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  • Cell & Developmental Biology  (41,698)
  • Analytical Chemistry and Spectroscopy  (25,705)
  • Industrial Chemistry  (9,655)
  • Nuclear reactions  (4,460)
  • Apoptosis
  • MRI
  • breast cancer
  • chemotherapy
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 775-781 
    ISSN: 1530-0358
    Keywords: Locally recurrent rectal cancer ; Survival ; Prognostic factor ; Angiogenesis ; Apoptosis ; PCNA labeling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. S23 
    ISSN: 1530-0358
    Keywords: Apoptosis ; Flat-type carcinoma ; Colorectal neoplasms ; p53 ; p21 (WAF1/CIP1) ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax). RESULTS: There was no significant difference in terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P〈0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P〈0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group. CONCLUSION: p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1530-0358
    Keywords: Anus ; High-grade squamous intraepithelial lesion ; Carcinoma ; Proliferation ; Apoptosis ; Microvessel density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
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  • 4
    ISSN: 1530-0358
    Keywords: MRI ; Ischiorectal abscess ; Pelvirectal abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: We evaluated the usefulness of magnetic resonance imaging for the preoperative diagnosis of deep anorectal abscesses. METHODS: Subjects were 21 patients with deep anorectal abscesses. Deep anorectal abscesses were classified into two types, ischiorectal and pelvirectal, according to their location. Patients were also classified into a single abscess group, which showed either an ischiorectal or pelvirectal abscess, and a double abscess group, which showed both ischiorectal and pelvirectal abscesses. The final diagnosis was made from surgical findings, and the types of deep anorectal abscesses determined by digital examination and magnetic resonance imaging were compared. RESULTS: Sensitivity of ischiorectal abscesses (20 lesions) with digital examination and magnetic resonance imaging was 75 and 95 percent, respectively, and that of pelvirectal abscesses (10 lesions) with digital examination and magnetic resonance imaging was 60 and 70 percent, respectively. Sensitivity of the magnetic resonance imaging was significantly higher than that of digital examination in ischiorectal abscesses. Diagnostic accuracy of digital examination and magnetic resonance imaging were both 83 percent in the single abscess group (12 patients), whereas in the double abscess group (9 patients) it was 22 and 78 percent, respectively. The rate of accurate diagnosis of magnetic resonance imaging compared with digital examination in the double abscess group was significantly higher than that in the single abscess group. CONCLUSION: Magnetic resonance imaging was useful for diagnosing and differentiating ischiorectal and pelvirectal abscesses.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Circuits, systems and signal processing 19 (2000), S. 267-278 
    ISSN: 1531-5878
    Keywords: MRI ; spectroscopic imaging ; sample selection ; k-space ; hexagonal sampling ; reconstruction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Certain types of magnetic resonance imaging (MRI) such as magnetic resonance spectroscopic imaging and three-dimensional (3D) MRI require a great deal of time to acquire the image data. The acquisition time can be reduced if the image has a limited region of support, such as when imaging the brain or a cross section of the chest. Hexagonal sampling of the spatial frequency-domain (k-space) yields a 13.4% sampling density reduction compared to rectangular sampling of thek-space for images with a circular region of support (ROS) without incurring spatial aliasing in the reconstructed image. However, certain nonuniform sampling patterns are more efficient than hexagonal sampling for the same ROS. Sequential backward selection (SBS) has been used in previous work to optimize a nonuniform set ofk-space samples selected from a rectangular grid. To reduce the selection time, we present SBS of samples from a hexagonal grid. A Smith normal decomposition is used to transform the nonrectangular 2D discrete Fourier transform to a standard rectangular 2D fast Fourier transform so that the spatial-domain samples are represented directly on a rectangular grid without interpolation. The hexagonal grid allows the SBS algorithm to begin with a smaller set of candidate samples so that fewer samples have to be eliminated. Simulation results show that a significantly reduced selection time can be achieved with the proposed method in comparison with SBS on a rectangular grid.
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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.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. 249-254 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Schultergelenk ; Basisdiagnostik ; Röntgendiagnostik ; Sonographie ; Computertomographie ; Kernspintomographie ; Arthrographie ; Keywords ; Shoulder joint ; Basic diagnosis ; X-rays ; Sonography ; Computed tomography ; MRI ; Arthrography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: It is its ball-and-socket anatomy that makes the shoulder joint the most flexible of all human joints. This high degree of freedom of movement means, however, on the one hand that early degenerative damage is likely to occur as a result of sports and occupational strains and on the other that it is particularly vulnerable to injuries. Diagnostic radiology from two different perspectives is the basic diagnostic procedure for unexplained shoulder pain and for shoulder injuries. Dislocating osseous injuries or luxations can be detected most precisely or assessed most reliably during follow-up by this means. Intra-articular findings and alterations to the soft tissues (degenerative, traumatic) can be delineated by sonography, computed tomography and magnetic resonance imaging, albeit with differing degrees of reliability and specificity. Sonography is generally available, but not reliably standardized. Computed tomography is the method of choice for diagnosis of osseous and joint injuries. Over the last 10 years magnetic resonance imaging (MRI) has improved in sensitivity and specificity with technical progress (coils, sequences, reconstruction modalities) and has therefore moved into the focus of clinical interest.
    Notes: Das Schultergelenk ist infolge seiner anatomischen Ausbildung als Kugelgelenk das beweglichste Gelenk des menschlichen Körpers. Die sich hieraus ergebenden Bewegungsmöglichkeiten bedingen einerseits bereits frühzeitig degenerative Schädigungen infolge beruflicher oder sportlicher Belastungen und andererseits eine besondere ¶Angriffsfläche für Verletzungen. Die Basisdiagnostik sowohl des unklaren Schulterschmerzes als auch verletzungsbedingter Schädigungen am Schultergelenk ist die Röntgendiagnostik in 2 Ebenen. Dislozierende ossäre Verletzungen bzw. Luxationen sind hiermit treffsicher nachzuweisen bzw. in der Verlaufskontrolle zu beurteilen. Intraartikuläre Befunde und Weichteilveränderungen (degenerativ, traumatisch) sind hingegen mit den Schnittbildverfahren der Sonographie, Computertomographie und Kernspintomographie mit unterschiedlicher Treffsicherheit und Spezifität nachzuweisen. Die klassische Gelenkarthrographie hingegen tritt gegenüber diesen Verfahren deutlich in ihrer Bedeutung zurück. Die Sonographie ist ein ubiquitär verfügbares, jedoch wenig standardisiertes Verfahren. Die Reproduzierbarkeit der Befunde ist fraglich. Die Computertomographie stellt die Methode der Wahl bei der Diagnostik von okkulten ossären bzw. Gelenkverletzungen dar. Die Methode ist breit verfügbar und mit vertretbarem Aufwand durchzuführen. In den letzten 10 Jahren hat die Kernspintomographie infolge der technischen Weiterentwicklung (Spulen, Sequenzen, Rekonstruktionsmöglichkeiten usw.) an Sensitivität und Spezifität gewonnen. In der Summe aller klinischen Fragestellungen stellt sie neben der Basisdiagnostik derzeit die effektivste Untersuchungsmethode des Schultergelenks dar.
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  • 10
    ISSN: 1436-2813
    Keywords: Key Words: genetic changes ; prognostic factor ; breast cancer ; amplification ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ERBB2 , INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.
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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    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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  • 15
    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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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Rechtsmedizin 10 (2000), S. 90-95 
    ISSN: 1434-5196
    Keywords: Schlüsselwörter Geschosse ; Verletzungen ; MRT ; Beurteilung ; Dokumentation ; Keywords Projectiles ; Injuries ; MRI ; Assessment ; Documentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: For the assessment of gunshot injuries, conventional X-ray examination, ultrasound and CT examinations are commonly used imaging techniques. With the exception of some authors, there is agreement that projectiles indicate a contraindication for MRI because of artificial imaging side-effects and the potential of secondary dislocation due to ferromagnetism. MRI testing was carried out on 56 projectiles for ferromagnetism and imaging quality in vitro and in pig carcasses with a 0.2 T and a 1.5T-MRI scanner. The image quality was compared to that of a CT scan. Projectiles with ferromagnetic properties can easily be distinguished from non-ferromagnetic ones by pretesting the motion of an projectile of the same type within the magnetic field of the MR scanner. When ferromagnetic projectiles were excluded, MRI yielded the more precise images compared to other imaging techniques. Projectile localization and associated soft tissue injuries were visualized without artifacts in all cases. When ferromagnetism is excluded MRI gives an excellent imaging procedure for the assessment and documentation of gunshot injuries. Therefore this imaging procedure may be also useful for medico-legal investigations.
    Notes: Zur Beurteilung des Ausmaßes von Schußverletzungen und zur Lokalisationsdiagnostik werden allgemein konventionelle Röntgenübersichtsaufnahmen sowie die Sonographie und die Computertomographie angewendet. Mit Ausnahme weniger Autoren wird generell davon ausgegangen, daß Projektile aufgrund der Generierung von Artefakten in der Bildgebung und der Gefahr einer sekundären Fremdkörperdislokation, bedingt durch den Ferromagnetismus, nicht mit der MRT beurteilt werden dürfen. 56 verschiedene Projektile wurden nach entsprechender Vortestung bezüglich ihrer Ferromagnetizität mit je einem 0,2-T- und 1,5-T-MRT-Gerät in vitro und anschließend in Schweinekadavern untersucht. Die Bildqualität wurde mit denen von CT-Bildern verglichen. Die ferromagnetischen Eigenschaften der Projektile können leicht beurteilt werden, indem man Vergleichsgeschosse desselben Typs in das Magnetfeld des MRT-Gerätes legt. Nach Ausschluß der Ferromagnetizität übertrifft die MRT alle anderen bildgebenden Verfahren. In allen Fällen gelang eine exakte Projektillokalisation sowie eine überlegene Darstellung der Weichteilverletzungen. Aufgrund der Ergebnisse ist die MRT, nach Ausschluß von ferromagnetischen Fremdkörpern, ein exzellentes Verfahren zur Beurteilung und Dokumentation von Schußverletzungen. Abhängig von den Fragestellungen kann dieses bildgebende Verfahren auch in der Rechtsmedizin eingesetzt werden.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. 111-117 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter Kiefergelenkfrakturen ; Kernspintomographie ; Achsiographie ; Diskusmobilität ; Diskusposition ; Key words TMJ fractures ; MRI ; Axiography ; Disc mobility ; Disc position
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Magnetic resonance imaging (MRI) assessment of traumatized temporomandibular joints (TMJ) usually focuses on disc position, defining regular joint function by normal, excentric or displaced disc position. So far, there are only few reports regarding disc position after open reduction of diacapitular or high condylar fractures of the TMJ with dislocation. The aim of the present study was to evaluate the role of the disc as regards postoperative functional outcome by electronic axiographic recordings of condylar movements and MRI, displacement of the disc and lesions of TMJ soft tissues being frequent in this type of mandibular fractures. A total of 30 subjects with 37 condylar fractures in whom osteosynthesis was performed using a preauricular approach were imaged postoperatively (mean 24 months) with a 1.5-Tesla MRI system to determine, (a) the position of the disc, (b) the range of mobility of the disc and (c) condylar mobility in closed and open mouth position, comparing fractured sides (FS) vs nonfractured sides (NFS). Linear movements between the two jaw positions in the sagittal plane were measured by superimposing transparencies. The results indicate: (1) more than 70% of the discs (FS) were found to be in normal position; there was no disc displacement without reduction. However, these data stood in contrast to severe limitations of the axiographic tracings as presented by almost 30% of the subjects. (2) Significant correlations were found between fixed (α = 0.05) or highly immobilized (α = 0.01) discs and axiographic limitations, suggesting disc mobility to be a valuable parameter for assessment of the postoperative functional outcome.
    Notes: Zusammenfassung Bei diakapitulären Frakturen bzw. hohen Kollumluxationsfrakturen mit Beziehung zum Lig. laterale sind Verlagerungen des Diskus häufig und werden nach konservativer Therapie mit einer Häufigkeit zwischen 50 und 100% angegeben. Informationen über die Diskusposition nach operativer Versorgung dieser Frakturgruppen liegen bisher nicht vor. Ziel der vorliegenden Studie war es, die Bedeutung von Position und Mobilität des Diskus für das postoperative funktionelle Ergebnis dieser Frakturgruppen zu klären. Die Objektivierung der operativen Ergebnisse bei 30 Patienten mit 37 über einen präaurikulären Zugang versorgten Gelenkfrakturen erfolgte mittels elektronischer Achsiographie und Kernspintomographie (1,5-T-System), im Mittel 24 Monate postoperativ. Erhoben wurden die Position und der Bewegungsumfang des Diskus bzw. des Kondylus im Seitenvergleich. Die linearen Bewegungen zwischen mundoffener und -geschlossener Position wurden durch Folienüberlagerung korrespondierender sagittaler MRT-Schichten ermittelt. Die Ergebnisse zeigten zum einen, dass 〉 70% der Disci auf der Frakturseite orthotop (Position A) lagen und keine fixierten anterioren Dislokationen (C) auftraten. Die achsiographischen Befunde zeigten in Diskrepanz dazu bei immerhin 30% der versorgten Gelenke höhergradige Limitationen der Exkursionsbahnen. Zum anderen bestehen signifikante Zusammenhänge zwischen fixierten (α = 0,05) bzw. hochgradig immobilisierten (α = 0,01) Disken und achsiographisch erfassten Limitationen der Translationsbewegung. Im Gegensatz zu bisherigen Studien sollten nach der operativen Versorgung von Gelenkfrakturen nicht nur die (statische) Diskusposition, sondern in erster Linie die Diskusmobilität als Parameter für das funktionelle Ergebnis berücksichtigt werden.
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  • 18
    ISSN: 1434-3940
    Keywords: Schlüsselwörter Kiefergelenk-MRT ; Diskusdislokation ; Kiefergelenkhistologie ; Keywords Temporomandibular joint (TMJ) ; MRI ; Anterior disk dislocation ; TMJ histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Problem. Anterior dislocation of the articular disk of the temporomandibular joint (TMJ) found by MRI tomography often presents a problem. It may persist in MRI despite improvement of articular symptoms and even be found in healthy persons free of any symptoms. Can this be explained by the similarity in structure of the anterior connective tissue of the disk and capsule and their pathological changes? Is a second coronal plane required for MRI investigation? Material and methods. The preauricular regions of 72 patients of the TMJ clinic were examined by oblique-sagittal and oblique-coronal MRI. A Siemens-Vision MRI was used. It was also possible to prepare 10 articular disks of the TMJ with anterior capsular tissue as well as 20 complete TMJs of adults from autopsy material. Sagittal, transversal, and horizontal serial sections were examined histologically. Results. In 49 of the 72 cases examined, an anterior dislocation without reduction found in the sagittal MRI was not confirmed in the oblique-coronal MRI. In the sagittal MRI it was possible to differentiate three, in the coronal MRI six typical forms of magnetic resonance signals, which are represented in figures. They are compared with anatomical and histological connective tissue findings adjacent to the TMJ. The structural similarity of the disk and anterior capsular tissue of the TMJ is demonstrated. The close connection of the disk and connective tissue surrounding the TMJ makes differentiation of MRI findings difficult especially following regressive and adaptive reactions. Conclusions. In MRI, anterior capsular tissue is able to simulate dislocation of the disk. Pathological tissue reactions may alter the MRI signal and lead to the wrong diagnosis of dislocation of the disk. Diagnosis of an anterior disk dislocation cannot be established solely on the basis of oblique-sagittal MRI findings.
    Notes: Zusammenfassung Fragestellung. Der Befund anteriore Diskusdislokation im sagittalen MRT beinhaltet 2 ungeklärte Probleme. Trotz Rückbildung einer Gelenksymptomatik können anteriore Diskusdislokationen im MRT unverändert bestehen, sie wurden sogar bei gesunden Probanden beschrieben. Ist die Ursache in der feingeweblichen Ähnlichkeit der anterioren Diskus- und Kapselbindegewebe und in deren pathologischen Strukturänderungen zu suchen? Kann auf die Befundung in der 2. koronalen Ebene verzichtet werden? Material und Methode. Die präartikulären Regionen im schräg-sagittalen und im schräg-koronalen MRT von 72 Patienten aus der Kiefergelenkspezialsprechstunde wurden befundet. Die Untersuchungen erfolgten mit dem Siemens-Vision-MRT. Bei unselektierten Sektionen konnten 10 Disci articulares mit dem anterioren Kapselgewebe sowie 20 Kiefergelenkpräparate Erwachsener präpariert werden. Sagittale, transversale und horizontale Serienschnitte wurden histologisch untersucht. Ergebnisse. Bei 49 von 72 ausgewählten Fällen gab es für eine anteriore Diskusdislokation ohne Reduktion im sagittalen MRT keine Bestätigung im schräg-koronalen MRT. Es konnten in den sagittalen MRT 3, in den koronalen MRT 6 sich wiederholende Signalformen differenziert werden. Sie sind skizziert. Ihre Zuordnung zu gelenkumgebenden Bindegeweben erfolgte mittels Vergleich dieser Signalformen mit den anatomischen und histologischen Kiefergelenkpräparaten. Die feingewebliche Ähnlichkeit des Discus articularis mit dem anterioren Kapselbindegewebe wird aufgezeigt. Seine enge Verbindung mit den gelenkumgebenden Bindegeweben erschwert die Differenzierung im MRT insbesondere beim Vorliegen regressiver und adaptiver Reaktionen. Schlussfolgerung. Das anteriore Kapselgewebe kann eine Diskusdislokation im MRT vortäuschen. Pathologische Gewebereaktionen ändern das MRT-Signal und tragen dazu bei, falsch-positive Befunde zur Diskusdislokation entstehen zu lassen. Schräg-sagittale MRT sind für die Diagnosefindung „anteriore Diskusdislokation mit und ohne Reposition“ nicht ausreichend.
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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: 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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  • 21
    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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  • 22
    ISSN: 1569-8041
    Keywords: BRCA1 ; breast cancer ; p53 ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The association between BRCA1 germ-linemutations and breast cancer prognosis is controversial. A historical cohortstudy was designed to determine the prognosis for women with axillary lymphnode negative hereditary breast cancer. Patients and methods:We tested pathology blocks from 118Ashkenazi Jewish women with axillary lymph node negative breast cancer for thepresence of the two common BRCA1 founder mutations, 185delAG and5382insC. Patients were followed up for a median of 76 months. SomaticTP53mutations were screened for by immunohistochemistry, and directsequencing was performed in the BRCA1-positive tumours. Results:Sixteen breast cancer blocks (13.6%) carried aBRCA1 mutation. Young age of onset, high nuclear grade, negativeestrogen receptor status and over-expression of p53 were highly associatedwith BRCA1-positive status (P-values all 〈0.01).BRCA1 mutation carriers had a higher mortality than non-carriers(five-year overall survival, 50% and 89.6%, respectively,P = 0.0001). Young age of onset, estrogen receptor negative status,nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Coxmultivariate analyses showed that only germ-line BRCA1 mutationstatus was an independent prognostic factor for overall survival (P= 0.01). Among nuclear grade 3 tumours, the BRCA1 mutation carrierstatus was a significant prognostic factor of death (risk ratio 5.8,95% confidence interval: 1.5–22, P = 0.009). Sequencingof BRCA1-related breast cancers revealed one TP53missensemutation not previously reported in breast cancer. Conclusions:Using a historical cohort approach, we haveidentified BRCA1 mutation status as an independent prognostic factorfor node negative breast cancer among the Ashkenazi Jewish women. Thosemanaging women carrying a BRCA1 mutation may need take these findingsinto consideration. Additionally, our preliminary results, taken together withthe work of others suggest a different carcinogenic pathway inBRCA1-related breast cancer, compared to non-hereditary cases.
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  • 23
    ISSN: 1569-8041
    Keywords: BCL-2 ; breast cancer ; HER-2 ; p53 ; predictive factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The selection of therapies for breast cancer is todaybased on prognostic features (chemotherapy, radiotherapy), hormone receptorstatus (hormonal therapy) and HER-2 status (trastuzumab therapy). HER-2,p53and BCL-2are tumour-related proteins that have thepotential to further improve individualisation of patient management, bypredicting response to chemotherapy, hormonal therapy and radiotherapy. Materials and methods:This paper reviews the rationale for theuse of these proteins as predictive factors, as well as the publishedliterature addressing the use of each one to predict response to hormonaltherapy, chemotherapy and radiotherapy. Results:HER-2, p53and BCL-2remaininadequately assessed as predictive factors in breast cancer. HER-2 evaluationis required for the selection of patients for trastuzumab (Herceptin®)therapy, as trials of this therapy have been limited to HER-2 overexpressors.HER-2 overexpression may be predictive of resistance to hormonal therapy.Anthracyclines are effective therapy for breast cancer regardless of HER-2status, but patients whose tumours overexpress HER-2 appear to receive thegreatest relative benefit from this therapy. Studies of HER-2 as a predictorof response to CMF and to radiotherapy are inconclusive at this time. No datayet exist to support the use of p53or BCL-2as predictivefactors in the therapy of breast cancer. Conclusions:At this point in time, there is inadequate evidenceto support the use of HER-2, p53or BCL-2to guide theselection of hormonal therapy, chemotherapy or radiotherapy for breast cancer.
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  • 24
    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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  • 25
    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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  • 26
    ISSN: 1569-8041
    Keywords: breast cancer ; camptothecins ; colorectal cancer ; GI147211 ; non-small-cell lung cancer ; topoisomerase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:GI147211 is a water-soluble synthetic analogue ofcamptothecin showing promising in vivoand in vitroantitumor activity and an acceptable toxicity profile. Patients and methods:Between April 1995 and November 1996, 67eligible patients with pretreated breast cancer (25 patients) andchemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23patients) were entered into three multicentric, non-randomized phase IItrials. Treatment schedule consisted of intravenous GI147211 administered ata dose of 1.2 mg/m2/day for five consecutive days every threeweeks. Results:Hematological toxicity was common with grade 3–4neutropenia in 54% of patients and neutropenic fever together or notassociated with infection in 14.5% of patients. Grade 3–4thrombocytopenia and grade 2–4 anemia were observed in 20% andin 68% of patients, respectively. Non-hematological toxicity wasgenerally mild to moderate and consisted mainly of gastrointestinal toxicity,asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d wasfeasible in 17 (25%) patients. The antitumor activity of GI147211 wasmoderate in breast cancer patients (3 partial responses (PRs), response rate(RR) 13%) and minimal in non-small cell lung cancer patients (2 PRs,RR 9%). No objective responses were obtained in colorectal patients. Conclusions:GI147211, at the dose and schedule employed in thisstudy, showed an acceptable safety profile but a modest antitumor activity inthe examined tumor types.
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  • 27
    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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  • 28
    ISSN: 1569-8041
    Keywords: chemotherapy ; chromosome aberrations ; malignant germ-cell tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 29
    Electronic Resource
    Electronic Resource
    Springer
    Biomedical microdevices 2 (2000), S. 305-316 
    ISSN: 1572-8781
    Keywords: membranes ; breast cancer ; oncology ; cell column regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Using microfabrication technology, we have developed a new experimental apparatus and technique which allow isolation of individual cells and which facilitate the study of kinetic volume changes and membrane permeability. The key component of the apparatus is a microdiffusion chamber which was constructed using silicon microfabrication technology and standard photolithography. The central unit of the chamber is a 1 μ m thick silicon nitride membrane with a center hole on the order of 2–3 μ m in diameter. The device is novel in its analysis of a single cell, instead of the traditional array of cells, and its avoidance of the damage artifacts and computational difficulties which are inherent in other, commonly used methods of cellular analysis. The device is used in conjunction with a predictive computer model which simulates the response of the entire membrane or a portion of the membrane to various permeant and impermeant concentrations. This study introduces the apparatus and the model, and illustrates the effectiveness of the new procedure by determining several membrane permeability coefficients for HBL-100 (healthy human breast line). The empirical data and theoretical data were combined to yield a water permability (L p) of 1.1 ± 0.5μ m/(min-atm) (mean ± 1 standard deviation) (N= 5) during the uncoupled transport of water at 22 ±C. In the presence of 6 M glycerol, the water permeability (L p), permeability coefficient (P S), and the reflection coefficient (σS) were determined to be 2.0 ± 0.63 μ m/(min-atm), 2.7E-5 ± 6.1E-6 cm-sec-1, and 0.76 ± 0.5 (N = 6). No previous values of these coefficients could be found for HBL-100 cells.
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  • 30
    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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  • 31
    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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  • 32
    ISSN: 1569-8041
    Keywords: biological/pathological characteristics ; breast cancer ; prognosis ; progression ; symptomatic/asymptomatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It is well known that mammographic screening reducesbreast cancer mortality. One possible explanation for this effect is thatscreening makes it possible to detect smaller breast cancers with fewerinvolved nodes, but another hypothesis is that some screening-detected tumorsare in a pathologically and biologically different phase of evolution fromthose that are detected clinically. The aim of the present study was tocompare the biological, pathological and clinical characteristics ofsymptomatic vs. asymptomatic breast cancers. Patients and methods:The study considers a series of 1916consecutive patients who underwent surgery for stage I and II infiltratingbreast cancer at Verona hospitals after having undergone ultrasound andmammography (at least one of which was positive). They were divided into twogroups on the basis of why they decided to undergo the imaging examinations:group A refers to the 1247 patients with a palpable lump, and group B to the616 who were asymptomatic. Results:The patients in group A were older, and had larger tumorsand a higher percentage of positive nodes than those in group B; they also hadsignificantly higher grade tumors, higher Ki-67 levels, and a higherpercentage of ER and PgR negative and c-erbB-2 positive tumors (allof the P-values were significant). A logistic regression analysisadjusted for tumor diameter and age showed a reduction in the significance ofeach of the considered variables, but all of them remained significantlyassociated with the modality of diagnosis except ER, PgR andc-erbB-2. Conclusions:Our results suggest that asymptomatic tumors arebiologically different from their clinically presenting counterparts, thusconfirming the hypothesis that progression towards greater malignancy mayoccur during the natural history of breast cancer.
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  • 33
    ISSN: 1569-8041
    Keywords: 4-OH-IF ; breast cancer ; drug combination ; human cell lines ; primary cultures ; VNB
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Vinorelbine and ifosfamide are active drugs againstbreast cancer, but the best treatment schedule has yet to be defined bypreclinical or clinical studies. The antitumor activity of4-hydroxy-ifosfamide (4-OH-IF), the active form of ifosfamide, and vinorelbine(VNB) and their interaction were investigated in two established breast cancercell lines (MCF-7 and BRC-230) and in 10 primary breast cancer cultures. Materials and methods:Cytotoxic activity was evaluated by ahighly efficient clonogenic assay (HECA). The median-effect principle wasapplied to evaluate synergistic and antagonistic interactions and thecorresponding combination index values were calculated. Cell cycleperturbations were analysed by flow cytometry. Results:In MCF-7 and BRC-230 cell lines the sequence VNB for 4hours followed by 4-OH-IF for 24 hours produced an antagonistic effect.Conversely, the inverse sequential scheme, 4-OH-IF → VNB providedsynergistic effects on both cell lines. The synergism was associated with astrong block in the G2-M phase. Synergistic activity of 4-OH-IF → VNBsequence was confirmed in 7 of 10 primary breast cancercultures. Conclusions:In conclusion, the sequence 4-OH-IF → VNBappeared to be the most effective scheme both in established cell lines andin primary breast cancer cultures.
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  • 34
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:Immediate adjuvant tamoxifen reduces disease recurrence andimproves survival in patients with early breast cancer. However, is it toolate to administer tamoxifen to patients who have already undergone treatment,but were unable to benefit from this adjuvant therapy? The French NationalCancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifenadministration in a randomized controlled trial. Patients and methods:From September 1986 to October 1989, womenwith primary breast cancer, who had undergone surgery, radiotherapy, and/orreceived adjuvant chemotherapy but not hormone therapy more than two yearsearlier, were randomized to receive either 30 mg/day tamoxifen or notreatment. The 10-year disease-free and overall survival rates of the twogroups of patients and of various subgroups were determined according to theKaplan–Meyer method and compared by the log-rank test. Results:This intention-to-treat analysis comprised 250 women inthe tamoxifen group and 244 in the control group. Patient characteristics(age, T stage, number of positive nodes, receptor status, and interval sincetumor treatment) were comparable in both groups. Delayed adjuvant tamoxifensignificantly improved overall survival only in node-positive patients and inpatients with estrogen receptor-positive (ER+) or progesteronereceptor-positive (PR+) tumors. Disease-free survival, however, wassignificantly improved in the global population and in several patientsubgroups (node-positive, ER+, PR+). Patients in whom the interval betweenprimary treatment and delayed adjuvant tamoxifen was greater than five yearsalso had significantly improved disease-free survival. Conclusions:Overall and disease-free survival results indicatethat delayed adjuvant tamoxifen administration (30 mg/day) is justified inwomen with early breast cancer, even if this treatment is initiated two ormore years after primary treatment.
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  • 35
    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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  • 36
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 37
    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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  • 38
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 1349-1351 
    ISSN: 1569-8041
    Keywords: breast cancer ; radiotherapy ; tumor lysis syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor lysis syndrome (TLS) is a rare serious acute complication of cancertherapy, reported mainly following chemotherapy in patients with large tumorload and chemosensitive disease. These are mainly patients with non-Hodgkin'slymphoma, leukemia and rarely in solid tumors. It is less frequently describedafter radiotherapy for lymphoid and hematological malignancies. TLS followingradiotherapy for solid tumors is a very rare complication. In thisreport/review we describe a seventy-three-year-old male patient withprogressive metastatic carcinoma of the breast to the lungs, liver and bone.He was referred for radiotherapy because of generalized bony pains. Thepatient was planned for sequential hemi-body irradiation starting with themore symptomatic upper half body. After premedication, he was given 8.5 Gy tothe mid point at the maximum chest separation with anterior lung attenuatorlimiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost tothe fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia,hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. Theseclinical and biochemical changes are typical of tumor lysis syndrome (TLS).Despite hydration, and treating the hyperuricemia, the patient developed comaand died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients aredescribed to avoid this frequently fatal complication.
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  • 39
    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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  • 40
    ISSN: 1569-8041
    Keywords: breast cancer ; erbB2 ; HER-2/neu ; tamoxifen ; therapy resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:We aimed to study the importance of erbB2 status in earlystage postmenopausal breast cancer for patients who participated in a trialof five vs. two years of adjuvant tamoxifen. Patients and methods:We analysed the erbB2 status of the tumoursfrom 577 patients participating in the trial, either by a DNA amplificationassay (n = 181) or by measurement of the protein level with flowcytometry (n = 396). Results:ErbB2 was overexpressed or gene amplified in 102 of thepatients (18%). Overall, erbB2-positive patients had a significantlylower recurrence-free probability than others, 62% at five years ascompared to 83%, and showed a significantly decreased breast cancersurvival rate (P = 0.0007). ErbB2 status was significantlyassociated with recurrence and death in Cox multivariate analysis, adjustingfor nodal status, tumour size and estrogen receptor status. The relative riskof recurrence (RR) for five vs. two years of tamoxifen was analysed inrelation to erbB2 status for patients still disease-free two years aftersurgery. Whereas erbB2-negative patients showed significant benefit fromprolonged treatment (RR = 0.62, 95% confidence interval (95%CI): 0.42–0.93), no benefit was evident for erbB2-positive patients (RR= 1.1, 95% CI: 0.41–3.2). When the same analysis was restrictedto ER-positive patients a similar difference in relative hazard was obtainedbut the difference was not strictly significant (P = 0.065). Conclusions:For early stage breast cancer patients treated withadjuvant tamoxifen, overexpression of erbB2 is an independent marker of poorprognosis. The results suggest that overexpression decreases the benefit fromprolonged tamoxifen treatment.
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  • 41
    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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  • 42
    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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  • 43
    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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  • 44
    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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  • 45
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; elderly ; idarubicin ; oral chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 46
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; docetaxel ; feasibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:Docetaxel is an active agent in thetreatment of metastatic breast cancer. We evaluated the feasibility ofdocetaxel-based sequential and combination regimens as adjuvant therapies forpatients with node-positive breast cancer. Patients and methods:Three consecutive groups of patients withnode-positive breast cancer or locally-advanced disease, aged ≤70 years,received one of the following regimens: a) sequential A → T → CMF:doxorubicin 75 mg/m2 q 3 weeks × 3, followed by docetaxel 100mg/m2 q 3 weeks × 3, followed by i.v. CMF days 1 + 8 q 4weeks × 3; b) sequential accelerated A → T → CMF: A and T wereadministered at the same doses q 2 weeks; c) combination therapy: doxorubicin50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks × 4,followed by CMF × 4. When indicated, radiotherapy was administeredduring or after CMF, and tamoxifen started after the end of CMF. Results:Seventy-nine patients have been treated. Median age was48 years. A 30% rate of early treatment discontinuation was observedin patients receiving the sequential accelerated therapy (23% duringA → T), due principally to severe skin toxicity. Median relativedose-intensity was 100% in the three treatment arms. The incidence ofG3–G4 major toxicities by treated patients, was as follows: skintoxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%;b: 20%; c: 3%. The incidence of neutropenic fever was a:30%; b: 13%; c: 48%. After a median follow-up of 18months, no late toxicity has been reported. Conclusions:The accelerated sequential A → T → CMFtreatment is not feasible due to an excess of skin toxicity. The sequentialnon accelerated and the combination regimens are feasible and under evaluationin a phase III trial of adjuvant therapy.
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  • 47
    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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  • 48
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 145-152 
    ISSN: 1432-1335
    Keywords: Key words Angiogenesis ; Apoptosis ; Glioma ; Thymidine phosphorylase ; Vascular endothelial growth factor ; AbbreviationsTP thymidine phosphorylase ; GBM glioblastoma ; AA anaplastic astrocytoma ; LGA low-grade astrocytoma ; VEGF vascular endothelial growth factor ; RT-PCR reverse transcriptase/polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
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  • 49
    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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  • 50
    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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  • 51
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Gliomatosis cerebri ; MRT-Diagnose ; Enzephalitis ; Key words Gliomatosis cerebri ; MRI ; Diagnosis ; Encephalitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure. The clinical course, differential diagnosis, and literature are summarized briefly.
    Notes: Zusammenfassung Die Diagnose der seltenen Gliomatosis cerebri kann nur in Zusammenschau von klinischen, radiologischen und histopathologischen Befunden gestellt werden. Im vorliegenden Artikel berichten wir über 2 Patienten, bei denen intra vitam nach stereotaktischer Hirnbiopsie die Diagnose Gliomatosis cerebri gesichert wurde. Da in beiden Fällen für Gliomatosis cerebri ungewöhnlich hochgradig entdifferenzierte Tumorzellen vorlagen, wurde die Diagnosefindung durch atypische Befunde wie Kontrastmittelaufnahme im MRT und klinische Zeichen der intrakraniellen Drucksteigerung erschwert. Klinischer Verlauf, Differentialdiagnosen und Literatur werden kurz dargestellt.
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  • 52
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Hallervorden-Spatz-Krankheit ; Parkinsonsyndrom ; MRT ; 123J-β-CIT ; 123J-IBZM ; Keywords Hallervorden-Spatz Disease ; Parkinson's syndrome ; MRI ; 123I-β-CIT ; 123I-IBZM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Hallervorden-Spatz disease (HSD), a rare extrapyramidal motor illness, is usually only confirmed after death. In vivo diagnosis has relied hitherto on the combination of typical magnetic resonance imaging (MRI) findings (the “eye of the tiger” sign) and heterogeneous clinical symptoms of movement disorder which have been regarded as almost pathognomonic. We report on the diagnostic contribution of 123J-β-CIT single photon emission computed tomography (SPECT) and 123J-IBZM SPECT in akinetic-rigid Parkinson's syndrome occurring in a case of HSD. In contrast to Parkinson's disease and multisystem atrophies, the results of both tests were normal. This constellation of findings shows that the degeneration lies primarily outside the nigrostriatal system, supporting arguments for the nosologic distinction of HSD from other extrapyramidal illnesses.
    Notes: Zusammenfassung Die Diagnose der Hallervorden-Spatz-Krankheit (HSD), einer seltenen extrapyramidal-motorischen Erkrankung, konnte gewöhnlich erst postmortal gesichert werden. Bislang galt der typische MRT-Befund mit dem “Tigerauge-Zeichen” in Kombination mit der heterogen klinischen Symptomatik von Bewegungsstörungen als nahezu pathognomonisch und diente zur Diagnosestellung zu Lebzeiten. In der vorliegenden Kasuistik soll der diagnostische Beitrag von 123J-β-CIT und 123J-IBZM-SPECT bei einem akinetisch-rigiden Parkinsonsyndrom im Rahmen einer HSD dargestellt werden. Für beide Untersuchungen wurden im Gegensatz zum M. Parkinson und Multisystematrophien Normalbefunde gefunden. Diese Befundkonstellation zeigt einerseits, dass die Degeneration primär außerhalb des nigrostriatalen Systems liegt, und andererseits unterstützt sie die Diskussion der nosologischen Abgrenzung der HSD von anderen extrapyramidalen Erkrankungen.
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  • 53
    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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  • 54
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    Der Nervenarzt 71 (2000), S. 91-95 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Creutzfeldt-Jakob-Krankheit ; Diagnostik ; Diffussionswichtung ; MRT ; Bildgebung ; Übertragbare spongiforme Enzephalopathien ; Key words Creutzfeldt-Jakob disease ; Diagnosis ; Diffusion-weighted image ; MRI ; Brain images ; Transmissible spongiform encephalopathies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Today the diagnosis of Creutzfeldt-Jakob disease (CJD) is proven only postmortem or by evidence of neuropathology. During the patient's lifetime EEG recordings or cerebrospinal fluid analysis may support the diagnosis. In most cases, T2-MRI scans show hyperintensities of the basal ganglia. A new imaging technique called diffusion-weighted MRI (DWI) has recently been established. The sensitivity of DWI was evaluated in five patients suspected of CJD. All five cases showed hyperintense signal changes in the basal ganglia on DWI sequences. These findings were more pronounced in DWI than in T2, FLAIR, or PD-weighted images. Thus, DWI seems to be the most sensitive sequence for detecting changes in patients with suspected CJD. Moreover, its short scanning time ensures that fewer artifacts occur, especially in the case of myoclonus.
    Notes: Zusammenfassung Die sichere Diagnose der Creutzfeldt-Jakob-Krankheit kann nur bioptisch oder autoptisch durch Untersuchung von Hirngewebe gestellt werden. Die klinische Verdachtsdiagnose erhärten können technische und laborchemische Untersuchungen; hierzu gehört neben dem EEG die Surrogatmarkerbestimmung im Liquor. Nachdem sich bei der Mehrzahl der Patienten Veränderungen der Basalganglien gezeigt haben, gehört das MRT zu den bildgebenden Verfahren, die bei Verdacht auf CJD eingesetzt werden können. Inzwischen ist die Diffusionswichtung (DWI) in die neuroradiologische Diagnostik eingeführt worden. DWI-gewichtete MRTs bei 5 CJD-Patienten wurden von uns untersucht. Alle 5 Fälle zeigten im DWI-MRT signalintense Veränderungen der Stammganglien. Diese Veränderungen waren jeweils deutlicher als in der T2, Flair- oder Protonenwichtung. Das DWI-MRT halten wir für sensitiver zum Nachweis kortikaler und basaler Veränderungen bei CJD-Patienten im Vergleich zu Standardsequenzen. Durch die kurze Untersuchungszeit können besonders bei den häufig vorhandenen Myoklonien andere Wichtungen aufgrund von Bewegungsartefakten oftmals nicht in der gewünschten Qualität durchgeführt werden.
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  • 55
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    Der Unfallchirurg 103 (2000), S. 1079-1085 
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Knie ; MRT ; Arthroskopie ; Meniskus ; Key words Knee ; MRI ; Arthroscopy ; Meniscus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In order to assure diagnostic accuracy, 172 knee joints were examined prospectively by MRI. After MRI, all knee joints were examined by arthroscopy. Tears of the medial meniscus were found in 102 patients, the lateral meniscus showed a tear in 29 cases. Assuming that arthroscopy represents the golden standard of diagnostic measure concerning the knee joint, it can be stated that false-positive MRI findings on the medial and lateral meniscus were diagnosed in three cases and false-negative MRI findings were diagnosed for two knee joints regarding the medial meniscus and four times regarding the lateral meniscus. For the medial meniscus a sensitivity of 98%, a specificity of 96%, an accuracy of 94%, and the positive and negative value of prediction were calculated at 97% each. Regarding the lateral meniscus, a sensitivity of 85%, a specificity of 98%, an accuracy of 92%, a positive predictive value of 88%, and a negative predictive value of 85% were found. Under the prerequisite that the MRI is carried out correctly and assessed by an experienced radiologist, the accuracy of the MRI for meniscus diagnosis is almost equivalent to the one by arthroscopy. Under these conditions, MRI can be recommended when no safe and sufficient clinical diagnosis can be made. The rate of unnecessary arthroscopies with a pure diagnostic purpose can be lowered significantly by means of MRI.
    Notes: Zusammenfassung Zur Überprüfung der diagnostischen Treffsicherheit wurden prospektiv 172 Kniegelenke mittels Magnetresonanztomographie (MRT) untersucht. Nach der MRT erfolgte bei allen Kniegelenken die arthroskopische Überprüfung der bildgebenden Diagnose. Rissbildungen des Innenmeniskus fanden sich bei 102 Patienten, am Außenmeniskus wurde 29-mal ein Riss befundet. Unter der Annahme, dass die Arthroskopie der “golden standard” diagnostischer Maßnahmen am Kniegelenk darstellt, ergab sich, dass falsch-positive MRT-Befunde am Innen- und Außenmeniskus in jeweils 3 Fällen und falsch-negative MRT-Befunde am Innenmenikus bei 2 Kniegelenken und am Außenmeniskus 4-mal erhoben wurden. Für den Innenmeniskus wurde eine Sensitivität von 98%, eine Spezifität von 96%, eine Genauigkeit von 94% und der positive bzw. negative Vorhersagewert mit jeweils 97% errechnet. Bezüglich des Außenmeniskus ließ sich eine Sensitivität von 85%, eine Spezifität von 98%, eine Genauigkeit von 92%, ein positiver Vorhersagewert von 88% und ein negativer Vorhersagewert von 85% ermitteln. Unter der Voraussetzung, dass die MRT korrekt durchgeführt und von einem erfahrenen Radiologen befundet wird, ergibt sich eine annähernd gleichwertige Treffsicherheit der MRT für die Meniskusdiagnostik wie mit der Arthroskopie. Die MRT kann daher unter diesen Voraussetzungen zur Anwendung empfohlen werden, wenn klinisch keine ausreichend sichere Diagnose zu stellen ist. Die Rate unnötiger rein diagnostischer Arthroskopien kann durch die MRT entscheidend gesenkt werden.
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  • 56
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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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  • 57
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    Der Nervenarzt 71 (2000), S. 411-415 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Kufs ; Neuronale Zeroidlipofuszinose ; Demenz ; PET ; MRT ; Key words Kufs disease ; Neuronal ceroid lipofuscinosis ; Dementia ; PET ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The case of a 35-year-old man with progressive dementia from the age of 17 is presented. Clinical examination showed mild extrapyramidal and cerebellar signs and rare myoclonus. Neuropsychological evaluation disclosed severe cognitive deficits. Magnetic resonance imaging (MRI) revealed moderate generalized atrophy with abnormal iron deposition in the basal ganglia. Positron emission tomography (PET) with 18-fluorodeoxyglucose (18-FDG) demonstrated clear temporoparietal hypermetabolism. The clinical symptoms and course are typical for the rare adult type of neuronal ceroid lipofusconoses (Kufs' disease). The diagnosis is supported by the electron microscope detection of an abnormal accumulation of lipid vacuoles and lipofuscin in the eccrine sweat glands and the rectal ganglia cells.
    Notes: Zusammenfassung Berichtet wird der Fall eines 35-jährigen Patienten mit langsam progredienter Demenz seit dem 18. Lebensjahr. Zum Zeitpunkt der Untersuchung fielen klinisch eine leichtgradige extrapyramidale und zerebelläre Symptomatik sowie seltene Myoklonien auf, während die neuropsychologische Testung ausgeprägte kognitive Defizite ergab. Die kraniale Magnetresonanztomographie zeigte eine mäßige globale Atrophie und eine abnorme Eisenablagerung in den Basalganglien. In der Positronenemissionstomographie mit 18-FDG war ein deutlicher temporoparietaler Hypometabolismus erkennbar. Klinik und Verlauf sind typisch für die seltene adulte Variante der neuronalen Zeroidlipofuszinosen (Kufs-Typ). Diese Diagnose wird gestützt durch den elektronenmiroskopischen Nachweis abnormer Akkumulationen von Fettvakuolen und Lipofuszinablagerungen in den ekkrinen Schweißdrüsen der Haut und in den rektalen Ganglienzellen.
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  • 58
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Manganintoxikation ; Parkinsonismus ; MRT ; Verlaufskontrolle ; L-Dopa-Therapie ; Key words Manganese intoxication ; Parkinsonism ; MRI ; Follow-up study ; L-dopa treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Manganese intoxication is an unusual, severe form of intoxication. This report deals with a patient now 80 years old who accidentally ingested a solution of potassium permanganate for a period of at least 4 weeks 14 years ago. Since then, the patient suffers from a mild parkinsonian syndrome and distally accentuated polyneuropathies. Psychiatric disorders, especially demential or depressive symptoms, were not observed. Manganese analysis of his hair still shows a clear increase in manganese concentration. The MRI of his brain showed no pathological changes, in particular none of those often described with symmetric signal elevation in T1 in the area of the basal ganglia. In this study, we present clinical, laboratory, and neuroradiological findings. Unusual in this case with a short exposition is the long duration and clinical improvement without L-dopa treatment.
    Notes: Zusammenfassung Eine Manganintoxikation ist eine ungewöhnliche, schwere Intoxikationsform. Wir berichten über einen jetzt 80-jährigen Patienten, der vor 14 Jahren über die Dauer von mindestens 4 Wochen versehentlich Kaliumpermanganat eingenommen hatte. Der Patient leidet weiterhin unter einem leichten Parkinsonsyndrom und einer distal betonten Polyneuropathie. Psychiatrische St¨rungen, insbesondere ein dementielles oder depressives Symptom, fanden sich nicht mehr. Die Mangananalysen der Haare zeigen auch jetzt noch deutlich erhöhte Konzentrationen. Das MRT des Gehirns erbrachte keinen pathologischen Befund, insbesondere keine häufig bei Manganintoxikationen beschriebenen Veränderungen mit symmetrischen Signalanhebungen in T1-Wichtung im Bereich der Basalganglien (Globus pallidus). In einer aktuellen Untersuchung werden klinische, laborchemische sowie neuroradiologische Ergebnisse vorgestellt. Die Besonderheit des Falles erklärt sich aus einer kurzen Expositionsdauer mit einer langen Verlaufszeit und klinischer Befundbesserung ohne L-Dopa-Behandlung.
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  • 59
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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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  • 60
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    International journal of clinical oncology 5 (2000), S. 200-203 
    ISSN: 1437-7772
    Keywords: Key words Small cell carcinoma of the ovary ; Pregnancy Paclitaxel ; MRI ; Facial palsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Small cell carcinoma of the ovary (SCCO) is a highly aggressive malignancy that affects young females. The disease is fatal in nearly all patients with disease categorized as higher than stage IA. A 30-year-old Japanese woman was diagnosed, while pregnant, as having bilateral small cell carcinoma, pulmonary type, a rare finding. She received three courses of JP chemotherapy (carboplatin, 525 mg; cisplatin, 120 mg) and three courses of PVP chemotherapy (peplomycin, 30 mg; vinblastin, 12 mg; cisplatin, 120 mg). Computed tomography scans were taken during and after the period in which she received chemotherapy showed growing multiple metastatic tumors and massive ascites. Third-line chemotherapy with paclitaxel (225 mg) was then initiated. Although the lymphadenopathy and massive ascites were alleviated, bone marrow suppression intervened. The patient died 18 months after being diagnosed. To our knowledge, this is third reported case of SCCO to be diagnosed during pregnancy, and the first reported case of bilateral disease diagnosed during pregnancy.
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  • 61
    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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  • 62
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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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  • 63
    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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  • 64
    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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  • 65
    ISSN: 1437-7772
    Keywords: Key words Endometrial carcinoma ; MRI ; Diagnosis ; Minimally invasive therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Magnetic resonance imaging (MRI) provides precise staging of endometrial carcinoma. However, we have sometimes experienced patients with microscopic extrauterine extension in whom MRI showed the disease as being limited to the uterus. We studied indirect MRI signs for microscopic extrauterine spread of endometrial carcinoma which outwardly seemed to be limited to within the uterus. Methods. MRI studies and the clinical records of 100 patients with surgically proven endometrial carcinoma were retrospectively reviewed. We evaluated: (1) MRI staging, (2) tumor growing at the orifices of the fallopian tube in the uterine fundus, (3) hydrosalpinx, and (4) ascites, in each MRI study. Results. Surgical specimens showed that 12 of the 100 patients had extrauterine spread, with 1 patient showing both ovarian extension and omental metastasis; there ovarian extension in 3, extension to the fallopian tubes in 3, omental metastasis in 1, and positive peritoneal cytology in 4. Tumor growing at the orifices of the fallopian tubes with deep myometrial invasion showed higher accuracy for predicting microscopic intrauterine spread (82.0%) although it was not significantly different from the accuracy of deep myometrial invasion anywhere within the uterus (75.0%). However, tumor growing at the orifices of the fallopian tubes in a patients with stage Ia disease showed a high negative predictive value (89.7%). Hydrosalpinx had the highest specificity (98.9%) and accuracy (88.0%); however, it did not seem to be practical because it was observed in only 2 patients. Ascites in postmenopausal patients showed higher specificity (93.5%), although it was not considered to be useful in the premenopausal patients. Conclusion. Tumor extension at the orifices of the fallopian tubes in patients with stage Ia disease, and ascites in postmenopausal patients on MRI seemed to be predictive factors for microscopic extrauterine spread.
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  • 66
    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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  • 67
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    Skeletal radiology 29 (2000), S. 40-44 
    ISSN: 1432-2161
    Keywords: Key words Subchondral insufficiency fracture ; Femoral head ; Medial femoral condyle ; Osteonecrosis ; MRI ; X-ray
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This case report documents the clinical, radiographic, and histologic findings in a 69-year-old obese man, who had subchondral insufficiency fracture both in the femoral head and medial femoral condyle. On plain radiographs, both lesions underwent subchondral collapse. Magnetic resonance images of the left hip showed a bone marrow edema pattern with associated low-intensity band on T1-weighted images, which was convex to the articular surface. The histopathologic findings in the hip and knee were characterized by the presence of a subchondral fracture with associated callus and granulation tissue along both sides of a fracture line. There was no evidence of antecedent osteonecrosis. To our knowledge, this is the first case report to describe the multiple occurrence of collapsed subchondral insufficiency fracture.
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  • 68
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    Skeletal radiology 29 (2000), S. 45-48 
    ISSN: 1432-2161
    Keywords: Key words Cystic fibrous dysplasia ; Giant cell tumor ; Femur ; X-ray ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report the case of a 43-year-old man who presented with an osteolytic and expansive lesion in the left distal femur mimicking a giant cell tumor. Magnetic resonance imaging (MRI) showed that most of the lesion was cystic, and histological examination revealed fibrous dysplasia with marked cystic degeneration. Radiographic findings of cystic fibrous dysplasia in the end of a long bone may be similar to those of a giant cell tumor, and a biopsy is essential for the final diagnosis.
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  • 69
    ISSN: 1432-2161
    Keywords: Key words Hemangiopericytoma ; Tibia ; MRI ; Angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The Magnetic Resonance Imaging (MRI) appearances of primary osseous hemangiopericytoma (HPC) have been rarely described. We report on a 46-year-old Chinese man with primary osseous HPC of the right tibia. The characteristic vascular distribution of this tumor, presenting with a ”spoke-wheel” appearance on MR images and with angiographic correlation, is described. Although not pathognomonic, this MR appearance may be an important finding in suggesting the diagnosis of osseous HPC.
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  • 70
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    Skeletal radiology 29 (2000), S. 555-562 
    ISSN: 1432-2161
    Keywords: Keywords Diffusion ; MRI ; Skeletal system ; Spine ; neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This article reviews the principles of diffusion-weighted imaging (DWI) and recent results in DWI of the musculoskeletal system. The potential of DWI in the diagnosis of pathology of the musculoskeletal system is discussed. DWI is a relatively new MR imaging technique that has already been established in neuroradiology, especially in the early detection of brain ischemia. The random motion of water protons on a molecular basis can be measured with DWI. To date DWI of the abdomen and of the musculoskeletal system has only been employed in scientific studies, but first results indicate that it may also be beneficial in these fields. Different diffusion characteristics have been found in normal tissues such as muscle, fat and bone marrow. Also, pathologic entities such as neoplasms, post-therapeutic soft tissue changes and inflammatory processes can be differentiated. Normal muscle shows significantly higher diffusion values than subcutaneous fat and bone marrow, due to a higher mobility of water protons within muscle. Soft tissue tumors exhibit a significantly lower diffusion value compared with post-therapeutic soft tissue changes and inflammatory processes. Necrotic tumor tissue can be distinguished from viable tumor due to significantly higher diffusion of water protons within necrotic tissue.
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  • 71
    ISSN: 1432-2161
    Keywords: Keywords Gaucher disease ; MRI ; Enzyme replacement therapy ; Liver ; Spleen ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose. To determine whether T1-weighted magnetic resonance (MR) images can demonstrate response in the marrow of patients with type 1 Gaucher disease treated with enzyme replacement therapy (ERT) and to determine whether a relationship exists between liver and spleen volume reductions and visible marrow changes. Patients. Forty-two patients with type 1 Gaucher disease were evaluated on at least two occasions. Thirty-two patients received ERT. Of these patients, 15 had a baseline examination prior to the initiation of ERT. The remaining 10 patients did not receive ERT. Design. T1-weighted and gradient recalled echo (GRE) coronal images of the femurs and hips were obtained. Concurrently, liver and spleen volumes were determined using contiguous breath-hold axial gradient-echo images. T1-weighted images of the hips and femurs were evaluated to determine change or lack of change in the yellow marrow. Results. Of the 32 patients receiving ERT, 14 (44%) demonstrated increased signal on T1-weighted images suggesting an increase in the amount of yellow marrow. If only the 15 patients with a baseline examination were considered, the response rate to ERT was 67%. Using Student’s t-test a highly significant correlation (P〈0.005) was found between marrow response and reduction in liver and spleen volume. Conclusions. Marrow changes in patients receiving ERT can be detected by T1-weighted images. This response correlated with reductions in visceral volumes (P〈0.0005).
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  • 72
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    Skeletal radiology 29 (2000), S. 597-600 
    ISSN: 1432-2161
    Keywords: Keywords Parosteal osteosarcoma ; Telangiectatic osteosarcoma ; Dedifferentiation ; Femur ; Radiography ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A unique case of parosteal osteosarcoma (POS) of the proximal femur, with areas of telangiectatic dedifferentiation, in a 28-year-old woman is reported. The patient had a 7-week history of pain and swelling in her right thigh. A biopsy diagnosis of POS was established. The patient was treated with two cycles of intra-arterial chemotherapy, followed by limb salvage surgery. Histological examination of the resected specimen showed POS with areas of dedifferentiation composed of high-grade telangiectatic osteosarcoma with associated secondary aneurysmal bone cyst change.
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  • 73
    ISSN: 1432-2161
    Keywords: Keywords Ewing sarcoma ; Primitive neuroectodermal tumour ; Radiography ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective.To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/ primitive neuroectodermal tumour (PNET). Design. Retrospective review of case notes and available imaging was carried out. Patients. Six patients (4 male, 2 female; mean age 27years, range 19–44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. Results and conclusions. Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous ”skip” metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear.
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  • 74
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    Skeletal radiology 29 (2000), S. 656-659 
    ISSN: 1432-2161
    Keywords: Keywords Osteoblastoma-like osteosarcoma ; Osteosarcoma ; Aggressive osteoblastoma ; Fibula ; Radiography ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an osteoblastoma-like osteosarcoma in the right proximal fibula in a 22-year-old woman. Radiographs showed an irregular osteolytic lesion from the metaphysis to the epiphysis in the proximal fibula with partial destruction of cortical bone. Tissue from a biopsy indicated a typical osteoblastoma. Curettage and bone graft was performed. One year after the surgery, local recurrence occurred, and a wide excision was performed. Histological examination of the en-bloc surgical specimen revealed the tumor had permeated through the host bony trabeculae, although the nuclear atypia was not marked. Immunohistochemical expression of MIB-1 was detected in 9.0% of cells.
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  • 75
    ISSN: 1432-2161
    Keywords: Keywords Acute lymphoblastic leukemia ; Chemotherapy ; Spine ; Tunneling Schmorl’s nodes ; CT ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We present a 70-year-old woman with pre-B acute lymphoblastic leukemia in whom serial imaging studies showed the development of multiple vertebral collapse, and communicating superior and inferior Schmorl’s nodes creating a longitudinal channel (”tunneling” Schmorl’s nodes) through the anterior aspect of T12 to L3 vertebral bodies of her osteoporotic thoracolumbar spine. This was observed after achieving complete remission of the disease and during maintenance therapy. The finding is felt to be secondary to iatrogenic exacerbation of osteoporosis.
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  • 76
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    Skeletal radiology 29 (2000), S. 664-667 
    ISSN: 1432-2161
    Keywords: Keywords Giant cell tumor ; Multiple mid-foot bones ; Reconstructive surgery ; Radiography ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report on a patient who had giant cell tumor involving multiple bones of the mid-foot. The tumor originated from the navicular bone, but also destroyed the cuboid, and all cuneiform bones. This unusual presentation of giant cell tumor presented a therapeutic challenge for the surgeons. The patient was treated with en bloc resection and the bony defect replaced with a massive iliac crest graft which united within 9 months and has remained stable for 7 years without local recurrence, and with excellent function of the foot.
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  • 77
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    Skeletal radiology 29 (2000), S. 224-226 
    ISSN: 1432-2161
    Keywords: Key words Intraosseous neurilemmoma (schwannoma) ; Primary bone neoplasm ; Metacarpal ; X-ray ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intraosseous schwannoma (neurilemmoma) is an extremely rare, benign neoplasm, constituting less than 0.2% of primary bone tumors. It infrequently involves the bones of the hand. We present a case of intraosseous neurilemmoma of the metacarpal.
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  • 78
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    Skeletal radiology 29 (2000), S. 231-234 
    ISSN: 1432-2161
    Keywords: Key words Hemangioma ; Ulna ; CT ; MRI ; X-ray
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  An 18-year-old woman presented with left elbow joint pain. Radiographs and computed tomographic scan showed a well-defined osteolytic lesion of the left ulna associated with a honeycomb appearance on the radiographs. Magnetic resonance images showed intermediate signal intensity on T1-weighted images and mixed intermediate and high signal intensities on T2-weighted images. Only the periphery of the lesion enhanced with intravenously injected gadolinium-diethylenetriamine pentaacetic acid. The lesion was curetted to avoid pathologic fracture, and a histologic diagnosis of cavernous hemangioma of bone was made. Hemangioma involving the ulna is rare, but should be included in the differential diagnosis of a radiographic osteolytic lesion with a honeycomb appearance.
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  • 79
    ISSN: 1432-2161
    Keywords: Key words Soft tissue neoplasm ; Metastasis ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To describe a series of patients with no known primary malignancy who presented with a solitary unsuspected soft tissue metastasis masquerading as a soft tissue sarcoma, and secondarily to describe the imaging appearance of these lesions. Design. Records of two academic hospitals with active orthopedic oncology services were reviewed for patients meeting the above criteria. Clinical charts were examined, and the imaging appearance of the soft tissue lesions retrospectively reviewed. Patients. Of 1421 patients examined for soft tissue lesions, 11 were found who met the above criteria. Results. Of the 11 patients whose initial presentation was a solitary soft tissue metastasis, eight were found to have a primary lung cancer, two were diagnosed with adenocarcinoma of unknown primary, and adenocarcinoma of the colon was discovered in the remaining patient. Conclusions. The clinical presentation of a solitary soft tissue metastasis without a known primary malignancy is a rare occurrence, with an incidence of approximately 0.8%. Lung cancer is the primary neoplasm in a high percentage of these cases.
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  • 80
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    Skeletal radiology 29 (2000), S. 293-297 
    ISSN: 1432-2161
    Keywords: Key words Angiomyolipoma (AML) ; Soft tissue ; Thigh ; MRI ; CT ; Angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 41-year-old man presented with an asymptomatic mass in the right medial thigh. Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the right adductor muscles. The margins of the mass exhibited high signal intensity and the rest showed low or iso signal intensity on T1-weighted MR images. However, the high signal intensity was decreased on T2-weighted images with fat suppression. The central part of the tumor was of inhomogeneous high signal intensity on T2-weighted images; after Gd-DTPA injection it enhanced inhomogeneously on T1-weighted images with fat suppression. On dynamic computed tomography (CT) in the arterial phase, there were strongly enhancing spotty areas in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological diagnosis of angiomyolipoma (AML) in the thigh was made.
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  • 81
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    Skeletal radiology 29 (2000), S. 346-348 
    ISSN: 1432-2161
    Keywords: Key words Amyloid tumor ; Tibia ; Periosteum ; Bilateral ; MRI ; Bilateral metachronous periosteal tibial amyloid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Localized primary periosteal amyloid tumors are extremely rare. A case of bilateral tibial amyloid tumor is presented. A 62-year-old woman initially presented with a painful mass in the anterior aspect of the right leg. There was no evidence of underlying systemic disease, including chronic infection or malignancy. Based on the results of resistance with Congo red staining to treatment with potassium permanganate and positivity for kappa light chain, we classified this particular case as AL-type amyloidosis. The patient noticed a swelling in the opposite leg 2 years later. The second tumor was also an AL-type amyloidoma. Amyloid tumors are generally solitary. This is the first case of bilateral periosteal amyloid tumors of the AL-type occurring in the tibiae.
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  • 82
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    Skeletal radiology 29 (2000), S. 387-391 
    ISSN: 1432-2161
    Keywords: Key words Trauma ; Hand ; Sonography ; Ultrasound ; Annular pulleys ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To evaluate the sonographic (US) appearance of digital annular pulley (DAP) tears in high-level rock climbers. Design and patients. We performed a retrospective analysis of the US examinations of 16 high-level rock climbers with clinical signs of DAP lesions. MRI and surgical evaluation were performed in five and three patients respectively. The normal US and MRI appearances of DAP were evaluated in 40 and three normal fingers respectively. Results. Nine of 16 patients presented a DAP tear. In eight subjects (seven with complete tears involving the fourth finger and one the fifth finger), US diagnosis was based on the indirect sign of volar bowstringing of the flexor tendons. Injured pulleys were not appreciated by US. Tears concerned the A2 and A3 in six patients and the A3 and A4 in two patients. A2 pulley thickening and hypoechogenicity compatible with a partial tear was demonstrated in one patient. MRI and surgical data correlated well with the US findings. Four patients had tenosynovitis of the flexor tendons but no evidence of pulley disruption. US examinations of three patients were normal. In the healthy subjects US demonstrated DAP in 16 of 40 digits. Conclusion. US can diagnose DAP tears and correlates with the MRI and surgical data. Because of its low cost and non-invasiveness we suggest US as the first imaging modality in the evaluation of injuries of the digital pulley.
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  • 83
    ISSN: 1432-2161
    Keywords: Key words Bones ; infection ; Bones ; radionuclide studies ; MRI ; comparative studies ; Bones ; MRI studies ; MRI ; extremities ; Bones ; immunoscintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. A retrospective study of the validity of combined bone scintigraphy (BS) and immunoscintigraphy (IS) using 99mTc-labelled murine antigranulocyte antibodies (MAB) and magnetic resonance imaging (MRI) in chronic post- traumatic osteomyelitis. Design and patients. The results of MRI and combined BS/IS of 19 lesions in 18 patients (13 men, 5 women; mean age 45 years, range 27–65 years) were independently evaluated by two radiologists and one nuclear medicine physician with regard to bone infection activity and extent. The patient group was a highly selective collection of clinical cases: the average number of operations conducted because of relapsing infection was eight (range 2–27), the average time interval between the last surgical intervention and the present study was 6.5 years (range 3 months to 39 years), and from the first operation was 14 years (range 1.5–42 years). Interobserver agreement on MRI was measured by kappa statistics. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for MRI and the nuclear medicine studies. Results. For MRI/nuclear medicine, a sensitivity of 100%/77%, a specificity of 60%/50%, an accuracy of 79%/61%, a PPV of 69%/58% and a NPV of 100%/71% were calculated. Four MR examinations were false positives because of postsurgical granulation tissue. A high degree of interobserver agreement was found on MRI (κ=0.88). A low-grade infection was missed on two scintigrams, while four were false positive because of ectopic haematopoietic bone marrow, and in one examination the anatomical distortion resulted in an inaccurate assignment of the uptake leading to false positive findings. Image analysis was frequently hindered by susceptibility artefacts due to residual abrasions of metallic implants after removal of orthopaedic devices (15/18 patients); this led to limited assessment in 17% (3/18 patients). Conclusion. Acute activity in a chronic osteomyelitis can be excluded with high probability if the MRI findings are negative. In the first postoperative year fibrovascular scar cannot be distinguished accurately from reactivated infection on MRI and scintigraphy may improve the accuracy of diagnosis. MRI is more sensitive in low-grade infection during the later course than combined BS/IS. Scintigraphic errors due to ectopic, peripheral, haematopoietic bone marrow can be corrected by MRI.
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  • 84
    ISSN: 1432-2161
    Keywords: Key words Tuberculosis ; Sternum ; Clavicle ; CT ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To describe the imaging findings in sterno-clavicular tubercular involvement. Design and patients. Fifteen patients with pathologically proven tuberculosis of the sternum and clavicle were retrospectively evaluated. Routine radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were used in some or all of the patients. Clinical information and imaging features were evaluated in each case. Results. Eight patients had sterno-clavicular joint (SCJ) involvement, five had isolated sternal involvement and two had isolated clavicular involvement. Seven patients were evaluated with only CT, six with only MRI and two with both. There were eight male and seven female patients, varying in age between 16 and 78 years. Fever, swelling and pain were common presenting symptoms. Two patients were HIV positive. Radiographs were positive in only eight patients. Destruction and signal intensity (SI) changes of the sternum and clavicle, destruction of the cartilage, soft tissue changes representing granulation tissue/abscess, displacement of the adjacent structures (vessels, trachea, etc.) and inflammatory changes in the adjacent structures in the form of cellulitis and myositis were common imaging features. Conclusions. All imaging methods can provide complementary information regarding sterno-clavicular tubercular involvement that is helpful for determination of the therapy. MRI is useful in determining the extent of the lesion, particularly marrow involvement and soft tissue extent.
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    Skeletal radiology 29 (2000), S. 477-480 
    ISSN: 1432-2161
    Keywords: Key words Diabetes mellitus ; Muscle, infarction ; Short T1 ; Hemorrhage ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We describe a case of diabetic muscle infarction which had atypical features of hyperintensity of the affected muscle on T1-weighted images. Biopsy was performed which revealed diffuse extensive hemorrhage within the infarcted muscle. We believe increased signal intensity on T1-weighted images should suggest hemorrhage within the infarcted muscle.
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  • 86
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    Skeletal radiology 29 (2000), S. 481-484 
    ISSN: 1432-2161
    Keywords: Key words Meniscal ossicles ; Ultrasound ; CT-arthrography ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A case of meniscal ossicles occurring in the left knee of a 23-year-old woman is presented. Radiographs showed two calcified lesions at the posteromedial aspect of the knee which were interpreted as loose bodies. Sonography, computed tomography arthrography and magnetic resonance imaging showed the fragments within the posterior horn of the medial meniscus permitting a diagnosis of meniscal ossicles. These techniques can detect meniscal ossicles and exclude intra-articular loose bodies.
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  • 87
    ISSN: 1432-2161
    Keywords: Key words Clear cell sarcoma ; Malignant melanoma of soft parts ; MRI ; Magnetic resonance ; Neoplasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.
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  • 88
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    Skeletal radiology 29 (2000), S. 227-230 
    ISSN: 1432-2161
    Keywords: Key words Erdheim-Chester Disease ; Lipogranuloma ; MRI ; Muscle ; Rectus femoris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report on a rare manifestation of Erdheim-Chester disease with intramuscular lipogranuloma. The patient was a 66-year-old man who noted a soft tissue mass in the right quadriceps femoris muscle. Radiographs revealed symmetrical osteosclerosis in the diametaphysis of both femora and tibiae. An open biopsy revealed a proliferation of lipid-laden histiocytes in the femoral bone marrow and the quadriceps femoris muscle. To our knowledge, this is the second case of Erdheim-Chester disease involving muscle.
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  • 89
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    Skeletal radiology 29 (2000), S. 235-238 
    ISSN: 1432-2161
    Keywords: Key words Femur echinococcosis ; MRI ; echinococcosis ; Hydatid cyst surgery ; Hydatid cyst ; anticestodal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Magnetic resonance (MR) findings of a rare case of osseous echinococcosis with involvement of the femur are described. Attention is drawn to the typical MR appearances and therapeutic management.
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  • 90
    ISSN: 1432-2161
    Keywords: Key words Tibial deficiency ; Fibular deficiency ; Congenital hip dislocation ; Transverse limb deficiency ; X-ray ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report two similar, but unrelated, patients with congenital bilateral partial deficiencies of the tibia and fibula associated with intact feet. In both patients, the tibia and fibula were absent on initial radiographs, while the femur and the tarsal bones were well developed and there was bilateral teratologic dislocation of the hips. Ultrasound and magnetic resonance imaging (MRI) studies suggested the presence of cartilaginous remnants of the tibia and fibula. There were multidirectional instabilities in the knees and ankles. The clinical and radiological features of these cases are distinct from those of congenital longitudinal deficiency of the tibia, in which the fibula is always preserved, and from longitudinal deficiency of the fibula, in which the tibia is present and the foot is usually involved. We suggest that the bilateral partial deficiencies of the tibia and fibula associated with the intact foot and teratologic dislocation of the hips is a single-entity disorder, possibly categorized as an intercalary transverse deficiency of the lower limb.
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  • 91
    ISSN: 1432-2161
    Keywords: Key words Metastatic bone tumor ; Knee ; Spontaneous osteonecrosis ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a case of a metastatic bone tumor that mimicked spontaneous osteonecrosis of the medial condyle of the femur on magnetic resonance imaging.
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  • 92
    ISSN: 1432-2161
    Keywords: Key words Chronic leg ulcers ; Squamous cell carcinoma ; Malignancy ; Snake bite ; X-rays ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chronic ulcers of the leg are common in Brazil, perhaps more common than in the developed world. We report a case of a chronic ulcer of the leg following extensive scarring due to a bite by a venomous snake, which eventually led to a squamous cell carcinoma.
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  • 93
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    Skeletal radiology 29 (2000), S. 417-420 
    ISSN: 1432-2161
    Keywords: Key words Arm ; Collagenous fibroma ; Desmoplastic fibroblastoma ; Short T2 ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recently proposed addition to fibrous tumors in soft tissue was first described as desmoplastic fibroblastoma and later renamed collagenous fibroma. This tumor is clinically and morphologically distinct and benign. However, only a few series have been reported, and the clinicopathologic features are not widely recognized. We present two cases of collagenous fibroma of the arm. Both patients presented with an enlarging, well-circumscribed and mobile soft tissue mass. Magnetic resonance imaging showed areas of low signal intensity on both T1- and T2-weighted sequences. Needle aspiration cytology revealed nondiagnostic samples because of the low cellularity of the tumors. Each of the resected tumors was composed of low-cellular spindle- to stellate-shaped cells in a fibrous matrix with clear margination. After the marginal excisions, no recurrences were observed. Clinicians should be aware of this entity to prevent overtreatment, because imaging findings and cytologic features are similar to those of desmoid tumor.
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  • 94
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    Skeletal radiology 29 (2000), S. 425-438 
    ISSN: 1432-2161
    Keywords: Key words Muscles ; MRI ; Myositis ; Muscles ; Abscess ; Dermatomyositis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Inflammatory myopathies encompass a group of acquired muscle disorders caused by infectious agents (bacteria, viruses, fungi and parasitic agents) or autoimmune processes (polymyositis, dermatomyositis and other types). In suspected infection sonography, CT and MRI are all able to show edema and fluid collections in soft tissues and muscles; sonography and CT may help guidance of a needle aspiration to establish a correct diagnosis. By offering better tissue differentiation, MRI appears to be more efficient than sonography and CT in diagnosing and managing autoimmune myopathies. MRI is indeed very sensitive to the presence of water and edema, and appears to be a very good indicator for an early diagnosis of diseases. MRI may also help to evaluate the extent and number of lesions, to guide a biopsy in an area of active disease and finally to follow the evolution under therapy.
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  • 95
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    Skeletal radiology 29 (2000), S. 354-357 
    ISSN: 1432-2161
    Keywords: Key words Intraosseous meningioma ; Microcystic meningioma ; Parietal bone ; X ray ; CT ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extradural ectopic meningioma is a rare tumor. We report on an example of microcystic meningioma arising in the skull of an elderly woman. Radiological examination revealed a localized osteolytic lesion in the left parietal bone. At surgery, it was discovered that the tumor was located within the skull without any evidence of extraosseous extension. The light microscopic, immunohistochemical and ultrastructural features were consistent with a microcystic variant of meningioma. To our knowledge, this is the first case of an intraosseous microcystic meningioma, and we believe that this type of meningioma should be considered in the differential diagnoses of myxoid bone tumors of the calvarium.
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  • 96
    ISSN: 1432-2161
    Keywords: Key words Chondrolipoma ; Liposarcoma ; Mesenchymoma ; Cartilage ; Metaplasia ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chondro-osseous differentiation of three benign or malignant fat tissue tumors – two chondrolipomas and a liposarcoma with cartilaginous metaplasia – was studied with magnetic resonance (MR) imaging and compared with their pathological findings. The results suggest that demarcation of cartilage tisssue can be clearly defined on MR imaging when the size of the cartilaginous area is large. Myxoid matrix, degenerative fat tissue and lipodystrophic change may decrease the delineation of the cartilage tissue.
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  • 97
    ISSN: 1432-2277
    Keywords: Key words Normothermic liver ischemia ; Apoptosis ; Caspases ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 μl PBS solution containing 1 % DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95 %) compared with that in nontreated rats (30 %, P 〈 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3–6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3–6 h after reperfusion in the control group, but significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.
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  • 98
    ISSN: 1434-3916
    Keywords: Key words Shoulder ; Calcifying tendinitis ; Shock wave ; MRI ; Prediction parameters ; Clinical outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This prospective study examined 62 patients (65 shoulders) with chronic courses of calcifying tendinitis of the shoulder before and after low-energy extracorporeal shockwave application (ESWA) in order to identify variables associated with the outcome of this treatment. Before ESWA, radiographs and contrast-enhanced magnetic resonance imaging (MRI) of the affected shoulders were obtained in order to document the size and morphology of the calcifications and the contrast media reactions in areas of interest (deposit, synovia, bursae), respectively. In addition, a clinical evaluation was performed. After ESWA (mean follow-up 18.2 months), clinical evaluations of all 65 shoulders revealed an increase in the Constant score from 44% to 78% (p 〈 0.0001). While size (p = 0.61) and morphology (p = 0.7) of the deposits before ESWA were not associated with the clinical outcome, negative contrast reactions around the deposits (p = 0.0001), synovia (p = 0.0049) and bursae (p 〈 0.01) were associated with improved clinical outcomes. After the total study group was divided into two groups, one with Constant scores ≥ 75% (n = 43) and the other with scores 〈 75% (n = 22), the positive predictive value (ppv), specificity (sp) and sensitivity (se) were determined for the negative reaction around the deposit (ppv: 0.94; sp: 0.95; se: 0.38), synovia (ppv: 0.84; sp: 0.82; se: 0.49) and bursae (ppv: 0.86; sp: 0.86; se: 0.44). In 5 cases (7.7%), surgery of the affected shoulder during the follow-up period was performed. No major side-effects were seen in the study group. In conclusion, our results suggest that in patients with chronic calcifying tendinitis, the absence of contrast enhancement, especially around the deposit, is a strong predictive parameter of a positive clinical outcome of ESWA.
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  • 99
    ISSN: 1434-0879
    Keywords: Key words Cryptorchidism ; Contralateral descended testis ; Apoptosis ; Fertility ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three rat strains have been studied, using a sensitive apoptotic detection method for germ-cell degeneration, to resolve the controversy regarding the effect of cryptorchidism on the contralateral descended testis (CDT). Sprague Dawley and Buffalo rats were made cryptorchid by operation at 20–22 days of age, while trans-scrotal (T-S) rats were a congenitally unilateral cryptorchid strain. Sham operated rats or normal T-S littermates were used as controls. Experiments were performed over a period ranging from 2 weeks to 18 months. Testis weight was assayed, as was the detection of apoptosis by agarose gel laddering and immunohistochemistry by using the TUNEL method. Labeled cells in 150 cross-sectioned testis tubules were counted on the TUNEL stained slides and the mean number of labeled cells per tubule was calculated. Paternity studies on Sprague Dawley and T-S rats were carried out at 12 and 24 weeks of age to assess fertility by the resultant number of pregnancies and litter sizes. Both Sprague Dawley and T-S rat models showed a biphasic distribution of apoptosis levels. This biphasic distribution was not observed in Buffalo rats as they were only studied at later time points (12–20 weeks). A significant effect on either testis weight or apoptosis in the CDT compared with the control descended testis (P ≥ 0.1) has not been found in these three cryptorchid models, and the present results are discussed with reference to observations of other researchers in rodents and humans. While the cryptorchid testis showed a high level of labeled apoptotic cells per tubule in all rat strains, fertility was not affected and remained the same as controls at 12 and 24 weeks. There was, however, a marked strain difference in fertility in T-S as compared with Sprague Dawley rats. After 24 weeks of cryptorchidism, both control and cryptorchid T-S rats had a 44% pregnancy incidence compared with a 90% pregnancy incidence in Sprague Dawley rats. In addition, litter size in T-S control and cryptorchid rats were small compared with those of Sprague Dawley rats at 12 and 24 weeks.
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  • 100
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    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S504 
    ISSN: 1434-3940
    Keywords: Schlüsselwörter CAD/CAM ; Knochenersatzmaterial ; MRT ; Qualitätskontrolle ; Titan ; Key words Bone substitute material ; CAD/¶CAM ; MRI ; Quality control ; Titanium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Computer-assisted prefabricated skull implants of pure titanium as a bone replacement material have been used in 22 departments since 1994. Our experience with 104 implants includes clinical aspects (indication; tissue quality; surgical technique; patient guidance), but also geometric and material-specific parameters (acquisition, transfer, and evaluation of CT data; construction; manufacturing; cleaning; postoperative use of radiologic techniques). While the clinical aspects are responsibly defined by the respective surgeon, the geometric and material-specific parameters of individual implants have to comply with the laws on medical products. Therefore, the prospective documentation for each implant includes: helical CT acquisition parameters; geometric data of the computer-based skull model and implant; the cleaning procedure; and the individual marking. Medically specified pure titanium is processed by milling only so that neither purity nor structure is impaired. A specially developed milling technique guarantees the fabrication of all constructed elements down to fine details of 50 μm. Considering the necessary radiologic follow-up of defects after tumor surgery, all patients in our hospital undergo postoperative MRI examination, partly with preoperative documentation as an intraindividual control. Such comprehensive documentation and quality assurance is essential for techniques of prefabricated bone substitution. Hand in hand with scientific research and clinical application, these formal criteria have to be elaborated and fulfilled for the respective techniques. The successful determination of specifically adapted MRI sequences goes even one step further: spin-echo sequences minimize inhomogeneities of the magnetic field induced by the titanium implants and enable accurate postoperative documentation and diagnostics especially in the follow-up after tumor surgery.
    Notes: Zusammenfassung Computergestützt vorgefertigte Schädelimplantate aus Reintitan als Knochenersatzmaterial werden seit 1994 in 22 Kliniken eingesetzt. Die Erfahrungen mit 104 Implantaten umfassen klinische (Indikationsstellung; Implantatlager; Operationstechnik; Patientenführung), aber auch geometrische und materialspezifische Aspekte (CT-Datenakquisition, -transfer und -auswertung; Konstruktion; Fertigung; Reinigung; postoperative Einsatzmöglichkeit bildgebender Verfahren). Während die klinischen Aspekte im Verantwortungsbereich ärztlichen Handelns definiert werden, gilt für die geometrischen und materialspezifischen Aspekte bei individuellen Implantaten das Medizinproduktegesetz. Prospektiv werden entsprechend für jedes Implantat die Spiral-CT-Akquisitionsparameter, die Geometriedaten des rechnerinternen Schädelmodells und des Implantats, das Reinigungsverfahren und die individuelle Kennzeichnung dokumentiert. Medizinisch spezifiziertes Reintitan wird ausschließlich durch Fräsung bearbeitet, sodass weder Reinheit noch Gefüge Änderungen erfahren. Eine eigens entwickelte Frästechnik garantiert die Umsetzung aller konstruierter Elemente bis zu einer Feinheit von 50 μm. Im Hinblick auf die bei tumorbedingten Defekten notwendige bildgebende Verlaufskontrolle werden sämtliche Patienten der eigenen Klinik postoperativ mit MRT untersucht, z. T. mit einer präoperativen Darstellung als intraindividuelle Kontrolle. Eine umfassende Dokumentation und Qualitätssicherung ist für Techniken des vorgefertigten Knochenersatzes unabdingbar. Parallel zur forscherischen Entwicklung und ärztlichen Anwendung müssen diese formalen Kriterien für das jeweilige Verfahren bearbeitet und erfüllt werden. Die erfolgreiche Erarbeitung von eigens adaptierten MRT-Sequenzen geht darüber noch hinaus: Spinechosequenzen minimieren die durch die Titanimplantate erzeugten Feldinhomogenitäten und erlauben eine aussagekräftige postoperative Dokumentation und Diagnostik insbesondere nach Tumoroperationen in der Verlaufsbeobachtung.
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