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  • Articles: DFG German National Licenses  (136)
  • 2000-2004  (136)
  • Prognosis  (77)
  • Cell & Developmental Biology
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  • Articles: DFG German National Licenses  (136)
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  • 1
    ISSN: 1530-0358
    Keywords: Abdominoperineal resection ; Laparoscopy ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although laparoscopic colorectal surgery is attracting ever more attention, its use for curative treatment of colorectal carcinoma in particular continues to be controversial. The present study was an attempt to analyze the results of the perioperative course, oncologic quality, and preliminary long-term results. METHOD: The data considered here were collected within the framework of a prospective, observational study initiated on August 1, 1995, and involving a total of 18 institutions in Germany and Austria. At the end of three years, the results are now being presented selectively,i.e., focusing only on abdominoperineal resection. RESULTS: A total of 116 patients underwent laparoscopic abdominoperineal resections, 98 (84.5 percent) of which were performed with curative intent. The mean operating time was 226 (confidence interval, 140–365) minutes. Seven patients (6 percent) experienced an intraoperative complication, which in more than one-half of the cases was a vascular injury involving the presacral venous plexus; the conversion rate was 3.4 percent. Postoperatively, 40 patients developed 97 complications—including those of a very minor nature—giving an overall morbidity rate of 34.4 percent. Reoperation in six patients (5.2 percent) had to be performed for an afterbleed in one-half of the cases and ileus in the other one-half. Postoperative mortality was a low 1.7 percent. In most of the curative resections, an oncologically radical operation with high transection of the inferior mesenteric artery and a complete dissection of the pelvis down to the floor was performed. The median number of lymph nodes investigated was 11.5, and there was wide fluctuation in the numbers among the individual institutions. Tumor cell dissemination occurred intraoperatively in five patients. In the meantime, 79 patients (81 percent) underwent at least one follow-up examination, the mean follow-up period being 491 days. Seven patients developed a local recurrence, and a further six patients developed distant metastases. For recurrence-free survival rate, the Kaplan-Meier estimation calculated a probability of 71 percent. CONCLUSION: Not all of the reservations about laparoscopic abdominoperineal resection, in particular with regard to resection with curative intent, have yet been eliminated. The present study does, however, show that a laparoscopic approach can in principle meet oncologic requirements of radicality and, with regard to the postoperative course, is associated with considerable benefits to the patient.
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  • 2
    ISSN: 1530-0358
    Keywords: Fistula-in-ano ; Surgery ; Imaging ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Magnetic resonance imaging of fistula-in-ano has been shown to predict surgical anatomy accurately and identify complex features. In addition, fistula complexity has been correlated with poor outcome after surgical intervention. We investigated whether preoperative magnetic resonance imaging could predict clinical outcome after surgery for fistulous disease better than clinical examination under anesthetic. METHODS: Seventy patients with clinically suspected fistula-in-ano underwent preoperative dynamic contrast-enhanced magnetic resonance imaging before surgical exploration. Outcome was assessed at a minimum of one year after surgical exploration and correlated in a blinded fashion with the surgical and magnetic resonance grading of the severity of the fistulous disease. RESULTS: Of 70 patients, 12 were not operated on and 6 were lost to follow-up, making 52 patients eligible for analysis. Assessment by dynamic contrast-enhanced magnetic resonance imaging more accurately predicted outcome than the findings at initial surgical exploration. Dynamic contrast-enhanced magnetic resonance imaging had a sensitivity of 81 percent, specificity of 73 percent, and positive predictive value of 75 percent; surgery had a sensitivity of 77 percent, specificity of 46 percent, and positive predictive value of 59 percent. Surgical assessment of apparent disease severity bore no relation to final outcome. Dynamic contrast-enhanced magnetic resonance imaging could accurately predict whether patients were likely to have a satisfactory or unsatisfactory outcome after surgery. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging better predicts clinical outcome of patients with fistula-in-ano than initial surgical exploration.
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  • 3
    ISSN: 1534-4681
    Keywords: Rectal cancer ; Intensive follow-up ; Local recurrence ; Reoperation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Because more than 90% of local recurrences after curative surgery for rectal cancer appear within the first 36 months after surgery, an intensive and strict follow-up program during this period could improve early diagnosis and, thus, prognosis of patients. Methods: Of the 216 patients who underwent surgery for rectal cancer, 127 entered an intensive follow-up program (median follow-up: 42 months); the clinical outcome of the remaining 89 patients was reconstructed with the help of their general practitioners. Results: Fifty eight (26.8%) of the 216 patients who were treated with curative surgery alone developed a local recurrence; pelvic recurrences were prevalent. Eleven (30.5%) of the 36 patients who had recurrence during follow-up, and 6 of the 22 who had not undergone follow-up, had a reoperation with curative intent; the median survival was 19 months vs. 8 months, respectively (P 5 ns). Four (44.4%) curative reoperations were performed on the 9 asymptomatic patients and in 13 (26.5%) of the 49 cases with symptomatic local recurrences. Median survival was 15 months vs. 14 months, respectively (P 5 n.s). All patients except one (living after 42 months from reoperation) died within 48 months. Conclusions: In our study, adherence to a strict follow-up program unfortunately proved to be ineffective for improving long-term survival for patients who underwent reoperation with curative intent.
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  • 4
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Prognosis ; Pepsinogen C ; Pepsinogen A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. Methods: Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. Results: A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P 〈 .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P 〈 .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P 〈 .001), and in 71 patients with resectable carcinomas (P 〈 .005). Multivariate analysis according to Cox’s model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P 〈 .05, for both). Conclusions: The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.
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  • 5
    ISSN: 1534-4681
    Keywords: Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival rate ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis. Methods: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1–6), Level II nodes (intermediate, No.7–9), and Level III nodes (distant, No.10–16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk. Results: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P 〈 .01), total number of positive nodes (P 〈 .01), number of positive Level I nodes (P 〈 .01), and number of positive Level II nodes (P 〈 .01), in addition to the tumor location (P 〈 .05), tumor size (P 〈 .05), gross type (P 〈 .01), and depth of wall invasion (P 〈 .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0–1 vs. ≥2) (62% vs. 19%, P 〈 .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P 〈 .01). Conclusions: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.
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  • 6
    ISSN: 1530-0358
    Keywords: Pravastatin ; ras p21 isoprenylation ; Colon carcinogenesis ; Flat colon tumor ; Azoxymethane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The effect of pravastatin, an inhibitor ofras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associatedras p21 in colon tumors. CONCLUSIONS: These findings suggest that theras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
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  • 7
    ISSN: 1530-0358
    Keywords: Microscopic peritoneal dissemination ; Colon-cancer ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. METHODS: Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. RESULTS: In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P=0.044 andP=0.0002), whereas immunocytology was only associated with M category (P=0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P〈0.0015/P=0.007 andP〈0.001/P=0.009, respectively). Positive immunocytology was additionally associated with pN category (P=0.05). In a univariate analysis of R0 resected patients (no residual tumor), positive immunocytology was significantly related to an unfavorable prognosis in patients with gastric cancer only (n=30). Mean survival time was significantly increased in patients with gastric cancer with negative cytology compared with positive cytology (1,205 (standard error of the mean, 91)vs. 771 (standard error of the mean, 147) days;P=0.007) but not in patients with colon cancer (1,215 (standard error of the mean, 95)vs. 1,346 (standard error of the mean, 106) days;P=0.55). CONCLUSIONS: Because microscopic peritoneal dissemination influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1222-1226 
    ISSN: 1530-0358
    Keywords: Colorectal neoplasms ; Young age ; Case-control study ; Pathology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Colorectal adenocarcinoma before the age of 40 is uncommon, and its prognosis is controversial, with many studies reporting a worse prognosis than in older patients and others showing no difference. The current study compared two groups of patients who had surgical resection for colorectal adenocarcinoma. METHODS: The case group was composed of 34 patients younger than 40 (34 ± 4) years. Detailed pathologic prognosis factors, tumor cell proliferation measured by proliferating cell nuclear antigen, survival, family history, and predisposing conditions were analyzed. Results were compared with a control group constituted of 34 patients older than 65 (75 ± 6) years matched by gender, cancer site, and Dukes stage. RESULTS: Tumor differentiation, presence of vascular and perineural neoplastic invasion, tumor growth pattern, tumor cell proliferation measured by proliferating cell nuclear antigen count, and survival according to the Kaplan-Meier method were not significantly different between younger and older patients. The only difference between the two groups was a higher prevalence of family history and predisposing conditions for colorectal cancer in younger patients (23vs. 3 percent;P=0.03). CONCLUSION: This case-control study documents that pathologic features and prognosis of colorectal adenocarcinoma are comparable in patients younger than 40 years compared with older patients for identical stages. The higher prevalence of positive family history in younger patients suggests a different genetic background compared with older patients.
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  • 9
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Younger patients ; Elderly patients ; Comparative study ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Gastric cancer is one of the most common gastrointestinal malignancies worldwide. Some studies have suggested that it has a worse prognosis in young than in elderly patients. Methods: All young and elderly patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a tertiary referral center in Mexico City were included. Demographic, clinical, and pathologic features of young patients (less than 40 years of age) with gastric cancer were compared with those of elderly patients (70 years of age or older) with the same diagnosis. Overall survival was the main outcome measure. Results: There were 38 patients in each group. The mean age of the young and elderly groups was 33 and 77 years, respectively. Family history of gastric cancer was reported by 6 patients of the younger group and by 1 patient in the older group (P 〈 .05). Most patients in both groups were symptomatic and had an advanced stage of the disease. With a mean follow-up of 17 months, the overall median survival for all patients was 12 months. By group, the median survival was 13 and 12 months for the young and elderly patients, respectively (P = .38). Variables with significant impact on survival were the stage of the disease, possibility of surgical resection, location of the tumor, and a family history of gastric cancer. Conclusions: Young patients represent a significant proportion of patients with gastric cancer in Hispanic populations. There were no significant differences in clinicopathological characteristics and outcome of gastric adenocarcinoma between young and elderly patients. Survival was determined by the stage of the tumor and the possibility of complete surgical resection.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Annals of surgical oncology 7 (2000), S. 520-525 
    ISSN: 1534-4681
    Keywords: Proximal gastric third ; Adenocarcinoma ; Total gastrectomy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The incidence of proximal gastric third carcinoma (PGC) has been rising in recent years. Classification and surgical therapy remain controversial. Methods: Between May 1986 and October 1997, 532 patients were operated for primary gastric carcinoma. All patient data were analyzed retrospectively comparing findings in patients with PGC and those with distal gastric carcinoma (DGC). Results: Two hundred fifty patients had a PGC, and 282 patients had a DGC. The rate of R0 resections was 79.3% for PGC and 81.6% for DGC. In 93.9% of the patients with PGC total gastrectomy was performed; for DGC total gastrectomy was done in 74.5% of patients. Postoperative morbidity and mortality were 29.2% for PGC and 23.8% for DGC, and 3.2% for PGC and 3.5% for DGC, respectively. Patients with advanced tumor stages (stage III and IV) were more common in the PGC group (73.3% vs. 53.6% in DGC). After R0 resection, the 5-year survival rate was 33.2% for PGC and 59.7% for DGC. Conclusions: There was no significant difference between the rates of R0 resections for PGC and DGC. Total gastrectomy can be performed with low postoperative morbidity and mortality. PGC and DGC represent the same tumor entity, and prognosis is similar, but due to more advanced tumor stages, the long-term survival is worse for patients with PGC than for those with DGC. Left retroperitoneal lymphadenectomy may be indicated for PGC.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
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  • 12
    ISSN: 1534-4681
    Keywords: Colorectal hepatic metastases ; Liver neoplasm ; Liver resection ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined. Methods: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed. Results: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4–20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median 5 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival. Conclusions: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.
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  • 13
    ISSN: 1436-3305
    Keywords: Key words EGC ; Prognosis ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. During the 1970s, a special type of Gastric Cancer with excellent prognosis (early gastric cancer; EGC) was identified by the Japanese Research Society for Gastric Cancer. EGC has been defined as a tumor which invades the mucosa and/or submucosa, regardless of the lymph node status. Using this definition, we identified an initial phase of tumor development which could be treated both endoscopically and surgically. Methods. We examined 412 EGC patients, recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an end-point of interest for the survival analysis. Results. Submucosal tumors (P = 0.008), Pen A (see definition below) type disease (P = 0.0001), and lymph node-positive cancers (P = 0.0002) were significant prognostic factors on univariate analysis. Moreover, bivariate analysis showed that the worst prognosis, in terms of survival, was for patients with nodal involvment, submucosal invasion, and node-positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a lesion with a diameter of less than 4 cm, which invades the submucosa diffusely. Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa extensively, with nodular masses, causing the complete destruction of the muscularis mucosae. Conclusion. In our series, Pen A type was an important prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49–19.86. For this reason, we believe it is important to evaluate the infiltration into the wall in all patients with EGC, paying particular attention to the growth pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a considerably worse prognosis and this finding was reinforced when lymph node metastases coexisted. We suggest, therefore, that surgical treatment with at least a D2 lymphadenectomy is performed in all these patients, as the lesions must be considered to be advanced, no longer being EGC.
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  • 14
    ISSN: 1436-3305
    Keywords: Key words Tumor marker ; CEA ; CA19-9 ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer. Methods. During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression. Results. Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression. Conclusion. Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S154 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Hinteres Kreuzband ; Isolierte Ruptur ; Therapie ; Prognose ; Key words ; Posterior cruciate ligament ; Isolated tears ; Treatment ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The treatment of injuries to the PCL is still controversial. There are still no answers to many questions on the biomechanics of PCL, the natural history of PCL injury, the surgical technique of PCL reconstruction and the biology of PCL healing. It is well established that primary repair of bony avulsions of the PCL provides good static and functional results. PCL tears should also be treated surgically in combined knee ligament injuries. For isolated midsubstance tears of the PCL, however, no prospective randomised long-term studies are available to date demonstrating that surgical treatment with current techniques leads to better results than nonoperative, functional treatment. Nonoperative management is advocated because the knee instability following isolated PCL midsubstance tear is only moderate, the natural history has been seen to end in acceptable functional stability, knee proprioception is preserved, and the incidence of late osteoarthritis is low.
    Notes: Zusammenfassung Die Behandlung von Rupturen des hinteren Kreuzbands wird international noch immer kontrovers diskutiert. Zahlreiche Fragen zur funktionellen Anatomie, zum Spontanverlauf nach Ruptur, zur chirurgischen Technik sowie zum Heilungsverlauf sind unbeantwortet. Gesichert ist, daß die primäre operative Versorgung von knöchernen Ausrissen des hinteren Kreuzbands zu guten Ergebnissen führt. Bei kombinierten Knieinstabilitäten sollte das verletzte hintere Kreuzband auch operativ versorgt werden. Für die isolierte, interligamentäre Ruptur des hinteren Kreuzbands konnte bisher jedoch mit keiner prospektiven, randomisierten Langzeitstudie bewiesen werden, daß die heutigen Operationsverfahren reproduzierbar zu besseren Ergebnissen führen als die konservativ-funktionelle Behandlung. Für die konservative Therapie sprechen die nur mäßige Instabilität nach isolierter Ruptur des hinteren Kreuzbands, der günstige Spontanverlauf und der Erhalt der Propriozeption des Kniegelenks sowie die im Verlauf nur geringe Arthroserate.
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  • 16
    ISSN: 1436-2023
    Keywords: Key words Adriamycin ; Rat ; Embryo ; VATER association ; Synovial joint ; Bones ; Limbs ; Vertebra ; Sirenomelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6–9 or 10–13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6–9, while it was low in the GD 10–13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6–9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.
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  • 17
    ISSN: 1436-2813
    Keywords: Key Words Adenosquamous carcinoma ; Remnant stomach ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein the case of a 59-year-old man found to have adenosquamous carcinoma of the remnant stomach which demonstrated rapid progression. The patient was admitted to our hospital to undergo surgery for a papillary tumor of the remnant stomach. Total resection of the remnant stomach with lymph node dissection was performed, and pathological examination confirmed a diagnosis of adenosquamous carcinoma with invasion into the muscularis propria and lymph node metastasis around the perigastric areas. Multiple liver metastases were found 6 months after the operation, for which a right hepatectomy was performed with curative intent; however, he died 2 months later due to lymphangitis carcinomatosa of the lung.
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  • 18
    ISSN: 1436-3305
    Keywords: Key words Hypergastrinemia ; Carcinoid tumor ; Prognosis ; Autoimmune gastritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Gastric carcinoid tumors associated with chronic atrophic gastritis type A have been reported to show good prognosis, because invasion and metastasis are rare. We report a case of gastric carcinoid tumor associated with hypergastrinemia that showed no malignant changes for 12 years. A 15-year-old man with abdominal discomfort underwent endoscopic examination. A polypoid lesion was detected on the atrophic mucosa of the fundus, and was diagnosed as a carcinoid tumor. Serological examination revealed a high level of anti-parietal-cell antibody, suggesting that the patient had chronic atrophic gastritis type A. The tumor was treated by endoscopic mucosal resection. Follow-up examinations were performed for 12 years, but showed no recurrence. This case confirms that gastric carcinoid tumors associated with chronic atrophic gastritis type A may have a good prognosis.
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  • 19
    ISSN: 1436-3305
    Keywords: Key words Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis. Methods. The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model. Results. The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]). Conclusion. In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.
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  • 20
    ISSN: 1432-2307
    Keywords: Keywords AgNORs ; Standardised AgNOR analysis ; Parathyroid tumour ; Proliferation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 µm2; SE 0.171) through PA (3.638 µm2; SE 0.125) to PC (4.701 µm2; SE 0.179); these differences were highly significant (P〈0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P〈0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 µm2; SE 0.106) than in nonrecurrent PH (2.261 µm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.
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  • 21
    ISSN: 1432-2307
    Keywords: Keywords 7 ; 12-dimethylbenz(a)anthracene ; Rat ; Submandibular gland ; Adenocarcinoma Myoepithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In an attempt to induce adenocarcinoma containing myoepithelial cells (MECs) in the rat submandibular gland, we injected 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone into the glands of rat pups at the age of 10 days. In both male and female pups, the glands, including their developing terminal secretory units, contained far greater numbers of cells positive for proliferating cell nuclear antigen (PCNA) than did adult glands. A single administration of 1% DMBA (0.05 ml/130 g b.w.) did not produce adenocarcinoma, but did induce occasional sarcomas, such as rhabdomyosarcoma and fibrosarcoma, in 2 months. Most glands regenerated with minimal scar formation. Microscopically, these glands were atypical in that they contained increased numbers of PCNA-positive cells, underdeveloped granular ducts, and striated ducts surrounded by MECs positive for alpha smooth muscle actin (αSMA). Though these features were also observed in the regenerated glands after acetone injection, the number of PCNA-positive cells was relatively high in the glands of DMBA-treated females, especially in the terminal secretory unit. The second DMBA injection at 10 weeks of age produced adenocarcinoma made up of αSMA-positive MECs and keratin 19-positive duct cells. Such MEC-associated adenocarcinoma was induced in the glands of more than half the female but not the male animals. Replacement of either of the double DMBA treatments with acetone, or DMBA treatment, single or double, of adult glands did not produce adenocarcinoma, but did produce sarcoma and squamous cell carcinoma. These results suggest that (1) at least two genetic mutations are necessary for induction of adenocarcinoma with MECs in the rat submandibular gland, (2) the mutation is efficiently introduced to pup glands whose terminal secretory units exhibit extreme proliferative activity, and (3) the second mutation is difficult to introduce in male glands, whose proliferative activity is relatively low, and/or transformed cells need some female hormone after the mutation to propagate.
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  • 22
    ISSN: 1432-1335
    Keywords: Key words erbB-3 ; Colorectal carcinoma ; Survival ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P 〈 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.
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  • 23
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    Journal of cancer research and clinical oncology 126 (2000), S. 27-32 
    ISSN: 1432-1335
    Keywords: Key words Heart irradiation ; Plasma enzyme levels ; Myocardial enzyme levels ; Rat ; AbbreviationsCK creatine kinase ; LDH lactate de-hydrogenase ; AST aspartate aminotransferase ; ALT alanine aminotransferase ; α-HBDHα-hydroxybutyrate dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma levels of myocardial enzymes present after local heart irradiation were studied in a rat model. The purpose was to investigate whether, within days after irradiation, these enzyme levels change to such an extent that they may be helpful in assessing the severity of cardiac damage after radiotherapy. Therefore, activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and α-hydroxybutyrate dehydrogenase (α-HBDH) were determined in the plasma and left ventricular myocardium of rats following local heart irradiation with a single dose of 20 Gy. A dose of 20 Gy is known to cause irreversible cardiac damage and to reduce survival times of the animals. Cardiac enzyme assays were performed directly after and twice daily for up to 2 weeks after radiation. Plasma CK, LDH, AST and α-HBDH levels were increased between 2 h and 24 h after irradiation. Plasma ALT levels remained unchanged. Myocardial enzyme levels, measured between 24 h and 16 days after radiation, did not differ between irradiated and control animals, although acute (first 12 h) reductions were observed in the irradiated group. The elevated enzyme levels in plasma appeared to correlate with the acutely reduced myocardial enzyme levels. Although irradiation with a dose of 20 Gy induced acute rises of cardiac enzyme levels in plasma, it is doubtful that fractionated radiation, as applied clinically for treatment of solid tumors, will induce plasma enzyme elevations that are large enough to indicate the extent of cardiac damage occurring acutely or chronically.
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  • 24
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    Journal of cancer research and clinical oncology 126 (2000), S. 48-52 
    ISSN: 1432-1335
    Keywords: Key words Enzyme-linked immunosorbent assay ; p53 protein ; WAF1 protein ; Lung cancer ; Prognosis ; AbbreviationsNSCLC non-small-cell lung cancer ; RR relative risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: p21WAF1, a cyclin-dependent kinase inhibitor, is an important mediator of the cell-cycle arrest and tumor suppression induced by the protein p53. Although alterations of the p53 gene and its overexpression are frequent in most malignancies, including non-small-cell lung cancer (NSCLC), and may be associated with poor patient prognosis, the clinical utility of p21WAF1 expression in NSCLC has not been established. Methods: We have used a commercial enzyme-linked immunosorbent assay (ELISA) kit for p21WAF1 to test soluble extracts of 54 NSCLC specimens with known clinicopathological properties. Results: There was no correlation between p21WAF1 and p53 concentrations, the latter being determined by a time-resolved immunofluorometric assay developed in-house. Furthermore, p21WAF1 levels were not associated with patient age, tumor/node/metastasis (TNM) stage, lymph node metastasis, histological grade or type, or smoking history, in Mann-Whitney analysis. χ2-tests, based on cutoffs equal to the 25th, 50th, or 75th percentiles of the p21WAF1 distribution, similarly did not reveal any statistically significant associations between p21WAF1 and other clinicopathological variables. Because of the small number of patients and the median follow-up of only 18 months, a meaningful survival analysis could not be performed. Conclusion: In summary, this preliminary study suggests that ELISA-quantified p21WAF1 levels in NSCLC extracts are weaker than p53 in terms of prognostic value and do not contribute to the further subclassification of patients.
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  • 25
    Electronic Resource
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    Der Ophthalmologe 97 (2000), S. 121-125 
    ISSN: 1433-0423
    Keywords: Schlüsselwörter Postoperative Endophthalmitis ; Prognose ; Visus ; Bakterien-Kultur ; Verlaufsform ; Key words Postoperative endophthalmitis ; Prognosis ; Visual acuity ; Microbiology culture ; Onset of endophthalmitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: The outcome of 20 patients is summarized in a retrospective study to identify clinical findings that influence the long-term prognosis of postoperative endophthalmitis. Patients: Between 1991 and 1997 a total of 20 patients with postoperative endophthalmitis were admitted. Median age was 80 years (range: 9–95), 11 patients were male, 9 female. Sixteen pars-plana vitrectomies, 2 anterior vitrectomies and 2 rinsings of the anterior chamber without vitrectomy were performed. Furthermore, all patients received intraocular and systemic antibiotic treatment. For microbiological investigation, specimens from vitreous, anterior chamber and conjunctiva were sent in. Long-term outcome was controlled for an average of 14 months after treatment of the endophthalmitis (range: 4–36 months). Results: At the end of treatment, 40% of patients had a visual acuity of 0.4 or better, 80% had 1/20 or better. Patients with a preoperative visual acuity of at least hand movement had a better postoperative visual outcome than patients with only light perception. Visual acuity was better in patients with chronic endophthalmitis than in patients with acute or subacute endophthalmitis. In patients with chronic or subacute endophthalmitis, improvement of visual acuity was found some months after the operation more often than in patients with acute endophthalmitis. However, in 40% of cases with an acute onset, no improvement or even worsening of the visual acuity was documented. Best postoperative results were found after infection with Staphylococcus epidermidis and Propionibacterium acnes. Conclusion: Important prognostic factors of postoperative endophthalmitis are visual acuity, the onset of the endophthalmitis (acute, subacute or chronic) and the microbiological findings. At the time of surgery and antibiotic treatment, visual acuity should be at least hand motion to expect an improvement in the visual outcome.
    Notes: Zusammenfassung Fragestellung: Im Rahmen einer retrospektiven Studie sollte das Patientengut mit postoperativer Endophthalmitis bezüglich prognostischer Gesichtspunkte ausgewertet werden. Patienten und Methode: 20 Patienten (9 weiblich, 11 männlich), im Alter von 9–95 Jahren (Median 80 Jahre) mit postoperativer Endophthalmitis wurden im Zeitraum von 1991 bis 1997 in unserer Klinik behandelt. 16mal wurde eine Pars-plana-Vitrektomie (PpV) durchgeführt, weiterhin 2 vordere Vitrektomien und 2 Vorderkammerspülungen ohne Vitrektomie. Alle Patienten erhielten intraokular und systemisch Antibiotika. Der postoperative Beobachtungszeitraum betrug 4 bis 36 Monate (im Durchschnitt 14,0). Die mikrobiologische Untersuchung umfaßte Kulturen von Glaskörper, Vorderkammer und Bindehaut. Ergebnisse: Bei 80% der Patienten war der letzte Visus 1/20 und besser, bei 40% mindestens 0,4. Bei einem präoperativen Visus von mindestens Handbewegung (HB) war der postoperative Visus besser als bei einem schlechteren Ausgangsvisus (Lichtschein). Die chronischen Endophthalmitiden hatten ein besseres Visusergebnis als die akuten und subakuten Endophthalmitiden. Bei den chronischen und subakuten Verläufen war häufiger als bei den akuten Verläufen noch ein Visusanstieg in den ersten Monaten nach der Operation möglich. Bei 40% der akuten Verläufe stagnierte der Visusanstieg, oder der Visus wurde schlechter. Der postoperative Visus war bei Staphylococcus epidermidis- und Propionibacterium acnes-Infektionen am besten. Schlußfolgerung: Prognostische Faktoren der postoperativen Endophthalmitis sind der Visus, das Kulturergebnis und die Verlaufsform (akut, subakut, chronisch). Zum Zeitpunkt der Operation und der intravitrealen Antibiotikagabe sollte der Visus nicht schlechter als Handbewegungen sein, um postoperativ einen besseren Visus zu erreichen.
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  • 26
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Plattenepithelkarzinom ; Kopf-Hals-Bereich ; CGH ; Prognose ; Cox-Regression ; Key words Squamous cell carcinoma ; Head and neck region ; CGH ; Prognosis ; Cox regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract In individual patients with head and neck squamous cell carcinomas (HNSCC), established prognostic factors do not satisfactorily predict clinical outcome. For the first time we investigated a total of 100 HNSCC by Comparative Genomic Hybridization (CGH) to define chromosomal alterations that are associated with the patients prognosis. Patients were followed for at latest 4 but at least 2 years after surgery or until death. During this observation period twenty-nine of them died because of cancer disease. The Kaplan-Meier method was used plotting survival curves for every single chromosomal alteration as well as every clinico-pathological parameter. The curves were tested for significance by the log rank as well as the Breslow test. Significance of particular prognostic parameters was then evaluated by the Cox regression model. The overall survival time as well as the recurrence free survival time were significantly lower in patients who's tumors showed amplifications of the chromosomal region 11q13 (p=0.0008 for LR and p=0.0024 for B). The survival time of the patients was also lower if the carcinomas carried overrepresentations of chromosome 3q (p=0.0299 for LR and p=0.0546 for B). Multivariate analysis (Cox's proportional hazards model) revealed both alterations as most important independent prognostic factors in HNSCC. None of the conventional clinico-pathological parameters (pT-, pN-status, UICC stage, grading) achieved statistical significance in the multivariate model. These results suggest that in HNSCC the occurence of 11q13 amplification and 3q overrepresentation are highly significant independent prognostic markers and of better value than the established TNM and grading criteria.
    Notes: Zusammenfassung Die Prognose von Patienten mit Kopf-Hals-Karzinomen lässt sich anhand der etablierten Stagingparameter oft nur sehr ungenügend einschätzen. Auf der Suche nach neuen Markern, die den Tumorphänotyp genauer charakterisieren, wurden in der vorliegenden Studie 100 primäre Plattenepithelkarzinome des Kopf-Hals-Bereichs mit Hilfe der Comparativen Genomischen Hybridisierung (CGH) molekularzytogenetisch untersucht. Die detektierten genetischen Veränderungen (Deletionen oder DNA-Überrepräsentierungen bzw. Amplifikationen) wurden für jeden Chromosomarm aufgeschlüsselt und statistisch zusammen mit den klinisch-pathologischen Daten uni- und multivariat hinsichtlich ihrer prognostischen Aussagefähigkeit überprüft. Alle Patienten dieser Studie wurden primär operiert und in Abhängigkeit vom Tumorstadium adjuvant nachbestrahlt. In dem längstens 4-jährigen Beobachtungszeitraum waren von den 100 Patienten 29 am Tumorleiden verstorben. Die kumulierten Überlebensraten nach der Kaplan-Meier-Methode zeigten, dass sowohl die rezidiv- und metastasenfreie als auch die Gesamtüberlebenszeit signifikant kürzer ist bei Patienten, deren Tumoren eine Amplifikation der chromosomalen Region 11q13 und/oder eine DNA-Überrepräsentierung des Chromsomarms 3q aufweisen (p=0,0008 bzw. p=0,0299 im Log-Rank-Test und p=0,0024 bzw. p=0,0546 im Breslow-Test). Die Cox-Regression wurde für das rezidiv- und metastasenfreie Überleben und für das Gesamtüberleben jeweils mit den klinisch-pathologischen Parametern pT-, pN-Status, UICC-Stadium, Grading und den genetischen Markern 11q13-Amplifikation sowie 3q-Überrepräsentierung durchgeführt. Die Analyse ergab die genetischen Veränderungen im Bereich von 11q13 und 3q als die wichtigsten Marker für die Einschätzung des Überlebens, während die klinisch-pathologische Tumorklassifikation ohne prognostischen Einfluss war (bei Signifikanzniveau p〈0,05). Das Ergebnis unserer Studie eröffnet die Möglichkeit eines “genetischen Tumorgradings”, das als Zusatzinformation einer verbesserten Prognoseeinschätzung bei Kopf-Hals-Karzinomen dient.
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  • 27
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    Der Nervenarzt 71 (2000), S. 822-828 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Alkoholdelir ; Prognose ; Alkoholfolgekrankheiten ; CCT ; Liquor ; Keywords Alcohol withdrawal ; Delirium tremens ; Prognosis ; CT-scan ; Cerebrospinal fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.
    Notes: Zusammenfassung Der Verlauf intensivmedizinisch behandelter Alkoholdelirien ist in 28% der Fälle durch eine begleitende ZNS-Erkrankung erschwert. Durch das Delir mitigierte neurologische Begleiterkrankungen, wie Meningoenzephalitiden, intrakranielle Hämatome oder eine zentrale pontine Myelinolyse können bei Vorliegen einer atypischen deliranten Symptomatik durch eine neurologische Zusatzdiagnostik mit Hilfe von CCT/MRT und Liquoranalyse ausreichend diagnostiziert werden. Der diagnostische und prognostische Wert dieser Zusatzdiagnostik wurde an 32 neurologisch-intensivmedizinisch behandelten Alkoholikern im Delir untersucht. Das Auftreten zerebraler Komplikationen korreliert dabei ebenso wie ein initialer Grand-mal-Anfall mit einem protahierten Verlauf und Beatmungspflichtigkeit. Eine Blut-Liquor-Schrankenstörung ließ sich bei 70% nachweisen. Es finden sich Hinweise für einen verlängerten Krankheitsverlauf dieser Patienten. Dem alleinigen Nachweis einer zerebralen Atrophie im CCT/MRT kommt dagegen kein prognostischer Wert hinsichtlich des Delirverlaufes zu. Ein Alkoholdelir mit jedoch typischem klinischem Bild erfordert nach unseren Ergebnissen keine bildgebende oder liquoranalytische Untersuchung.
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  • 28
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Paraneoplastische zerebelläre Degeneration ; Opsoklonus-Myoklonus-Syndrom ; Limbische Enzephalitis ; Therapie ; Prognose ; Key words Paraneoplastic cerebellar degeneration ; Opsoclonus-myoclonus syndrome ; Limbic encephalitis ; Therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Paraneoplastic neurological syndromes are rare diseases that occur in relation to cancer. Supporting the hypothesis of an autoimmune mechanism, specific antineuronal antibodies have sometimes been detected. The current possibilities for treatment are limited. A female patient, aged 57, suffering from a breast cancer, developed a severe paraneoplastic cerebellar syndrome and limbic encephalitis within a few weeks. It is possible that the impressive partial remission that occurred during the ensuing 6 months was not due to therapy. Although the patient was still bound to a wheelchair, discharge from hospital was possible because she was still able to perform daily tasks by herself. A recurrence of the cerebellar symptoms with mild alterations of mental status occurred 2 months later but again showed a good remission.
    Notes: Zusammenfassung Paraneoplastische neurologische Syndrome sind seltene Erkrankungen in Assoziation mit einem Tumor, die bei vermutetem Autoimmunmechanismus mit antineuronalen Antikörpern einhergehen können und deren Verlauf therapeutisch nur bedingt beeinflussbar ist. Berichtet wird von einer 57-jährigen Patientin mit Mammakarzinom, die in engem zeitlichen Rahmen sowohl eine schwere paraneoplastische Zerebellopathie als auch eine limbische Enzephalitis entwickelte. In unklarem Zusammenhang zur Therapie kam es innerhalb von 6 Monaten zu einer vergleichsweisen guten Rückbildung beider Syndrome, so dass zwar noch eine partielle Rollstuhlpflichtigkeit bestand, bei weitgehender Selbständigkeit aber eine Entlassung nach Hause möglich war. Ein Rezidiv 2 Monate später mit im Vordergrund stehender zerebellärer Symptomatik verlief ebenfalls günstig.
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  • 29
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Kryptogene Temporallappenepilepsie ; MR-Spektroskopie ; Prognose ; Epilepsiechirurgie ; Key words Cryptogenic temporal lobe epilepsy ; MR spectroscopy ; Prognosis ; Epilepsy surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The preoperative localization of pharmaco-resistent focal epilepsies before surgery and the prognosis concerning seizure outcome are both of importance. In addition to conventional MRI diagnostics for the detection of small epileptogenic lesions, proton magnetic resonance spectroscopic imaging (HMR spectroscopy) can be useful for assessing the bilaterality of pathological changes in cryptogenic temporal lobe epilepsies. The technique and findings of HMR spectroscopy are reported in patients with cryptogenic temporal lobe epilepsies. The findings indicate that chemical shift imaging (CSI) investigations of the ipsilateral and contralateral hemispheres provide important information for the prediction of seizure outcome after epilepsy surgery.
    Notes: Zusammenfassung Bei der epilepsiechirurgischen Behandlung kryptogener Temporallappenepilepsien kommt neben der Lokalisation des epileptischen Fokus der Beurteilung der Prognose hinsichtlich der postoperativen Anfallskontrolle Bedeutung zu. Hierbei kann die Protonen-MR-Spektroskopie (1 HMR-Spekroskopie oder Chemical Shift Imaging CSI) nützliche Informationen liefern. Technik und Befunde des CSI im Vergleich zu einem Normkollektiv werden bei Patienten mit kryptogenen Temporallapenepilepsien dargestellt. Hierbei werden Ergebnisse der 1HMR-Spekroskopie (NAA/Cholin) und der T2-Relaxometrie mit der postoperativen Anfallskontrolle verglichen. Die Ergebnisse zeigen, dass die 1HMR-Spekroskopie mit NAA/Cholin wichtige Informationen für die Prädiktion hinsichtlich der postoperativen Anfallskontrolle liefert.
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  • 30
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    Trauma und Berufskrankheit 2 (2000), S. S57 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Proximale Ulnafraktur ; Olekranonfraktur ; Osteosynthese ; Prognose ; Key words ; Fracture of the proximal ulna ; Fracture of the olecranon ; Internal fixation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The pathogenesis, diagnosis, treatment and prognosis of fractures of the ulna and olecranon are described. It appears that both the potential benefits of using internal fixation techniques in the proximal ulna and the olecranon and the risks involved are heavily influenced by concomitant injuries, which means that the diagnosis and appropriate treatment of these are of decisive importance for the outcome.
    Notes: Zusammenfassung Pathogenese, Diagnostik, Therapie und Prognose von Ulna- und Olekranonfrakturen werden beschrieben. Dabei zeigt sich, daß die Chancen und Gefahren bei Osteosynthesen der proximalen Ulna und des Olekranons wesentlich von den Begleitverletzungen beeinflußt werden, deren Diagnose und adäquate Behandlung demzufolge für das Outcome entscheidende Bedeutung besitzt.
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  • 31
    ISSN: 1437-7799
    Keywords: Key words VEGF ; Glomeruli ; Ribonuclease protection assay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Vascular endothelial growth factor (VEGF) is a selective endothelial growth factor which potently enhances microvascular permeability. In the kidney, VEGF mRNA is known to be highly expressed in visceral epithelial cells in glomeruli. However, the physiological role of VEGF in glomerular function and its involvement in the pathogenesis of proteinuria are not clear. The present studies were designed to determine whether altered expression of VEGF mRNA was observed in the course of puromycin aminonucleoside (PAN) nephrosis in rats (a model of human minimal change nephrosis). Methods. The message level of VEGF in isolated glomeruli of PAN nephrosis rats was measured using a ribonuclease protection assay. Results. VEGF expression began to decrease 4 days after PAN injection and could not be detected in the nephrotic stage of PAN nephrosis (on days 8 and 16). In the remission of stage of PAN nephrosis (on day 28), mRNA was restored to the control level. Conclusions. According to our results, a functional defect in the VEGF expression of visceral epithelial cells was observed in PAN nephrosis. VEGF could be a functional marker of visceral epithelial cells, and the loss of normal expression of VEGF after damage to visceral epithelial cells could affect glomerular endothelial cell function in PAN nephrosis.
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  • 32
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    International journal of clinical oncology 5 (2000), S. 217-228 
    ISSN: 1437-7772
    Keywords: Key words Colorectal carcinoma ; Cytokines ; IL-6 ; IL-10 ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Host-tumor interactions are primarily controlled by paracrine interactions between adjacent normal host cells and malignant cells. Recent evidence from experimental and clinical neoplasms indicates that neoplasms, or their products, produce levels of circulating pro- and anti-inflammatory cytokines that modulate these local paracrine interactions in such a way that promotes tumor growth. This brief review focuses on several cytokines (interleukin-6, interleukin-10, transforming growth factor-beta, and vascular endothelial growth factor) that have systemic effects in experimental models and are associated with prognosis in patients with colorectal carcinoma. The primary focus of this review is on colorectal carcinoma, but implications for other malignancies are also considered. Colorectal and similar carcinomas may exert systemic control over neoplastic progression by modulating circulating levels of cytokines that then influence the growth of distant metastasis by affecting local paracrine interactions.
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  • 33
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    Pediatric surgery international 16 (2000), S. 485-487 
    ISSN: 1437-9813
    Keywords: Key words Duodenum ; Apoptosis ; Fetus ; Rat ; Duodenal atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.
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  • 34
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    International journal of clinical oncology 5 (2000), S. 121-125 
    ISSN: 1437-7772
    Keywords: Key words Splenic metastasis ; Colorectal cancer ; Splenectomy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The value of splenectomy for secondary splenic tumors remains unclear. The aim of this study was to disclose the clinical significance of splenectomy for colorectal cancer metastases to the spleen by reviewing our two patients and the 24 other patients reported thus far. Methods. We report two patients with splenic metastasis from colonic cancer. A review of 26 cases, including ours, was conducted. Results. One of our patients had isolated splenic metastasis and is alive with no evidence of disease 14 months after splenectomy, while the other had non-isolated splenic metastasis and died of disseminated disease 17 months after splenectomy. In the 26 patients overall, the outcome of those with isolated splenic metastasis (n = 20) was significantly better than that for those with non-isolated splenic metastasis (n = 6; P = 0.05). There were three long-term (more than 3 years) survivors; all three were patients with isolated splenic metastasis, with the longest survival being 110 months. Patients with mucinous carcinoma showed a better survival rate than patients with other histological types (P = 0.08). In patients with isolated metastasis, metastases after splenectomy occurred in the peritoneum (n = 3), liver (n = 1), and lung (n = 1) within 2 years. Conclusions. Splenectomy may provide long-term survival for patients with isolated colorectal cancer metastasis to the spleen. The mucinous variant may be a favorable prognostic factor after splenectomy. Recurrence after splenectomy is likely to occur within 2 years, mainly in the peritoneum.
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  • 35
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    Pediatric surgery international 16 (2000), S. 285-292 
    ISSN: 1437-9813
    Keywords: Key words Major histocompatibility complex (MHC) ; Rat ; Immunohistochemistry ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
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  • 36
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Proliferation ; Adrenal glands ; Addisonian crisis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated the histologic maturation, proliferative capacity, and steroid production of fetal adrenal transplants (Tx) in adrenalectomized rats. A pair of fetal adrenal glands (18–20 days of gestation) was transplanted into the omentum of syngeneic Lewis rats (n=45). Four weeks later, in 5 animals the grafts were excised for morphologic evaluation. Proliferation was investigated by immunohistochemical staining for KI-67 protein and quantified by the proliferation index (PI = positive cells/100 counts). All other hosts (Tx; n = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis. Postoperatively, survival and concentrations of potassium, sodium, aldosterone, and corticosterone were recorded for 6 months. These data were compared to controls (C = only AE; n = 30) and a sham group (S; n = 10). At the end of the study period all surviving hosts were killed for histologic examination of grafts. At 4 weeks post-Tx the adrenal grafts demonstrated a distinct zona glomerulosa and frequent proliferation with a PI of 0.084, comparable to normal control (0.092). Following AE survival was significantly prolonged in Tx (86% vs 12% of C, P 〈 0.05). Control animals developed severe hyponatremia and hyperkalemia, whereas in Tx only transient signs of Addisonian crisis were recorded. Levels of aldosterone dropped within 7 days in the Tx and C groups, but returned to normal for Tx within 8 weeks. Corticosterone levels of Tx animals fell to 25% within week, but steadily increased to 70% by the end of the study. At 6 months, grafts revealed a mature adrenocortical structure with little proliferative activity, which was comparable to controls. In a syngeneic rat model fetal adrenal transplants thus mature and proliferate to provide sufficient steroid production for adrenalectomized hosts.
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  • 37
    ISSN: 1437-9813
    Keywords: Key words Biliary atresia ; Bile lake ; α-glutathione-s-transferase (GST) ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. α-Glutathione-s-transferase (α-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum α-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 ± 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum α-GST was determined using a specific ELISA. Tissue α-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum α-GST was significantly higher in group II (20.7 ± 8.4 ng/ml) than in groups I (4.7 ± 1.3 ng/ml) and III (8.0 ± 1.2 ng/ml) (P 〈 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens α-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III α-GST was only found in regenerative nodules. We conclude that α-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of α-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.
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  • 38
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    Pediatric surgery international 16 (2000), S. 351-355 
    ISSN: 1437-9813
    Keywords: Key words Extrahepatic biliary atresia ; Hepatoportoenterostomy ; Prognosis ; Long-term results
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical and histologic findings from 206 patients operated upon for extrahepatic biliary atresia (EHBA) are analyzed in order to define the prognosis of patients with EHBA. The prospective study took into consideration both initial fibrosis of the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier survival estimates and statistical calculations demonstrated a relationship between long-term survival and histologic findings in the liver and porta hepatis. The efficacy of HPE is significantly influenced by the morphology of the PH and to a lesser extent by the initial liver fibrosis. Surgery should thus achieve pattern 1 morphology of the PH, but this is problematic because of the close relationship of the vascular and biliary structures in its two lateral zones.
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  • 39
    ISSN: 1437-9813
    Keywords: Key words Congenital diaphragmatic hernia ; Hypoplastic lung ; Bromodeoxyuridine (BrdU) ; Antenatal glucocorticoids ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 ± 3.01) compared to groups I (9.16 ± 2.20) and III (6.83 ± 1.70) (P 〈 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.
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  • 40
    ISSN: 1437-7772
    Keywords: Key words c-erb B-2 ; Prognosis ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The prognostic significance of c-erb B-2 in breast cancer remains controversial. The aim of this study was to determine the practical prognostic significance of c-erb B-2 protein status in breast cancer extracts, using an enzyme immunoassay. Methods. An enzyme immunoassay was used to measure levels of c-erb B-2 protein prospectively in 360 patients with breast cancer, using cytosol fractions prepared for steroid receptor assay. The status of c-erb B-2 protein was assessed using a cut-off value for positivity of 18 ng/mg protein. Univariate and multivariate analyses were performed. To evaluate the prognostic significance of c-erb B-2 protein status. Results. Levels of c-erb B-2 protein in tumor tissue extract ranged from 0 to 213.0 ng/mg protein (mean, 15.5 ng/mg protein). In 52 tumors (14.4 %) more than 18.0 ng/mg protein was detected, and these tumors were regarded as c-erb B-2 protein-positive. Correlations were found between c-erb B-2 protein positivity and large tumor size (〉3 cm; P = 0.0095), higher histological grade (P 〈 0.0001), estrogen receptor negativity (P 〈 0.0001), and progesterone receptor negativity (P 〈 0.0001). There was also a marginally significant correlation between c-erb B-2 protein positivity and lymph node positivity. Multivariate analysis showed that c-erb B-2 protein status was a significant independent prognostic factor for disease-free survival, being strongly significant in patients with positive lymph nodes. Conclusion. c-erb B-2-positive breast cancers are biologically more aggressive and c-erb B-2 protein status could be a candidate as a prognostic factor for patients with breast cancer, being particularly valuable in patients with positive lymph nodes.
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  • 41
    ISSN: 1437-7772
    Keywords: Key words Breast cancer ; Breast-conserving therapy ; Local recurrence ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery.
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  • 42
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    International journal of clinical oncology 5 (2000), S. 36-40 
    ISSN: 1437-7772
    Keywords: Key words Renal cell carcinoma ; Contralateral adrenal metastasis ; Clinicopathological characteristics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Metachronous solitary metastasis of renal cell carcinoma (RCC) to the contralateral adrenal gland is very rare. We assessed the clinocopathological findings of such patients who received adrenalectomy. Methods. We retrospectively reviewed the records of all 495 patients who underwent nephrectomy for RCC; excluding those in stage IV, between 1980 and 1993. Of these patients, 5 who showed metachronous solitary metastasis to the contralateral adrenal gland, and also received adrenalectomy were the subjects of this study. Results. The adrenal metastasis was found between 14 and 132 months (median, 81 months) after nephrectomy. After the solitary adrenalectomy, patient survival ranged from 450 to 2160 days (median, 660 days); 2 patients were alive with no evidence of disease at 660 and 1830 days, respectively, and 3 patients died of this disease, at 450, 480, and 2160 days, respectively, after adrenalectomy. The overall survival rate was 100% at 5 years, 80% at 6 years, 60% at 7 years, and 40% thereafter. The 2 patients with no evidence of disease did not receive steroid supplementation, because they had not received ipsilateral adrenalectomy. No significant difference was observed between survivors and non-survivors in terms of clinicopathological factors such as affected side, location of the tumor, tumor size of primary/metastatic lesion, and stage or grade of primary/metastatic lesion. From the viewpoint of outcome, patients with early recurrence tended to show an unfavorable prognosis compared with prognosis in those with late recurrence. Conclusion. The prediction of outcome in patients with RCC who undergo, adrenalectomy for metachronous solitary metastasis to the contralateral adrenal gland is difficult. Although the factors that affect prognosis are uncertain, long-term observation for unusual metachronous metastasis to the contralateral adrenal gland is mandatory in patients with RCC.
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  • 43
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    International journal of clinical oncology 5 (2000), S. 164-170 
    ISSN: 1437-7772
    Keywords: Key words P-glycoprotein ; Osteosarcoma ; Soft-tissue sarcoma ; Prognosis ; Immunohistochemistry ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The purpose of this study was to investigate the correlation between P-glycoprotein status and outcome in adult patients with high-grade osteosarcomas and soft-tissue sarcomas. Methods. P-glycoprotein status was determined im-munohistochemically in specimens from 28 patients with osteosarcoma and 34 patients with soft-tissue sarcoma. The polyclonal antibody mdr(Ab-1) was used for either decalcified or undecalcified tissue samples which were formalin-fixed and paraffin-embedded. The expression of P-glycoprotein mRNA was also determined by the polymerase chain reaction in 23 fresh sarcoma specimens. P-glycoprotein status was analyzed in relation to the duration of event-free survival. Results. Positivity for P-glycoprotein was found in 29% of the osteosarcomas and 34% of the soft-tissue sarcomas. Consistent results were obtained at both the immunohistochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) levels in 19 of 23 sarcomas (83%). In patients with osteosarcoma, the presence of increased levels of P-glycoprotein was significantly associated with a decreased probability of event-free survival after diagnosis (P = 0.022). In contrast, in patients with soft-tissue sarcoma there was no correlation between the level of P-glycoprotein and prognosis. Conclusions. In patients with high-grade osteosarcomas, the presence of increased levels of P-glycoprotein detected by polyclonal antibody mdr(Ab-1) was associated with a significantly increased risk of adverse events. This association was not found in patients with soft-tissue sarcomas.
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  • 44
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Split tolerance ; FK 506 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0–5 in the rejection model and from days 0–9 in the long-term functional model. Mean survival time in the rejection model was 98 ± 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term ( 〉 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely ( 〉 70 days). In vitro, mixed leukocyte reactivity of CD4 + T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.
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  • 45
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
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  • 46
    ISSN: 1432-2277
    Keywords: Key words Hypoxia-reoxygenation ; JNK1/SAPK1 ; Rat ; Hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 μM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.
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  • 47
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    Urological research 28 (2000), S. 141-146 
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Nitric oxide ; Ischemia-reperfusion injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we attempted to clarify the release of nitric oxide (NO) and its role in the ischemia-reperfusion rat kidney. After right nephrectomy, male Wistar rats were divided into four groups: one sham operated and three groups who underwent ischemia (30 min) and reperfusion of the left renal artery. Thirty minutes prior to ischemia-reperfusion, two groups were injected intraperitoneally with 10 and 30 mg/kg of NG-nitro-l-arginine methylester (L-NAME). Real-time monitoring of blood flow and NO release in the rat kidney was measured with a laser Doppler flowmeter and an NO-selective electrode, respectively. Serum creatinine and blood urea nitrogen (BUN) levels were measured 1 and 7 days after the induction of ischemia-reperfusion. Clamping of the renal artery decreased blood flow to 1–5% of the basal level measured before clamping. After removal of the clip, the blood flow of the 30 mg/kg L-NAME rats was significantly lower than that of the controls. Immediately following the clipping of the renal artery, NO release rapidly increased. After removing the clip, NO release immediately returned to three-quarters of the basal level. Serum creatinine and BUN levels of the ischemia-reperfusion rats were slightly but not significantly higher and those of 30 mg L-NAME rats were significantly higher than those of the control or ischemia-reperfusion rats 1 day and 7 days after ischemia-reperfusion. Our data suggest that NO acts as a cytoprotective agent in ischemia-reperfusion injury of the rat kidney.
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  • 48
    ISSN: 1434-0879
    Keywords: Key words Castration ; Epidermal growth factor ; Insulin-like growth factor I ; Prostate ; Testosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated Wistar rats were treated with growth factors (EGF 35 μg/rat per day; IGF-I 350 μg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme-linked immunosorbent assay (ELISA). Treatment with EGF inhibited the involution of the prostate (P 〈 0.05), whereas treatment with IGF-I did not affect the prostate involution as compared to castrated controls. EGF treatment significantly increased the endogenous rat EGF in the ventral prostate, but cellular proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration. Compared with testosterone, the effects of EGF treatment on the prostate involution were moderate, and the effects of EGF were not related to cellular proliferation.
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  • 49
    ISSN: 1434-0879
    Keywords: Key words Bladder ; Rat ; Aging ; Obstruction ; Cystometrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies.
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  • 50
    ISSN: 1434-0879
    Keywords: Key words Superficial bladder cancer ; p21WAF1/CIP1 ; Prognosis ; Cyclin D1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (≥5% of cells positive) and cyclin D1 positive (≥10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P 〈 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P=0.001), WHO grade (P=0.006), MIB-1 score (P=0.014), p53 expression (P=0.001), and bcl-2 (P=0.011) immunoreactivity. In univariate analysis, T category (P=0.0001), WHO grade (P 〈 0.0001), MIB-1 score (P 〈 0.0001), bcl-2 (P=0.0092), p53 (P=0.0016) and p21WAF1/CIP1 (P=0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P=0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P=0.03), whereas tumor grade (P=0.002) and cyclin D1 expression (P=0.04) were independent predictors of tumor recurrence. Only the WHO grade (P=0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.
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  • 51
    ISSN: 1432-0568
    Keywords: Key words Nerve repair ; Nerve fiber regeneration ; Sciatic nerve ; Muscle-vein-combined graft ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.
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  • 52
    ISSN: 1432-0568
    Keywords: Key words GABAB receptor ; CNS ; Dorsal root ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The anatomical distribution of the GABAB receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells.
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  • 53
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    Anatomy and embryology 202 (2000), S. 247-255 
    ISSN: 1432-0568
    Keywords: Key words Enteric neurons ; Interstitial cells of Cajal ; Smooth muscle cells ; Guinea-pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tachykinin receptors NK1r, NK2r and NK3r bind tachykinins with different affinities and share pharmacological and molecular differences among animal species. NK1r, NK2r, NK3r and tachykinin (SP/NKA) distribution was studied by immunohistochemistry in the ileum of mouse since no data are available for this species. The results were then compared to those obtained in the rat and guinea pig either by us or by others to ascertain interspecies similarities and/or differences. NK1r- and NK3r-immunoreactivity (IR) were detected in neurons and NK1r-IR in the interstitial cells of Cajal at the deep muscular plexus. At variance with rat and guinea pig, NK1r-IR was also found in the myoid cells of the villi, while NK2r-IR was never detected in nerve varicosities. This latter datum suggests that the NK2r does not play a presynaptic role in the mouse. Unexpectedly, a high NK2r-IR and the presence of NK3r-IR were observed at the inner portion of the circular muscle layer in the mouse as well as in the rat and guinea pig, demonstrating a subregional distribution of these receptors. Tachykinin distribution did not show noticeable species-related differences. The present findings show species-related differences in the tachykinin receptor distribution that might be related to a different tachykinin controlof intestinal motility.
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  • 54
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    Annals of hematology 79 (2000), S. 455-458 
    ISSN: 1432-0584
    Keywords: Key words Anterior chamber ; Hypopyon ; Leukemia ; Extramedullary ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We encountered a patient with acute myelogenous leukemia (AML) who developed leukemic hypopyon. Leukemia initially spread into the pharynx, gingiva, lymphnode, and bone marrow. He achieved complete remission after chemotherapy but developed blurred vision and hypopyon. Anterior chamber paracentesis disclosed leukemic infiltration of the anterior chamber. Infiltration of the central nervous system also occurred. He received systemic chemotherapy, intrathecal chemotherapy, and local chemotherapy. However, he did not achieve prolonged remission. These findings suggest that these chemotherapy treatments have an inadequate effect for AML with anterior chamber infiltration. This rare complication is associated with extramedullary infiltration of leukemia.
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  • 55
    ISSN: 1279-8509
    Keywords: Acute myeloid leukemia ; Chemotherapy ; Allogenic transplantation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to assess the place of HLA-identical allogeneic bone marrow transplantation (BMT) and to compare it to other post-induction therapies, we analyzed patient outcome in intention-to-treat based on the presence or not of an HLA-identical familial donor in young adults with de novo acute myeloid leukemia (AML) in first complete remission (CR). Between 1985 and 1998, 152 consecutive AML patients aged less than 41 years old, seen in our institution, were treated according to 3 different successive protocols (LYLAM85, LAM90, AML10). 144/152 patients entered our prospective study in which they were registered at time of diagnosis for presence or absence of HLA-identical donor and analyzed in intention-to-treat. In this study, 52 patients (36%), who had at least one identical sibling donor (group 1), were offered allogeneic BMT after CR achievement. The 92 patients without donor were allocated to group 2 and were assigned to receive chemotherapy or autologous transplantation as post-remission according to the protocol they were initially included in. Patients from both groups had similar disease characteristics at diagnosis. Karyotypes at diagnosis were defined as low risk (t(8;21) or t(15;17) or chromosome 16 abnormalities(, intermediate risk (normal karyotypes), or high risk (other abnormalities). Overall, 114/152 patients (75%) achieved a CR. Of the 144 eligible patients, 46/52 (88%) with a donor and 68/92 (74%) without a donor achieved a CR. The median follow-up duration of the 144 patients was 21.2 months. The relapse rate was higher in group 2 (56%) than in group 1 (31%). However, the overall survival was not different between patients with and without donor (median survival respectively at 16.7 months and 26.6 months with estimated survival at 5 years respectively at 32% and 34%). Thirty-four patients from group 1 (65%) were actually transplanted in first CR. The probability of 5-year survival for patients receiving effectively allogeneic BMT was 44% and was not significantly better than that of patients who did not. In univariate as in multivariate analysis, karyotypic status was the main prognostic factor for CR achievement (p = 0.002), CR duration (p 〈 0.0001), and overall survival (p 〈 0.0001). There were no significant differences between group 1 and group 2 when survivals were compared with adjustment for karyotypes. We conclude that the availability of an HLA-identical sibling donor did not confer any prognostic advantage in terms of outcome for young adults with AML in first CR. These results make allogeneic BMT process questionable as systemic post-remission therapy in patients with an HLA-identical familial donor.
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  • 56
    ISSN: 1248-9204
    Keywords: Hernia ; Strangulation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is believed that direct hernias are less likely to strangulate because, in contrast to an indirect inguinal hernia, the neck of the direct hernia is wide. For this reason, some surgeons do not repair direct hernias in I elderly patients. We analyzed all incarcerated hernias repaired on an emergency basis during a 3-year period in order to discover the extent of incarcerated direct hernias in our practice. A total of 293 patients with incarcerated hernia were evaluated; of these, 222 were inguinal (193 indirect −86.9%- and 29 direct −13.1%-). The strangulation rate for inguinal hernias was found to be 29.7%. There was a significant difference between indirect and direct inguinal hernias in respect to strangulation rate (32.6% vs 10.3% p = 0.014). However, we did not find any difference between bowel resection rates in incarcerated-strangulated indirect and direct hernias (14/193 −7.3%- vs 2/29 −6.9%-, p = 0.95). Hospitalization time was significantly longer for the patients who developed strangulation than those who did not. The side of direct hernia had no effect on strangulation (10.5% for right-sided vs 10.0% for left-sided, p = 0.97). The only prognostic factor for strangulation and resection in regression analysis was the age-group of the patients (〈 60 vs. 60 or older). At operation the average diameter of the defect in the transversalis fascia was 23.8 mm. The diameter of the defect had no effect on strangulation.
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  • 57
    ISSN: 1279-8517
    Keywords: Gastric carcinomas ; Cardiac carcinomas ; TNM-classification ; Prognosis ; Lesser and greater omenta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in « understaging » and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.
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  • 58
    ISSN: 1432-0533
    Keywords: Key words Hypothermia ; Immunohistochemistry ; Microtubule-associated protein 2 (MAP2) ; Rat ; Spinal cord injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
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  • 59
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    Acta neuropathologica 100 (2000), S. 75-81 
    ISSN: 1432-0533
    Keywords: Key words Fas ; Fas ligand ; Rat ; Spinal cord ; Trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This immunohistochemical study evaluated Fas and Fas ligand (FasL) in the rat nervous system and their changes in the spinal cord subjected to compression. Normal spinal cord showed a low level of Fas and FasL immunoreactivity in the white matter except in the corticospinal tracts. Fas and FasL immunoreactivity seemed to be located in axons and their myelin sheaths. Other regions of the nervous system did not show immunoreactivity to Fas and FasL. Moderate and severe compression injury of the spinal cord resulted in a reduction of Fas and FasL immunoreactivity in the white matter of injured T8–9 segments at 4 h and a complete loss at 1 day after trauma. This was seen even in the remaining white matter. In contrast, increased immunoreactivity to Fas and FasL was present in the cranial T7, caudal T10 (moderate injury) and T12 (severe injury) segments at day 4 with most intense staining were seen at day 9 after trauma. Increased Fas and FasL immunoreactivity may have pathophysiological implications for the development of secondary injuries after trauma to the spinal cord. Fas-FasL interactions may for instance be involved in apoptosis of oligodendrocytes which occurs as a delayed phenomenon after trauma to the spinal cord. The integrity of myelin sheaths may in this way be jeopardized by apoptosis of oligodendrocytes.
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  • 60
    ISSN: 1432-0843
    Keywords: Key words 7-Hydroxymethotrexate ; Methotrexate ; Maximum tolerated dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD50 for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX.
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  • 61
    ISSN: 1432-0851
    Keywords: Key wordsαvβ3 ; Integrins ; Melanoma ; Blood vessels ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The αvβ3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of αvβ3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information is available about the clinical significance of αvβ3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that αvβ3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared αvβ3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we have examined the lesions for expression of the αv subunit to gain information on the regulation of αvβ3 expression on endothelial cells and on cells of the melanocyte lineage. αvβ3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions. However, αvβ3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The αv subunit and the αvβ3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways control their expression. This finding may account for the differential clinical significance of αvβ3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, αvβ3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of all metastatic lesions tested and its restricted distribution in normal tissues.
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  • 62
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
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  • 63
    ISSN: 1432-1238
    Keywords: Key words Mortality ; Oliguria ; Multiple organ failure ; Severity-of-illness ; Prognosis ; Scoring systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Design: Prospective, multicenter, observational cohort analysis. Setting: Forty ICUs in 16 countries. Patients: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Measurements and results: Of the patients, 348 (24.7 %) developed ARF, as diagnosed by a serum creatinine of 300 μmol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p 〈 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8 % vs 14.0 %, p 〈 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95 %: 1.23–2.06], p 〈 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. Conclusion: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.
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  • 64
    ISSN: 1432-1238
    Keywords: Key words Acute renal failure ; 80 years old ; Etiology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old.¶Design: Historical cohort analysis.¶Setting: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris.¶Patients and participants: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 μmol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50 % over the basal creatininemia.¶Measurements and results: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29 % of the patients received dialysis. Global mortality at the hospital was 40 %. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months.¶Conclusion: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.
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  • 65
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    Intensive care medicine 26 (2000), S. S064 
    ISSN: 1432-1238
    Keywords: Key words Bacteraemia ; Sepsis ; Septic shock ; Epidemiology ; Prognosis ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and 〉 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in 〉 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in 〉 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.
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  • 66
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    Journal of cancer research and clinical oncology 126 (2000), S. 280-284 
    ISSN: 1432-1335
    Keywords: Key words Thymoma ; Prognostic factors ; Prognosis ; DNA cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. Patients and methods: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6–164) months. Results: Masaoka's stage was predictive of aneuploidy (P 〈 0.01) and disease-free survival (P 〈 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P 〈 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. Conclusion: DNA image cytometry may provide additional information about the prognosis of resected thymoma.
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  • 67
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    Experimental brain research 130 (2000), S. 100-104 
    ISSN: 1432-1106
    Keywords: Key words NF-κB ; p65 ; Hippocampal neurons ; Glia ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  NF-κB is found in many neuronal cell types in different states of activity. This study aimed to define which conditions induce constitutive NF-κB activity in cultured hippocampal neurons using activity-specific antibody staining. In co-culture with astroglia, hippocampal neurons were devoid of activated NF-κB. In these co-cultures, NF-κB could not be activated via kainate or glutamate. In contrast, separating neurons from the glial compartment resulted in a time-dependent increase of activated neuronal NF-κB. In this line, activation of NF-κB by kainate or glutamate is very effective in freshly separated cultures, but inhibited when the cultures are reassembled after stimulation. These findings suggests that a neuronal-glial interaction may regulate gene expression via NF-κB.
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  • 68
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
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  • 69
    ISSN: 1432-1238
    Keywords: Key words Cardiopulmonary bypass ; Coronary artery bypass graft ; Valve surgery ; Thoracic aortic surgery ; Prognosis ; Hypotension ; Systemic inflammatory response syndrome (SIRS) ; Procalcitonin ; Endotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate procalcitonin (PCT) levels in patients undergoing cardiopulmonary bypass (CPB) in order to assess the prevalence and prognostic capacity of elevated PCT levels following CPB in open heart surgery.¶Design: prospective observational study in consecutive patients.¶Setting: Twenty-four-bed ICU, department of thoracic and cardiovascular surgery, university hospital.¶Patients: Seven hundred and twenty two patients, 691 of whom underwent CPB, i. e., 476 had coronary bypass surgery (CABG), 130 valve replacement, 34 combined CABG and valve replacement, and 23 thoracic aortic surgery.¶Interventions: Standard perfusion techniques were used with cardioplegic arrest and mild hypothermia (28–32 °C). With the exception of thoracic aortic procedures, full–flow perfusion was performed.¶Measurements and results: PCT was measured prior to surgery and daily thereafter until ICU discharge or death. PCT significantly increased at day 1 postoperatively compared to baseline values (0.25 ± 1.65 vs 6.49 ± 22.0 ng/ml, p 〈 0.005). However, in 55.1 % of patients PCT was below 1.0 ng/ml. In 12.8 % of CABG patients PCT was increased to 〉 5.0 ng/ml, compared to 39 % in valve patients and 35 % of patients with aortic surgery. An elevated PCT level 〉 1.0–5.0 ng/ml at day 1 was highly predictive of mortality (P 〈 0.03, vs 〈 1.0 ng/ml), with an additional accuracy when levels 〉 5.0 ng/ml were measured (P 〈 0.002 vs 〈 1.0 ng/ml).¶Conclusions: These results provide evidence that PCT might serve as an early prognostic marker in patients undergoing CPB in open heart surgery. It may be worth considering immunomodulating approaches in patients presenting elevated PCT levels in the early phase after CPB.
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  • 70
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Gastrointestinaltrakt ; Karzinoid ; Neuroendokrine Tumoren ; DNA-Zytophotometrie ; Prognose ; Key words Gastrointestinal tract ; Carcinoid ; Neuroendocrine tumors ; DNA cytophotometry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A total of 123 manifestations (97 primary tumours and 26 metastases) of neuroendocrine tumours of the gastrointestinal tract observed in 95 patients was investigated for the prognostic value of clinical, histological and DNA cytophotometric parameters. Metastases almost exclusively occurred among ileal carcinoids, which also were responsible for all 14 cases of lethal outcome observed during the follow-up period of mean 42 months. Aneuploid DNA values could be determined significantly more frequently among ileal than in non-ileal carcinoids and showed – upon analysis of the total group of gastrointestinal neuroendocrine tumours – a significant correlation to lethal course of disease. In addition, among 18 cases with primary and secondary carcinoid manifestations available for DNA cytophotometry, an association between the DNA content of metastatic neuroendocrine tumours and prognosis came to light. When applicated to the group of ileal neoplasms, however, the parameter DNA content did not allow a better prognostic assessment.
    Notes: Zusammenfassung Untersucht wurden 123 Manifestationen (97 Primärtumoren und 26 Metastasen) von bei 95 Patienten beobachteten neuroendokrinen (NE-)Tumoren des Gastrointestinaltrakts auf die prognostische Bedeutung verschiedener klinischer, histologischer und DNA-zytophotometrischer Parameter. Metastasen traten fast ausschließlich bei ilealen Karzinoiden auf, denen auch sämtliche 14 während der durchschnittlichen Nachbeobachtungszeit von 42 Monaten aufgetretenen letalen Erkrankungsverläufe zuzuordnen waren. Aneuploide DNA-Verteilungsmuster wurden signifikant häufiger bei ilealen als bei nichtilealen Karzinoiden angetroffen und waren – bezogen auf die Gesamtgruppe – signifikant mit tödlichem Krankheitsausgang korreliert. Darüber hinaus zeigte sich bei 18 Fällen mit DNA-zytophotometrisch auswertbaren primären und sekundären Karzinoidmanifestationen eine Assoziation zwischen dem DNA-Histogrammtyp metastatischer Karzinoide und der Prognose. Innerhalb der Gruppe der Ileumtumoren erlaubte der Parameter DNA-Gehalt aber keine Verbesserung der Prognoseabschätzung.
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  • 71
    ISSN: 1432-198X
    Keywords: Key words Metabolic acidosis ; Growth ; Growth hormone ; Insulin-like growth factor-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean±SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26±2 vs. 49±6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41±3 vs. 104±10 ADU) transcripts and low serum GHBP (25±1 vs. 32±1 ng/ml) and IGF-I (279±50 vs. 366±6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.
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  • 72
    ISSN: 1432-198X
    Keywords: Key words Apoptosis ; Ceramide ; Development ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content.
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  • 73
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Apoptose ; Proliferation ; Hämatopoetischer Zellumsatz ; Topoisomerase II α ; PCNA ; Chronische myeloproliferative Erkrankungen ; Prognose ; Reaktive Läsionen ; Key words Apoptosis ; Proliferation ; Hematopoietic turnover index ; Topoisomerase II α ; PCNA ; Chronic myeloproliferative disorders ; Prognosis ; Reactive lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow. Therefore, dynamics of hematopoiesis is mainly defined by these two parameters. However, since only few data are available from previous studies, we performed a retrospective analysis to elucidate some aspects of this complex pathomechanism. A total of 400 patients with chronic myeloproliferative disorders (CMPDs) and corresponding reactive bone marrow lesions were enrolled into this study. Apoptosis was detected in bone marrow tissue by the ISEL-technique and topoisomerase II α expression was demonstrated by the monoclonal antibody Ki-S1. Furthermore, by determination of the proliferating-cell nuclear antigen labeling (PCNA) index, we were able to calculate the proportion of cells in the G2/M phase, because both nuclear antigens are expressed in different phases of the cell cycle. Patients with IMF, PV, and ET revealed a normal range of apoptosis, whereas in chronic myeloid leukemia (CML) a significant increase could be observed. On the other hand, IMF and PV were characterized by a raised proliferative activity. Dynamics of hematopoiesis was assessed by calculation of the so called hematopoietic turnover index. In CML and reactive lesions no alterations of this parameter were detectable, but IMF and PV showed a significant increase. Survival analysis disclosed a relevant worsening of life expectancy for patients with reduced apoptosis and proliferation. In conclusion, our in-situ results confirm and extend previous experimental data on hematopoietic cell kinetics. In this context, a greater regenerative capacity of hematopoiesis may be reflected by an increased rate of apoptosis and/or proliferation and therefore is associated with a more favorable outcome.
    Notes: Zusammenfassung Apoptose und Proliferation stellen im Rahmen einer funktionsgerechten Regelung der Hämatopoese einen integralen Bestandteil für die Aufrechterhaltung des zellulären Gleichgewichts im Knochenmark dar. Insofern ist die Dynamik des hämatopoetischen Zellumsatzes durch diese beiden Parameter gekennzeichnet. Da weiterführende Untersuchungen in dieser Hinsicht lediglich vereinzelt am Knochenmark durchgeführt worden sind, haben wir im Rahmen einer retrospektiven Analyse versucht, einige Aspekte dieses komplexen Mechanismus zu beleuchten. Insgesamt wurden 400 Patienten mit chronischen myeloproliferativen Erkrankungen (CMPE) sowie korrespondierenden reaktiven Veränderungen in die Untersuchung aufgenommen. Neben dem direkten Nachweis der Apoptose im Knochenmark durch die ISEL-Technik haben wir die Topoisomerase II α Expression mittels des monoklonalen Antikörpers Ki-S1 gemessen. Zusätzlich konnten wir durch die Bestimmung der PCNA-Markierung aufgrund der Zellzyklus-spezifischen Färbereaktion beider nukleärer Antigene den Anteil der in G2-/M-Phase befindlichen Zellen ermitteln. Während die IMF, die PV sowie die ET eine im Normbereich liegende Apoptoserate erkennen ließen, war dieser Wert bei der CML signifikant erhöht. Auf der anderen Seite wiesen IMF und PV eine deutlich gesteigerte proliferative Aktivität im Knochenmark auf. Bei der Berechnung eines hämatopoetischen Zellumsatz Index (HZI) zeigten diese beiden CMPE-Subtypen einen signifikanten Anstieg, wohingegen bei der CML sowie den reaktiven Läsionen keine relevante Verschiebung dieses Parameters festzustellen war. Im Rahmen prognostischer Analysen hatten IMF und PV Patienten mit reduzierter Proliferation und Apoptoserate jeweils eine signifikant kürzere Überlebenszeit. Unsere in-situ Ergebnisse erweitern und bestätigen vorausgegangene experimentelle Studien zur hämatopoetischen Zellkinetik. Darüber hinaus lassen sich aus unseren Daten prognostische Überlegungen ableiten, da insbesondere bei der PV und IMF Apoptose und Proliferation signifikanten Einfluß auf das Überleben der Patienten hatten. In diesem Zusammenhang spiegelt eine vermehrte Apoptose- und Proliferationsrate im Knochenmark offenbar eine größere regenerative Kapazität der Hämatopoese wieder und könnte daher für einen günstigeren Verlauf verantwortlich gemacht werden.
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  • 74
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    Der Pathologe 21 (2000), S. 456-459 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Undifferenziertes kleinzelliges Hepatoblastom ; Immunhistochemie ; Keywords Undifferentiated small-cell hepatoblastoma ; Immunohistochemistry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Undifferentiated small-cell hepatoblastoma (HB) is a rare malignant tumor of childhood. The cell of origin is supposed to be a pluripotential, probably entodermal, stem-cell. Differential diagnosis of this type of HB is difficult among the group of small round and blue cell malignant tumors of children. The immunohistochemically determined coexpression of cytokeratin 8, 18, and 19 and of vimentin and actin, regularly in the absence of α-fetoprotein expression may be diagnostically helpful. We present the case of an undifferentiated small-cell HB of a 15-month-old girl with agenesis of the right kidney. As morphological peculiarity the tumor presented disseminated histiocytic giant cells.
    Notes: Zusammenfassung Undifferenzierte kleinzellige Hepatoblastome (HB) zählen zu den seltenen malignen Tumoren der Leber im Kindesalter. Da der Tumor in der Regel kein α-Fetoprotein exprimiert, ist der Nachweis von Zytokeratin 8, 18 und 19 sowie Vimentin und Aktin diagnostisch wegweisend. Als Ausgangszelle wird eine pluripotente, wohl entodermale Stammzelle vermutet. In der Gruppe der klein-, rund- und blauzelligen malignen Tumoren des Kindesalters bietet diese Variante des HB differenzialdiagnostische Schwierigkeiten. Wir berichten über ein undifferenziertes kleinzelliges HB eines 15 Monate alten weiblichen Kleinkindes mit Agenesie der rechten Niere. Als morphologische Besonderheit des Tumors werden disseminierte histiozytäre Riesenzellen beschrieben.
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  • 75
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
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  • 76
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    Psychopharmacology 148 (2000), S. 106-110 
    ISSN: 1432-2072
    Keywords: Key words Interferon ; Depression ; Forced swimming test ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. Methods: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. Results: Single intravenous (IV) administration of human IFN-α (6×104 IU/kg), but not of human IFN-β or -γ, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-α (6×103 IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-α, -β and -γ, 6×104 IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. Conclusions: These findings suggest that human IFN-α has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-β and -γ, and that the effect of human IFN-α might not be mediated through IFN-α/β receptors.
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  • 77
    ISSN: 1432-2072
    Keywords: Key words Opiate receptor ; Antinociception ; Habituation ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia. Methods: In experiments 1–3, different groups of male, Wistar rats (275–300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the µ-selective antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), the δ-receptor selective antagonist naltrindole, or the κ-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5°C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the µ and δ, but not the κ, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
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  • 78
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
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  • 79
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    Psychopharmacology 149 (2000), S. 115-120 
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
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  • 80
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    Psychopharmacology 149 (2000), S. 181-188 
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition. Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition. Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition. Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.
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  • 81
    ISSN: 1432-2072
    Keywords: Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
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  • 82
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
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  • 83
    ISSN: 1432-1084
    Keywords: Key words: MR imaging ; Non-small cell lung cancer ; Therapeutic effect ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The aim of this study was to evaluate the therapeutic effect more accurately and predict the prognosis of treated non-small cell lung cancer by using contrast-enhanced magnetic resonance imaging (CE-MRI). Contrast-enhanced computed tomography (CE-CT) and CE-MRI were examined 90 non-small cell lung cancer patients treated with conservative therapies. Enhancement patterns of CE-MRI were classified into three types: peripheral; mottled; and homogeneous. Reduction ratio of tumor size (RRT) based on the World Health Organization response criteria and a new response rate; reduction ratio of viable tumor size (RRVT) which evaluates not only the reduction of tumor size but also changes in necrosis and/or cavity size, were evaluated. Changes of enhancement pattern were compared and correlated with pathological diagnosis. The RRTs, RRVTs, and interobserver agreements evaluated by all modalities were compared. The RRTs and RRVTs in each subgroup were correlated and compared with prognoses. Change of enhancement pattern depended on therapy had no tendency (p = 0.06). Enhancement pattern had significant correlation with pathological diagnosis (p 〈 0.0001). Partial response (PR) case of RRVT had significant difference between imaging techniques (p = 0.04). The RRVT of other cases and RRT had no significant difference. Interobserver agreements of RRT and RRVT were almost perfect (ϰ≥ 0.93). Prognosis had better correlation with RRVT than with RRT. Differences of relapse-free survival and survival between patients considered as having no change (NC) by RRT and PR by RRVT (NC-PR) and patients considered as having NC by RRT and RRVT were significant (p = 0.03, p = 0.01). There were no significant differences of relapse-free survival and survival between NC-PR patients and patients considered as having PR by RRT and RRVT. The CE-MRI technique could accurately evaluate the therapeutic effect and predict the prognosis of treated non-small cell lung cancer.
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  • 84
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    European journal of orthopaedic surgery & traumatology 10 (2000), S. 199-202 
    ISSN: 1432-1068
    Keywords: Abscess ; Prognosis ; Spinal epidural abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five patients suffering from spinal epidural abscess associated with neurologic deficit are reported. Four patients underwent a decompressive procedure for abscess drainage, and one patient was medically treated. One of the patients showed a neurologic deterioration at the early postoperative period. The long-term follow-up showed a good outcome in all patients. It is concluded that epidural abscess associated with progressive neurologic deficit requires immediate decompression and administration of antibiotic. Postoperative neurological deterioration may be seen despite proper and immediate decompression and in such a case neurologic improvement is observed in the late postoperative period.
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  • 85
    ISSN: 1432-0851
    Keywords: Key words IL-2 serum levels ; NSCLC ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P 〈 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P 〈 0.0001), although they were still significantly higher than controls (P 〈 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P 〈 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P 〈 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
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  • 86
    ISSN: 1432-0738
    Keywords: Key words Flutamide ; Androgen antagonist ; Rat ; Enhanced OECD Test Guideline 407 ; Endocrine disrupters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In association with the international validation project to establish a test protocol for the `Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, serum biochemistry and sperm analysis. Thus, among the parameters tested in the present experimental system, the weight of endocrine-linked organs and their histopathological assessment, serum hormone levels, and estrous cycle stage allowed the detection of endocrine-related effects of flutamide.
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  • 87
    ISSN: 1432-0738
    Keywords: Key wordsα2u-Globulin ; Diethylstilbestrol ; Endocrine disrupter ; Rat ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α2u-Globulin (AUG) is a major rat urinary protein, which has a molecular weight of 16 kDa (kidney type) or 19 kDa (native type). The biosynthesis of this protein is under multi-hormonal regulation. In this study, we investigated changes in serum AUG level and their association with changes in the reproductive organs of male rats after the administration of the estrogenic chemical, diethylstilbestrol (DES) at doses ranging from 0.01 mg/kg per day to 100 mg/kg per day by gavage for 14 days. Our aim was to establish basic data for the development of a new screening method for endocrine disrupting chemicals based on serum AUG levels. DES treatment decreased the weight of testes in a dose-dependent manner; and was accompanied by atrophic histopathological changes in testes. Testis weights were significantly decreased by the group given 1 mg/kg per day DES; however, histopathological abnormalities were found in the group given 0.1 mg/kg per day DES. In four of five animals in the group given 1 mg/kg per day there was no significant decrease in testis weight and only a slight or moderate degeneration of the pachytene spermatocytes. Despite these findings, serum AUG levels in this group decreased markedly, while the serum AUG level markedly decreased even in the animals with no histopathological change in the 1 mg/kg per day or 0.1 mg/kg per day groups with no histopathological change also showed decreased serum AUG level. These results suggest that the serum AUG level may be a sensitive parameter for detecting the activity of estrogenic chemicals in intact male rats. Although a uterotropic assay has been proposed for immature female or ovariectomized female rats and is currently undergoing validation studies internationally, there is no screening method for estrogenic chemicals in intact male animals. More data on AUG changes by treatment with other estrogenic chemicals are needed in order to determine the sensitivity and specificity of this response to estrogens. Nonetheless, an AUG-based screening test for estrogenic chemicals may be useful owing to its applicability to conventional toxicity studies and an apparently higher sensitivity of this parameter compared to organ weight change or histology of testis in intact male rats and applicability to conventional toxicity studies.
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  • 88
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    Journal of neurology 247 (2000), S. 943-948 
    ISSN: 1432-1459
    Keywords: Key words Transverse myelitis ; Motor evoked potentials ; Somatosensory evoked potentials ; Electromyography ; Prognosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with miscle power, tone, reflec and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP.
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  • 89
    ISSN: 1432-1459
    Keywords: Key words Sarcoidosis ; Spinal cord ; Magnetic resonance imaging ; Corticosteroid therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.
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  • 90
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    Archives of gynecology and obstetrics 264 (2000), S. 13-19 
    ISSN: 1432-0711
    Keywords: Key words Fallopian tube cancer ; Radiotherapy ; Chemotherapy ; Lymph node metastasis ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To contribute toward the understanding of the therapeutic management of fallopian tube cancer. Methods: Recent studies related to the treatment of fallopian tube cancer were reviewed. Results: Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. Conclusions: This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.
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  • 91
    ISSN: 1432-1335
    Keywords: Key words Blood group antigen ; ABH isoantigens ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.
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  • 92
    ISSN: 1433-0350
    Keywords: Keywords Intracranial cyst ; Prenatal ; Fetus ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This review evaluates the contribution of prenatal diagnosis to the understanding of intracranial cysts. We describe the outcome of 54 fetuses in which prenatal investigations indicated the presence of such lesions. The cysts were diagnosed between 20 and 30 weeks of gestation. Most (63%) were supratentorial and interhemispheric. There was only a single sylvian cyst. In the infratentorial compartment, median retrocerebellar cysts were predominant. Incisural cysts accounted for 14.8% of the series. Nine pregnancies were interrupted because of the presence of associated brain disorders. Forty-five children are alive. Thirty-four had neuropsychological tests. Cysts rarely progressed, most frequently stabilized and often regressed postnatally. Hydrocephalus was rare. In two cases delivery was precipitated at 36 weeks to allow urgent treatment of rapidly evolving cysts. Thirteen children (28.2%) were treated postnatally, in general for developing cysts. The median follow-up for the whole series exceeds 4 years. Behavior, neurological development, and intelligence are normal in 88% of the cases, and 91% have a normal neurological status. Prognosis at the time of the prenatal consultation was correct in 89% of the cases. We emphasize the value of prenatal magnetic resonance imaging and karyotype studies to limit risks of incorrect prognosis.
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  • 93
    ISSN: 1432-2307
    Keywords: Key words Endometrium ; Endometrial carcinoma ; Lectins ; Con A ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Lectins are proteins and glycoproteins of non-immune origin which bind specifically to carbohydrate residues, agglutinate cells and/or precipitate complex carbohydrates. Lectin-binding patterns in normal, hyperplastic and neoplastic endometria were studied using four biotinylated lectins (Con A, LCA, e-PHA, l-PHA) and the avidin-biotin-peroxidase technique. Canavalia ensiformis agglutinin (ConA) and Lens culinaris agglutinin (LCA) reacted strongly with the luminal borders and the cytoplasm of epithelial cells but, whilst in normal and benign endometrial tissues the cytoplasmic staining was confined to the apical and the basal aspect of the cells, in endometrial carcinomas and in some atypical hyperplasias lectin binding also occurred in the lateral cytoplasm (Con-A-lat), although in differing proportions of cells. Interestingly, extensive Con-A-lat in the tumour cells was much more frequent in non-endometrioid carcinomas (P〈0.05) and was significantly associated with poor histological differentiation (P〈0.0001), low oestrogen and progesterone receptor content (P〈0.01 and P=0.0001, respectively) and an unfavourable long-term survival (P〈0.05). With Phaseolus vulgaris erythroagglutinin (e-PHA) and leucoagglutinin (l-PHA) a linear, rather inconsistent, staining at the level of the basement membranes was observed in the glands: this, also noted with LCA, appeared intact in normal and hyperplastic glands without cytological atypia, and fragmented or absent in malignant glandular structures and in most hyperplastic glands showing cytological atypia. It is concluded that changes in the distribution of lectin-binding molecules in the endometrial cells are associated with the malignant state, whilst the extent of Con-A-lat reflects the biological behaviour of the tumours.
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  • 94
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    Virchows Archiv 436 (2000), S. 102-108 
    ISSN: 1432-2307
    Keywords: Key words Oral ; Squamous cell carcinoma ; Proliferation ; Apoptosis ; Tumour suppressor gene ; Oncogene ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P〈0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P〈0.001) and correlated negatively with apoptosis (P〈0.001). Proliferation (P〈0.006) and apoptosis (P〈0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.
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  • 95
    ISSN: 1432-2307
    Keywords: Key words T-type calcium channel blockade ; Mibefradil ; Myocardial infarction ; Cardiac remodeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dtmax were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dtmax were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.
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  • 96
    ISSN: 1432-2307
    Keywords: Key words CD44 ; Adhesion molecules ; Prognosis ; Soft tissue sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.
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  • 97
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    Child's nervous system 16 (2000), S. 21-24 
    ISSN: 1433-0350
    Keywords: Key words Children ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Prognosis ; Traumatic brain stem lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Glasgow Coma Scale (GCS) scores on admission may be predictors of outcome in patients with brain injuries. This study correlated the outcomes of children with traumatic brain stem lesions with their initial GCS scores and morphological patterns of injury as shown on computed tomography (CT) or magnetic resonance (MR) imaging. During the last 16 years, we have treated 1,108 children with brain injuries. The entire series included only 21 (1.9%) children who had clinical signs of brain stem lesions with morphological correlates on CT or MR imaging. Clinical findings were assessed according to the GCS and compared with scores on the Glasgow Outcome Scale (GOS). Of these 21 children, 16 (76%) had morphological lesions seen on CT scans. In 5 (24%) of the children only the MR images revealed brain stem lesions and their CT scans were negative. Generalized severe brain swelling was present in 6 cases (28%). There was a significant difference in GOS scores between patients with initial GCS scores of 3 and 4 and those with GCS scores between 5 and 7 (P〈0.02). Children with intracranial pressure higher than 40 mmHg had poorer outcomes than patients whose intracranial pressure was lower, but the differences were not significant. Outcome did not correlate significantly with morphological patterns of injury or the presence of extracranial injuries. The GCS is a reliable indicator of severity of injury and of outcome in children with brain stem injuries. MR imaging was more sensitive than CT in detecting brain stem lesions.
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  • 98
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    Child's nervous system 16 (2000), S. 760-764 
    ISSN: 1433-0350
    Keywords: Keywords Children ; Brain-injury ; Network ; Prognosis ; Visuo-spatial neglect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A care network has been created in the Paris area according to two criteria – the continuity and the specificity of the care, with a single place to manage pediatric neurosurgical emergencies. This network makes possible research about brain-injured children. Until recently, the ”Kennard principle”, that is, the assumption that recovery after similar lesions is greater in children than in adults has been supposed to be always true. In fact, if the lesions are diffuse, recovery is not greater in children compared with adults, or in younger children compared with older ones: the prognosis depends on the remaining ability to learn new practices. Normal IQ does not mean absence of sequelae. The cognitive deficits are very similar to those found in adults at the acute phase. For instance, visuo-spatial neglect appears as rather frequent when systematically looked for. The final assessment of outcome after childhood traumatic brain-injury should be done only after several years.
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  • 99
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
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  • 100
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    Child's nervous system 16 (2000), S. 451-456 
    ISSN: 1433-0350
    Keywords: Keywords Intracranial pressure ; CSF dynamics ; Infusion test ; Rat ; H-Tx rat ; Outflow resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or – as the pressure volume index (PVI) – not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm (”dynamic infusion test”), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the ”dynamic infusion test”, is representative only for the CSF compartment which is directly exposed to the bolus application.
    Type of Medium: Electronic Resource
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