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  • Electronic Resource  (21,354)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 775-781 
    ISSN: 1530-0358
    Keywords: Locally recurrent rectal cancer ; Survival ; Prognostic factor ; Angiogenesis ; Apoptosis ; PCNA labeling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. S23 
    ISSN: 1530-0358
    Keywords: Apoptosis ; Flat-type carcinoma ; Colorectal neoplasms ; p53 ; p21 (WAF1/CIP1) ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax). RESULTS: There was no significant difference in terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P〈0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P〈0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group. CONCLUSION: p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.
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  • 3
    ISSN: 1530-0358
    Keywords: Anus ; High-grade squamous intraepithelial lesion ; Carcinoma ; Proliferation ; Apoptosis ; Microvessel density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
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  • 5
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Apoptosis ; Fas ; Fas ligand ; Cytotoxic T lymphocyte.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients’ age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.
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  • 6
    ISSN: 1436-2813
    Keywords: Key words Lung lobectomy ; Magnetic resonance imaging ; Left ventricular geometry ; Mediastinum ; Diaphragm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thoracic cage after a lung resection is filled by the remaining lobes, the elevated diaphragm, the diminished thoracic cage, and by mediastinal shifting. The changes in the thorax after a lung resection were quantified using magnetic resonance imaging. The study group consisted of 39 patients who had undergone a lobectomy, four who had undergone a pneumonectomy, and 14 controls. The left ventricular angle, ascending aortic angle, mediastinal shift, longitudinal length of the thoracic cage, the distance between the thoracic apex and the level of the aortic valve, and diaphragmatic elevation were all measured. After a right lower lobectomy, the mediastinum shifted more rightward than after a right upper lobectomy. The diaphragm became more greatly elevated after a right upper lobectomy than after a right lower lobectomy. When a chest wall resection was added to a right upper lobectomy, the mediastinal anatomical changes decreased. After a left upper lobectomy, the degree of mediastinal shifting was greater than after a left lower lobectomy. A left upper lobectomy shifted the mediastinum at the level of the right atrium. This method is easily reproducible and was found to be effective for quantifying the changes in the thorax after a lung resection.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Gastric cancer 3 (2000), S. 39-44 
    ISSN: 1436-3305
    Keywords: Key words Chemosensitivity ; Apoptosis ; TUNEL ; Gastric cancer ; Small specimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Because chemosensitivity tests usually require a large amount of tissue, they are not used routinely in patients with unresectable gastric cancer. The aim of this study was to investigate whether apoptosis can be used as a sensitivity assay for chemosensitivity in small gastric cancer specimens. Methods. Apoptosis, detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL), was investigated in small specimens of the MKN-1, MKN-45, and TMK-1 human gastric cancer cell lines as a marker of chemosensitivity following exposure to antineoplastic agents. Results. Doxorubicin (DXR), SN-38 (active metabolite of irinotecan), and paclitaxel (Taxol) induced DNA fragmentation in MKN-45 and TMK-1 cells, but not in MKN-1. In contrast, neither 5-fluorouracil (5-FU) nor cisplatin (CDDP) induced DNA fragmentation in any of the three cell lines. Small pieces cut from tumors implanted in nude mice were exposed to the antineoplastic agents in culture medium for 24 h, and the percentage of TUNEL-positive cancer cells (TUNEL positivity) was examined. TUNEL positivity in all three cancers increased after exposure to DXR, SN-38, and Taxol, but not after exposure to CDDP or 5-FU. MKN-45 showed the highest TUNEL positivity with SN-38 and Taxol, and TMK-1 TUNEL positivity was highest with DXR. MKN-45 and TMK-1 were the most sensitive to these three antineoplastic agents in vitro, while MKN-1, with the lowest TUNEL positivity, was the least sensitive to these three antineoplastic agents. TUNEL positivity after exposure to Taxol correlated with the antitumor effects of this compound in an animal model. Conclusion. These results suggest that, in small gastric cancer specimens where apoptosis is implicated, TUNEL positivity may be applicable to a chemosensitivity test.
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  • 8
    ISSN: 1436-3771
    Keywords: Key words Age ; Children ; Dental fluorosis ; Severity ; Tooth eruption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this study was to investigate the influence of age on the severity of dental fluorosis in children exposed to drinking water with either low or high fluoride concentrations. The children selected for this study were aged 10–14 years, with 28 permanent teeth and at least 1 tooth pair with fluorosis. The children were permanent residents of districts in western Uganda with either 0.5 mg (n=33) or 2.5 mg fluoride/l in drinking water (n=186). All vestibular tooth surfaces were examined for fluorosis using the modified Thylstrup and Fejerskov (TF) index. In the high fluoride community, the proportion of teeth per child with TF scores ≥4, and ≥5 was significantly higher among children aged 13–14 years compared to those aged 10–12 years. Children’s chronological age correlated positively and significantly with the median TF scores for all teeth, including early erupting (first molars and incisors) and late erupting teeth (canines, premolars and second molars). In linear regression analyses, the median TF score for all teeth, as well as for early erupting and late erupting teeth, increased significantly with age. On the other hand, in the low fluoride community there was no significant association between age and the severity of fluorosis. This study showed a significant increase in the severity of fluorosis with increasing age in a high fluoride community, whereas no change in severity with age was observed in a low fluoride community.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S270 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter ; Röntgendiagnostik ; Panoramaschichtaufnahme ; Strahlenexposition ; Computertomographie ; Kernspintomographie ; Key words ; X-ray diagnostics ; Panoramic X-ray ; Radiation exposure ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A vital X-ray imaging technique in oral and craniomaxillofacial surgery is the panoramic X-ray. Due to its variety of special projections, including imaging of the transversal level and low exposure to radiation, it is suitable for answering many clinical questions and for diagnostics of various findings. It has become possible to minimize the necessary doses by further development of technology and devices, as well as of X-ray films and by new detection systems, such as sensors or screens. In some clinical cases, the diagnostic deficiencies of conventional imaging techniques make computed tomography (CT) and magnetic resonance (MR) imaging indispensable. Although MR is particularly suitable for soft tissue imaging, it has also become helpful in finding cortical changes by shorter measuring times. In certain cases, e. g., changes to bone metabolism, differentiated methods of nuclear medicine make image-aided analysis of function possible.
    Notes: Zusammenfassung Zentrale Aufnahmeart in der Röntgendiagnostik der Mund-, Kiefer- und Gesichtschirurgie ist die Panoramaschichtaufnahme. Mit ihren zahlreichen Spezialprojektionen einschließlich der Abbildung der Transversalebene ist sie für die Abklärung zahlreicher Fragestellungen mit geringer Strahlenexposition geeignet. Die Verringerung des Dosisbedarfs ist weiterhin durch Fortentwicklungen der Gerätetechnik, der Röntgenfilme und durch neue Detektionssysteme wie z. B. Sensoren oder Speicherfolien möglich geworden. Diagnostische Unzulänglichkeiten der konventionellen Aufnahmearten machen bei zahlreichen klinischen Fragestellungen der Mund-, Kiefer- und Gesichtschirurgie eine Bildgebung mittels Computertomographie und Kernspintomographie unumgänglich. Obgleich die Kernspintomographie v. a. für die Weichteildiagnostik vorrangig geeignet ist, erlaubt sie mittlerweile, aufgrund der Verkürzung der Messzeiten, auch Veränderungen der Kortikalis abzubilden. Bei bestimmten Fragestellungen, wie z. B. Veränderungen des Knochenmetabolismus, ermöglichen differenzierte nuklearmedizinische Verfahren eine abbildungsunterstützte Funktionsanalyse.
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  • 10
    ISSN: 1432-2307
    Keywords: Key words Colon ; Nonpolypoid adenoma ; Apoptosis ; Proliferation ; Morphogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.
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  • 11
    ISSN: 1432-2307
    Keywords: Keywords Medullary thyroid carcinoma ; MEN2 ; Proliferation ; Apoptosis ; bcl ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n=16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.
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  • 12
    ISSN: 1279-8517
    Keywords: Spinal cord ; Dorsal horn ; Magnetic resonance imaging ; Radiologic anatomy ; Dorsal root entry zone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The spinal dorsal horn is known for its important functional role in the field of transmission and modulation of sensory afferents. Because of this, the dorsal horn represents a target for numerous analgesic and antispastic procedures. Thus, it would be interesting to develop imaging dedicated to this spinal structure. The purpose of this study was to investigate the radiologic anatomy of the cervical dorsal horn by magnetic resonance imaging (MRI) (1.5T). The first step consisted in the validation of the anatomic information provided by MRI on 5 human cadavers. A spin-echo sequence (T2, 2000/45) enabled the demonstration of good correlations between histologic sections and axial MRI slices performed at the corresponding cervical levels. The second step was the 〈〈in vivo〈〈 exploration of 20 subjects, aiming at the development of a gradient echo sequence (T2*) with a conventional MRI unit, compatible with a routine clinical examination. The dorsal horn was clearly identified in 77% of the axial slices performed (n = 300). The angle between the dorsal horn axis and the sagittal plane was measured as from 25.5˚ at C2 to 40˚ at C8 segments. The results of this anatomico-radiologic study of the cervical dorsal horn suggest that preoperative MRI could be useful to design the surgical approach to this structure, as performed during cervical microsurgical drezotomy (DREZ = dorsal root entry zone) for the treatment of selected cases of chronic pain or disabling spasticity in the upper limbs.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Techniques in coloproctology 4 (2000), S. 129-131 
    ISSN: 1128-045X
    Keywords: Key words Colonscopy ; CT scanning ; Magnetic resonance imaging ; Virtual colonoscopy ; Pneumocolography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colonoscopy is an invasive technique, frequently incomplete and often poorly tolerated in elderly patients. New, less invasive modalities are being developed to diagnose moderate-sized adenomatous polyps and colorectal caners which involve pneumo- or hydrocolography with high-resolution surface imaging, either by CT or MR scanning. This approach has recently been supplemented by complex image post-processing to provide a form of virtual colonoscopy which takes account of projected colonic direction and which can map for mucosal anomalies. It remains to be seen how sensitive these newer techniques are and whether defined algorithms for colonic representation can be agreed upon which will prove both accurate and cost-effective both in symptomatic and screening populations.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    The journal of headache and pain 1 (2000), S. 67-71 
    ISSN: 1129-2377
    Keywords: Key words Chronic daily headache ; Migraine ; Magnetic resonance imaging ; Red nucleus ; Substantia nigra ; Image processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using BOLD-fMRI we have previously documented activation of the red nucleus (RN) and substantia nigra (SN) during spontaneously and visually activated migraine headache. These observations prompted us to study brainstem function in chronic daily headache patients using high-resolution magnetic resonance imaging (MRI) techniques. Seventeen chronic daily headache (CDH) patients, ten episodic migraine (EM) patients and fifteen controls (N) were imaged with a 3 tesla MRI system. For each subject, the relaxation rates R2, R2* and R2' were obtained for RN and SN. There was a significant decrease in R2' and R2* values for RN and SN in CDH compared to N and EM groups (p 〈 0.05), but no significant difference between the N and EM groups. A decrease in R2' and R2* indicates reduced deoxyhemoglobin and hence persistent activation of the RN and SN in CDH patients most likely secondary to ongoing headache at the time of study. The imaging data provide objective evidence of disturbed central nervous system function in CDH.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    The journal of headache and pain 1 (2000), S. 169-172 
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Sleep ; Sleep apnea ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In our previous study we found a high prevalence of disordered sleep breathing in migraine children vs. controls. Since no quantitative studies about sleep respiratory disorders have been carried out in migraine children, we performed a polysomnographic (PSG) study in 10 migraine patients (7 boys, 3 girls; mean age 8.11 years, range, 5.8–14.5) attending the Headache Center of our department, to evaluate the presence of sleep apnea. Mothers completed a headache diary and a sleep diary for at least 1 month and filled out a sleep questionnaire. PSG data showed a normal sleep architecture in 3 cases, an insomnia pattern in 2, a reduction of slow wave sleep in 3 and a reduction of REM sleep in 2. Respiratory analysis revealed that 2 of 10 patients had obstructive sleep apnea. These 2 patients presented habitual snoring and associated sleep disturbances such as restless sleep and hypnic jerks. Sleep apnea may be a subtle and often undiagnosed symptom in several migraine patients. The report of habitual snoring associated with other sleep disturbances such as restless sleep and other parasomnias may be a sign of sleep apnea in migraine children.
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  • 16
    ISSN: 1129-2377
    Keywords: Key words Coeliac disease ; Headache ; Children ; HLA antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The linkage between HLA antigens and disease susceptibility has been investigated in several diseases. Two different mechanisms are known to act in the relation between the HLA system and headache: linkage and association of alleles. Among neurological disorders associated with coeliac disease (CD) we focused on headache in 1997. From a group of 70 coeliac children, we studied 10 children with headache (3 boys and 7 girls). For each subject we evaluated clinical history and HLA antigens. The incidence of headache was not different with respect to the prevalence of headache in the general population. The HLA setting is not different between the 2 groups examined. However, we highlight 2 cases for the particular HLA setting.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Neurosurgical review 23 (2000), S. 98-103 
    ISSN: 1437-2320
    Keywords: Key words Computed tomography ; Magnetic resonance imaging ; Lateral ventricle ; Subependymoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Four subependymomas of the lateral ventricle were reviewed with regard to clinical presentation, neuroimaging features, treatment, histopathological features, and long-term follow-up. There were two male and two female patients ranging in age from 27 to 60 years (mean 48.3 years). While two patients presented with symptoms and signs of raised intracranial pressure, two others were found incidentally during neuroimaging investigations to have intraventricular tumors. Neuroimaging characteristics of these tumors included no paraventricular extension, iso- or hypodensity with minimal enhancement on computerized tomography (CT), or iso- or hypointensity on T1-weighted and hyperintensity on T2-weighted magnetic resonance images (MRI). The usual finding on MRI was of no or scarce contrast enhancement, but one case showed heterogeneous enhancement. Three patients underwent total resection of the tumor and one underwent partial resection. No patients received postoperative radiation therapy. All patients have been doing well 4.8 to 15.4 years (mean 8.8 years), after surgery. Although there are no absolutely specific features to distinguish these tumors from other intraventricular tumors preoperatively, subependymoma should be kept in mind for differential diagnosis, as this tumor may safely be removed without sacrificing contiguous normal tissue and with good long-term results.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    International journal of colorectal disease 15 (2000), S. 9-20 
    ISSN: 1432-1262
    Keywords: Keywords Rectal cancer staging ; Computed tomography ; Endorectal sonography ; Magnetic resonance imaging ; Systematic review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  With the widespread introduction of preoperative radiotherapy for rectal cancer and the development of transanal endoscopic microsurgery for selected early lesions, preoperative radiological staging of these tumours has taken on increasing importance. This study is a systematic review to evaluate computed tomography (CT), endorectal sonography (ES) and magnetic resonance imaging (MRI) as preoperative staging modalities in rectal cancer. A Medline-based search identifying studies using CT, ES, or MRI in preoperative staging of rectal cancer between 1980 and 1998 was undertaken. The list of papers was supplemented by extensive cross-checking of citation lists. Studies were included if they met predetermined criteria. Data from the accepted studies were entered into pooled tables comparing radiological and pathological staging results for each modality both in determining bowel wall penetration and involvement of lymph nodes. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were determined for the pooled results. Eighty-three studies from 78 papers including 4897 patients met the inclusion criteria. In determining the wall penetration of the tumour the values for sensitivity for CT, ES, MRI and MRI with endorectal coil were 78%, 93%, 86% and 89%; for specificity 63%, 78%, 77% and 79%; and for accuracy 73%, 87%, 82% and 84%, respectively. In determining the nodal involvement by tumour the sensitivity values for CT, ES, MRI and MRI with endorectal coil 52%, 71%, 65% and 82%; for specificity 78%, 76%, 80% and 83%; and for accuracy 66%, 74%, 74% and 82%, respectively. MRI with an endorectal coil is the single investigation that most accurately predicts pathological stage in rectal cancer.
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  • 19
    ISSN: 1432-1335
    Keywords: Key words Genistein ; Eicosapentaenoic acid ; Apoptosis ; Bax ; Bcl-xL ; Caspase-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 μM) with an IC50 of 7.0–274.2 μM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL-100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM–37 μM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein 〉 93.2 μM and EPA 〉 210.9 μM) and on MDA-MB-231 cells (genistein 〉 176.1 μM and EPA 〉 609.3 μM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 145-152 
    ISSN: 1432-1335
    Keywords: Key words Angiogenesis ; Apoptosis ; Glioma ; Thymidine phosphorylase ; Vascular endothelial growth factor ; AbbreviationsTP thymidine phosphorylase ; GBM glioblastoma ; AA anaplastic astrocytoma ; LGA low-grade astrocytoma ; VEGF vascular endothelial growth factor ; RT-PCR reverse transcriptase/polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
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  • 21
    ISSN: 1432-1335
    Keywords: Key words Cycloprodigiosin hydrochloride ; Breast cancer ; Apoptosis ; Intracellular acidification ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of cycloprodigiosin hydrochloride (cPrG · HCl), a H+/Cl− symporter, on five human breast cancer cell lines (KPL-1, T-47D, MCF-7, MKL-F, and MDA-MB-231), a human breast epithelial cell line (HBL-100), and a human fibroblast cell line (WI-38–40) was examined. cPrG · HCl inhibited the growth of all five breast cancer cell lines (IC50: 0.46–0.62 μM) and slightly inhibited HBL-100 and WI-38–40 cell growth (IC50: 1.75 μM and 2.26 μM respectively). cPrG · HCl treatment in KPL-1 cells increased the pH of acidic organelles, decreased intracellular pH, and caused apoptosis, which was confirmed by the appearance of a sub-G1 population by flow cytometry and DNA fragmentation. In addition, cPrG · HCl-induced apoptosis was strongly suppressed by imidazole, a cell-permeable base, suggesting that intracellular acidification was essential for the apoptosis. Further, cPrG · HCl treatment up-regulated Bax and Bak expression, down-regulated Bcl-2 expression, and activated caspase-3. Therefore, the intracellular acidification by cPrG · HCl treatment suppressed the growth of human breast cancer cell lines by inducing apoptosis.
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  • 22
    ISSN: 1432-1335
    Keywords: Key words 5-Fluorodeoxyuridine ; Heterodinucleoside dimers ; Prodrugs ; Prostate cancer ; Cytotoxicity ; Cell cycle ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: Current therapies have limited impact on the progression of metastatic hormone-refractory prostate cancer. Therefore, we investigated the utility of new heterodinucleoside phosphate dimers of 5-fluorodeoxyuridine (5-FdUrd) in p53-mutated and androgen-independent DU-145 human prostate tumour cells. Methods: The effects of the dimers were assessed in vitro by a cell proliferation assay for cytotoxicity, flow cytometry for cell cycle distribution, confocal laser scanning microscopy for the detection of apoptotic bodies, poly(ADP-ribose) polymerase cleavage for caspase 3 activity and by a thymidylate synthetase assay. Results: The new dimers N 4-palmitoyl-2′-deoxycytidylyl-(3′→5′)-5-fluoro-2′-deoxyuridine (dCydPam-P-FdUrd) and 2′-deoxy-5-fluorouridylyl-(3′→5′)-2′-deoxy-5-fluoro-N 4-octadecylcytidine (5-FdUrd-P-FdCydOct) caused marked cytotoxicity with IC50 values of 3–4 μM. 5-FdUrd-P-FdCydOct at 200 μM was capable of eradicating 100% of tumour cells whereas 10% of the cells were resistant to 5-FdUrd. Cytotoxicity was caused by a dramatic S-phase arrest, resulting in an increase of this cell population from 34% to 85% with 5-FdUrd-P-FdCydOct and to 81% with dCydPam-P-FdUrd. S-phase arrest was followed by apoptosis, as shown by 85% of the cells staining positive for Apo 2.7 antibody, a six- to eight-fold increased caspase 3 activity and DNA fragmentation. Thymidylate synthase activity was inhibited by 50% at 0.6–0.7 μM dimer concentration. The dimers were hydrolysed in vitro by phosphodiesterase I and human serum to the corresponding nucleosides and nucleoside monophosphates. Conclusions: The new dimers dCydPam-P-FdUrd and 5-FdUrd-P-FdCydOct are effective prodrugs of 5-FdUrd and have potential value for the treatment of p53-mutated and hormone-independent human prostate carcinomas.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Der Nervenarzt 71 (2000), S. 164-172 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Psychisch kranke Eltern ; Depressive Eltern ; Entwicklungsbedingungen ; Psychosoziale Bedingungen ; Kinder ; Forschungsprobleme ; Forschungsaufgaben ; Forschungskriterien ; Key words Parents with psychiatric disorders ; Depressive parents ; Developmental conditions ; Psychosocial condition ; Children ; Research problems ; Research tasks ; Research criteria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Children of psychiatrically ill parents represent a risk group that has received growing attention during the last years. The risk for this group to develop a psychiatric illness is markedly increased due to genetic and psychosocial factors. The development of effective preventive concepts requires a thorough knowledge of the psychosocial factors. In this paper, deficits and problems of research in psychosocial transmission mechanisms are discussed taking the example of children of depressive parents. Conclusions from this exemplary considerations may serve as guidelines for future research. The authors suggest that the focus be rather placed on coping strategies and developmental psychopathology. Further, research criteria are formulated that refer to theoretical models as well as to study design.
    Notes: Zusammenfassung Kinder psychisch kranker Eltern stellen in psychiatrischer Hinsicht eine Risikogruppe dar, die in den letzten Jahren zunehmend in den Blickpunkt gerückt ist. Die Wahrscheinlichkeit für psychische Erkrankungen ist bei dieser Gruppe aufgrund von genetischen und psychosozialen Faktoren deutlich erhöht. Die Entwicklung von effektiven Präventionskonzepten setzt eine genaue Kenntnis der psychosozialen Faktoren voraus. In der vorliegenden Arbeit werden Defizite und Probleme bei der Erforschung der psychosozialen Transmissionsmechanismen am Beispiel der Kinder von depressiven Eltern diskutiert, und es werden Schlussfolgerungen herausgearbeitet, an denen sich die künftige Forschung orientieren sollte. Es wird vorgeschlagen, bewältigungsorientierte und entwicklungspsychopathologische Konzepte stärker zu berücksichtigen; darüber hinaus werden Forschungskriterien formuliert, die sich sowohl auf die theoretischen Modelle ebenso wie auf die Untersuchungsdesigns beziehen.
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  • 24
    Electronic Resource
    Electronic Resource
    Springer
    HNO 48 (2000), S. 828-831 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Cochlear Implant ; Resthörige Kinder ; Indikation ; Bildung ; Keywords Cochlear implant ; Children ; Indication ; Education ; Residual hearing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and objective. Recent indications for cochlear implant in children are bilateral total cochlear deafness and an age of 2 or more. Reports on successful implantations in adults with residual hearing pose the question of whether this indication might be expanded to children with residual hearing. Patients/Methods. In a retrospective analysis of 106 hearing-impaired children with binaural amplification, we were able to ask parents in 90 cases about their children's education. The pure-tone average of the frequencies of 1–4 kHz was correlated to education. Results. The results showed that all children except one with a pure-tone average of ≤90 dB could successfully attend regular school or kindergarten. However, those with a pure-tone average of ≥91 dB had to be educated in special units for children with impaired hearing. Conclusions. Our results indicate that amplification in children with profound hearing loss (pure-tone average ≥91 dB) is not sufficiently effective to enable them to attend regular schools or kindergarten. We conclude that the only chance to integrate these children into the world of hearing might be cochlear implantation.
    Notes: Zusammenfassung Hintergrund und Fragestellung. Die derzeit gültigen Richtlinien zur Indikation eines “Cochlear Implants” (CI) bei Kindern sind eine beidseitige cochleäre Taubheit sowie ein Lebensalter von über 2 Jahren. Berichte über die guten Hörerfolge nach Implantation von resthörigen, nicht tauben Erwachsenen werfen die Frage nach dieser Indikationserweiterung auch bei Kindern auf. Ziel unserer Arbeit war es, die Effizienz der Hörgeräteversorgung von schwerhörigen Kindern an Hand des Bildungsweges zu beurteilen um daraus Schlüsse zur Indikationserweiterung für ein CI zu ziehen. Patienten/Methodik. In einer retrospektiven Analyse von 106 beidseitig schwerhörigen, mit Hörgeräten versorgten Kindern konnte der Bildungsweg durch Befragung der Eltern in 90 Fällen erhoben werden. Ergebnisse. Durch Ermittlung der mittleren Hörschwelle in den Frequenzen 1–4 kHz und Vergleich mit dem Bildungsweg konnte gezeigt werden, dass nahezu alle Kinder (bis auf eines) mit einer Hörschwelle ≤90 dB Regelschulen oder -kindergärten mit Erfolg besuchen konnten. Alle Kinder mit einer Hörschwelle ≥91 dB mussten spezielle Einrichtungen für Hörbehinderte besuchen. Schlussfolgerungen. Da nach unseren Ergebnissen schwerhörige Kinder mit einer mittleren Hörschwelle ≥91 dB trotz Hörgeräteversorgung nicht in der Lage sind, Regelschulen oder -Kindergärten erfolgreich zu besuchen, schließen wir daraus, dass das Hauptziel einer Versorgung, nämlich der Erwerb einer ausreichenden Sprachkompetenz und -Produktion, nur durch ein CI erreicht werden kann.
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  • 25
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Cochlear Implant ; Ambulante Rehabilitation ; Kinder ; Erwachsene ; Ergebnisse ; Keywords Cochlear implant ; Outpatient rehabilitation ; Cost effectiveness ; Results ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and objective. This study compares the results of the outpatient-based program of the Cochlear Implant Center Ruhr with inpatient-based rehabilitation, which is almost exclusively performed in Germany. Patients/methods. The Department of Otorhinolaryngology at the University of Essen in Germany provided 52 patients with either 22- or 24-channel Nucleus cochlear implants from March 1996 to July 1999. Almost all patients (n=49) were rehabilitated on an outpatient basis, which is the standard in many cochlear implant centers outside Germany. Results. The longest follow-up period at the University of Essen Department of Otorhinolaryngology was 36 months. Minor complications occurred in 10% of the patients. After 24 months, the first three implanted patients were able to discriminate 100% of numbers and over 60% of syllables in the Freiburg speech discrimination test. The patients who developed an understanding of open speech were able to discriminate 31 words per minute with cochlear implant and without lipreading after 24 months. Children were seen to double their Schmid-Giovannini scores at 6 months postimplantation. Conclusions. The Essen outpatient-based cochlear implant program demonstrates results in speech development and speech understanding equal to those of centers providing inpatient rehabilitation. A special advantage is continuous rehabilitation with professionals known to the child for several years. In children especially, exhaustive commuting reduces school attendance and is a burden on the accompanying guardians. As an inpatient, however, the child is torn from his familiar environment. Parents with several children have particular difficulties in accompanying their child and indeed this may not always be possible.
    Notes: Zusammenfassung Hintergrund und Fragestellung. In dieser Arbeit werden die Ergebnisse der ambulanten Rehabilitation nach Cochlear-Implant-Versorgung mit denen der stationären Rehabilitation verglichen, die bisher in Deutschland fast ausschließlich durchgeführt wird. Von März 1996 bis Juli 1999 wurden an der Universitäts-Hals-Nasen-Ohren-Klinik Essen 52 taube oder an Taubheit grenzende Patienten mit einem 22-kanaligen bzw. 24-kanaligen Nucleuscochlear-Implant versorgt. Fast alle Patienten (n=49) konnten wohnortnah ambulant rehabilitiert werden, wie dies dem internationalen Standard entspricht. Ergebnisse. Der längste bisherige Nachbeobachtungszeitraum an der Universitäts-Hals-Nasen-Ohren-Klinik Essen sind 36 Monate. Nach 2 Jahren wurden von den 3 am längsten nachbeobachteten Patienten 100% der Zahlen und über 60% der Einsilber im Freiburger Sprachtest verstanden. Im “speech tracking” erreichten Patienten mit CI und ohne Lippenabsehen nach 24 Monaten 31 Wörter/min. Die Kinder zeigten 6 Monate nach Implantation eine Verdopplung des Scores im Test nach Schmid-Giovannini. Schlussfolgerungen. Das Essener Modell zeigt, dass eine ambulante Rehabilitation nach CI zu vergleichbaren Ergebnissen in der Sprachentwicklung und im Sprachverstehen führt, wie sie von anderen Zentren vorgelegt wurden, in denen fast ausschließlich stationär rehabilitiert wird. Besonders bei Kindern bedeuten lange Anfahrtswege mit einwöchigem stätionärem Aufenthalt Schulausfälle und eine Belastung für die begleitenden Eltern und Familienangehörigen zu Hause, sowie erhebliche Fahrtkosten. Stationäre Aufenthalte zur Rehabilitation reißen zudem das Kind aus seiner gewohnten Umgebung und sind für Eltern mit mehreren Kindern oft unmöglich.
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  • 26
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörstörung ; Prävalenz ; Konnatale Hörstörungen ; Erworbene Hörstörungen ; Progredienz ; Infektionen ; Kinder ; Keywords Hearing loss ; Prevalence ; Connatal hearing loss ; Acquired hearing loss ; Progressive hearing loss ; Infections ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The results of international investigations on connatally acquired hearing loss are compared with the data of the German Registry on Childhood Hearing Loss (4058 cases). The connatal hearing disorders have shown a notable change in the last years regarding to aetiology and prevalence. In contrast to countries of the third world in developed nations the prevalence of permanent childhood hearing loss has been reduced down to 1 in 1.000 births. The results let assume a prevalence of approximately 1:1.200 births in Germany. For instance the number of rubella embryopathia decreased effectively. In contrast CMV infections and alcohol fetopathia are playing an increasing role. In the patients of the German Registry on Childhood Hearing Loss the percentage of certainly progressive hearing loss is 10.3 within the 4058 children with permanent hearing impairment. Diagnostic procedures first of all for the early diagnosis of CMV but also of toxoplasmosis are considerable because these infections may result in treatable hearing loss. Also consequent hearing tests are demanded in children with alcohol fetopathia.
    Notes: Zusammenfassung Im vorliegenden Beitrag werden die Daten internationaler Studien zu angeborenen erworbenen Hörstörungen mit den Ergebnissen aus 4058 Fällen im Deutschen Zentralregister für kindliche Hörstörungen (DZH) verglichen und ausgewertet. Die angeborenen Erkrankungen des Hörvermögens haben innerhalb der letzten Jahre bezüglich Ätiologie und Prävalenz einen deutlichen Wandel erlebt. Im Gegensatz zu Ländern der 3. Welt ist die Prävalenz permanenter kindlicher Hörstörungen in den westlichen Industrienationen auf ca. 1:1.000 gesunken. In Deutschland liegt die Prävalenz nach ersten Ergebnissen des DZH bei ca. 1,2:1.000. So ist beispielsweise der Anteil der Rötelnembryopathien stark zurückgegangen. Dagegen spielen heute die Zytomegalievirus-(CMV)-Infektion und die Alkoholfetopathie eine größere Rolle. Im Patientenkollektiv des DZH mit 4058 permanent hörgestörten Kindern beträgt der Anteil gesichert progredienter Verläufe 10,3%. Diagnostische Verfahren, vor allem zur Früherkennung von CMV und Toxoplasmose, gewinnen zunehmend an Bedeutung. Ebenso ist eine konsequente Hördiagnostik auch bei Kindern mit Alkoholfetopathie zu fordern.
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  • 27
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Cochlear Implant ; Kinder ; Eltern ; Psychische Belastung ; Erwartungshaltung ; Keywords Cochlear Implant ; Children ; Parents ; Psychosocial stress ; Expectations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Established knowledge. It is known that parents of hard-of-hearing children suffer from an increase in psychosocial stress. Scientific question. How does the psychosocial situation of parents with children who have cochlear implants change during rehabilitation? Aim of study. It was the aim of this study to demonstrate how parents evaluate retrospectively their own psychological well-being during the process of rehabilitation. Methods and results. We interviewed 87 parents by questionnaire which were mailed to them. Fifty-seven mothers and 46 fathers responded (59% return rate). Parents reported a significant increase in stress, as perceived by themselves, after the time of diagnosis. Of the parents, 25% continued to suffer from psychic stress during rehabilitation as could be demonstrated by the SCL-90-R questionnaire criteria. The expectations by parents were realistic prior to implantation but thereafter increased significantly with time. Conclusions. The psychological state of parents during the critical phase, after a diagnosis of deafness has been made for their child, has to be considered. Even after an initial phase of shock, parents seemed to be stressed to an extent that required therapeutic intervention.
    Notes: Zusammenfassung Bisheriges Wissen zum Thema. Eine generell erhöhte psychosoziale Belastung der Eltern hörbehinderter Kinder ist aus der Literatur bekannt. Wissenschaftliche Fragestellung. Wie verändert sich die psychosoziale Situation der Eltern von mit einem Cochlear Implant (CI) versorgten Kindern im zeitlichen Verlauf der Rehabilitation? Ziel der Arbeit. Ziel war es darzustellen, wie die Eltern ihr eigenes psychisches Befinden während der Rehabilitation ihres Kindes retrospektiv einschätzen. Methoden und Arbeitsergebnisse. 87 Elternpaare wurden getrennt in einer postalischen Fragebogenerhebung befragt; 57 Mütter und 46 Väter antworteten (59% Rücklauf). Die Eltern gaben ab dem Zeitpunkt der Diagnosestellung eine subjektiv deutlich erhöhte Belastung an. 25% der Eltern waren auch im weiteren Verlauf der Rehabilitation anhand der Beurteilungskriterien des SCL-90-R in einem klinisch relevanten Ausmaß psychisch belastet. Die Erwartung der Eltern vor der Implantation war realistisch und stieg im Verlauf der Rehabilitation statistisch signifikant an. Schlussfolgerungen. Die starke psychische Belastung in der Selbsteinschätzung der Eltern von CI-Kindern in der Phase der Diagnosestellung bestätigt die Theorie und klinische Praxis, dass die Eltern in dieser kritischen Phase besonderer Betreuung bedürfen. Auch über die Phase des initialen Schocks hinaus scheinen die Eltern in einem Ausmaß psychisch belastet zu sein, welches eine gezielte zusätzliche psychologische Betreuung der Eltern erforderlich machen könnte.
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  • 28
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Epidemiologie ; Cholezystolithiasis ; Kinder ; Sonographie ; Risikofaktoren ; Key words Epidemiology ; Cholecystolithiasis ; Children ; Ultrasound ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objective. To assess the prevalence of and risk factors (e. g., obesity and positive family history) for the development of cholecystolithiasis in a non-selected collective of children and adolescents. Design and participants. A series of 482 children and adolescents aged 6–18 years underwent upper abdominal diagnostic ultrasound examinations as part of a whole-community investigation (response rate: 78%) for Echinococcus multilocularis in a town in southern Germany. Results. Gallbladder stones were identified in three of 482 children, corresponding to a prevalence of 0.6%. None of the three children was overweight at the time of the examination. Additional risk factors (pronounced weight reduction and Wilson's disease) were present in one study subject. Conclusions. Findings of the present study do not confirm the significance of obesity as a risk factor for cholecystolithiasis in children and adolescents.
    Notes: Zusammenfassung Fragestellung. Ziel der Studie war es, Häufigkeit und Risikofaktoren der Cholezystolithiasis, insbesondere Adipositas und familiäre Belastung, an einem unselektierten Kollektiv von Kindern und Jugendlichen zu untersuchen. Methode und Studienkollektiv. Ein Studienkollektiv von 482 Kindern einer Gemeinde in Süddeutschland zwischen 6 und 18 Jahren wurde in einer Vollerhebung (Responserate: 78%) im Rahmen einer Screeninguntersuchung zu Echinococcus multilocularis sonographisch untersucht. Ergebnisse. Bei 3 von 482 Kindern, entsprechend einer Prävalenz von 0,6%, wurden Gallenblasensteine festgestellt. Keines der 3 Kinder war zum Zeitpunkt der Untersuchung übergewichtig. Als weitere Risikofaktoren fanden sich bei einem Studienteilnehmer eine starke Gewichtsreduktion sowie ein M. Wilson. Schlussfolgerungen. Adipositas konnte bei Kindern und Jugendlichen in der vorliegenden Studie nicht als Risikofaktor für die Cholezystolithiasis bestätigt werden.
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  • 29
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Multiple Sklerose ; Apoptose ; Immunpathogenese ; CD95 ; TNF ; Keywords Multiple sclerosis ; Apoptosis ; Immunopathogenesis ; CD95 ; TNF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Apoptosis, or programmed cell death, is a physiological cell suicide program mainly leading to selective elimination of useless cells. This mechanism is important for the homeostasis of the immune system and presumably plays a two-sided role in the pathogenesis of multiple sclerosis (MS). On the one hand, evidence has been provided that impaired apoptosis might result in increased numbers or persistence of activated myelin-specific T cells, thus inducing the pathophysiologic processes in MS. On the other hand, local tissue damage might involve apoptosis of glial and neuronal cells and lead to the clinical symptoms. Here, an overview is presented on the current knowledge of the role of apoptosis in the pathogenesis of MS, and implications for related therapeutic strategies are discussed.
    Notes: Zusammenfassung Apoptose, auch programmierter Zelltod genannt, stellt einen physiologischen Prozess zur selektiven Eliminierung vor allem von unerwünschten körpereigenen Zellen dar. Dieser für die Homöostase des Immunsystems wichtige Mechanismus nimmt wahrscheinlich eine ambivalente Schlüsselrolle in der Ätiopathogenese der multiplen Sklerose (MS) ein. So existieren Hinweise dafür, dass bei der MS eine eingeschränkte Apoptose zur pathologischen Existenz und Persistenz aktivierter myelinspezifischer T-Zellen führt, die wiederum für die charakteristische intrazerebrale Entzündung verantwortlich gemacht werden. Gleichzeitig deuten aktuelle Arbeiten aber darauf hin, dass auf der Endstrecke der entzündlichen Reaktion der apoptotische Untergang von Glia- und evtl. auch Nervenzellen zur Gewebeschädigung und somit entscheidend zur klinischen Symptomatik beitragen. Ziel dieser Übersicht ist die Zusammenstellung der bislang gewonnenen Erkenntnisse zur Bedeutung von Apoptose für die Pathogenese der MS und eines Ausblicks auf mögliche apoptoseorientierte Therapiestrategien.
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  • 30
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Thoraxtrauma ; Atelektasen ; Pädiatrie ; Bauchlage ; Keywords Thoracic trauma ; Atelectasis ; Children ; Prone position
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract We report on the ventilation in prone position in a 5-year-old traumatized child with severe thoracic and abdominal injuries (lung contusion, rib fractures, rupture of liver and spleen). Under continuous analgosedation, the young patient was ventilated in prone position for 6 h, since acute lung injury and atelectasis persisted despite various therapeutic measures (artifical ventilation in the pressure controlled mode, fiberoptic bronchoscopy, reexpansion maneuver). After initiation of the prone position, we observed a rapid increase i narterial oxygenation, which persisted in the following period. The hemodynamic situation remained stable. The complete disappearance of atelectasis was demonstrated radiologically after supine repositioning. After cessation of analgosedation, the extubation was performed 2 days later. Furthermore, we found no side effects of the prone position on the injured abdomen, and the liver function improved rapidly. Although there is a lack of experience with ventilation in prone position in pediatric intensive care, our report might be a recommendation for the indication of this technique in children.
    Notes: Zusammenfassung In dieser Kasuistik wird über die erfolgreiche Anwendung der Beatmung in Bauchlage bei einem 5-jährigen Mädchen berichtet, welches von einem Pkw überrollt worden war und sich Thorax- und Abdominalverletzungen (Rippenserienfraktur, Lungenkontusion, Leber- und Milzeinrisse) zugezogen hatte. Wegen des akuten Lungenversagens mit persistierenden Atelektasen, die durch wiederholte fiberoptische Bronchiallavagen und durch Reexpansionsmanöver nicht zu beheben waren, wurde der Entschluss zur 6-stündigen Lagerung auf den Bauch gefasst, obwohl über den Effekt dieser Lagerungsmaßnahme bei traumatisierten Kindern wenig bekannt ist und zu möglichen negativen Auswirkungen auf das schwerverletzte Abdomen eine Informationen vorliegen. Die Beatmung in Bauchlage führte zur raschen Verbesserung des pulmonalen Gesaustausches, die hämodynamische Situation wurde nicht beeinflusst. Die radiologische Kontrolle nach Rücklagerung zeigte eine vollständigen Rückgang der Atelektasen; die kleine Patientin konnte bald darauf extubiert werden. Weder laborchemisch noch klinisch wurde ein schädigender Einfluss auf das verletzte Abdomen gefunden. Die Beatmung in Bauchlage hat sich als Routineverfahren bei der Behandlung des Lungenversagens des Erwachsenen etabliert; nach der hier beschriebenen Erfahrung ist diese Maßnahme auch bei traumatisierten Kindern in Betracht zu ziehen, insbesondere wenn andere Maßnahmen nicht ausreichend sind.
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  • 31
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    Monatsschrift Kinderheilkunde 148 (2000), S. 113-117 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter ; Kinder ; Säuglinge ; Protonenpumpenhemmer ; Omeprazol ; Pharmakologie ; Gastroösophageale Refluxkrankheit ; Ösophagitis ; Helicobacter-pylori-Infektion ; Ulkus ; Key words ; Children ; Infants ; Omeprazole ; Gastroesophageal reflux disease ; Esophagitis ; Pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Proton pump inhibitors (omeprazole, lansoprazole, and pantoprazole) have revolutionized the therapy of peptic disease of the upper gastrointestinal tract and reduced the indications for surgical intervention. These substances inhibit the H+/K+-ATPase in the parietal cells with an acid suppressing potency that is much higher than that of H2-receptor-antagonists. The first proton pump inhibitor, omeprazole, has been introduced ten years ago. Since then, sufficient experience with this drug in children has accumulated. Omeprazole is released for children aged one year or older. A new formulation makes the drug applicable in tube fed patients. The main indications for the use of omeprazole are endoscopically verified peptic esophagitis and gastric and duodenal ulcerations of different etiologies. In the treatment of Helicobacter pylori-infection a sufficient acid suppression is essential for the efficacy of the antibiotics. The recommended pediatric dose ranges between 0,7–1,4 mg/kg bodyweight and day. However, some children with ulcerative esophagitis may need daily doses up to 3.5 mg/kg. Healing of the esophageal mucosa should be monitored by endoscopy. After remission, doses can often be reduced for maintenance therapy. Side effects are rare and do not seem to increase with higher doses. Possibly interactions with other medications, i.e. antiepileptic drugs, may occur. A long-term therapy lasting more than 6 months in a child should be monitored by an experienced pediatric gastroenterologist.
    Notes: Zusammenfassung Protonenpumpeninhibitoren (Omeprazol, Lansoprazol, Pantoprazol) haben die Therapie peptischer Erkrankungen im oberen Gastrointestinaltrakt revolutioniert und die Indikation für chirurgische Therapiemaßnahmen deutlich eingeschränkt. Diese Substanzen hemmen die H+-/K+-ATPase in den Parietalzellen und haben eine sehr viel stärkere säuresuppressive Wirkung als H2-Rezeptor-Antagonisten. Mit dem ersten Vertreter dieser Substanzklasse, Omeprazol, liegen nach 10jähriger Anwendung inzwischen ausreichend Erfahrungen bei Kindern vor. Die Substanz ist für Kinder ab dem 1. Lebensjahr zugelassen und in einer neuen Darreichungsform auch bei Sondenernährung anwendbar. Die wichtigsten Indikationen für den Einsatz von Omeprazol sind eine endoskopisch gesicherte peptische Ösophagitis und Ulzerationen verschiedener Genese im Magen und Duodenum. Für eine effektive Therapie der Helicobacter-pylori-Infektion ist die ausreichende Säuresuppression essentiell für die Wirksamkeit der eingesetzten Antibiotika. Die therapeutische Dosis liegt zwischen 0,7 und 1,4 mg/kg KG und Tag, in Einzelfällen werden zur Abheilung einer Refluxösophagitis bis zu 3,5 mg/kg und Tag benötigt. Die Abheilung erosiver und ulzeröser Läsionen muß endoskopisch kontrolliert werden. Für die Erhaltungstherapie nach Abheilung sind niedrigere Dosen angemessen. Bei kurzfristiger Anwendung sind Nebenwirkungen selten und scheinen nicht dosisabhängig zu sein. Potentielle Wechselwirkungen mit anderen Medikamenten, besonders Antikonvulsiva, müssen beachtet werden. Eine Langzeittherapie bei Kindern über Monate oder Jahre muß gut überwacht werden und gehört in die Hand eines damit erfahrenen Kindergastroenterologen.
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  • 32
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    Der Urologe 39 (2000), S. 214-221 
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Krebs ; Karzinogenese ; Zellzyklus ; Protoonkogene ; Tumorsupressorgene ; DNA-Reparaturgene ; Apoptose ; Telomere ; Key words Multi-step carcinogenesis ; Cell cycle ; Proto-oncogene ; Tumor suppressor gene ; DNA repair gene ; Apoptosis ; Telomeres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The development of cancer is one of the most intensively studied areas of medical research resulting in an immense quantity of data. Therefore, the purpose of this article is to give an overview of the basic principles of cancer development. Key words such as multi-step carcinogenesis, cell cycle, proto-oncogene, tumor suppressor gene, DNA repair gene, apoptosis and telomeres are explained and described in examples. This paper aims to connect recent information of molecular and cellular biology in an overview of cancer origin and development.
    Notes: Zusammenfassung Die Entstehung von Tumoren und die Entwicklung von entsprechenden Modellen gehört zu den sehr intensiv untersuchten Fragestellungen medizinischer Forschung mit einer schier unerschöpflichen Datenflut. Ziel dieses Artikels ist daher die möglichst anschauliche und daher sicher vereinfachende Darstellung grundlegender Prinzipien der Krebsentstehung. Es werden Begriffe wie Mehrschrittkarzinogenese, Zellzyklus, Protoonkogene, Tumorsupressorgene, DNA-Reparaturgene, Apoptose und Telomere in Zusammenhang gebracht und anhand von Beispielen erklärt. Dieser Artikel soll damit zum Verständnis der Zusammenhänge der Molekular- und Zellbiologie bei der Krebsentstehung beitragen.
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  • 33
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    Trauma und Berufskrankheit 2 (2000), S. S136 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vordere Kreuzbandverletzung ; Kinder ; Rekonstruktion ; Indikation ; Key words ; ACL lesion ; Children ; Reconstruction ; Indications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract For ACL lesions in children near to the end of the growth phase the treatment can be treated identical to that in adults. For younger children (8–12 years) the treatment must be conservative, combined with controls at short intervals. Behaviour during sport should be modified. If instability is experienced in activities of daily life or during sport a reconstruction of the ACL should be done using a central tibial transepiphyseal hamstring reconstruction with a femoral over-the-top position to avoid possible growth disturbances.
    Notes: Zusammenfassung Kreuzbandverletzungen bei Kindern, die nahe ihres Wachstumsabschlusses sind (14. bis 17. Lebensjahr) können wie Kreuzbandverletzungen von Erwachsenen behandelt werden. Kreuzbandverletzungen bei Kindern, die 13 Jahre und jünger sind, sollten zunächst abwartend behandelt werden (Kniebandage, Koordinationstraining, Belastungsreduzierung). Stellt sich im täglichen Leben oder bei sportlicher Belastung eine Instabilität im Sinne eines Giving way heraus, so sollte das Kreuzband rekonstruiert werden. Dabei ist es nach allen vorliegenden Daten unbedenklich, die Tibia zentral mit einem 8-mm-Bohrloch zu durchbohren und ein ligamentäres Transplantat durchzuziehen. Femoral ist es aus Sicherheitsgründen eher sinnvoll, statt einer transossären Bohrung die Over-the-top-Position zu wählen. Auch andere, rein epiphysäre Verankerungsmethoden (Semitendinosusplastik mit transossärer Drahtfixation) sind möglich.
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  • 34
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    Trauma und Berufskrankheit 2 (2000), S. S138 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vorderes Kreuzband ; Kind ; Wachstumsfuge ; Fehlwachstum ; Key words ; Anterior cruciate ligament ; Children ; Growth plate ; Growth disturbance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Lesions of the anterior and posterior cruciate ligaments are relatively rare in childhood and adolescence; in this age group they need even more consistent and aggressive treatment than in adults as far as conservation of the menisci and definitive stabilization are concerned. Virtually no cases in which serious growth disturbance has arisen following transepiphyseal drilling are known from the literature. Thus, cruciate ligament suturing should also not be done in children, because the long-term efficacy has not been confirmed. The operative procedure is presented in detail and is related to bone age. Early transepiphyseal drilling is permissible.
    Notes: Zusammenfassung Ligamentäre Kreuzbandverletzung beim Kind und im Adoleszentenalter sind relativ selten, sie bedürfen im Vergleich zum Erwachsenen ¶einer noch konsequenteren und aggressiven Behandlung bezüglich Meniskuserhalt und definitiver Stabilisierung. In der Literatur sind praktisch keine Fälle bekannt, bei denen es tatsächlich zu einem gravierenden Fehlwachstum nach transepiphysärer Bohrung gekommen ist. Insofern sollte auch die Kreuzbandnaht beim Kind wegen der nicht bewiesenen Langzeiteffizienz unterlassen werden. Das Vorgehen im Einzelnen in Bezug zum Skelettalter wird dargestellt. Frühzeitige transepiphysäre Bohrungen sind erlaubt.
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  • 35
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    Clinical and experimental nephrology 4 (2000), S. 24-28 
    ISSN: 1437-7799
    Keywords: Key words Uranyl acetate ; ARF ; Glycine ; Apoptosis ; Tubular damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although uranyl acetate (UA) is known to induce apoptosis in renal tubular cells, the pathophysiological role of apoptotic cell death in UA-induced acute renal failure (ARF) is not clear. In this study, we examined whether glycine, which is known to provide protection against nephrotoxic acute renal failure, attenuated tubular damage in UA-induced ARF in rats, and, if so, whether the attenuation of tubular damage was associated with reduced apoptotic cell death. Methods. Sprague-Dawley rats were allocated to three groups; normal controls, UA-treated, and UA plus glycine-treated. Acute renal failure was induced by the intravenous injection of UA (5 mg/kg). UA plus glycine-treated rats were given glycine at 1 g/kg, i.v. over 3 min at the same time as the UA injection. Serum creatinine concentration (Scr) and tubular damage score were examined 5 days after UA administration. Apoptosis was evaluated by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in the outer stripe of the outer medulla. Results. Glycine significantly decreased the UA-induced increases in Scr (3.73 ± 0.31 vs 2.74 ± 0.11 mg/dl; P 〈 0.05) and the tubular damage score (3.83 ± 0.13 vs 2.58 ± 0.01; P 〈 0.01). UA significantly increased the number of TUNEL-positive cells in the outer stripe of the outer medulla (0.16 ± 0.04 vs 7.45 ± 0.46/high power field at ×400 magnification; P 〈 0.01 vs normal control value). Glycine infusion significantly lessened the number of TUNEL-positive cells (5.84 ± 0.31/ high power field at ×400 magnification; P 〈 0.01 vs UA-treated rats). A significant correlation was found between the number of TUNEL-positive cells and the tubular damage score (r = 0.93; P 〈 0.01). Conclusion. Glycine ameliorated the severity of UA-induced ARF and the degree of apoptotic cell death. This finding suggested that the protective effect of glycine in UA-induced ARF may be mediated, at least in part, through a reduction of apoptosis.
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  • 36
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    Clinical and experimental nephrology 4 (2000), S. 318-322 
    ISSN: 1437-7799
    Keywords: Key words IgA nephropathy ; Nephrotic syndrome ; Children ; Age at onset
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The prognostic significance of nephrotic syndrome (NS) in children with IgA nephropathy (IgAN) is unclear. Methods. NS was found in eight children with IgAN (mean onset age, 9.3 years). The clinicopathological findings of these eight children were investigated. Results. Five patients presented with macroscopic hematuria, while the remaining three were discovered in a school urinary screening program or by chance urinalysis. Six patients developed NS at the onset, and two developed NS later in the course of IgAN. All patients were treated with corticosteroids. At the end of follow-up, heavy proteinuria persisted in four children, one of whom had renal dysfunction at the onset of NS and developed end-stage renal failure, and two of whom developed NS after the onset of IgAN. Proteinuria decreased to less than 1 g/day 3 months after NS in four patients, two of whom showed disappearance of proteinuria afterward. Renal biopsy specimens revealed mesangial proliferation and crescent formation in all patients. The degree of persisting proteinuria was correlated with the presence of glomerular sclerosis, fibrous crescents, tubulo-interstitial changes on light microscopy, and depositions of C3 on immunofluorescence microscopy. Conclusions. Children who developed NS after the onset of IgAN developed renal dysfunction; the prognosis of those who showed chronic histopathological changes on renal biopsy specimens was poor, even in these young children.
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  • 37
    ISSN: 1437-9813
    Keywords: Key words Adriamycin ; Apoptosis ; Embryogenesis ; Esophageal atresia ; Notochord ; VATER association
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The adriamycin-induced rat model of the VATER association has provided a means of studying the morphogenesis of a variety of major congenital structural abnormalities similar to those seen in humans with the VATER association. Most interest has been centered on the foregut, where the model has clarified some aspects of the development of esophageal atresia (EA), tracheal agenesis, and other communicating bronchopulmonary foregut malformations. It has demonstrated aberrations in the nerve supply to the esophagus in EA and allowed the study of tracheomalacia. A relationship between an abnormal notochord, foregut abnormalities, and vertebral defects has been shown, and the model has reignited interest in the role of the notochord as a regional organizer of axial development. The normal temporospatial characteristics of apoptosis during fore- and hindgut development is disturbed in this model, resulting in abnormal morphology. The indications are that this model will continue to clarify the processes that lead to many of the structural congenital abnormalities that are seen in infants born with the VATER association.
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  • 38
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    Pediatric surgery international 16 (2000), S. 485-487 
    ISSN: 1437-9813
    Keywords: Key words Duodenum ; Apoptosis ; Fetus ; Rat ; Duodenal atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.
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  • 39
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    Pediatric surgery international 16 (2000), S. 589-591 
    ISSN: 1437-9813
    Keywords: Key words Domestic animals ; Children ; Injury ; Evaluation ; Prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Domestic animals are a potential cause of serious injury to handlers and children. In developed countries dogs are the most common cause of such injuries, but in developing countries childhood injuries from domestic animals have not been given much attention. A retrospective analysis of major injuries from domestic animal attacks in children aged 12 years or less in a developing country showed 17 injuries in 16 children. The locations were the abdomen (6), head and neck (4), extremities (3), external genitalia (3), and back (1). A big-horned cow was the cause of injury in 11 patients, a donkey in 4 and a ram in 1. Children under 10 years were injured by provoked animals, mostly as bystanders, while older children were handlers. Four abdominal injuries were penetrating with evisceration and contusion of bowel and required a laparotomy. One blunt splenic injury was managed non operatively and one by partial splenectomy. Two head injuries were managed non operatively. All other injuries were examined and explored with the child under general anaesthesia. These injuries were debrided and closed primarily or closure was delayed when contamination was heavy or adequate debridement was limited by vital neighbouring structures. Broad-spectrum antibiotics and tetanus prophylaxis were given for all open wounds. The average duration of hospital stay was 7.3 days. Three patients had wound infections resulting in long hospitalizations. Two patients died (12.5%), 1 from a severe head injury and 1 from an overwhelming infection. The management of major injuries from domestic animals in children requires meticulous evaluation and examination during general anaesthesia to establish the extent of injury and avoid missed injuries. Prevention of these injuries requires public education about the proper and compassionate handling of domestic animals.
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  • 40
    ISSN: 1437-9813
    Keywords: Key words Insulinoma ; Arterial stimulation ; Calcium ; Localization ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of pre- and intraoperative procedures for the localization of insulinomas has been extensively debated. We report a case of successful treatment using preoperative selective intra-arterial calcium injection and intraoperative glucose monitoring. A 12-year-old boy with hypoglycemic attacks had a large insulinoma in the head of the pancreas on computed tomography. Preoperative selective angiography combined with arterial stimulation-venous sampling (ASVS) by intra-arterial injection of calcium revealed no other insulinomas in the body and tail of the pancreas. Elevation of serum glucose on intraoperative monitoring confirmed complete enucleation of the insulinoma. Preoperative ASVS can accurately localize an insulinoma, and may help to increase the success rate of surgery and avoid blind pancreatectomy.
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  • 41
    ISSN: 1437-7772
    Keywords: Key words Photodynamic therapy ; Cervical cancer ; Apoptosis ; MnSOD ; Gene induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Photodynamic therapy (PDT) is a cancer treatment modality in which systemic administration of a tumor-localizing photosensitizer is followed by irradiation of the tumor with visible light. Although PDT is undergoing clinical trials for various cancers, the mechanisms of its action are not fully understood. To investigate the mechanism of cell death by PDT, we performed in-vitro PDT, using Photofrin II as a photosensitizer, in two human cervical carcinoma cell lines, HeLa and CaSki. Methods. Cells were incubated with Photofrin II for 24 h, followed by illumination, using a YAG-OPO laser. Cell survivability after PDT was evaluated by an MTT assay. Cytotoxicity was assayed by measuring the release of lactate dehydrogenase (LDH) into the supernatant. DNA of the PDT-treated cells was electrophoresed in an agarose gel to determine fragmentation. In situ detection of apoptosis in the PDT-treated cells was performed by identification of the 3′-OH ends of DNA. In addition, induction of manganese superoxide dismutase mRNA (MnSOD) was analyzed in the PDT-treated cells. Results. The CaSki cells were more sensitive to this PDT treatment than were the HeLa cells. DNA fragmentation was observed with less than 5 μg/ml of Photofrin II in both cell lines, whereas PDT-induced cell membrane destruction, determined by LDH release, was observed only at 10 μg/ml. The MnSOD mRNA was induced in the HeLa cells in the early hours after PDT with a non-lethal dose of Photofrin II, but was reduced with a high dose, whereas the CaSki cells did not show any induction of the MnSOD gene by PDT. Conclusion. The present results suggest that PDT induces cell death by a mechanism involving membrane destruction and apoptosis. Differences in cell susceptibilities to PDT may depend upon a protective mechanism, such as MnSOD gene induction.
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  • 42
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    Pediatric surgery international 16 (2000), S. 595-598 
    ISSN: 1437-9813
    Keywords: Key words Pleuropulmonary blastoma ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pleuropulmonary blastoma (PPB) is a rare malignant neoplasm affecting children. A retrospective review was carried out of patients diagnosed as having PPB at one institute over a period of 16 years. The presentation, diagnosis, treatment, and family history were studied. PPB usually presents with symptoms and signs of respiratory tract infection, and the diagnosis may be delayed. There are no distinguishing clinical features or imaging studies. The diagnosis is made on histologic examination of tumour material and is sometimes difficult to differentiate from benign cystic lung lesions. The treatment is primarily complete excision of the tumour, followed in some cases by intense chemotherapy. PPB is a strong predictor of the presence of tumours in close relatives. Four patients treated at our institute are discussed along with a review of the literature.
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  • 43
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    Pediatric surgery international 16 (2000), S. 132-133 
    ISSN: 1437-9813
    Keywords: Key words Sigmoid volvulus ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sigmoid volvulus is a common cause of large-bowel obstruction in elderly individuals, but is quite rare in childhood. We report six cases in patients under 20 years of age. One had Hirschprung's disease. Gangrenous sigmoid colon was found in three cases and resection was performed. Sigmoidopexy (one case) and extraperitonealization (two cases) were performed for viable sigmoid colon. There were no recurrences after 5.7 years of follow-up.
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  • 44
    ISSN: 1437-9813
    Keywords: Key words Echinococcosis ; Liver/interventional procedure ; Cyst/percutaneous drainage ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the efficacy of ultrasound (US) guided percutaneous sclerotherapy in the pediatric population, 14 hydatid liver cysts (HLC) in eight male patients whose ages ranged between 6 and 16 years (mean 9.9 years) were treated. The maximum diameter was 110 mm. Albendazole was administered orally to all patients for 1 week before percutaneous treatment and for 3–6 months after the procedure to prevent dissemination of the disease. Cyst puncture was performed with 20 G Chiba needles using US guidance. More than one-half of the estimated cyst volume was aspirated, then 20% hypertonic saline (7 cysts) or sterile 96% alcohol (7 cysts) equivalent to one-third of the estimated cyst volume was injected into the cavity and left for 5–15 min. Finally, all the fluid in the cavity was reaspirated. Catheterization was not performed. Follow-up US examinations were performed every month during the first 6 months and every 3 months thereafter. The follow-up period ranged between 6 and 51 months (mean 15 months). No major complications were seen during or after the procedures. Two cysts in two patients completely disappeared. Volumes of the 11 cysts in five patients who were followed for 6–21 months were markedly reduced (22%–64% of the initial volume) and thick septations and solid debris-like structures were seen within the cyst cavities. There was no significant change in 1 cyst. US-guided percutaneous sclerotherapy is thus a safe and effective treatment of HLC in children.
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  • 45
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    Pediatric surgery international 16 (2000), S. 388-391 
    ISSN: 1437-9813
    Keywords: Key words Anorectal injury ; Children ; Diagnosis ; Morbidity ; Mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anorectal injuries (ARI) are uncommon in children in civil practice. In developed countries the injuries are mainly due to sexual abuse and firearms. This report reviews the experience in tropical Africa. A retrospective study of children aged 12 years or less managed for ARI over 10 years was undertaken. There were seven children, four girls and three boys. Four injuries were due to blunt trauma and three to penetrating trauma. Six patients presented within 6 h of injury and one after 24 h. Five had rectal bleeding, which was associated with vaginal bleeding in one girl. One girl each had vaginal bleeding and vaginal discharge without rectal bleeding. Diagnosis was by rectal examination and proctoscopy. In three patients a laparotomy was necessary to exclude an intraperitoneal rectal injury (IRI); this was positive in one case. One patient with abdominal findings had a laparotomy as the primary procedure. Overall, five patients had rectal injuries (extraperitoneal 3, intraperitoneal 2), which were associated with an anal injury in three while one patient had only an anal injury. An IRI was missed at initial assessment in one girl. Associated injuries were to the vaginal wall (3), urethra (1) and head (1). IRIs were treated by repair and proximal colostomy. Extraperitoneal injuries were treated by colostomy and drainage; in two patients the injuries were accessible and were repaired. Anal and external-sphincter injuries were repaired in two cases. Vaginal lacerations were repaired and other associated injuries treated accordingly. Three patients had wound infections. Faecal continence was maintained in all patients who had anal and external-sphincter injuries. One girl died of peritonitis from a missed IRI. It is concluded that ARI remains uncommon in children. Morbidity and mortality can, however, be high. Meticulous rectal palpation and visualisation is necessary to avoid missing injuries.
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  • 46
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    Pediatric surgery international 16 (2000), S. 411-413 
    ISSN: 1437-9813
    Keywords: Key words Central venous catheters ; Children ; Ultrasound assessment of venous patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the value of Doppler ultrasound scan (USS) assessment of internal jugular vein (IJV) patency after previous open central-venous cannulation (CVC), a prospective study of 66 consecutive children (median age 4.5 years; range 4 months–17 years) who had previously undergone open insertion of at least one indwelling IJV line and required further CVC for completion of therapy was undertaken. All underwent Doppler USS examination prior to surgery. Where patency of the previously cannulated vein was suggested ultrasonographically, the accuracy of this finding was confined at open surgical exploration. Initial CVCs were in situ for a median of 9 months (1 month–4 years) prior to removal. The median interval to repeated CVC was 11 months (3 weeks–45 months). In 79 Doppler USS, 70 (88.6%) veins appeared patent, 3 (4.2%) stenosed, and 6 (7.6%) obliterated. Of the 70 “USS patent” veins, 66 were explored. Patency was confirmed surgically in 59 (89.4%) and a new CVC successfully inserted. Seven (10.6%) apparently patent veins on USS were found to be obliterated at open exploration. Review of USS images in these cases suggested that enlarged collateral veins were usually responsible. Overall, successful recannulation was possible in 74.6% of all previously accessed veins. In children requiring repeated CVC, Doppler USS of neck veins is a valuable but not entirely reliable guide to the presence of underlying vessel patency and should be interpreted with caution. At least three-fourths of previously cannulated IJVs remain patent after catheter removal and can be reused for CVC.
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  • 47
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    Pediatric surgery international 16 (2000), S. 429-430 
    ISSN: 1437-9813
    Keywords: Key words Amebic liver abscess ; Children ; Pediatric ; Stomach ; Rupture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The occurrence of an amebic liver abscess (ALA) rupturing into the stomach is reported. ALAs in children can have atypical presentations, resulting in delayed diagnosis and increased morbidity and mortality. Timely treatment is usually followed by complete recovery.
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  • 48
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    Pediatric surgery international 16 (2000), S. 433-436 
    ISSN: 1437-9813
    Keywords: Key words Hernia ; Spigelian hernia ; Children ; Cryptorchidism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Congenital spigelian hernia (SH) is very rare in the pediatric age group. This is a report of two cases of SH in 1-week and 3-month-old male infants. A review of the literature revealed only 35 cases of SH in children younger than 17 years of age, bringing the total including our 2 cases to 37. There were 25 males and 12 females, a ratio of 2.1:1. Their ages ranged from 6 days to 17 years (mean 4.52 years). The hernia was situated on the right side in 13, the left side in 19, and was bilateral in 4. In one case the side of the hernia was not mentioned. In 29 cases the hernia was spontaneous while in 5 it was caused by trauma. In 3 children the hernia developed postoperatively, in 2 following repair of a congenital diaphragmatic hernia and in 1 following excision of a mediastinal neuroblastoma. Two children presented with a strangulated SH. Eleven of the 35 previously reported children had associated conditions; in 5 there was an ipsilateral undescended testis (UDT). Our two infants with SH also had an ipsilateral UDT. The significance of this association is discussed.
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  • 49
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    Pediatric surgery international 16 (2000), S. 454-456 
    ISSN: 1437-9813
    Keywords: Key words Priapism ; Children ; Arteries ; Fistula ; Embolisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Priapism is an uncommon problem in childhood. Most of the reported cases are in boys with sickle-cell disease or leukaemia. It occurs as a result of venous outflow obstruction, resulting in engorgement of the corpora cavernosa, and is termed “low-flow” priapism. In a small group of children priapism is due to uncontrolled arterial inflow, usually as a result of direct trauma. The authors report a case of post-traumatic arterial priapism in a child, successfully treated with selective embolisation of the internal pudendal artery. Recognition of this distinct entity is important, as it carries a good prognosis when appropriately treated.
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  • 50
    ISSN: 1437-7780
    Keywords: Key words Gastric cancer ; Low-dose FP ; Pharmacokinetics ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To analyze the clinical efficacy of a protracted infusion of low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP), a phase II study was performed in 36 patients with advanced gastric cancer. The treatment schedule of the low-dose administration of 5-FU and CDDP (FP) was a continuous infusion of 5-FU (250 mg/m2) for 28 consecu-tive days and a drip infusion of CDDP (3.5 mg/m2) for 5 consecutive days, followed by a 2-day interval each week in one cycle. The overall response rate was 47.2%. Of importance, the improvement in quality of life assessed by performance status (PS) and oral intake was 13.9% and 33.3%, respectively. The toxicity in low-dose FP treatment was less than grade 2, including gastrointestinal toxicities and bone marrow suppression, and this was tolerable during the treatment. The median survival time (MST) and 1-year survival rate were 8 months and 36.2%, respectively. In a pharmacokinetic analysis following the protracted infusion of low-dose FP, the plasma concentrations of 5-FU and CDDP were increased to about 120–130 ng/ml and 0.3–0.5 μg/ml on day 21 after the treatment, respectively. The plasma concentrations of 5-FU and CDDP were not significantly different between responders and non-responders. The tumor response to low-dose FP treatment was associated with the induction of apoptotic cell death and with the overexpression of apoptosis-related genes, such as Bax and Bcl-Xs, in cancer cells. These results indicate that the protracted infusion of low-dose FP could be a useful regimen for patients with advanced gastric cancer, in terms of the high response rate and low toxi-city, possibly leading to the prolongation of survival and improvement in the quality of life.
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  • 51
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    Clinical and experimental nephrology 4 (2000), S. 225-230 
    ISSN: 1437-7799
    Keywords: Key words Peritoneal dialysis ; Dialysis index ; Urea kinetics ; Adequacy ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Peritoneal dialysis (PD) is an established treatment for children with end-stage renal failure. Creatinine clearance and urea kinetics are used to quantitate the dialysis treatment, but the means to assess the adequacy of dialysis in children are still controversial. Methods. We studied serum chemistry, dietary protein intake (DPI), protein catabolic rate (PCR), weekly urea clearance/body water (Kt/Vurea), weekly creatinine clearance (Ccr/week), clinical signs and symptoms during PD treatment, and peritoneal transport function in 17 children (4 to 18 years of age) with end-stage renal disease treated with PD. Fourteen children were on continuous ambulatory peritoneal dialysis (CAPD) and 3 were on automated peritoneal dialysis. Results. The mean values of the parameters tested were: blood urea nitrogen, 71 mg/dl; creatinine, 9.8 mg/dl; total protein, 6.4 g/dl; albumin, 4.0 g/dl; total Ccr, 70 l/week per 1.73 m2; DPI, 1.76 g/kg per day; PCR, 1.17 g/kg per day, and total Kt/Vurea, 2.28/week. The mean patient's clinical assessment score was 11.7, out of 15 and the mean doctor's clinical assessment score was 11.7, out of 14. The correlation between Kt/Vurea and creatinine clearance was 0.84 (P 〈 0.0001). Kt/Vurea and clinical assessment scores (patient's and doctor's scores) did not show a good correlation (r = 0.32; P = 0.228, and r = 0.47; P = 0.064, respectively). Peritoneal function seemed to be preserved after an average duration of 32 months on PD. Conclusions. These patients appeared to be fairly well dialyzed, judging from the values for the various dialysis indices obtained in this study and comparing them with adult indices.
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  • 52
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    Pediatric surgery international 16 (2000), S. 562-564 
    ISSN: 1437-9813
    Keywords: Key words Inguinal hernia ; Children ; Direct ; Recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Among 109 children treated laparoscopically for inguinal hernias, 5 had direct hernias, more than would normally be anticipated. Two of the hernias were recurrences of indirect hernias operated upon previously using the open technique. Direct hernias are easier to detect with the laparoscopic technique.
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  • 53
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    Pediatric surgery international 16 (2000), S. 50-52 
    ISSN: 1437-9813
    Keywords: Key words Intestinal volvulus ; Children ; Idiopathic ; Adhesion/bands ; Resection rate ; Outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In developed countries, intestinal volvulus in children is most frequently due to malrotation. To review the experience in Nigeria, a retrospective analysis of 28 patients managed over 25 years at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, was undertaken. There were 22 boys and 6 girls with an age range of 4 days to 14 years (median 4 years). There were equal numbers over and less than 5 years of age. Vomiting (89%) and abdominal distension (79%) were the most prominent features. Thirteen children (46%) had fever, associated with bowel gangrene in 5, while 8 (29%) presented with severe dehydration and shock. A plain abdominal radiograph was the only investigation performed, but the features were not specific for volvulus. In 11 children (39%) the volvulus was idiopathic, in 9 (32%) due to adhesions or bands, in 5 (18%) to malrotation, and in 1 each a Meckel's diverticulum, internal herniation, and ventriculoperitoneal shunt. Twenty-three patients had a small-bowel, 4 sigmoid, and 1 caecal volvulus. The bowel resection rate for gangrene was 46% (small bowel 9, sigmoid 3, caecum 1). All patients with malrotation had Ladd's procedure performed. Wound infections occurred in 10 patients (36%), complete wound dehiscence in 1, and recurrence in 1 (idiopathic terminal ileal volvulus). The mortality was 21%, mostly from overwhelming infection (2 neonates, 11-year-old, 3 ≥ 5 years). Intestinal volvulus in our environment differs in aetiology from other reports. The resection rates are similar, however. This condition carries high morbidity and mortality.
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  • 54
    ISSN: 1437-9813
    Keywords: Key words Macrodystrophia lipomatosa ; Fibrolipomatous hamartoma ; Magnetic resonance imaging ; Median nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Macrodystrophia lipomatosa (MDL) is a rare disease typically causing localized gigantism and is often associated with a fibrolipomatous hamartoma (FH) of the median or plantar nerve. A previously unreported case of MDL with associated FH of the median nerve is presented.
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  • 55
    ISSN: 1437-7772
    Keywords: Key words BAK cells ; T24 cells ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. We previously reported the basic characteristics of BCG (bacille Calmette-Guérin)-activated killer (BAK) cells, which exhibited antitumor effects against the bladder cancer cell line T24. Our study suggested that both BCG and BAK cells were responsible for the inhibition of tumor cell proliferation; however, the basic mechanism of BCG or BAK cells in this inhibition was not clear. We here report the antitumor effects of BAK cells, which correlated with the induction of apoptosis in T24 cells. Methods. Lymphocytes were cultured with BCG to examine 3H-thymidine uptake, and the subpopulation was evaluated by immunocytometry. T24 cells were then cultured with BAK cells for the analysis of 3H-thymidine uptake and apoptosis induction by DNA electrophoresis; pathology study, and cell-cycle analysis were also done. Culture supernatants of BAK and T24 cells were also investigated to detect interferon-γ (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Results. The 3H-thymidine uptake study of lymphocytes showed that BCG activated the lymphocytes. Evaluation by immunocytometry revealed that CD4+ and CD8+ T cells were induced by BCG. The 3H-thymidine uptake study of T24 cells revealed that BAK cells inhibited tumor cell proliferation. DNA electrophoresis, the morphological study, and cell-cycle analysis by immunocytometry demonstrated that apoptosis in T24 cells was induced when they were cultured with BAK cells. IFN-γ, IL-6, and TNF-α were detected in the culture supernatants of BAK and T24 cells. Conclusions. Cytokine production and the induction of apoptosis may, together, be the major mechanisms of the antitumor action seen when BAK cells were employed against T24 cells; BAK cells could be employed as clinical effectors against bladder cancer.
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  • 56
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    Pediatric surgery international 16 (2000), S. 35-39 
    ISSN: 1437-9813
    Keywords: Key words Pancreatic trauma ; Duodenal trauma ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Diagnosis of duodenal and pancreatic injuries is frequently delayed, and optimal treatment is often controversial. Fourteen children with duodenal and/or pancreatic injuries secondary to blunt trauma were treated between 1980 and 1997. The pancreas was injured in all but 1 child. An associated duodenal injury was present in 4. The preoperative diagnosis was suspected in only 6 patients based on clinical signs and ultrasonography. One patient was treated successfully conservatively; all the others required surgical management. At operation, three procedures were used: peripancreatic drainage, suture of the gland or duodenum with drainage, and primary distal pancreatic resection without splenectomy. A duodenal resection with reconstruction by duodeno-duodenostomy was performed in 1 case. The overall complication rate was 14%: 1 fistula and 1 pseudocyst. Pancreatic ductal transection was recognized 3 days after the initial laparotomy by endoscopic retrograde cholangiopancreatography (ERCP). The mortality was 7%; 1 patient died from septic and neurologic complications. When the diagnosis of pancreatic ductal injuries is a major problem, ERCP may be a useful diagnostic procedure. Pancreatic injuries without a transected duct may often be treated conservatively. The surgical or conservative management of duodenal hematomas is still controversial; other duodenal injuries often need surgical treatment.
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  • 57
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    Skeletal radiology 29 (2000), S. 605-608 
    ISSN: 1432-2161
    Keywords: Keywords Plant-thorn synovitis ; Monoarticular arthritis ; Elbow ; Magnetic resonance imaging ; Ultrasound ; Power Doppler
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We describe a case of plant-thorn synovitis of the elbow resulting from a thorn injury. This caused recurrent pain and swelling of the elbow over a 3-month period. A magnetic resonance imaging examination was initially requested to exclude septic arthritis, and demonstrated a joint effusion, synovitis, and a 2-cm linear opacity embedded in the synovium. Ultrasound was performed prior to surgery to confirm these findings and provide accurate localization of the thorn fragment, later removed at surgery. To our knowledge this is the first example of this condition that has been confirmed by radiological imaging prior to surgery.
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  • 58
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    Skeletal radiology 29 (2000), S. 217-223 
    ISSN: 1432-2161
    Keywords: Key words Spinal canal ; Low back posture ; Morphologic change ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To define the possible mechanism of posture-dependent symptoms of spinal stenosis by measuring the effect of low back posture on morphologic changes of the intervertebral discs and spinal canal in healthy young people. Design.Twenty healthy young volunteers underwent magnetic resonance imaging while supine with their spine in neutral, flexed, extended, and right and left rotational positions. The axial MR images at the middle of the intervertebral discs of L3–4 and L4–5 were analyzed to measure the difference in the size and shape of the intervertebral discs and spinal canal in each posture. Results.  Extension or rotation decreased the sagittal diameters and cross-sectional areas of the dural sac and spinal canal and increased the thickness of the ligamentum flavum, whereas flexion had the opposite effects. The gap between the convex posterior disc margin and the anterior margin of the facet joint on each side, represented as the subarticular sagittal diameter, increased with flexion and decreased with extension or rotation. The direction of rotation did not result in asymmetry of the subarticular sagittal diameter, but right rotation caused thickening of the right ligamentum flavum, and vice versa. The shape and dimensions of the disc did not change significantly according to the positions of the low back. Conclusions.With extension or rotation, the thickness of the ligamentum flavum increased and the posterior margin of the intervertebral disc was approximated to the facet joint without any change in shape and size of the disc. These phenomena result in a decrease in the size of the spinal canal and dural sac in extension or rotation postures in young healthy people without disc degeneration, and may explain the posture-dependent symptom of spinal stenosis.
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  • 59
    ISSN: 1432-2161
    Keywords: Key words Hamstring muscles ; Semimenbranosus ; Tear ; mass ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Complete rupture of the hamstring muscles is a rare injury. The proximal musculo-tendinous junction is the most frequent site of rupture. We present two cases of complete rupture of the distal semimenbranosus tendon, which clinically presented as soft-tissue masses. MR imaging permitted the correct diagnosis. There has been only one other such case reported.
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  • 60
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    Skeletal radiology 29 (2000), S. 470-473 
    ISSN: 1432-2161
    Keywords: Key words Aneurysmal bone cyst ; Humerus ; Giant cell reparative granuloma ; Pathological fracture ; Radiography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report on a 69-year-old woman with a solid variant of aneurysmal bone cyst (solid ABC) in the left humerus with a pathological fracture. Radiographically, the lesion exhibited a relatively well-defined osteolytic lesion in the diaphysis of the left humerus. On magnetic resonance (MR) imaging, the medullary lesion exhibited a homogeneous signal intensity isointense with surrounding normal muscles on the T1-weighted images and a mixture of low and high signal intensity on the T2-weighted images. Contrast-enhanced T1-weighted images revealed diffuse enhancement of the entire lesion. The pathological study showed a proliferation of fibroblasts, histiocytes, chronic inflammatory cells and numerous multinucleated giant cells in a collagenous matrix. Abundant osteoid formation in the matrix was observed, but the cells were devoid of nuclear atypia. Aneurysmal cystic cavities were absent. A review of the English literature found 22 cases of solid ABC of the long bones.
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  • 61
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    Skeletal radiology 29 (2000), S. 535-537 
    ISSN: 1432-2161
    Keywords: Key words Computed tomography ; Intraosseous hemangioma ; Magnetic resonance imaging ; Epiphysis equivalent ; Tibia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report on a rare case of an intraosseous hemangioma involving the proximal tibia in a 70-year-old man. Radiographically, the lesion was a well-defined osteolytic lesion with marginal sclerosis. The CT images demonstrated a well-defined osteolytic lesion with partial cortical breakthrough. T1-weighted MR images showed a hypointense lesion, while T2-weighted images revealed hyperintense areas, with internal, hypointense septa. Gadolinium-enhanced T1-weighted images showed lattice-like enhancement of the lesion.
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  • 62
    ISSN: 1432-2161
    Keywords: Key words Soft tissue ; Magnetic resonance imaging ; Sparganosis ; Sparganosis ; magnetic resonance imaging ; Sparganosis ; ultrasonography ; Parasitic infection ; Sparganum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To document the imaging characteristics of subcutaneous and musculoskeletal sparganosis. Design and patients. Ten patients with musculoskeletal sparganosis were examined, with a variety of imaging modalities including MRI (n=6), ultrasonography (n=8), plain radiography (n=7) and CT (n=1). Pathologic correlation was carried out in all cases. Results. Nine lesions involved soft tissues, of which seven were in the thigh, two in the trunk and one involved a vertebral body. The majority of the lesions in soft tissue were confined to the subcutaneous layer but two extended deep into underlying muscles. Sonography revealed low-echoic serpiginous tubular tracts (8/8), and an intraluminal echogenic structure (4/8). MRI revealed multiple serpiginous tubular tracts and peripheral rim enhancement. Two patients showed perilesional soft tissue edema. Pathologically, the lesion consisted of a larva surrounded by three layers of inflammation: an inner epithelioid granulomatous cell layer, middle chronic inflammatory cell layers, and an outer fibrous layer. Conclusion. The study suggests that if serpiginous tubular tracts are seen at imaging studies, musculoskeletal sparganosis should be included in the differential diagnosis.
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  • 63
    ISSN: 1432-2161
    Keywords: Key words Pectoralis major muscle ; Magnetic resonance imaging ; Tendons ; injuries ; Tendons ; magnetic resonance imaging ; Muscles ; injuries ; Muscles ; magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To assess the accuracy and utility of magnetic resonance (MR) imaging in the detection and grading of pectoralis major muscle and tendon tears. Design and patients. A retrospective review was carried out of 10 patients referred for MR imaging for suspected pectoralis muscle injury and possible operative therapy. The pectoralis muscle and tendon were imaged using thin (3–4 mm) axial sections with a variety of sequences combined for anatomical delineation (T1-weighted SE or PD SE) and fluid detection (T2-weighted SE, T2-weighted FSE with fat suppression, or STIR). Surgical correlation was available in six patients. Clinical follow-up was available in four patients treated by nonoperative therapy. Results. MR imaging identified five complete tears, four partial tears and one normal tendon. One complete and one partial tear were at the myotendinous junction. The remaining seven injuries were at the enthesis. Surgical correlation consisted of five complete tears and one partial tear. One complete and one partial tear were at the myotendinous junction with the remaining four complete tears at the enthesis. The MR interpretation and surgical findings were in agreement in all six cases. All four patients treated with nonoperative therapy demonstrated improvement at a clinical follow-up examination, with restoration of function and strength consistent with a healed prior partial injury. Conclusion. MR imaging is accurate and useful in detecting and grading tears involving the pectoralis major muscle and tendon, facilitating the identification of patients with complete tears who are candidates for operative therapy.
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  • 64
    ISSN: 1432-2161
    Keywords: Key words Sacral ; Tuberculosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To review imaging studies of isolated involvement of the sacrum due to tuberculosis and determine the role of imaging in the diagnosis and management of these patients. Design and patients. A retrospective analysis of 15 cases of isolated sacral tuberculosis imaged with MR imaging was performed. The CT images were also reviewed where available, and the various lesion characteristics were identified. We also reviewed the medical records in an attempt to determine the impact of the imaging studies on the management of these patients. Results. Fifteen patients (5 male, 10 female) presented with symptoms of 3–15 months’ duration. Chronic localized backache with muscle spasm was the commonest presenting symptom; discharging sinuses with abscess formation was found in six patients, five of whom were children. MR imaging of the sacrum revealed a hypointense marrow signal on T1-weighted images and hyperintense signal on T2-weighted images in 14 of 15 patients, the S2 vertebra being always involved. CT revealed osteolytic changes in the sacrum in all the five patients in whom CT was performed. All patients showed marked clinical improvement within 1 year of anti-tuberculous chemotherapy. Conclusion. Isolated tuberculosis of the sacrum is uncommon but should be suspected in patients presenting with chronic low backache or children with discharging sinuses/abscesses and showing sacral destruction on CT or MR imaging. MR imaging can identify cases and enables early institution of anti- tuberculous chemotherapy.
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  • 65
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    Skeletal radiology 29 (2000), S. 466-469 
    ISSN: 1432-2161
    Keywords: Key words Bone neoplasm ; Chondromyxoid fibroma ; Femur ; Apophysis ; Radiography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We present a rare case of juxtacortical chondromyxoid fibroma arising in the lesser trochanter of the right femur which corresponds to an apophysis. Radiography showed a well-defined expansive lesion with a sclerotic margin measuring 5×3.5 cm in diameter in the lesser trochanter. On spin echo T1-weighted images, the lesion revealed low signal intensity similar to muscle. On spin echo T2-weighted images, the lesion revealed high heterogeneous signal intensity, which after gadolinium injection showed heterogeneous enhancement. The inner margin of the cortex was intact and adjacent bone marrow was of normal signal intensity. The outer margin of the lesion was also clearly defined and extension into adjacent soft tissue beyond the exophytic cortical outgrowth was not evident.
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  • 66
    ISSN: 1432-2277
    Keywords: Key words Normothermic liver ischemia ; Apoptosis ; Caspases ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 μl PBS solution containing 1 % DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95 %) compared with that in nontreated rats (30 %, P 〈 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3–6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3–6 h after reperfusion in the control group, but significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.
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  • 67
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    Archives of orthopaedic and trauma surgery 120 (2000), S. 349-351 
    ISSN: 1434-3916
    Keywords: Key words Glenoid dysplasia ; Magnetic resonance imaging ; Multidirectional shoulder dislocation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glenoid dysplasia is a rare abnormality of the shoulder. We report glenoid dysplasia in two consecutive generations: a boy and his father. Both suffered recurrent shoulder dislocations, and radiological examination revealed bilateral glenoid dysplasia. Our cases confirm dominant inheritance of this osseous malformation.
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    Archives of orthopaedic and trauma surgery 120 (2000), S. 336-337 
    ISSN: 1434-3916
    Keywords: Key words Pulled elbow ; Children ; Trauma ; Immobilization ; Nursemaid’s elbow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effectiveness in decreasing recurrence of cast application after manual reduction of pulled elbow. Sixty-four children with pulled elbow were randomized into two treatment groups: Group A underwent manipulative reduction followed by splinting the elbow in a flexed and supinated position for 2 days; group B underwent manipulative reduction only. Both groups were examined 2, 5, and 10 days later. None of the 33 patients in group A had a pulled elbow at follow-up. Four (13%) of 31 patients in group B had a pulled elbow 2–5 days later. Immobilizing the elbow for 2 days after manipulative reduction improves the success of treatment of a pulled elbow.
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  • 69
    ISSN: 1434-0879
    Keywords: Key words Cryptorchidism ; Contralateral descended testis ; Apoptosis ; Fertility ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three rat strains have been studied, using a sensitive apoptotic detection method for germ-cell degeneration, to resolve the controversy regarding the effect of cryptorchidism on the contralateral descended testis (CDT). Sprague Dawley and Buffalo rats were made cryptorchid by operation at 20–22 days of age, while trans-scrotal (T-S) rats were a congenitally unilateral cryptorchid strain. Sham operated rats or normal T-S littermates were used as controls. Experiments were performed over a period ranging from 2 weeks to 18 months. Testis weight was assayed, as was the detection of apoptosis by agarose gel laddering and immunohistochemistry by using the TUNEL method. Labeled cells in 150 cross-sectioned testis tubules were counted on the TUNEL stained slides and the mean number of labeled cells per tubule was calculated. Paternity studies on Sprague Dawley and T-S rats were carried out at 12 and 24 weeks of age to assess fertility by the resultant number of pregnancies and litter sizes. Both Sprague Dawley and T-S rat models showed a biphasic distribution of apoptosis levels. This biphasic distribution was not observed in Buffalo rats as they were only studied at later time points (12–20 weeks). A significant effect on either testis weight or apoptosis in the CDT compared with the control descended testis (P ≥ 0.1) has not been found in these three cryptorchid models, and the present results are discussed with reference to observations of other researchers in rodents and humans. While the cryptorchid testis showed a high level of labeled apoptotic cells per tubule in all rat strains, fertility was not affected and remained the same as controls at 12 and 24 weeks. There was, however, a marked strain difference in fertility in T-S as compared with Sprague Dawley rats. After 24 weeks of cryptorchidism, both control and cryptorchid T-S rats had a 44% pregnancy incidence compared with a 90% pregnancy incidence in Sprague Dawley rats. In addition, litter size in T-S control and cryptorchid rats were small compared with those of Sprague Dawley rats at 12 and 24 weeks.
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  • 70
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Ureter ; Urinary obstruction ; Hydronephrosis ; Hyperoxaluria ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperoxaluria is a well-known cause of renal stone disease and in vitro studies have shown that oxalate crystals have a stimulatory effect on apoptosis of renal tubular epithelial cells. Total and partial ureteral obstruction also have an accelerating effect on apoptosis of renal tubular epithelial cells. The aim of the present study was to investigate the apoptotic effect of unilateral ureteral obstruction in the presence of hyperoxaluria on the rat kidney. Twenty-eight male Wistar rats were divided into four groups, with seven rats in each. The groups were named G1 (control), G2 (hyperoxaluric), G3 (obstructive) and G4 (hyperoxaluric + obstructive). G2 and G4 rats were given 1% ethylene glycol (a precursor for oxalates) in their drinking water. G1 and G2 rats underwent sham operation, while left proximal ureteral ligation with a 5-zero silk suture was performed on G3 and G4 animals. The rats were sacrificed 2 weeks after the operation; left nephrectomy was then performed. We searched for the apoptotic cells by direct immuno-peroxidase detection of digoxigenin-labeled genomic DNA. The mean ± SD values of the apoptotic cell count was 0.86 ± 0.90 in G1 and 4.33 ± 3.81 in G2. The values for G3 and G4 were 30.17 ± 16.85 and 302.67 ± 184.45, respectively. We found a statistically significant difference between all groups (P 〈 0.001). When compared with the control group (G1), the mean apoptotic cell count was fivefold that of G2 and 35- and 351-fold those of G3 and G4, respectively. Our study demonstrated that hyperoxaluria with complete ureteral obstruction induces an excessive level of apoptosis, which is responsible for renal damage, and that ureteral obstruction is a more important factor for apoptosis than hyperoxaluria. Considering these data, we also believe that research studies for medical preventive measures must be considered for patients with ureteral obstruction and/or hyperoxaluria.
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  • 71
    ISSN: 1434-3916
    Keywords: Key words Spondylodiscitis ; Magnetic resonance imaging ; Computed tomography ; Diagnostic algorithm ; Therapeutic algorithm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifty-nine patients with spondylodiscitis (SD) of the thoracic and/or lumbar spine were followed-up clinically and radiologically [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] over a mean time of 2.2 years (1–6.5 years). All patients without abscess formation (n = 35) were treated conservatively. Out of the group with abscess formation (n = 24) 6 patients were also treated conservatively, 11 were drained under CT control and 7 were operated. At time of diagnosis, “signs of florid inflammation” were seen in 60% of the roentgenograms, in 93% of the CTs and in all of the MRIs. The sensitivity to differentiate between SD with and without abscess formation was 85% by MRI and 69% by CT. “Signs of regressive inflammation” and “signs of increasing osseous consolidation”, essential facts for starting remobilization, could first be seen using CT 6 weeks after onset of therapy. Using MRI these signs were seen with a considerable delay at 12 weeks. Clinically, only 3 of the 59 analyzed patients developed recurrent SD. In conclusion, MRI is the radiological method of choice for establishing the diagnosis of SD, in particular with regard to differentiating between cases with and without abscess formations. In contrast, CT is superior for performing success control after treatment. Therapeutically, conservative, minimal-invasive and operative procedures are not rival but rather complementary.
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  • 72
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    Reading and writing 13 (2000), S. 81-103 
    ISSN: 1573-0905
    Keywords: Children ; Reading comprehension ; Working memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Education
    Notes: Abstract Working memory capacity is described as a pool of limited resources that carry out processing and storage functions. Its role has been emphasised in adults' reading comprehension. The present study had two aims: First, to study the relationship between working memory capacity and reading comprehension in fourth-grade children. Second, to study the nature of the working memory resources involved in reading comprehension, i.e., are they specific or general?To test the first point, the predictive power of working memory capacity was compared with two reading-related basic skills, vocabulary and decoding skills. To test the second point, different working memory tasks were devised using verbal, numerical and spatial materials. All the tasks were administered to 48 fourth-grade children. The results showed that working memory capacity was a direct predictor of reading comprehension when contrasted with vocabulary and decoding skills. Moreover, it seemed that working memory would be better described as a system specialised for the processing of symbolic information in that only the verbal and in a lesser extent the numerical working memory tasks were significant predictors of reading comprehension. The spatial task did not correlate with reading comprehension. The reasons accounting for the predictive power of working memory tasks were discussed.
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  • 73
    ISSN: 1432-0533
    Keywords: Key words Ki-67 labeling index ; Magnetic resonance imaging ; Optic nerve glioma ; p53 ; Pilocytic ¶astrocytoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of 〈 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2–3%, and a p53 LI of 〈 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2–12%, a p53 LI of 2–8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI 〈 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2–3% and a p53 LI of 〈 1%. Diffuse astrocytomas have both Ki-67 and p53 LI 〉 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of 〉 1% appears to favor the diagnosis of diffuse astrocytoma.
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  • 74
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    Acta neuropathologica 99 (2000), S. 402-408 
    ISSN: 1432-0533
    Keywords: Key words Ageing ; Dog brain ; Apoptosis ; DNA ¶fragmentation ; TUNEL method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal DNA fragmentation, as revealed with the method of in situ end-labeling of nuclear DNA fragmentation (TUNEL), has been reported in both the canine and human brains in normal ageing, and in some human age-related neurodegenerative diseases. These results have suggested that apoptosis plays an important role in age-related neuronal loss. It is not clear, however, whether the TUNEL method is highly specific for apoptosis, as DNA fragmentation also occurs in the late stages o necrosis. In this study we have examined 27 dogs aged from ¶8 to 18 years, to investigate the occurrence of nuclear DNA fragmentation. An autolysis index based on current histological criteria was assigned to each animal to evaluate the effects of autolysis on nuclear DNA integrity. Our results have shown that neuronal nuclear DNA fragmentation is frequent in aged dogs, although it is not accompanied by apoptotic morphology. Yet, a positive relation between TUNEL labelling and the degree of tissue autolysis was observed. In contrast, no TUNEL labelling was detected in young control dogs despite autolysis indices being similar to those in aged dogs. Taken together, these results suggest that neuronal nuclear DNA fragmentation is an age-related phenomenon, not due to apoptosis, whenever other factors render neuronal DNA more susceptible to autolytic fragmentation. We confirm the effect of autolysis in a subpopulation of neurons in the aged canine brain, inducing nuclear DNA fragmentation.
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  • 75
    ISSN: 1432-0533
    Keywords: Key words Cerebellar selective injury ; Acrylamide ; Granule cell degeneration ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral administration of N-[4-(3-ethoxy-2-hydropropoxy)phenyl] acrylamide (EHA) induced selective granule cell destruction in the granular layer of the cerebellar cortex together with neurological signs, such as delayed righting reflex, gait or truncal ataxia, and convulsion. Neuropathologically, it caused multifocal granule cell destruction with nuclear pyknosis and spongiosis of the neuropile in the granular layer. Other neurons, including Purkinje cells, were spared. Ultrastructurally, damaged granule cells showed aggregation of nuclear chromatin and cytoplasmic edema, but cytoplasmic organelles were preserved. The brain uptake index of 14C-labeled EHA was similar to that of H2O. When EHA was added to rat cerebellar tissue cultures, only the granule cells showed nuclear pyknosis, aggregation of nuclear chromatin, and karyorrhexis with cytoplasmic swelling. These granule cells were positive for DNA fragmentation by the TUNEL method. These results suggest that EHA permeates the blood vessel wall and directly affects the cerebellar granule cells, resulting in selective granule cell apoptosis.
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  • 76
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    Acta neuropathologica 99 (2000), S. 317-320 
    ISSN: 1432-0533
    Keywords: Key words Perineuritis ; Neuropathy ; Nerve biopsy ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 71-year-old man presented a 6-month history of progressive paresthesia of all four limbs. Sural nerve biopsy specimens showed dense mononuclear infiltrates in the perineurium and subperineurium, indicating sensory perineuritis. One section revealed disruption of the perineurial barrier. Perforin and granzyme B were present in the infiltrates, and apoptosis of perineurial cells was indicated by a terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. These findings suggest T cell-mediated apoptosis of the perineurium and nerve injury caused by perineurial damage.
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  • 77
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    Der Anaesthesist 49 (2000), S. 275-278 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Tropisetron ; postoperatives Erbrechen ; Adenotonsillektomie ; Antiemetika ; Kinder ; Key words Tropisetron ; PONV ; Adenotonsillectomy ; Antiemetics ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Postoperative nausea and vomiting (PONV) after tonsillectomy is a common problem in children. Tropisetron is a new 5HT3 receptor antagonist and is successfully used in paediatric patients receiving cancer therapy. The aim of the study was to assess efficacy and safety of a single intravenous dose of tropisetron for prevention of PONV in paediatric patients at risk for postoperative vomiting. Methods: In a randomised, double-blind, placebo-controlled trial, we studied 98 children aged 2–12 years undergoing tonsillectomy or adenotonsillectomy. Patients received placebo or tropisetron 0.1 mg (=0.1 ml)/kg body weight immediately after induction of anesthesia. A standard general anesthetic technique (Sevoflurane/N2O/O2 without neuromuscular blockers or opioids) was used. Perioperative vital signs, grade of sedation and episodes of postoperative nausea and vomiting were recorded. Results: No vomiting episodes occurred in 65.3% of the tropisetron treated patients compared to 34.7% of the placebo group (p=0.0024). Only 10.2% of the tropisetron treated patients vomited more than 3 times compared to 22.4% of the control patients (p=0.0004). The need for antiemetic rescue medication was significantly lower in the study group (10.4%) compared to 28.6% (p=0.025). No significant adverse effects of the study medication were shown. Conclusion: A single intravenous prophylactic dose of tropisetron effectively reduces the incidence of PONV during the first 24 postoperative hours after tonsillectomy and/or adenoidectomy. Because of the low incidence of adverse effects, the prophylactic use of tropisetron seems to be safe and justified in paediatric surgical patients at high risk for postoperative vomiting.
    Notes: Zusammenfassung Fragestellung: Erbrechen und Übelkeit nach Tonsillektomien bei Kindern sind ein häufiges Problem. Aufgrund der positiven Erfahrungen mit Tropisetron, einem neueren 5HT3 Rezeptor-Antagonisten bei Chemotherapien in der pädiatrischen Onkologie und mit anderen 5HT3 Rezeptor-Antagonisten in der Kinderchirurgie, prüften wir die Wirksamkeit und Sicherheit einer Einzeldosis Tropisetron zur Prävention von postoperativem Erbrechen bei chirurgischen Kindern mit erhöhtem Risiko für postoperatives Erbrechen. Methodik: Bei 98 Kindern im Alter von 2– 12 Jahren, die eine Tonsillektomie oder Adenotonsillektomie benötigten, führten wir eine randomisierte, doppelblinde, plazebokontrollierte Studie durch. Die Patienten erhielten Tropisetron oder Plazebo in einer Dosis von 0,1 mg (=0,1 ml)/kg KG i.v. unmittelbar nach der Narkoseeinleitung. Die Narkose erfolgte standardisiert mit Sevofluran/N2O/O2 ohne Einsatz von Opioiden und Muskelrelaxanzien. Vitalparameter, Sedationstiefe, das Auftreten von postoperativem Erbrechen und unerwünschte Wirkungen wurden aufgezeichnet. Ergebnisse: In der Tropisetrongruppe zeigten 65,3% der Kinder kein postoperatives Erbrechen, im Gegensatz zu nur 34,7% der Kinder in der Plazebogruppe (P=0,0024). Mehr als 3 Episoden von postoperativem Erbrechen zeigten nur 10,2% der Patienten in der Tropisetrongruppe im Vergleich zu 22,4% der Patienten der Kontrollgruppe (P=0,0004). Auch der Bedarf an antiemetischer Zusatzmedikation war in der Tropisetrongruppe mit 10,4% signifikant niedriger als in der Kontrollgruppe mit 28,6% (P=0,025). Bedeutsame Nebenwirkungen der Studienmedikation konnten nicht dokumentiert werden. Schlussfolgerungen: Eine prophylaktische intravenöse Einzelgabe von Tropisetron reduziert bei Kindern wirksam das Auftreten von postoperativem Erbrechen während der ersten 24 h nach einer Tonsillektomie oder Adenotonsillektomie. Die geringe Inzidenz von Nebenwirkungen rechtfertigt unserer Ansicht nach die prophylaktische Anwendung von Tropisetron bei Kindern nach Tonsillektomien.
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  • 78
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    Archives of dermatological research 292 (2000), S. 522-523 
    ISSN: 1432-069X
    Keywords: Key words Serum soluble Fas ; Systemic sclerosis ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 79
    ISSN: 1432-069X
    Keywords: Key words Docosahexaenoic acid (DHA) ; 15-hydroxyeicosatrienoic acid (15-HETrE) ; AP-1 ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to ascertain whether the antiproliferative effect of 15-hydroxyeicosatrienoic acid (15-HETrE), a monohydroxy fatty acid generated from dihomo-Á-linolenic acid, in an experimentally induced guinea pig hyperproliferative model involves alterations in nuclear transcription factor (AP-1) and apoptosis. The topical application of docosahexaenoic acid (DHA) to normal guinea pig skin elicited a severe hyperplasia which was accompanied by the suppression of AP-1 expression in a time-dependent manner. Since apoptosis is pivotal in tissue turnover, the expression of two apoptotic proteins (Bcl-2 and caspase-3) after DHA and 15-HETrE treatment was explored. DHA-induced hyperproliferation enhanced the expression of Bcl-2 (an antiapoptotic protein) but inhibited the expression of caspase-3 (an apoptotic protein). 15-HETrE, on the other hand, reversed the DHA-induced epidermal hyperplasia, and upregulated epidermal AP-1 expression. These events paralleled the suppression of Bcl-2 and the elevation of caspase-3. Taken together, these results suggest that the antiproliferative effect of 15-HETrE may, at least in part, be via the modulation of AP-1 and apoptosis.
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  • 80
    ISSN: 1432-0584
    Keywords: Nitric oxide ; Bone marrow ; Proliferation ; Apoptosis ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: α , interferon γ and interleukin-1β for 48 h. The basal proliferation rate of the cells remained unchanged, but granulocyte–macrophage colony stimulating factor-induced proliferation was suppressed and the percentage of apoptotic cells significantly raised. Levels of nitrite in the culture supernatants were inversely correlated with the suppression of proliferation, but directly correlated with apoptosis. The NO synthesis inhibitor N-methyl-arginine inhibited the suppression of proliferation as well as the induction of apoptosis and NO synthesis. Our results indicate that NO is a negative feedback regulator of cell turnover in sepsis, which limits growth-factor-induced proliferation and induces apoptosis of bone marrow cells.
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  • 81
    ISSN: 1432-0584
    Keywords: Key words Acute myelofibrosis ; Acute megakaryoblastic leukemia ; Scintigraphy ; Magnetic resonance imaging ; Interferon gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Acute myelofibrosis is a rare, malignant hematological disorder of unknown etiology with an inevitably fatal outcome. Here we present the study of a 63-year-old Caucasian man with acute onset of pancytopenia. Repeated bone marrow biopsies showed dense fibrosis and hypoplastic hematopoiesis raising various differential diagnoses of malignant and nonmalignant conditions. Bone marrow scintigraphy and magnetic resonance imaging (MRI) showed areas suggesting neoplastic infiltration, mainly in both femurs and tibias. Histological examination of a surgical biopsy of the left tibia revealed acute megakaryoblastic leukemia. As the patient refused polychemotherapy, therapy with interferon gamma was initiated but discontinued prematurely because of intolerable side effects. The presented case therefore suggests that the combination of bone marrow scintigraphy and MRI is a valuable diagnostic tool in patients presenting with myelofibrosis of unknown origin.
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  • 82
    ISSN: 1432-0568
    Keywords: Key words Mouse ; Gene expression ; Insulin-like growth factor (IGF) ; IGF binding protein (IGFBP) ; Hypodactyly (Hd) ; Limb bud ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Insulin-like growth factor-I (IGF-I) mediated signalling has been implicated to be of significant importance during vertebrate embryonic development. IGF-I signalling has also been shown to be modulated by a number of IGF binding proteins that are thought to act as either agonists or antagonists of IGF activity. IGF-I has been implicated in a number of cellular processes, including cell division and programmed cell death (apoptosis). We have used the mouse mutant Hypodactyly (Hd) as a tool to determine the role of IGF-I and two key IGF binding proteins (IGFBP-2 and IGFBP-5) during embryonic development. The Hd mutant is a good model with which to study developmental cascades, since it has a distinct phenotype in the limb where cellular and molecular circuits have been thoroughly investigated. The distinctive pointed limb buds observed in Hd mutant embryos have been shown to be the result of a massive increase in apoptosis. We show that all three genes, IGF-1, IGFBP-2 and IGFBP-5, display restricted expression patterns during limb development. Indeed, IGFBP-5 shows a remarkable similarity to the expression of Engrailed-1, which is the vertebrate homologue of the Drosophila selector gene Engrailed. We show that there is downregulation in the expression of IGFBP-2 in the entire apical ectodermal ridge (AER) in homozygous Hd/Hd limb buds, whereas IGFBP-5 is downregulated in specific regions in the mutant AER. IGF-I expression is downregulated in Hd limb buds in regions undergoing high levels of cell death, consistent with its proposed role as an anti-apoptotic factor, while IGFBP-5 is found at higher levels in regions of cell death, consistent with reports of its association with apoptosis in adult tissues. We propose that these three components of the IGF axis could be involved in the manifestation of the mutant phenotype in Hypodactyly, and that this is probably a result of their ability to regulate cell survival and cell death.
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  • 83
    ISSN: 1432-069X
    Keywords: Keywords HSP70 ; Human melanoma cells ; Ultraviolet B ; Apoptosis ; Caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The heat shock response is a highly conserved reaction common to all cells and organisms. It has been reported that hyperthermic treatment can induce the expression of the heat shock protein (HSP) and can protect cells from ultraviolet (UV) B radiation. In this study, we evaluated the effects of induced HSP70 on resistance to UV radiation. G361 amelanotic human melanoma cells were irradiated with increasing doses of UVB. UVB irradiation caused apoptotic cell death in these cells. Following transfection with MFG.hsp70.puro plasmid, the expression of HSP70 was determined. Compared to control vector-transfected cells, hsp70-transfected cells showed significantly elevated levels of HSP70 and were highly resistant to UVB irradiation. In order to investigate the effects of HSP70 on the apoptotic pathway, the changes in caspase-3 and PARP were analyzed. Following UVB irradiation, activation of caspase-3 and cleavage of PARP were observed in control vector-transfected cells, and the changes in these molecules were inhibited in the hsp70-transfected cells. These results suggest that UVB-induced apoptosis of melanoma cells is accompanied by caspase-3 activation and PARP cleavage, which can be prevented by an overexpression of HSP70.
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  • 84
    ISSN: 1432-069X
    Keywords: Key words Granuloma annulare ; Cytokine ; Apoptosis ; Lymphocytes ; Macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-Á as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-· and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3+ lymphocytes express interferon-Á. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3+ lymphocytes and CD68+ macrophages contained tumor necrosis factor-·. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-· coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-Á+ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-α and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells.
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  • 85
    ISSN: 1432-069X
    Keywords: Key words Ceramide ; 1α,25-Dihydroxyvitamin D3 ; TNFα ; Apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During the last few years increasing evidence has shown that sphingolipid metabolites are highly bioactive compounds that play important roles in cellular regulation. The induction of ceramide signalling in primary human keratinocytes and HaCaT keratinocytes has recently been demonstrated using 1·,25-dihydroxyvitamin D3. The data obtained indicate that approximately one-third of the proapoptotic effect of 1·,25-dihydroxyvitamin D3 is mediated by an intracellular ceramide increase induced via tumor necrosis factor · expression and autocrine stimulation of sphingomyelin hydrolysis. In the present study the role of bcl-2 in this process was investigated. HaCaT keratinocytes were transfected with bcl-2 and the effects of C2-ceramide, tumor necrosis factor · and 1·,25-dihydroxyvitamin D3 on HaCaT keratinocytes stably overexpressing bcl-2 were determined. Apoptosis was measured by detection of soluble DNA-histone complexes using the ELISA technique. In situ analysis of apoptotic cells was also carried out by detecting phosphatidylserine flip using the annexin V method and by detecting DNA fragmentation using the TUNEL assay. The results obtained showed that apoptosis induced by C2-ceramide, tumor necrosis factor · or 1·,25-dihydroxyvitamin D3 occurred in a vector-transfected clone but not in a bcl-2-transfected HaCaT clone. This indicates the important role of bcl-2 in the regulation of ceramide-mediated signalling pathways in human keratinocytes and supports the involvement of ceramide as a signalling molecule in 1α,25-dihydroxyvitamin D3-induced biological responses.
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  • 86
    ISSN: 1432-0584
    Keywords: Key words Down syndrome ; Transient abnormal myelopoiesis ; Apoptosis ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transient abnormal myelopoiesis (TAM) is a haematological complication found in Down syndrome. To determine the mechanisms of sustained proliferation of TAM cells, we studied the expression of apoptosis-related proteins, such as bcl-2, Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2 protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs, cultured in the absence of serum factors, revealed no marked fragmentation. Our findings suggest that bcl-2 overexpression may be associated with prolonged cell survival of TAM cells.
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  • 87
    ISSN: 1432-0584
    Keywords: Key words Gemcitabine ; Apoptosis ; Chronic lymphocytic leukemia ; Acute myeloid leukemia ; Cell lines ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Induction of apoptosis in vitro using gemcitabine (dFdC) in combination with cladribine (2-CdA) and other cytotoxic drugs on malignant mononuclear cells (MNCs) of patients with acute myeloid leukemia (AML, n=20) and chronic lymphocytic leukemia (CLL, n=20) in myeloid (HL60, HEL) and lymphatic cell lines (HUT78, JURKAT) was investigated using different incubation conditions (simultaneous and consecutive). Furthermore, the influence of dFdC on the level of intracellular metabolites of 2-CdA was studied using high-performance liquid chromatography (HPLC). Apoptosis was evaluated using flow cytometry with 7-aminoactinomycin D. In MNCs of patients with CLL, dFdC+2-CdA showed an antagonistic effect when applied simultaneously. This antagonism was reduced by consecutive application. The combination of dFdC with doxorubicin was synergistic, independent of incubation schedule. In blasts from newly diagnosed patients with de novo AML, all drug combinations (dFdC+2-CdA, doxorubicin, or cytosine arabinoside) were antagonistic by simultaneous incubation. Reduced antagonism or even synergism was shown (P〈0.001) by consecutive incubation. The simultaneous combination of dFdC with 2-CdA in all tested cell lines resulted in a competitive inhibition on the rate of apoptosis. By changing the incubation period to a consecutive schedule, the antagonism was diminished or synergism of apoptosis was measured (P〈0.001). Using similar incubation conditions, these experiments were supported by HPLC measurement of intracellular metabolites of 2-CdA influenced by dFdC application. In conclusion, we demonstrated that the efficacy of dFdC in vitro in combination with other cytotoxic drugs depends on the incubation condition and on the origin of neoplastic cells (lymphatic vs myeloid). The data suggest that simultaneous combination therapy with purine and pyrimidine analogues may not improve the clinical efficacy of one or the other drug administered alone.
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  • 88
    ISSN: 1423-0127
    Keywords: Apoptosis ; Differential display ; Glioma ; Okadaic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To identify novel genes associated with apoptosis in glioma cells, we treated T98G glioma cells with okadaic acid (OA). Differential display using 15 random primers was performed on RNA extracted from these cells. Upregulated bands were excised from polyacrylamide gels and cloned. Northern blots were used to confirm RNA expression in T98G cells. 18 RNA fragments corresponding to the untranslated region of genes were identified and sequenced. Three unknown gene fragments were used to screen a fetal brain cDNA library resulting in three complete cDNA sequences. The three sequences corresponded to a human gene homologous to the yeast translation initiation factor Sui-1, a cAMP-regulated phosphoprotein, ARPP-16/19, and a novel gene designated O48. Transcription of Sui-1 increased in response to all stress factors tested, whereas ARPP only responded to OA. 2-kb and 4-kb O48 RNA species were identified. OA and stress factors increased 2-kb expression while K252a (protein kinase inhibitor) increased 4-kb expression. Differential display is effective for identifying genes associated with apoptosis. Novel genes may be identified by further analysis of the gene fragments identified in this study. The function of O48 is unknown.
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  • 89
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    Journal of biomedical science 7 (2000), S. 195-199 
    ISSN: 1423-0127
    Keywords: Opioid ; Enkephalin ; DADLE ; Transplantation ; Hibernation ; Apoptosis ; Methamphetamine ; Dopamine ; Ischemia ; Reperfusion ; PC12 cells ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By studying the hibernation in ground squirrels, a protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Further purification of HIT yielded an 88-kD peptide that is enriched in winter hibernator. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Delta opioid [D-Ala2,D-Leu5]enkephalin (DADLE) also induced hibernation. HIT and DADLE were found to prolong survival of peripheral organs preserved en bloc or as a single preparation. These organs include the lung, the heart, liver and kidney. DADLE also promotes survival of neurons in the central nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (DA) terminals in the brain. DADLE blocked and reversed the DA terminal damage induced by METH. DADLE acted against this effect of METH at least in part by attenuating the mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. DADLE also blocked the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DADLE are reviewed.
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  • 90
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    Journal of biomedical science 7 (2000), S. 322-333 
    ISSN: 1423-0127
    Keywords: Apoptosis ; HIV ; SIV ; Vpr ; Vpx ; Bcl-2 ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The growth inhibitory effects of Vpr and Vpx are species-and cell type-dependent. HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our previous studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differential cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: Virology, 230:103–112; 1997]. Here, we further examined the apoptosis function of HIV-1 Vpr in different species of mammalian cells and investigated if other primate lentiviral Vpr and Vpx exert similar functions. Our results show that none of the primate lentiviral Vpr or Vpx we tested induces apoptosis in nonhuman species of mammalian cells. However, HIV-1 Vpr, but not HIV-2 or SIV Vpr and/or Vpx, induced apoptosis in different types of human cell lines. Further, the apoptotic effect of HIV-1 Vpr can be distinguished from that of the human interferon-γ, a known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or bystander effect. When coexpressed with Bcl-2 or Bcl-XL, the apoptotic effect of HIV-1 Vpr became markedly attenuated. These results indicate that the apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly modulated by the Bcl-2 family of proteins. Our study also suggests that the proapoptotic function of HIV-1 Vpr is developmentally associated with human but not nonhuman primate species.
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  • 91
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    Surgical and radiologic anatomy 22 (2000), S. 181-190 
    ISSN: 1279-8517
    Keywords: Masseter muscle ; Architecture ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors carried out an anatomic and magnetic resonance imaging study of the architecture of the elevator muscles of the mandible in 169 cadavers. The aim of this study was to define the architectural organization of the human masseter muscle, temporalis and pterygoid muscles. Layered dissections and anatomic sections in different spatial planes showed that the masseter muscle exhibited a typical pennate structure consisting of a succession of alternating musculoaponeurotic layers. The muscle had three well-differentiated parts the superficial, intermediate and deep masseter muscles. The same pattern was constantly found 1) for the superficial masseter, two alternate musculoaponeurotic layers oriented at 60∘ in relation to the plane of occlusion, 2) for the intermediate masseter, a single musculo-aponeurotic layer oriented at 90∘ in relation to the occlusal plane, 3) for the deep masseter, three musculoaponeurotic layers whose general orientation was at 90∘ for the bounding layers and 110∘ for the intermediate layer. The MRI study confirmed the reality of this architectural arrangement.
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  • 92
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    Accreditation and quality assurance 5 (2000), S. 409-413 
    ISSN: 1432-0517
    Keywords: Key words Metrology ; Comparisons ; Chemistry ; Standards
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract  After stressing the importance in the modern world of accurate and reproducible measurements, the actions taken by the Bureau International des Poids et Mesures to set up, together with the regional metrology organizations, a series of key comparisons are described. They are the technical foundation of a mutual recognition of national measurement standards arrangement prepared in conjunction with the National Metrology Institutes (NMIs). This arrangement also includes the recognition of calibration and measurement certificates issued by these institutes. Then, the consequences of this arrangement for trade are described. The case of chemical analysis is illustrated by the application of the Kyoto protocol on the reduction of greenhouse gases. But the global workload to be taken up by the International Committee of Weights and Measures, its Consultative Committee for Amount of Substance and the NMIs is huge.
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  • 93
    ISSN: 1432-0533
    Keywords: Key words HSV ; Immunohistochemistry ; Apoptosis ; p53 ; Transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the mechanism of neuronal apoptosis induced by herpes simplex virus (HSV) infection in vivo, the distribution of viral antigen, the appearance of apoptotic bodies, and the expressions of the tumor suppressor gene p53 and several transcription factors such as c-fos, c-jun and NF-κB were examined immunohistochemically and histopathologically after corneal infection of mice with HSV type 2 strain 186. Five days after HSV infection, viral antigen was diffusely detected in the corneal epithelium, the trigeminal ganglion and the pars caudalis of the spinal trigeminal nucleus. Neuronal apoptosis was observed in the brain stem ipsilateral to the HSV-infected side with the immunoreactivities of c-fos, c-jun, NF-κB and p53. Dual-labeling immunohistochemical studies revealed that almost all of the viral antigen-positive neurons and glia in the brain stem also showed p53 immunoreactivity. On the other hand, no neuronal apoptosis but only with the expression of c-jun was found in the trigeminal ganglion. Our results suggest that the different expression of transcription factors between the brain stem and the trigeminal ganglion may influence the neuronal apoptosis induced by HSV infection.
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  • 94
    ISSN: 1432-0533
    Keywords: Key words Alzheimer’s disease ; Apoptosis ; β-Amyloid load ; Astrocytes ; Microglia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The extent of DNA fragmentation analysed using the TUNEL technique was evaluated in post-mortem human brain tissue. Twenty-four patients with clinical and histopathological diagnosis of Alzheimer’s disease (AD) and a short post-mortem delay were analysed. We report an increase in the count of TUNEL-labelled cells as the pathology of AD intensifies. Our results point out a significant correlation between neurofibrillary tangle and senile/neuritic plaque score and TUNEL-labelled cells. Patients with two copies of apolipoprotein (Apo) E ɛ4 allele had highest number of histopathological hallmarks lesions of AD, whereas the ApoE genotype did not significantly influence the density of TUNEL-positive cells. No significant correlation was found between β-amyloid protein load and TUNEL-labelled cells. There was no relationship between the age at death, age at onset, extent of astrogliosis or microgliosis and TUNEL-labelled cells in our material.
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  • 95
    ISSN: 1432-0533
    Keywords: Key words Skeletal muscle ; Eccentric exercise ; Apoptosis ; Dystrophin ; Dystrophin-associated proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated the basis for the high severity of damage to skeletal muscle due to eccentric exercise, i.e., to muscles generating force while lengthened. Fast and slow rat leg muscles maintained in an extended position were examined after 2–24 h of continuous stimulation. The treatment caused the injury to some regions of both muscles. Within the better preserved parts of the muscles, i.e., those without signs of necrotic processes, dystrophin, spectrin, and some of the dystrophin-associated proteins (β-dystroglycan, α-sarcoglycan, and γ-sarcoglycan) disappeared from sarcolemma of many fibers. The reduction or loss of dystrophin from the sarcolemma was more evident than that of other proteins examined, with sarcoglycans apparently being the most preserved. Several muscle fibers devoid of dystrophin contained apoptotic nuclei. Simultaneously, Bax, Bcl-2 and caspase-3 proteins appeared in many fibers. Our results indicate that a normal muscle overworking in an extended position undergoes the loss of several membrane skeletal proteins because of the excessive stress to the membrane cytoskeleton, which can lead to fiber death by either apoptosis or necrosis. This experimental model may represent a good model for mimicking the pathogenetic events in several muscular dystrophies.
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  • 96
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    Journal of biomedical science 7 (2000), S. 459-465 
    ISSN: 1423-0127
    Keywords: Apoptosis ; Thermal brain injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis has been implicated recently as a prominent response of the brain to a variety of insults, such as ischemia and trauma. In this study, we demonstrate that apoptosis is a prominent part of the brain's response to a thermal insult. To examine the brain's response to a thermal insult, a new model of thermal brain injury in the laboratory rat was developed. Water heated to 60°C was passed over an area of thinned calvarium for 1 min. This resulted in an actual brain temperature of 47–48°C. A uniform area of 2,3,5-triphenyl-tetrazolium chloride pallor was demonstrated and pyknotic neurons were seen in the area of injury by hematoxylin-eosin staining. Apoptosis was demonstrated by the characteristic DNA fragmentation seen by agarose gel electrophoresis, ApopTag in situ staining and electron microscopy. The findings of apoptosis were localized to the area of thermal injury and were time dependent, starting 6 h after the insult and peaking approximately 18 h after the insult. This represents one of the first demonstrations that apoptosis occurs in the brain in response to a thermal injury.
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  • 97
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    Journal of biomedical science 7 (2000), S. 2-15 
    ISSN: 1423-0127
    Keywords: Apoptosis ; Mitochondria ; Necrosis ; Oxidative stress ; Reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mitochondria are the major ATP producer of the mammalian cell. Moreover, mitochondria are also the main intracellular source and target of reactive oxygen species (ROS) that are continually generated as by-products of aerobic metabolism in human cells. A low level of ROS generated from the respiratory chain was recently proposed to take part in the signaling from mitochondria to the nucleus. Several structural characteristics of mitochondria and the mitochondrial genome enable them to sense and respond to extracellular and intracellular signals or stresses in order to sustain the life of the cell. It has been established that mitochondrial respiratory function declines with age, and that defects in the respiratory chain increase the production of ROS and free radicals in mitochondria. Within a certain concentration range, ROS may induce stress responses of the cell by altering the expression of a number of genes in order to uphold energy metabolism to rescue the cell. However, beyond this threshold, ROS may elicit apoptosis by induction of mitochondrial membrane permeability transition and release of cytochrome c. Intensive research in the past few years has established that mitochondria play a pivotal role in the early phase of apoptosis in mammalian cells. In this article, the role of mitochondria in the determination of life and death of the cell is reviewed on the basis of recent findings gathered from this and other laboratories.
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  • 98
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    Journal of biomedical science 7 (2000), S. 64-70 
    ISSN: 1423-0127
    Keywords: p53 ; Chemosensitivity ; Cell cycle ; Apoptosis ; Non-small cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This study examined the effects of p53 gene status on DNA damage-induced cell death and chemosensitivity to various chemotherapeutic agents in non-small cell lung cancer (NSCLC) cells. A mutant p53 gene was introduced into cells carrying the wild-type p53 gene and also vice versa to introduce the wild-type p53 gene into cells carrying the mutant p53 gene. Chemosensitivity and DNA damage-induced apoptosis in these cells were then examined. This study included five cell lines, NCI-H1437, NCI-H727, NCI-H441 and NCI-H1299 which carry a mutant p53 gene and NCI-H460 which carries a wild-type p53 gene. Mutant p53-carrying cells were transfected with the wild-type p53 gene, while mutant p53 genes were introduced into NCI-H460 cells. These p53 genes were individually mutated at amino acid residues 143, 175, 248 and 273. The representative cell line NCI-H1437 cells transfected with wild-type p53 gene (H1437/wtp53) showed a dramatic increase in susceptibility to three anticancer agents (7-fold to cisplatin, 21-fold to etoposide, and 20-fold to camptothecin) compared to untransfected or neotransfected H1437 cells. An increase in chemosensitivity was also observed in wild-type p53 transfectants of H727, H441, H1299 cells. The results of chemosensitivity were consistent with the observations on apoptotic cell death. H1437/wtp53 cells, but not H1437 parental cells, exhibited a characteristic feature of apoptotic cell death that generated oligonucleosomal-sized DNA fragments. In contrast, loss of chemosensitivity and lack of p53-mediated DNA degradation in response to anticancer agents were observed in H460 cells transfected with mutant p53. These observations suggest that the increase in chemosensitivity was attributable to wild-type p53 mediation of the process of apoptosis. In addition, our results also suggest that p53 gene status modulates the extent of chemosensitivity and the induction of apoptosis by different anticancer agents in NSCLC cells.
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  • 99
    ISSN: 1432-0843
    Keywords: Key words Head and neck cancer ; Cisplatin ; Glutathione ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the correlation between cisplatin sensitivity, intracellular glutathione, and platinum/DNA adduct formation (measured by atomic absorption spectroscopy) in a series of seven head and neck cancer cell lines, and to evaluate the effect of biochemical modulation of glutathione on platinum/DNA adduct formation and repair. Methods: Cisplatin/DNA adducts were measured by atomic absorption spectroscopy. Glutathione content was measured by enzymatic assay and was modulated with buthionine sulfoximine. Apoptosis was measured by double-labeled flow cytometry. Results: Intracellular glutathione concentration was strongly correlated with cisplatin resistance (P = 0.002, R 2=0.7). There was also a statistically significant inverse correlation between cisplatin/DNA adduct formation and the IC50 for cisplatin in these cell lines. (P=0.0004, R 2=0.67). In addition, resistant cells were able to repair approximately 70% of cisplatin/DNA adducts at 24 h, while sensitive cells repaired less than 28% of adducts in the same period. However, despite the positive correlation between cellular glutathione and cisplatin resistance, there was no direct correlation between intracellular glutathione concentration and platinum/DNA adduct formation. Further, depletion of intracellular glutathione by buthionine sulfoximine did not dramatically alter formation of cisplatin/DNA adducts even though it resulted in marked increase in cisplatin cytotoxicity and was associated with increased apoptosis. Conclusions: These results suggest that glutathione has multiple effects not directly related to formation of cisplatin/DNA adducts, but may also be an important determinant of the cell's ability to repair cisplatin-induced DNA damage and resist apoptosis.
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  • 100
    ISSN: 1432-0843
    Keywords: Key words Taxanes ; Cervical cancer ; Apoptosis ; Tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the α and β subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of “in vivo” anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d × 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained “in vitro” IC50 values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G2/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the α subunit of tubulin in the G0/1 phase of the cell cycle, and an overexpression of the β subunit in the G2/M phase. A strong anti-tumour activity was obtained “in vivo” for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both “in vitro” and “in vivo” toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed “in vitro” using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.
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