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  • Artikel: DFG Deutsche Nationallizenzen  (1.081)
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  • Artikel: DFG Deutsche Nationallizenzen  (1.081)
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  • 1
    Digitale Medien
    Digitale Medien
    p21Waf1/Cip1 Expression Is a Prognostic Marker in Curatively Resected Esophageal Squamous Cell Carcinoma, but Not p27Kip1, p53, or Rb (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 481-488 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Esophageal cancer ; Treatment ; Prognosis ; Cell cycle ; Immunohistochemistry ; Cyclin-dependent kinases inhibitor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). Methods: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. Results: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. Conclusions: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0481-x
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  • 2
    Digitale Medien
    Digitale Medien
    Prognostic Value of Laurén Classification and c-erbB-2 Oncogene Overexpression in Adenocarcinoma of the Esophagus and Gastroesophageal Junction (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 290-297 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Laurén classification ; C-erbB-2 oncogene ; Esophageal adenocarcinoma ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ). Methods: Forty-one adenocarcinomas of the esophagus and/or GEJ were reviewed for tumor stage, lymph node status, Laurén classification, and c-erbB-2 overexpression, as assessed by immunohistochemical analysis. Results: According to the Laurén classification, tumors were classified as intestinal-, mixed-, or diffuse-type (54%, 32%, and 15%, respectively). Diffuse-type tumors were associated with a significantly worse prognosis than were intestinal-type tumors (P = .018; log-rank test). The prognostic value of the Laurén classification was independent of stage (P = .048; Cox regression model). Overexpression of c-erbB-2 was detected in 24% of the tumors and was present exclusively in intestinal-type tumors and in intestinal-type areas of mixed-type tumors. Ten of the 30 stage III/IV tumors (33%) were c-erbB-2-positive, whereas none of the 11 stage I/II tumors (0%) overexpressed the oncogene product (P = .04; Fisher exact test). The prognostic value of c-erbB-2 overexpression was not independent of stage (P = .7; Cox regression model). Conclusions: (1) The Laurén classification is an independent prognostic factor in adenocarcinoma of the esophagus and GEJ. (2) c-erbB-2 overexpression is limited to (areas of) intestinal-type tumors, indicating that intestinal- and diffuse-type tumors differ oncogenetically. (3) c-erbB-2 overexpression is associated with the stage of disease, indicating that it is a late event during tumor progression.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0290-2
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  • 3
    Digitale Medien
    Digitale Medien
    Expression of p53 and RB Proteins in Squamous Cell Carcinoma of the Esophagus: Their Relationship With Clinicopathologic Characteristics (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 489-494 
    Details
    ISSN: 1534-4681
    Schlagwort(e): P53 ; Retinoblastoma (RB) ; Prognosis ; Esophageal cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Cancer of the esophagus is one of the most malignant tumors and has a poor prognosis. The p53 and retinoblastoma (RB) genes are involved in the regulation of cell population by suppressing cell proliferative activity. Our goal was to clarify whether expression of p53 and RB genes could be prognostic factors in squamous cell carcinoma of the esophagus. Methods: Tumor samples taken from 73 patients undergoing subtotal esophagectomy were immunohistochemically stained for the p53 and RB genes. An image analyzer was used for quantitative assessment of the staining, and clinicopathologic characteristics of those patients were investigated. Results: Patients in whom p53 expression was high had greater tumor diameter, deeper tumor invasion, and worse prognosis compared with patients in whom p53 expression was low. Patients in whom RB expression was low had a higher incidence of lymph node metastasis and more advanced disease than did those in whom RB expression was high. The combination of p53 and RB expression revealed that the cases with high p53 and low RB expression had significantly worse survival rates and deeper tumor invasion compared with other groups. In various clinicopathologic parameters, (e.g., age, sex, tumor-diameter, tumor type, location, differentiation, TNM classification,TNM stage) tumor type, tumor size, depth of invasion, lymph node involvement, distant metastasis, and combined p53 and RB expression showed significant differences in survival by univariate analysis. Among those six variables, only lymph node involvement showed an independent prognostic factor for survival (P = .0055) by multivariate analysis. Conclusions: The combination of p53 and RB expression is not a prognostic indicator in the surgical treatment of esophageal cancer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0489-2
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  • 4
    Digitale Medien
    Digitale Medien
    Use of preoperative ultrasound staging for treatment of rectal cancer (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 159-166 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Rectal cancer ; Rectal neoplasms therapy ; Rectal neoplasms radiotherapy ; Neoplasms staging ; Neoplasms recurrence ; Treatment outcomes ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract INTRODUCTION: Transrectal ultrasound is the standard method for preoperative staging of rectal cancer. This study reviews the accuracy of transrectal ultrasound staging for T3 disease and its use in the selection of patients for neoadjuvant chemoradiation. METHODS: One hundred seventeen patients underwent preoperative transrectal ultrasound evaluation for rectal cancer. Accuracy of transrectal ultrasound was evaluated among 70 patients not receiving preoperative chemoradiation. Forty-seven patients received neoadjuvant chemoradiation based on transrectal ultrasound results. Tumor downstaging and early recurrence were evaluated among 45 of 47 patients receiving neoadjuvant chemoradiation. RESULTS: Among 70 nonirradiated patients, 19 were pathologic Stage pT3. Transrectal ultrasound correctly identified 18 of 19 patients with Stage pT3 (sensitivity, 94.7 percent). Transrectal ultrasound correctly identified 44 of 51 patients with less than pT3 disease (specificity, 86.3 percent). After preoperative chemoradiation in 45 patients with ultrasound Stage uT3 or uT4 tumors, 56 percent of them experienced a reduction in T stage. Residual nodal disease was found in 31 percent of patients. A complete pathologic response with no residual disease at operation was observed in 22 percent of patients. During a median follow-up period of 21 months after diagnosis, seven patients experienced a recurrence of their disease at a median of 12 months after diagnosis. Five of seven patients with recurrence were among a subgroup of ten patients who both failed to downstage T and had residual nodal disease at operation. CONCLUSION: Transrectal ultrasound is an accurate modality for selecting patients for neoadjuvant treatment. Preoperative chemoradiation produced downstaging in 56 percent of patients. Factors related to early recurrence included residual nodal disease and failure to downstage T after neoadjuvant chemoradiation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02237121
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  • 5
    Digitale Medien
    Digitale Medien
    Laparoscopicvs. open abdominoperineal resection for cancer (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 930-939 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Rectal cancer ; Laparoscopy ; Abdominoperineal resection ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer. METHODS: Records of 194 patients who underwent laparoscopic abdominoperineal resection (42 patients) or open abdominoperineal resection (152 patients) at three institutions between 1991 and 1997 were reviewed. Follow-up was through office charts, American College of Surgeons cancer registry, or telephone contact. Tumors included (laparoscopic abdominoperineal resection and open abdominoperineal resection, respectively) adenocarcinoma (86 and 92 percent), squamous (12 and 7 percent), and gastrointestinal stromal (2 and 1.4 percent) types; Stages I (17 and 26 percent), II (24 and 33 percent), III (43 and 32 percent), and IV (14 and 9 percent); and those with invasion of pelvic structures (14 and 16 percent). RESULTS: Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury (33 percent), poor exposure (22 percent), adhesions (22 percent), inguinal hernia (11 percent), or radiation fibrosis (11 percent). Perineal infections occurred more often in the laparoscopic abdominoperineal resection group (24vs. 8 percent;P=0.02). Late stoma complications were similar. Mean hospital stay was shorter after laparoscopic abdominoperineal resection (7vs. 12 days). Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens. Tumor recurrence was similar for both local (19 and 14 percent) and distant (38 and 26 percent) recurrence. Survival rates were similar by Kaplan-Meier curves, with median follow-up of 19 and 24 months, respectively (P=0.22; log rank). CONCLUSION: Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay. A randomized, prospective trial is needed to determine the long-term outcome of cancer treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02237105
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  • 6
    Digitale Medien
    Digitale Medien
    Accurate lymph-node detection in colorectal specimens resected for cancer is of prognostic significance (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 143-154 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Colorectal cancer ; Lymph node ; Pathology ; Prognosis ; Local recurrence ; Metastasis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: Lymph-node involvement is the most important prognostic factor in colorectal cancers. Many staging systems adopted node status as a parameter of tumor classification. However, the number of identified and positive glands varies across articles, depending on specimen examination. There is a consistent risk of substaging tumors and undertreating patients. Aim of this study was to investigate the prognostic significance of different pathologic methods. METHODS: Eight hundred one patients who underwent curative resection of colorectal cancer entered the study and were divided into two groups. In Group 1 the specimen was “en bloc” fixed, and nodes were identified by sight and palpation. In Group 2 the mesentery of the excised specimen was dissected away from the bowel, stretched, and pinned to cork board. The mesenteric segment surrounding the origin of principal vessels was divided from the segment surrounding the colic vessels. All specimen segments were fixed, node identification being performed by sight and palpation. Examined and positive nodes were recorded, and metastatic rate and incidence was calculated in the two groups. Patients were classified with used of different staging systems. Survival rates were calculated, related to tumor stage, and compared statistically. Pathologic procedures were included in a multivariate analysis. RESULTS: A significantly higher number of detected and positive nodes and metastatic rate (37.5vs. 30.2 percent;P〈0.05) were observed in Group 2; 45.2 percent of Group 2 and 25.3 percent of Group 1 cases had more than three positive nodes (P〈0.05). In Group 2 several patients shifted from earlier to more advanced stages compared with Group 1 cases. Five-year and ten-year survival rates were significantly higher (P=p.pr) in Group 2 (81.5 and 77.2 percent) than in Group 1 (76.7 and 61.5 percent), mostly in patients with TNM Stage N0. Survival analysis related to Astler and Coller's and Tang's classifications confinrmed such features. Higher rates of local recurrences and distant metastases were found in Group 1, particularly if related to node status (P〈0.05). Multivariate analysis demonstrated the pathologic method is an independent prognostic factor. CONCLUSIONS: This study demonstrates the prognostic impact of specimen examination. Inaccurate methods could downstage the tumor and exclude the patient from adjuvant therapies, with detrimental effects on the outcome of the case.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02237119
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  • 7
    Digitale Medien
    Digitale Medien
    Prognostic value of nuclear morphometry in colorectal cancer (1999)
    Springer
    Diseases of the colon & rectum 42 (1999), S. 386-392 
    Details
    ISSN: 1530-0358
    Schlagwort(e): Nuclear morphometry ; Colorectal cancer ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: In many types of cancer, certain morphometric characteristc of tumor cells correlate with patient survival. Our observations suggested that the survival of patients with colorectal carcinomas is negatively correlated with tumor-cell nucleus size. METHODS: We investigated relationships between postsurgery survival and nucleus morphometrics in 90 patients who had undergone resection for a colorectal tumor. The nucleus-size variables considered were maximum diameter, minimum diameter, perimeter, area, and form factor (means for 100 nuclei from each patient were used in all cases). RESULTS: Our results confirmed that patients with large maximum nucleus diameter (where large = greater than the first quartile) have significantly worse survival than patients with smaller maximum nucleus diameter (mean survival, 28vs. 43 months). Similar results were obtained for the other nucleus-size variables. Stepwise Cox regression analysis was then performed, with postsurgery survival time as the dependent variable and the following candidate independent variables: age, gender, Dukes class, degree of histologic differentiation, the various nucleus-size variables, and relative frequencies of different nucleus shapes (spherical, oval, cylindrical, fusiform, and irregular). The variables selected for the prognostic model were Dukes class, relative frequency of irregular nuclei, and maximum nucleus diameter. CONCLUSIONS: These findings indicated that nucleus size and shape are useful predictors of survival. Even if Dukes class is known, consideration of nucleus size and shape significantly improves prediction of survival.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02236359
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  • 8
    Digitale Medien
    Digitale Medien
    Current Advances and Changes in Treatment Strategy May Improve Survival and Quality of Life in Patients With Potentially Curable Gastric Cancer (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 46-56 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Gastric cancer ; Early ; Advanced gastric cancer ; Surgery ; Splenectomy ; Pancreatectomy ; Extensive (D2) lymph node dissection ; Endoscopic mucosal resection ; (Neo)adjuvant chemotherapy ; Prognosis ; Quality of life.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The treatment strategy for gastric cancer is determined by the stage of disease. Advances in diagnostic techniques such as endoscopic ultrasound (EUS) and in staging have increased the accuracy of pretreatment staging. Correct staging is a prerequisite for the optimal treatment of gastric cancer patients. Long-term expected survival and quality of life (QOL) are the major criteria determining the therapeutic strategy. Results: Surgical resection offers excellent survival rates for early gastric cancer (EGC) patients. D1 resection is sufficient for mucosal cancers (T1m) and for most submucosal cancers (T1sm); however, for the rest (about 5%) of these patients with N2 disease a D2 resection is required for complete tumor resection (R0). Considering QOL, endoscopic mucosal resection (EMR) or laparoscopic wedge resection is the best frontline therapy for several mucosal cancers. Prediction and selection of node-negative patients with the help of certain macroscopic and histologic criteria can eliminate the possibility for residual disease in perigastric lymph nodes. However, long-term survival data are needed before these new techniques become more generally accepted. In contrast, an aggressive approach is necessary for the treatment of advanced gastric cancer. Total gastrectomy, with the exception of distal tumors that can be treated by subtotal gastrectomy, is the procedure of choice. Splenectomy is indicated for proximal advanced tumors. Distal pancreatectomy should be avoided, however, because its adverse effect has been documented in all randomized trials. Although the survival benefit of extended (D2) lymphadenectomy is unproven in randomized trials, D2 resection increases the R0 resection rate and may improve survival in some selected nodepositive patients. D2 resection has little effect on preventing peritoneal tumor spread and liver metastasis, and the traditional late administration of chemotherapeutic drugs has been proven ineffective. Current data suggest a possible beneficial effect of combined treatment for patients with local advanced gastric cancer (LAGC). Ongoing phase III randomized trials will prove whether patients with LAGC treated by neoadjuvant chemotherapy plus D2 resection versus surgery alone or surgery plus intraoperative intraperitoneal chemotherapy derive any benefit from these combined treatment modalities. Conclusion: Evaluation of all information concerning tumor stage, location, histologic type, expected survival, and QOL after resection is of paramount importance for the surgeon planning the extent of surgery. The therapeutic approach should be stratified according to the stage of disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0046-z
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  • 9
    Digitale Medien
    Digitale Medien
    New Approach to the Substaging of Node-Positive Colorectal Adenocarcinoma (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 161-165 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Node-positive colorectal adenocarcinoma ; Prognosis ; Staging ; Substaging ; Systemic adjuvant treatment ; Venous invasion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Future developments in adjuvant modalities may require substaging of nodepositive colorectal adenocarcinoma that is accurately indicative of individual prognoses, upon which therapeutic decisions (e.g., choice of agents and intensity of treatment) may be based. This study compares substaging of node-positive colorectal cancer by venous invasion with substaging by three currently used methods, with respect to the ability of each method to define patient subsets that differ significantly in both disease-free and cancer-related survival rates. Methods: A total of 171 patients with node-positive colorectal cancer, who had undergone potentially curative resection at least 5 years earlier, were retrospectively substaged by the tumor, node, metastasis (TNM) N1/N2, Astler-Coller C1/C2, Gastrointestinal Tumor Study Group (GITSG) C1/C2, and venous invasion (positive/negative) methods. Disease-free and cancer-related survival curves were calculated (by the Kaplan-Meier method) and compared for statistical significance (using the log-rank test). Results: The separation of disease-free and cancer-related survival curves using the four methods of substaging node-positive colorectal cancer was as follows: TNM, P = .16 (not significant) and P = .12 (not significant); Astler-Coller, P 〈.01 and P = .006; GITSG, P = .067 (not significant) and P = .03; venous invasion, P = .016 and P = .007, respectively. Conclusions: Numerical substaging of node-positive colorectal cancer (TNM and GITSG methods) is an inferior predictor of prognosis, compared with substaging by the T value (Astler-Coller) or venous invasion methods. We think that the latter method is the method of choice, because it separates patients who have only lymphatic metastasis from patients who display microscopic hematogenous spread as well. This separation obviously has biological/oncological significance, and it may have practical therapeutic implications in the future.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0161-x
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  • 10
    Digitale Medien
    Digitale Medien
    Does the Extent of Operation Influence the Prognosis in Patients With Melanoma Metastatic to Inguinal Nodes? (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 263-271 
    Details
    ISSN: 1534-4681
    Schlagwort(e): Melanoma ; Lymphadenectomy ; Extent ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The role of pelvic lymphadenectomy in melanoma metastatic to the superficial inguinal region remains controversial. Some researchers advocate aggressive surgical management,whereas others feel that outcome depends more on extent of disease rather than extent of treatment.We reviewed our recent experience to investigate possible therapeutic effects of extended surgery. Methods: We performed a retrospective clinical and pathological review of 227 consecutive patients having superficial (SLND) or combined inguinal lymphadenectomy (CLND) for cutaneous melanoma. Results: A total of 174 SLNDs and 53 CLNDs were performed. Overall 5-year survival for node-positive patients was 39%. Survival for patients with positive superficial nodes was 40%; for those with positive deep nodes it was 35% (P = ns). In node-positive patients, number and size of involved lymph nodes and the presence of extranodal spread, failure to receive adjuvant therapy, and tumor ulceration were associated with poorer prognosis. Extent of surgery was not associated with differential survival, although CLND patients had worse pathological features. Subgroup analysis showed no significant survival difference between SLND and CLND. Conclusions: Some patients with deep nodal involvement apparently are cured by CLND. However, it is the biology of the disease and not the extent of surgery that primarily governs outcome. Patients with clinical or radiological evidence of pelvic nodal disease without evidence of systemic disease should have a CLND, but we find no evidence to support CLND if the pelvic nodes are clinically and radiologically negative.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10434-999-0263-5
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  • 11
    Digitale Medien
    Digitale Medien
    Technology and prognostic predicaments (1999)
    Springer
    AI & society 13 (1999), S. 44-51 
    Details
    ISSN: 1435-5655
    Schlagwort(e): Assessment ; Ethics ; Prognosis ; Research and development ; Side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Informatik
    Notizen: Abstract As societies become increasingly technologised, the need for careful and critical assessment rises. However, attempts to assess or normatively evaluate technological development invariably meet with an antinomy: both structurally and historically, technologies display multistable possibilities regarding uses, effects, side effects and other outcomes. Philosophers, usually expected to play applied ethics roles, often come to the scene after these effects are known. But others who participate at the research and development stages find even more difficulties with prognosis. Recent work on ‘revenge’ effects (Tenner) and negative side effects (Kevles) are examined, as well as several cases of philosophers in ‘R&D’ roles. After sketching the antinomy,I outline a heuristic pragmatics of prognosis that addresses this quandary.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01205256
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  • 12
    Digitale Medien
    Digitale Medien
    Tumor cells in breast tumors: significance of their presence for prognosis (1999)
    Springer
    Hematology and cell therapy 41 (1999), S. 66-70 
    Details
    ISSN: 1279-8509
    Schlagwort(e): Tumor cells ; Monoclonal antibodies ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Through two clinical studies, tumor cells were searched for in the bone biopsies and cytapherisis of patients suffering from inflammatory tumors and who had undergone intensive therapy and autografts (Pegase 2 program). In these studies we used immunocytochemical test with two monoclonal antibodies. The results have shown the presence of tumor cells in 14 of the patients (respectively 18), with no correlation to the appearance of metastases after 4 years in the first study. Nevertheless, the presence of these tumor cells seems to be an important factor in the number of relapses. It seems important to develop research into tumor contamination especially in the selection of grafts over the next few years.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s00282-999-0066-y
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  • 13
    Digitale Medien
    Digitale Medien
    Gender-related differences in polyamine oxidase activity in rat tissues (1999)
    Springer
    Amino acids 17 (1999), S. 139-148 
    Details
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Polyamine oxidase ; Polyamines ; Gender ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Variations in level of polyamines and their related enzymes are frequently observed in response to some treatments which affect in a different way male and female. The possibility of a gender-related difference in the oxidation of polyamines was investigated in rats by measuring the activity of polyamine oxidase, a ubiquitous enzyme of vertebrate tissues, which transforms spermine into spermidine and spermidine into putrescine. The study was carried out on thymus, spleen, kidney and liver of young rats of both sexes, and female rats showed a lower polyamine oxidase activity than male rats in all the tissues. We also found higher values of spermidine acetylation in female than male rats in thymus and liver. Owing to these gender-related differences, a higher spermidine N-acetyltransferase/ polyamine oxidase ratio was found in female than in male rats. A second gender-related difference was a higher spermidine/spermine ratio in female than in male, the only exception being the thymus. These basal differences possibly account for the gender-related differences of polyamine metabolic enzyme activities in response to some treatments, including drugs or hormones.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01361877
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  • 14
    Digitale Medien
    Digitale Medien
    Evidence that taurine modulates osmoregulation by modification of osmolarity sensor protein ENVZ — expression (1999)
    Springer
    Amino acids 17 (1999), S. 347-355 
    Details
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Osmoregulation ; Rat ; Osmolarity sensor protein ENVZ
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Although the involvement of taurine in osmoregulation is well-documented and widely accepted, no detailed mechanism for this function has been reported so far. We used subtractive hybridization to study mRNA steady state levels of genes up- or downregulated by taurine. Rats were fed taurine 100mg/kg body weight per day for a period of three days and hearts (total ventricular tissue) of experimental animals and controls were pooled and used for mRNA extraction. mRNAs from two groups were used for subtractive hybridization. Clones of the subtractive library were sequenced and the obtained sequences were identified by gen bank assignment. Two clones were found to contain sequences which could be assigned to the osmolarity sensor protein envZ, showing homologies of 61 and 65%. EnvZ is an inner membrane protein in bacteria, important for osmosensing and required for porine gene regulation. It undergoes autophosphorylation and subsequently phosphorylates OmpR, which in turn binds to the porin (outer membrane protein) promoters to regulate the expression of OmpF and OmpC, major outer membrane porines. This is the first report of an osmosensing mechanism in the mammalian system, which was described in bacteria only. Furthermore, we are assigning a tentative role for taurine in the osmoregulatory process by modifying the expression of the osmoregulatory sensor protein ENVZ.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01361660
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  • 15
    Digitale Medien
    Digitale Medien
    Taurine modulates expression of transporters in rat brain and heart (1999)
    Springer
    Amino acids 17 (1999), S. 301-313 
    Details
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Transporter ; Rat ; Brain ; Heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In pro- and eucaryotic life, cellular and subcellular compartments are separated by membranes and the regulated and selective passage of specific molecules across these membranes is a basic and highly conserved principle. We were interested whether taurine, a naturally occuring amino acid, would be able to induce or suppress expression of transporters with the Rationale that taurine was shown to detoxify a series of endogenous toxins and xenobiotics of various chemically non-related structures. For this purpose we used a gene hunting technique, subtractive hybridization, subtracting mRNAs of taurine-treated rat brain and heart from untreated controls. Subtracted mRNAs were then converted to cDNAs, amplified, sequenced and identified by gene bank data. We found five transporter transcripts, the phosphonate transport ATPase PHNC, multidrug transporter homolog MTH104, protein-exportmembrane protein SECD, oligopeptide transporters oppA and oppD, in the brain and two: ABC-transporter BRAF-2 and cation-transport ATPase PACS, in the heart. Homologies of the sequences found were in any case 〉50% thus permitting the identification of transporters with high probability. The biological meaning could be that a naturally occuring amino acid, taurine, modulates complex transport systems. The most prominent finding is the upregulation of a multidrug transporter transcript, explaining a mechanism for the nonselective detoxifying action of taurine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01366929
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  • 16
    Digitale Medien
    Digitale Medien
    High blood levels of nitric oxide in rats subjected to prolonged respiratory arrest and their modulation during adrenocorticotropin-induced resuscitation (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 53-59 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Key words Asphyxia ; Nitric oxide ; Electron spin ; resonance ; Adrenocorticotropin ; Resuscitation ; S-Methylisothiourea ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Anaesthetized rats, endotracheally intubated and mechanically ventilated with room air, were subjected to a 5-min period of asphyxia by turning off the ventilator. The ventilator was then turned back on and, simultaneously, the animals were treated with either the adrenocorticotropin fragment 1–24 [ACTH-(1–24), 160 µg/kg in a volume of 1 ml/kg i.v.] or an equivalent volume of saline. Nitric oxide (NO)-haemoglobin formation was detected ex vivo in arterial blood by electron spin resonance spectrometry; arterial blood pressure, electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for a 60-min observation period, or until prior death. During asphyxia, there was massive formation of NO (red cell concentrations 40–80 µM), associated with a dramatic fall in mean arterial pressure and pulse pressure, marked bradycardia and ECG signs of ischaemic damage, as well as an isoelectric EEG. Treatment with ACTH-(1–24) produced a prompt (within 15 min) and long-lasting drop in NO blood levels, associated with an almost immediate (within 1 min) restoration of cardiovascular function and with a more gradual recovery of EEG, which became normal after 30–40 min; all parameters remained stable throughout the 60-min observation period. In saline-treated rats, on the other hand, there was a further increase in NO blood levels, as detected 3 min after treatment, and all died within 5–8 min. Moreover, pretreatment and treatment with S-methylisothiourea sulphate (SMT, 3 mg/kg i.v.), a relatively specific inhibitor of inducible NO synthase, inhibited NO formation, but did not affect the mortality rate (100% within 5–8 min). The present results provide the first evidence that prolonged asphyxia is associated with high blood concentrations of NO, and that the life-saving effect of melanocortin peptides in severe hypoxic conditions is associated with a complete normalization of NO blood levels. However, the lack of SMT protection in this experimental model seems to rule out the possibility that the ACTH-(1–24)-induced resuscitation is due to an effect on NO overproduction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00005323
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  • 17
    Digitale Medien
    Digitale Medien
    Ethanol discrimination in the rat: lack of modulation by restraint stress and memantine (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 117-122 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Key words Ethanol ; Restraint stress ; NMDA receptor complex ; Memantine ; Drug discrimination ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is a large body of experimental evidence that both stress and N-methyl-d-aspartate (NMDA) receptor antagonists may alter acute behavioural effects of ethanol. Notably, an uncompetitive, low-affinity NMDA receptor antagonist, memantine, has been recently claimed to possess anti-craving properties in rats with a long-term history of ethanol consumption. The aim of the present study was to assess the effects of restraint stress and memantine on the dose-response curve of ethanol discrimination. Rats were trained to discriminate 1 g/kg ethanol from saline in the two-lever drug discrimination procedure. When ethanol discrimination was acquired, the subjects were exposed to 30-min sessions of acute restraint stress, and different doses of ethanol (0.25, 0.5 or 1 g/kg) or saline were administered. In subsequent experiments the effects of memantine (2.25 or 4.5 mg/kg) on the cueing effects of ethanol were tested. Neither the stress sessions nor memantine influenced the ethanol discrimination dose-response curve. Moreover, the stress did not alter the rate of responding. However, both doses of memantine tended to increase the rate of responding when given in combination with lower doses of ethanol (0.25–0.5 g/kg). In contrast, 4.5 mg/kg memantine decreased the response rate when combined with 1 g/kg ethanol. These results suggest that: (1) pre-exposure to acute restraint stress or memantine does not affect the dose-response curve of ethanol discrimination; (2) memantine given in combination with low doses of ethanol may stimulate operant behaviour in the food-reinforced drug discrimination procedure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00005330
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  • 18
    Digitale Medien
    Digitale Medien
    The prognostic significance of tumor vascularization in patients with localized colorectal cancer (1999)
    Springer
    International journal of colorectal disease 14 (1999), S. 272-276 
    Details
    ISSN: 1432-1262
    Schlagwort(e): Key words  Colorectal cancer ; Angiogenesis ; Vessel density ; Prognosis ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a ×200 field in the area of the most dense neovascularization. Vascular density was found to be 75±27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (〉75) than in those of less vessel density (〈75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003840050227
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  • 19
    Digitale Medien
    Digitale Medien
    bcl-2 immunoreactivity but not p53 accumulation associated with tumour response to radiotherapy in cervical carcinoma (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 55-60 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words: Cervix ; p53 ; bcl-2 ; Radiotherapy ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose : This study seeks to define the role of pretreatment expression of the tumour-suppressor p53 protein and the anti-apoptotic protein bcl-2 and their relationship to tumour response to radiotherapy in cervical carcinoma. Methods : A total of 101 patients were evaluated and the possibility of a correlation done between the pretreatment status of the two proteins and clinical outcome following radiotherapy was investigated. Such patients were either disease-free (group 1, n = 65) or had residual/recurrent disease (group 2, n = 36) at a 16-month follow-up. p53 and bcl-2 protein expression was determined by immunocytochemistry. The presence of mutant p53 was detected by a mutant specific p53 enzyme-linked immunosorbent assay. Results : There was no correlation between p53 immunoreactivity or the presence of mutant p53 protein and disease status after treatment. Expression of bcl-2 protein, however, showed significant pretreatment correlations with the final disease outcome (r = 0.643, P = 0.0001). Moreover the odds ratio of a tumour expressing moderate to intense levels of bcl-2 responding poorly to radiotherapy was 27.2 (95% CI 6.0, 123.3). Conclusions : bcl-2 protein functions in an anti-oxidant pathway to prevent apoptosis. Since radiotherapy efficacy depends on adequate DNA damage caused by free-radical generation, increased expression of bcl-2 may result in tumours becoming less responsive to radiation. Mutation of the p53 gene, however, is a rare event in cervical cancer. Since bcl-2 is negatively regulated by p53, it could be presumed that the p53 detected in the tumour cells may be non-functional or inactive possibly because of interaction with proteins such as E6 or mdm-2.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050242
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  • 20
    Digitale Medien
    Digitale Medien
    E-cadherin expression in oesophageal carcinoma treated with high-dose radiotherapy; correlation with pretreatment parameters and treatment outcome (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 641-645 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words E-cadherin expression ; Radiotherapy ; Oesophageal carcinoma ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background and purpose: E-cadherin plays an important role in the cell-cell contact of normal epithelium. Loss of E-cadherin expression may be related to tumour invasiveness and metastatic potential. In a group of patients treated for oesophageal carcinoma by radiotherapy only, we found that immunohistochemically detected p53 expression correlated with reduced survival, mainly because of the occurrence of distant metastases. We questioned whether, in this group of patients, E-cadherin expression was concomitantly altered and served as a predictive factor for the development of distant metastases. Materials and methods: Immunostaining for E-cadherin was performed on paraffin- embedded biopsy specimens from patients with adenocarcinoma and squamous cell carcinoma of the oesophagus. E-cadherin status and its correlation with regard to pretreatment parameters and treatment outcome were determined. Results: An aberrant staining pattern of E-cadherin did not correlate with any of the pretreatment parameters. In a univariate analysis, a significantly reduced metastatic potential was found for tumours that had an aberrant cellular staining pattern for E-cadherin, which was strongest for squamous cell carcinomas. However, in a multivariate analysis only p53 status correlated significantly with the occurrence of distant metastases. Conclusion: Although, in univariate analysis, aberrant E-cadherin expression served as a better, rather than a worse prognostic factor, p53 status remained the only significant parameter in multivariate analysis, in this group of patients with oesophageal carcinoma. No relationship between p53 status and E-cadherin expression was found.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050328
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  • 21
    Digitale Medien
    Digitale Medien
    Expression of CD44 variants in osteosarcoma (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 646-652 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Osteosarcoma ; CD44 ; Immunohisto-chemistry ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells, epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44 has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated 44 tumour specimens in 39 patients with osteosarcoma immunochemically to analyse the expression of CD44 standard (CD44H) and variant exon-encoded gene products (CD44v3, v4, v5, v6, v7, v9, and v10). Furthermore, the relationship between CD44 expression and the clinical outcome of patients with osteosarcoma was analysed. Membrane accentuation and exclusive cytoplasmic reactivity were analysed as separate staining patterns. Tumour cells and some multinucleated giant cells were markedly stained. CD44H, v3, v4, v5, v6, v7, v9, and v10 were expressed in 85%, 49%, 54%, 59%, 46%, 5%, 28%, and 10% of the specimens respectively. The cumulative 5-year metastasis-free survival was 58% in CD44v6-negative cases and 24% in CD44v6-positive cases (P=0.046). However, the cumulative 5-year metastasis-free survival was not significantly different between cases positive and negative for other variants of CD44. Multivariate analysis (Cox proportional-hazard model) with CD44v6 expression (positive or negative), chemotherapy (intensive or non-intensive), tumour site (proximal or distal), and age (at least 30 years or less than 30 years) showed that expression of CD44v6 and chemotherapy were important prognostic factors in patients with osteosarcoma. Overexpression of CD44 isoforms containing variant v6 is correlated with poor prognosis in patients with osteosarcoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050329
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  • 22
    Digitale Medien
    Digitale Medien
    Immune functions, clinical parameters and hormone receptor status in breast cancer patients (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 313-320 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Breast cancer ; Immune function ; Tumour burden ; Hormone receptors ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have carried out a detailed analysis of the cellular immune functions of breast cancer patients in comparison with healthy controls. A possible correlation between immune and clinical parameters was analysed in 50 breast cancer patients. Immune parameters, natural killer cell and T lymphocyte functions and the numbers of circulating T lymphocytes were analysed against the clinical parameters comprising the tumour burden, the stage of the disease and the expression of hormone receptors on the tumour. In order to analyse the immune function data effectively, low responders were identified with stringent cut-off values. Considerably higher proportions of low responders were found among the patient population. Elevated numbers of circulating T lymphocytes and CD3-directed cytolysis correlated with the expression of oestrogen receptors independently of the clinical/histological parameters.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050280
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  • 23
    Digitale Medien
    Digitale Medien
    Microvessel density of hepatocellular carcinoma: its relationship with prognosis (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 419-426 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Key words Angiogenesis ; Hepatocellular carcinoma ; Prognosis ; Microvessel density
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To elucidate the relationship between angiogenesis and prognosis after curative resection of hepatocellular carcinoma (HCC). Methods: An immunohistochemical study using anti-CD34 monoclonal antibody was carried out on surgical specimens from 78 HCC patients who had undergone curative resection; microvessel density (MVD) was counted and the overall survival and disease-free survival were analyzed retrospectively. Results: Blood vessels in the tumor were strongly stained by anti-CD34 antibody, but not those in the surrounding liver parenchyma. There were three types of tumor vessels: capillary-like (n = 59), sinusoid-like (n = 16) and mixed-type (n = 3). The median MVD count was 100 per field. The HCC were designated as hypovascular (n = 36) with an MVD count below 100, and hypervascular (n = 42) with an MVD count of 100 or more per field. The 5-year survival and disease-free survival rates were 49.7% and 42.8% respectively, and statistical analysis showed that the MVD level was not correlated with tumor size, capsule status, Edmondson's grade, α-fetoprotein level, associated cirrhosis, γ-glutamyltransferase, and serum HBsAg status. The sinusoid-like tumor vessels appeared more frequently in the more differentiated tumors (P 〈 0.05). No statistical difference in overall and disease-free survival between different MVD levels and microvessel types was found. Tumor size was the only predicting factor in the entire series. In patients with small HCC (≤ 5 cm, n = 40), 5-year survival and disease-free survival rates were 58.9% and 52.7% respectively, higher than the values in large HCC (39.8% and 32.0% respectively, P 〈 0.05). The MVD level was an independent predicting factor of disease-free survival, 5-year disease-free survival in the hypovascular group (74.6%) being better than that in the hypervascular group (34.7%, P 〈 0.05). Conclusions: The MVD level was not related to tumor size, capsule statuo, Edmondson's grade, α-fetoprotein level, associated cirrhosis, γ-glutamyltransferase and serum HBsAg status. In the entire series, tumor size was the only factor influencing survival after curative resection. However, in patients with small HCC, the MVD level was an independent factor of disease-free survival. The pathological and clinical implications of different types of tumor vessels in HCC remain to be studied.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004320050296
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  • 24
    Digitale Medien
    Digitale Medien
    Onkogene humane Papillomaviren Schlüsselrolle bei Plattenepithelkarzinomen der Tonsillen mit Defekt im Retinoblastomprotein* (1999)
    Springer
    HNO 47 (1999), S. 796-803 
    Details
    ISSN: 1433-0458
    Schlagwort(e): Schüsselwörter Tonsillenkarzinome ; Onkogene humane Papillomaviren (HPV) ; Retinoblastomprotein (pRb) ; Prognose ; Key words Tonsillar squamous cell carcinomas ; Oncogenic human papillomavirus ; Retinoblastoma protein ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In order to identify squamous cell carcinomas of the head and neck (HNSCC) with common biological and clinical features, we investigated the incidence and properties of carcinomas lacking retinoblastoma protein (pR6) cell cycle control. Of 208 HNSCC investigated, 23 (11%) showed a lack of pRb expression. The majority of these tumors (65%) were tonsillar carcinomas. The pRb-negative tonsillar tumors were all stage IV, had metastasized to lymph nodes at the time of diagnosis and were in general poorly differentiated or undifferentiated. Very significantly, the pRb-negative phenotype was strongly associated with the presence of oncogenic human papilloma viruses, implying a viral etiology and functional inactivation of pRb by the viral E7 oncoprotein. Despite the very adverse histopathological factors, patients with pRb-negative tonsillar carcinomas had a better clinical outcome, which was consistent with a uniform favorable responsiveness of these tumors to postoperative radiation therapy.
    Notizen: Zusammenfassung Hinsichtlich biologischer Tumorcharakteristika, Genese und klinischen Eigenschaften von Plattenepithelkarzinomen im Kopf-Hals-Bereich bestehen viele Unklarheiten. Zur besseren Charakterisierung dieser Karzinome wurde geprüft, ob es Tumoren mit Defekten im Retinoblastomstoffwechsel gibt und ob weitere molekulare und klinische Gemeinsamkeiten vorliegen. Bei 11% der untersuchten Plattenepithelkarzinome des Kopf-Hals-Bereichs (23 von 208) lag ein Defekt im Retinoblastomstoffwechsel vor; 15 dieser 23 Tumoren (65%) waren in der Tonsille lokalisiert. Die pRb-negativen Tumoren lagen überwiegend als Stadium IV (UICC) vor, hatten bereits in regionäre Lymphknoten metastasiert und wiesen eine geringgradige Differenzierung auf. Dagegen waren klinische Verläufe und Gesamtüberlebenszeiten nach Operation und Strahlentherapie günstig. Die molekularbiologischen Analysen zeigten folgende Gemeinsamkeiten innerhalb dieser Gruppe der Tonsillenkarzinome: Der Retinoblastom-Protein (pRb)- und Cyclin-D1-Spiegel waren erniedrigt, p16INK4a erhöht. Es zeigte sich eine starke Assoziation mit onkogenen humanen Papillomaviren (HPV), durch deren Onkogen E7 wahrscheinlich die pRb-Inaktivierung erfolgt. Damit kommt den Papillomaviren eine wesentliche Rolle für die Entstehung und besonderen klinischen Eigenschaften dieser Tonsillenkarzinome zu.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001060050462
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  • 25
    Digitale Medien
    Digitale Medien
    The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients (1999)
    Springer
    Supportive care in cancer 7 (1999), S. 128-133 
    Details
    ISSN: 1433-7339
    Schlagwort(e): Key words Advanced cancer ; Palliative care ; Prognosis ; Prediction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Although accurate prediction of survival is essential for palliative care, few clinical methods of determining how long a patient is likely to live have been established. To develop a validated scoring system for survival prediction, a retrospective cohort study was performed with a training–testing procedure on two independent series of terminally ill cancer patients. Performance status (PS) and clinical symptoms were assessed prospectively. In the training set (355 assessments on 150 patients) the Palliative Prognostic Index (PPI) was defined by PS, oral intake, edema, dyspnea at rest, and delirium. In the testing sample (233 assessments on 95 patients) the predictive values of this scoring system were examined. In the testing set, patients were classified into three groups: group A (PPI≤2.0), group B (2.0〈PPI≤4.0), and group C (PPI〉4.0). Group B survived significantly longer than group C, and group A survived significantly longer than either of the others. Also, when a PPI of more than 6 was adopted as a cut-off point, 3 weeks' survival was predicted with a sensitivity of 80% and a specificity of 85%. When a PPI of more than 4 was used as a cut-off point, 6 weeks' survival was predicted with a sensitivity of 80% and a specificity of 77%. In conclusion, whether patients live longer than 3 or 6 weeks can be acceptably predicted by PPI.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s005200050242
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  • 26
    Digitale Medien
    Digitale Medien
    Dendritische Zellen, T-und B-Lymphozyten und Makrophagen im supraglottischen und glottischen Plattenepithelkarzinom Lokalisation und Korrelation zur Prognose der Erkrankung (1999)
    Springer
    HNO 47 (1999), S. 466-471 
    Details
    ISSN: 1433-0458
    Schlagwort(e): Schlüsselwörter Schleimhautimmunsystem ; Tumorabwehr ; Prognose ; Key words Mucosal immune system ; Squamous cell carcinoma ; Tumor defense ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Dendritic cells play an important role within the mucosal immune system of the upper aerodigestive tract. They process exogenous and endogenous antigens and are able to induce a cytotoxic TC/S lymphocyte reaction against tumors. Recently published data indicate that the in vitro application of tumor lysate incubated dendritic cells can provide a defense against melanoma. Before these new therapeutic strategies are available for the therapy of laryngeal cancer, basic studies have to be performed concerning the distribution of dendritic cells and other subpopulations, such as T- and B-lymphocytes and macrophages. In the present study the distribution of these subpopulations were examined within the epithelial and connective tissue compartments (”tumor front”) of 20 T2 squamous cell carcinomas of the supraglottis and glottis. The number of dendritic cells was compared with clinical parameters to check whether a high number of dendritic cells could be correlated with a better prognosis. In contrast to T-lymphocytes, results showed that dendritic cells were mainly located within the epithelial compartment of the tumors, their number ranging from 20 cells/mm2 to 〉700 cells/mm2. By comparing each patient’s clinical course with the number of dendritic cells, findings showed that those patients who died within the first postoperative year were characterized by a very small number of dendritic cells within their tumor tissue (〈100 cells/mm2). Although the number of patients was low, results indicate that a high number of dendritic cells within tumor tissue suggest a better prognosis.
    Notizen: Zusammenfassung Dendritische Zellen nehmen eine zentrale Stellung in der Initialisierung der Immunantwort ein, denn sie sind die potenteste Subpopulation des Schleimhautimmunsystems, die T-Lymphozyten via MHC-Rezeptor aktivieren können. Dies gilt insbesondere für die Initialisierung einer zytotoxischen T-Zell-Antwort gegenüber Malignomen. Erste klinische Studien an Patienten mit therapieresistentem Melanom und Lymphom zeigen, daß in vitro mit Tumorantigen sensibilisierte dendritische Zellen erfolgreich in vivo zur Immuntherapie eingesetzt werden können. Da für das Larynxkarzinom bisher kaum grundlegende Daten über das Vorkommen von dendritischen Zellen im Tumorgewebe und deren Funktion bekannt sind, wurde in der vorliegenden Studie die Lokalisation von dendritischen Zellen und anderen Subpopulationen des Schleimhautimmunsystems, wie T- und B-Lymphozyten und Makrophagen in Plattenepithelkarzinomen der Supraglottis und der Glottis immunhistologisch untersucht. Die Daten wurden mit klinischen Parametern wie Lymphknotenstatus und postoperatives Überlebensintervall verglichen. Die Resultate zeigen, daß dendritische Zellen im Gegensatz zu T-Lymphozyten vor allem im epithelialen Kompartiment der Plattenepithelkarzinome nachweisbar sind. Ihre Anzahl weist starke Schwankungen auf (20 bis zu 〉700 Zellen/mm2). Beim Vergleich mit den klinischen Parametern zeigt sich, daß die Patienten, bei denen die Zahl der dendritischen Zellen im Karzinom gering war (〈100/Zellen/mm2), die geringste postoperative Überlebenszeit (1 Jahr) aufwiesen. Dies deutet darauf hin, daß eine hohe Zahl dendritischer Zellen im Larynxkarzinom einen günstigen Prognosefaktor der Erkrankung darstellt.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001060050406
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  • 27
    Digitale Medien
    Digitale Medien
    Möglichkeiten der Rezidivbehandlung des Zervixkarzinoms (1999)
    Springer
    Der Gynäkologe 32 (1999), S. 312-321 
    Details
    ISSN: 1433-0393
    Schlagwort(e): SchlüsselwörterZervixkarzinom ; Rezidivbehandlung ; Therapieformen ; Prognose ; Key wordsCarcinoma of the cervix ; Treatment of recurrences ; Types of therapy ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Approximately one out of every three patients with carcinoma of the cervix must be expected to experience a recurrence. The treatment of such relapses is dependent on the site and extension of the recurrence, the type of primary therapy administered and the patient's general condition. The limit conditions for the application of the established forms of therapy available – surgical operation, radiotherapy, chemotherapy – are complex and seldom documented by randomized studies. In general, empiric observations and historical analyses determine the backdrop against which therapy is planned. The main experiences available are compiled in this paper to give a basis for individual treatment of patients with recurrences.
    Notizen: Zusammenfassung Etwa jede dritte Patientin mit einem Zervixkarzinom muß mit einem Rezidiv rechnen. Die Behandlung dieser Rezidive ist abhängig vom Sitz und der Ausbreitung des Rezidivtumors, der Art der vorangegangenen Primärtherapie und dem Allgemeinzustand der Patientin. Die Rahmenbedingungen für den Einsatz der verfügbaren etablierten Therapieformen – Operation, Bestrahlung, Chemotherapie – sind komplex und nur selten durch randomisierte Studien belegt. Im wesentlichen bestimmen Anwendungsbeobachtungen und historische Analysen den Hintergrund der Therapieplanung. Die wesentlichen verfügbaren Erfahrungen sollen im folgenden zusammengestellt werden als eine Entscheidungsgrundlage für die individuelle Behandlung von Rezidivpatientinnen.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00003231
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  • 28
    Digitale Medien
    Digitale Medien
    Kritische Lebensereignisse im 2-Jahresverlauf der „Major Depression”Eine prospektive Studie mit stationär behandelten Patienten (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 637-644 
    Details
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Kritische Lebensereignisse/Lebensbedingungen ; Endogene Depression ; Prospektivstudie ; Krankheitsverlauf ; Gesunde Kontrollgruppe ; Key words Life events/life conditions ; Endogenous depression ; Prospective study ; Prognosis ; Healthy controls
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary A number of studies has shown a significant relationship between life events/life conditions and depression. However, there is only a small number of studies investigating the effect of life events/life conditions in patients with severe depression from the endogenous subtype. The results are inconsistent. The present study examines the significance of the patients’ life events/life conditions for the two year outcome of the illness in a prospective study with assessments every three months. Patients are compared to healthy controls with regard to the period three months prior to the admission to the hospital at the index episode. The results confirm the importance of life events and life conditions for the long term outcome of depressed patients with endogenous subtype respectively severe major depression in-patients. Relapsers show considerably more undesirable life conditions than non-relapsers three to six months prior to their relapse. Depressed patients indicate significantly more undesirable life events and life conditions and fewer desirable life conditions in comparison to the control group for the time span three months prior to their hospitalisation. Clinical implications are discussed.
    Notizen: Zusammenfassung In zahlreichen Studien konnten signifikante Zusammenhänge zwischen kritischen Lebensereignissen/Lebensbedingungen und Depressionen nachgewiesen werden. Es liegen jedoch nur wenige und inkonsistente Befunde zu der Bedeutsamkeit von kritischen Lebensereignissen bei schwer depressiven Patienten des endogenen Subtyps bzw. schwer depressiven stationär behandelten Patienten mit Major Depression vor. Die vorliegende Studie untersucht in einem prospektiven Längsschnittdesign über einen Zeitraum von zwei Jahren in dreimonatigen Abständen die rückfallprädiktive Bedeutung von kritischen Lebensereignissen für den Krankheitsverlauf endogen depressiver Patienten. Des weiteren werden gesunde Kontrollpersonen in einem Querschnittdesign mit den depressiven Patienten in dem Zeitraum drei Monate vor der Kliniksaufnahme verglichen. Rückfallpatienten weisen drei und sechs Monate vor dem Rückfall signifikant mehr unerwünschte Lebensbedingungen auf als Patienten mit einem günstigen Verlauf. Bezogen auf die drei Monate vor dem Klinikaufenthalt geben die endogen depressiven Patienten signifikant mehr unerwünschte Lebensereignisse und Lebensbedingungen und weniger erwünschte Lebensbedingungen an als die gesunden Kontrollpersonen. Die Ergebnisse werden unter klinischen Gesichtspunkten diskutiert.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001150050489
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  • 29
    Digitale Medien
    Digitale Medien
    Further accumulation of Cd in renal cellular membranes caused by administration of desferrioxamine to Cd-burdened rats (1999)
    Springer
    Clinical and experimental nephrology 3 (1999), S. 23-28 
    Details
    ISSN: 1437-7799
    Schlagwort(e): Key words Desferrioxamine ; Cadmium ; Metallothionein ; Nephrotoxicity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Desferrioxamine (DFO) a chelating agent, is used to treat metal toxicity caused by iron and aluminum in patients on hemodialysis. We hypothesized that DFO could also be used to treat cadrium-induced nephropathy. Animal experiments were therefore performed to explore whether DFO removed cadmium (Cd) from the kidneys of rats with a Cd burden. Methods. Rats received subcutaneous injections of Cd chloride (3 mg Cd/kg per day, days 0–7) followed by DFO (50 mg/kg per day, days 8–14). Levels of Cd were determined in liver, kidneys, and plasma. Enzymes assays and histopathological examination were performed in kidneys. Results. In liver, Cd injections elevated Cd levels; subsequent injections of DFO lowered the Cd levels compared with levels after injections of Cd alone. In kidneys, Cd injections increased levels of total Cd and Cd bound to cellular membranes (Mem-Cd), and decreased leucine aminopeptidase (LAP) activity (a marker of renal injury); subsequent injections of DFO elevated levels of total Cd and Mem-Cd, and lowered LAP activity compared with fundings after the injection of Cd alone. After the injections of Cd alone and DFO following Cd the renal levels of Cd were below the critical concentration required to cause renal injury, since no histopathological changes were observed in the kidney. Conclusion. DFO administration to Cd-burdened rats removed Cd from the liver, but led to accumulation of Cd in the kidneys, particularly in the cellular membranes. These results suggest that if DFO is given long-term to Cd-burdened patients, the Cd level in kidneys, particularly in renal cellular membranes, could reach concentrations that could cause manifest renal injury.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101570050004
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  • 30
    Digitale Medien
    Digitale Medien
    Effect of antenatal glucocorticoid administration on insulin-like growth factor I and II levels in hypoplastic lung in nitrofen-induced congenital diaphragmatic hernia in rats (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 175-179 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Congenital diaphragmatic hernia ; Rat ; Glucocorticoid ; Antenatal therapy ; Insulin-like growth factor I and II ; Reverse transcription-polymerase chain reaction (RT-PCR)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is increasing evidence to suggest that insulin-like growth factors (IGF) I and II play a crucial role in fetal lung development. Expression of IGF-I and II has been demonstrated to be predominant during fetal life and decreases prior to birth. Antenatal glucocorticoids are reported to improve lung immaturity. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on IGF-I and II expression in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term = 22 days). Dexamethasone (0.25 mg/kg) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21. The fetuses were divided into three groups: I, normal controls; II, nitrofen-induced CDH; and III, nitrogen-induced CDH with antenatal dexamethasone treatment. mRNA was extracted from whole lung and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of IGF I and II mRNA. Levels of mRNA were expressed as a ratio of the band density divided by that of β-actin, a housekeeping gene known to be expressed at a constant level. Immunohistochemistry using anti-rat IGF I and II antibody was also performed in each group. Levels of IGF I mRNA were significantly increased in group II (0.50 ± 0.08) compared to group I (0.34 ± 0.10) or group III (0.32 ± 0.06) (P 〈 0.05). Levels of IGF II mRNA were also significantly increased in group II (0.95 ± 0.20) compared to group I (0.42 ± 0.07) or group III (0.31 ± 0.09) (P 〈 0.05). Strong IGF I and II expression was observed in the hypoplastic CDH lung (group II), mainly in the bronchiolar epithelium. IGF I and II expression in group I and III lungs was either absent or weak. The finding of significant reductions in IGF I and II mRNA and protein levels in dexamethasone-treated CDH lung suggest that dexamethasone may accelerate the fetal stage of lung development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050548
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  • 31
    Digitale Medien
    Digitale Medien
    Notochord involvement in experimental esophageal atresia (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 201-205 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Esophagus ; Atresia ; Notochord ; Adriamycin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Esophageal atresia (EA) is often accompanied by vertebral defects and other anomalies. The adriamycin rat model of EA has disclosed the embryology of the malformation and shown that the vertebrae and notochord are also abnormal. This study describes the nature of notochord malformations in rat embryos exposed to adriamycin. Time-mated rats received either 1.75 mg/kg adriamycin or vehicle i.p. on gestational days (E) 6 to 9; E-12, E-12.5, and E-13 embryos were harvested, embedded in paraffin, and serially sectioned at 3 μm in transverse plane from the head to the stomach for subsequent PAS staining. The findings in both groups were compared at the three endpoints. Control embryos had neither tracheoesophageal nor notochord malformations. On day 12, only 11/36 adriamycin embryos were normal; 7/36 had abnormal notochords, 11/36 had EA, and 7/36 had both. The corresponding figures for 12.5 days were 12/27, 0/27, 7/27, and 8/27 and those for the day 13 7/23, 5/23, 3/23, and 8/23. The malformed notochords were thickened, bifurcated, or trifurcated in the sagittal plane. The simultaneous presence of notochord and esophageal malformations suggests a direct link between both defects, but our observation of isolated occurrence of both shows that they reflect two expressions of the profound disturbance of embryonic para-axial organization responsible for the cluster of malformations rather than a cause-effect association.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050555
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  • 32
    Digitale Medien
    Digitale Medien
    Unilateral blunt testicular trauma in pre-pubertal rats (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 457-460 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Blunt testicular injury ; Rat ; DNA flowcytometry ; Antisperm antibodies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Injury to the testis breaching the tunica albuginea is known to affect fertility. Blunt testicular trauma with an intact tunica albuginea has been reported to have no effect on contralateral testicular histology and Johnsen testicular maturation score. However, sensitive techniques like DNA flowcytometry have not been utilized so far to evaluate contralateral testicular germ-cell changes. Sixty-four male Wistar rats aged 20 days were randomized into groups I (control), II (unilateral blunt testicular trauma, UBTT), III (UBTT and excision of ipsilateral testis at 6 h), and IV (UBTT and cyclosporine for 30 days). Fertility, DNA flowcytometry of contralateral testicular tissue, and anti-sperm antibodies (ASA) were evaluated. Fertility and haploid-cell percentage of the contralateral testis were significantly decreased compared to controls in early adulthood (100 days). Around 150 days of age, as ASA decreased significantly, fertility and contralateral testicular haploid-cell population recovered and were comparable to the controls. Excision of the traumatized testicle around 6 h after injury or administration of cyclosporine for 30 days protected fertility and the contralateral testis. In contrast to group II rats, ELISA for ASA was negative in group III and IV rats. UBTT affects the contralateral testis and fertility. ASA mediate this damage. Orchidectomy performed around 6 h after trauma or short-term cyclosporine therapy prevents the damage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050637
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  • 33
    Digitale Medien
    Digitale Medien
    Long-term follow-up in patients with bilateral testicular germ cell tumors: a report of ten cases (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 244-247 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Bilateral testicular tumor ; Treatment ; Follow-up ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several risk factors have been identified for the development of testicular germ cell tumors with history of a testicular tumor in the contralateral testis being one of the most important factors; the incidence of bilateral tumors in large series ranges from 2% to 5%. The aim of this study was to evaluate the results of long-term follow-up in patients with bilateral testicular germ cell tumors. In a series of 247 patients with testicular germ cell tumors treated at Kobe University Hospital between 1966 and 1995, 10 patients (4.0%) had bilateral testicular tumors. Clinicopathological data are presented for these 10 patients and the literature is reviewed. Of the 10 patients with bilateral tumors, 2 had a simultaneous bilateral tumor, and in the remaining 8 patients, the second tumor was diagnosed after an interval of 2 months to 16 years. All 10 patients were diagnosed as stage I or II in both the initial and secondary tumors. Five patients had identical histological findings in both tumors. Eight patients were free of disease after a median observation period of 13.5 years, and the remaining 2 patients died of metastatic disease. The present results are essentially consistent with previous studies analyzing the features of bilateral testicular germ cell tumors. Considering these findings, close clinical follow-up and patient education appeared to be an appropriate follow-up strategy in patients with testicular tumors, as the secondary tumors can generally be cured with current treatment regimens.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050062
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  • 34
    Digitale Medien
    Digitale Medien
    Safe limits for ovarian conservation in patients with adenocarcinoma of the cervix (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 384-389 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Adenocarcinoma of the uterine cervix ; Ovarian conservation ; Ovarian transposition ; Ovarian recurrence ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Our study had two aims: (1) to evaluate the effect of ovarian conservation on the prognosis of patients with adenocarcinoma of the cervix and (2) to determine the method by which – and the stage up to which – ovaries can be conserved without adversely affecting a favorable prognosis. Methods. We performed either radical hysterectomy with lymphadenectomy or simple hysterectomy on 70 patients in stages 0 to IIIab of adenocarcinoma of the cervix (International Federation of Gynecology and Obstetrics). The postmenopausal patients underwent oophorectomy, while the ovaries of premenopausal patients were left in situ or transposed laterally. We then followed the subsequent condition of the patients to see whether or not ovarian conservation affected their ability to survive for up to 5 years. Results. We found no evidence of ovarian metastasis among patients in stages 0 to IIab of the disease, while three cases were found in patients whose carcinoma was in stage IIIab; 94% of the patients whose ovaries had been conserved survived for 5 years; of the patients who underwent oophorectomy, 100% survived. However, the difference was not significant. Two patients (stages Ib and IIb) suffered a recurrence of cancer in the transposed ovaries: at the time of the initial surgery the lymph nodes in both patients had been positive. Conclusions. If patients with adenocarcinoma of the cervix are operated on during stages 0 to Ia of the disease, ovarian conservation will not affect survival; ovaries can be left in situ or can be transposed laterally without affecting the survival prognosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050089
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  • 35
    Digitale Medien
    Digitale Medien
    Neoadjuvant chemotherapy with carboplatin, ifosfamide, and peplomycin in advanced cervical squamous cell carcinoma (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 358-363 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Uterine cervical carcinoma ; Neoadjuvant chemotherapy ; Prognosis ; Carboplatin ; Ifosfamide ; Peplomycin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. To control advanced cervical squamous cell carcinoma more effectively and more easily, we used neoadjuvant chemotherapy, with three drugs carboplatin, ifosfamide, and peplomycin (PIP), in a study performed from July 1990 to October 1994 in nine Institutions. Methods. Sixty-five patients with untreated, inoperable squamous cell carcinoma of the cervix were treated with carboplatin (300 mg/m2 IV; low-dose PIP regimen, or 400 mg/m2 IV; high-dose PIP regimen) on day 1, ifosfamide (1000 mg/m2, IV) on days 1–3, and peplomycin (5 mg/body, IM) on days 1–6. The low-dose PIP was given between July 1990 and April 1992, and the high-dose PIP from May 1992 to October 1994. Results. Response rates for the low- and high-dose PIP regimens were 42.9% (12/28) and 59.5% (22/37), respectively. Measurable lesions were recognized in the cervix, pelvic lymph node (PeN), paraaortic lymph node (PAN), lung, and supraclavicular lymph node. Response rates in these individual lesions to our low- and high-dose PIP regimens were 35.7% (10/28) and 55.6% (20/36), respectively in the cervical lesion and more than 50% for both regimens in the PeN and PAN metastatic lesions, while the supraclavicular lymph node metastatic lesions responded poorly to both regimens. After low-dose PIP, surgery was performed in 2 patients (2/28; 7.1%), while after high-dose PIP, 12 patients (12/37; 32.4%) underwent surgery. The 3-year survival rate of patients with high-dose PIP was significantly higher than that of those with low-dose PIP (P 〈 0.01). Conclusions. Neoadjuvant chemotherapy with PIP appears feasible and effective. The link between dosage and treatment response and achievable surgery rate and survival rates suggests that results might be further optimized by considering patients' renal function, and utilizing the Calvert formula for dosing analysis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050085
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  • 36
    Digitale Medien
    Digitale Medien
    Experimental unilateral undescended testis: gubernaculectomy and anchoring or direct suture fixation? (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 461-464 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Unilateral undescended testis ; Rat ; Testicular injury ; DNA flowcytometry ; Anti-sperm antibody
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study was designed to evaluate whether creation of a unilateral undescended testis (U/L UDT) in rats by direct fixation of the testis can lead to changes in the contralateral (C/L) descended testis, and if so, whether this inherent problem of the model could be eliminated by anchoring the divided gubernaculum to indirectly fix the testis. Thirty male newborn rats were divided into three groups of 10 each and the procedure done on the 2nd day of life to create U/L UDT according to the group allocated: group I: sham-operated; group II: anchoring the gubernaculum after gubernaculectomy; group III: Direct suture fixation of the testis. Fertility, C/L testicular weight (TW), Johnsen score, seminiferous tubular diameter (STD), DNA flowcytometry, and serum anti-sperm antibodies (ASA) were studied. Fertility, C/L TW, Johnsen score, STD, and haploid cell population were significantly reduced in group III compared to group II, while significantly higher titers of ASA were found in group III. Gubernaculectomy and anchoring the gubernaculum to the anterior abdominal wall is a better technique of creation of experimental UDT, as direct fixation of the testis is potentially detrimental to the C/L normal, descended testis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050638
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  • 37
    Digitale Medien
    Digitale Medien
    Sacrococcygeal teratoma: clinical course and prognosis with a special view to long-term functional results (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 573-576 
    Details
    ISSN: 1437-9813
    Schlagwort(e): Key words Sacrococcygeal teratoma ; Prognosis ; Functional impairment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract From 1976 to 1995, 23 children, 4 boys and 19 girls, were treated at our department for sacrococcygeal teratomas (SCT). Their records were analyzed retrospectively, considering age at operation, histopathology, recurrences, and long-term evolution. One died on the 1st day of life following tumor rupture with hemorrhagic shock without surgical intervention. All others were operated upon at a mean age of 4.2 days for those 19 (=82%) who were diagnosed in the neonatal period and whose histology proved benign. In the remaining 3 children, in whom tumor manifestation did not occur before 11 months, 13 months, and 10 years of age, respectively, histopathologic evaluation revealed 2 carcinomas and 1 yolk-sac tumor, and all 3 recurred. Overall, 5 patients died, the 1 mentioned above, 1 due to volvulus after laparotomy, and 1 from multiple associated congenital malformations. Two deaths were related to malignancy, whereby only 1 was a malignant teratoma diagnosed at the original operation. Eight children had recurrences, 2 were benign and 6 malignant, with 3 of the latter having been graded benign on histology of the primary tumor. Of the 18 surviving patients, 17 (93.5%) returned for clinical review following a standardized protocol. The average interval from the primary surgery was 12.3 years (range 3.5–22 years). Four had malignant tumors with a recurrence-free period of from 9 to 14 years; 5 (29.4%) had urinary or anorectal functional impairment. One child with a patulous anus presented with fecal soiling. Two reported nocturnal enuresis, 1 associated with perineal anesthesia. One had a neurogenic bladder with overflow voiding and bilateral third-degree vesicoureteral reflux. Second-degree reflux was found in the last patient. We conclude that follow-up after surgery for SCT should not only search for tumor recurrence but include the diagnosis and treatment of possible secondary urinary and/or fecal incontinence.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003830050675
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  • 38
    Digitale Medien
    Digitale Medien
    Effect of dose intensity of methotrexate, doxorubicin, and ifosfamide on the prognosis of patients with osteosarcoma (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 36-40 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Osteosarcoma ; Chemotherapy ; Dose inten-sity ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. The prognosis of patients with osteosarcoma has improved due to the introduction of systemic chemotherapy. The current study tried to identify the effect of each anti-tumor drug on the prognosis of patients with osteosarcoma. Methods. The records of 29 patients with osteosarcoma who received systemic chemotherapy were retrospectively analyzed. All tumors were classified as stage IIB (Enneking's surgical stage) and were located around the knee joint or more distal areas. The histologic response to preoperative chemotherapy was determined in 20 patients: 9 patients had grade 1, 4 grade 2, 5 grade 3, and 2 grade 4. The mean follow-up period was 102 months. Results. The 5-year overall survival and relapse-free survival (RFS) in the 29 patients was 47.7% and 41.4%, respectively. The 5-year RFS for the 7 good responders (grade 3 and 4) was 85.7%, and that for the 13 poor responders (grade 1 and 2) was 23.1% (P = 0.008). The mean preoperative dose intensity (DI) of methotrexate (MTX) for good responders was significantly higher than that for poor responders (P = 0.028). In 23 patients who received MTX and doxorubicin (ADR) but not ifosfamide (IFOS), the DI of MTX significantly influenced the RFS (P = 0.0128). In the 13 poor responders, 6 of whom received IFOS, the DI of IFOS and ADR significantly influenced RFS (P = 0.0112, 0.0395). Conclusion. The preoperative DI of MTX was related to the histologic response rate. The DI of MTX was significartly associated with the patients' RFS. In poor responders, the DI of IFOS and ADR influenced the patients' RFS.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050021
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  • 39
    Digitale Medien
    Digitale Medien
    Wheat germ agglutinin binding is a useful prognostic indicator in stomach cancer (1999)
    Springer
    International journal of clinical oncology 4 (1999), S. 96-100 
    Details
    ISSN: 1437-7772
    Schlagwort(e): Key words Wheat germ agglutinin ; Stomach cancer ; Lectin histochemistry ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Recent studies suggest that lectin binding activity is correlated with the metastasis and prognosis of several human carcinomas. Wheat germ agglutinin (WGA) is a lectin that recognizes mainly N-acetyl-glucosamin (GalNAc) and acetyl-neuramic acid. However, little is known about WGA expression in gastric carcinoma. The purpose of this investigation was to clarify the significance of WGA expression in human gastric carcinoma. Methods. WGA binding was examined immunohistochemically in 353 specimens of primary gastric carcinomas from patients surgically treated at the First Department of Surgery, Fukushima Medical School, between 1980 and 1990. We studied the relationship between WGA expression and various clinicopathologic features and long-term survival. Results. Overall, 145/353 of the tumors (41%) were stained for WGA. WGA expression correlated with mean patient age, lymph node metastasis, venous invasion, and liver metastasis. Patients with tumors that were nonimmunoreactive for WGA had significantly lower 5-year survival rates than those with immunostained tumors (P 〈 0.05). WGA expression emerged as an independent prognostic factor on Cox's multivariate analysis. Conclusion. WGA binding is a useful prognostic indicator. Careful follow-up and intensive postoperative therapy are required for patients with gastric carcinomas that are nonimmunoreactive for WGA.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s101470050034
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  • 40
    Digitale Medien
    Digitale Medien
    Proliferation marker Ki-S11 – a prognostic indicator for squamous cell carcinoma of the hypopharynx (1999)
    Springer
    Virchows Archiv 435 (1999), S. 590-595 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Hypopharynx carcinoma ; Prognosis ; Proliferation ; Ki-S11 ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (〉45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050445
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  • 41
    Digitale Medien
    Digitale Medien
    Irregular expression of hyaluronan and its CD44 receptor is associated with metastatic phenotype in laryngeal squamous cell carcinoma (1999)
    Springer
    Virchows Archiv 434 (1999), S. 37-44 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Hyaluronic acid ; CD44 receptor ; Adhesion ; Laryngeal neoplasms ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The distributions of hyaluronan (HA) and its CD44 receptor were studied in 24 normal, 27 dysplastic samples of laryngeal epithelium and in 172 squamous cell carcinomas (LSCC), using a specific probe prepared from cartilage proteoglycan (bHABC, biotinylated hyaluronan binding complex) and a monoclonal antibody (Hermes 3). HA and CD44 were expressed similarly in all normal and about 90% of dysplastic and neoplastic laryngeal epithelia. In the normal epithelium HA and CD44 were homogeneously distributed throughout the epithelium, whereas the most superficial layers were negative. This was in contrast to the picture in dysplastic epithelium and well-differentiated invasive carcinomas, which were entirely HA and CD44 positive. Local areas with a low signal for HA and CD44 were present in 11% and 22% of the samples with dysplasia, and in 27% and 28% of those with carcinoma, respectively. The presence of this staining irregularity was associated with poor differentiation of the carcinoma, a significantly elevated mitotic index and a high frequency of nodal spreading and metastases. Furthermore, the irregular staining showed a trend towards poor disease-free survival, suggesting that an altered metabolism of HA is a common feature in LSCC and is associated with an aggressive growth pattern.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050302
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  • 42
    Digitale Medien
    Digitale Medien
    Expression of pyruvate kinase M2 in preneoplastic hepatic foci of N-nitrosomorpholine-treated rats (1999)
    Springer
    Virchows Archiv 434 (1999), S. 213-220 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Pyruvate kinase isoenzymes ; N-Nitrosomorpholine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The expression of the pyruvate kinase (PK) isoenzymes L and M2 was analysed in the livers of rats treated with the hepatocarcinogenic agent N-nitrosomorpholine (NNM) in the drinking water. In control animals L-PK expression was restricted to liver parenchymal cells, whereas M2-PK was detected in bile duct epithelial, blood vessel wall, endothelial and Kupffer cells. In rats treated with NNM proliferating oval cells were consistently L-PK negative and M2-PK positive, while the ductal cells of cholangiofibroses were clearly L-PK positive and coexpressed M2-PK. However, no morphological differentiation of ductal cells into hepatocyte-like cells was observed. In the clear and acidophilic cell foci storing glycogen in excess strong staining for L-PK was observed. In glycogen-poor foci induced by NNM a shift from L-PK to M2-PK expression takes place.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050330
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  • 43
    Digitale Medien
    Digitale Medien
    Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma (1999)
    Springer
    Virchows Archiv 434 (1999), S. 325-332 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Key words Medullary thyroid carcinoma ; Basement membrane ; Laminin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The α2, β1 and γ1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6–23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of α2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of α2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004280050348
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  • 44
    Digitale Medien
    Digitale Medien
    Ureteral growth in animal models with increased renal excretion of urine (1999)
    Springer
    Urological research 27 (1999), S. 41-47 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key words Ureter ; Histology ; Polyuria ; Diabetes mellitus ; Nephrectomy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The influence of increased functional load on the macroscopical and histological appearance of the ureter was investigated. Sixty rats were divided into five groups: (1) sucrose-fed rats with non-osmotic polyuria; (2) diabetic rats with osmotic polyuria; (3) uninephrectomized rats; (4) sham-operated control rats; and (5) control rats. The 24-hour urinary volume was measured on days 7, 14 and 21. Growth of the kidney, ureter and bladder was investigated and the histological appearance of the ureter was further evaluated. Diabetic and sucrose-fed rats had comparable polyuria with a seven-fold increase in urinary output. The urinary volume for the remaining kidney was doubled in uninephrectomized rats. After 3 weeks, diabetic rats had increased weight of the kidney, ureter and bladder, sucrose-fed rats had increased weight of the bladder, whereas uninephrectomized rats had increased weight of the kidney and ureter. The cross-sectional area (CSA) of the ureter wall from control rats increased from the proximal to the distal portion. The size of the whole ureter from diabetic rats was dramatically increased, the CSA of the wall of the distal ureter portion being four times that of the controls. The CSA of the ureter wall from sucrose-fed rats was increased only in the distal portion, whereas the ureter from uninephrectomized rats was increased only in the proximal portion. The results demonstrate the importance of differentiating between different portions of the rat ureter when examining histological sections of this organ. Moreover, polyuria per se is shown to induce growth of the bladder and of the adjacent distal part of the ureter, whereas uninephrectomy and diabetes caused growth of the kidney and the upper parts of the ureter, in addition to the growth induced by polyuria.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050087
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  • 45
    Digitale Medien
    Digitale Medien
    Nonbacterial prostatitis caused by partial urethral obstruction in the rat (1999)
    Springer
    Urological research 27 (1999), S. 346-350 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key words Nonbacterial prostatitis ; Animal model ; Partial urethral obstruction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pathogenesis of nonbacterial prostatitis (NBP) is not understood mainly due to the lack of appropriate experimental models. We developed a new experimental model of NBP by inducing a partial obstruction of the urethra (PUO) in the rat. Male Wistar rats aged 12 weeks were used. PUO was produced by a nylon ligature on the urethra over a rubber tube. The tube was slipped out after the ligature had been tied. Two rats were examined histologically 6 h, 1 day, 3 days and 7 days after PUO. In another group, two rats were killed at 1, 3 and 7 days after the release of the PUO that had been left in place for 3 days. On day 3, another eight rats with PUO and eight control rats had 2 ml of urine in the bladder replaced by the same volume of lucifer yellow (LY; 10 μg/ml, MW 500), microperoxidase (MP; 20 μg/ml, MW 1900), horseradish peroxidase (HRP; 10 μg/ml, MW 40 000), or saline as control, respectively. Lymphocytic infiltration and interstitial edema were noted in the prostate following PUO, being most prominent on day 3. After the release of the PUO, these inflammatory changes gradually disappeared. Only LY was noted within the prostatic stroma of the rats 2 h after bladder instillation. Intraprostatic urinary reflux may be an etiologic factor in NBP. The present study showed that lower urinary tract obstruction caused NBP in the rat. Penetration of prostatic tissue by low-molecular-weight substances in the urine may trigger NBP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050161
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  • 46
    Digitale Medien
    Digitale Medien
    Sprouting of bladder nerves into cystoplastic cecal segment in the rat (1999)
    Springer
    Urological research 27 (1999), S. 476-482 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key words Urinary bladder ; Enterocystoplasty ; Cecocystoplasty ; Innervation ; Nerve growth ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to α-agonists and ATP) to that of the bladder (contraction to α-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050138
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  • 47
    Digitale Medien
    Digitale Medien
    Transient ischemia induces apoptosis in the ventral prostate of the rat (1999)
    Springer
    Urological research 27 (1999), S. 174-179 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Key words Apoptosis ; Ischemia-reperfusion ; Blood flow ; Ischemia ; Prostate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mechanisms involved in the castration-induced involution of the ventral prostate (VP) are not fully understood. It was recently reported that castration decreases blood flow in the VP in rats and that this occurs before the apoptotic involution of the organ. However, it is unknown whether a decrease in blood flow may trigger apoptosis in the VP, and this was therefore examined in this study. The right iliac artery was clamped for 1 h in adult male rats. After 24 h of reperfusion, the VPs were frozen or fixed. In situ end-labeling (ISEL) was used to identify apoptotic cells, and testosterone repressed prostatic message-2 (TRPM-2) was measured. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was used to identify proliferating cells. Clamping the right iliac artery reduced blood flow in the right VP to 0.17 of that in the contralateral lobe. This relative ischemia resulted in a threefold increase in the volume density of apoptotic epithelial cells on the treated side, but left cell proliferation unaffected. Testosterone substitution did not change this pattern. This study suggests that a transient period of relative ischemia may induce apoptosis in the rat ventral prostate. This may be of importance for the understanding of castration-induced prostatic involution.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002400050106
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  • 48
    Digitale Medien
    Digitale Medien
    p27/kip1 expression in oligodendrogliomas and its possible prognostic role (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 629-634 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words p27/kip1 ; Oligodendrogliomas ; Histological grading ; Prognosis ; MIB-1
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract p27/kip1 regulates the G1-S transition of the cell cycle by inhibiting cyclinD-CDK4, cyclinE-CDK2 and cyclinA-CDK2 complexes. Regulation of p27 levels occurs mainly post-translationally by ubiquitin-mediated proteasomal proteolysis. Although genetic changes of p27/kip1 are extremely rare, in many human carcinomas p27 levels are reduced, correlate with histological malignancy, and are associated with poor prognosis. In astrocytic gliomas, p27 decreases with anaplasia and is almost absent in glioblastomas. p27/kip1 was immunohistochemically studied in 37 oligodendrogliomas, categorized according to WHO classification. In this series, the immunohistochemical reaction for p27 was confined to nuclei. p27 score showed a tendency to decrease with malignancy. When the p27 score was considered as high versus low expression (cut-off of p27 labeling index, LI, at 25%), it represented an independent prognostic factor in univariate (P = 0.02) and in multivariate analysis (P = 0.04). The risk ratio suggested that the p27 low expression group had a threefold increased possibility to show a reduced survival. Moreover, p27 levels did not correlate with MIB-1 LI, suggesting that p27 is not merely associated with the control of proliferation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051128
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  • 49
    Digitale Medien
    Digitale Medien
    Distribution of various neurochemicals within the zona incerta: an immunocytochemical and histochemical study (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 265-280 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Cat ; Rat ; Immunocytochemistry ; NADPH-diaphorase ; Thalamus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  To gain insight into the cellular organisation of the zona incerta, we have examined the chemoarchitectonic properties of this ”uncertain zone”. The brains of Sprague-Dawley rats and common cats were processed for immunocytochemistry or NADPH-diaphorase histochemistry using standard methods. For the immunocytochemistry, antibodies to γ-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), parvalbumin, calbindin, tyrosine hydroxylase, somatostatin, serotonin and glutamate were used. Two general patterns of distribution in the zona incerta were seen. First, labelled cells were restricted largely to one of the cytoarchitectonically defined sectors of the zona incerta. For instance, GABA, GAD and parvalbumin-immunoreactive cells were found principally within the ventral sector, NADPH-diaphorase and glutamate-immunoreactive cells within the dorsal sector and tyrosine hydroxylase- and somatostatin-immunoreactive cells within the rostral sector. Second, labelled cells were scattered somewhat across all incertal sectors, with no clear region of concentration. This pattern included the calbindin- and serotonin-immunoreactive cell groups. These results indicate that the zona incerta is made up of many neurochemically distinct cell groups, some of which respect the well-defined cytoarchitectonic boundaries of the nucleus, whilst others do not. This rich neurochemical diversity in the zona incerta suggests that this nucleus may have differential effects on the different structures that it projects to.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050227
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  • 50
    Digitale Medien
    Digitale Medien
    Does the perireticular thalamic nucleus project to the neocortex? (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 521-531 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Development ; Internal capsule ; Nucleus basalis ; Rat ; Thalamus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study defines several features of the early connections of the developmentally transient perireticular thalamic nucleus of rats. The neocortex of developing rats was injected with either DiI, biotinylated dextran, WGA-HRP (wheatgerm agglutinin conjugated-horseradish peroxidase), fluorescent latex beads or cholera toxin subunit B (CTB) and their brains were processed for tracer detection with standard methods. In general, tracer injections into various regions of the developing neocortex revealed no labelled neurones within the perireticular nucleus, although some of these tracers (WGA-HRP, dextran) labelled many of the amoeboid microglial cells that are found within this nucleus. There were, however, many retrogradely labelled neurones in a region adjacent to the perireticular nucleus, within the nucleus basalis of the basal forebrain (medial edge of globus pallidus). Their identity was confirmed as neurones of the nucleus basalis since they were all were similar in morphology and somal size to neurones that were immunoreactive to NGFr (nerve growth factor receptor), an antigen found only among neurones of the nucleus basalis and basal forebrain. Moreover, double labelling experiments revealed that most, if not all, of the cortically labelled neurones were NGFr-immunoreactive also. Thus, in conclusion, our results suggest that the perireticular nucleus does not project to the neocortex; the only neurones in the general vicinity of the perireticular nucleus that have a cortical projection form part of the nucleus basalis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050300
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  • 51
    Digitale Medien
    Digitale Medien
    Prenatal development of coronary arteries in the rat: morphologic patterns (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 533-540 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Coronary vasculogenesis ; Angiogenesis ; Coronary artery ; Development ; Rat ; Embryonic heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The aim of this work was to address spatiotemporal and morphologic patterns of coronary artery development in rats, based on immunohistochemical and ultrastructural studies of hearts at different stages of prenatal development. Griffonia simplicifolia I lectin and α-smooth muscle antibody were used to demonstrate endothelial cells and/or their precursors and smooth muscle cells, respectively. Ultrastructural examination was performed on ED14–16 hearts to study the morphology of the developing coronary arteries in different regions of the truncus arteriosus and adjacent myocardium. On ED14 endothelial-like cells present within the mesenchyme surrounding the outflow tract penetrated the aortic wall and the truncoconal proximal myocardium. On ED15 these penetrating cells formed vascular clusters, which were the first signs of presumptive vascular channels. Development of the coronary artery proceeded by coalescence of discontinous vascular clusters, formation of the lumen (vascular channels) and establishing a connection of the proximal part with the aorta. The second layer of cells around vascular channels (embryonic media) consisted of mesenchymal cells that were attracted to the immature vessel and were first seen on ED15. At this time no lumenized connection of the coronary artery with the aorta has been seen. After the lumenized connection of the coronary artery with the aorta had been established perivascular cells of the media started to differentiate into vascular smooth muscle, as was shown by α-smooth muscle actin-staining. Further development and differentiation of the media and adventitia proceeded distally (towards the apex).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050301
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  • 52
    Digitale Medien
    Digitale Medien
    Developmental changes of sugar occurrence and distribution in the rat submandibular and sublingual glands (1999)
    Springer
    Anatomy and embryology 199 (1999), S. 113-123 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Morphogenesis ; Histochemistry ; Lectins ; Carbohydrates ; Salivary glands ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050214
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  • 53
    Digitale Medien
    Digitale Medien
    Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 22-30 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Clomethiazole ; Rat ; Spinal cord-injury ; Neuroprotection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 × 5.0 mm) for 5 min at T8–9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 ± 4% in untreated animals but only to 38.5% ± 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 ± 2.7% in saline-treated injured animals and to 22.7 ± 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051047
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  • 54
    Digitale Medien
    Digitale Medien
    Neuropathology and prognosis of foetal brain tumours (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 567-576 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Congenital brain tumour ; Prenatal ; diagnosis ; Prognosis ; Teratoma ; Ultrasound
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A survey of brain tumours that had been diagnosed prenatally by foetal sonography yielded 89 cases. The most commonly found tumour entities were teratomas (53.9%), glioblastomas (14.6%), lipomas (9.0%), plexus papillomas (7.9%) and craniopharyngiomas (5.6%). The mean gestational age at ultrasound diagnosis was 30.0 weeks, ranging between 25.4 weeks in craniopharyngiomas and 35.3 weeks in lipomas. Girls were more frequently affected (57.4%; P 〈 0.05). The average maximum tumour size at diagnosis was 6.5 cm, ranging between 1.6 cm in lipomas and 8.2 cm in teratomas. Tumours diagnosed between 1979– 1988 accounted for 29.2% of all cases and were larger when identified than the ones reported between 1989– 1998 (5.9 vs 8.4 cm; P = 0.08). Of all patients, only 18.8% were alive after the first week and 10.5% after the 1st year of life. Prognosis was particularly poor among foetuses with brain tumours detected before 30 weeks’ gestation of which 96.9% died. Significantly longer survival was found for lipomas (12.0 vs 3.8 months), tumour detection after gestational age of 30 weeks (6.3 vs 1.2 months) and in cases reported after 1988 (5.3 vs 2.9 months, all P 〈 0.05). Cytogenetic data was given for eight teratomas of which three showed a pathological and five cases a normal karyotype for both foetus and tumour. In conclusion, foetal brain tumours are rare neoplasms of whose cytogenetics little is known. They are mainly detected at the beginning of the third trimester of pregnancy with teratomas being the most common entity. Foetal brain tumours have a mainly unfavourable clinical outcome. However, their prognosis has improved in the last decade.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051120
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  • 55
    Digitale Medien
    Digitale Medien
    Axonal growth of newly formed vomeronasal receptor neurons after nerve transection (1999)
    Springer
    Anatomy and embryology 200 (1999), S. 413-417 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Receptor cell ; Axon ; Vomeronasal organ ; Regeneration ; Rat ; HRP-WGA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Chemosensory neurons in the vomeronasal epithelium (vomeronasal neurons) regenerate following experimentally induced degeneration. Transection of the vomeronasal nerves leads to retrograde degeneration of vomeronasal neurons followed by replacement of the cell population. The projection of the axons of regenerated vomeronasal neurons was examined by horseradish peroxidase(HRP) histochemistry and electron microscopy. HRP-wheat germ agglutinin (WGA) was placed on the surface of the vomeronasal organ of the rat. Dense distribution of HRP-labeled fibers was observed in the vomeronasal nerve and glomerular layers in the accessory olfactory bulb (AOB) of the intact rat. At one week after transection, HRP-labeled fibers were not found in the AOB, and no labeled fibers could be observed on the medial surface of the olfactory bulb where the vomeronasal nerve traversed. Three weeks after transection, labeled fiber bundles were observed on the medial surface of the olfactory bulb in all animals. No labeled fibers were detected in the AOB. From 12 to 32 weeks after transection, projection of HRP-labeled fibers was identified in the AOB in 8 out of 26 rats (the incidence of projection was 30%). But the number of projection fibers on the operated side was much smaller than on the control side. Electron microscopy confirmed that the HRP-labeled terminals make synaptic contacts with neurons in the AOB.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050290
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  • 56
    Digitale Medien
    Digitale Medien
    Management of mantle cell lymphoma (1999)
    Springer
    Annals of hematology 78 (1999), S. 485-494 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Key words Mantle cell lymphoma ; Classification ; Pathology ; Prognosis ; Immunology ; Genetics ; Antineoplastic agents ; Combined ; Therapeutic use ; Radiotherapy ; Hematopoietic stem cell transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002770050545
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  • 57
    Digitale Medien
    Digitale Medien
    The role of interferon-α in the treatment of idiopathic myelofibrosis (1999)
    Springer
    Annals of hematology 78 (1999), S. 533-538 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Key words Idiopathic myelofibrosis ; Pathogenesis ; Prognosis ; Treatment ; Interferon-α
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow, varying degrees of extramedullary hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic peripheral blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and calmodulin. Because of the variable clinical course of IMF, attempts have been made to define prognostic parameters that can be helpful in detecting patients with a shortened life expectancy. The most important adverse prognostic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. However, no standardized prognostic score for IMF has yet been established. Therapeutic strategies in IMF remain predominantly supportive. The most common are blood transfusions, androgens, and cytoreductive agents such as hydroxyurea. Bone marrow transplantation is increasingly being taken into consideration, but it still has to be regarded as an experimental approach. Interferon-α (IFN-α) has shown promising results in early hyperproliferative stages of IMF but has no or only very little effect in more advanced stages of the disease. Whether IFN-α is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002770050554
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  • 58
    Digitale Medien
    Digitale Medien
    Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis (1999)
    Springer
    Annals of hematology 78 (1999), S. 65-72 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Key words Idiopathic myelofibrosis ; PCNA labeling ; Apoptosis ; Dynamic disease features ; Prognosis ; Proportion of life loss ; Bone marrow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous studies, our cohort comprised the full spectrum of the disease, from initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed significant differences between early and advanced fibrosclerotic stages of disease. Decrease in proliferation indicated a significantly shorter survival, whereas a higher frequency of apoptotic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is accompanied by a higher incidence of apoptosis reflects the regenerative (turnover) capacity of hematopoiesis. This may apply especially to early hypercellular stages without relevant myelofibrosis. In consideration of a recently published multivariate risk model, a simplified synthesis score for stratification of a patient's prognosis was constructed. Age, degree of anemia, leukocytes, and platelet count were regarded as the most important parameters. A substantial improvement of prognostic efficiency was further achieved by including PCNA index and frequency of apoptosis. Our results are in keeping with the assumption that generalization, indicated by myeloid metaplasia, has a prodigious impact on prognosis in IMF. Furthermore, in this context dynamic features such as proliferative activity and frequency of apoptosis exert an additional predictive value.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002770050474
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  • 59
    Digitale Medien
    Digitale Medien
    Central nervous system involvement in patients with mantle cell lymphoma (1999)
    Springer
    Annals of hematology 78 (1999), S. 145-149 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Key words CNS involvement ; Mantle cell lymphoma ; Non-Hodgkin's lymphoma ; Prognosis ; Incidence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. Survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002770050491
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  • 60
    Digitale Medien
    Digitale Medien
    Bound sulphadimidine residues in raw fermented sausage: release under acidic conditions and bioavailability in rats (1999)
    Springer
    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 183-188 
    Details
    ISSN: 1431-4630
    Schlagwort(e): Key words Sulphadimidine ; Fermented sausage ; Carbon-14-labelling ; Rat ; Bound residues
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract  Sulphadimidine (SDM), a drug frequently administered to pigs, is partially converted into other compounds by processing meat to produce raw, fermented sausage. With the aid of 14C-labelled SDM, evidence was obtained that part of the radioactive matter was covalently bound to the matrix. Part of these bound residues could be released in vitro by 4 M HCl at 21  °C or by 0.024 M HCl at 37  °C. Female rats were also able to release bound SDM residues and to excrete these in their urine, in amounts approaching those obtained by treatment with 4 M HCl. Both the parent compound and its main metabolite, N 4-acetyl-SDM, were observed in the urine of rats.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002170050399
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  • 61
    Digitale Medien
    Digitale Medien
    Nucleotide sequences of three distinct complementary DNA clones encoding rat class II major histocompatibility complex RT1.D β-chain proteins (1999)
    Springer
    Immunogenetics 49 (1999), S. 735-737 
    Details
    ISSN: 1432-1211
    Schlagwort(e): Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002510050676
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  • 62
    Digitale Medien
    Digitale Medien
    Mechanical ventilation of patients on long-term oxygen therapy with acute exacerbations of chronic obstructive pulmonary disease: prognosis and cost-utility analysis (1999)
    Springer
    Intensive care medicine 25 (1999), S. 452-457 
    Details
    ISSN: 1432-1238
    Schlagwort(e): Key words Lung disease ; obstructive ; Long-term oxygen therapy ; Prognosis ; Quality of life ; Cost analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Astract Objective: To analyze the prognosis and costs of mechanical ventilation in patients with exacerbations of chronic obstructive pulmonary disease (COPD) treated with long-term oxygen therapy. Design: A prospective cohort study. Follow-up at 1 and 5 years. Cost utility analysis. Setting: A medical-surgical intensive care unit (ICU) in a university hospital. Patients: 20 patients with previous COPD treated with long-term oxygen therapy and needing mechanical ventilation due to acute respiratory failure. Measurements and main results: Mortality in the ICU, in-hospital mortality (ICU plus ward), and mortality at 1 and 5 years, and factors associated with prognosis and cost–utility were assessed. The mean Acute Physiology and Chronic Health Evaluation II score was 20 (median 20 range 12–36). Cumulative mortality was 35 % in the ICU, 50 % in hospital, 75 % at 1 year, and 85 % at 5 years. Factors significantly associated with mortality in the ICU were low levels of albumin (p = 0.05) and sodium (p = 0.01) at admission. Patients who died in hospital and in the first year after discharge had a lower forced expiratory volume in 1 s (FEV1) than survivors (p = 0.03 and p = 0.05, respectively). The cost per Quality Adjusted Life Year (QALY) was U. S. $ 26 283 and U. S. $ 44 602 in a “best” (cost/QALY calculated for the life expectancy in Spain) and a “worst case scenario” (cost/QALY calculated for a 68-year life expectancy), respectively. Conclusions: Applying mechanical ventilation to COPD patients treated with long-term oxygen therapy carries a high mortality and cost. Factors significantly associated with mortality in the ICU were albumin and sodium concentrations and FEV1 in hospital and in the first year after discharge.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001340050879
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  • 63
    Digitale Medien
    Digitale Medien
    The epidemiology of occupational contact dermatitis (1999)
    Springer
    International archives of occupational and environmental health 72 (1999), S. 496-506 
    Details
    ISSN: 1432-1246
    Schlagwort(e): Key words Occupational dermatitis ; Contact dermatitis ; Allergy ; Irritation ; Exposure ; Atopy ; Prevention ; Prognosis ; Risk
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Occupational contact dermatitis (OCD) ranks first of all occupational diseases in many countries. The incidence rate is believed to be around 0.5–1.9 cases per 1000 full-time workers per year. Epidemiological studies play an important role in observing disease trends, analysing risk factors, and monitoring the effect of preventive measures. In this review article the lack of truly epidemiologic data on OCD and the difficulties of those studies are illustrated. The following issues are highlighted: case ascertainment and bias, the distribution of allergic and irritant contact dermatitis in the working population, the interrelationship between exogenous (allergens, irritants) and endogenous factors, the prognosis, the social and economic impact, and the need for intervention studies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004200050407
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  • 64
    Digitale Medien
    Digitale Medien
    Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin (1999)
    Springer
    Experimental brain research 126 (1999), S. 270-280 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Coherence ; Entorhinal cortex ; Cortex ; Hippocampus ; Amygdala ; 192 IgG-saporin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 µg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%–84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050736
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  • 65
    Digitale Medien
    Digitale Medien
    Cerebellar contribution to spatial event processing: characterization of procedural learning (1999)
    Springer
    Experimental brain research 127 (1999), S. 1-11 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Spatial function ; Water maze ; Procedural learning ; Cerebellum ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Recently, we demonstrated the prevalent role of cerebellar networks in the acquisition of the procedural components of spatial information by testing hemicerebellectomized (HCbed) rats in a classical spatial task, the Morris water maze (MWM). As procedures used in the water maze are a mixture of different components (that is, general procedures, exploration procedures, direct reaching procedures), for optimally solving a spatial task all procedural components must be opportunely managed. Thus, severely impaired procedural learning of cerebellar origin can be better comprehended by fractionating the procedural facets. To this aim, a two-step water-maze paradigm was employed. Normal rats were first trained to search for a hidden platform moved to a different position in each trial, utilizing a water maze setting in which visual cues were abolished by heavy black curtains surrounding the tank. In this paradigm, normal animals solved the task by using general and exploration procedures, but they could not use direct reaching skills. A subgroup of these pretrained animals was then HCbed and, after recovery from cerebellar lesion, was tested in a water maze with normal environmental cues available, a paradigm in which normal animals develop abilities for reaching the target with very direct trajectories. Pretrained HCbed animals, however, did not display the typical spatial deficits of naive HCbed rats, persisted in exhibiting the scanning strategy learned during pretraining, and never displayed direct reaching skills. In conclusion, cerebellar networks appear to be involved in the acquisition of all procedural facets necessary for shifting behavior within the maze until direct reaching of the platform. The lack of flexibility in changing exploration strategies displayed by pretrained HCbed rats is interpreted by taking into account the well-known cerebellar frontal interplay sculpting a specific cerebellar role in the acquisition of spatial procedural steps.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050768
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  • 66
    Digitale Medien
    Digitale Medien
    Ground reaction forces in locomoting hemi-parkinsonian rats: a definitive test for impairments and compensations (1999)
    Springer
    Experimental brain research 126 (1999), S. 307-314 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Striatal dopamine depletion ; Rat ; Locomotion ; Ground reaction forces ; Gait ; Unilateral ; Kinetic ; Centre of mass
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Hemi-parkinsonian rats have preserved postural reflexes but are impaired in initiation of voluntary movements. Surprisingly, these rats can walk and run, suggesting that they can access some compensatory strategy to overcome the rigidity in their impaired limbs. The purpose of the present experiment was to investigate the locomotor compensations made by hemi-parkinsonian rats by measuring the forces exerted by the limbs on the ground throughout the stride during trotting. Rats with unilateral dopamine depletion produced by injection of 6-hydroxydopamine into the nigrostriatal bundle were trained to run back and forth in an alley for food reinforcement. Ground reaction forces were measured in three orthogonal directions using a force plate embedded in the runway. Rats were also videotaped so that limb movements were synchronized with force recordings. Although locomotion was obviously impaired, the affected limbs could support weight and provide some braking forces. In addition, the impaired hindlimb provided significant propulsive force, and a relatively large laterally directed force. Analysis of vertical movement of the centre of mass suggested that the impaired hindlimb was being used partly as a spring. The most significant abnormalities were seen during the diagonal couplet of the impaired forelimb and the unimpaired hindlimb, partly reflecting the important compensatory role of the unimpaired hindlimb. These results demonstrate that this method is useful in the analysis of hemi-parkinsonian gait and provide insights as to how rats can use an impaired limb to produce weight support and propulsion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050739
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  • 67
    Digitale Medien
    Digitale Medien
    Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C1 spinal neurons in the rat (1999)
    Springer
    Experimental brain research 126 (1999), S. 351-358 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Tooth pulp ; Phrenic nerve ; Electrical stimulation ; C1 spinal neuron ; Digastric electromyogram ; Somatic receptive field ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C1 spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C1 spinal neurons and the amplitude of a digastric electromyogram (dEMG, n=10) increased proportionally during the TP stimulation at an intensity of 1–3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C1 spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C1 spinal neurons in the rat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050742
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  • 68
    Digitale Medien
    Digitale Medien
    Facilitation of long-term potentiation in layer II/III horizontal connections of rat motor cortex following layer I stimulation: route of effect and cholinergic contributions (1999)
    Springer
    Experimental brain research 127 (1999), S. 279-290 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Acetylcholine ; Brain slices ; Cerebral cortex ; Long-term depression ; Rat ; Synaptic plasticity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The ability of layer I activation to facilitate the induction of long-term potentiation (LTP) in layer II/III horizontal connections of motor cortex (MI) was examined in rat brain slice preparations. Field potentials evoked in layer I and layer II/III horizontal pathways were recorded from radially aligned MI sites. While theta burst stimulation (TBS) of layer II/III pathways alone failed to induce LTP, simultaneous TBS of layer I and layer II/III inputs on alternate sides of the recording electrodes induced LTP in the layer II/III input in 8 out of 13 slices (mean change +20±6%; N=13). In the same cases, the layer I connections showed mixed effects: LTP in three cases, LTD in five cases, and no modification in five slices. Despite the facilitatory effect of layer I activation on layer II/III LTP induction, we found that the critical circuitry for this effect was outside layer I. Cutting the layer I fibers selectively in the slice did not prevent layer II/III LTP induction, while cuts preserving only layer I blocked layer II/III LTP after conjoint I+II/III TBS. Cholinergic fibers were evaluated as candidates for the facilitatory effect because they branch widely in both layers and they are thought to participate in synaptic modification. The cholinergic contribution to layer II/III LTP facilitation was investigated using bath application of muscarinic antagonists. Muscarinic blockade prevented facilitation of layer II/III LTP by layer I coactivation. Instead, conjoint stimulation in 10 µM atropine produced long-term depression (LTD) of layer II/III (–18±9%; N=11) as well as of layer I (–21±6%; N=11) horizontal responses. These results indicate that connections formed within layer I are ineffective in promoting LTP in the deeper-lying horizontal connections; the critical route by which layer I stimulation influenced LTP induction required the circuitry in the deeper layers, particularly the cholinergic system. Thus, it appears that diffuse cholinergic afferents provide an additional route to regulate activity-dependent synaptic modificaton in horizontal cortical connections.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050797
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  • 69
    Digitale Medien
    Digitale Medien
    The influence of changes in the stimulation pattern on force and fusion in motor units of the rat medial gastrocnemius muscle (1999)
    Springer
    Experimental brain research 127 (1999), S. 298-306 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Motor unit ; Contraction ; Stimulation pattern ; Rat ; Medial gastrocnemius
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The effects of irregularity in the pattern of stimulation on the tension produced by motor units in the rat medial gastrocnemius muscle were investigated. The effects of decreasing as well as increasing the interpulse intervals were observed for each motor unit in tetani fused to different degrees. For each motor-unit type, it was found that the effects of these changes depended on the extent of tetanic fusion. Decreasing the interpulse interval produced an increase in tension during the tetanus: the more fused the profile of tetanus, the smaller the tension increase. Increasing the interpulse interval resulted in a decrease in tetanic tension. This effect was most prominent when the tetanic fusion index was approximately 0.75. This phenomenon resulted from the prolongation in relaxation when tetanic fusion increased, thereby preventing a decrease in tension when the interpulse interval increased. We also investigated the effects of introducing a short interpulse interval (”doublet”) at the beginning of the stimulation. The doublets produced increased tetanic tension with a more fused profile. However, the doublet enhanced the sensitivity of the tetanus to increases in interpulse interval and decreased its sensitivity to decreases in interpulse intervals. Slow-twitch motor units appeared to be significantly less sensitive to both increases and decreases in interpulse interval than fast-twitch units. This suggests that slow-twitch units are better suited for producing long-lasting contractions with a constant tension level. Conversely, the high sensibility of fast-twitch units to changes in stimulation frequency enhances their participation in regulation of tension of the muscular contraction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050799
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  • 70
    Digitale Medien
    Digitale Medien
    Modulation of mRNA expression of the neurotrophins of the nerve-growth-factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment. II. Effects on p75 and trk receptor expression (1999)
    Springer
    Experimental brain research 127 (1999), S. 307-313 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words Thyroid hormone ; RT-PCR ; p75 receptor ; trkA ; trkB ; trkC ; Septum ; Hippocampus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes of the septo-hippocampal cholinergic and the hippocampal mossy fiber systems. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be involved in these effects. In a recent study, we showed that, after thyroxine application, the mRNA expression of neurotrophins of the nerve-growth-factor (NGF) family is significantly upregulated both in septum and hippocampus. To test whether the neurotrophin receptors (the low-affinity neurotrophin receptor p75 and the specific high-affinity receptors trkA, trkB, and trkC) were also affected by hormone administration, newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day 12 (P12) at latest. Control animals received corresponding injections of saline. The pups were sacrificed at defined intervals from P9 to P14. The septal areas and the hippocampi were analyzed using the reverse-transcription polymerase chain reaction (RT-PCR) method for quantification of p75, trkA, trkB, and trkC mRNA levels. Analysis of variance over the total investigation period revealed no significant general increases of the gene expressions of either neurotrophin receptor, neither in the septum nor in the hippocampus, although previous results have shown marked changes in neurotrophin levels. On particular postnatal days, significant upregulation could be observed in hippocampus for trkB and trkC. From these and recent data, we conclude that modulation of neurotrophin expression rather than neurotrophin-receptor expression contributes to the morphological modifications within the hippocampal mossy fiber system and the septo-hippocampal cholinergic system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050800
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  • 71
    Digitale Medien
    Digitale Medien
    The birthdates of GABA-immunoreactive amacrine cells in the rat retina (1999)
    Springer
    Experimental brain research 128 (1999), S. 309-314 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Key words GABA ; Bromodeoxyuridine ; Proliferation ; Immunohistochemistry ; Retina ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The birthdates of GABAergic amacrine cells in the rat retina were investigated by immunocytochemistry using anti-GABA and anti-bromodeoxyuridine (BrdU) antisera. The ratio of co-localization of GABA to BrdU increased gradually from embryonic-day 13 (E13) and showed a peak value on E18 in the central retina and on E20 in the periphery. After birth, until postnatal-day 3 (P3), a few co-localized cells were observed in the inner nuclear layer (INL). However, in the peripheral retina, co-localized cells were observed in the INL and ganglion cell layer until P5. Our results suggest that the birthdates of GABA-immunoreactive cells vary, depending on cell-type and that there is a temporal lag in the GABA-immunoreactive cell production in the peripheral retina relative to the central retina.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002210050851
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  • 72
    Digitale Medien
    Digitale Medien
    S-100β-Protein im Serum als Tumormarker beim malignen Melanom Aktueller Kenntnisstand und klinische Erfahrungen (1999)
    Springer
    Der Hautarzt 50 (1999), S. 250-256 
    Details
    ISSN: 1432-1173
    Schlagwort(e): Schlüsselwörter Serum-S-100-Protein ; Tumormarker ; Malignes Melanom ; Prognose ; Key words Serum S100 protein ; Tumor marker ; Malignant melanoma ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary S100 is an acidic-calcium-binding protein, composed as a heterodimer of two isomeric subunits α and β and was first described in cells of neuroendocrine origin. It plays an important role in various cellular processes such as cell differentiation and proliferation and interacts with the tumour suppressor gene p53. S100 is also present in melanoma cells and its immunhistochemical detection is widely used in the histopathological diagnosis of malignant melanoma. S100 has been detected in the serum of patients with malignant melanoma and many clinical studies have been performed to establish this protein as a tumor marker in different stages of the disease. The data suggest that S-100β-protein in serum of patients with malignant melanoma could be an independent prognostic marker and an additional clinical parameter for progression of metastatic disease and serological monitoring during systemic therapy. However there are patients in stage of lymph node- or systemic metastasis with negative S-100β-serum levels and no correlation to the course of disease. Our results confirm the findings for patients in stage III/IV. However, the percentage of S-100β-positive patients in stage III/IV is lower than reported in the literature, if repeatedly positive samples are excluded from statistical analysis. For monitoring in stage I and II it seems to be not helpful.
    Notizen: Zusammenfassung S-100 ist ein saures, kalziumbindendes Protein, das als Heterodimer aus 2 isomeren Untereinheiten α und β besteht und erstmalig in Zellen neuroendokrinen Ursprungs beschrieben wurde. Es spielt eine Rolle bei verschiedenen zellulären Prozessen, wie z.B. der Zelldifferenzierung und der Proliferation und interagiert mit dem Tumorsuppressorprotein p53. S-100 ist ebenfalls in Melanomzellen vorhanden, und sein immunhistochemischer Nachweis ist bei der histopathologischen Diagnostik des malignen Melanoms weit verbreitet. Nachdem S-100β im Serum von Patienten mit malignem Melanom nachgewiesen wurde, folgten zahlreiche klinische Studien zur Etablierung dieses Proteins als Tumormarker in verschiedenen Stadien der Erkrankung. Die Resultate zeigen, daß S-100β-Protein im Serum von Patienten mit malignem Melanom ein unabhängiger prognostischer Marker und ein ergänzender klinischer Parameter für die Progression der metastasierten Erkrankung sowie für das Monitoring der Patienten während einer systemischen Therapie sein kann. Bei Lymphknoten- oder Fernmetastasierung gibt es jedoch auch Patienten mit negativen S-100-β-Werten, bei denen eine Korrelation mit dem Krankheitsverlauf nicht hergestellt werden kann. Eigene Ergebnisse bestätigen diese Grundaussage für Patienten im Stadium III/IV. Werden aber wiederholt positive S-100β-Serumwerte bei der statistischen Auswertung nur einmalig berücksichtigt, zeigt sich ein deutlich geringerer Anteil von Patienten im Stadium III/IV mit positiven S-100-Werten, als in der Literatur angegeben. Für das Monitoring im Stadium I und II scheint S-100β nicht geeignet.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001050050897
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  • 73
    Digitale Medien
    Digitale Medien
    Severe head injury patients in a multidisciplinary ICU: are they a burden? (1999)
    Springer
    Intensive care medicine 25 (1999), S. 855-858 
    Details
    ISSN: 1432-1238
    Schlagwort(e): Key words Head injury ; Outcome ; Prognosis ; Age ; Intensive care
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objective: Patients with severe head injury (HI) are often considered to be a burden in a multidisciplinary intensive care unit (ICU). This study was undertaken to compare the severe closed HI patients with all other patients in the ICU in terms of age group involved, stay in the unit, complications and outcome. Design: Retrospective analysis. Setting: Multidisciplinary ICU of a tertiary care hospital in Northern India. Patients and participants: All the patients admitted to the ICU between January 1995 and December 1997. The patients were classified into two groups: group A comprising patients with severe closed HI and group B consisting of all other patients. Results: The mean age of the patients was around 30 years in both the groups. The average stay of the patients in the unit was 12.71 ± 11.9 days in group A, compared to 9.9 ± 14.4 days for group B (p 〈 0.05). The duration on the ventilator or on an endotracheal airway was not different between the groups (p 〉 0.05). The mortality in group A was 46.8 % and that in group B was 38.5 % (p 〉 0.05). The mortality was directly proportional to the age in group A. Hypotension, renal failure and septicaemia were the commonest complications in both the groups but the difference was not statistically significant. Conclusions: This study demonstrates that patients with severe HI do not pose an extra burden in a multidisciplinary ICU.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001340050965
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  • 74
    Digitale Medien
    Digitale Medien
    Control of mesenteric arterial tone in vitro in humans and rats (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 322-330 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K+ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca2+ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca2+-induced contractions in human arteries.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00005358
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  • 75
    Digitale Medien
    Digitale Medien
    Influence of three different types of hypercalciuria on bone (1999)
    Springer
    Pediatric nephrology 13 (1999), S. 396-400 
    Details
    ISSN: 1432-198X
    Schlagwort(e): Key words Hypercalciuria ; Idiopathic hypercalciuria ; Bone mineral content ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The relationship between bone mineral status and hypercalciuria is controversial. The effect on bone composition of different forms of hypercalciuria was studied in female rats made hypercalciuric by 7-week administration of oral furosemide (F, n=12), intraperitoneal 1,25-dihydroxy vitamin D (VD, n=11), or oral ammonium chloride (AC, n=12). Seven untreated rats served as controls (C). Hypercalciuria (mg/100 g per 24 h, mean ±SEM) of F (4.3±0.2), VD (4.1±0.4), and AC (3.9±0.3) groups was of similar intensity (C rats 1.3±0.1, P〈0.01). Weight and length gains and serum CO2, sodium, potassium, calcium, and phosphate were no different among the four groups. Bone was studied by dual-energy X-ray absorptiometry of left tibiae. AC rats had significantly less bone area (1.505±0.018 cm2) than VD and C (1.602±0.020 and 1.587±0.019 cm2). Bone mineral content was decreased in F (0.357±0.007 g) and AC (0.362±0.006 g) compared with VD (0.407±0.008 g) and C (0.389±0.009 g) groups. Bone mineral density was different between F (0.231±0.002 g/cm2) and VD and C rats (0.254±0.004 and 0.245±0.003 g/cm2), and also between AC (0.240±0.003 cm2) and VD rats. In these rat models, hypercalciuria of renal origin (F) and hypercalciuria caused by acid load (AC) adversely impaired bone mass.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004670050629
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  • 76
    Digitale Medien
    Digitale Medien
    Hochdifferenziertes Plattenepithelkarzinom als Spätkomplikation einer posttraumatischen Osteomyelitis (1999)
    Springer
    Der Pathologe 20 (1999), S. 236-241 
    Details
    ISSN: 1432-1963
    Schlagwort(e): Schlüsselwörter Osteomyelitis ; Plattenepithelkarzinom ; Fistelkarzinom ; Differentialdiagnose ; Prognose ; Key words Osteomyelitis ; Squamous cell carcinoma ; Fistula carcinoma ; Diagnosis ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Squamous cell carcinoma as a late complication of chronic osteomyelitis is a well known phenomenon in traumatology, often occurring as a consequence of bone fractures. The majority of cases are observed in men between 50 and 60 years of age. The time from onset of inflammatory bone disease to malignant transformation differs but usually takes 30 years. In general, prognosis is thought to be favorable when adequate surgical therapy is carried out. Nowadays, it is important to recall this condition, because it has become rare. The cases reported here illustrate the difficulties that may be encountered in diagnosing malignant transformation, especially in lesions that develop in deep tissue layers and which may be responsible for various biopsies failing to reveal the true pathology.
    Notizen: Zusammenfassung Plattenepithelkarzinome als Spätfolge chronischer Osteomyelitiden sind in der Traumatologie im Verlauf von offenen Frakturen beschrieben und insbesondere bei Männern in der 5. und 6. Lebensdekade zu beobachten. Von Beginn der Knochenentzündung bis zur malignen Transformation vergehen im Durchschnitt etwa 30 Jahre. In aller Regel ist die Prognose bei frühzeitiger Diagnosestellung und adäquater chirurgischer Therapie gut. Heutzutage ist die Erkrankung nur noch selten zu beobachten und droht daher, in Vergessenheit zu geraten. Insbesondere der erste der beiden vorgestellten Fallberichte verdeutlicht die Schwierigkeit der Diagnosestellung, da die klinische Präsentation uncharakteristisch war und erst in der Tiefe der Läsion gewonnene Probebiopsien die karzinomatöse Entartung erfaßten.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002920050351
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  • 77
    Digitale Medien
    Digitale Medien
    Prognostic factors in fetal hydronephrosis: a multivariate analysis (1999)
    Springer
    Pediatric nephrology 13 (1999), S. 859-864 
    Details
    ISSN: 1432-198X
    Schlagwort(e): Key words Fetal ; Hydronephrosis ; Ultrasonography ; Oligohydramnios ; Prognosis ; Multivariate analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  With the increasing use of obstetric echography fetal hydronephrosis has been reported more frequently. The purpose of this study was to identify prognostic factors associated with adverse outcome, such as renal failure and death, in fetal hydronephrosis. One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol, and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings on admission were studied. The median follow-up was 39 months. The analysis was conducted in two steps. In a univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis. This analysis, using the multivariate Cox’s model, was performed to identify variables that were independently associated with a worse prognosis. Only variables that remained independently associated with adverse outcome were included in the final model. After final adjustment by Cox’s multivariate model, three variables were identified as independent predictors of adverse outcome: oligohydramnios, prematurity, and glomerular filtration rate lower than 20 ml/min. Thus, in the presence of oligohydramnios, prematurity, and abnormal renal function, the medical team must plan appropriate follow-up for infants at health centers prepared to investigate and treat uropathies in newborns.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004670050716
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  • 78
    Digitale Medien
    Digitale Medien
    Age-dependent expression of protein phosphatase 2A in the developing rat kidney (1999)
    Springer
    Pediatric nephrology 13 (1999), S. 800-805 
    Details
    ISSN: 1432-198X
    Schlagwort(e): Key words In situ hybridization ; Kidney development ; Nephrogenesis ; Phosphatase activity ; Serine/threonine protein phosphatase 2A ; Protein phosphorylation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Several lines of evidence suggest that the serine/threonine protein phosphatase (PP)2A is of vital importance for cell cycle regulation, cell differentiation, and signal transduction. This prompted us to study the expression of the mRNA for PP2A catalytic isoforms α and β in the developing rat kidney using in situ hybridization histochemistry. The expression patterns of the two isoforms were strikingly similar. Both were ubiquitously expressed in early metanephric kidneys. Later in gestation they were expressed in the nephrogenic zone. Strong expression was observed on postnatal day (PN) 10. This was followed by a downregulation at PN20, i.e., when nephrogenesis is completed. The expression in the adult kidney was very weak and mainly confined to the medulla. In a phosphatase activity assay, PP2A accounted for 78% of the total serine/threonine phosphatase activity in embryonic day 15 rat kidneys. PP1 was the main contributor to the remaining activity. In conclusion, PP2A is the major serine/threonine phosphatase in fetal kidneys. The age-dependent expression pattern supports the concept that this enzyme is of particular importance during renal morphogenesis and development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004670050704
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  • 79
    Digitale Medien
    Digitale Medien
    Pathologie der Rhabdo- myosarkome des Kindes- und Adoleszentenalters Ein Bericht des Kindertumorregisters bei der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) (1999)
    Springer
    Der Pathologe 20 (1999), S. 87-97 
    Details
    ISSN: 1432-1963
    Schlagwort(e): Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notizen: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002920050326
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  • 80
    Digitale Medien
    Digitale Medien
    Effects of pre- and postnatal cysteamine exposure on renal function in the rat (1999)
    Springer
    Pediatric nephrology 13 (1999), S. 812-815 
    Details
    ISSN: 1432-198X
    Schlagwort(e): Key words Cystinosis ; Cysteamine ; Renal function ; Rat ; Prenatal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5–18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5–19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4–21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004670050706
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  • 81
    Digitale Medien
    Digitale Medien
    Mecamylamine blocks the development of tolerance to nicotine in rats: implications for the mechanisms of tolerance (1999)
    Springer
    Psychopharmacology 141 (1999), S. 332-338 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Mecamylamine ; Tolerance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Chronic injections of nicotine in rats produce upregulation of nicotinic cholinergic receptors. It has been proposed that this upregulation is a reflection of receptor desensitization and is the basis of functional tolerance. Mecamylamine, a non-competitive antagonist that blocks activation of nicotinic receptors, does not prevent upregulation produced by nicotine injections. This suggests that receptor activation is not a prerequisite for nicotine-induced receptor upregulation. Therefore, the present experiments tested whether mecamylamine would also fail to prevent the development of tolerance to nicotine. Six daily pairings of mecamylamine (1 mg/kg SC) with nicotine did block the development of tolerance to nicotine-induced antinociception (0.35 mg/kg) and to the ability of nicotine to suppress milk intake (0.66 mg/kg). In another experiment, six daily injections of mecamylamine, when given alone, did not alter the effects of a subsequent, acute injection of nicotine (0.35 mg/kg) in inducing antinociception in rats. There was no evidence that after six pairings of mecamylamine with nicotine, the cues associated with mecamylamine delivery took on conditioned antagonistic properties. These findings suggest that, unlike the receptor upregulation that results from either continuous or repeated nicotine administration, the tolerance following a short series of intermittent nicotine injections is dependent on receptor activation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050842
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  • 82
    Digitale Medien
    Digitale Medien
    Can the ”state-dependency” hypothesis explain prevention of amphetamine sensitization in rats by NMDA receptor antagonists? (1999)
    Springer
    Psychopharmacology 141 (1999), S. 351-361 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Amphetamine ; Behavioral sensitization ; MK-801 ; NMDA receptor ; State-dependency ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Many laboratories have reported that coadministration of N-methyl-d-aspartate (NMDA) receptor antagonists with psychomotor stimulants prevents the development of behavioral sensitization and therefore concluded that NMDA receptor transmission is necessary for sensitization. According to an alternative ”state-dependency” interpretation, NMDA receptor antagonists do not prevent sensitization. Rather, they become a conditioned stimulus for the sensitized response, i.e., it is only elicited in response to combined administration of the NMDA receptor antagonist and the stimulant. This hypothesis is supported by progressive augmentation of the locomotor response to the drug combination during the induction phase, and expression of sensitization when challenged with the combination but not the stimulant alone. To test this hypothesis, rats were treated during a 6-day induction phase with amphetamine (Amph) alone or in combination with the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg) or the non-competitive NMDA receptor antagonist MK-801 (0.05, 0.1 and 0.25 mg/kg). When CGS 19755 was coadministered with Amph, there was no progressive augmentation of response to the drug combination. When challenged with Amph alone, rats did not exhibit the biphasic pattern of locomotor activity characteristic of Amph sensitization. No sensitization of stereotyped behaviors was evident, although the ambulatory response was greater than that exhibited by naive rats. Results with MK-801 were complex, but progressive augmentation of response to the drug combination appeared to in part reflect sensitization to MK-801 and could be dissociated from the ability of MK-801 to prevent the development of sensitization as assessed by response to challenge with Amph alone. Many of these findings are inconsistent with predictions of the ”state-dependency” hypothesis. Moreover, the ability of NMDA receptor antagonists to prevent biochemical and electrophysiological correlates of sensitization is difficult to reconcile with the idea that sensitization develops in the presence of NMDA receptor blockade but cannot be expressed. Together, these findings suggest that the ability of NMDA receptor antagonists to prevent Amph sensitization reflects a requirement for NMDA receptor transmission during its induction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050844
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  • 83
    Digitale Medien
    Digitale Medien
    Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction (1999)
    Springer
    Psychopharmacology 141 (1999), S. 421-427 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words SSRI ; Cytochrome P450 ; Serotonin ; Microdialysis ; Norfluoxetine ; Locomotor activity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5–1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050852
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  • 84
    Digitale Medien
    Digitale Medien
    Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 9-17 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words NMDA (N-methyl-D-aspartate) ; Schizophrenia ; Prepulse inhibition (PPI) ; Sensory gating ; P50 ; Auditory evoked potentials (AEP) ; Ketamine ; d-Amphetamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, IP) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, IP) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050856
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  • 85
    Digitale Medien
    Digitale Medien
    Calcium channel agonist (−)-BAY k 8644 suppresses free and limited access intake of alcohol in genetic drinking rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 261-269 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Alcoholism ; Alcohol drinking ; Alcohol intake ; Calcium channells ; Genetic model of alcoholism ; Pharmacotherapy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Drugs which possess selective actions on a given voltage operated calcium (Ca2+) channel (VOCC) are reportedly involved in the pharmacological actions of alcohol. Recently it was shown that the 1,4-dihydropyridine (−)-BAY k 8644, an L-type VOCC agonist, reduces alcohol intake relatively selectively in the genetic drinking AA rat. This study determined whether (−)-BAY k 8644 would alter volitional alcohol drinking in two other genetic models of alcoholism, male P rats and a new strain of male and female high ethanol preferring (HEP) rats. By use of a standard 10-day preference test for water versus 3 to 30% alcohol, the maximally preferred concentration of alcohol was first determined for each rat individually, i.e. 9%, 13% or 15%. Then the rats were allowed free access over 24 h or limited access to alcohol for only 2 h, during which time the intakes of water and preferred solution of alcohol were recorded. After the drinking patterns stabilized for 4 days, saline, a solutol vehicle solution or (−)-BAY k 8644 was administered: (1) in a dose of 0.125, 0.25 or 0.5 mg/kg given intraperitoneally twice daily for 4 days during free access to alcohol; and (2) for 3 days in a dose of 0.125 or 0.25 mg/kg given subcutaneously 30 min prior to 2 h of limited access to alcohol. Fluid intakes were recorded for either 4 or 8 days after limited and free access conditions, respectively. Whereas the control solutions were without effect during 24 h access, (−)-BAY k 8644 caused a significant dose-dependent suppression of up to 80% in absolute g/kg and proportion of alcohol to total fluid consumed; this decline persisted in the post drug period. During the limited access paradigm, (−)-BAY k 8644 similarly reduced alcohol drinking maximally within the first 15 min of presentation of alcohol; again, this reduction persisted over the remaining 105 min of alcohol access. Also, individual levels of blood alcohol declined concurrently with the suppression of drinking. These results demonstrate that (−)-BAY k 8644 possesses a short latency of action on alcohol intake and that its salutary effects on drinking persist after the drug is terminated. Finally, the hypothesis that L-type calcium channel agonists may be useful as a therapeutic adjunct in the treatment of alcoholism is extended.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050888
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  • 86
    Digitale Medien
    Digitale Medien
    The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716 (1999)
    Springer
    Psychopharmacology 142 (1999), S. 302-308 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Alcohol ; Beer ; Craving ; Rat ; Naloxone ; SR 141716 ; Ritanserin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were given two weeks of home cage access to either “near-beer” (a beverage that tastes like beer but contains 〈0.5% ethanol v/v) or near-beer with added ethanol (4.5% v/v), which is simply referred to as “beer”. The two groups of rats (near-beer and beer) were then trained on a “lick-based progressive ratio paradigm” in operant chambers in which an ever increasing number of licks had to be emitted for each successive fixed unit of near-beer or beer delivered. Break points (the ratio at which responding ceased) for near-beer and beer were approximately equal under baseline conditions. Rats were then tested for the effects of the 5HT2A/2C receptor antagonist ritanserin (0.625, 2.5 or 10 mg/kg), the opioid receptor antagonist naloxone (0.625, 2.5 or 10 mg/kg) or the cannabinoid CB1 receptor antagonist SR 141716 (0.3, 1 or 3 mg/kg). All three drugs caused a dose-dependent reduction of break-points and locomotor activity in both the beer and near-beer groups. However, the effects of SR 141716 and naloxone, but not ritanserin, on break-points were significantly more pronounced on rats drinking beer compared to those drinking near-beer. There were no such differential effects of any of the drugs on locomotor activity across the two groups. These results suggest that both SR 141716 and naloxone differentially affect the motivation to consume alcoholic beverages and may thus have potential as drugs for the treatment of alcohol craving.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050893
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  • 87
    Digitale Medien
    Digitale Medien
    AND and AND-OR drug mixture discriminations in rats: generalization to single drugs and drug mixtures (1999)
    Springer
    Psychopharmacology 143 (1999), S. 54-63 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Midazolam ; Caffeine ; Cocaine ; Amphetamine ; Pentobarbitone ; Ethanol ; Drug discrimination ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. Methods: Rats were trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050919
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  • 88
    Digitale Medien
    Digitale Medien
    Cognitive enhancing effects in young and old rats of pBC264, a selective CCKB receptor agonist (1999)
    Springer
    Psychopharmacology 143 (1999), S. 141-149 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words BC264 ; Cholecystokinin ; CCKB receptor ; Memory ; Ageing ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: The implication of CCKB receptors in cognitive processes is far from fully understood. Objective: The present study investigated the effect of propionyl-BC264, a selective agonist of CCKB receptors, in young and old rats. Methods: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. Results: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 μg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCKB receptor antagonist. Conclusions: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050929
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  • 89
    Digitale Medien
    Digitale Medien
    The interaction of cocaethylene and cocaine and of cocaethylene and alcohol on schedule-controlled responding in rats (1999)
    Springer
    Psychopharmacology 145 (1999), S. 153-161 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Cocaethylene ; Cocaine ; Alcohol ; Interaction ; Schedule-controlled responding ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Cocaethylene is a unique metabolite of cocaine, produced only in the presence of alcohol. This metabolite is pharmacologically, physiologically and behaviorally active. Further, it has been reported to interact pharmacokinetically with both cocaine and alcohol, an interaction that may mediate, in part, the interaction of cocaine and alcohol. Although cocaethylene has been shown to interact with both cocaine and alcohol, behavioral assessments of these interactions are limited. Objectives: To examine directly the behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol, the present study assessed the effects produced by these combinations on schedule-controlled responding. Methods: Rats were first administered cumulative doses of cocaethylene, cocaine and alcohol to assess their effects alone on responding. Following this, doses of cocaethylene were combined with cumulative doses of cocaine or alcohol. Additionally, doses of cocaine or alcohol were given in combination with cumulative doses of cocaethylene. Results: When administered alone, cocaethylene, cocaine and alcohol produced dose-related decreases in responding. Further, cocaethylene shifted the dose–response functions for both cocaine and alcohol to the left and down, while cocaine and alcohol shifted the dose–response function for cocaethylene to the left and down. An isobolographic analysis revealed that these interactions were additive in nature. Conclusions: The present study suggests behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol. The contribution of cocaethylene to the enhanced effects produced by the co-administration of cocaine and alcohol was discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051044
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  • 90
    Digitale Medien
    Digitale Medien
    Pretreatment with the putative anti-addictive drug, ibogaine, increases the potency of cocaine to elicit locomotor responding: a study with acute and chronic cocaine-treated rats (1999)
    Springer
    Psychopharmacology 145 (1999), S. 227-233 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Ibogaine ; Cocaine ; Dose-response ; Locomotor activity ; Sensitization ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine, on drug-induced locomotor behavior depends on the previous drug history of the animal. Objectives: To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically with either saline or cocaine. Methods: Rats were chronically treated with either cocaine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later, a cocaine dose-locomotor response test was conducted (0, 5, 10, 20 and 40 mg/kg, IP). Results: Chronic cocaine administration augmented the locomotor response to cocaine in chronic cocaine-treated rats, compared to acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine groups. Furthermore, due to the shape of the dose-response curve, in chronic cocaine but not in acute cocaine rats, ibogaine pretreatment enhanced the locomotor response to 5 and 10 mg/kg cocaine while decreasing the locomotor response to 40 mg/kg cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine, an effect which depends, in part, on the previous cocaine history of the animal.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051053
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  • 91
    Digitale Medien
    Digitale Medien
    Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys (1999)
    Springer
    Psychopharmacology 146 (1999), S. 49-59 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Dextromethorphan ; Dextrorphan ; Phencyclidine ; Self-administration ; Drug discrimination ; Monkey ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have neuroprotective and anticonvulsant properties through their activity as N-methyl-d-aspartate (NMDA) receptor channel blockers. Based on this receptor activity, coupled with reports of DXM abuse, both were evaluated for abuse potential and phencyclidine (PCP)-like behavioral effects in two animal models. Objectives and methods: The discriminative stimulus properties of DXO and DXM were tested in rats (3–56 mg/kg DXM, i.p. and 2.2–40.9 mg/kg DXO, i.p.) and rhesus monkeys (0.3–10 mg/kg DXM, i.m. and 0.25–8.0 mg/kg DXO, i.m.) trained to discriminate PCP from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set of experiments, i.v. self-administration of DXO (10–100 µg/kg/infusion) and DXM (10–1000 µg/kg/infusion) were tested under a FR schedule of reinforcement in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. Results: In rats, both DXM and DXO produced a dose-dependent substitution for PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) substitution for PCP, while DXO substituted fully for PCP in all four subjects tested. In the self-administration study, in five of the six subjects, at least one dose of DXM served as a positive reinforcer, maintaining infusion rates above those for saline. For DXO, at least one dose maintained infusion numbers well above mean saline infusion numbers in all subjects. Conclusions: Taken together, these data show that DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM may have some PCP-like abuse potential in humans but this potential may be associated with, or enhanced by, metabolism of DXM to DXO.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051087
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  • 92
    Digitale Medien
    Digitale Medien
    Modulation of behaviour on trials 1 and 2 in the elevated plus-maze test of anxiety after systemic and hippocampal administration of nicotine (1999)
    Springer
    Psychopharmacology 144 (1999), S. 54-60 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotinic receptor ; Dorsal hippocampus ; Anxiety ; Phobia ; Elevated plus-maze ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: The elevated plus-maze provides a test situation in which distinctive states of anxiety are elicited on trials 1 and 2 and the dorsal hippocampus has previously been shown to mediate the anxiogenic effects of (–)-nicotine in the social interaction test. Objective: To determine the effects of a wide dose range of (–)-nicotine on trial 1 and 2 in the plus-maze after systemic administration and whether the dorsal hippocampus is a site mediating the anxiogenic effect of nicotine. Methods: (–)-Nicotine (0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 mg/kg) was injected IP 30 min before testing for 5 min in the plus-maze. Rats receiving dorsal hippocampal infusions received bilateral infusions of 0.5 μl of artificial CSF or (–)-nicotine (0.1, 1, 4 or 8 μg). The needle was left in place for 50 s after injection and testing took place 3 min later. Rats tested on trial 1 were naive to the plus-maze, those tested on trial 2 had received a previous 5-min undrugged exposure to the maze 48 h earlier. Results: Low doses of (–)-nicotine (0.001, 0.005, 0.01, 0.05 and 0.1 mg/kg, IP) were without effect on either trial, but higher doses (0.5 and 1 mg/kg, IP) had anxiogenic effects on both trials, as shown by decreases in percentage time spent and percentage entries onto the open arms. Infusion of (–)-nicotine (0.1, 1, 4 and 8 μg) bilaterally into the dorsal hippocampus was without effect on trial 1, but 1 μg had an anxiolytic effect on trial 2, shown by an increased percentage time spent on the open arms. Conclusions: The results on both trials in the plus-maze after systemic administration of nicotine add to previous reports from the social interaction test that high doses of nicotine have anxiogenic effects. However, the effects of nicotine in the dorsal hippocampus are different in all three anxiety tests (anxiogenic in social interaction, ineffective on trial 1, anxiolytic on trial 2) showing that nicotinic cholinergic control in this brain region may vary depending on the state and/or type of anxiety generated by the test. The brain region(s) underlying the anxiogenic effects of IP nicotine on both trials in the plus-maze remain to be identified.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050976
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  • 93
    Digitale Medien
    Digitale Medien
    Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats (1999)
    Springer
    Psychopharmacology 144 (1999), S. 77-82 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Acquisition ; Cocaine ; Heroin ; Rat ; Self-administration ; Sex difference
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated sex differences in drug-reinforced behavior. Objectives: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. Methods: An autoshaping procedure was used to train rats to press a lever that resulted in either a 0.2 mg/kg infusion of cocaine or a 0.015 mg/kg infusion of heroin under a fixed-ratio 1 (FR 1) schedule. Daily sessions consisted of six 1-h autoshaping components followed by a 6-h self-administration component. During each autoshaping component, a retractable lever briefly (15 s) extended into the test chamber on a random interval schedule with a mean of either 90 s (cocaine groups) or 480 s (heroin groups) and either ten (cocaine groups) or five (heroin groups) computer-automated infusions were delivered each hour. During each 6-h self-administration component, the lever remained extended and each response on the lever resulted in an infusion of either cocaine (0.2 mg/kg) or heroin (0.015 mg/kg). The criterion for acquisition of cocaine self-administration was a mean of at least 100 infusions and the criterion for heroin self-administration was a mean of at least 20 infusions during the self-administration component over five consecutive sessions. Results: Female rats acquired both cocaine and heroin self-administration more rapidly than males. Acquisition of cocaine self-administration occurred in a greater percentage of female rats compared to males. Female rats self-administered more cocaine than males after acquisition criteria had been met. Conclusions: These findings indicate that female rats were more vulnerable than males to the acquisition of cocaine and heroin self-administration under the conditions of the present experiment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050979
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  • 94
    Digitale Medien
    Digitale Medien
    Enhancement of sustained attention performance by the nicotinic acetylcholine receptor agonist ABT-418 in intact but not basal forebrain-lesioned rats (1999)
    Springer
    Psychopharmacology 144 (1999), S. 175-182 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotinic acetylcholine receptor ; ABT-418 ; Methylphenidate ; Basal forebrain ; 192 IgG-saporin ; Sustained attention ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: Loss of telencephalic cholinergic projections has been postulated to contribute significantly to the cognitive decline associated with aging and dementia. Objective: The effects of the nicotinic acetylcholine receptor agonist ABT-418, a potential therapeutic drug for the treatment of the age- and dementia-associated cognitive disorders, were tested in an animal model of the cortical cholinergic deafferentation-induced impairments in sustained attention. Methods: Animals were trained in an operant task designed to test sustained attention performance. A partial loss of cortical cholinergic inputs was produced by infusions of 192 IgG-saporin into the basal forebrain. The effects of the systemic administration of ABT-418 (0.04, 0.13, 0.39 mg/kg) and the psychostimulant methylphenidate (0.2, 0.4, 0.8 mg/kg) were assessed. Results: Compared with sham-lesioned animals, this lesion resulted in a decrease in the relative number of hits while the relative number of correct rejections remained unaffected. Administration of ABT-418 significantly improved the relative number of hits. Furthermore, this effect of ABT-418 interacted with the effects of the lesion. Unexpectedly, this interaction was based on a significant enhancement of the performance of sham-lesioned animals while no effects were found in 192 IgG-saporin-lesioned animals. Administration of methylphenidate did not affect performance. Conclusions: While these data do not support the hypothesis that administration of ABT-418 attenuates the impairments in attentional performance that result from loss of cortical cholinergic inputs, they support previous notions about this drug’s ability to enhance cognitive processes in intact subjects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050991
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  • 95
    Digitale Medien
    Digitale Medien
    Initiation of ethanol self-administration in the rat using sucrose substitution in a sipper-tube procedure (1999)
    Springer
    Psychopharmacology 147 (1999), S. 274-279 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Ethanol ; Initiation ; Sucrose-substitution ; Appetitive-consummatory ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: The concepts of appetitive and consummatory behaviors provide a framework for examining ethanol-drinking behavior. However, traditional studies of ethanol self-administration using dipper procedures make separating the appetitive from the consummatory components difficult. Objective: This study compared the ability to initiate ethanol self-administration using a new sipper-tube self-administration procedure with the older established sucrose-substitution initiation model that employed dipper presented reinforcement. The new model was developed to allow for an assessment of the appetitive and consummatory components in ethanol self-administration. Methods: For the sipper-tube procedure, the rats were initiated to self-administer ethanol using a sucrose-substitution procedure that provided limited access to a sipper tube containing ethanol. This procedure required the completion of a fixed ratio requirement (FR4) in order to gain access to a sipper tube for 20 min. Initially, a 20% sucrose solution with no ethanol was provided in the sipper tube. Over sessions, the concentration of sucrose was reduced and the ethanol concentration increased, until 10% ethanol in water was the solution presented. A second group of animals was initiated to self-administer ethanol using the dipper-presentation procedure employed in our laboratory for many years. This group was used for comparison of the effectiveness of initiation in the sipper-tube procedure. Results: Following initiation, the sipper-tube rats self-administered 10% ethanol in water with intakes averaging 0.75 g/kg during the 20-min drinking period. Increasing the ethanol concentrations as high as 20%, increased intakes as high as 1.5 g/kg. The ethanol intakes observed were similar to those obtained with the dipper initiation procedure but occurred in one-third of the time. Conclusions: The sipper-tube procedure employed here results in similar ethanol self-administration behavior as has been found with a dipper presentation procedure. More importantly, however, it allows for a separation of the appetitive and consummatory components of ethanol self-administration. This separation may prove useful for examining the strength of ethanol-seeking behaviors without the confound of increasing levels of ethanol interacting with the appetitive seeking behaviors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051167
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  • 96
    Digitale Medien
    Digitale Medien
    Mild social stress abolishes the effects of isolation on anxiety and chlordiazepoxide reactivity (1999)
    Springer
    Psychopharmacology 144 (1999), S. 311-315 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Anxiety ; ACTH ; Corticosterone ; GH ; Stress ; Anxiolytic ; Chlordiazepoxide ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: Social isolation is anxiogenic and may change the effects of anxiolytic drugs. These effects are generally attributed to ”isolation stress”. However, isolation does not affect basal corticosterone levels; thus, it cannot be considered stressful. On the contrary, isolation deprives animals of mild daily stressors that are inherent to social life. Since mild stressors were shown to be anxiolytic in rats, it was postulated that short-term, repeated stressors may abolish the effects of isolation. Objectives: The aim of the present study was to investigate whether short-term, repeated, mild social stress can abolish the consequences of isolation on anxiety and on the effects of chlordiazepoxide. Methods: Rats were housed in groups or in individual cages for 5 days (isolates). Half of isolates were daily submitted to the attacks of a resident rat for 30 min per day, on 4 consecutive days (stressed isolates). On day 5, rats were treated either with vehicle or with chlordiazepoxide and submitted to the elevated plus-maze test. Endocrinological consequences of experimental manipulations were assessed in a different set of rats. Results: Plasma ACTH and corticosterone levels were similar in the three groups. Weight gain was higher, while plasma growth hormone was lower in stressed isolates, both effects being consistent with a mild stress. Isolation had a clear anxiogenic effect. This effect was completely abolished by the daily experience of social stress. Chlordiazepoxide had a significant anxiolytic effect in all three groups. Its effects on classical plus-maze variables did not differentiate the three groups. However, chlordiazepoxide decreased risk assessment activity only in isolates. Conclusions: The lack of appropriate endocrinological changes challenges the concept of ”isolation stress”. However, isolation was anxiogenic in our study and it also induced subtle changes in the effects of chlordiazepoxide. It appears that mild daily stressors have a protective effect against the effects of isolation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051012
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  • 97
    Digitale Medien
    Digitale Medien
    Alterations of the dopaminergic and glutamatergic neurotransmission in adult rats with postnatal ibotenic acid hippocampal lesion (1999)
    Springer
    Psychopharmacology 145 (1999), S. 61-66 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Hippocampus ; Lesion ; Glutamate receptor and release ; Dopamine receptor ; Locomotor activity ; Schizophrenia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In 6-week and 8-week-old rats (pre- and postpubertally) with neonatal excitotoxic lesions of the ventral hippocampus with ibotenic acid (IBO), we have studied apomorphine-induced motor activity and glutamate and dopamine D1 and D2 binding sites in the hippocampus, striatum, nc. accumbens and frontal cortex as well as K+-stimulated (3H)-D-aspartate release from hippocampal and frontal cortical slices. Specific glutamate binding was enhanced in the frontal cortex of 8-week-old IBO-treated animals, whereas that in other brain regions remained unchanged. Both D1 and D2 binding sites were downregulated in the striatum without changes in other brain structures. In 6-week-old rats, neither the glutamate nor the dopamine binding sites were altered. The amino acid release from hippocampal and frontal cortical slices of adult IBO treated rats was significantly decreased in comparison to controls, whereas in 6-week-old rats, no significant alterations were detectable. The additionally monitored motor activity was enhanced only in adult IBO-lesioned rats after apomorphine pretreatment. The present data are in agreement with the hypothesis of hyperactive dopamine and hypoactive glutamate systems in schizophrenia and are discussed in the light of schizophrenia-like behavioral changes in rats after postnatal hippocampal IBO lesion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051032
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  • 98
    Digitale Medien
    Digitale Medien
    Differential effects of withdrawal from chronic amphetamine or fluoxetine administration on brain stimulation reward in the rat – interactions between the two drugs (1999)
    Springer
    Psychopharmacology 145 (1999), S. 283-294 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Amphetamine ; Fluoxetine ; Intracranial self-stimulation thresholds ; Withdrawal ; Depression ; Selective serotonin reuptake inhibitors ; Psychostimulant ; Reward ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. Objectives: The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. Methods: A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. Results: Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1–5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. Conclusions: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051060
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  • 99
    Digitale Medien
    Digitale Medien
    Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine (1999)
    Springer
    Psychopharmacology 145 (1999), S. 442-451 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Nornicotine ; Behavioral sensitization ; Locomotor activity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051079
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  • 100
    Digitale Medien
    Digitale Medien
    Fluoxetine blocks expression but not development of sensitization to morphine-induced oral stereotypy in rats (1999)
    Springer
    Psychopharmacology 146 (1999), S. 19-23 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Serotonin ; Sensitization ; Rat ; Dopamine opiate ; Movement disorder
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: Repeated high doses of morphine in the rat cause stereotypic gnawing behavior that can be re-expressed by a low dose of morphine weeks and even months after the initial treatment. The determination of the role of serotonin in this sensitized morphine-induced behavior has both empirical and theoretical relevance. Objectives: To determine whether the serotonin-reuptake blocker fluoxetine will block the development and/or the expression of this opiate-induced stereotypy. Methods: Rats were given four 10-mg/kg injections of morphine alone or with 5.0 mg/kg fluoxetine over a 36-h period. At weekly intervals for 6 weeks after the last of the sensitizing morphine doses, all rats were challenged with 4.0 mg/kg morphine. At week 2 and week 4, however, the morphine was co-administered with fluoxetine. Results: Fluoxetine completely blocked the expression of the morphine-induced stereotypy; however, when the morphine/fluoxetine-treated rats were challenged with morphine alone, they expressed similar degrees of stereotypy as the rats that initially only received morphine. Conclusions: The results indicate that increasing synaptic serotonin will block the expression but not the development of sensitization to the oral stereotypic effects of repeated high doses of morphine. Also, despite the complete blocking of the morphine effect by fluoxetine during the sensitization phase, the presence of significant biting by these rats during the challenge with morphine alone argues that conditioning factors are not a necessary component for the morphine sensitization to develop.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130051083
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