , Wierenga Eddy A.
Published: April 2003

The central effector cells in the pathogenesis of atopic allergic diseases are type 2 T helper (Th2) cells, which display an aberrant cytokine profile dominated by type 2 cytokines. Initial reports from mouse studies indicated that established and committed Th2 cells are stable and unsusceptible to modulation. However, there is a growing awareness that in humans, established effector Th2 cells are more flexible and can be reverted to predominant Th1 phenotypes. In fact, the Th1-driving cytokine interleukin (IL)-12 is the crucial factor in this respect. IL-12 is mainly produced by dendritic cells (DC), which can be primed for high or low IL-12 production, depending on inflammatory and/or microbial signals they encounter during their residence in the peripheral tissues. Accordingly, both the regulation of and the priming for IL-12 production in DC form ideal targets for therapeutic intervention. The development of new therapies for atopic allergy now focuses on local IL-12-promoting substances to target both the development of new Th2 cells and the persistent population of established allergen-specific Th2 cells.
Equal Allergenic Potency of Beta-Lactam Antibiotics Produced by Chemical or Enzymatic Manufacturing – Mouse IgE Test
Authors: Coenen T.M.M. , Ratajczak H.V.
Published: April 2003

Background: Cephalexin and amoxicillin are semisynthetic β-lactam antibiotics with a broad spectrum of antibacterial activity against gram-positive and gram-negative microorganisms. Both antibiotics are produced by a new ‘green’ process in which enzyme technology is used to combine the intermediate structure and the side chain in an aqueous medium to yield cephalexin or amoxicillin, thus avoiding the use of several chemical reagents and volatile organic solvents. As a result of the enzyme technology a new residual protein impurity has been identified. To check for the sensitizing capacity of the residual protein, a mouse IgE test was used to detect differences in the production of specific IgE by chemical or enzymatic preparations of the antibiotics. Methods: Balb/c female mice were immunized intraperitoneally with alum and conjugates of different amoxicillins or cephalexins with ovalbumin (OVA). After 16 days, the amoxicillin mice were injected with one half the original amount of antigen. After 19–23 days, the sera were tested for specific IgE by the passive cutaneous anaphylaxis assay in Sprague-Dawley rats. The greatest dilution of sera which resulted in a positive response was the titer of specific IgE. Results: No significant differences were found between the titers of specific IgE caused by the chemically and enzymatically produced β-lactam antibiotics, indicating that the antibiotics are equal in allergenicity. Conclusions: The data show that a residual level of 35 ppm protein did not affect the allergenic potency of these β-lactam antibiotics as determined by the mouse allergenicity model.
The Prevalence of Parasite Infestation and House Dust Mite Sensitization in Gabonese Schoolchildren
Authors: van den Biggelaar Anita H.J. , Lopuhaa Christa , van Ree Ronald , van der Zee Jaring S. , Jans Judith , Hoek Annet , Migombet Brigitte , Borrmann Steffen , Luckner Doris , Kremsner Peter G. , Yazdanbakhsh Maria
Published: April 2003

Background: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. Methods: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. Results: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Conclusions: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.
Role of the IgE-Mediated System in Eosinophil Recruitment Triggered by Two Consecutive Cycles of Sensitisation and Challenge in Rats
Authors: Calheiros Andreia Surrage , Aguiar Pires Ana Lucia , Pereira da Silva Juliane , Balão Cordeiro Renato Sérgio , Martins Marco Aurélio , Ramos Lima Marcia Coronha
Published: April 2003

In this study, we postulated that repeated cycles of IgE passive sensitisation and antigen challenge may play a role in up-regulating eosinophil response in allergic conditions. Antigen-mediated stimulation of the pleural cavity of rats passively sensitised with a single injection of IgE anti-DNP resulted in mast cell degranulation, increase in vascular permeability and mild neutrophilia, but no pleural eosinophilia. In contrast, a second cycle of sensitisation and challenge, performed within 7 days, showed a marked eosinophilia in parallel with a lower plasma leakage and comparable neutrophilia. The eosinophilic phenomenon was not reproduced when (1) IgE sensitisation or antigen challenge was omitted in the first cycle, or (2) the first cycle was replaced by either a histamine and 5-HT dual challenge or a PAF challenge. Furthermore, we found an increase in eotaxin levels in animals subjected to two rather than one cycle of sensitisation and challenge. Treatment with the PAF receptor antagonist BN 52021 or with the lipoxygenase inhibitor zileuton, but not mast cell granule depletion, prevented the allergen-evoked eosinophil accumulation in rechallenged animals. Our results indicate that repeated cycles of IgE-driven inflammation may lead to eosinophil accumulation in a mechanism dependent on eotaxin, PAF and leukotrienes.
Seroma Prevention by Using Corynebacterium parvum in a Rat Mastectomy Model
Authors: Tekin E. , Kocdor M.A. , Saydam S. , Bora S. , Harmancioglu O.
Published: April 2003

Seroma formation is the most common complication after mastectomy and continues to be an important problem during the early postoperative period. Several surgical and medical methods have been developed to try to overcome this problem; however, so far none have been used successfully in the routine clinical practice. The aim of this study is to evaluate the effects of Corynebacterium parvum (CP) as a sclerosing agent in both prevention and treatment of seromas after mastectomy and axillary dissection in an animal model. Sixty female Sprague-Dawley rats underwent mastectomy and axillary dissection under general anaesthesia. Following surgery, the rats were treated in 1 of 3 ways. In the prevention group, 1 cm3 (0.35 mg) CP solution was injected beneath the skin flap just before closure of the incision after mastectomy. In the treatment group, animals in which a seroma was formed, the fluid was aspirated, and 1 cm3 CP solution was injected beneath the flap. In the control group, animals in which seromas formed, aspiration only was performed. The frequency of seroma formation decreased when CP solution was injected immediately after the operation (p < 0.01). In addition, seroma formation was effectively treated by CP injection when compared with the control group (p < 0.05). CP was effective as a prophylactic agent in the prevention group and as a therapeutic agent in the treatment group in this experimental model. CP injection may be useful for the management of this problem in a clinical setting.
Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock
Authors: Pape A. , Kemming G. , Meisner F. , Kleen M. , Habler O.
Published: April 2003

In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O2 content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dtmin) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.
Activation of Intracellular Neutrophil Elastase in the Transplantation of Ischemic Liver
Authors: Otsuka M. , Takada Y. , Fukunaga K. , Taniguchi H. , Todoroki Todoroki
Published: April 2003

Ischemia-reperfusion injury is an important cause of primary nonfunction of transplanted organs, and neutrophil elastase has been implicated in the pathophysiology of ischemia-reperfusion injury. We assessed the kinetics of intracellular neutrophil elastase (INE) activity in canine liver transplantation. Mongrel dogs underwent orthotopic whole-liver transplantation. The animals in group I (n = 6) received fresh liver grafts, and all of the dogs survived longer than 24 h. The animals in group II (n = 5) received liver grafts injured by 30 min of warm ischemia. Only 1 animal survived longer than 24 h after reperfusion. A significant increase in the serum ALT and LDH levels was observed in group II after reperfusion of the graft. Isolated peripheral neutrophils were homogenized, and the neutrophil elastase activity in the supernatant was determined by using a spectrophotometric assay. The INE activity was expressed as the neutrophil elastase value per 1 × 1010 peripheral neutrophils. In group I, the INE activity 10 min and 2 h after reperfusion was 7.6 ± 2.6 and 6.1 ± 2.4 U, respectively. In group II, this activity was 25.9 ± 7.4 and 44.3 ± 23.7 U, respectively. There was a significant correlation between serum LDH levels and INE activity 10 min after reperfusion (γ = 0.70, p < 0.02). In conclusion, the INE activity increased more sharply after the reperfusion of ischemically injured liver grafts. The INE activity correlates with serum LDH levels immediately after reperfusion, suggesting that the increase in the INE activity depends on the severity of ischemic damage.
Pathogenic Significance and Organic Virus Levels in Patients Infected with TT Virus
Authors: Suzuki Fumitaka , Chayama Kazuaki , Tsubota Akihito , Akuta Norio , Someya Takashi , Kobayashi Masahiro , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: April 2003

Previous reports documented the recovery of a DNA virus from a patient with posttransfusion non-A–G hepatitis and named TT virus (TTV). Although the virus was initially detected as a causative agent of hepatitis, there is doubt about its pathogenicity. The aim of this study was to clarify the relationship between TTV and liver diseases. Histopathological examination of liver biopsies from 14 patients with TTV genotype 1 positive non-B, non-C and non-G chronic hepatitis showed mild fibrosis and periportal/piecemeal necrosis. Using the real-time detection (RTD)-PCR method, we found that TTV DNA levels of genotype 1 in liver samples from 3 such patients were 100- to 1,000-fold higher than those in the paired serum samples. Further investigation using various tissues from 2 autopsies of patients with hepatitis C with hepatocellular carcinoma revealed that the concentrations of TTV DNA in the liver were also higher than in serum samples. However, the highest TTV DNA concentrations in these 2 autopsies were found in the lung and bone marrow, respectively. Our results suggest that TTV may replicate in various tissues including the liver and may cause only mild liver damage.
Novel Hepatitis B Virus Strain from a Chimpanzee of Central Africa (Pan troglodytes troglodytes) with an Unusual Antigenicity of the Core Protein
Authors: Takahashi Kazuaki , Mishiro Shunji , Prince Alfred M.
Published: April 2003

We and others have previously reported a hepatitis B virus (HBV)-like hepadnavirus strain which seemed to be indigenous to West African chimpanzees (Pan troglodytes verus). After that, we obtained an HBsAg-positive serum sample from a chimpanzee from Central Africa, named Bassi, belonging to another subspecies (P. troglodytes troglodytes). The full-genome nucleotide sequence of the hepadnavirus from Bassi showed a significant difference (9–26%) from those so far reported from primates including humans, chimpanzees and gorillas, suggesting a novel strain. More interestingly, however, the core antigen (HBcAg) deduced from Bassi’s sequence showed only 78–82% similarity to known primate strains at the amino acid level, whereas the other strains shared more than 90% similarity. HBcAg expressed from Bassi HBV failed to react with monoclonal antibodies that were directed at an epitope borne by codons 135–145 of HBcAg of conventional hepadnaviruses. This could explain why Bassi was negative for anti-HBc in a routine test. Here we report the novel HBV strain presumably indigenous to P. troglodytes troglodytes in Central Africa.
Three Cases with TT Virus Infection and Idiopathic Neonatal Hepatitis
Authors: Tajiri Hitoshi , Tanaka Tatsuya , Sawada Atsushi , Etani Yuri , Kozaiwa Kosuke , Mushiake Sotaro , Mishiro Shunji
Published: April 2003

We present three cases of infants with idiopathic neonatal hepatitis showing diffuse intrahepatic fatty degeneration. Prolonged cholestasis has improved immediately upon intravenous administration of a high-dose gammaglobulin treatment in all three patients. The TT virus (TTV) genome was detectable in the serum of two patients, in the duodenal fluid of one and in the liver of all three. By analyzing sequence homology, we observed that the respective TTV isolated from serum, duodenal fluid and liver tissue were completely identical in cases 2 and 3. These findings suggest that TTV infection was one of the contributing factors for neonatal cholestasis in these patients. TTV was isolated from the serum of two out of the three mothers. The viruses were either completely or almost identical in sequence to those isolated from their respective infants, suggesting that they had been transmitted from mother to infant in these 2 cases. The patients presented here, whose livers were infected with the TTV and showed a favorable response to gammaglobulin therapy, may represent a subset of idiopathic neonatal hepatitis patients.