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Biomedical subjects

B Mann

Publications and source records attributed to B Mann.

At least 37 records · Page 2Linked to original sources
PubMed2000

A comparison of bolus versus continuous cardiac output in an experimental model of heart failure.

OBJECTIVE: The majority of studies examining cardiac output measurement have been done in physiologically stable models with low thermal background noise. Research comparing continuous cardiac output (CCO) with bolus thermodilution cardiac output (COTD) measures in human and animal models have reported high correlations, negligible bias, but large limits of agreement. The purpose of this project was to compare CCO with COTD measures in an experimental model of heart failure where the cardiac output values were low and the range was narrow. DESIGN: A one-group experimental design with preintervention control measures and repeated CCO and COTD measures across nine time points. SETTING: Cardiovascular research laboratory. SUBJECTS: Thirty dogs. MEASURES AND MAIN RESULTS: Univariate and multivariate versions of repeated-measures analysis were used to assess the influences of temperature, weight, and stage of the experimental protocol on CCO, COTD, and the differences between them. The two measures CCO and COTD were assessed for agreement by using methods proposed by Bland and Altman. Two hundred and fifty pairs of measurements were obtained during sinus rhythm. The range for COTD measures was 0.5-4.67 L/min and for CCO measures 1.0-5.40 L/min. Of the 250 cardiac outputs estimated by the continuous method, 73.4% of the values were within +/-15% of that estimated by the repetitive, single thermodilution method. The mean bias for the entire protocol was 0.01 (SD = 0.51) with a range of 4.33 L/min. CONCLUSION: Agreement between the two measures may be the function of biological variability, responses to anesthesia, and technique. Bland and Altman evaluation demonstrated low bias and precision and similar levels of agreement when compared with previous studies in an experimental model where the cardiac output was low and the range was narrow.

Animals↗
PubMed1999

Differential gene expression in colon carcinoma cells and tissues detected with a cDNA array.

Expression of selected genes coding for proteins with defined cellular functions was analysed in human cell lines derived from normal colonic mucosa, non-mucinous colonic carcinomas and mucinous colonic carcinomas. Altered expression of 10 genes in colon carcinoma cells was found by using a cDNA array; 6 of these alterations (60%) were confirmed by Northern blotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Among these 6 genes, 3 transcription factors as well as the topoisomerase II alpha and the mitosis inhibitor WEE1Hu gene were significantly suppressed in the tumour cell lines. In addition, the gene coding for the cell cycle inhibitor p21 was overexpressed only in cell lines derived from mucinous carcinomas. The significant suppression of the kinase WEE1Hu gene in carcinoma cells of both phenotypes and the tendency of the mucinous phenotype to overexpress p21 protein were confirmed in human colon carcinoma tissues. Our data show that the cDNA array method permits a correct identification of changes in gene expression with a relatively high accuracy. The different expression of the p21 gene in the non-mucinous and mucinous carcinoma cells supports the hypothesis that these phenotypes may develop along different genetic pathways. The detection of WEE1Hu gene suppression in colon carcinoma cells and tissues suggests its potential role in tumourigenesis.

Adenocarcinoma, Mucinous↗
PubMed1999

Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas.

Mutations in the adenomatous polyposis coli or beta-catenin gene lead to cytosolic accumulation of beta-catenin and, subsequently, to increased transcriptional activity of the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex. This process seems to play an essential role in the development of most colorectal carcinomas. To identify genes activated by beta-catenin overexpression, we used colorectal cell lines for transfection with the beta-catenin gene and searched for genes differentially expressed in the transfectants. There are four genes affected by beta-catenin overexpression; three overexpressed genes code for two components of the AP-1 transcription complex, c-jun and fra-1, and for the urokinase-type plasminogen activator receptor (uPAR), whose transcription is activated by AP-1. The direct interaction of the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex with the promoter region of c-jun and fra-1 was shown in a gel shift assay. The concomitant increase in beta-catenin expression and the amount of uPAR was confirmed in primary colon carcinomas and their liver metastases at both the mRNA and the protein levels. High expression of beta-catenin in transfectants, as well as in additionally analyzed colorectal cell lines, was associated with decreased expression of ZO-1, which is involved in epithelial polarization. Thus, accumulation of beta-catenin indirectly affects the expression of uPAR in vitro and in vivo. Together with the other alterations, beta-catenin accumulation may contribute to the development and progression of colon carcinoma both by dedifferentiation and through proteolytic activity.

Adenocarcinoma↗
PubMed1999

[Thyroidectomy and lymphadenectomy].

In benign goiter, thyroidectomy is only indicated in patients with nodular alterations of the complete thyroid gland. There is no evidence indicating that total thyroidectomy could improve the postoperative results in patients with Graves' disease. In Germany, thyroidectomy with cervicocentral lymph node dissection is the standard procedure for all differentiated thyroid carcinomas. However, there are no data to prove that this approach is superior to less radical procedures. Avoidance of reoperations and optimal conditions for effective postoperative radioiodine therapy are arguments for this aggressive strategy. In patients with medullary carcinoma or with detected ret-proto-oncogene mutations, thyroidectomy with cervicocentral lymphadenectomy should be the initial operation. The cervicolateral and mediastinal compartments should be dissected when clinically obvious lymph node metastases are present in patients with differentiated carcinomas. In patients with medullary carcinomas, persistently increased calcitonin levels after the initial operation are sufficient indication for this procedure. Thyroidectomy is an important part of the multimodal approach in patients with anaplastic carcinomas. The operative technique of thyroidectomy is presented as well as the technique of cervical lymphadenectomy in consideration of the lymphatic drainage of the thyroid gland.

Adenocarcinoma, Follicular↗
PubMed1999

Primary gastric non-Hodgkin's lymphoma: clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma.

BACKGROUND: Primary gastric non-Hodgkin's lymphoma (PG-NHL) is common in Saudi Arabia. This has prompted the analysis of a large series of patients with PG-NHL having high-grade diffuse large B-cell lymphoma (DLCL) in order to define the clinical features and outcome of this disease. PATIENTS AND METHODS: The data of all adult patients in the series with PG-NHL having DLCL histology were retrospectively reviewed. Patients were eligible if they had biopsy-confirmed diagnoses obtained by endoscopy or following laparotomy. RESULTS: Over a 16-year period, 185 patients with DLCL PG-NHL were identified and their data were reviewed. Patients had a median age of 54 years. In 53% of them only one initial therapeutic modality was given, while 47% were managed by a multi-modality approach. One hundred forty patients (76%), 19 (10%), and 26 (14%) attained complete remission (CR), partial remission, and no response/progressive disease, respectively. Multivariate analysis showed that poor performance status and advanced stage were negatively associated with the likelihood of attaining CR. Over a median follow-up of 54 months, 118 (64%) of the patients were alive and disease-free, 17 (9%) were alive with evidence of disease, and the remaining 50 (27%) were dead. The projected 5-year and 10-year overall survivals (OS) (+/- SD) were 68% (+/- 4%) and 61% (+/- 6%), respectively. The Cox proportional hazards model identified the same variables of response as adverse prognostic factors of survival. Using the influence of performance status, and stage, a prognostic index was constructed to recognize three prognostically distinctive risk categories with overall survival proportions of 87%, 61%, and 45%, respectively. The unadjusted International Prognostic Index, however, failed to classify patients into prognostically meaningful risk strata. Of the 140 patients who achieved CR, the median disease-free survival (DFS) was not reached, but the predicted 5- and 10-year DFS were 82% and 75%, respectively. A multivariate analysis identified poor performance status as the only independent prognostic covariate that adversely influenced DFS. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous OS and DFS. CONCLUSIONS: This large series characterized the clinico-pathologic features and outcome of patients with DLCL PG-NHL. Performance status, and stage significantly influenced patient outcome. A prognostic index was developed and it identified three prognostically distinctive risk groups; however, prospective validation is warranted.

Adult↗
PubMed1999

FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas.

Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in the same samples. The frequency of FasL detection was 30-40% in T and was 60-100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms.

Colorectal Neoplasms↗
PubMed1999

Differential regulation of renal prostaglandin receptor mRNAs by dietary salt intake in the rat.

BACKGROUND: In this study, we tested the hypothesis that prostaglandin (PG) receptor expression in the rat kidney is subject to physiological regulation by dietary salt intake. METHODS: Rats were fed diets with 0.02 or 4% NaCl for two weeks. PG receptor expression was assayed in kidney regions and cells by ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. Functional correlates were studied by measurement of PGE2-induced cAMP formation and renin secretion in juxtaglomerular (JG) cells isolated from animals on various salt intakes. RESULTS: EP1 and EP3 receptors were predominantly expressed, and the EP2 receptor was exclusively expressed in the rat kidney medulla. The EP4 receptor was strongly expressed in glomeruli and in renin-secreting JG granular cells. IP receptor transcripts were found mainly in cortex. Maintaining rats on a low- or high-NaCl diet did not affect the expression of EP1 or IP receptors, whereas EP4 transcripts in glomeruli were increased twofold by salt deprivation. Consistent with this, we found that PGE2-evoked cAMP production and renin secretion by JG cells from salt-deprived animals were significantly higher compared with cells obtained from salt-loaded animals. In the outer medulla, EP3 transcripts correlated directly with salt intake, and mRNA abundance was increased twofold by a high-NaCl diet. CONCLUSIONS: Our results suggest that subtype-specific, regional changes in PG receptor expression are involved in the renal adaptation to changes in salt intake. The results are in accord with the general concept that renocortical PGE2 stimulates renin secretion and maintains renal blood flow during low-salt states, whereas medullary PGE2 promotes salt excretion in response to a high salt intake.

Animals↗
PubMed1998

Expression of functional P2-purinergic receptors in primary cultures of human colorectal carcinoma cells.

Primary cell cultures of human colorectal carcinomas were established and characterized immunocytochemically. In the isolated cancer cells intracellular Ca2+ concentrations ([Ca2+]i) were measured by the fura-2 method. Stimulation with either extracellular ATP or UTP caused a biphasic rise of [Ca2+]i in a dose-dependent manner and cross-desensitization between both nucleotides was observed. The rank order of potency was ATP >== UTP > ATP-gamma-S > ADP > adenosine which is characteristic for a P2U-receptor subtype. Selective agonists of P1-, or P2X- purinoceptors had no effect on [Ca2+]i. The initial rise in [Ca2+]i was independent of extracellular calcium [Ca2+]e, whereas the second phase was not observed under [Ca2+]e-free conditions suggesting a capacitative Ca2+-entry-mechanism. Intracellular Ca2+ mobilization was proven by use of the Ca2+-ATPase inhibitor thapsigargin. P2U-specific mRNA could be detected by RT-PCR in both colorectal tumor tissues and in the human colorectal cancer cell line HT 29. In HT 29 cells, the hydrolysis-resistant ATP analog ATP-gamma-S inhibited cell proliferation and, also, induced apoptosis in a dose-dependent manner. Thus, human colorectal cancer cells express functional P2U-receptors which may play a role in the regulation of cell proliferation and apoptosis.

Adenosine Triphosphate↗
PubMed1998

Inhibition of L-type calcium channels by octreotide in isolated human neuroendocrine tumor cells of the gut.

The observation that somatostatin and its analogue octreotide inhibit the release of various peptide hormones and transmitters from neuroendocrine tumors has stimulated interest in the signal transduction pathway mediated by these compounds. Using the whole cell mode of the patch-clamp technique, we investigated the inhibitory effects of somatostatin and octreotide on voltage-dependent calcium channels (VDCC) in isolated human neuroendocrine tumor cells of the gut. Both peptides dose dependently and reversibly inhibited VDCC. Somatostatin (100 nM) reduced the current amplitude by 38 +/- 19% and 100 nM octreotide by 35 +/- 14%. Human neuroendocrine gut tumor cells preferentially express dihydropyridine-sensitive L-type VDCC, since most of the inward current was sensitive to the dihydropyridine isradipine. The inhibitory effects of isradipine and octreotide were not additive and octreotide had little effect on the isradipine-resistant inward current. Since octrotide selectively binds to the somatostatin receptor subtypes 2 and 5, these results suggest that inhibition of calcium-dependent hormone release by somatostatin from human neuroendocrine gut cells appears to involve somatostatin receptor subtypes 2 and 5, as well as dihydropyridine-sensitive L-type VDCC.

Calcium Channel Blockers↗
PubMed1998

A modification of the JAM test is necessary for a correct determination of apoptosis induced by FasL+ adherent tumor cells.

Tumor cells from several organs including colon have recently been shown to express Fas ligand (FasL) in vitro and in vivo. The expression, which in some tumours occurs de novo, was suggested to facilitate immune escape of malignant cells by killing tumor-infiltrating lymphocytes via Fas-FasL-induced apoptosis. An argument to support this hypothesis is the detection of tumor cell-induced apoptosis in Jurkat cells (as model T cells) by means of the widely used JAM test. In the present work the validity of this test for the analysis of colon carcinoma cell-mediated apoptosis in Jurkat cells was scrutinized in detail. The presented data show that the JAM test as described previously is prone to false-positive detection of apoptosis, when adherent epithelial cells are used as effectors. Furthermore, three lines of evidence indicated that several FasL+ colon carcinoma cell lines did not induce detectable apoptosis in Jurkat cells in vitro. We conclude that: (1) The JAM test must be modified for testing DNA fragmentation induced through adherent effector cells and (2) FasL+ colon carcinoma cells may be unable to induce apoptosis in vitro.

Apoptosis↗
PubMed1998

[Vascular surgery techniques in peripheral vascular embolism].

Acute limb ischemia is an emergency which regularly requires operative treatment in departments of general surgery. In about 70% of cases there is an embolic reason for acute ischemia. In the majority of cases urgent operative desobliteration is required to guarantee limb salvage. The introduction of balloon catheters reduced the surgical trauma significantly in cases of long secondary thromboses. More complex procedures are required in patients with preexisting chronic arterial occlusive disease. The mortality of these emergency operations is still 10-20% with a limb salvage rate of 80-90%.

Arteries↗
PubMed1998

Surgical training and vocal-cord paralysis in benign thyroid disease.

INTRODUCTION: Operations performed by a trainee surgeon should not result in a higher risk of complications. However, there is little information about identifying risk factors for primary surgery of benign, non-autoimmune goiter. METHODS: This study correlates experience of the surgeon and other potential risk factors with palsy rates of the recurrent laryngeal nerve over an 18-month period. Radical removal of all nodular thyroid tissue and principal nerve identification were standard procedures. RESULTS: Of a total of 405 operations per side, 55.8% were subtotal resections, 11.8% extended subtotal (near total) resections and 33.1% lobectomies. The overall initial and permanent palsy rates of "nerves at risk" were 8.9% and 1.2%, respectively. Patients' age, gender and weight, as well as endocrine activity of the thyroid gland were not associated with increased complications. CONCLUSION: The risk of nerve damage increased significantly and independently with size of goiter and extent of resection, but did not correlate with the surgical experience. In conclusion, the training of surgeons is safe if cases are carefully selected and the surgeons in training are supervised.

Clinical Competence↗
PubMed1998

Lymph node dissection in patients with differentiated thyroid carcinoma--who benefits?

INTRODUCTION: Papillary and follicular thyroid carcinomas are the most common thyroid malignancies and are usually indolent. Lymph-node involvement increases the rate of tumor recurrence and reduces long-term survival. However, characteristics such as age, long-term iodine deficiency, histological grade, extrathyroidal extension and distant metastases are clearly much more potent adverse factors than cervical lymph node metastases. Although there are no prospective randomised studies showing the overall benefit of routine cervicocentral lymph-node dissection in addition to total thyroidectomy, we propose this procedure as a standard part of primary surgery in differentiated thyroid carcinoma (DTC). RESULTS: In specialised centres, morbidity is not higher than for thyroidectomy alone. However, there is a significant increase in morbidity after re-operation in the cervicocentral compartment. Modified neck dissection of the cervicolateral compartment should only be performed if there is clinical evidence of lymph-node involvement in this area. CONCLUSIONS: This strategy provides the optimal surgical treatment for all subgroups of patients with DTC and creates optimal conditions for effective postoperative radioiodine ablation, which is another prognostic factor strongly associated with recurrence and survival in these patients.

Adenocarcinoma, Follicular↗
PubMed1998

A phase II trial of vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Forty patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated weekly with vinorelbine 30 mg/m2. Thirty-five patients received prior surgery, 20 prior chemotherapy, and 38 prior radiation therapy. Five patients were not evaluable for response and were assumed to be nonresponders. There were three confirmed responders (one complete response, two partial responses) for a response rate of 7.5% (95% confidence interval, 1.6%-20.4%). The median survival time for all patients was 5 months (range, 0.5-50 months), the median progression-free survival time was 2 months (range, 1-49 months). The most common toxicity was myelosuppression, with 60% of patients experiencing grade 3 or higher leukopenia. There was one treatment-related death resulting from sepsis. Vinorelbine has minimal activity in patients with SCCHN that does not exceed that of other currently used agents.

Adult↗
PubMed1998

[Increased methylation of promotor region suppresses expression of MUC2 gene in colon carcinoma cells].

MUC2 is known to be the main intestinal mucin carrying the carbohydrate moiety sialyl-Le(x), which interacts with the endothelial molecule E-selectin. This interaction may contribute to the extravasation of tumor cells and thus to the metastatic process. We analysed MUC2 expression in normal colonic, carcinomatous and metastatic tissue and the regulation of MUC2 gene expression. In metastases MUC2 expression was significantly lower than in normal tissue and primary tumors and seems not to be related to the metastatic process. In several colorectal carcinoma cell lines the methylation of the 5'-flanking region of MUC2 correlated with the suppression of the MUC2 gene. The increase of the MUC2 expression after the inhibition of the methylation with 5-aza-2' deoxycytidine strongly support the notion that the suppression of MUC2 gene is causally related to the methylation of the promoter.

Cell Transformation, Neoplastic↗
PubMed1998

[beta-catenin overexpression in metastasized colorectal carcinoma--an important mechanism in progression of the disease?].

The protein beta-catenin can not be degraded in CRC due to different reasons. This leads to an increased formation of beta-catenin/Tcf4 complex, which has a strong transcription factor activity. We investigated the mRNA expression of beta-catenin and Tcf4 in N, T and M in 12 cell lines and in tissues samples of 14 patients. We found a significant increase of beta-catenin mRNA expression in the primary tumors and in the metastases. These data show for the first time that apart from the known mechanisms the overexpression of beta-catenin mRNA can be an additional factor contributing to the increase of beta-catenin amount in cells of CRC. The resulting increased transcription of hitherto unknown target genes might be involved in the progression and the metastatic process of CRC.

Colorectal Neoplasms↗