[Low-dosage methotrexate in pre-Sézary syndrome].
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Biomedical subjects
Publications and source records attributed to J Böhm.
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INTRODUCTION: The prognostic significance of tumor DNA ploidy and cell cycle analysis for long-term survival has been examined in 19 patients with liposarcoma or malignant fibrous histiocytoma. In many cases, different tumor areas of primary tumors and local recurrences have been analyzed to reveal intratumoral heterogeneity. RESULTS: Among the primary tumors, there were eight aneuploid tumors, three of which showed diploid and aneuploid tumor regions. Correlations among DNA ploidy, grading, percentage of S-phase cells and infiltrative growth pattern of the tumors could be demonstrated. Poorly differentiated tumors (G3) showed aneuploidy in six of eight patients. Aneuploid tumors showed S-phase cells in 17.2% (range 3.2-38.1%), which was higher than the percentage of S-phase cells in diploid tumors (9.4%, range 2.1-27.4%). Aneuploid tumors showed a more infiltrative growth pattern (6 of 8 patients) than diploid tumors (6 of 11 patients). The median survival time of patients with diploid tumors was 86.5 months (8-144 months), compared with 40.9 months (11-54 months) for patients with aneuploid tumors. CONCLUSION: DNA ploidy and percentage of S-phase cells may be considered as prognostic factors.
Neuroendocrine tumours (NET) of the lung are divided in subtypes with different malignant potential. The first is the benign or low-grade malignant tumours, well-differentiated, called typical carcinoids (TC) and the second is the high-grade malignant tumours, poorly differentiated of small (SCLC) or large cell type (LCLC). Between these tumour types lies the well-differentiated carcinoma with a lower grade of malignancy (WDNEC). In clinical routine it is very important with regard to prognosis to distinguish patients with low malignant potential from those with higher ones. In this study 32 cases of SCLC, 13 of WDNEC and 14 of TC with a follow-up time up to 7 years were collected. Sections 4 microm thick from paraffin embedded tissue were Feulgen stained. By means of high resolution image analysis 100 nuclei per case were randomly gathered to extract morphometric, densitometric and textural quantitative features. To investigate the ploidy status of the tumour the corrected DNA distribution was calculated. Stepwise linear discriminant analysis to differentiate the classes and Cox regression analysis for the survival time analysis were applied. Using chromatin textural and morphometric features in two two-class discriminations, 11 of the 14 TC cases and 8 of the 13 WDNEC cases were correctly classified and 11/13 WDNEC cases and 28/32 SCLC cases, respectively. The WDNEC cases are more similar in chromatin structure to TC than to SCLC. For the survival analysis, only chromatin features were selected to differentiate patients with better and worse prognosis independent of staging and tumour type.
OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage.
Alveolar adenomas of the lung may be a rare cause of solitary coin lesions on chest radiographs. We report a case of this neoplasm, describe its morphological and immunohistochemical characteristics and give further evidence that alveolar adenomas of the lung represent a benign proliferation of both the alveolar epithelium and the septal mesenchyme.
The spectrum of neuroendocrine lung tumours ranges from highly aggressive small cell carcinomas (SCLC) to carcinoid tumours (CD) of low malignant potential. Between these two extremes, the 'well-differentiated neuroendocrine carcinomas' (WDNEC) form a transitional group with uncertain biological behaviour. This study investigated the prognostic value of the proliferation marker MIB-1 (paraffin Ki-67) in 59 neuroendocrine lung tumours (32 SCLC, 13 WDNEC, 14 CD) by immunostaining of routinely processed paraffin sections. Morphometric evaluation was done by semi-automatic image analysis. The results were compared with survival data (mean follow-up: 42 months). The proliferation rates of the tumours as determined by MIB-1 immunoreactivity (MIB-1-PR) were significantly different between the tumour types (SCLC > WDNEC > CD) and showed a strong inverse correlation with survival time. In CD, the percentage of MIB-1-labelled nuclei never exceeded 1.1 per cent; higher values would therefore favour the diagnosis of WDNEC over that of CD. Among WDNEC, MIB-1 was able to differentiate a subgroup with excellent prognosis (MIB-1-PR: 0.3-3.4 per cent) from another subgroup with a death rate of 50 per cent (MIB-1-PR: 7.3-20.3 per cent). Within each tumour type, all patients without distant metastases at diagnosis survived when MIB-1-PR was < or = 9.4 per cent, suggesting a potential threshold for prognosis. Although the status of metastases are complementary prognostic indicators and are best used in combination to characterize the biological behaviour of neuroendocrine lung tumours.
Metastases of signet ring cell carcinomas to the scrotum are rare. We present 2 patients with this kind of tumor. In 1 patient, the scrotal pathologic examination helped to detect an adenocarcinoma of the appendix with a signet ring cell component, with an extent that had not been apparent clinically. The other patient was seen at an advanced stage of signet ring cell carcinoma of the sigmoid colon following surgical therapy and palliative chemotherapy. The route of metastases seems to be via seeding along the testicular cord and via lymphatic dissemination.
OBJECTIVES: Subsequent to total gastrectomy, many patients develop maldigestion and weight loss. The mechanisms that underlie these changes are not known. Therefore, in a prospective study, we have analyzed endocrine and exocrine pancreatic function in patients before and 3 months after total gastrectomy. METHODS: In 15 patients (12 male, three female, median age 62.4 yr) undergoing total gastrectomy due to gastric cancer, a direct exocrine pancreatic function test (secretin-cerulein test) was performed. In addition, a standard test meal was given to all patients to study endocrine pancreatic function and the pattern of hormones that influence exocrine pancreatic secretion. In nine patients, both function tests were repeated 3 months after total gastrectomy. Before and at 11 points after the application of the test meal, blood samples were taken for the measurement of glucose, insulin, glucagon, gastrin, pancreatic polypeptide, and cholecystokinin. In addition, a secretin-cerulein test was performed to analyze trypsin, chymotrypsin, amylase, bicarbonate, and the juice volume in the duodenal aspirates. RESULTS: Three months after total gastrectomy, all patients exhibited severe primary exocrine pancreatic insufficiency. Secretin-cerulein tests revealed that pancreatic juice secretion, trypsin, chymotrypsin, and amylase were significantly reduced by 76%, 89%, 91%, and 72%, respectively, 3 months after total gastrectomy and secretin and cerulein stimulation. Post-operatively, the patients had a pathological glucose tolerance with increased postprandial insulin and glucagon secretion. The baseline and postprandial gastrin and pancreatic polypeptide secretion were significantly decreased after total gastrectomy. In contrast, early postprandial cholecystokinin secretion was significantly increased postoperatively. CONCLUSIONS: After total gastrectomy, patients develop severe primary exocrine pancreatic insufficiency with decreased gastrin, decreased late postprandial pancreatic polypeptide, and increased cholecystokinin levels. These findings may explain why many patients with total gastrectomy have maldigestion and weight loss postoperatively. Therefore, gastrectomized patients should be given pancreatic enzymes to avoid these symptoms.
In a group of 10 subjects, nine schizophrenic patients and one healthy twin (seven men and three women, i.e. two monozygotic twin pairs: two patients and a healthy man and his sick twin brother, one dizygotic pair of two female patients, three male patients and one female patient without their appropriate twin siblings) Halstead-Reitan Neuropsychological Battery (HRNB) was used and partial neuropsychological tests (Wechsler Memory Scale, the Stroop Color-Word Test, Tonal Memory). The parameters of white matter density were evaluated by computed tomography. The fundamental findings include: In our small group numerous statistically significant correlations were found between neuropsychological tests and white matter density. 2. Higher density is associated with poorer neuropsychological efficiency. There are very similar correlations between neuropsychological variables and density parameters in different areas of the brain. 4. The majority of correlations of neuropsychological parameters is from the area of tactile and motor functions. 5. It is striking that there are statistically significant correlations of density with the simultaneous performance of both hands and the performance of the non-dominant hand but not with the performance of the dominant hand alone. 6. Some correlations pertain in addition to density also to the very controversial problem of the brain size of schizophrenic patients. In the investigated group an association between better neuropsychological performance and larger size of the brain was found. All findings will have to be tested in larger groups of patients and healthy subjects.
von Hippel-Lindau (VHL) disease is an autosomal dominant heritable disease that often occurs in association with various benign and malignant tumours. Clinically the disease is classified as VHL 1 (without phaeochromocytoma) and VHL 2 (with phaeochromocytoma). Genetically, VHL is caused by germline mutations in the VHL tumour suppressor gene. More than 100 germline mutations and rearrangements have been identified, but the biological function of a hypothetical VHL protein is not yet known. Genotype-phenotype correlations should aid in the understanding of this biological role. All VHL manifestations subsequently develop to VHL mutations, but some mutations may act in a tissue-specific manner. Whereas missense mutations cause tumour suppression to fail in adrenal cells, more severe structural mutations are usually necessary for tumour development in renal cells. As predicted by the tumour suppressor theory, the VHL gene also plays a critical part in the pathogenesis of sporadic non-VHL-associated tumours. In a large number of sporadic renal clear cell carcinomas, mutations and hypermethylation cause inactivation of the VHL gene. Together with allelic 3p loss, these constitute rate-limiting events in renal tumourigenesis. Insights into the molecular basis of phenotypic variability in VHL disease and the confirmation of the tumour-suppressor criteria in VHL and non-VHL sporadic tumours indicate an important role of the VHL gene in the development of these tumours.
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On the basis of various laboratory researches and field experiments with 959 alternating first inseminations the traditional tris-extender and a yolk-free medium for semen freezing on soy lecithin base were compared in studies using a split-sample technique. Concerning important criteria such as non-return-rate, conservation quality, and standard of hygiene and practicability, the alternative product was found at least of equal quality. The renunciation of chicken yolk is to be seen as a general advantage. Here, the development of cryomedia has been enriched by a useful and sensitive new component. Apart from being competitive this product is also the first to conform to future demands in standardization through ISO-norm.
Spores of Fusarium sacchari var. subglutinans isolated from broiler feed BR1 were obtained at an average concentration of 1.5/mg in 25% of tested samples. The spore concentration was increased from 1 to 100/mg of solid substrate (BR2; biscuit) or to 1/nL of Sabouraud broth after 3 weeks of cultivation. Mycotoxin analyses of these three substrates showed negative reactions for T-2 toxin and zearalenone but a positive reaction for deoxynivalenol (DON) which was found in concentrations of 5 ppm in Sabouraud broth, 50 ppm in BR2 and 220 ppm in biscuit. Therefore, our F. sacchari isolate appeared to be a DON producer.
Archival specimens of 25 pulmonary carcinoids including 15 cases of typical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrine carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gene. Mutations were identified in 4 tumors, including 3 out of 15 (20%) typical carcinoids and the single large-cell neuroendocrine carcinoma, but none of the atypical carcinomas showed a mutation. The mutations were acquired during tumor development since they were not present in the corresponding nontumorous tissue. All mutations in the typical carcinoids, a tumor type without epidemiological link to cigarette smoking, were G to A transitions. The level of p53 protein was investigated by immunohistochemistry with the polyclonal antibody CM-1. None of the pulmonary carcinoids investigated showed a positive reaction, despite the presence of missense mutations in two cases. Negative staining of carcinoids with mutations was also observed with the monoclonal antibodies pAb1801 and DO-1. Our data suggest that point mutations of the p53 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer. Moreover, negative immunostaining for p53 is no indicator for the absence of p53 missense mutations in typical carcinoids.
The value of the number and size of the nucleolar organizer regions (NORs) as prognostic indicators in human neuroendocrine lung tumours was evaluated in a quantitative study of 57 cases, including 33 small cell carcinomas (SCLCs), 9 well-differentiated neuroendocrine carcinomas (WDNECs) and 15 "classic" carcinoids. NORs were visualized on paraffin sections by an argyrophilic technique (AgNOR) and measured by automatic image analysis. In each case, the mean number and area of AgNORs were evaluated; the results were compared with clinical follow-up and survival. AgNOR values for both number and area were significantly higher in SCLCs than in WDNECs and carcinoids. WDNECs had insignificantly higher AgNOR values than carcinoids. Among SCLCs, AgNOR values of the oat cell subtype and the intermediate cell subtype did not differ significantly. Regardless of the histological tumour type, AgNOR values strongly correlated with prognosis, with more and larger AgNORs indicating a more progressive clinical course. In the present study we demonstrate for the first time that the biological behaviour of neuroendocrine lung tumours is correlated with the number and size of AgNORs. Thus the measurement of AgNORs may serve as an additional prognostic indicator in these neoplasms, particularly in the separation of SCLCs from WDNECs with a more favourable prognosis.
After gastrointestinal surgery, patients often suffer from maldigestion. The extent of this maldigestion syndrome depends on the type of surgical procedure performed. After total pancreatectomy, subtotal left resection, resection for chronic pancreatitis. Whipple operation with ductal occlusion, and total gastrectomy, patients need obligatory enzyme treatment. After partial pancreatectomy without duct occlusion or partial gastrectomy, enzyme treatment should be initiated when exocrine pancreatic insufficiency occurs.
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