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  • 2010-2014
  • 2000-2004  (364)
  • Immunohistochemistry  (100)
  • Apoptosis  (93)
  • Children  (91)
  • chemotherapy  (81)
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Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 396-401 
    ISSN: 1530-0358
    Keywords: Colorectal carcinoma ; Cathepsin D ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although it has been suggested that cathepsin D, a lysosomal protease, is involved in tumor invasion and metastasis in human colorectal cancers, conflicting studies have also been reported recently. In addition, this issue has been only rarely studied in human colorectal tumors by use of immunohistochemical methods. The aim of the study presented here was to clarify not only the correlation between cathepsin D expression and tumor invasion or metastasis but also the correlation between the intracellular immunostaining pattern of cathepsin D and tumor invasion and metastasis in human colorectal tumors. METHODS: Thirty-four primary colorectal adenocarcinomas and 24 adenomas were immunostained by use of an anticathepsin D antibody. Both the incidence and the immunostaining patterns of cathepsin D were investigated in all tissue samples. RESULTS: Three different immunostaining patterns,i.e., supranuclear, basal, and diffuse, were observed in samples containing cathepsin D. Although the incidence of cathepsin D-positive carcinomas was not correlated with tumor progression, invasion, or metastasis, the immunostaining pattern was significantly correlated with lymphatic invasion. CONCLUSIONS: The results of this study suggest that abnormal cathepsin D immunostaining patterns (basal or diffuse) can be used to predict a potential for lymphatic invasion in colorectal carcinoma.
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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    ISSN: 1534-4681
    Keywords: Melanoma ; Sentinel node analysis ; Tyrosinase RT-PCR ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Immunohistochemistry (IHC) of serial sectioning is considered the gold standard for detection of melanoma activity in sentinel node (SN) biopsies. However, this is cost and labor intensive. In contrast, tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) is simple and quick, but it is hampered by its extreme sensitivity. This study was performed to test whether a strategy that combines the two methods, using tyrosinase RT-PCR to preselect nodes for IHC, could be accurate and cost effective. Methods: In 36 patients, SNs were identified by scintigraphy and patent blue uptake. Of each SN, one cross section was analyzed first by hematoxylin and eosin staining. Next, all nodes were examined by serial sectioning and IHC of one-half and tyrosinase RT-PCR of the other. Before comparison, all results were documented in a blinded manner. Material costs and workload estimates were noted per SN. Results: Fifty-five SNs were retrieved from the 36 patients. Hematoxylin and eosin staining of the first cross section revealed tumor positivity in 3 patients (6 SN). Tyrosinase RT-PCR was positive in 11 of the remaining 33 patients (19 of 49 SN). Of these same 11 patients, only 5 were shown to have tumor-positive SNs by using IHC on serial sections (7 SN). All these nodes had been positive for tyrosinase on PCR. For IHC, an average of 40 sections were prepared and examined per SN at a cost of $200(U.S.)/SN. In contrast, routine tyrosinase RT-PCR costs $37(U.S.)/SN, and takes 5% of the time necessary for IHC. A strategy including hematoxylin and eosin staining on the first cross section, followed by tyrosinase RT-PCR on half of each negative (half) node, could preselect nodes to be taken through serial sectioning. In these series, such a strategy would have prevented serial sectioning and IHC of 30 SN from 22 patients. Apart from a considerable gain in efficiency, this would have reduced material costs by a minimum of $6000 (U.S.). This iscrepancy would be even higher if work intensity of analysts and pathologists were considered. Conclusions: In routine analysis of SN biopsies in melanoma patients, tyrosinase RT-PCR can be used effectively to preselect nodes for further IHC of serial sections. This method seems both time and cost effective.
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  • 6
    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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  • 7
    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.
    Type of Medium: Electronic Resource
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  • 8
    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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  • 9
    ISSN: 1436-3305
    Keywords: Key words Mucosal gastric cancer ; Micrometastasis ; Cytokeratin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Endoscopic mucosal resection is frequently used in the treatment of mucosal gastric cancer. Micrometastasis in the lymph nodes of mucosal gastric cancer remains unclear. Methods. We examined 2526 lymph nodes from 84 patients with mucosal gastric cancer. Two consecutive sections were prepared, for simultaneous staining with hematoxylin and eosin and immunostaining with CAM 5.2 monoclonal antibody against cytokeratin (CK), respectively. A clinicopathological comparison was made between patients with and without lymph node involvement. Results. Lymph node involvement was detected in 45 of 2526 (1.8%) lymph nodes. The incidence of nodal involvement was significantly increased, from 1.2% (1/84 patients) with hematoxylin and eosin staining, to 19% (16/84 patients) with CK immunostaining. Although no significant difference was found, micrometastasis to lymph nodes was more frequently detected in tumors larger than 1.0 cm (15/72 patients, 21%) than in those less than or equal to 1.0 cm (1/12 patients; 8%, P = 0.307). However, discrete CK-positive cancer cells or clusters of CK-positive cancer cells were detected only in tumors larger than 2 cm. Conclusion. Because mucosal gastric cancer of more than 1.0 cm in superficial diameter may indicate a risk of micrometastasis to lymph nodes, endoscopic mucosal resection is not recommended for these patients.
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  • 10
    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.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 113 (2000), S. 268-271 
    ISSN: 1437-1596
    Keywords: Key words Surfactant-associated protein A ; Immunohistochemistry ; Asphyxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract We evaluated the usefulness of pulmonary surfactant protein A (SP-A) as a practical diagnostic marker of fatal mechanical asphyxia in forensic autopsy cases. ¶A total of 27 cases of asphyxia were examined histologically and immunohistochemically and compared with a control group consisting of 16 cases of poisoning (n = 9) and peracute death (n = 7). Both groups showed histological findings of local atelectasis and local emphysema, congestion, intra-alveolar and interstitial edema in most cases and pulmonary hemorrhages in some cases. The mechanical asphyxia group showed a significantly increased intensity of SP-A staining in the intra-alveolar space accompanied by many massive aggregates in approximately 60% of cases, which was not found in the control group. These structures may be interpreted as aggregates of pulmonary surfactant released from the alveolar wall due to enhanced secretion caused by strong forced breathing or over-excitement of the autonomic nervous system by mechanical asphyxia. The results of our investigation suggest the practical usefulness of the immunohistochemical detection of SP-A in distinguishing mechanical asphyxia from other types of hypoxia.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 113 (2000), S. 288-292 
    ISSN: 1437-1596
    Keywords: Key words Brain injury ; Cortical contusion ; Vascular ¶reaction ; Immunohistochemistry ; Wound age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract In a total of 104 individuals who had sustained traumatic brain injury (TBI), the time-dependent vascular response was investigated at the injured cortical area during the first 30 weeks after the trauma. The immunohistochemical staining of the cerebral blood vessels was performed with antibodies against laminin, type IV collagen, tenascin, thrombomodulin and factor VIII associated antigen. Compared to the immunoreactivity in unaltered control tissue, a significantly increased vascular expression could be detected in cortical contusions after a postinfliction interval of at least 3 h for factor VIII, after 1.6 days for tenascin or after 6.8 days for thrombomodulin, whereas the immunostaining for laminin and type IV collagen was regularly positive even in the vascular endothelium of uninjured brain tissue.
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  • 13
    ISSN: 1436-3305
    Keywords: Key words Gastric cancer ; Beta-catenin ; E-cadherin ; Immunohistochemistry ; Western blot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers. Methods. The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined. Results. Beta-catenin expression was classified into two patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the latter being subclassified as overexpressed (7.3%; 6 patients) and reduced (69.5%; 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration (P = 0.0154), but was not associated with lymph node metastasis (P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression (P 〈 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis; however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival. Conclusion. Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Journal of gastroenterology 35 (2000), S. 907-911 
    ISSN: 1435-5922
    Keywords: Key words: gastric cancer ; liver neoplasms ; secondary ; interventional radiology ; chemotherapy ; chemoembolization ; therapeutic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Little is known about the effectiveness of transcatheter chemotherapy in liver metastases from gastric cancer. The aim of this study was to evaluate the initial results of hepatic artery infusion and oily chemoembolization in these liver secondaries. Courses of transcatheter arterial infusion with 5-fluorouracil/doxorubicin (12 patients) and oily chemoembolization with doxorubicin-in-iodized oil and gelatin sponge (12 patients) were performed in 24 patients with histologically proven unresectable gastric cancer liver metastases. A positive effect of treatment (partial response + stabilization) was seen in 92% of the patients after chemoinfusion and in 50% after chemoembolization. The 1- and 2-year actuarial survival rates were 92% and 53% for infusion vs 50% and 17% for chemoembolization, respectively (log-rank test, P = 0.0009). For patients who had already died, the mean survival was 19.2 months vs 9.5 months (Student's t-test, P 〈 0.05) with median survivals of 23 months vs 8 months, respectively. The results with arterial infusion were very close to those reported for liver resection. Transcatheter therapy appears to be useful for the palliation of unresectable liver metastases from gastric cancer. If regional chemotherapy is used, arterial infusion should be the first-choice treatment, with oily chemoembolization being reserved for patients who do not respond to infusion.
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  • 15
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gastric cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:A multi-centric trial was performed to explore theclinical activity, in terms of response and toxicity (primary objectives),duration of response and survival (secondary objectives), of docetaxel withcisplatin in advanced gastric cancer (AGC). Patients and methods:Patients with measurable unresectable and/ormetastatic gastric carcinoma, performance status ≤1, normal hematological,hepatic and renal functions and not pretreated for advanced disease bychemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2d1, cisplatin 75 mg/m2 d1) q3w. Dose escalation to 100mg/m2 was performed in five patients and was discontinued forexcessive toxicity. Results:Forty-eight patients were accrued. A median of 5cycles/patient was given. We observed 2 complete and 25 partial responses foran overall intent to treat response rate of 56% (95% CI:41%–71%). Twelve patients had stable disease for ≥9weeks (3 cycles). The median time to progression and overall survival were 6.6and 9 months, respectively. Grade ≥3 toxicities were neutropenia81%, anemia 32%, thrombocytopenia 4%, alopecia36%, fatigue 9%, mucositis 9%, diarrhea 6%,nausea/vomiting 4%, neurologic 2%, and one anaphylaxisprecluding treatment administration. We recorded nine episodes of non-fatalfebrile neutropenia in eight patients, two of them with docetaxel at 100mg/m2. There were no direct treatment-related deaths. Conclusions:TC is active in AGC with a high response rate in amulticentric trial. Despite its hematotoxicity, this regimen is well toleratedand can be recycled as originally planned in 78% of the cases. Theseresults may serve as basis for further developments of docetaxel containingregimens in this disease.
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  • 16
    ISSN: 1569-8041
    Keywords: chemotherapy ; concomitant chemoradiotherapy ; head and neck cancer ; paclitaxel ; radiation ; reirradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Concomitant chemoradiotherapy is an effectivetreatment modality for advanced head and neck cancer, but improved regimensare needed. We sought to define the toxicities, recommended phase II dose, andoutcome of a combination chemotherapy regimen with concomitanthyperfractionated radiotherapy in patients with poor prognosis cancers of thehead and neck, including those having received prior curative intentradiotherapy. Patients and methods:From 1995 until 1997, 54 patients weretreated, 25 of whom had received a prior full course of radiotherapy to thehead and neck. Patients were treated with 5-fluorouracil (5-FU) 600mg/m2/day continuous infusion × 5 days (days 1–5),hydroxyurea, 500 mg p.o. bid × 11 doses (days 1–6) and paclitaxel(60–150 mg/m2) by one-hour infusion on day 2 using a doseescalation strategy. Radiotherapy was given concomitantly on days 2–6,150 cGy bid. Each of 4–5 cycles was delivered every other week. Results:The MTD of paclitaxel was 100 mg/m2. Theregimen was feasible; radiotherapy was delivered at a median of 7300 cGy and83% of patients received ≥80% planned dose intensity.Hematological toxicity, with granulocyte colony stimulating factor, was verymild. Dose limiting toxicities were mucositis and dermatitis. Despite poorprognosis, two-year survival was 45%. Conclusions:The recommended phase II dose of this regimen is 5-FU600 mg/m2/day × 120 hours (days 1–5), hydroxyurea 500mg p.o. b.i.d. × 11 doses (days 1–6), paclitaxel 100mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days2–6. Concomitant chemotherapy and re-irradiation was feasible on thisprotocol and resulted in long-term survival in patients without other curativeintent options.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 887-889 
    ISSN: 1569-8041
    Keywords: chemotherapy ; lung metastases ; spontaneous pneumothorax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pneumothorax occurring in the absence of obvious lungdisease is defined as spontaneous pneumothorax. Spontaneous pneumothoraxoccurs in a variety of settings in patients with malignancies. Patients and methods:We present a case report of spontaneouspneumothorax in malignancy and review the literature. Results:No correlation was found between the occurrence ofpneumothorax with age, sex or smoking history. Pneumothorax occurred with avariety of primary tumors. However it was always associated with lungmetastases or lung involvement with tumor. In certain cases the metastaseswere detected after the occurrence of pneumothorax. Conclusions:The occurrence of pneumothorax in a patient withmalignancy should prompt a search for lung metastases.
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  • 18
    ISSN: 1569-8041
    Keywords: carboplatin ; chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The combination of paclitaxel (P) and carboplatin (C)is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active newdrug. We planned a phase I study to find the maximum tolerated dose (MTD) ofthe PCG combination. A phase II study was subsequently conducted to evaluatethe activity and toxicity of PCG. Patients and methods:Forty-five patients entered the study.Twenty-eight had stage IIIA–B disease, 17 stage IV. In the phase Istudy, with a fixed dose of C at AUC = 6 on day 1, P was escalated usingincrements of 25 mg/m2 starting from 175 mg/m2 on day1 and G with increments of 200 mg/m2 starting from 800mg/m2 on day 1 and 8. Results:Fourteen patients entered the phase I study. The MTD wasreached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2.Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities.Thirty-one patients were treated in the phase II study with P 175mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was57% (68% in stage III and 47% in stage IV).Myelosuppression was the main toxicity, with grade 3–4 leukopeniaoccurring in 35% of cases. Grade 3 anemia was observed in 24%of cases and grade 3–4 thrombocytopenia occurred in 34% ofpatients. Non-hematological toxicity was mild. Median survival and one-yearactuarial survival were 20.5 months and 74% for stage III and 11.5months and 47% for stage IV. Conclusions:PCG is a promising regimen for treating advancedNSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin inadvanced NSCLC is ongoing. On the other hand, we are planning to introduce thePCG regimen in the treatment of stage II–III patients in the setting ofa multimodality treatment.
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  • 19
    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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  • 20
    ISSN: 1432-2307
    Keywords: Key words Oral cancer ; pN upgrading ; Immunohistochemistry ; Micrometastasis ; Semiserial sectioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The International Union Against Cancer (UICC) does not define the number of sections required from each regional lymph node to record pTNM classification. This study was designed to clarify the incidence of occult metastasis and to assess the pN upgrading of patients with oral cancer. Ultimately, this study led to a proposal for appropriate semiserial sectioning guidelines. Five hundred fifty-four nonmetastatic cervical lymph nodes taken from 73 patients with oral cancer were subjected to hematoxylin-eosin (HE) staining and keratin immunohistochemistry. Micrometastases, defined as foci ≤3 mm, were detected in 29 sites of 23 lymph nodes (4.2%) of 16 patients (21.9%). In 9 patients (12.3%) pN upgrading was needed: in 6 from pN0 to pN1, in 1 from pN0 to pN2b, and in 2 from pN1 to pN2b. The remaining 13 lymph nodes with occult metastasis were found in 5 pN2b and 2 pN2c patients, resulting in no pN upgrading. Occult metastasis was also detected in 6 small lymph nodes ≤5 mm in diameter. The average minor axis of the micrometastasis was 1.36±0.85 mm. We propose that the lymph nodes should be cut and examined at 1-mm intervals to detect micrometastatic foci and to evaluate the pN classification accurately.
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  • 21
    ISSN: 1432-2307
    Keywords: Keywords Small round cell tumors ; Ewing’s sarcoma ; Translocation ; Immunohistochemistry ; Differential diagnosis ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is now widely accepted that the EWS/FLI-1 fusion transcript is associated with tumors of the Ewing family. To test whether it is possible to detect the fusion transcript by means of combining polymerase chain reaction (PCR) methodology and immunohistochemistry, we investigated tumors of the Ewing family using in situ reverse transcriptase (RT)-PCR. We were able to demonstrate the t(11;22) fusion transcript in five of six cases of Ewing’s sarcoma and four of four peripheral primitive neuroectodermal tumors. These results were confirmed using fluorescence in situ hybridization in seven tumor samples. In situ RT-PCR-labeled fusion transcripts were found in virtually all tumor cells within a given sample, indicating that each cell possessed the t(11;22) transcript. We conclude from these results that in situ RT-PCR can be used for the rapid detection of EWS/FLI-1 fusion transcripts in biopsy material. The findings also suggest that all cells of the tumors of the Ewing family carry the EWS/FLI-1 fusion transcript.
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  • 22
    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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  • 23
    ISSN: 1432-2307
    Keywords: Keywords Gonadotropin-releasing hormone receptor ; Pituitary gland ; Immunohistochemistry ; Colocalization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH- and prolactin (PRL)-cell, and α-subunit (α-SU)/null-cell adenomas. The findings of this study suggest that the interaction between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and pituitary adenomas.
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  • 24
    ISSN: 1432-2307
    Keywords: Keywords CD99 antigen ; Neuroendocrine tumours ; Immunohistochemistry ; Cell-to-cell adhesion ; Proliferative activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although considered a specific marker for Ewing’s sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours. The present study evaluated immunohistochemically the prevalence of CD99 expression in a series of 68 neuroendocrine tumours of different gastrointestinal and pulmonary sites. We now report on membrane and/or granular cytoplasmic immunoreactivity in 25% of these tumours, independent of their anatomical sites. In lung neuroendocrine tumours, CD99 was preferentially confined to typical carcinoids (P=0.009). A statistically significant relationship was observed between the number of CD99 positive cells but not the immunostaining patterns and the presence of local invasion and/or distant metastases (P〈0.001). Moreover, there was a tendency for CD99-reactive tumours to show a reduced proliferative activity expressed by a Ki67 index of 2% (P=0.119). The number of CD99 immunoreactive cells or patterns of immunoreactivity did not correlate with the presence of associated clinical syndrome or particular hormonal immunostaining. Although the molecular basis underlying CD99 expression in neuroendocrine tumours is still poorly understood, our data suggest that CD99 may be involved in cell-to-cell adhesion of neuroendocrine tumour cells and in downregulation of their proliferative activity.
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  • 25
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 437 (2000), S. 445-449 
    ISSN: 1432-2307
    Keywords: Keywords Solitary fibrous tumour ; Adrenal gland ; Pregnancy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Solitary fibrous tumour (SFT), first described as a pleural lesion, has been reported in several extrathoracic sites over the past 10 years. We describe a SFT of the left adrenal gland incidentally discovered in a 23-year-old, 22-week pregnant woman and characterised by a rapid growth during the third trimester of pregnancy. Elevated serum and urinary levels of cortisol and elevated blood levels of delta 4 androstendione and 17-OH progesterone were observed. After spontaneous delivery, the patient underwent laparoscopic resectioning of the mass and of the left adrenal gland from which the tumour was apparently originating. The kidney was not involved, and no other abdominal tumours were found. Histological and immunohistochemical features were typical of SFT of pleura and other locations. Only one case of adrenal SFT is on record, and the adrenal gland is to be added to the long list of extrathoracic locations of SFT. The association with pregnancy was a previously unrecognised event in SFT. The focal expression of progesterone receptors in the tumour cells may be related to pregnancy. This observation prompted an analysis of steroid hormone receptors in SFT of classical sites (pleura). Two of five cases had focal progesterone receptors too, a finding which deserves further investigations in a much larger series of SFTs.
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  • 26
    ISSN: 1432-2307
    Keywords: Keywords Non-Hodgkin’s lymphoma ; Immunohistochemistry ; ALK1 ; T-cell lymphoma ; Splenic rupture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a 22-year-old male with a 10-day history of fever, painful swelling in the left groin, and abdominal complaints, emergency surgery was performed because of spontaneous splenic rupture. At histology, a cellular infiltrate of intermediate-sized atypical lymphocytes was seen in the splenic white pulp, staining for T-cell markers. In addition, CD30 and anaplastic lymphoma kinase 1 (ALK) were diffusely positive, thus, representing a case of anaplastic large cell lymphoma (ALCL), T-cell, ALK-positive, small cell monomorphic variant. ALK-positive ALCL patients generally bear a much better prognosis than patients with T-cell lymphomas, unspecified, or ALK-negative ALCL. Therefore, besides the very unusual clinical presentation, this case highlights the importance of immunostaining for CD30 and ALK in all T-cell lymphomas. This report is the first extensive description of ALK-positive ALCL involvement of the spleen.
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  • 27
    ISSN: 1129-2377
    Keywords: Key words Dopamine receptors ; Pial arteries ; Immunohistochemistry ; Prejunctional receptors ; Post-junctional receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial arteries. This was done to further understand the pathophysiology of cerebrovascular dopaminergic system in migraine. The study was performed in sections of dog brain including the pia-arachnoid membrane, which were processed for indirect immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. A faint dopamine D1 receptor protein immunoreactivity was observed in smooth muscle of the tunica media of different sized pial arteries. Dopamine D2 receptor protein immunoreactivity was located in the adventitia and adventitia-media border of pial arteries. In the same area tyrosine hydroxylase immunoreactive nerve fibers were found. No dopamine D3 receptor immunoreactivity was detectable in dog pial arteries. A faint dopamine D4 receptor protein immunoreactivity was observed in dog pial arteries, with a localization similar to that of D2 receptor protein. A moderate dopamine D5 receptor protein immunostaining was observed in smooth muscle of the tunica media. These findings indicate that dog pial arteries express dopamine D1-like (D1 and D5) and D2-like (D2 and D4) receptor subtypes and display, respectively, a muscular (post-junctional) and probably prejunctional localization. These results, the first analysis of dopamine D1-D5 receptor subtype distribution in the cerebrovascular tree, suggest that dopamine is involved in the regulation of cerebral circulation. These finding may help evaluate the role of cerebrovascular dopaminergic mechanisms in the pathogenesis of migraine.
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  • 28
    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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  • 29
    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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  • 30
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; malignant glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:We conducted a phase II multicentre study of gemcitabinein patients with anaplastic astrocytoma and glioblastoma multiforme at firstrelapse. Patients and methods:Patients with anaplastic astrocytoma orglioblastoma multiforme receiving a stable dose of steroids and ECOGperformance status ≤3 were eligible for this study at the time of firstrelapse. One adjuvant chemotherapy regimen was permissible. Patients receivedgemcitabine 1000 mg/m2 i.v. weekly × 3, repeated on afour-weekly cycle. Results:Of 20 patients enrolled, 15 were evaluable for response,19 for non-hematological toxicity and 18 for hematological toxicity. Sevenpatients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme(GBM). Age ranged from 28–71 years (median 50). Fifteen patientsdiscontinued therapy due to disease progression. The median number of cyclesadministered was 1 (range 1–11); only two patients received more thanthree cycles. Hematologic toxicity was acceptable and no grade 4 toxicity wasseen. One patient developed Pneumocystispneumonia and eventualpulmonary embolism; one died of gastric hemorrhage related to steroid therapy.No objective responses were seen. Nine patients had stable disease (medianduration 2.7 months, range 0.9–11.2). Conclusions:Gemcitabine given in this dose and schedule seemswell tolerated but is not active in patients with recurrent high-gradegliomas.
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  • 31
    ISSN: 1569-8041
    Keywords: alkylating agents ; bendamustine ; chemotherapy ; phase I study ; solid tumours ; weekly chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The cytotoxic agent bendamustine combines apurine-like benzimidazol and alkylating nitrogen mustard group. The clinicallytolerated dose for single bolus bendamustine is 215 mg/m2, forfractionated therapy on four consecutive days 85 mg/m2. The maximumtolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recentlyfound to be 160 mg/m2, mouth dryness and fatigue weredose-limiting. Our current phase I trial was designed to define therecommended dose of a new weekly short infusion schedule. Patients and methods:Patients with refractory malignant tumoursqualified for the trial after written informed consent was obtained.Bendamustine was given as a 30-min i.v. infusion weekly for up to eightconsecutive weeks. Results:Twelve patients (8 male, 4 female, median age 57.5 years,range 42–64) were enrolled in this trial. At the starting dose of 80mg/m2, two patients had dose-limiting toxicity (fatigue grade 3,mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). Nodose-limiting events were observed in six patients treated at 60mg/m2. An intermediate dose level of 70 mg/m2 wasstudied in three younger, less heavily pre-treated patients, was welltolerated and not associated with dose-limiting events. Haematologicaltoxicity was mild except for grade 3–4 lymphocytopenia, occurring in 11of 12 patients. Bendamustine was found to induce long-lastingpanlymphocytopenia with predominant B-cell cytotoxicity. Conclusions:The maximum tolerated dose of weekly bendamustinegiven as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigueand fever are dose-limiting. The recommended dose for phase II trials is 60mg/m2.
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  • 32
    ISSN: 1569-8041
    Keywords: anthracycline ; chemotherapy ; liposomal daunorubicin ; lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m2, V 1.4mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC 〈500/mm3 for 〉5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m2,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m2in the COP-X regimen was well tolerated with little non-hematologic toxicity.
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  • 33
    ISSN: 1569-8041
    Keywords: adjuvant ; chemotherapy ; gastric cancer ; meta-analysis ; randomised clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P 〈 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.
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  • 34
    ISSN: 1569-8041
    Keywords: chemotherapy ; chromosome aberrations ; malignant germ-cell tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 35
    ISSN: 1438-2199
    Keywords: Keywords: Amino acids ; Basal ganglia ; Dopamine ; Nitric oxide ; Excitatory amino acids ; Organotypic culture ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The nigrostriatal and mesolimbic systems of the rat have been re-constructed using the organotypic culture model, whereby neonatal brain tissue is grown in vitro for approximately one month. The nigrostriatal cultures consisted of tissue from the substantia nigra, dorsal striatum and frontoparietal cortex; while the mesolimbic cultures included the ventral tegmental area, ventral striatum and cingulate cortex. The cultures were grown at 35°C in normal atmosphere, using a tube-roller device placed in a cell incubator and changing the medium every 3–4 days. The in vitro development was evaluated with an inverted microscope equipped with a variable relief contrast function. Samples were taken directly from the medium in the culture tube and analysed for several amino acids with HPLC. After a month the cultures were fixed and processed for immunohistochemistry. High levels of glutamate and aspartate were observed every time the medium was changed, but the levels rapidly decreased reaching a steady state after approximately 24 h. A decrease in the levels was also observed along development, reaching stable values (∼2 μM and ∼0.12 μM for glutamate and aspartate, respectively) at approximately two weeks, but only when the cultures showed an apparently healthy development. The levels were approximately 10 times higher in deteriorating or apparently damaged cultures. Glutamine levels were in the mM range and remained stable along the entire experiment. No differences were observed among nigrostriatal and mesolimbic cultures. Immunohistochemistry confirmed the impressions obtained from microscopic and biochemical analysis along the in vitro development, revealing apparently healthy neuronal systems with characteristics similar to those observed in vivo, when tyrosine hydroxylase and nitric oxide synthase, markers for dopamine and nitric oxide containing neurons, respectively, were analysed. In the substantia nigra, nitric oxide synthase-positive networks surrounded tyrosine hydroxylase-positive neurons, while in the striatum nitric oxide synthase dendrites were surrounded by tyrosine hydroxylase-positive nerve terminals, suggesting a reciprocal interaction among dopamine and nitric oxide containing neurons. Thus, the organotypic model appears to capture many of the neurochemical and morphological features seen in vivo, providing a valuable model for studying in detail the neurocircuitries of the brain.
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  • 36
    ISSN: 1438-2199
    Keywords: Keywords: Amino acids ; Spinal cord injury ; Heme oxygenase ; Heat shock protein ; Carbon monoxide ; Growth factors ; BDNF ; IGF-1 ; Immunohistochemistry ; Cell injury ; Spinal cord edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The influence of brain derived neurotrophic factor (BDNF) or insulin like growth factor-1 (IGF-1) on spinal cord trauma induced carbon monoxide (CO) production and cellular stress response was examined using immunostaining of the constitutive isoform of the hemeoxygenase (HO-2) enzyme and the heat shock protein (HSP 72 kD) expression in a rat model. Subjection of rats to a 5 h spinal trauma inflicted by an incision into the right dorsal horn at T10–11 segment markedly upregulated the HO-2 and HSP expression in the adjacent spinal cord segments (T9 and T12). Pretreatment with BDNF or IGF-1 significantly attenuated the trauma induced HSP expression. The upregulation of HO-2 was also considerably reduced. These results show that BDNF and IGF-1 attenuate cellular stress response and production of CO following spinal cord injury which seems to be the key factors in neurotrophins induced neuroprotection.
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  • 37
    ISSN: 1569-8041
    Keywords: chemotherapy ; drug interaction ; in vitroassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Chemotherapy using multi-drug regimens is consideredmore active than single-agent therapy. This may be due to synergisticinteractions or, simply, a higher probability of administering an activeagent. We investigated in vitrothe type of drug interactions in arecognized regimen in relationship to tumour type and drug sensitivity. Patients and methods: The possibility of synergistic and additiveinteractions between individual cytotoxic drugs was investigated for thecomponent drugs of the established FEC regimen, i.e., 5-fluorouracil,epirubicin and cyclophosphamide, in 243 patient tumour samples representingvarious drug sensitivity using the non-clonogenic fluorometric microculturecytotoxicity assay. Results: Using a cell survival of ≤50% as a limit fordrug activity and sample sensitivity, the overall response rates to the mostactive single drug (Dmax) and the combination were 56% and64%, respectively, with a distribution among diagnoses similar to thatin the clinic. For 86% of the samples there was concordance withrespect to judgement of activity using either Dmax or thecombination. For samples being sensitive to at least one single drug,95% were also sensitive to the combination whereas for samples withinsignificant Dmax effect, only 2% were sensitive to thecombination. In samples with modest Dmax effects, i.e., cellsurvival in the range 〉50%–≤80%, 45%responded to the combination. The effect of the combination was generally wellpredicted from the Dmax effect. Conclusions:The superior antitumour effect of drug combinationscompared with single drugs may be due to the higher chance of selecting anactive agent. However, for intermediately sensitive tumours, additionalinteraction effects of a combination may be of clinical significance.
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  • 38
    ISSN: 1569-8041
    Keywords: chemotherapy ; ovarian cancer ; second-line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine is active in patients with otherwiseresistant or refractory ovarian cancer. As the drug is well tolerated, studiesusing gemcitabine combined with other antineoplastic agents are needed. Theaim of the study was to determine the maximum tolerated dose (MTD) ofepirubicin combined with gemcitabine, with and without support of G-CSF. Patients and methods:Patients with platinum-resistant orrefractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800mg/m2 day 1 and 8; 200 mg/m2 escalation per level) andepirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2escalation per level) were given every 21 days for four to six cycles. G-CSF(filgrastim 5 µg/kg/die) was given in case of grade 4 neutropenia(levels without support) or from day 9 up to leukocyte count〉10,000/mm3 after nadir (levels with support). Cohorts of threepatients were enrolled at each level, and another three patients were planned,if one dose-limiting toxicity (DLT) was registered. MTD was determined firstwithout and then with G-CSF. Results:Four levels were studied (G 800 + E 60; G 1000 + E 60;G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and threepatients enrolled, respectively. DLT (grade 4 febrile neutropenia) wasobserved in two patients at level 3. Thus, G1000 + E 60 mg/m2 wasthe MTD without G-CSF. The addition of prophylactic G-CSF did not allow afurther increase of the dose and grade 4 thrombocytopenia was the DLT at level4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in fourpatients. Among the 13 patients with measurable or evaluable disease, 3partial responses were observed for an overall response rate of 23.1%. Conclusions:The combination of gemcitabine 1000 mg/m2(day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasibletherapy. Grade 4 neutropenia is frequent and G-CSF support is often required.With prophylactic support of G-CSF, the DLT is thrombocytopenia.
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  • 39
    ISSN: 1569-8041
    Keywords: brain tumor ; chemotherapy ; encephalopathy ; late neurological toxicity ; leucoencephalopathy ; primary cerebral lymphoma ; radiochemotherapy ; systematic follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Primary cerebral non-Hodgkin's lymphomas (NHL) inimmunocompetent patients (PCL) are located exclusively in the central nervoussystem, the eye, or meninges. Clinical management of these patients remainscontroversial. Patients and methods:Clinical characteristics of the patients andparameters influencing their outcome as of December 1998 were investigated andregistered in a database of 226 patients treated in the French Federation ofCancer Centers between 1980 and 1995. Results:Most PCL are diffuse large-cell NHL with a B phenotype.The incidence of PCL has been steadily increasing over the past 20 years insome but not all countries. The overall survival of primary cerebral lymphoma(PCL) patients in the published series, a median of 12–16 months and afive-year survival of 5%–20%, is poor. Several series havenow reported long-term survivals of more than 10 years and PCL may thereforebe a curable tumor in some patients. The optimal treatment of PCL is notknown. Complete resection of the tumor does not improve outcome andmultidisciplinary approaches combining chemotherapy and radiotherapy are nowcommonly used, although the superiority of combination over radiotherapy- orchemotherapy-alone has never been demonstrated in a phase III trial. Theoptimal chemotherapy regimen, the dose and even the usefulness of brainradiotherapy after chemotherapy are therefore still matters of debate.Recently, several authors have reported a relatively high incidence of lateneurological sequelae after PCL treatment. Conclusions:The optimal treatment of PCL patients remains to bedefined. Large cooperative international phase III trials are now required todefine and improve the optimal treatment of PCL and reduce its sequelae.
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  • 40
    Electronic Resource
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    Annals of oncology 11 (2000), S. 81-85 
    ISSN: 1569-8041
    Keywords: ABVD ; BEACOPP ; chemotherapy ; clinical trials ; COPP ; dose intensification ; Hodgkin's disease ; radiotherapy ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Treatment strategies in Hodgkin's disease (HD) arechanging fundamentally over the last decades. Both radiotherapy andcombination chemotherapy are effective treatment modalities. However, theoptimal choice of treatment or combinations of treatment is still debated fordifferent prognostic groups. Patients and methods:The German Hodgkin's Lymphoma Study Group(GHSG) initiated randomized clinical trials since 1978. Over the past 20years, more than 6000 patients with HD in all stages were randomized, treatedand followed by the GHSG. Patients are now being recruited from more than 300clinical centers. Results:As a consequence of different clinical trials, it is nowthe policy of the GHSG to tailor treatment to the individual risk of patients,giving favorable patients less intensive and less toxic therapy thanunfavorable patients. The treatment for early and intermediate stage HDbecomes quite similar with few cycles of polychemotherapy followed by involvedfield irradiation. In advanced stage HD, the introduction of dose intensifiedchemotherapy (BEACOPP), has improved treatment results and thus willsubstitute the MOPP or ABVD regimens. Conclusions:Although most of the patients with HD will be curedby modern treatment stategies, several questions are still subjects of ongoingclinical trials: 1) which chemotherapy regimen in which quantity will be thebest with respect to efficacy and toxicity and 2) which dose and field sizeof radiotherapy is adequate within the combined modality.
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  • 41
    ISSN: 1569-8041
    Keywords: antifolate ; chemotherapy ; pancreatic cancer ; thymidylate synthase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To determine the safety and activity of LY231514(ALIMTA™, MTA, pemetrexed disodium, Eli Lilly and Co.,Indianapolis, IN) in chemotherapy-naïve patients with advanced pancreaticcancer. Patients and methods:Patients with unresectable or metastaticpancreatic cancer received LY231514 600 mg/m2 as a 10–minuteinfusion every three weeks. Results:Forty-two patients were enrolled in this phase II trial.The median age was 60.3 (range 37–77) years; 79% had metastaticdisease. Neutropenia was common (40% of patients ≥ grade 3) butinfectious complications were rare. Significant anemia or thrombocytopeniaoccurred in 〈20% of patients. Non-hematologic toxicities includedgrade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevationsof bilirubin or transaminases were infrequent (〈25% of patients) anddid not require dose reductions or treatment delays. Thirty-five patientsreceived two cycles of therapy and were evaluable for response. One complete(duration 16.2 months) and one partial (duration 6.9 months) were observedresulting in an objective response rate of 5.7% for evaluable patients.In addition, 17 patients (40%) had stable disease that lasted ≥6months in 5 patients. The median survival was 6.5 months, with 28% ofpatients alive at one year. Conclusions:LY231514 is a well-tolerated agent with minimalobjective antitumor activity in pancreatic cancer. The median and one yearsurvival times, which may be important indicators in phase II trials of newagents, are of interest. Combination trials of LY231514 in pancreatic cancerare planned.
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  • 42
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-FU ; folinic acid ; gemcitabine ; Gemzar® ; pancreas cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine (Gemzar®) and 5-fluorouracil (5-FU)plus folinic acid (FA) both have proven activity in the treatment of patientswith advanced pancreatic cancer. The present study was initiated toinvestigate the efficacy of gemcitabine in combination with 5-FU–FA. Patients and methods:Thirty-eight patients, median age 60 years(range 34–70) with inoperable, stage IV, pancreatic cancer were enrolledinto the study and treated on an outpatient basis. All except one patientreceived at least one cycle of treatment with gemcitabine (1000mg/m2), followed by FA (200 mg/m2) and 5-FU (750mg/m2) administered as a 24-hour continuous infusion on days 1, 8,15 and 22 of a 42-day schedule. No patient had received prior chemotherapy orradiotherapy. All 38 patients were assessed for efficacy, toxicity and timeto progressive disease. Results:Two patients (5%), achieved a partial response andthirty-four patients (89%) achieved stable disease. There were twoearly deaths (≤4 weeks). The median time to progression was 7.1 months(range 0.4–18.1+; 95% confidence interval (95% CI):5.3–7.9 months). Three patients had a progression-free interval ofgreater than 12 months and 12 of 38 patients (32%) survived longer than12 months. The median overall survival was 9.3 months (range 0.5–26.5;95% CI: 7.3–13.0 months). The incidence of grade 3 and 4toxicities was low. Conclusions:The combination of gemcitabine and 5-FU–FA isactive and well tolerated and seems to offer an improvement inprogression-free interval over both gemcitabine monotherapy and 5-FU–FAtherapy.
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  • 43
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; arterial access device ; chemotherapy ; colorectal cancer ; hepatic arterial chemotherapy ; liver metastases ; port-a-cath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m2/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.
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  • 44
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; follicular lymphoma ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Among the 566 patients with follicular lymphomas (FL)included in the GELF 86 prospective trials from October 1986 to September1995, 372 with progressive/relapsing disease were analyzed retrospectively toidentify prognostic factors at first relapse. Patients and methods:For progressive FL, patients received mono-(22%) or polychemotherapy (78%) followed by high-dose therapy(HDT) with ASCT for 83 patients (22%). The median time toprogression from initial treatment was 23 months (range 3–102 months)and 24% of documented patients (52 of 217) had histologicaltransformation (HT). Salvage therapy produced an overall response in64% of patients and the five-year survival from progression was42%. Results:For patients who underwent HDT with ASCT compared tostandard treatment, five-year freedom from second failure was at 42%vs. 16% (P = 0.0001) and five-year survival was58% vs. 38% (P = 0.0005), respectively. Thebenefit of HDT and ASCT remained if we consider only patients less than 65years (five-year survival at 60% vs. 40%; P =0.001). Multivariate analysis of parameters significant according tounivariate analysis found that no ASCT at first progression, age at relapse〉50 years, progression on-therapy were adversely significant onsurvival. Conclusions:HDT with ASCT compared to standard treatmentprolonged remission and survival after first progression of FL patients.
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  • 45
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; chemotherapy ; colorectal cancer ; cost/effectiveness analysis ; irinotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It has been shown that irinotecan is superior toinfusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancerafter 5-FU failure. In a recent trial, median survival was 10.8 months forpatients treated with irinotecan, compared to 8.5 months in patients receivinginfusional 5-FU. Considering the statistically significant but clinicallyrelatively small advantage of irinotecan over 5-FU, cost effectiveness shouldalso be part of treatment decision. Purpose:To relate the costs of each management approach tooverall survival in patients with metastatic colorectal cancer. Patients and methods:The healthcare costs and medical benefits(treatment-added survival) of second-line chemotherapy in patients (infusional5-FU: 129, irinotecan: 127) were compared. Data on overall survival were drawnfrom a multicenter randomised trial that compared infusional 5-FU (continuousinfusion, AIO, or LV5-FU2 regimens) to irinotecan alone. Costs were derivedfrom the accounting system in two university hospitals in Paris, France. Results:The range in total healthcare costs was 14,135 to 12,192US$ patient between management approaches, with irinotecan chemotherapycosting most and 5-FU-continuous infusion least. If survival was included asa treatment benefit, the cost-effectiveness ratio of irinotecan over 5-FUranged from 9,344 to 10,137 US$ per year of added survival. Conclusions:The least expensive management for metastaticcolorectal was 5-FU infusion but the additional cost of irinotecan wasbalanced by the added months of survival, with a cost-effectiveness ratioclose to that of other cancer treatments.
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  • 46
    ISSN: 1569-8041
    Keywords: chemotherapy ; esophageal cancer ; gemcitabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,–difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite. Gemcitabine has shown interesting clinical activity in initial phase II clinical trials in a variety of malignancies, including the aerodigestive malignancies, squamous-cell carcinoma of the head/neck and both non-small-cell and small-cell lung cancer. Patients and methods:A total of 21 patients with chemotherapy-naïve metastatic esophageal carcinoma were entered. Nineteen patients were evaluable for toxicity and seventeen patients were evaluable for response. Gemcitabine was administered intravenously at 1250 mg/m2 over 30–60 minutes on days 1, 8, and 15 followed by 1 week of rest. This four-week schedule defined a cycle of treatment. Patients may have received a maximum of six cycles. Results:Gemcitabine was well tolerated with minimal non-hematologic toxicity and grade 3–4 anemia, granulocytopenia, and thrombocytopenia occurring in 10.5%, 21%, and 0% of patients, respectively. No responses were seen in the seventeen evaluable patients. Conclusions:At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.
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  • 47
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    Anatomy and embryology 201 (2000), S. 149-156 
    ISSN: 1432-0568
    Keywords: Key words Cell differentiation ; Cell proliferation ; Collagen ; Fetal development ; Fibronectin ; Immunohistochemistry ; Keratin ; Laminin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  At gestational day 16 the epithelium of the rat stomach consists of a stratified layer of undifferentiated cells, and two days later glandular structures appear. The present study was carried out to identify extracellular matrix proteins that could be involved in the epithelial cell proliferation and differentiation processes that occur in the fetal rat stomach during this period. For comparative purposes the expression of the same components in the adult gastric mucosa was examined. Pregnant Sprague-Dawley rats received an intraperitoneal injection of 5-bromo-2’-deoxyuridine to label proliferating cells. One, 3.5, or 6 h post-injection the stomachs were excised and immediately frozen. The specimens were sectioned and stained with hematoxylin and eosin or for 5-bromo-2’-deoxyuridine, cytokeratin no. 8, H,K-ATPase, and the extracellular matrix proteins fibronectin, laminin, and collagens type I and IV. A stratified layer of proliferating cells was observed in the epithelium of the fetal stomachs, while in adult stomachs proliferating cells were detected in the isthmus/neck region of the glands. Cytokeratin, an epithelial cell marker, was sparse at gestational day 16 but abundant both at gestational day 18 and in the isthmus/neck region of gastric glands of the adult stomach. The parietal cell marker H,K-ATPase could not be detected in the fetal stomachs during this period. Fibronectin was observed in the stroma of both fetal and adult stomachs. Collagen type I could only be detected in the stroma close to the oesophagus at gestational day 16. Two days later, collagen type I was abundant in the lamina propria, the submucosa and in the serosa of the fetal stomachs. In adult tissue collagen type I was detected in the surface epithelium, the submucosa and in the serosa of the stomach. Collagen type IV and laminin were expressed in the lamina propria, the basement membranes around blood vessels, muscle cells, and nerve bundles, as well as in the serosa of both 16- and 18-day-old fetal and adult rat stomachs. In conclusion, a high cell proliferation rate was observed in the epithelium at both gestational days 16 and 18. The increased expression of cytokeratin observed during this period indicates that the epithelial character of the embryonic cells becomes more distinct, while the remarkable change in the expression of collagen type I might reflect an important role of collagen type I in the development of the gastric epithelium.
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  • 48
    ISSN: 1432-0568
    Keywords: Key words Intramembranous ossification ; Immunohistochemistry ; Muscle fiber type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies using parathyroid hormone-related protein (PTHrP) null mutant mice have indicated severe abnormalities in the endochondral ossification, suggesting that PTHrP affects chondrocyte differentiation. In this study, we found in newborn PTHrP-deficient mice some deformities in the mandible that is formed via intramembranous ossification. The mandibular ramus was bent downwards and a prominent bone crest to which the deep layer of masseter muscle was tendinously attached was observed in the mandibular body. Transmission electron microscopic studies showed that active bone formation was progressing along the tendon fibers of the masseter muscle. The examination of 3-D reconstruction models indicated that the mandibular ramus was bent at the site of muscle attachment, which was shifted in the direction of the muscle fibers. Muscle fiber type analysis using myosin ATPase staining showed that the masseter muscle in the newborn PTHrP-deficient mice contained numerous type 2B fibers, demonstrating premature maturation of this muscle. Based on these findings, we speculated that premature maturation of the masseter muscle leads, probably due to increased tensile forces, to accelerated bone crest formation and subsequent bending of the mandibular ramus. These results further suggest that PTHrP is involved in the regulation of muscle development in normal animals.
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  • 49
    ISSN: 1432-0843
    Keywords: Key words Monoclonal antibody ; A33 ; Gastric cancer ; Immunohistochemistry ; Tumor targeting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Murine monoclonal antibody A33 (mA33) was developed by the Memorial Sloan-Kettering Cancer Center and by the New York Branch of the Ludwig Institute for Cancer Research. It is an immunoglobulin (Ig)G2a antibody that detects a protease- and neuraminidase-resistant, periodate-sensitive epitope. Serological analysis of the antigen showed that it is expressed in a few colorectal cancer cell lines and a pancreatic cancer cell line, but is basically not reactive with other types of cell line. Normal fibroblasts and normal kidney cell lines reacted negatively to mA33. Immunohistochemical study of normal tissues identified the large and small intestinal mucosa as the principal site of A33 expression. Tests in tumor samples demonstrated that only tumors of the gastrointestinal tract are consistently A33 positive. A33 is found in 95% of primary and metastatic colorectal cancers, with uniform expression throughout the tumors in most cases. A33 is also detected in 63% of gastric cancers, with uniform expression in 45% of cases. Eighty-three percent of intestinal-type gastric cancers were positive for A33, and about 50% of the diffuse-type and mucinous cancers were mA33 positive. A33 was expressed in 50% of the pancreatic cancers but with marked heterogeneity. Other epithelial cancers, sarcomas, neuroectodermal tumors, and lymphoid neoplasms were generally A33 negative. A33 is the first example of a constitutively expressed, organ-specific epithelial membrane antigen permitting highly specific tumor targeting in patients with gastrointestinal cancer. Encouraged by the success of the biodistribution and imaging characteristic studies performed at Memorial Sloan-Kettering Cancer Center by the New York Branch of the Ludwig Institute in colorectal cancers, a new clinical study of humanized monoclonal antibody huA33 against A33 antigen-positive gastric cancers has been initiated in Japan.
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  • 50
    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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  • 51
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    Journal of cancer research and clinical oncology 126 (2000), S. 667-670 
    ISSN: 1432-1335
    Keywords: Key words Chondrosarcoma ; Heat shock protein ; Differentiation ; Diagnosis ; Immunohistochemistry ; Chondroma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Heat shock proteins (hsp) are involved in tumor immunity, and a correlation with survival, occurrence of metastases, and drug resistance has been reported. It was the aim of this study to investigate the expression of heat shock proteins in chondrosarcomas and chondromas. Methods: Hsp expression was investigated immunohistochemically on paraffin-embedded sections of 37 consecutive patients (24 male and 13 female, mean age 48 years) with chondrosarcoma and of ten patients (six male, four female, mean age 36 years) with chondroma. Results: Chondromas showed a positive staining for hsp27 in 100%, for hsp60 in 30%, for hsp72 in 80%, for hsp73 in 80%, and for hsp90 in 90%. In chondrosarcoma a decreased expression was found for hsp27 (62% positive, P 〈 0.05) and hsp72 (43% positive, P 〈 0.05), whereas no significant difference to chondromas was detected in the expression of hsp60 (49% positive), hsp73 and hsp90 (73% and 81% positive, respectively). In addition, hsp72 expression showed a correlation with differentiation of the tumors (P 〈 0.05); the lowest hsp72 expression was found in G3 chondrosarcomas (only 13% positive). No correlation with respect to differentiation was found for the expression of the other hsps. Conclusions: This study shows a different expression of hsps in chondrosarcomas and chondromas. Together with the correlation of hsp72 expression with low differentiation, this finding could lead to new experimental and diagnostic strategies.
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  • 52
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    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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  • 53
    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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  • 54
    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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  • 55
    Electronic Resource
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    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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  • 56
    Electronic Resource
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    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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  • 57
    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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  • 58
    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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  • 59
    ISSN: 1433-0458
    Keywords: Schlüsselwörter ; Nasenrachenkarzinom ; Epstein-Barr-Virus ; Immunhistologie ; Polymerasekettenreaktion ; Keywords ; Nasopharyngeal carcinoma ; Epstein-Barr virus ; Immunohistochemistry ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract We report the case of a 36-year-old women who was found to have a malignant tumor extending from the side of her right nasal cavity to the nasopharynx. Magnetic resonance imaging and computed tomography were not able to define the primary site of the tumor. Histologic evaluation demonstrated an undifferentiated squamous cell carcinoma. Because of the different treatment concepts for carcinomas of the nasal cavity and nasopharynx, we tried to identify the primary site by diagnosing Epstein-Barr virus (EBV) infection, which is associated with carcinoma of the nasopharynx. By using immunohistochemistry and polymerase chain reaction EBV could be identified in the cells of the carcinoma. This showed that the primary site of the tumor was located in the nasopharynx and resulted in the patient being treated with simultaneous radiochemotherapy.
    Notes: Zusammenfassung Eine 36 Jahre alte Patientin stellte sich mit einem ausgedehnten Tumor der rechten Nasenhöhle und des rechten Nasenrachens vor. Die histologische Untersuchung ergab ein undifferenziertes Plattenepithelkarzinom. Sowohl mit Hilfe der computertomographischen, als auch der kernspintomographischen Befunde, war keine eindeutige Bestimmung der Primärtumorregion möglich. Anhand der bekannten Assoziation zwischen Karzinomen des Nasenrachens und Epstein-Barr Virus (EBV) wurde versucht, die Primärlokalisation des Tumors zu klären. Immunhistologisch und durch „polymerase chain reaction” war es möglich, eine EBV-Infektion im Tumor nachzuweisen. Die Primärlokalisation des Tumors wurde damit dem Nasenrachen zugeordnet und die entsprechende Therapie für diese Lokalisation in Form einer simultanen Radiochemotherapie eingeleitet.
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  • 60
    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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  • 61
    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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  • 62
    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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  • 63
    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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  • 64
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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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  • 65
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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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  • 66
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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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  • 67
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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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  • 68
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    International journal of legal medicine 113 (2000), S. 70-75 
    ISSN: 1437-1596
    Keywords: Key words Brain injury ; Cortical contusion ; GFAP ¶expression ; Immunohistochemistry ; Wound age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract The course of GFAP expression by astrocytes has been immunohistochemically investigated during the first 30 weeks after human brain injury. In order to provide reliable data for a forensic wound age estimation, a quantitative morphometric analysis was performed considering the different topographic regions of the cortex as well as of the white matter. Compared to the GFAP immunoreactivity in unaltered control tissue, significantly increased numbers of GFAP positive astroglial cells could be detected adjacent to the cortical contusion from 1 day up to 4 weeks after brain injury.
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  • 69
    ISSN: 1437-1596
    Keywords: Key words Ganglion cells ; Hippocampus ; Immunohistochemistry ; Mean optical density (MOD) ; Morphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract To investigate the topography of morphine distribution in the human brain, a method has been developed to detect morphine immunohistochemically. In this study hippocampus tissue from victims of heroin overdose (blood morphine concentrations 220 ng/g–1500 ng/g; 6-MAM positive urine sample), known for its high concentration of μ-opiate receptors was used. The immunohistochemical staining was performed with an anti-morphine antiserum originally developed for radio-immuno-assays. In comparison with control specimens from cases of sudden death without morphine exposition or a history of heroin abuse, the brains from victims of heroin overdose showed selectively stained ganglion cells, axons and dendrites, suggesting a massive concentration of morphine in the neuronal structures.
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  • 70
    ISSN: 1437-773X
    Keywords: Key words Mitogen-activated protein kinase (MAPK) ; Ischemia reperfusion injury ; Heart ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.
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  • 71
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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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  • 72
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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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  • 73
    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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  • 74
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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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  • 75
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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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  • 76
    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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  • 77
    ISSN: 1437-773X
    Keywords: Key words Gonadotroph adenoma ; FSH ; Childhood ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-β monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140–260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.
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  • 78
    ISSN: 1437-773X
    Keywords: Key words Minimal change nephrotic syndrome ; α-Smooth muscle actin ; Vimentin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with minimal change nephrotic syndrome (MCNS) occasionally show frequent relapses with proteinuria after cessation of steroid treatment, even though no significant pathological abnormalities are found in the glomeruli, compared with those in nonrelapsed and good-prognosis cases of MCNS. To resolve this contradiction, we immunohistochemically and ultrastructurally examined a biopsied renal tissue of a patient who showed glomerular features of MCNS and frequent clinical relapses. Immunohistochemistry demonstrated the overexpression of α-smooth muscle actin (ASMA) and vimentin in glomerular mesangial cells despite no mesangial cell proliferation, compared with nine nonrelapsed cases of MCNS. These facts may be an important clue to the investigation of the pathogenesis of steroid-dependent MCNS with frequent relapses. Furthermore, the immunohistochemical examination of ASMA and vimentin may be useful to detect mesangial myofibroblastic transformation that is not demonstrated in conventional light microscopy and immunofluorescence study.
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  • 79
    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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    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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    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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    Pediatric surgery international 16 (2000), S. 282-284 
    ISSN: 1437-9813
    Keywords: Key words Desmin ; Infantile hypertrophic pyloric stenosis ; Immunohistochemistry ; Fetus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal elements are altered in infantile hypertrophic pyloric stenosis (IHPS). Desmin is a cytoskeletal protein that is important for the organization and function of muscular fibers. It has been found to be increased in the smooth muscle in chronic intestinal pseudo-obstruction and in skeletal muscle in some forms of myopathies as well as in unexplained hypertrophic cardiomyopathies. The aim of this study was to analyze the expression of desmin in IHPS. Full-thickness muscle-biopsy specimens were obtained from 8 IHPS patients (age range 23 to 41 days) at pyloromyotomy, from 8 age-matched controls without evidence of gastrointestinal (GI) disease at autopsy, and from 2 stillborns who died at 27 and 30 weeks of gestation without evidence of GI disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-desmin and visualized by development with 3-diaminobenzidine tetrahydrochloride. Pyloric muscle in IHPS demonstrated strong desmin immunoreactivity. The expression of desmin was also strong in the muscular layers of fetal pylorus. In the age-matched controls absent or weak desmin immunoreactivity was seen in the pyloric muscle layer. The increased amount of desmin in hypertrophied pyloric muscle in IHPS may result in inco-ordination of contraction and relaxation of the pylorus, thus causing motility dysfunction. The similar pattern of desmin expression in IHPS and fetal pylorus suggests that the organization of intermediate filaments in IHPS is in a fetal stage of development.
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    Pediatric surgery international 16 (2000), S. 285-292 
    ISSN: 1437-9813
    Keywords: Key words Major histocompatibility complex (MHC) ; Rat ; Immunohistochemistry ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
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  • 84
    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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    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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  • 86
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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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  • 87
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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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  • 88
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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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  • 89
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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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  • 90
    ISSN: 1437-773X
    Keywords: Key wordsα-Smooth muscle actin ; Transforming growth factor-β1 ; Bile ductule ; Bile duct ligation ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the early in vivo response of hepatic stellate cells in biliary fibrosis, we examined rat livers during the first 7 days after bile duct ligation using light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. At day 1 after bile duct ligation, α-smooth muscle actin-positive fibroblasts appeared and then increased in number around the proliferating bile ductules. With time, the destruction of the external limiting plate became accentuated because of the invasion of the proliferating bile ductules and periductural fibrosis. At day 7, stromal cells containing fat droplets appeared in the fibrous tissue adjacent to the periportal parenchyma; these are termed denuded hepatic stellate cells. In the fibrous tissue disconnected from the liver parenchyma, the denuded hepatic stellate cells were replaced by myofibroblast-like cells. Meanwhile, the expression of transforming growth factor-β1 on biliary epithelial cells increased. These results indicate the dual origin of myofibroblasts in experimental biliary fibrosis, the periductural and periductal fibroblasts in the initial stage, and the denuded hepatic stellate cells in the subsequent stage. These two types of stromal cells may undergo myofibroblastic transformation by the transforming growth factor-β1 secreted by the proliferating biliary epithelial cells.
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  • 91
    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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  • 92
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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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  • 93
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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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  • 94
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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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  • 95
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    International journal of clinical oncology 5 (2000), S. 164-170 
    ISSN: 1437-7772
    Keywords: Key words P-glycoprotein ; Osteosarcoma ; Soft-tissue sarcoma ; Prognosis ; Immunohistochemistry ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The purpose of this study was to investigate the correlation between P-glycoprotein status and outcome in adult patients with high-grade osteosarcomas and soft-tissue sarcomas. Methods. P-glycoprotein status was determined im-munohistochemically in specimens from 28 patients with osteosarcoma and 34 patients with soft-tissue sarcoma. The polyclonal antibody mdr(Ab-1) was used for either decalcified or undecalcified tissue samples which were formalin-fixed and paraffin-embedded. The expression of P-glycoprotein mRNA was also determined by the polymerase chain reaction in 23 fresh sarcoma specimens. P-glycoprotein status was analyzed in relation to the duration of event-free survival. Results. Positivity for P-glycoprotein was found in 29% of the osteosarcomas and 34% of the soft-tissue sarcomas. Consistent results were obtained at both the immunohistochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) levels in 19 of 23 sarcomas (83%). In patients with osteosarcoma, the presence of increased levels of P-glycoprotein was significantly associated with a decreased probability of event-free survival after diagnosis (P = 0.022). In contrast, in patients with soft-tissue sarcoma there was no correlation between the level of P-glycoprotein and prognosis. Conclusions. In patients with high-grade osteosarcomas, the presence of increased levels of P-glycoprotein detected by polyclonal antibody mdr(Ab-1) was associated with a significantly increased risk of adverse events. This association was not found in patients with soft-tissue sarcomas.
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  • 96
    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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  • 97
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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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  • 98
    ISSN: 1437-9813
    Keywords: Key words Short-bowel syndrome ; Intestinal adaptation ; Sugar absorption test ; Gut hormones ; Electrophysiology ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Short bowel syndrome is the malabsorptive state that often follows extensive resection of the small intestine. Long-term survival without parenteral nutrition depends on the process of intestinal adaptation, through which the remaining small bowel gradually increases its absorptive capacity. The process of intestinal adaptation is almost exclusively luminal nutrient dependent. To date the clinical management of short bowel patients is mostly based on a “trial and error” regimen because human data and randomised trials using trophic substances are lacking due to the small number of patients annually present in pediatric surgical centres. We evaluate here the currently available as well as some more recently developed methods of measuring intestinal absorption and adaptation in short bowel patients. New techniques such as measurements of (1) intestinal permeability and carbohydrate absorption using the sugar absorption test, (2) gastrointestinal hormone production of gastrin, cholecystokinin and peptide YY, (3) transmural potential difference of the gastrointestinal tract using electrophysiology and (4) mucosal enzyme expression of lactase and sucrase-isomaltase using immunohistochemistry were evaluated. These new techniques are promising in monitoring the process of adaptation of the remaining intestine and evaluating the effect of therapeutic interventions in patients with short bowel syndrome.
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  • 99
    ISSN: 1432-2161
    Keywords: Key words Giant rice body ; Ultrastructure ; Immunohistochemistry ; Histogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. Design and patients: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. Results: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. Conclusion: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
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  • 100
    ISSN: 1432-2307
    Keywords: Key words Unusual lung tumors ; Papillary adenoma ; Surfactant proteins ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Peripheral papillary adenomas of the lung are uncommon neoplasms (only ten cases have been described so far in the English literature) composed predominantly of type-II pneumocytes and generally considered benign. We describe here two additional cases of this lung tumor. In both cases histological examination revealed an encapsulated papillary neoplasm with invasion of the capsule and, in one case, invasion of the adjacent alveoli and visceral pleura too. The proliferative index (Ki67) was less than 2% and the epithelial cells were positive for cytokeratins, surfactant apoproteins (SP), and nuclear thyroid transcription factor-1 (TTF-1). Ultrastructurally, the epithelial cells showed the characteristic surface microvilli and cytoplasmic lamellar inclusions of type-II cells. Review of the literature has revealed two other cases of peripheral papillary adenoma of type-II pneumocytes with infiltrative features. Thus, we propose replacing the term peripheral papillary adenoma with peripheral papillary tumor of undetermined malignant potential.
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