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  • 1995-1999  (1,739)
  • 1980-1984
  • 1999  (1,739)
  • Chemistry  (1,469)
  • Life and Medical Sciences  (96)
  • Apoptosis  (93)
  • Children  (81)
Source
Material
Years
  • 1995-1999  (1,739)
  • 1980-1984
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Gemcitabine-Induced Programmed Cell Death (Apoptosis) of Human Pancreatic Carcinoma Is Determined by Bcl-2 Content (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 279-285 
    Details
    ISSN: 1534-4681
    Keywords: Gemcitabine ; bcl-2 ; Pancreatic cancer ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Gemcitabine is a new nucleoside analogue that produces a clinical response in 30% of patients with unresectable pancreatic carcinoma. The cytotoxic effects of many chemotherapeutic agents occur through induction of programmed cell death (apoptosis), which is controlled by the bcl-2 gene family. We determined whether induction of apoptosis by gemcitabine in pancreatic carcinoma is associated with cellular Bcl-2 content. Methods: Four pancreatic carcinoma cell lines (MIA-PaCa-2, AsPC-1, Panc-1, and Panc-48) were screened by Western blotting for Bcl-2 protein expression. Dose-response relationships for the cytotoxic effects of gemcitabine were determined using methylthiotetrazole assays, and induction of apoptosis was confirmed by fluorescence-activated cell sorting analysis. MIA-PaCa-2 cells transfected with human bcl-2 were also analyzed for gemcitabine-induced apoptosis. Results: Pancreatic cancer cell lines expressed varying amounts of Bcl-2, and the 50% lethal dose for gemcitabine-induced apoptosis was correlated with Bcl-2 content. Furthermore, Bcl-2 overexpression was associated with a significant increase in the 50% lethal dose for gemcitabine-induced apoptosis. Conclusions: Cellular Bcl-2 content was directly correlated with the cytotoxicity of gemcitabine in pancreatic carcinoma. Therefore, routine immunohistochemical analyses may be useful in predicting gemcitabine efficacy, and patients who would likely not benefit could be spared gemcitabine administration. Furthermore, the effectiveness of gemcitabine and other chemotherapeutic agents may be increased by gene therapy-mediated alteration of bcl-2 gene family members.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10434-999-0279-x
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  • 2
    Electronic Resource
    Electronic Resource
    Vergiftungs- und Todesfälle durch Substitutionsmittel im Umfeld von substituierten Drogenabhängigen (1999)
    Springer
    Rechtsmedizin 9 (1999), S. 90-93 
    Details
    ISSN: 1434-5196
    Keywords: Key words Methadone ; Dihydrocodeine ; Substitution ; Poisoning ; Children ; Schlüsselwörter Methadon ; Dihydrocodein ; Substitution ; Intoxikationen ; Kinder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Es wird über 3 überlebte und 4 tödlich verlaufene akzidentelle Intoxikationen, sechs mit Methadon, eine mit Dihydrocodein, berichtet. Die Intoxikationen betrafen nicht die Substituierten selbst, sondern deren Familienangehörige, Bekannte oder Mit-Patienten. In allen Fällen wurden die Substitutionsmittel weitgehend ungesichert und teilweise vermutlich auch unbeschriftet stehengelassen. Den Substituierten selbst war dabei die Gefahr, die von ihrem Substitutionsmittel ausging, offenbar nicht ausreichend bewußt. Diese Fälle zeigen deutlich, daß qualitätssichernde Maßnahmen bei der immer großzügigeren Substitutionspraxis, insbesondere in Hinblick auf „take-home“-Dosen, notwendig sind.
    Notes: Abstract A total of seven cases of accidental ingestion of methadone or dihydrocodeine by four children and three adults are reported of which four were fatal. In each case, someone in the environment was taking methadone or dihydrocodeine as a substitute drug for heroin addiction who obviously did not realize the dangers of methadone for non-addicts. Possible preventive measures are the usage of child-proof containers with adequate labels for take-home medications. Furthermore substituted addicts have to be thoroughly indoctrinated concerning the toxicity and hazards of methadone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001940050087
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  • 3
    Electronic Resource
    Electronic Resource
    Recommendations for treatment of contralateral inguinal hernias in children (1999)
    Springer
    Hernia 3 (1999), S. 53-56 
    Details
    ISSN: 1248-9204
    Keywords: Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is impossible to determine whether or not a child will develop a contralateral hernia after inguinal hernia repair. There exists no risk score for the occurrence of a contralateral hernia. This well-known fact prompted us to perform the underlying study. In a retrospective trial, we reviewed the files of all children operated on for inguinal hernias in our department from January 1986 until December 1994. During this period, we performed 1721 hernia repairs on 1708 children aged 0–16 years. In 96 (5.6%) of these patients, the indication to operate was a contralateral hernia following previous unilateral repair. Comparison of the ages at the time of primary inguinal repair of those children who developed a contralateral hernia (n=96) and those who did not (n=1612) showed a significantly increased incidence of contralateral hernias if the primary operation was performed before the age of two months (p〈0.0001). Diseases predisposing to hernias were found in 38% of all children (prematurity, dystrophia, ventriculo-peritoneal shunt, ascites, asthma). The authors recommend a contralateral exploration for children under the age of two months if they have any predisposing disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01194602
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  • 4
    Electronic Resource
    Electronic Resource
    Word-list learning in normally developing children: effects of semantic organization and retention interval (1999)
    Springer
    Italian journal of neurological sciences 20 (1999), S. 119-128 
    Details
    ISSN: 1126-5442
    Keywords: Key words Learning ; Development ; Memory ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720050019
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  • 5
    Electronic Resource
    Electronic Resource
    Chronic neuroborreliosis in infancy (1999)
    Springer
    Italian journal of neurological sciences 20 (1999), S. 303-307 
    Details
    ISSN: 1126-5442
    Keywords: Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%–50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100720050045
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of retinol on follicular porcine thyrocytes in culture (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 189-192 
    Details
    ISSN: 1432-1440
    Keywords: Key words Thyroid ; Cell culture ; Retinoids ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinoids influence proliferation and differentiation in transformed thyroid cell lines. Retinoids are able to damage cells by destabilizing lysosomal membranes and induce apoptosis in certain cell lines. In normal thyrocytes retinol modulates iodine metabolism. At concentrations higher than 50×10–6 M retinoids are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this cytotoxicity is unknown. We studied the effect of 7–80×10–6 M retinol on porcine follicular thyrocytes in culture. In order to differentiate between membrane-destabilizing effects and apoptosis we investigated cultures after incubation with retinol by light- and electron-microscopy and by labeling of potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP mediated DNA nick end labeling. We conclude that the observed cytotoxicity is caused mainly by the induction of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050334
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  • 7
    Electronic Resource
    Electronic Resource
    Molecular pathogenesis of chronic lymphocytic leukemia: factors and signaling pathways regulating cell growth and survival (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 282-293 
    Details
    ISSN: 1432-1440
    Keywords: Key words Chronic lymphocytic leukemia ; Apoptosis ; Cell growth ; Signaling ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic lymphocytic leukemia is a malignant disease characterized by clonal expansion of relatively mature B-lymphocytes with a high percentage of cells arrested in the nonproliferative G0/G1 cell cycle phase. Possibly reflecting the clinical heterogeneity observed in patients, various signaling pathways may become affected during the initiation and course of this disease. This review discusses frequent alterations concerning proliferative, differentiation-inducing, and apoptotic pathways elucidated in the recent years that have improved our understanding of this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050351
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  • 8
    Electronic Resource
    Electronic Resource
    Analysis of otolith chemistry in Nassau grouper (Epinephelus striatus) from the Bahamas and Belize using solution-based ICP-MS (1999)
    Springer
    Coral reefs 18 (1999), S. 171-178 
    Details
    ISSN: 1432-0975
    Keywords: Key words Otolith ; Chemistry ; ICP-MS ; Stock discrimination ; Epinephelus striatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract  We examined the utility of otolith minor and trace element chemistry, assayed with inductively coupled plasma mass spectrometry (ICP-MS), as a means of delineating population structure in the Nassau grouper (Epinephelus striatus). We characterized the elemental composition of otoliths collected in 1993 from three locations in Exuma Sound, Bahamas and from Glover Reef, Belize in 1995. A single location in Exuma Sound was sampled in 1994 to test temporal variability in otolith composition. Five elements (Ca, Zn, Sr, Ba and Pb) were routinely detected, at levels significantly above background, by solution-based ICP-MS. Results from analysis of variance of elemental data, expressed as a ratio to Ca, indicated that there were no significant differences among the Exuma locations for any element, but significant variability was found between Glover Reef and the pooled Exuma localities for Zn/Ca, Sr/Ca and Ba/Ca ratios. Significant inter-annual differences at one Exuma Sound location was restricted to Ba/Ca ratios. Discriminant function analysis correctly classified 86% and 95% of the Belize and pooled Exuma sites, respectively. Otoliths from Belize were characterized by low Zn/Ca and high Ba/Ca and Pb/Ca ratios compared to otoliths from fish collected in Exuma Sound. Although differences in Ba levels may be related to upwelling at Glover Reef, more data are needed to definitely link otolith composition with regional differences in water chemistry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003380050176
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 1-8 
    Details
    ISSN: 1432-1335
    Keywords: Key words Cell proliferation ; Apoptosis ; Cell death ; Cultured cells ; Hepatocellular carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There are conflicting results for experiments aimed at determining whether anticancer drug therapy of human hepatocellular carcinoma prolongs the survival rate effectively. The purpose of this study was to assess the effect of low concentrations of doxorubicin, mitomycin C, and ethanol on cell replication (cell number and proliferation), and cell apoptosis of cultured human hepatocellular carcinoma (Hep-G2) cells. After 1 day of exposure doxorubicin inhibited cell replication initially by 72%, but a partial recovery of the cell number was observed. Mitomycin C inhibited to the same extent but without recovery. Ethanol reduced the cell number even further, the maximum inhibition (12 days after exposure) being 96.4%. After 3 days of exposure all three agents stopped cell replication at a level of 2%–4% of the control (P 〈 0.001). Cell apoptosis was activated most strikingly by mitomycin C (5 μg/ml) after 1 day of exposure and by ethanol (150 μl/ml) after 3 days of exposure. Two-way repeated-measures analysis of variance showed statistically significant differences, with ethanol being the most significant followed by mitomycin C doxorubicin, and the control (P 〈 0.01). Thus, a low dose of ethanol combined with an exposure time of up to 3 days appears to be an effective regimen to control growth of human hepatocellular carcinoma cells in vitro. The strong induction of apoptosis by ethanol might be of additional benefit for a local application in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050235
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  • 10
    Electronic Resource
    Electronic Resource
    Basic fibroblast growth factor potentiates cisplatinum-induced cytotoxicity in MCF-7 human breast cancer cells (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 556-562 
    Details
    ISSN: 1432-1335
    Keywords: Key words Basic fibroblast growth factor ; Cisplatinum ; Apoptosis ; Bcl-2 ; MCF-7
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF inhibits the growth of MCF-7 human breast cancer cells. The aim of the present study was to examine the effect of bFGF on cis-diamminedichloroplatinum(cisplatin)-induced cytotoxicity in MCF-7 breast cancer cells as compared to normal endothelial cells. MCF-7/NCF cells transduced with a vector expressing the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduced with the backbone vector were incubated with a combination of bFGF and cisplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforhodamine B colorimetric cytotoxicity assay. Apoptosis was quantitatively determined by flow-cytometric analysis for DNA damage and the apoptotic death assay for DNA fragmentation, and qualitatively by electron microscopy. Reverse transcriptase/polymerase chain reaction analysis and an enzyme immunoassay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-induced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced proliferation of normal endothelial cells and did not increase cisplatin-induced cytotoxicity. This effect was accompanied by down-regulation of the anti-apoptotic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis. We suggest that the improved understanding of the role of bFGF in the differential modulation of the response of breast cancer and normal endothelial cells to chemotherapy may enable active intervention to alter the therapeutic ratio favorably in breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050316
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  • 11
    Electronic Resource
    Electronic Resource
    Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 660-668 
    Details
    ISSN: 1432-1335
    Keywords: Keywords Chemosensitivity ; Human gastric carcinoma ; Micrometastasis ; Apoptosis ; Circulating tumor cells ; Fluoropyrimidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antimetastatic effects of 5-FU and its derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU) on human gastric cancer micrometastasis and their mode of action were evaluated, using a spontaneous lung metastasis model (HY-1) in nude mice. Metastases were first detected in the lung from 4 weeks after subcutaneous transplantation, growing intravascularly and forming micrometastases at 100% incidence by 6 weeks after implantation. Lung metastasis in mice bearing subcutaneous tumors was significantly inhibited by HCFU at doses of 100–150 mg kg−1 day−1 without severe toxic side-effects, when orally administered three times per week either from week 4 or week 6 to 9 weeks after implantation. Spontaneous lung metastasis was also inhibited by the administration of 5-FU, but to lesser extent than with HCFU at equimolar low doses. Apoptosis within primary tumors and lung metastatic foci, as detected by the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling method, was found to be significantly enhanced by HCFU as well as 5-FU administration at doses of more than 100 mg kg−1 day−1 and 50 mg kg−1 day−1 respectively. However, proliferating activity of the metastatic foci, as evaluated by MIB-1 immunostaining, was not significantly suppressed by HCFU or 5-FU treatment. Furthermore, polymerase chain reaction analysis using human specific primers for the β-globin gene, which proved to be capable of detecting 10 tumor cells/ml mouse blood, revealed that circulating tumor cells in the peripheral blood of mice bearing primary tumors were reduced by HCFU or 5-FU administration. These results indicate that circulating tumor cells in blood and micrometastases in the lung are sensitive to these chemotherapeutic agents, and suggest that the anti-metastatic effect of these agents is mediated, at least in part, by enhanced apoptosis rather than by inhibition of cell proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050331
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  • 12
    Electronic Resource
    Electronic Resource
    The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 166-173 
    Details
    ISSN: 1432-1335
    Keywords: Key wordsIGF ; Apoptosis ; Transformation ; Chemosensitivity ; Signaling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050259
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  • 13
    Electronic Resource
    Electronic Resource
    Subnuclear distribution of DNA topoisomerase I and Bax protein in normal and xeroderma pigmentosum fibroblasts after irradiation with UV light and c rays or treatment with topotecan (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 193-208 
    Details
    ISSN: 1432-1335
    Keywords: Key words Immunohistochemistry ; DNA repair ; Radiation-inducible response ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical methods were used to determine abundance and subnuclear distribution of DNA topoisomerase I and the Bax protein in normal and excision-repair-deficient xeroderma pigmentosum (XP) fibroblasts after irradiation of cells with γ rays or UV light, or exposure to the topoisomerase I inhibitor topotecan. DNA topoisomerase I and Bax were monitored using antisera raised against the human proteins. In addition, topoisomerases IIα and IIβ were made visible with specific antibodies. In untreated cells, DNA topoisomerase I was found to occur in the cytoplasm and in nucleoli. Irradiation with γ rays (2–12 Gy) or UV light (0.3–1.2 mW/cm2) changed the staining pattern in nuclei such that a multitude of small topoisomerase-I-rich centers occurred, which were evenly distributed over the karyoplasm. Simultaneously nucleoli disintegrated. Treatment of fibroblasts with topotecan (6–100 μM concentrations) resulted in similar alterations although the changes were much more pronounced. Combinations of topotecan and γ irradiation caused additive effects. We conclude that the increase in the number of topoisomerase-I-positive spots and the high fluorescence intensity of the latter may reflect three biological processes: (i) enhanced transcriptional activity (e.g. of DNA damage response genes), (ii) tagging of damaged DNA sites for repair, or (iii) initiation of apoptosis. In separate assays using normal and XP cells, a dose-dependent increase in protein reacting with Bax antibody was observed in nuclei, following treatment with γ rays or topotecan. In addition, topotecan induced a netlike arrangement of this Bax protein in nuclei. The meshes of the net structure resembled vesicles. DNA staining with 4′,6-diamidino-2-phenylindole dihydrochloride revealed that the vesicle-type structures contained DNA. Upon further incubation with topotecan, cells showing the netlike Bax arrangement eventually died. We conclude that topotecan-induced changes made visible by nuclear Bax protein are associated with apoptosis. XP cells, when treated with topotecan, responded more readily than normal cells with both an increase in nuclear Bax protein and rearrangement of Bax, indicating that UV repair functions may be required to process DNA damage inflicted by topotecan. Monitoring of DNA topoisomerases IIα and IIβ in γ-irradiated cells with antibodies revealed a dramatic increase in the IIα form and a redistribution of the IIβ form representing fragmentation of nucleoli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050263
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  • 14
    Electronic Resource
    Electronic Resource
    The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 357-360 
    Details
    ISSN: 1432-1335
    Keywords: Key words Colorectal neoplasms ; Apoptosis ; Chemosensitivity ; p53 gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose : The p53 gene is considered one of the most important in the control of apoptosis, and its mutations have a close relationship with chemosensitivity. The aim of this work was to investigate the role of p53 in the apoptosis of colorectal cancer cells in vitro, induced by 5-fluorouracil (5-FU) and hydroxy-camptothecin (HCPT). Methods : A total of 39 colorectal cancer samples from patients were treated in vitro with 5-FU (10 μg/ml), 5-FU (10 μg/ml) + leucovorin (5 μg/ml), HCPT (0.1 μg/ml) and HCPT (0.1 μg/ml) + Salvia mitorrhiza (6 μl), using an in situ terminal deoxynucleotidyltransferase assay to detect chemosensitivity. p53 gene mutations from tumor DNA were detected, after amplification by the polymerase chain reaction of exons 5–8, by non-radioactive single-strand conformation polymorphism. Results : p53 gene mutations were observed in 43.6% (17/39) of colorectal carcinomas, when the terminal deoxynucleotidyltransferase assay was used to detect the tumor apoptotic rate. Cells with mutated p53 had lower chemosensitivity than those without (p 〈 0.01). Conclusion : Routine assessment of p53 status may be helpful in selecting patients with the wild-type p53 gene, who have a predictably better response to chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050286
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  • 15
    Electronic Resource
    Electronic Resource
    Inhibition of epidermal-growth-factor-receptor-dependent signalling by tyrphostins A25 and AG1478 blocks growth and induces apoptosis in colorectal tumor cells in vitro (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 379-388 
    Details
    ISSN: 1432-1335
    Keywords: Key words EGF receptor signalling ; Tyrphostin ; Apoptosis ; Colon cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Growth effects of tyrphostins A25 and AG1478 on colorectal tumor cells were studied to explore therapeutic potential. Cell number, DNA synthesis and apoptotic index were measured as growth parameters and cell-death-associated proteins Bcl-2 and Bak and protein phosphorylation were analyzed. Both tyrphostins inhibited DNA synthesis and induced apoptosis in tumor cell cultures with different patterns of activity. A25 displayed strong selectivity for the cell lines expressing high levels of epidermal growth factor (EGF), HT29/HI1 and SW480. Inhibition of DNA synthesis was efficient in all cells except T84, and the apoptotic index increased two- to fivefold. By contrast, AG1478 was highly effective in all cell lines. In addition, it caused cell loss in VACO235 adenoma cells at concentrations lower than those necessary to inhibit BrdU incorporation, reflecting preferential retention of cells actively synthesizing DNA. Induction of apoptosis was more efficient with AG1478 than with A25 (tenfold in VACO235). Insulin-like growth factor (IGF1) did not rescue cells exposed to A25 or to high concentrations of AG1478, but was effective with suboptimal amounts of AG1478. Both compounds inhibited phosphorylation of the EGF receptor as well as additional proteins. AG1478 induced expression of Bak and down-regulated Bcl-2. In summary, tyrphostins may provide alternatives for colorectal tumor treatment. Their broader range of activities and the lower susceptibility to interactions with IGF1 can be an advantage over receptor antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050290
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  • 16
    Electronic Resource
    Electronic Resource
    Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 444-452 
    Details
    ISSN: 1432-1335
    Keywords: Key words Experimental pancreatic cancer ; Hormonal therapy ; Bombesin antagonist ; Somatostatin analog ; LH-RH antagonist ; EGF receptor ; Apoptosis ; AgNOR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 μg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of down-regulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050301
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  • 17
    Electronic Resource
    Electronic Resource
    Nachbarschaft von Tic und Zwang (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 1-10 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notes: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050394
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  • 18
    Electronic Resource
    Electronic Resource
    Charakterisierung der Lymphozytensubpopulationen bei Patienten mit Ataxia teleangiectatica (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 927-931 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Ataxia teleangiectatica ; Immunfunktionsstörung ; Lymphozytensubpopulationen ; Apoptose ; CD45RO ; CD45RA ; Key words Ataxia teleangiectasia ; Immunodeficiency ; Lymphocyte subset ; Apoptosis ; CD45RO ; CD45RA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: Can a characterisation of the lymphocyte subset in patients with ataxia teleangiectasia offer an explanation for the cellular defect of their immunfunction? Methods: In ten patients with ataxia teleangiectasia and a corresponding control group of individuals of similar age and sex, immunophenotyping was carried out by means of flow cytometric analysis and the use of monoclonal antibodies. Results: Patients with ataxia teleangiectasia showed a reduction of the number of T-cells with a decrease in the T-helper cell subset (CD3: 990/µl, p〈0.0005 and CD4: 568/µl, p〈0.0005). The number of B-cells was low (CD19: 39/µl, p〈0.005). Moreover, there was an increase in highly activated T-lymphocytes which can be seen from a higher percentage of the HLA-DR- and CD45RO-expression in patients with ataxia teleangiectasia compared to the individuals of the control group (HLA-DR: 57%, p〈0.0005 and CD45RO: 82%, p〈0.001). At the same time, the expression of CD95 (Fas/AP01) was clearly increased (CD95: 74%, p〈0.001). Interpretation: The lymphocyte subset of the patients suffering from ataxia teleangiectasia shows a significant decrease of the B- and T-cell subsets. The reduced number of T-helper cells – caused by a CD45RA-cell loss – leads to a change in the relation „RA/RO”. It is possible that there is a link between the imbalance of „RA/RO”, the increase of highly activated T-lymphocytes and the higher expression of CD95 (Fas/APO1).
    Notes: Zusammenfassung Fragestellung: Können durch eine Charakterisierung der Lymphozytensubpopulationen bei Patienten mit Ataxia teleangiectatica Rückschlüsse auf den zellulären Defekt der Immunfunktionsstörung gezogen werden? Methodik: Mit Hilfe der Durchflußzytometrie und des Einsatzes monoklonaler Antikörper führten wir eine Immunophänotypisierung bei jeweils 10 Patienten mit Ataxia teleangiectatica und eines bezüglich des Alters und des Geschlechts gleichverteilten Kontrollkollektivs durch. Ergebnisse: Die Patienten mit Ataxia teleangiectatica zeigten verminderte T-Zell-Zahlen mit Abnahme der T-Helferzell-Subpopulationen (CD3: 990/µl, p〈0,0005 und CD4: 568/µl, p〈0,0005). Auch die B-Zell-Zahl war erniedrigt (CD19: 39/µl, p〈0,005). Die T-Lymphozyten befanden sich darüber hinaus vermehrt im aktivierten Zustand, erkennbar an einer prozentual erhöhten HLA-DR- und CD45RO-Expression (HLA-DR: 57%, p〈0,0005 und CD45RO: 82%, p〈0,001) sowie an einer Verschiebung der Relation „RA/RO” zugunsten der „RO”-Expression. Gleichzeitig war die Expression von CD95 (Fas/APO1) deutlich gesteigert (CD95: 74%, p〈0,001). Schlußfolgerung: Die Veränderungen der Lymphozytensubpopulationen zeigen bei den Patienten mit Ataxia teleangiectatica eine verminderte B- und T-Zell-Zahl. Die CD4-Lymphopenie – verursacht durch einen CD45RA-Zellverlust – bedingt eine Verschiebung der Relation „RA/RO”. Möglicherweise besteht ein Zusammenhang zwischen der Störung der Homöostase „RA/RO” und dem erhöhten Aktivierungsgrad der Zellen sowie der vermehrten CD95(Fas/APO1)-Expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050519
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  • 19
    Electronic Resource
    Electronic Resource
    Asthma bronchiale bei türkischen und deutschen Schulkindern Häufigkeit, Schweregrad und Behandlung (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: In Germany 4.2% (in Munich 8.6%) of all children under 15 years of age are of Turkish origin, representing the largest ethnic minority in this age group. However, very little is known about the prevalence, severity and management of asthma and other atopic diseases in Turkish children living in Germany. Methods: In a cross-sectional survery the prevalence, severity and treatment of asthma and other atopic diseases was assessed in 7,445 schoolchildren aged 9 to 11 years, living in Munich, southern Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin-prick tests and cold-air hyperventilation challenge. Results: Of those returning the questionnaires (n = 6490/87%), 5,030 (77.5%) were of German and 451 (7%) of Turkish origin. Turkish children showed a significantly lower prevalence of asthma (5.3% versus 9.4%, P 〈 0.05) than their German peers. Furthermore, Turkish children with asthma were less frequently free of symptoms (10.5% versus 34.6%, P 〈 0.05), reported more severe symptoms (41.2% versus 10.9%, P 〈 0.05) and more hospital admissions (55.6% versus 21.6%, P 〈 0.05) due to asthma than German children. Conclusions: The results of this study indicate that despite the lower prevalence of asthma and allergy in the Turkish population living in Germany, asthma is a major health problem for Turkish children. Furthermore, these findings suggest inadequate management of asthma in Turkish children.
    Notes: Zusammenfassung Fragestellung: Türkische Kinder stellen in der Bundesrepublik Deutschland mit 4,2% und in München mit 8,6% den größten Anteil nicht-deutscher Kinder in der Altersgruppe bis 15 Jahren. Wenig ist jedoch bisher über Häufigkeit, Symptome und Behandlung von Asthma bronchiale und anderer atopischer Erkrankungen der türkischen Minderheit in Deutschland bekannt. Methodik: In einer Querschnittstudie wurde bei 7445 Schulkindern im Alter von 9 bis 11 Jahren im Großraum München die Häufigkeit, der Schweregrad und die Behandlung des Asthma bronchiale und anderer atopischer Erkrankungen untersucht. Fragebögen wurden von den Eltern ausgefüllt, Lungenfunktionsuntersuchungen und Hautpricktests wurden bei den Kindern durchgeführt. Ergebnisse: Von denen, die die zugeschickten Fragebögen ausfüllten (n = 6490/87%), waren 5030 (77,5%) deutscher und 451 (7%) türkischer Nationalität. Die türkischen Kinder zeigten eine niedrigere Prävalenz von Asthma bronchiale (5,3% versus 9,4%, p 〈 0,05) und Neurodermitis (1,6% versus 12,9%, p 〈 0,001) im Vergleich zu den deutschen Kindern. Signifikante Unterschiede bestanden zwischen türkischen und deutschen Kindern in Art der Symptome und der Krankheitswahrnehmung. Türkische Kinder mit Asthma bronchiale waren seltener beschwerdefrei (10,5% versus 34,6%, p 〈 0,05) berichteten von schwereren Symptomen (41,2% versus 10,9%, p 〈 0,05) und von einer größeren Anzahl von Krankenhausaufenthalten (55,6% versus 21,6%, p 〈 0,05) aufgrund von Asthma bronchiale. Schlußfolgerung: Die Ergebnisse der Studie legen den Schluß nahe, daß Asthma bronchiale trotz der niedrigeren Prävalenz in der türkischen Bevölkerungsgruppe ein erhebliches Gesundheitsproblem bei türkischen Schulkindern darstellt. Die höhere Anzahl von Fehltagen in der Schule und die deutlich höhere Anzahl von Klinikaufenthalten aufgrund von Asthma bronchiale sprechen für eine mangelhafte präventive Behandlung dieser Erkrankung bei türkischen Kindern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050430
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  • 20
    Electronic Resource
    Electronic Resource
    Dokumentation der Auswirkungen von Kinderknallpistolen (1999)
    Springer
    HNO 47 (1999), S. 535-540 
    Details
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor premanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family-life but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40.000 Euro).
    Notes: Zusammenfassung Im Rahmen einer Studie wurden 20 Fälle von Knalltraumata durch Kinderpistolen erfaßt und ausgewertet. Die Problematik betrifft fast nur männliche Personen und schwerpunktmäßig den Altersbereich von 6–11 Jahren. Die Hälfte der Vorfälle waren Angriffe, bei denen die Kinderpistole als Waffe eingesetzt wurde, 2 Typen von Hörschäden sind festzustellen, die jedoch beide durch eine Senke im Bereich von 10–14 kHz charakterisiert sind. Bei Kindern kann der Schuß in eines der Ohren auch das andere Ohr schädigen. Sehr große Unterschiede bestehen im Auftreten von Tinnitus. Die Fälle mit starkem Tinnitus haben keine oder nur geringe bleibende Hörschäden. Die von Knalltraumata betroffenen Kinder leiden oft sehr stark unter langanhaltendem Tinnitus. Dabei wird nicht nur das Leben der Familien beeinträchtigt, sondern auch die schulischen Leistungen der Kinder leiden teilweise sehr stark darunter. Für die Therapie dieser 20 Fälle entstanden Gesamtkosten von ca. 80.000,- DM
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001060050420
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  • 21
    Electronic Resource
    Electronic Resource
    Die Chirurgie der erworbenen laryngotrachealen Stenosen im Kindesalter. Erfahrungen und Ergebnisse von 1988–1998 Teil II: Die cricotracheale Resektion (1999)
    Springer
    HNO 47 (1999), S. 611-622 
    Details
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Laryngotracheale Stenose ; Cricotracheale Resektion ; Kinder ; Tracheotomie ; Key words Laryngotracheal stenosis ; Cricotracheal resection ; Tracheostomy ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Approximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children’s voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.
    Notes: Zusammenfassung Kinder mit schweren, erworbenen subglottischen laryngotrachealen Stenosen sind zu 90% tracheotomiert und daher in ihrer körperlichen und sprachlichen Entwicklung beeinträchtigt. Zusätzlich sind mit einer Trachealkanüle versorgte Kinder, insbesondere Kleinkinder, gefährdet, so daß die chirurgische Beseitigung der Stenose dringend geboten ist. Wir haben innerhalb der vergangenen 10 Jahre 18 Kinder mit einer schweren subglottischen laryngotrachealen Stenose operiert; 10 Kinder, über die kürzlich berichtet wurde, konnten mit der modifizierten Cotton-Technik erfolgreich dekanüliert werden. Über 8 Kinder (Alter 7 Monate bis 15 Jahre, 4mal Stenose II. Grades, 3mal Stenose III. Grades, einmal Stenose IV. Grades), die wir mit cricotrachealer Resektion (CTR) und thyrotrachealer Anastomose operierten, wird in der vorliegenden Arbeit berichtet. 3 Kinder waren anderenorts bereits tracheotomiert. Da die Stomata zu weit kaudal lagen, konnten sie nicht in die Resektion einbezogen werden. Alle 8 Kinder konnten inzwischen dekanüliert werden und sind beschwerdefrei: Die 5 nicht tracheotomierten Kinder konnten problemlos am 5. postoperativen Tag extubiert werden. Die zuvor tracheotomierten Kinder konnten erst nach endotrachealer Schienung (2mal nach zusätzlicher Trachealplastik mit Rippenknorpel bei suprastomaler Tracheomalazie) dekanüliert werden. Bei keinem der Kinder trat eine Recurrensparese auf. Die Stimme bei allen Kindern ist unbeeinträchtigt. Die CTR, über die bei kindlichen laryngotrachealen Stenosen mit dieser Arbeit in der Literatur zum 3. Mal berichtet wird, ist eine sehr effektive, einzeitige, komplikationsarme Operationsmethode, deren Resultate für Atmung und Stimme günstiger sind, als mit der Erweiterungsplastik nach Cotton.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001060050434
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  • 22
    Electronic Resource
    Electronic Resource
    Körperliche Beschwerden bei Kindern in Deutschland und in den Niederlanden (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 122-127 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Körperliche Beschwerden ; CBCL/4 ; 18 ; Kultur-vergleichend ; Kinder ; Jugendliche ; Key words Somatic complaints ; CBCL/4 ; 18 ; Cross-cultural ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Question: What is the frequency of parent-reported somatic complaints of children in Germany and the Netherlands dependent on their age, sex and the education of their parents. Methods: 4876 CBCL (Child Behaviour Checklist) of children aged 4 through 17 years from the general population were analysed. Results: Dutch children were scored higher by their parents than German children. Moreover somatic complaints increased with age and girls were scored higher. The frequencies of somatic complaints varied from 2% for ’problems with eyes’ to 15% for ’headaches’. The presence of one somatic complaint increased the likelihood of concomitant somatic complaints. Conclusion: Somatic complaints of children without any known cause are often seen. Some symptoms are often reported together. More, especially causal studies on the somatic symptoms of children are recommended.
    Notes: Zusammenfassung Fragestellung: Wie verhält sich die Häufigkeit körperlicher Beschwerden bei Kindern in Deutschland und den Niederlanden nach Laieneinschätzung, gibt es Unterschiede abhängig vom Alter und Geschlecht der Kinder und des Ausbildungsniveaus der Eltern? Methode: 2757 deutsche und 2119 niederländische CBCL (child behavior checklist) über Kinder und Jugendliche im Alter zwischen 4 und 17 Jahren aus repräsentativen Studien wurden mit Hilfe von Varianzanalysen ausgewertet. Ergebnisse: Niederländische Eltern beschrieben mehr körperliche Beschwerden als deutsche. Die Ausprägung auf der Symptomskala stieg mit zunehmendem Alter und zeigte höhere Werte für Mädchen. Die Häufigkeit der Beschwerden variiert von 2% für „Augenbeschwerden” bis zu 15% für „Kopfschmerzen”. Bei Anwesenheit eines körperlichen Symptoms stieg die Frequenz zusätzlicher Beschwerden. Schlußfolgerung: Körperliche Beschwerden bei Kindern treten häufig ohne bekannte Ursache auf, bestimmte Beschwerden werden häufig gleichzeitig beschrieben, wobei die Koinzidenz nicht umkehrbar ist. Weitere, besonders ursächliche Studien auf dem Gebiet der körperlichen Beschwerden bei Kindern sind auch hinsichtlich steigender Kosten im Gesundheitswesen empfehlenswert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050409
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  • 23
    Electronic Resource
    Electronic Resource
    Naturlatexallergie-Screening bei Kindern mit neurogener Blasenentleerungsstörung (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: The risk to suffer from natural latex allergy is increased in children with congenital neurogenic bladder dysfunction. We, therefore, evaluated whether or not a serologic screening for detection of sensitization to latex is reasonable in these children. Patients and Methods: 40 children aged from 6 months to 17 years were examined by specific questionnaire-based patient histories, and by determination of total serum immunoglobuline E (total IgE) and natural latex-specific serum immunoglobulin E (latex-IgE) by solid-phase immunoassays. Results: 5 children had a history of allergic reaction to rubber containing materials. In 10 children, latex-IgE was elevated 〉 0.35 kU/l, 6 out of these 10 children without a history of allergic reactions to rubber containing materials. There was a positive correlation of elevated latex-IgE values and the number of former surgical procedures (p 〈 0.006), while no correlation was found between elevated latex-IgE values and clean intermittent catheterization (p = 0.408). Conclusion: Compared to questionnaire-based patient histories, serologic screening examination including determination of latex-IgE values may better identify children at risk to suffer from sensitization to natural latex.
    Notes: Zusammenfassung Fragestellung: Naturlatexallergien kommen bei Kindern mit angeborener neurogener Blasenentleerungsstörung gehäuft vor. Es wurde deshalb untersucht, ob bei dieser Patientengruppe ein serologisches Screening zur Erfassung einer Sensibilisierung gegenüber Naturlatex sinnvoll ist. Patienten und Methode: Untersucht wurden 40 Kinder im Alter von 6 Monaten bis 17 Jahren. Die Untersuchung umfaßte eine gezielte Anamneseerhebung durch Fragebogen sowie die Bestimmung des Gesamtimmunglobulin E (Gesamt-IgE) und des naturlatexspezifischen Immunglobulin E (Latex-IgE) im Serum durch Festphasenimmunoassays. Ergebnisse: 5 Kinder hatten anamnestisch Zeichen einer allergischen Reaktion nach Gummikontakt. 10 Kinder wiesen im Serum erhöhte Werte des Latex-IgE auf, wobei 6 dieser Kinder bisher noch keine Zeichen einer Latexallergie hatten. Pathologische Werte für das Latex-IgE korrelierten statistisch signifikant mit der Anzahl operativer Eingriffe (p 〈 0,0006), nicht aber mit einem durchgeführten sauber intermittierenden Einmalkatheterismus (p = 0,408). Schlußfolgerung: Im Vergleich zur alleinigen fragebogengestützen Anamneseerhebung können durch ein serologisches Screening mit Bestimmung des Latex-IgE mehr Kinder entdeckt werden, die durch eine Sensibilisierung gegenüber Naturlatex gefährdet sind.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050434
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  • 24
    Electronic Resource
    Electronic Resource
    Graded compression ultrasonography in the assessment of the “tough decision” acute abdomen in childhood (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 32-35 
    Details
    ISSN: 1437-9813
    Keywords: Key words Appendicitis ; Ultrasonography ; Children ; Graded compression ultrasonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The diagnosis of acute appendicitis in childhood is frequently difficult. In some situations the need to operate is clear, but in others the decisions may be much “tougher” because the clinical findings are equivocal. This is a retrospective study of a consecutive series of 253 children presenting with “acute abdominal pain? appendicitis” who had graded compression ultrasonography (GCUS) because the clinical scenario did not warrant immediate laparotomy. This represents 30% of all cases seen in the study period. The aim of the study was to examine the role of GCUS and a clinical scoring system (the Alvarado score) in patients in whom the diagnosis is uncertain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050506
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  • 25
    Electronic Resource
    Electronic Resource
    Inhalation burns in children (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 50-55 
    Details
    ISSN: 1437-9813
    Keywords: Key words Burns ; Inhalation injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Survival from serious burns in children has improved substantially in recent years. Mortality is predominantly determined by the total body surface area burned and the often unrecognised inhalation injury. A retrospective review of 4,451 consecutive children with thermal injuries over a 10-year period was undertaken to determine the incidence, clinical presentation, and pathology of inhalation injury and its contribution to morbidity and mortality. Inhalation burns were diagnosed clinically and confirmed endoscopically and post-mortem in 97 (2.2%) children; 77 sustained fire burns (mean age 4 years) and 20 hot-water burns (mean age 18 months). The Moylan classification stratified them into upper-airway burns in 59 children, major–airway burns in 29, and parenchymal burns in 44. Major-airway burns were always seen in conjunction with either upper-airway or parenchymal injury. Stridor and acute progressive respiratory distress were the two main symptoms, the onset of which was occasionally delayed for up to 72 h. Endoscopy was most helpful in confirming the diagnosis and determining airway management. Endotracheal intubation was needed in more than 50% of children, usually for less than 5 days, and was converted to tracheostomy in only 6. Persistent laryngeal and tracheal damage was identified in 4. Secondary pneumonia occurred in 41.5% of children with fire burns and 55% with hot-water burns. Extensive surface burns, parenchymal injury, and secondary pneumonia all contributed to the significant mortality. Post-mortem findings corroborated clinical and endoscopic evidence. This study suggests that inhalation burns were often not recognised, could present late, and usually had significant consequences. Early clinical diagnosis, supported by endoscopic findings and appropriate management, is essential if the high morbidity and mortality amongst these children is to be improved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050511
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  • 26
    Electronic Resource
    Electronic Resource
    Actinomycosis of the appendix in childhood (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 63-65 
    Details
    ISSN: 1437-9813
    Keywords: Key words Actinomycosis ; Antibiotic treatment ; Appendicitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abdominal actinomycosis (AMC) is a rare infection in children. The appendix is the most common intra-abdominal organ involved. It presents as an undifferentiated mass, forming abscesses and fistulas in the right lower quadrant. The case of a 15-year-old girl with a AMC of the appendix detected by the pathologist after routine appendectomy is discussed. Long-term antibiotic treatment and follow-up by ultrasound and laboratory controls are necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050515
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  • 27
    Electronic Resource
    Electronic Resource
    A conservative treatment for ingrown toenails in children (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 121-122 
    Details
    ISSN: 1437-9813
    Keywords: Key words Ingrowing nails ; Conservative treatment ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ingrowing nails are not uncommon in children, and even so receive little attention in the pediatric surgery literature. The purpose of the present study was to demonstrate our modification of the conservative treatment of ingrowing nails. Our technique of local treatment combined with patient education for better foot and toe care was successfully used and well tolerated by 19 out of 20 young patients with ingrown toenails.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050531
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  • 28
    Electronic Resource
    Electronic Resource
    Oxidation of lipoprotein in injury and repair of obstructive nephropathy (1999)
    Springer
    Clinical and experimental nephrology 3 (1999), S. 254-260 
    Details
    ISSN: 1437-7799
    Keywords: Key words Low density lipoprotein ; Apoptosis ; Malondialdehyde ; TGFβ1 ; Unilateral ureteral obstruction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. To test the hypothesis that oxidized low density lipoprotein (oLDL) is involved in the renal injury of obstructive nephropathy, male Sprague-Dawley rats weighing 125–150 g were used. Methods. Three days after arrival, the rats were randomly assigned to undergo: (1) sham operation, (2) left unilateral ureteral obstruction (UUO), or (3) reversal of the unilateral ureteral obstruction (R-UUO). Seven days after the reversal operation or 10 days after the sham or UUO procedure, all animals were killed by exsanguination under anesthesia, with blood taken from the abdominal aorta. LDL was prepared by gradient ultracentrifugation and used immedi-ately after isolation. Rat mesangial cells were utilized with an LDL concentration of 100 μg/ml/protein in the media. After 72 h, cell survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method. Cell survival was determined by comparing the optical density between the control wells and the experimental wells. In order to investigate the mechanisms of injury and repair of obstructive nephropathy, data for kidney apoptosis, malondialdehyde (MDA), and transforming growth factor β1 (TGFβ1) mRNA were obtained in the sham-operated, UUO, and R-UUO groups. Results. Our results showed that LDL malondialdehyde during UUO was increased 87% over baseline values (P 〈 0.005). With R-UUO, the oxidized LDL dropped 23% from the peak values during UUO (P 〈 0.005), but was still different from that of the baseline values (P 〈 0.025). Rat mesangial cell survival, after 72 h exposure to oLDL, inversely correlated to oLDL cytotoxicity and showed a 14% drop during UUO compared with sham-operated animals (P 〈 0.01). Cell survival increased 11% after R-UUO (P 〈 0.02) and was not different from control values (P = NS). The apoptotic counts by the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) technique showed significant increases during UUO and a noticeable reduction after R-UUO. Conclusion. Our data support the proposition that UUO stimulates oxidation of LDL. The cytotoxicity of oLDL plays a significant role in the injury of UUO. A decrease in cytotoxicity was associated with the repair in R-UUO. Our observations that apoptosis follows this same pattern, point to the importance of apoptosis in the injury and repair of obstructive nephropathy. Future studies to interrupt these processes of injury may lead to novel treatment modalities in reversing the injury and hastening the repair of obstructive nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101570050044
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  • 29
    Electronic Resource
    Electronic Resource
    Apoptosis and bcl-2 oncogene expression in Wilms' tumor (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 243-247 
    Details
    ISSN: 1437-9813
    Keywords: Key words Wilms' tumo ; Apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wilms' tumor (WT) usually has a good outcome, although a poor prognosis is often related to more advanced stages and anaplastic features. Apoptosis occurs with variable frequency in malignant tumors, and may have a role in reducing their growth rate. The bcl-2 proto-oncogene inhibits apoptosis, and the consequent increase in the number of cells may play a role in the development of tumors. The aim of this study was to analyze the role of apoptosis and bcl-2 expression in WT. Twenty-six resected WT specimens were studied; 12 patients had stage I tumor, 4 stage II, 5 stage III, 3 stage IV, and 2 stage V. Twenty-three tumors were classified as favorable histology (FH) and 3 as unfavorable (UH). The mean follow-up was 34 months; 22 patients were alive and 4 were dead (2 with FH: 1 stage III and 1 stage IV, and 2 with UH stages 4). Apoptosis was detected by the in-situ end-labelling technique; bcl-2 expression was detected by immunohistochemistry. An apoptotic index (AI) was calculated as the ratio of apoptotic to normal cells in each specimen. The AI was lower in higher tumor stages, with a significant difference between stages I and IV (P 〈 0.05). In cases with UH, Al was lower than in tumors with FH (P 〈 0.01). The AI was also lower in patients who died than in those who survived (P 〈 0.01). In all specimens no correlation between AI and bcl-2 expression was observed. Progression to advanced stages of WT and a poor prognosis f anaplastic tumors may be linked with disruption of the mechanisms that control apoptosis. Bcl-2 does not play a role as a regulator of apoptosis in WT, other oncogenes and tumor-suppression genes may be more involved in inhibiting apoptosis in WT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050567
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  • 30
    Electronic Resource
    Electronic Resource
    Acute scrotal pain in children: results of 543 surgical explorations (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 353-357 
    Details
    ISSN: 1437-9813
    Keywords: Key words Testis torsion ; Scrotum ; Appendage ; Cremasteric reflex ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A total of 543 boys suffering from acute scrotal pain underwent emergency surgery between 1986 and 1996. Of these, 91 had a testicular torsion (TT) (16.8%) and 250 had an appendage torsion (AT) (46%). The cause varied with patient age, with most TTs in newborns and boys of 15 years and most ATs in 10–11-year-olds; 21.5% were operated upon within 6 h of the onset of pain and 69.2% within 24 h. Most stayed in hospital for less than 24 h. Pre-surgical examination identified no criterion for excluding TT. We therefore believe that all children complaining of acute scrotal pain should undergo surgery. As release of an inflamed AT reduces pain, three-fourths of the children benefited directly from surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050598
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  • 31
    Electronic Resource
    Electronic Resource
    Small-cell carcinoma of the ovary of the hypercalcemic type in an 8-year-old girl (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 431-434 
    Details
    ISSN: 1437-9813
    Keywords: Key words Ovarian tumor ; Children ; Hypercalcemia ; Small-Cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumors of the ovary in girls represent about 80% of pediatric genital tumors; approximately 30% of these tumors are malignant. The risk of malignancy increases with decreasing age. The most frequent finding is a teratoma; other tumors are rare. Small-cell carcinoma (SCCO) of the ovary is extremely rare, occurring mostly in young women. We present an 8-year-old girl with a SCCO of the hypercalcemic type. The findings and treatment are discussed with emphasis on the poor prognosis in these patients, even in stage 1 disease. The current literature is reviewed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050625
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  • 32
    Electronic Resource
    Electronic Resource
    Effect of cell plating density and extracellular matrix protein on cell growth of epithelial rests of Malassez in vitro (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 127-132 
    Details
    ISSN: 1437-773X
    Keywords: Key words Epithelial rest of Malassez ; Cell ; cell interaction ; Extracellular matrix ; In vitro ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigated how cell plating density and extracellular matrix protein influence cell survival of epithelial rests of Malassez (ERM) in vitro. ERM cells were plated on culture dishes coated with laminin (LM), type IV collagen (type IV), or fibronectin (FN), or on noncoated dishes, (Non) at a cell density of 2 × 104–1 × 105/ml in a nonserum culture medium. XTT assays were performed to calculate the number of cells attached on the substrata after 6, 24, 48, and 72 h. Mean cell numbers were calculated, and significant differences were determined using ANOVA. When epithelial cells were cultured on various matrices at a cell density of less than 2 × 104/ml, the cells did not grow and then fell into apoptotic cell death, which was confirmed by transmission electron microscopy. The cell number was significantly increased in cells plated on FN compared to those on Non at a cell density of 4 × 104/ml–8 × 104/ml. These results suggest that both extracellular matrix proteins and cell–cell interactions may contribute to prevent apoptosis of ERM in vitro. Cell–cell interactions may be a more important factor than exogenous extracellular matrix proteins for the survival of ERM cells in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950050019
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  • 33
    Electronic Resource
    Electronic Resource
    Effect of anticancer agents on Fas-mediated cytotoxicity against bladder cancer cells (1999)
    Springer
    Journal of infection and chemotherapy 5 (1999), S. 139-143 
    Details
    ISSN: 1437-7780
    Keywords: Key words Fas ; ADR ; Bladder cancer ; Synergy ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fas and Fas ligand play an important role in cytotoxic T lymphocyte-mediated cytotoxicity. Like Fas ligand, anti-Fas monoclonal antibody (mAb) induces apoptosis of cells expressing Fas and mimics tumor necrosis factor-α (TNF-α) in its cytotoxic activity, but not in regard to other TNF-α-mediated activities. Since combination treatment with TNF-α and some anticancer chemotherapeutic agents results in synergistic cytotoxicity against various cancer cells, anti-Fas mAb may also synergize with anticancer agents in exerting cytotoxicity. The present study examined this hypothesis using bladder cancer cells. Cytotoxicity was examined by a 1-day microculture tetrazolium dye assay. Treatment of T24 cells with anti-Fas mAb in combination with mitomycin C, methotrexate, or 5-fluorouracil did not overcome their resistance to these agents. However, combination treatment with anti-Fas mAb and adriamycin (ADR) resulted in a synergistic cytotoxic effect on T24 cells, three other bladder cancer lines, and fresh bladder cancer cells derived from four patients. Treatment with ADR enhanced the expression of Fas on T24 cells. The expression of P-glycoprotein was not affected by the antibody-mediated sensitization. This study showed that combination treatment of bladder cancer cells with anti-Fas mAb and ADR can overcome their resistance and that the upregulation of Fas expression by ADR may play a role in the enhanced cytotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101560050023
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  • 34
    Electronic Resource
    Electronic Resource
    Expression of Fas and Bcl-2 proteins and induction of apoptosis in human hepatocellular carcinoma cell lines (1999)
    Springer
    Medical electron microscopy 32 (1999), S. 199-203 
    Details
    ISSN: 1437-773X
    Keywords: Key words Hepatocellular carcinoma ; Apoptosis ; Fas protein ; Bcl-2 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because the induction of apoptosis in cancer cells is very important in clinical management, it is useful to examine the association with the Fas–Fas ligand pathway and Bcl-2 protein family in apoptosis. We morphologically examined the expression of Fas and Bcl-2 proteins and induction of apoptosis by anti-Fas in four human hepatocellular carcinoma cell lines, PLC/PRF/5, Huh-6, and Huh-7, as well as OCUH-16, which was originally established in our university. Fas protein was expressed in 96% of OCUH-16 cells in cytoplasm, 24% of PLC/PRF/5 cells, 20% of Huh-6 cells, and no Huh-7 cells. Bcl-2 protein was expressed in 43%–72% of cells in cytoplasm and nuclei of the four lines examined. Administration of anti-Fas induced apoptosis in about 40% of OCUH-16 cells, but did not induce apoptosis in the other three cell lines. In conclusion, an original cell line, OCUH-16 cells, expressed Fas and Bcl-2 proteins and underwent apoptosis following treatment with anti-Fas, but the other three cell lines examined did not undergo apoptosis. OCUH-16 cells are thus very useful for the study of apoptosis and molecules related to apoptosis at the levels of cell-surface receptors and intracytoplasmic regulation of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950050002
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  • 35
    Electronic Resource
    Electronic Resource
    Hydatid cyst of the pancreas: a case report with 5 years' follow-up (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 579-581 
    Details
    ISSN: 1437-9813
    Keywords: Key words Hydatid disease ; Pancreas ; Children ; Echinococcosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary hydatid disease of the pancreas is rare. The authors report a 3-year-old girl who had a cystic mass in the head of the pancreas with no other viscera involved. At laparatomy the entire endocyst was totally extracted from the surrounding pancreatic parenchyma. The postoperative course was uneventful. She is currently disease-free with a follow-up of 5 years. Only four other pediatric cases have been reported in the English literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050677
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  • 36
    Electronic Resource
    Electronic Resource
    Effects of interleukin-6 (IL-6) on chemotherapy-induced apoptosis in human ovarian cancer cell lines (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 84-89 
    Details
    ISSN: 1437-7772
    Keywords: Key words Ovarian cancer ; Apoptosis ; IL-6 ; CDDP ; Taxol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Apoptosis is a cascade of events that is regulated by many factors. We studied the effects of interleukin-6 (IL-6) on chemotherapy-induced apoptosis in three human ovarian cancer cell lines (JV, GG, and NF). Methods. Cells were treated with the anticancer drugs cis-diamminedichloroplatinum (II) (CDDP) and paclitaxel (Taxol; Bristol-Myers Squibb Pharmacessticals, Noble Park, Australia) over a period of 72 h. The treatments were repeated in combination with human recombinant IL-6 or anti-IL-6 monoclonal antibody (anti-IL-6 mAb). The induction of cell death was examined by morphology and by internucleosomal DNA fragmentation. Results. Reduced cytotoxicity and fewer apoptotic cells were observed after treatment with CDDP or Taxol combined with IL-6 compared with treatment with CDDP or Taxol alone. However, treatment with CDDP or Taxol combined with anti-IL-6 mAb enhanced the cytotoxic effects of the drugs and increased the number of apoptotic cells. These findings indicated that apoptosis caused by CDDP or Taxol was influenced negatively by high doses of IL-6. Conclusion. The use of CDDP or Taxol combined with anti-IL-6 mAb may have therapeutic value for patients with ovarian cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101470050032
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  • 37
    Electronic Resource
    Electronic Resource
    A method to overcome the inability to draw blood from central venous lines in children (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 525-526 
    Details
    ISSN: 1437-9813
    Keywords: Key words Central venous catheters ; Children ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The insertion of central venous catheters has become an established practice in the management of children with different types of malignancies for the administration of chemotherapeutic agents, antibiotics, blood and blood products, as well as drawing blood for various investigations. A commonly encountered problem is that despite the catheter being patent it may be impossible to draw blood from it. We believe this is related to the cut of the catheter tip. To overcome this problem, a technique for cutting the tip of the catheter is described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050659
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  • 38
    Electronic Resource
    Electronic Resource
    Reduced expression of CD99 and functional disturbance in anencephalic cortical thymocytes (1999)
    Springer
    Virchows Archiv 434 (1999), S. 443-449 
    Details
    ISSN: 1432-2307
    Keywords: Key words Anencephaly ; Thymic hyperplasia ; CD99 ; Apoptosis ; Aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a significant proportion of cases, anencephaly is associated with thymic enlargement, suggesting a possibility that anencephalic fetuses have a functional disturbance in thymocyte differentiation and development. In this report, we demonstrated that CD99 expression was consistently reduced in cortical thymocytes of all anencephalic fetuses. In addition, the CD99-dependent aggregation of immature cortical thymocytes was almost completely impaired and apoptosis of thymocytes was markedly reduced in several cases. These results are in agreement with previous findings that CD99 regulates the aggregation and apoptosis of various types of cells. These data strongly suggest that functional disturbance of thymocytes and thymic hyperplasia are related to the reduced expression of CD99 molecule in anencephalic fetuses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050364
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  • 39
    Electronic Resource
    Electronic Resource
    Hemmung der Tumorneoangiogenese und Induktion von Apoptose als Eigenschaften von Docetaxel (Taxotere®) (1999)
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 3 (1999), S. 210-212 
    Details
    ISSN: 1434-3940
    Keywords: Schlüsselwörter Plattenepithelkarzinom ; Tumorneoangiogenese ; Apoptose ; Key words Squamous cell carcinoma ; Tumor neoangiogenesis ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Paclitaxel and docetaxel are potent drugs that are effective in the treatment of malignant tumors. The cytotoxic action of these drugs is not fully understood, but it appears to be mediated mainly through mitotic arrest and subsequent apoptosis. Because no information is available on the antiangiogenesis action of docetaxel, the investigations were performed to determine whether inhibition of neoangiogenesis plays a role in docetaxel’s antitumor efficacy. Four different mouse tumors, two squamous cell carcinomas (SCC-IV; SCC-VII) and two adenocarcinomas (MCA-4; MCA-29) were assayed for angiogenic activity using the in vivo i.c. angiogenesis assay. Tumor cells (5 × 105) were injected i.c. into the skin flap over the abdominal wall, and the number of new blood vessels at the tumor cell injection site was determined 2, 4, 6, 8, 10 and 12 days later. The mice were treated with docetaxel (Taxotere – 31.3 mg/kg i.v.) 1 or 4 days after tumor cell injection. The number of new blood vessels increased with time. Docetaxel reduced the number of newly formed blood vessels in MCAs, but not in SCCs. The reduction was associated with slower tumor growth. In a separate set of experiments we observed that docetaxel’s inhibitory effect on the two MCAs was histologically associated with massive tumor cell destruction by means of both apoptosis and necrosis. This was not observed for the two SCCs. Since no reduction in blood vessels occurred in tumors unresponsive to docetaxel, the inhibition of neoangiogenesis in docetaxel-responsive tumors was likely the result of a decrease in angiogenic stimuli due to docetaxel’s destruction of tumor cells.
    Notes: Die zytotoxische Aktivität der Taxane Paclitaxel und Docetaxel ist zum jetzigen Zeitpunkt noch nicht vollständig erklärt. Diese, zur Behandlung maligner Tumoren eingesetzten antineoplastischen Chemotherapeutika, scheinen jedoch weitgehend über die Blockierung der Mitose und die nachfolgende Induktion der Apoptose zu wirken. Über eine evtl. Hemmung der Neoangiogenese, wie sie kürzlich für Paclitaxel beschrieben wurde, liegen für Docetaxel noch keine Studienergebnisse vor. Es wurde deshalb untersucht, ob die therapeutische Aktivität von Docetaxel zur Hemmung der Neoangiogenese im Tumor beitragen kann. 4 murine Tumoren, 2 Plattenepithelkarzinome (SCC-VII; SCC-IV) und 2 Adenokarzinome (MCA-4; MCA-29), wurden in einem quantitativen intrakutanen In-vivo-Angiogenese-Assay experimentell untersucht. 5 · 10 5 Tumorzellen wurden in einen Abdominallappen der Maus injiziert. Die Anzahl neuformierter Blutgefäße und das Tumorwachstum wurden im 2tägigen Intervall über einen Zeitraum von zwischen 10 und 14 Tagen bestimmt. 2 Behandlungsgruppen wurde am 1. oder 4. Tag nach der Tumorzellinokulation Docetaxel (Taxotere – 31,3 mg/kg) i.v. injiziert. Die Plattenepithelkarzinome waren gegenüber der Therapie mit Docetaxel nicht sensibel, während die Adenokarzinome mit einer Abnahme der Gefäßzahl und einer Reduktion des Tumorvolumens reagierten. Histologisch zeigten die Adenokarzinome außerdem eine massive Tumorzelldestruktion durch Apoptose und Nekrose. Da die gegenüber Docetaxel nichtsensiblen Tumoren (Plattenepithelkarzinome) nicht mit einer Abnahme der Gefäßzahl reagierten, ist der beschriebene Effekt in den Adenokarzinomen am ehesten als indirekte Wirkung von Docetaxel zu werten. Die Tumorzelldestruktion führte in den betroffenen Tumoren zu einer verminderten Freisetzung endothelialer Mitogene wie VEGF und bFGF und zur Hemmung der Tumorneoangiogenese.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100060050132
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  • 40
    Electronic Resource
    Electronic Resource
    Differential expression of heat shock proteins 70-1 and 70-2 mRNA after ischemia-reperfusion injury of rat kidney (1999)
    Springer
    Urological research 27 (1999), S. 306-311 
    Details
    ISSN: 1434-0879
    Keywords: Keywords Ischemia-reperfusion ; Heat shock ; HSP70 ; Kidney ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i –HSP70-1 gene and HSP70-2 gene – is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10–60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA – which was generally expressed at a far lower level than HSP70-1 mRNA – was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050155
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  • 41
    Electronic Resource
    Electronic Resource
    Apoptosis in human embryonal cell carcinoma: preliminary results (1999)
    Springer
    Urological research 27 (1999), S. 368-375 
    Details
    ISSN: 1434-0879
    Keywords: Keywords Testicular neoplasms ; Embryonal cell ; carcinoma ; Apoptosis ; Lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Disorders in the regulation of apoptotic cell death may contribute to cancer. Furthermore, lymphocytes are supposed to play a role in counteracting tumorigenesis by inducing apoptosis in different human tumors. In this study, for the first time, tumor cell and lymphocyte apoptosis were investigated systematically in human embryonal cell carcinoma. DNA fragmentation and DNA condensation were measured simultaneously on double-fluorescence-labeled testis tumor sections using immunofluorescence microscopy. Different apoptotic indices (AIs), based either on biochemical (DNA fragmentation) or morphological criteria (DNA condensation) alone or on a combination of both, were determined in different histological regions in and around the tumor. Using morphological criteria alone, 40–75% of all apoptotic cells were not detected. Based on previous observations this finding might be related to subsets of apoptotic cells which induce the process of DNA condensation without activation of processes responsible for DNA fragmentation. Moreover, the AIs of tumor cells and lymphocytes were highest in the tumor region, compared with regions around the tumor and distant from it; these findings are discussed in the context of the Fas/FasL system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050165
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  • 42
    Electronic Resource
    Electronic Resource
    Localization and expression of Jun-like immunoreactivity in apoptotic neurons induced by colchicine administration in vivo and in vitro depends on the antisera used (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 119-128 
    Details
    ISSN: 1432-0533
    Keywords: Key words c-Jun ; Jun B ; Jun D ; Apoptosis ; Colchicine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of members of the Jun family of transcription factors was examined by immunohistochemistry, Western blotting, in situ hybridization and Northern blotting in the developing and adult rat brain following colchicine administration. Apoptotic cells, as revealed by their typical morphology and positive staining with the method of in situ end-labeling of nuclear DNA fragmentation, were restricted to granule cells of the dentate gyrus and olfactory bulb, and a few cells in the upper layers of the entorhinal cortex in adult rats, whereas widespread apoptosis occurred in developing rats after colchicine administration. No modifications in the expression of Jun D and Jun B, except for a generalized and moderate Jun B expression in glial cells, were observed in colchicine-treated rats. Generalized and strong c-jun mRNA induction and c-Jun/AP-1 (Ab-1) protein expression was observed in the cerebral neocortex, entorhinal and piriform cortices, CA1 and CA3 areas of the hippocampus and granule cell layer of the dentate gyrus in adult treated rats, thus indicating a generalized c-Jun response to colchicine administration. In contrast, c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) immunoreactivity was restricted to apoptotic cells in colchicine-treated adult and developing brains. Western blots of hippocampal homogenates and total brain homogenates in adult and developing rats, respectively, demonstrated a band of 39 kDa for the c-Jun/AP-1 (Ab-1) antibody in control animals, the intensity of which increased in colchicine-treated rats. However, a band of 37 kDa, the intensity of which also increased following colchicine administration, was observed for the c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) antibodies. Selective c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) expression was also observed in apoptotic cells of the SH-SY5Y neuroblastoma line after the addition of colchicine to the culture medium. Taken together, the present in vivo and in vitro results indicate a generalized c-Jun response to colchicine in sensitive cells, whereas the antibodies c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) recognize vulnerable cells dying via apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051059
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  • 43
    Electronic Resource
    Electronic Resource
    Neuronal vacuolation in young Rottweiler dogs (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 192-195 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuronal vacuolation ; Rottweiler dog ; Bcl-2 ; Bax ; c-Jun ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal vacuolation, involving the cerebellar roof nuclei, Purkinje cells, selected nuclei of the brain stem, thalamus, Clarke’s column, anterior and posterior horns of the spinal cord, visceral autonomic ganglia and myenteric plexus, as well as axonal degeneration of the white matter of the brain stem, cerebellar pedunculi, dorsolateral columns of the spinal cord and ventral roots of the spinal cord, were observed in two young Rottweiler dogs which were clinically afflicted with hind limb weakness progressing to paraparesia, ataxia, intention tremor, and difficulty in swallowing and barking. The absence of modifications in Bcl-2 and Bax immunoreactivity, a lack of strong c-Jun/AP-1 (N) immunoreactivity in vacuolated cells, and the absence of DNA breaks, as seen with the method of in situ end-labeling of nuclear DNA fragmentation, all suggest that there is no involvement of the apoptotic pathway in vacuolated cells in this new neurodegenerative disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050973
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  • 44
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    Electronic Resource
    Increased lipocortin-1 (annexin-1) expression in the sciatic nerve of Lewis rats with experimental autoimmune neuritis (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 583-589 
    Details
    ISSN: 1432-0533
    Keywords: Key words Glucocorticosteroids ; Apoptosis ; Guillain-Barré syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lipocortin-1 exerts a potent immunosuppressive effect on pathogenic T cells. In multiple sclerosis and experimental autoimmune encephalomyelitis levels of lipocortins are raised, suggesting their involvement in the recovery from an immunological insult or in neural regeneration. To further understand the role of lipocortins in the peripheral nervous system we have characterized lipocortin-1 levels and cellular distribution of lipocortin-1 immunoreactivity in sciatic nerves of rats with experimental autoimmune neuritis (EAN), a model of human Guillain-Barré syndrome. EAN was induced actively by immunization with bovine peripheral myelin (active EAN) or by adoptive-transfer (AT-EAN) of P2-specific T cells. Cellular infiltrates in serial and semithin cryosections were characterized by immunohistochemistry. In parallel, lipocortin-1 levels in tissue extracts were quantified by a sandwich-ELISA. Only weak lipocortin-1 immunoreactivity was found in nerves of control animals injected with non-pathogenic T cells. The majority of macrophages and lymphocytes in EAN lesions exhibited lipocortin-1 immunoreactivity. Some very heavily stained cells showed a distribution and morphology similar to ED-2-positive macrophages which were abundant during early stages of EAN. Lipocortin-1 expression in T cells and macrophages was proven by immunocytochemical studies in semithin serial sections. In tissue extracts, lipocortin-1 levels increased from 0.24 ± 0.14 μg/mg protein in controls receiving non-pathogenic T cells to a maximum of 0.55 ± 0.1 μg/mg protein in AT-EAN at the peak of disease, and then slowly decreased during clinical recovery but still remained elevated. In dose-response studies in AT-EAN, highest values of lipocortin-1 (0.71 ± 0.23 μg/mg protein) were recorded after transfer of 2 × 107 T cells. Increased levels of lipocortin-1 were also measured in active EAN but occurred during the recovery phase (0.65 ± 0.27 μg/mg protein). By analogy with other immune-mediated disorders, increased lipocortin-1 expression in the inflamed sciatic nerve in EAN may exert immunoregulatory functions in-situ and contribute to the termination of the autoimmune response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051122
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  • 45
    Electronic Resource
    Electronic Resource
    Immunoelectron microscopic study of c-Fos, c-Jun and heat shock protein after transient cerebral ischemia in gerbils (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 22-30 
    Details
    ISSN: 1432-0533
    Keywords: Key words Immediate early gene ; Heat shock protein ; Cerebral ischemia ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neuroprotective role of the expression of heat shock protein (HSP) and immediate early gene remains unclear. Using immunoelectron microscopy, we examined the ultrastructural integrity of the neurons with expression of c-Fos, c-Jun and HSP70 in gerbils after transient cerebral ischemia and repefusion. Induction of c-Fos and c-Jun was observed in the CA3 region resistant to ischemia, while HSP70 was expressed not only in the CA3 but also in the vulnerable CA1 region. With immunoelectron microscopy, the expression of c-Fos/c-Jun and HSP70 was observed in the neurons which retained neuronal integrity except for mitochondrial swelling and polyribosomal disaggregation. In contrast, the CA1 neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and parallel stacking of rough endoplasmic reticulum, the features associated with the process of delayed neuronal death. These findings suggested that c-Fos and c-Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up-regulated even in neurons with irreversible damage, but was more preferentially and intensely expressed in neurons with reversible damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050951
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  • 46
    Electronic Resource
    Electronic Resource
    Nuclear DNA fragmentation in Creutzfeldt-Jakob disease: does a mere positive in situ nuclear end-labeling indicate apoptosis? (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 5-12 
    Details
    ISSN: 1432-0533
    Keywords: Key words Creutzfeldt-Jakob disease ; Apoptosis ; Cell death ; Prion protein ; In situ end-labeling of nuclear DNA fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The method of in situ end-labeling of nuclear DNA fragmentation was used in the study of ten patients (two biopsies, eight autopsies) with sporadic Creutzfeldt-Jakob disease (CJD). All the patients had the typical morphological lesions including neuron loss, spongiform change and astrocytosis. Four of them also showed prion protein (PrP) deposits in the cerebral cortex, and two of them kuru-like plaques in the cerebellum. A few cells with DNA breaks were found in the two biopsy cases; one of them, suffering from a panencephalopathic form of the disease, showed positive nuclei not only in the cerebral cortex but also in the subcortical white matter. Variable numbers of positive nuclei were observed in the gray and white matter in the eight autopsy cases, in which, although the distribution of positive cells roughly correlated with the distribution of neuron loss, no clear relationship was found as regards the distribution and degree of cell labeling and the degree of neuron loss. Furthermore, large numbers of positive cells were concentrated in a particular area, whereas a few cells were seen in a neighboring equally affected area. Positive glial cells in the plexiform layer of the CA1 area of the hippocampus, and in the frontal white matter were frequently encountered. Staining of the cytoplasm in a minority of cells was interpreted as the result of nuclear DNA leakage. None of the stained cells had the typical morphology of apoptosis; most particularly, peripheral chromatin condensation and formation of apoptotic bodies were not seen in any case. PrP deposits did not result in an increase of nuclear DNA breaks either within the area or in adjacent regions. Although positive cells were also observed in autopsy cases of controls which were processed in the same way, positive labeling as a whole was higher in CJD than in age-matched controls. These results show that brain nuclear DNA is vulnerable in CJD, and suggest that increased DNA vulnerability has a role in cell death and neuron loss. Since nuclear shrinkage and positive nuclear staining with the method of in situ end-labeling of nuclear DNA fragmentation are not exclusive to apoptosis, further information is needed to categorize cell death in CJD as apoptosis. Necrosis or other forms of cell death, as well as increased DNA vulnerability to agonal changes of the individuals, and to postmortem delay in the fixation of the tissues, may account for additional positive staining in cases examined at autopsy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050949
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  • 47
    Electronic Resource
    Electronic Resource
    Epithelial involution and basement membrane loss during early rhombencephalic tectoria lamina development (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 203-214 
    Details
    ISSN: 1432-0568
    Keywords: Key words Extracellular material ; Cell proliferation ; Apoptosis ; Anoikis ; Tenascin ; Laminin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular material molecules play a key role in the regulation of morphogenesis and differentiation of a large number of organs including the central nervous system. However, the role of the neural basement membrane in the growth of different parts of the neural tube has yet to been delineated. Here, the structural and compositional modifications of the basement membrane (BM) of rhombencephalic tectoria lamina anlage (RTLA) have been examined during the process of RTLA epithelial attenuation. Between stages 10 to 11– the presumptive RTLA epithelium showed a structure, thickness and cell-proliferating capacity similar to those observed in other zones of the rhombencephalic walls. Moreover, the rhombencephalic vesicles were surrounded by a continuous BM that was heterogeneous both ultrastructurally and with regard to ruthenium red, laminin and tenascin distribution. After stage 11, the RTLA epithelium underwent a rapid process of attenuation and change to a stratified flattened epithelium. During this remodelling process, apoptosis and inhibition of both PCNA expression and 3H-thymidine uptake occurred in the RTLA epithelium. The BM of the RTLA underwent a process of degration at the beginning of the remodelling, and apoptosis and cell proliferation inhibition of RTLA epithelium were also observed. The loss of the biochemical signals encoded within the BM could lead to cell shape changes, cell proliferation inhibition and to the anoikis type of cell death. Our findings support the idea that the BM surrounding the neural tube plays a key role in controlling both the structure and growth of the CNS during the early developmental stages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050273
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  • 48
    Electronic Resource
    Electronic Resource
    Sonic hedgehog enhances somite cell viability and formation of primary slow muscle fibers in avian segmented mesoderm (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 239-252 
    Details
    ISSN: 1432-0568
    Keywords: Key words Somite explant culture ; Sonic hedgehog protein ; Myogenic induction ; Primary fiber type diversity ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Primary skeletal muscle fibers first form in the segmented portions of paraxial mesoderm called somites. Although the neural tube and notochord are recognized as crucial in patterning myogenic cell lineages during avian and mammalian somitic myogenesis, the source, identities, and actions of the signals governing this process remain controversial. It has been shown that signals emanating from the ventral neural tube and/or notochord alone or Shh alone serve to activate MyoD expression in somites. However, beyond a role in initiating MyoD expression, little is known about the effects of Shh on primary muscle fiber formation in somites of higher vertebrates. The studies reported here investigate how the ventral neural tube promotes myogenesis and compare the effects of the ventral neural tube with those of purified Shh protein on fiber formation in somites. We show that purified Shh protein mimics actions of the ventral neural tube on somites including initiation of muscle fiber formation, enhancement of numbers of primary muscle fibers, and particularly, the formation of primary fibers that express slow myosin. There is a marked increase in slow myosin expression in fibers in response to Shh as somites mature. The effects of ventral neural tube on fiber formation can be blocked by disrupting the Shh signaling pathway by increasing the activity of somitic cyclic AMP-dependent protein kinase A. Furthermore, it was demonstrated that apoptosis is a dominant fate of somite cells, but not somitic muscle fibers, when cultured in the absence of the neural tube, and that application of Shh protein to somites reduced apoptosis. The block to apoptosis by Shh is a manifestation of the maturity of the somite with a progressive increase in the block as somites are displaced rostrally from somite III forward. We conclude that purified Shh protein in mimicking the effects of the ventral neural tube on segmented mesoderm can exert pleiotropic effects during primary myogenesis, including: control of the proliferative expansion of myogenic progenitor cells, antagonism of cell death pathways within the precursors to muscle fibers, and during the crucial process of primary myogenesis, can exert an effect on diversification of muscle fiber types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050276
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  • 49
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    Electronic Resource
    Cell death and apoptosis regulating proteins in Parkinson’s disease – a cautionary note (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 408-412 
    Details
    ISSN: 1432-0533
    Keywords: Key words Parkinson’s disease ; Apoptosis ; Bcl-2 ; Bax ; Bcl-x
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the substantia nigra of three Parkinson’s disease (PD) patients and three age-matched individuals by in situ DNA-end labeling (ISEL) and immunohistochemistry for the apoptosis regulating proteins Bcl-2, Bax and Bcl-x on 50 consecutive sections per patient. No melanin-containing cell was identified with typical apoptotic changes in either patient or control substantia nigra. With prolonged reaction-time the terminal transferase-mediated DNA-end labeling revealed a signal in 2.0 ± 1.2% melanin-containing cells in PD compared to 1.3 ± 1.1% in control. This difference did nor reach statistical significance and no condensation or margination of the chromatin was evident. No significant changes of any of the apoptosis regulating proteins were apparent in PD substantia nigra. These findings do not support the hypothesis that apoptosis plays a central role in the pathogenesis of PD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051005
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  • 50
    Electronic Resource
    Electronic Resource
    Oligodendroglial degeneration in distemper: apoptosis or necrosis? (1999)
    Springer
    Acta neuropathologica 97 (1999), S. 279-287 
    Details
    ISSN: 1432-0533
    Keywords: Key words Canine distemper virus ; Oligodendrocytes ; Apoptosis ; Necrosis ; Demyelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Canine distemper virus (CDV) causes a multifocal demyelinating disease in dogs. It was previously shown that the initial demyelinating lesions are directly virus induced since a correlation between the occurrence of demyelination and CDV replication in white matter cells was observed. During the course of infection oligodendrocytes undergo distinct morphological alterations, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as well as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infection can induce cell death, it was investigated whether apoptosis or necrosis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells were not detected within the demyelinating lesions using morphological and biochemical cell death criteria. In chronic distemper, apoptotic cells – presumably inflammatory cells – were seen within the perivascular cuffs. These in vivo findings were correlated to the in vitro situation using CDV-infected primary dog brain cell cultures as well as Vero cells. Infection with culture-adapted CDV lead to massive necrosis but not to apoptosis. After infection with virulent CDV neither apoptosis nor necrosis was a predominant feature in either culture system. These findings suggest that virus-induced demyelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible for the observed morphological alterations of oligodendrocytes, ultimately leading to demyelination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050986
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  • 51
    Electronic Resource
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    Differential maturational patterns of nitric oxide synthase-I and NADPH diaphorase in functionally distinct cortical areas of the mouse cerebral cortex (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 27-41 
    Details
    ISSN: 1432-0568
    Keywords: Key words Brain ; Cortical parcellation ; Development ; Proteoglycans ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nitric oxide (NO) regulates several functions both in the developing and the adult central nervous systems (CNS). During development, NO is assumed to contribute to the histogenetic differentiation of the CNS especially through the modulation of programmed neuronal death. The embryonal and postnatal changes in the distribution of the cortical NO producing system were studied in Balb/c mice using immunocytochemistry for nitric oxide synthase-I (NOS-I) and NADPH-diaphorase (NADPH-d) enzyme histochemistry. NOS-I reactive neurons (RN) appeared first at embryonic day 14 (E14) in the spinal cord in the vicinity of the central canal, and later, at E16–18, in the thalamus and striatum. The first cortical region to present NOS-I reactivity was the parietal cortex, which happened at E18–20. After E20 the number of NOS-I RN increased in every cortical area, plateauing at postnatal day 4 (P4). In parietal regions, however, the highest density of NOS-I RN was observed already at P1. The neuronal packing density (PD) of NOS-I RN declined until adulthood, interrupted by a transient increase in some cortical areas at the onset of puberty. The heterochronous appearance of NOS-I during pre- and postnatal development of different brain regions and the sequence of up- and downregulation of expression until adult stages points to an important role of NO in brain development and functional differentiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050256
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  • 52
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    Development of glomerular synaptic complexes and immunohistochemical differentiation in the superficial dorsal horn of the embryonic primate spinal cord (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 125-148 
    Details
    ISSN: 1432-0568
    Keywords: Key words Synaptogenesis ; Primate ; Spinal cord ; Apoptosis ; Neuropeptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Development of glomerular synapses in the superficial dorsal horn has been studied in the embryonic macaque spinal cord using light and electron microscopic techniques including Golgi impregnation, 3H-thymidine radioautography and pre-embedding immunohistochemistry of substance P (SP), calcitonin gene related peptide (CGRP), calbindin D-28 K (CB) and parvalbumin (PV). The study revealed that substantia gelatinosa cells of the primate dorsal horn are generated last, but unlike in rodents, synaptogenesis in this region starts at early embryonic (E) stages of the 165-day long gestation. Already by E30, both Type 1 (light) and 2 (dark) dorsal root axons and their growth cones are identifiable within the oval bundle of His, before they form synaptic contact with their final target cells. Subsequently they invade the dorsal horn and enter the bisecting interfaces formed by orderly programmed cell death. Each type of scalloped (sinusoid) central primary afferent terminal (i.e. DSA, RSV and LDCV) have well defined pre- and post-synaptic specializations already by E40. Among the neuropeptides studied, SP appears first at E67 and CGRP at E70 in the lateral position but within a few days both of them are spread to the entire superficial dorsal horn. Both SP and CGRP are present in the thin dorsal root axons and their growth cones, giving rise to scalloped and simple axon terminals. PV is transiently present in the entire length of the thick dorsal root afferents before becoming concentrated in the synaptic boutons. CB is displayed mainly in neurons of the lamina I and III. Dendrites of CB-immunoreactive cells establish synaptic connection with each type of dorsal root afferents, including glomerular synaptic complexes. These data reveal that the superficial dorsal horn in the primate spinal cord develops its characteristic synaptic complexes much earlier in gestation than in any other mammalian species studied. Furthermore, characteristic cytological features of the prospective glomerular complex emerge before establishment of the final synaptic contacts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050215
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  • 53
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    UV irradiation induces downregulation of bcl-2 expression in vitro and in vivo (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 212-216 
    Details
    ISSN: 1432-069X
    Keywords: Key words UV irradiation ; Solar-simulated irradiation ; Apoptosis ; bcl-2 ; bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, the proto-oncogenes bcl-2 and bax have emerged as important regulators of the apoptotic form of cell death. We examined UV irradiation-elicited apoptosis and regulation of bcl-2 and bax expression both in vivo in human skin and in vitro in HeLa cells. Using flow cytometric analysis, HeLa cells were found to undergo apoptosis at the 12-h time-point after exposure to UVB irradiation (100 mJ/cm2). The expression of bcl-2 mRNA was found to decrease after a single dose of UVB radiation (doses 10–200 mJ/ cm2). In contrast, the expression of bax mRNA was not significantly changed. When human skin was irradiated with a single dose of solar-simulated radiation (40 mJ/cm2), Bcl-2-positive cells were significantly reduced in the epidermis at the 3- and 6-h time-points. Our results suggest that UV irradiation downregulates bcl-2 expression both in vitro at the mRNA level and in vivo at the protein level, and that downregulation of bcl-2 constitutes a mechanism of potential importance in UV-induced apoptosis in human epidermis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050396
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  • 54
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    Detection of apoptosis in hair follicles and acrosyringium of normal human scalp skin by labeling of nick ends of fragmented DNA (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 300-302 
    Details
    ISSN: 1432-069X
    Keywords: Key words TUNEL ; Apoptosis ; Trichilemmal ; keratinization ; Epidermal appendages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050412
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  • 55
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    Electronic Resource
    Langerhans cells enclosing sunburn cells in acute UV erythema in vivo (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 303-305 
    Details
    ISSN: 1432-069X
    Keywords: Key words Langerhans cells ; Sunburn cells ; UV ; erythema ; Apoptosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050413
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  • 56
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    Subphysiological concentrations of extracellular calcium sensitize normal human keratinocytes to UVB-induced apoptosis (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 37-46 
    Details
    ISSN: 1432-069X
    Keywords: Key words Keratinocyte ; UVB ; Apoptosis ; Calcium ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normal human keratinocytes are stimulated to proliferate in serum-free medium containing subphysiological concentrations of calcium (0.09 mM, low calcium). In this study, we examined the effect of increased levels of extracellular calcium (2.0 mM, normal calcium) on UVB-induced apoptosis. Apoptosis was assessed by changes in cellular morphology, annexind V-FITC flow cytometry, and the formation of internucleosomal DNA ladders. High doses of UVB induced keratinocytes grown in low calcium medium to undergo apoptosis. In contrast, keratinocytes grown for 72 h in normal calcium medium were completely resistant to UVB-induced apoptosis. No apoptosis was observed even at UVB doses as high as 1200 J/m2. However, despite the lack of UVB-induced cell death, keratinocytes grown in normal calcium medium lost the ability to proliferate following high levels of UVB irradiation. High doses of UVB also increased the expression of the differentiation-specific proteins involucrin and cytokeratin 10 in a dose-dependent manner. In addition, growth in normal calcium medium lowered the UVB-induced stimulation of the p53 protein and altered the normal subcellular localization pattern of p53. UVB irradiation of human keratinocytes grown in normal calcium medium may be inducing further cell differentiation in the absence of overt cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050381
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  • 57
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    Cell cycle regulation and induction of apoptosis by IL-6 variants on the multiple myeloma cell line XG-1 (1999)
    Springer
    Annals of hematology 78 (1999), S. 13-18 
    Details
    ISSN: 1432-0584
    Keywords: Key words IL-6 variants ; Cell cycle ; Apoptosis ; Multiple myeloma ; Cell line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin-6 (IL-6) serum levels and the proliferative activity of bone marrow plasma cells have been described as important prognostic factors for survival duration in multiple myeloma (MM) patients. Since growth of neoplastic plasma cells is frequently promoted by IL-6, inhibition of its activity has been considered for the management of MM patients. With a similar rationale, IL-6 variants characterized by wild-type or increased affinity for the ligand-specific IL-6 α receptor chain and reduced ability to bind and/or dimerize the gp 130 chain have recently been generated. In the present study, the antiproliferative effects of the variants Sant1, Sant5, and Sant7, characterized by increasing antagonistic activity, were investigated by means of a detailed cell kinetic and apoptotic analysis of the IL-6-dependent MM XG-1 cell line. A significant reduction in the mean percent of XG-1 cells in active S-phase (DNA/bromodeoxyuridine incorporation) from 41% to 28.1% (p=0.04), 25.8% (p=0.04), and 15.3% (p=0.02), respectively, was observed using Sant1, Sant5, and Sant7. These effects were confirmed using the acridine-orange (AO) flow-cytometric technique, which showed a similar reduction of S-phase (34.2% of baseline value) in the presence of Sant1, Sant5, and Sant7, as well as a significant G1b arrest (from 44.5% to 47.6%, 48%, and 64.9%). Furthermore, IL-6 variants were capable of down-regulating the G1 cell cycle regulatory protein cyclin D1 expression. Cell cycle effects were coupled with a significant increase of apoptosis, measured by the AO and the terminal deoxynucleotidyl transferase assays, from 12.9% (control culture with IL-6) to 21.2% (Sant1), 29.1% (Sant5), and 23.5% (Sant7). These results were comparable to those obtained by depriving XG-1 of recombinant IL-6. Our study documents the antiproliferative activity exerted by IL-6 mutants on the XG-1 cell line, thus supporting the investigation of these molecules on primary MM cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050465
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  • 58
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    Polyclonal hypergammaglobulinemia at the onset of acute myeloid leukemia in children (1999)
    Springer
    Annals of hematology 78 (1999), S. 445-448 
    Details
    ISSN: 1432-0584
    Keywords: Key words Hypergammaglobulinemia ; Polyclonal ; Acute myeloid leukemia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050596
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  • 59
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    Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis (1999)
    Springer
    Annals of hematology 78 (1999), S. 65-72 
    Details
    ISSN: 1432-0584
    Keywords: Key words Idiopathic myelofibrosis ; PCNA labeling ; Apoptosis ; Dynamic disease features ; Prognosis ; Proportion of life loss ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous studies, our cohort comprised the full spectrum of the disease, from initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed significant differences between early and advanced fibrosclerotic stages of disease. Decrease in proliferation indicated a significantly shorter survival, whereas a higher frequency of apoptotic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is accompanied by a higher incidence of apoptosis reflects the regenerative (turnover) capacity of hematopoiesis. This may apply especially to early hypercellular stages without relevant myelofibrosis. In consideration of a recently published multivariate risk model, a simplified synthesis score for stratification of a patient's prognosis was constructed. Age, degree of anemia, leukocytes, and platelet count were regarded as the most important parameters. A substantial improvement of prognostic efficiency was further achieved by including PCNA index and frequency of apoptosis. Our results are in keeping with the assumption that generalization, indicated by myeloid metaplasia, has a prodigious impact on prognosis in IMF. Furthermore, in this context dynamic features such as proliferative activity and frequency of apoptosis exert an additional predictive value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050474
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    Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias (1999)
    Springer
    Annals of hematology 78 (1999), S. 401-407 
    Details
    ISSN: 1432-0584
    Keywords: Key words Thrombopoietin ; Interleukin-11 ; Interleukin-6 ; Thrombocytopenia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050538
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  • 61
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    Propionibacterium acnes induces acute TNFα-mediated apoptosis of hepatocytes followed by inflammatory T-cell-mediated granulomatous hepatitis in mice (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 349-356 
    Details
    ISSN: 1423-0127
    Keywords: TNFα ; Fas ; FasL ; Apoptosis ; Cytokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The CD3+/TCRαβ+ T-cell-mediated hepatic inflammation induced byPropionibacterium acnes could be divided into an acute and a chronic phase. The acute phase occurred within 72 h after injection and displayed hepatic apoptosis. Anti-TNFα antibody inhibited both theP. acnes-induced hepatic apoptosis and lymphocyte infiltration seen in this phase, indicating the involvement of this cytokine. Thereafter, a chronic phase was manifested from days 7 to 14 after injection. It was characterized as granulomatous inflammation admixed with apoptosis of infiltrating lymphocytes and some hepatocytes. Immunohistochemical staining showed that the infiltrating lymphocytes displayed TNFα, TNF type I receptor and a variety of cytokines including IL-1β, IL-4, IL-6, IL-10, IFNγ or IL-12. Interestingly, in naive mice, the arteries in the liver constitutively expressed IFNγ. Its expression appeared to be substantially increased at 48 h, decreased at 72 h, and increased again on day 14 afterP. acnes injection. Furthermore, Fas or FasL was only detected on the lymphocytes within the granuloma. We conclude thatP. acnes can induce a TNFα-mediated acute hepatic apoptosis which subsequently progress to a T-cell-mediated granulomatous hepatitis with increased expression of multiple cytokines and Fas/FasL.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253524
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  • 62
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    Kynostatin and 17β-estradiol prevent the apoptotic death of human neuroblastoma cells exposed to HIV-1 protease (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 433-438 
    Details
    ISSN: 1423-0127
    Keywords: AIDS dementia complex ; Antioxidants ; Apoptosis ; Cerebral atrophy ; gp120 ; HIV-1 protease ; Human neuroblastoma cell ; Neuroprotection ; Protease inhibitor (KNI-272)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A significant number of adult male patients with acquired immunodeficiency syndrome develop cerebral atrophy and progressive brain disorders such as dementia complex and neuropsychiatric problems. Upon entering the brain via activated macrophages or microglias, the human immunodeficiency type 1 virus (HIV-1) may produce cytotoxic factors such as HIV-1 envelope protein (gp 120) and protease. Owing to significant proteolysis of nonviral proteins, the protease derived from HIV-1 may be detrimental to brain cells and neurons. Our results revealed that HIV-1 protease, at nanomolar concentrations, was as potent as gp 120 in causing neurotoxicity in human neuroblastoma neurotypic SH-SY5Y cells. As shown by the Oncor ApopTag staining procedure, HIV-1 protease significantly increased the number of apoptotic cells over the serum-free controls. Moreover, HIV-1 protease-induced neurotoxicity was blocked by a selective protease inhibitor, kynostatin (KNI-272). Antioxidants such as 17β-estradiol, melatonin, andS-nitrosoglutathione also prevented protease-induced neurotoxicity. These findings indicate that oxidative proteolysis may mediate HIV-1 protease-induced apoptosis and the degeneration of neurons and other brain cells. Centrally active protease inhibitors and antioxidants may play an important role in preventing cerebral atrophy and associated dementia complex caused by HIV-1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253675
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  • 63
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    Contributions of p53 and PMA to g-irradiation induced apoptosis in Jurkat cells (1999)
    Springer
    Hematology and cell therapy 41 (1999), S. 153-161 
    Details
    ISSN: 1279-8509
    Keywords: p53 ; Apoptosis ; PKC ; g-irradiation ; Transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several mutations prevent the expression of p53 in the human lymphoblastoid T cell line Jurkat. Restoration of p53 in Jurkat cells had no effect on the cell growth but markedly increased the amount of apoptosis induced by g-irradiation. Inhibition of RNA synthesis using 5,6-dichlorobenimidizole riboside had little effect on apoptosis induced by irradiation in the presence of p53 and did not affect the p53-independent apoptotic pathway. Expression of p53 also had no effect on the expression levels of proteins such as Fas, GADD45, Bax, Bcl-2, Bcl-xL or p53 induced proteins (PIGS) in resting cells or after irradiation. Activation of protein kinase C by phorbol 12-myristate 13-acetate produced an almost complete inhibition of p53-independent apoptosis following irradiation, whereas no significant effect was observed on the rate of p53-induced apoptosis. Although phorbol 12-myristate 13-acetate strongly induced p21 and stabilised p53 in the resting transfected Jurkat cells, neither apoptosis nor cell arrest was observed. In summary, this work shows that p53 enhances the radiosensitivity of Jurkat cells through an apoptotic process that is triggered by irradiation and is largely independent of RNA synthesis and protein kinase C activation. Apoptosis in p53- negative Jurkat cells is strongly inhibited by PMA indicating that the pathway triggered by p53 may be distinct from apoptotic pathways used in its absence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00282-999-0153-0
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  • 64
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    Hypothesis: A recurrent, moderate activation fosters systemic autoimmunity — the apoptotic roles of TCR, IL-2 and fas ligand (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 306-313 
    Details
    ISSN: 1423-0127
    Keywords: Autoimmunity ; Apoptosis ; IL-2 ; FasL ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Studies of several gene knockout mice suggest an interesting association of a moderate T cell response with systemic autoimmune diseases. In addition, CD95 ligand (FasL) expression in some strains of these mice is impaired. Because FasL is critically involved in regulating peripheral tolerance, there may be a link between autoimmune diseases and a moderate T cell response that cannot activate the FasL gene. Here, we propose that there are two thresholds of T cell activation. When moderately stimulated, T cells can be activated to the low (1st) threshold, which permits the induction of CD40L, IL-2, IL-4, and other components that help the immune response. The high (2nd) activation threshold can only be achieved by a strong and concurrent stimulation through TCR and IL-2R. Once the high threshold is reached, FasL is produced to induce apoptosis of the activated T and B cells. In the absence of the FasL-mediated downregulation, the activated B cells become efficient antigen-presenting cells for self-antigens and excellent responders for T cell help. Such an exacerbating condition, induced by recurrent and moderate activation, favors the development of autoreactive T cells and autoantibody production. Evidence supporting this hypothesis and some predictions that can be tested are described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253519
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  • 65
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    Sodium vanadate inhibits apoptosis in malignant glioma cells: A role for Akt/PKB (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 213-218 
    Details
    ISSN: 1423-0127
    Keywords: Glioma ; Apoptosis ; Vandate ; Akt ; PKB
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dual signal hypothesis of apoptosis holds that a common signal can activate both apoptotic and proliferative pathways. The fate of a cell is dependent on which of these two pathways predominates. In the MAPK family of kinases, ERK and JNK have been proposed to mediate apoptosis whereas the PI3K-stimulated kinase, Akt/PKB, has been shown to inhibit apoptosis. The object of this study was to determine the role of these kinases in a glioma model of apoptosis. We have previously shown that K252a induces apoptosis and inhibits kinase activity. In this study we confirm these results and shown that the protein tyrosine phosphatase inhibitor sodium vanadate activates ERK, JNK and Akt/PKB, but does not stimulate proliferation. Vanadate did protect T98G cells from K252a-induced apoptosis, an effect that was abolished by addition of the PI3K inhibitor wortmannin. This suggests that PI3K and Akt/PKB may be responsible for mediating vanadate's protective effect on glioma cells. We conclude that the intracellular balance between protein phosphorylation pathways is a critical determinant of both cell proliferation and cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02255905
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  • 66
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    In vitro evaluation of flavopiridol, a novel cell cycle inhibitor, in bladder cancer (1999)
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. 81-87 
    Details
    ISSN: 1432-0843
    Keywords: Key words Cyclin-dependent kinase ; Cytotoxicity ; Apoptosis ; Multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the in vitro effects of flavopiridol on bladder cancer cell lines, immortalized urothelial cell lines, and normal urothelial cells well characterized for defects in p53, pRb, and p16. Methods: Growth inhibition was assessed via an MTT assay and apoptosis via DAPI nuclear staining. Cell cycle analysis was performed via propidium iodide staining and fluorescent activated cell sorting (FACS). Multidrug-resistant cells were generated by continuous exposure to doxorubicin. Results: Growth inhibition was not correlated with inactivation of p53, pRb, or p16. All cells experienced G2/M arrest within 24 h of flavopiridol exposure. Modest apoptosis was observed but required 72 h of continuous drug exposure to become evident. There was no obvious synergistic or antagonistic toxicity when flavopiridol was combined with radiotherapy or cisplatin dosed at the IC50 despite the observation that radiotherapy and flavopiridol led to more profound G2/M arrest than either agent alone. Doxorubicin-resistant cells, demonstrated to overexpress the MDR1 multidrug-resistance protein were equally as sensitive to flavopiridol as the parental cells. Conclusions: Flavopiridol is a novel cell cycle inhibitor that may be a useful agent in bladder cancers with tumor suppressor gene alterations and/or multidrug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050948
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  • 67
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    Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification (1999)
    Springer
    Cancer chemotherapy and pharmacology 43 (1999), S. 507-515 
    Details
    ISSN: 1432-0843
    Keywords: Key words Dolastatin ; Lung cancer ; Apoptosis ; Xenografts ; Experimental therapeutics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Dolastatin 10 is a natural cytotoxic peptide which acts through the inhibition of microtubule assembly. Studies have suggested that such agents can induce apoptosis in association with bcl-2 phosphorylation. Since bcl-2 overexpression is common in small-cell lung cancer (SCLC), we evaluated the activity of dolastatin 10 in SCLC cell lines and xenografts. Methods: In vitro growth inhibition was evaluated with a standardized MTT assay and apoptosis with fluorescent microscopy and a TUNEL assay. Immunoblot analysis and phosphatase digestion were used to determine bcl-2 modification. In vivo activity was evaluated in subcutaneous and metastatic SCLC xenograft models in SCID mice. Results: Dolastatin 10 had growth inhibitory activity against four SCLC cell lines (NCI-H69, -H82, -H446, -H510) with IC50 values ranging from 0.032 to 0.184 nM. All four cell lines exhibited evidence of apoptosis after 48 h of exposure to 1.3 nM dolastatin 10. Immunoblot analysis revealed that 1.3 nM dolastatin 10 altered the electrophoretic mobility of bcl-2 in NCI-H69 and -H510 cells within 16 h of treatment. Incubation of protein extract from dolastatin 10-treated NCI-H69 and -H510 cells with calcineurin resulted in the disappearance of the altered mobility species, suggesting dolastatin 10-induced bcl-2 phosphorylation. In in vivo studies, 450 μg/kg of dolastatin 10 IV × 2 given after intravenous injection of NCI-H446 cells completely inhibited tumor formation. In established subcutaneous NCI-H446 xenografts, 450 μg/kg of dolastatin 10 IV induced apoptosis in the majority of tumor cells within 96 h, resulting in a log10 cell kill of 5.2 and an increase in median survival from 42 to 91 days. Conclusions: These findings suggest that dolastatin 10 has potent activity against SCLC and that the modulation of apoptotic pathways deserves further evaluation as an anticancer strategy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050931
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  • 68
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    Electronic Resource
    Vincristine pharmacokinetics after repetitive dosing in children (1999)
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. 203-209 
    Details
    ISSN: 1432-0843
    Keywords: Key words Vincristine ; Pharmacokinetics ; Repetitive dosing ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050968
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  • 69
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    Apoptotic cell death induced by baccatin III, a precursor of paclitaxel, may occur without G2/M arrest (1999)
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. 444-452 
    Details
    ISSN: 1432-0843
    Keywords: Key words Baccatin III ; Paclitaxel ; Apoptosis ; Mitotic arrest ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Paclitaxel has been demonstrated to possess significant cell-killing activity in a variety of tumor cells by induction of apoptosis, but the mechanism by which paclitaxel leads to cell death and its relationship with mitotic arrest is not entirely clear. In this study, baccatin III, a synthetic precursor of paclitaxel, was used to analyze whether paclitaxel-induced apoptosis can be a separate event from microtubule bundling and G2/M arrest. Methods: Several different methods including DNA fragmentation, flow cytometric analyses, TdT-mediated dUTP nick end labeling (TUNEL) and time-lapse video microscopy were used to analyze apoptotic cell death induced by baccatin III and its possible correlation with cell cycle distribution. Results: Our results demonstrated that baccatin III could also cause apoptotic cell death in both BCap37 (a human breast cancer cell line) and KB cells (derived from human epidermoid carcinoma), but had less effect on microtubule bundling and G2/M arrest. Furthermore, we demonstrated that most apoptotic events induced by baccatin III were not coupled with G2/M arrest. Instead, these apoptotic events occurred predominantly in the cells in other phases of the cell cycle. Conclusion: Baccatin III, which contains the core taxane ring, is the fundamental piece of paclitaxel structure. The finding of baccatin III-induced apoptosis independent of cell cycle arrest, on the one hand, implies that the core taxane ring may play a critical role in inducing cell death and, on the other hand, suggests that paclitaxel might induce apoptosis from other phases of the cell cycle by a similar mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051117
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    Enhanced antitumor activity of a combination treatment with a mouse/human chimeric anti-MK-1 antibody and lymphokine-activated killer cells in vitro and in a severe combined immunodeficient mouse xenograft model (1999)
    Springer
    Cancer immunology immunotherapy 48 (1999), S. 165-171 
    Details
    ISSN: 1432-0851
    Keywords: Key words Immunotherapy ; MK-1 antigen ; Chimeric antibody ; ADCC ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mouse monoclonal antibody FU-MK-1, raised against a human gastric adenocarcinoma, recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas and seems to be valuable in immunodiagnosis and immunotherapy of various cancers. In a recent study, we constructed a mouse/human chimeric antibody, designated Ch FU-MK-1, by fusing the FU-MK-1 VH and Vκ genes to the human Cγ1 and Cκ genes, respectively. In the present study, we tested combination immunotherapy of Ch FU-MK-1 with human lymphokine-activated killer (LAK) cells in vitro and in mice with severe combined immunodeficiency (SCID) bearing human MK-1-expressing tumors. In in vitro experiments, Ch FU-MK-1 effectively mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against MK-1-expressing MKN-74 cells, which was completely blocked by an anti-FcR antibody. Since the apoptotic pathway as well as the necrotic pathway have been shown to be utilized in various cytotoxic effector mechanisms, we investigated the role of apoptosis in ADCC mediated by LAK cells and Ch FU-MK-1 against MKN-74 cells. The implication of the apoptosis during ADCC was demonstrated by means of both a terminal-deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay and a propidium iodide staining method. In vivo antitumor activity of combination treatment with LAK cells and Ch FU-MK-1 was estimated using SCID mice inoculated s.c. with MKN-74 cells. The i.v. administration of LAK cells and i.p. administration of Ch FU-MK-1 and interleukin-2 (IL-2) produced a marked growth inhibition of MKN-74 tumors in SCID mice. When the actual tumor weights were measured 16 days after initiation of treatment, more than 70% reduction was observed in the group receiving LAK cells plus Ch FU-MK-1 plus IL-2 as compared to the control untreated group. Together these results suggest that Ch FU-MK-1 may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050561
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    Dietary resistant starch and chronic inflammatory bowel diseases (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 201-211 
    Details
    ISSN: 1432-1262
    Keywords: Key words Inflammatory bowel disease ; TNBS rat model ; Resistant starch ; Absorption of short-chain fatty acids ; Butyrate functions ; Proliferation ; Apoptosis ; Matrix proteins ; Intestinal microflora
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  These studies were performed to test the benefit of resistant starch on ulcerative colitis via prebiotic and butyrate effects. Butyrate, propionate, and acetate are produced in the colon of mammals as a result of microbial fermentation of resistant starch and other dietary fibers. Butyrate plays an important role in the colonic mucosal growth and epithelial proliferation. A reduction in the colonic butyrate level induces chronic mucosal atrophy. Short-chain fatty acid enemas increase mucosal generation, crypt length, and DNA content of the colonocytes. They also ameliorate symptoms of ulcerative colitis in human patients and rats injected with trinitrobenzene sulfonic acid (TNBS). Butyrate, and also to a lesser degree propionate, are substrates for the aerobic energy metabolism, and trophic factors of the colonocytes. Adverse butyrate effects occur in normal and neoplastic colonic cells. In normal cells, butyrate induces proliferation at the crypt base, while inhibiting proliferation at the crypt surface. In neoplastic cells, butyrate inhibits DNA synthesis and arrests cell growth in the G1 phase of the cell cycle. The improvement of the TNBS-induced colonic inflammation occurred earlier in the resistant starch (RS)-fed rats than in the RS-free group. This benefit coincided with activation of colonic epithelial cell proliferation and the subsequent restoration of apoptosis. The noncollagenous basement membrane protein laminin was regenerated initially in the RS-fed group, demonstrating what could be a considered lower damage to the intestinal barrier function. The calculation of intestinal short-chain fatty acid absorption confirmed this conclusion. The uptake of short-chain fatty acids in the colon is strongly inhibited in the RS-free group, but only slightly reduced in the animals fed with RS. Additionally, RS enhanced the growth of intestinal bacteria assumed to promote health. Further studies involving patients suffering from ulcerative colitis are necessary to determine the importance of RS in the therapy of a number of intestinal diseases and the maintenance of health.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003840050212
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  • 72
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    The necessity of building population specific prediction equations for clinical assessment of pulmonary function tests (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 519-522 
    Details
    ISSN: 1432-1076
    Keywords: Key words Pulmonary function test ; Adjustment ; Children ; Prediction equations ; Population specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fitting adequate prediction equations for pulmonary function test (PFT) parameters is crucial in the analysis of lung function tests and their interpretation. Our work aimed at studying the necessity of building population specific prediction equations, rather than using prediction equations built-in in commercial equipment. We used as an example results of studies carried out among Israeli schoolchildren. Second to sixth grade children (7–13 years old), 1064 boys and 1211 girls, were studied in Tel-Aviv. PFT (forced vital capacity, forced expiratory volume in 1st second, peak expiratory flow, forced expiratory flow in 50% volume, forced expiratory flow in 75% volume) performed by these children were adjusted for height, weight and age, for each sex separately, by a multiple regression procedure. Predicted PFT parameters of 300 boys and 301 girls aged 7–13 years, living along the southern shore of Israel, were calculated using the equations built for the same aged Tel-Aviv children as well as the prediction equations built-in in the spirometer used. The ratios between the observed PFT parameters in the southern children and their expected values, using the Israeli population specific equations, were around 1.00. Using the built-in equations resulted in ratios around 0.90. Conclusion The development of population specific prediction equations for PFT parameters is necessary. Such equations should be used both in clinical assessment to minimize misclassification (healthy/sick child) and in epidemiological studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051133
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    Lethal encephalopathy complicating childhood shigellosis (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 550-552 
    Details
    ISSN: 1432-1076
    Keywords: Key wordsShigella ; Toxic encephalopathy ; Children ; Brain oedema ; Shiga toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. Conclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051144
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  • 74
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    Development of anticipatory postural adjustments in a bimanual load-lifting task in children (1999)
    Springer
    Experimental brain research 126 (1999), S. 200-204 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050729
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    Expression of CD69 on T-cells from HIV-1-infected children and adolescents increases with increasing viral load (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 638-644 
    Details
    ISSN: 1432-1076
    Keywords: Key words HIV-1 ; T-cells ; CD69 ; Activation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the use of a whole-blood assay that measures spontaneous and activation-induced CD69 expression on peripheral blood T-cells in vitro for assessment of T-cell function in HIV-1-infected paediatric patients. Heparinized venous blood from 28 HIV-1 positive children and adolescents and 23 healthy controls was incubated for 4 h with or without 5 μg/ml phytohaemagglutinin (PHA). Thereafter, analysis of CD69 expression on CD4+ and CD8+ T-cells was done by flow cytometry; simultaneously we determined CD4+ T-cell counts and plasma HIV-1 viral load. Neither spontaneous nor PHA-induced CD69 expression differed significantly between HIV-1 positive patients and healthy controls. However, T-cells from HIV-1 positive patients with plasma HIV-1 viral load levels above 70 × 103 copies/ml showed a higher spontaneous CD69 expression than T-cells from patients with lower plasma viral load levels in different stages of the disease. Antiretroviral treatment in four patients reduced spontaneous CD69 expression in CD4+ T-cells and PHA-induced CD69 expression in CD4+ and CD8+ T-cells significantly after 8 weeks of therapy. Conclusion Spontaneous and activation-induced expression of the early (activation) antigen CD69 on peripheral blood T-cells does not distinguish HIV-1 positive patients from HIV-1 negative healthy controls and is not correlated with peripheral blood CD4+ T-cell counts. This test may not be a reliable marker for functional T-cell deficiency during early stages of HIV disease. Increased spontaneous as well as PHA-induced CD69 expression on T-cells from HIV-1-infected children and adolescents in vitro may rather reflect HIV-induced pre-activation of T-cells in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051167
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  • 76
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    Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 662-667 
    Details
    ISSN: 1432-1076
    Keywords: Key words Somatosensory evoked potentials ; Far-field potentials ; Achondroplasia ; Foramen magnum stenosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Children with achondroplasia may have high cervical myelopathy due to stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia aged 13 months to 18 years (mean 6 years). In addition to the conventional technique of recording the cortical N20 and the central conduction time (CCT), we employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the cranio-cervical junction. The findings were related to the clinical status and MRI results. Eighteen patients had MRI evidence of spinal cord compression with indentation or narrowing of the upper cervical cord, and 13 showed signs of myelomalacia. Seven patients had neurological abnormalities. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. However, the conventional SEPs were highly specific in the most severely affected patients; here the specificity was 1.0 for patients with myelomalacia and 0.96 for symptomatic patients. Postoperative SEPs improved after occipital decompression in two children. Conclusion The analysis of somatosensory evoked potentials, in particular of subcortical tracings, is useful in the detection of early cervical myelopathy in children with achondroplasia. Early neurosurgical decompression may prevent irreversible damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051172
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  • 77
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    Electronic Resource
    Treatment of consumption coagulopathy with antithrombin concentrate in children with acquired antithrombin deficiency – A feasibility pilot study (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S187 
    Details
    ISSN: 1432-1076
    Keywords: Key words Antithrombin concentrate ; Children ; Septicaemia ; Acquired antithrombin deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Consumption coagulopathy is a serious problem in childhood. In addition to treatment of the underlying disease, consumption coagulopathy was previously treated with heparin. Nowadays it is treated by substitution of coagulation factors, especially antithrombin (AT) concentrate, alone or in combination with heparin. In this pilot study we administered AT concentrate (dosage 80 U/kgbw/d), without additional heparin treatment, to 29 children beyond infancy with acquired AT deficiency. Antithrombin, platelet count, fibrinogen, PT, and APTT were assayed before and during the course of AT substitution. These coagulation parameters returned to normal 48 hours after normalisation of the plasma AT level. AT levels normalised within 24 h of initial substitution in all children. Lethal outcome due to the underlying disease was observed in only two children. Conclusion Data of this pilot study suggest that, concomitantly with the treatment of the underlying disease, consumption coagulopathy in childhood can be managed successfully with early substitution of AT concentrate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014353
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  • 78
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    Electronic Resource
    Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S197 
    Details
    ISSN: 1432-1076
    Keywords: Key words Coagulation ; Fibrinolysis ; Head injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) 〈10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3–5, 7–9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P 〈 0.01) and the occurrence of DIC (P 〈 0.005) showed the strongest association with the patients' clinical outcome. Conclusion Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014355
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  • 79
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    Electronic Resource
    Pulmonary anthracosis in children (1999)
    Springer
    European radiology 9 (1999), S. 485-486 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Lung disease ; Pneumoconiosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report two cases of children with malignancies and subpleural nodules found on computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This pathologic condition has never been reported in children. Causes of anthracosis include a smoking environment, living in urban areas and air pollution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050699
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  • 80
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    Electronic Resource
    The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat (1999)
    Springer
    Experimental brain research 124 (1999), S. 241-247 
    Details
    ISSN: 1432-1106
    Keywords: Key words Melatonin ; Kainate ; Glutathione ; Apoptosis ; Excitotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol in 1 µl) was directly injected to unilateral striatum. Melatonin (10 mg/kg) was administrated intraperitoneally 1 h before and 1, 3, and 5 h after intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after kainate injection, a significant neuronal damage was found, as determined by Nissl staining and the TUNEL method, not only in the injected striatum, but also in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic neuronal death was significantly attenuated by treatment with melatonin compared with the vehicle control group. However, no detectable changes were observed in the contralateral side of the brain in either vehicle- or melatonin-treated rats. Moreover, the biochemical results indicated that kainate can indeed induce oxidative stress, such as a decrease in the content of total glutathione (GSH), oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the striatum and cortex compared with the contralateral brain regions. In the kainate-injected striatum, melatonin did not reduce the oxidative stress, but in the neighborhood of injected area-cortex, kainate-induced oxidative stress was significantly reduced by melatonin. Enhancement of glutathione-peroxidase activity was induced by intrastriatal kainate injection, not only in the cortical area of control and melatonin-treated rats, but also in striatum of control rats. However, a large elevation was found in the melatonin-treated cortex. Taking the morphological and biochemical data together, the present results suggest that melatonin functions as an antioxidant by upregulating the glutathione antioxidative defense system, thereby reducing neuronal death caused by excitotoxicity and preventing the kainate-induced damage from spreading to adjacent brain regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050619
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  • 81
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    Electronic Resource
    MRI of primary meningeal tumours in children (1999)
    Springer
    Neuroradiology 41 (1999), S. 512-516 
    Details
    ISSN: 1432-1920
    Keywords: Key words Meninges ; Tumours ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050794
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  • 82
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    Electronic Resource
    Suppressive effect of pentoxifylline on natural killer cell activity; experimental and clinical studies (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 228-234 
    Details
    ISSN: 1432-1912
    Keywords: Key words Natural killer ; Pentoxifylline ; Macroangiopathic patients ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The methylxanthine derivative pentoxifylline, widely used in the treatment of vascular diseases, also has numerous immunological effects. In in vitro experiments, the human natural killer cell cytotoxicity was investigated in the presence of pentoxifylline. A clinical trial involved an investigation of the natural killer cell activity in patients to whom pentoxifylline had been administered for different periods. The natural cytotoxicity in macroangiopathic patients treated with pentoxifylline was compared with that in healthy controls and that in patients with vascular diseases who did not receive pentoxifylline therapy. A total of 62 macroangiopathic patients and 20 healthy controls were investigated. The natural killer cell activity in patients receiving pentoxifylline therapy for more than a year proved to be significantly lower (P〈0.005). The presence of vascular disease did not influence the natural killer activity. In the in vitro cytotoxicity reaction, pentoxifylline at a concentration of 100 µg/ml was found to suppress the natural killer cell cytotoxicity at any stage of the reaction. The influence of pentoxifylline on the natural killer cell activity was not due to inhibition of the expression of intercellular adhesion molecule-1. However, this drug significantly decreases (P〈0.05) the apoptosis of target cells. It is presumed that the suppressor effect of pentoxifylline on natural killer cell activity should be taken into consideration in the treatment of clinical diseases where this drug is administered chronically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005346
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  • 83
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    Electronic Resource
    Changes in brain water diffusion during childhood (1999)
    Springer
    Neuroradiology 41 (1999), S. 929-934 
    Details
    ISSN: 1432-1920
    Keywords: Key words Magnetic resonance imaging ; diffusion weighted ; Myelination ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050869
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  • 84
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    Electronic Resource
    Das maligne epitheloide Hämangioendotheliom der Leber Ein sehr seltener Tumor im Kindesalter (1999)
    Springer
    Der Pathologe 20 (1999), S. 345-350 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Epitheloides Hämangioendotheliom ; Leber ; Kindesalter ; Proliferation ; Apoptose ; Key words Epithelioid hemangioendothelioma ; Liver ; Childhood ; Proliferation ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary We report on a 12-year old boy suffering from malignant epithelioid hemangioendothelioma of the liver, which is a very rare tumor in childhood. The tumor was detected by ultrasound examination at the age of 10 and appeared at that time as a solitary intrahepatic nodular lesion. During the following 2 years multiple nodular lesions developed in both hepatic lobes. There were neither any suspect anamnestic findings nor abnormal clinical or laboratory data. The tumor showed the typical histomorphological, immunohistochemical, and ultrastructural features of this entity, which is usually seen in older patients. We investigated proliferative activity, apoptotic regulation, and expression of VEGF and VEGF-receptor flk-1 by means of immunohistochemical techniques. According to the known slow growth activity of these tumors we found only a few Ki-67 positive tumor cells. We did not detect any apoptotic cells using TUNEL technique. The positive immunoreaction of the tumor cells with antibodies against VEGF and VEGF-receptor flk-1 may indicate the regulation of tumor growth by angiogenetic factors. We present our findings together with a summary of the most important publications of recent years concerning these tumors.
    Notes: Zusammenfassung Bei einem 12 Jahre alten Jungen wurde ein im Kindesalter sehr seltenes malignes epitheloides Hämangioendotheliom der Leber diagnostiziert. Im Alter von 10 Jahren fiel erstmals sonografisch ein solitärer Leberrundherd auf, im Verlauf der nächsten zwei Jahre entwickelten sich multiple Rundherde in beiden Leberlappen. Die Anamnese des Patienten war hinsichtlich möglicher prädisponierender Faktoren unauffällig. Die klinischen und laborchemischen Parameter befanden sich im Normbereich. Der Tumor wies die für diese, üblicherweise bei Erwachsenen auftretenden Entität typischen histomorphologischen, immunhistochemischen und ultrastrukturellen Merkmale auf. Mittels immunhistochemischer Untersuchungen wurde das Tumorgewebe hinsichtlich Proliferationsaktivität, Apoptoseregulation und Expression angiogenetischer Faktoren (VEGF und VEGF-Rezeptor flk-1) untersucht. Bei bekanntermaßen langsamer Wachstumstendenz dieser Tumoren fand sich ein geringer Anteil Ki-67-positiver Tumorzellen. Mittels TUNEL-Technik wurden keine Apoptosen gefunden. Die positive Immunreaktion der Tumorzellen mit Antikörpern gegen VEGF und den VEGF-Rezeptor flk-1 deutet auf eine Regulation des Tumorwachstums durch angiogenetische Faktoren hin. Die Ergebnisse werden in Verbindung mit einer Zusammenstellung der wichtigsten Publikationen der letzten Jahre über diese seltenen Tumoren diskutiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050369
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  • 85
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    Electronic Resource
    Childhood cancer and residential radon exposure – results of a population-based case-control study in Lower Saxony (Germany) (1999)
    Springer
    Radiation and environmental biophysics 38 (1999), S. 211-215 
    Details
    ISSN: 1432-2099
    Keywords: Key words Case-control study ; Children ; CNS tumour ; Environmental exposure ; Indoor radon ; Leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract  A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m–3) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m–3, no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32–5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96–7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004110050158
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  • 86
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    Electronic Resource
    Fremdkörperingestion (1999)
    Springer
    Der Radiologe 39 (1999), S. 472-477 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Ingestion ; Kinder ; Diagnostik ; Key words Foreign body ; Ingestion ; Children ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Foreign body ingestion is not infrequent in infants and children. The diagnosis of radiopaque foreign body ingestion does not pose a major problem. It is crucial to take an X-ray from the pharynx to the level of the pylorus. If a foreign body that might get stuck at the ileocoecal valve is ingested, it is necessary to perform a radiograph of the whole abdomen. Foreign bodies that do not pass the cardia must be extracted endoscopically. In the case of foreign bodies with a smooth contour that have passed the pylorus, parents are advised to check the child’s stool or collect it and bring it for X-raying. If after a week there is no definite evidence that the foreign body has been excreted a follow-up radiograph is carried out. If the foreign body is still in the stomach or duodenum, endoscopy is necessary. The detection of nonopaque foreign bodies can be facilitated by giving oral contrast medium, making the depiction of the foreign body as a filling defect possible. As a complication, perforation can occur, the diagnosis of which may entail the use of sonography, conventional radiography and, to a lesser extent, CT.
    Notes: Zusammenfassung Fremdkörperingestion ist im späten Säuglings- und frühen Kleinkindalter kein seltenes Ereignis. Die Diagnose röntgendichter Fremdkörper bereitet keine Schwierigkeiten. Hierbei ist jedoch zu beachten, daß die Region vom Pharynx bis zum Pylorus abgebildet sein sollte. Wurden Fremdkörper verschluckt, bei denen die Gefahr der Einklemmung in der Bauhin’schen Klappe besteht, sollte das komplette Abdomen bis zum Anus dargestellt werden. Fremdkörper, welche die Kardia nicht passieren, müssen endoskopisch extrahiert werden. Haben glatt begrenzte Fremdkörper den Pylorus passiert, werden die Eltern aufgefordert, den Stuhl zu untersuchen oder zu sammeln und ihn zur röntgenologischen Untersuchung mitzubringen. Sollte der Fremdkörper innerhalb einer Woche nicht auffindbar sein, wird eine Kontrolluntersuchung durchgeführt. Ist der Fremdkörper dann noch im Magen oder im Duodenum, sollte er ebenfalls extrahiert werden. Der Nachweis nicht röntgendichter Fremdkörper kann mittels Gabe von positivem Kontrastmittel als Aussparungsfigur gelingen. Als Komplikation kann eine Perforation auftreten. Hierbei dienen Sonographie, konventionelles Röntgen und gegebenenfalls CT zur Diagnosefindung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050537
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  • 87
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    Electronic Resource
    Antithrombin treatment of severe hepatic veno-occlusive disease in children with cancer (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S154 
    Details
    ISSN: 1432-1076
    Keywords: Key words Veno-occlusive disease ; Antithrombin ; Children ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatic veno-occlusive disease (VOD) is a well-known complication of chemotherapy in Wilms tumor patients, particularly young children. Although this complication resolves uneventfully in most patients, fatal cases have been reported. Severe VOD after transplantation has a high mortality rate ranging from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usually has a good prognosis. We describe two patients with Wilms tumor and one with acute lymphoblastic leukemia, who developed severe veno-occlusive disease of the liver according to the Baltimore criteria while undergoing chemotherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, weight gain and, in one patient, short-term lethargy. Elevated LDH levels of 872 to 12,000 U/l were observed in our patients. All patients had thrombocytopenia between 29,000 and 40,000/μl and decreased antithrombin (AT) and protein C levels; two patients had gastrointestinal bleeding. All patients developed a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy was rapidly changed to AT supplementation (20–80 IU/kg bw 2× per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occurred. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D overdosage in view of the severity of symptoms. The remaining two patients received chemotherapy according to the therapy protocol after restitution. All patients survived without sequelae with a median follow-up of 28 months (range 8–48 months). Conclusion Hepatic veno-occlusive disease is a rare but increasingly recognized complication in pediatric cancer patients receiving conventional chemotherapy. AT supplementation constitutes a good alternative treatment of severe VOD in comparison with other thrombolytic therapies, particularly in patients at high risk of bleeding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014344
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  • 88
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    Electronic Resource
    Hepatic steatosis: a frequent non-specific finding in HIV-infected children (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 971-974 
    Details
    ISSN: 1432-1076
    Keywords: Keywords Liver ; Steatosis ; HIV ; AIDS ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty HIV-infected children were cross-sectionally examined for morphologic hepatic abnormalities, using ultrasonography or histology. Abdominal ultrasonography was performed in 27 children. The liver structure was normal in four patients, one of whom had moderate symptoms of the HIV infection and three of them severe symptoms. Abnormal liver structure, compatible with hepatic steatosis, was found in 23 (85%) patients. Five of them were in an early stage of the HIV infection (category N or A), three patients were ranked in category B and 15 patients in category C. Histological examination of the liver was performed in 11 children and steatosis was documented in ten (91%). In seven (70%) of these ten children steatosis had been suspected by ultrasonography. In conclusion, steatosis is common in HIV-infected children. It is non-specific and has no impact on disease, diagnostic evaluation or management. Conclusion Ultrasonography is a sensitive, accurate, non-invasive screening tool. It is more reliable than liver function tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051260
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  • 89
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    Electronic Resource
    Parental attitude towards alternative medicine in the paediatric intensive care unit (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 12-17 
    Details
    ISSN: 1432-1076
    Keywords: Key words Alternative medicine ; Complementary therapies ; Critical care ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interest in alternative medicine (AM) is growing. In the USA and Canada, studies showed that 34% of adults and 11% of children use AM. In a prospective cohort study, we investigated the interest in AM among parents of critically ill children in the paediatric Intensive Care Unit (ICU) of a university hospital. From January 1996 to April 1997, we distributed questionnaires to the parents of critically ill children. These strictly anonymous questionnaires were completed at home and returned by mail. Exclusion criteria were short (〈1 day) or repeated hospitalizations, and insufficient proficiency of the German language. The inclusion criteria were fulfilled by 591 patients; 561 received the questionnaire (95%) and 289 (52%) were returned. Of the respondents, 70% would appreciate AM as a complementary therapy on the ICU, 23% found AM equally or more important than conventional medicine whereas only 7% regarded AM as unimportant. On the ICU, 18% used AM; surprisingly 41% of them did not discuss it with physicians or nurses. An additional 21% would have liked to use AM, but did not do so. Typically, AM-users administered AM also at home to their children and themselves. Their children were however, older. Conclusions A substantial proportion of parents used measures of alternative medicine in the intensive care unit, or would have like to do so. However, few had the confidence to discuss this wish with the medical personal. This suggests that alternative medicine is of great interest, even on an intensive care unit. Nevertheless, discussion about alternative medicine seems to be taboo in doctor-patient relations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051001
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  • 90
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    Electronic Resource
    Mild closed head injury in children compared to traumatic fractured bone; neurobehavioural sequelae in daily life 2 years after the accident (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 249-252 
    Details
    ISSN: 1432-1076
    Keywords: Key words Mild head injury ; Fractured bone ; Late sequelae ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two years after an accident resulting in either a mild head injury or a fractured bone, two groups of 22 children each, aged 4–14 years, were examined for the existence of any neurobehavioural symptoms by means of a standardized questionnaire filled out by their caretakers. Selection of the children was based on reports of the Accident and Emergency Department in 1 year. Significantly more symptoms were reported after mild head injury. The main symptoms reported were headache, dizziness, fatigue and memory problems. The total number of symptoms in the children with mild head injury exceeded four times this in the group of children with a fractured bone. Conclusion Even 2 years after a mild head injury there are still residual symptoms in daily life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051061
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  • 91
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    Electronic Resource
    Prothrombotic risk factors in childhood stroke and venous thrombosis (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S117 
    Details
    ISSN: 1432-1076
    Keywords: Key words Stroke ; Coagulation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0–16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0–17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1; combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92–17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6–65.6; P 〈 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. Conclusion Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014333
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  • 92
    Electronic Resource
    Electronic Resource
    Risk factors for type I diabetes mellitus in children in Austria (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 362-366 
    Details
    ISSN: 1432-1076
    Keywords: Key words Type 1 diabetes ; Children ; Risk factors ; Case control ; Environmental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P 〈 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051092
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  • 93
    Electronic Resource
    Electronic Resource
    Thyroid antibodies in children of mothers with auto-immune thyroid disease (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 24-28 
    Details
    ISSN: 1432-1076
    Keywords: Key words Hashimoto thyroiditis ; Graves disease ; Children ; TSH function-blocking antibody ; Cytotoxic antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051003
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  • 94
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    Electronic Resource
    Gastro-intestinal bleeding caused by leiomyoma of the small intestine in a child with neurofibromatosis (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 460-462 
    Details
    ISSN: 1432-1076
    Keywords: Key words Gastro-intestinal bleeding ; Children ; Jejunal leiomyoma ; Neurofibromatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of “smooth muscle tumour of undetermined malignant potential”. There were no recurrence of symptoms for 4 years after the operation. Conclusion Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051120
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  • 95
    Electronic Resource
    Electronic Resource
    Liver transplantation in mitochondrial respiratory chain disorders (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S081 
    Details
    ISSN: 1432-1076
    Keywords: Key words Respiratory chain ; Mitochondria ; Children ; Infancy ; Liver failure ; AbbreviationsMRCD mitochondrial respiratory chain disease ; OLT orthotopic ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up. Pre-transplant evaluation should aim to rule out neurological disease, which may be difficult to differentiate from signs accompanying liver insufficiency. Cerebrospinal fluid lactic acid levels, compared to blood lactate, may be suggestive of central nervous system involvement. Of 11 cases with respiratory chain disorders who had liver transplantation in various centres, 4 are alive and well on follow up, and 6 died, three of them having developed neurological disease post orthotopic liver transplantation. All three patients with initial liver and gastro-intestinal disease died early after transplantation, indicating that these may be poor candidates for this procedure. Conclusion Liver transplantation is feasible in hepatic respiratory chain disorders, but extra-hepatic disease should be ruled out before transplantation. Extra-hepatic manifestations may, however, appear and cause patient death despite successful transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014328
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  • 96
    Electronic Resource
    Electronic Resource
    Liver transplantation in α1-antitrypsin deficiency (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S085 
    Details
    ISSN: 1432-1076
    Keywords: Key wordsα1-Antitrypsin ; Liver disease ; Liver transplantation ; Children ; AbbreviationsAATα1-antitrypsin deficiency ; OLT orthotopic liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Only a minority of infants born with α1-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014329
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  • 97
    Electronic Resource
    Electronic Resource
    Isolated sphenoidal sinusitis in children (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 298-301 
    Details
    ISSN: 1432-1076
    Keywords: Key words Isolated ; Sphenoid ; Sinusitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous condition which is often misdiagnosed because of its nonspecific symptoms and paucity of clinical signs. We present eight children with isolated sphenoiditis who were managed in our medical centre during the last 2 years and review the literature. All the patients were adolescents or pre-adolescents and all experienced moderate to severe refractory oppressive headache. Four had a history of sinusitis or allergic rhinitis. None had fever or any other directing clinical sign. Diagnosis was made by cranial computer tomography. All were treated with antibiotics and recovered completely without infectious or neurological complications. Conclusion Acute isolated infectious sphenoiditis should be considered in adolescents and pre-adolescents who present with constant moderate to severe oppressive headache. Awareness of this entity will enable early diagnosis and initiation of antibiotic treatment which is essential to avoid complications and surgical intervention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051076
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  • 98
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    Electronic Resource
    Heparin-induced thrombocytopenia in paediatric patients – a review of the literature and a new case treated with danaparoid sodium (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S130 
    Details
    ISSN: 1432-1076
    Keywords: Key words Heparin treatment ; Heparin-induced thrombocytopenia ; HIT antibodies ; Children ; Catheter patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fcγ receptors. Cross-linking of multiple Fcγ receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis. In children, data on HIT are sparse. This review of the literature reports on 8 children aged 3 months to 15 years and 14 newborns suffering from HIT. Additionally, we report one new case treated with danaparoid sodium. Thrombotic complications were venous (n = 12) and arterial (n = 15). The children received heparin either for a spontaneous thrombotic event, for severe cardiac diseases or to maintain patency of intravascular catheters which are used for nutrition, blood sampling, and for application of medication. After diagnosis of HIT they were further anticoagulated with aspirin, warfarin, danaparoid sodium, lepirudin or low molecular weight heparin. Conclusion Although HIT is less frequently reported in newborns and children, paediatricians should be aware of HIT in childhood as a potential complication of heparin application. The widespread practice of flushing catheters with heparin should also be debated in view of the risk of triggering the primary immune-response of HIT. In 1999, treatment options for further parenteral anticoagulation of HIT patients are danaparoid sodium (a low-molecular weight heparinoid) and lepirudin (a direct thrombin inhibitor).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014338
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  • 99
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    Electronic Resource
    Clinical importance of prothrombotic risk factors in pediatric patients with malignancy – impact of central venous lines (1999)
    Springer
    European journal of pediatrics 158 (1999), S. S147 
    Details
    ISSN: 1432-1076
    Keywords: Key words Factor V G1691A ; Prothrombin G20210A ; Lipoprotein (a) ; Central venous lines ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single defect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. Conclusion The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014342
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  • 100
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    Electronic Resource
    Bilateral optic neuritis in a child diagnosed with Gd-enhanced MR imaging using fat-suppression technique (1999)
    Springer
    European radiology 9 (1999), S. 731-733 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Optic nerves ; Neuritis ; Children ; Central nervous system ; MR imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A 4-year-old boy developed bilateral optic neuritis. Although precise neuro-ophthalmological evaluation was difficult, the diagnosis was made with gadolinium-enhanced MR imaging using fat-suppression technique in the initial stage of the disease. Enhancement and enlargement of the intraorbital and intracanalicular optic nerve were demonstrated bilaterally as well as protrusion of the optic nerve head. The disease responded dramatically to intravenous steroid therapy. The etiologies in children usually differ from those in adolescent and adult patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050744
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