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Biomedical subjects

S Braun

Publications and source records attributed to S Braun.

At least 37 records · Page 2Linked to original sources
PubMed2004

Comparative analysis between the HER2 status in primary breast cancer tissue and the detection of isolated tumor cells in the bone marrow.

The presence of isolated tumor cells in the bone marrow (ITC-BM) of breast cancer patients is an independent prognostic parameter, indicating hematogenous tumor cell dissemination. While the HER2 status of breast cancer tissue has predictive value for the efficacy of different therapies, its prognostic relevance is controversial. To investigate the relationship between HER2 and ITC-BM, we retrospectively analyzed tumor tissues of 327 patients who underwent bone marrow aspiration at primary diagnosis or during the disease-free interval. Screening for ITC-BM was performed immunocytochemically, using the anti-cytokeratin antibody A45 B/B3. HER2 was determined by immunohistochemistry (IHC) with the antibody CB 11 (n = 277) and by fluorescence in situ hybridization (FISH, PathVision, Vysis, n = 206). ITC-BM were found in 83 of 327 patients (25.4%), with a median of 2.0 per 2 x 10(6 ) mononuclear cells. HER2 positivity (2+ /3+ ) was demonstrated in 18.8% of the tumors, amplification by FISH in 56 of 206 cases (27.2%). Established pathological parameters,tiviathological parameters, such as tumor size (p = 0.15), lymph node status (p = 0.93) and HER2 did not predict the presence of ITC-BM. After a median follow-up of 49 months (1-255), the presence of ITC-BM was a significant prognostic factor for distant disease free and overall survival, as well in univariate (log-rank-test, p = 0.024) as in multivariate analysis (cox-regression, p = 0.033 ). This also was confirmed in subgroups of patients by aease free survival (p = 0.013) and local recurrence (p = 0.003). The detection of ITC-BM is superior in predicting overall survival, compared to the HER2 status of the primary tumor. The direct identification of HER2 on ITC-BM is the aim of ongoing research, potentially synergizing the prognostic relevance of ITC-BM and the predictive value of the HER2 status.

Adult↗
PubMed2004

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans.

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (P<0.001). In normotensive DD ACE subjects, NEP activity was 0.30+/-0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity was 0.47+/-0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (P<0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.

Analysis of Variance↗
PubMed2004

[Concept and validation of a simple model of the intrathyroidal iodine kinetics].

UNLABELLED: AIM of this study is the introduction and validation of a simple model of the intrathyroidal iodine kinetics, designed for optimizing radioiodine therapy planning and dose measurement in a routine clinical setting. METHODS: The new model defines the intrathyroidal iodine kinetics as balance of the thyroidal iodine intake and -excretion, characterized by the two exponential equations A(t) = A(0) * (1-exp(-lambda(1) t)) and A(t) = A(0) * (exp(-lambda(2) t) -1), respectively. A(0) describes the theoretically maximum iodine uptake when the thyroidal iodine excretion is ignored, lambda(1) and lambda(2) represent the constants characterizing the iodine intake and excretion, respectively. The thyroidal iodine content at the time t equals the sum of both functions, which is A(t) = A(0) * (exp(-lambda(2) t)-exp(-lambda(1) t)). In 25 patients with autonomous goiter / nodules (n = 18), Graves' disease (n = 5), or endemic euthyroid goiter (n = 2), the iodine uptake in the thyroid during the radioiodine therapy as fraction of the applied activity was determined daily, with the remaining body covered by a lead shield. On average, 7.2 measurements were performed per patient (minimum 4, maximum 13). With these uptake values, individual regression curves were fitted using the above equation, and the difference between the actual measurements and the corresponding values of the regression curves was determined. RESULTS: The average deviation of the 179 uptake values from the calculated points of the respective regression curves was only 1.4%. There was no significant difference between the three disease groups. The distribution of the relative deviations during the individual courses was constant, systematic errors were not detected. CONCLUSION: Our results suggest that the intrathyroidal iodine kinetics can be precisely described with the model A(t) = A(0) * (exp(-lambda(2) t)-exp(-lambda(1) t)). With only three measurements, the trend of the curve can be calculated, which allows to determine the total radioiodine storage in the thyroid.

Biological Transport↗
PubMed2003

Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus.

Subjective tinnitus is a phantom sound sensation that does not result from acoustic stimulation and is audible to the affected subject only. Tinnitus-like sensations in animals can be evoked by procedures that also cause tinnitus in humans. In gerbils, we investigated brain activation after systemic application of sodium salicylate or exposure to loud noise, both known to be reliable tinnitus-inductors. Brains were screened for neurons containing the c-fos protein. After salicylate injections, auditory cortex was the only auditory area with consistently increased numbers of immunoreactive neurons compared to controls. Exposure to impulse noise led to prolonged c-fos expression in auditory cortex and dorsal cochlear nucleus. After both manipulations c-fos expression was increased in the amygdala, in thalamic midline, and intralaminar areas, in frontal cortex, as well as in hypothalamic and brainstem regions involved in behavioral and physiological defensive reactions. Activation of these non-auditory areas was attributed to acute stress, to aversive-affective components and autonomous reactions associated with the treatments and a resulting tinnitus. The present findings are in accordance with former results that provided evidence for suppressed activation in auditory midbrain but enhanced activation of the auditory cortex after injecting high doses of salicylate. In addition, our present results provide evidence that acute stress coinciding with a disruption of hearing may evoke activation of the auditory cortex. We interpret these results in favor of our model of central tinnitus generation.

Animals↗
PubMed2003

[Traveler's thrombosis].

Travel induced disorders have become more and more evident in a society of mass tourism. The link between travel in sitting position and risk of venous thromboembolic disease has been widely accepted. But the risk is not quantifiable because of a lack of epidemiological and pathophysiological data. It is likely to be small and mainly effect passengers with additional risk factors for venous thromboembolism. Therefore, prophylaxis of thromboembolic events during long distance journeys can only be considered good advice (with the exception of leg exercise) instead of an evidence-based recommendation.

Adult↗
PubMed2003

[Therapy of ulcus cruris venosum].

Wound healing in venous leg ulcers is a highly complex, dynamic process that is influenced by a number of factors. The primary task of local therapy is to support this natural healing process. While a number of therapeutic agents are available, in most cases their efficacy has yet to be established in controlled prospective studies in the sense of evidence-based medicine. Thus, the physician is left with the task of drawing up individual therapy plans for each patient according to the state of the wound. Compression bandages or stockings form the mainstay of treatment, generally in combination with moist dressings for chronic wounds.

Anti-Infective Agents, Local↗
PubMed2003

Systemic scleroderma patients have improved skin perfusion after the transdermal application of PGE1 ethyl ester.

BACKGROUND: Patients with systemic scleroderma exhibit a noticeable slowing of blood cell velocities or even stasis in the capillaries of the skin. In this study the effects of transdermally applied prostaglandin PGE1 ethyl ester on nutritive cutaneous perfusion and on Raynaud's symptoms were investigated. PATIENTS AND METHODS: 24 patients with systemic scleroderma were treated transdermally over a period of 14 days with prostaglandin E1 ethyl ester patches. The response of blood cell velocity in the nailfold capillaries to cold exposure was tested in 20 patients, and all of the patients recorded the number of Raynaud's episodes in a journal over a period of two weeks. RESULTS: After the transdermal application of prostaglandin E1 ethyl ester there was an increase in blood cell velocity in the nutritive capillaries of systemic scleroderma patients (increase from 0.35 +/- 0.14 mm/s to 0.47 +/- 0.11 mm/s, (p < 0.05)). At the same time there was a decrease in the number of Raynaud's episodes (2.9 +/- 2.4 per day to 2.6 +/- 2.0 per day (p < 0.05)). CONCLUSION: The transdermal application of prostaglandin E1 ethyl ester was shown to have a favourable effect on nutritive blood flow in the capillaries of the skin in systemic scleroderma patients.

Administration, Cutaneous↗
PubMed2003

Influence of VEGF on the viability of encapsulated pancreatic rat islets after transplantation in diabetic mice.

After pancreatic islet transplantation, insufficient blood supply is responsible for the loss of islet viability. The aim of our study was: 1) to determine the influence of vascular endothelial growth factor (VEGF) on the survival of encapsulated rat islets transplanted into healthy and diabetic mice and 2) to evaluate the metabolic efficiency of the VEGF-supplemented grafts. Twenty-four hours after culture, 50 rat islets immobilized into collagen in the presence of VEGF (100 ng/ml) and encapsulated (AN69 membrane, HOSPAL) were grafted in the peritoneal cavity of healthy or streptozotocin-induced diabetic mice (n = 6). Seven, 14, and 28 days after implantation, the encapsulation device and tissue surrounding the device were removed and the following parameters were analyzed: the number and the diameter of buds, the distance between devices and buds, the amount of cellular adhesion on the capsule surface, and the level of insulin secreted by encapsulated islet. For reversal of diabetes, 1000 rat islets encapsulated in the presence of VEGF were implanted in the peritoneal cavity of diabetic mice and fasting glycemia was analyzed. After 7 days of islet implantation in the absence of VEGF, the bud diameter was 16.1 +/- 6.9 microm in diabetic mice and 34.4 +/- 3.9 microm in healthy mice. However, the number of buds increased by a factor 2.5 in the presence of VEGF in both types of mice. Furthermore, when islets were transplanted in the presence of VEGF, the distance between the device and the buds was significantly decreased in both types of mice (p < 0.001) after 7, 14, and 28 days of islet implantation. Capsule analysis showed a decrease in cellular adhesion when the islets were encapsulated in the presence of VEGF. Insulin secretion of the islets was higher in the presence of VEGF compared with islets alone at all steps of the study. When 1000 rat islets were transplanted in the presence of VEGF, the glycemia level decreased to 6.2 +/- 0.8 mmol/L after 3 days and remained stable until at least 28 days. In contrast, in the absence of VEGF, the initial decrease in the glucose level was rapidly followed by a relapse in hyperglycemia. In summary, VEGF increased the viability of engrafted encapsulated islets, increasing the duration of a normalized glycemia in diabetic mice following transplantation. Local adjunction of VEGF may therefore improve the clinical outcome of islet transplantation.

Animals↗
PubMed2002

A major CYP2D6 autoepitope in autoimmune hepatitis type 2 and chronic hepatitis C is a three-dimensional structure homologous to other cytochrome P450 autoantigens.

Liver-kidney microsomal antibodies type 1 (LKM) are a diagnostic marker for autoimmune hepatitis type 2 (AIH-2), however, LKM autoantibodies are also detected in a small percentage of patients with chronic hepatitis C. The major target of LKM antibodies as evidenced by indirect immunofluorescence is cytochrome P4502D6 (CYP2D6). Anti-CYP2D6 titers of 62 LKM positive sera, 196 sera of patients with hepatic and rheumatic diseases and 33 sera of healthy blood donors (BD) were determined by an in vitro transcription/in vitro translation assay (ITT). Twenty five out of 26 AIH-2 sera and 33/36 LKM positive hepatitis C virus (HCV) sera were anti-CYP2D6 positive by ITT and antibody titers were similar in both patient groups. Epitope mapping experiments were performed by a series of truncated CYP2D6 proteins and by single epitopes of 257-269, 321-351, 373-389 and 410-419 amino acid (aa) expressed as DHFR-fusion proteins in Escherichia coli. The major linear epitope consists of 257-269 aa. This epitope is recognized with a significantly higher prevalence (64%) in AIH-2 than in LKM sera from patients with chronic hepatitis C (24%) (p < 0.001). None of the other autoepitopes showed significant differences in the prevalence of recognition by sera from both patient groups. Minor binding sites consisted of 321-351 aa, which was recognized by less than 20% of LKM sera and in the C-terminal region of 350-494 aa, which was recognized by less than 5% of LKM sera Our study revealed an epitope of 321-379 an on CYP2D6, which was shown to be conformation dependent. It was recognized by the vast majority of LKM sera, specifically by 76% of sera from HCV positive LKM patients and also by 76% of sera from patients with AIH-2. This epitope is homologous to three-dimensional epitopes detected by autoantibodies directed against hepatic cytochromes P450s in drug induced hepatitis and to an autoepitope on CYP21B associated with adrenal failure.

Amino Acid Sequence↗
PubMed2002

[About type and incidence of heart disease in psittacines kept in captivity in Germany].

It was the aim of the study to get an overview about spectrum and incidence of pathological aberrations in hearts and proximal vessels of psittacines which are kept in captivity in Germany. 107 psittacines which had been sent for routine necroscopy were examined especially for evidence of pathological alterations of the heart and/or the proximal vessels. In 36.4% of these birds macroscopic alterations could be verified. 99.0% of all hearts examined resp. proximal vessels showed at least mild histological alterations. This study allocates that especially noninfectious heart disease is of markedly importance in psittacines and that their evidence is much higher than it might be suspected on the basis of publications.

Animals↗
PubMed2002

[Technical aspects of immunocytochemical detection of disseminated tumor cells in bone marrow].

Early and clinically occult hematogenous dissemination of tumour cells is considered a sign of systemic tumour progression, since recent data suggest that these cells are seminal precursors of subsequent distant metastasis. Single isolated tumour cells can be detected by means of immunocytochemical and molecular techniques at frequencies as low as 10(-5) to 10(-6) exploring different body compartments, such as bone marrow, peripheral blood and lymph nodes. This review summarises the currently available data on techniques that can be used to detect metastatic breast cancer cells in bone marrow and values their opportunities and limitations.

Biomarkers, Tumor↗
PubMed2002

[Importance of occult metastatic cells in the treatment of patients with breast and gastrointestinal cancers].

Early and clinically non-apparent hematogenous dissemination of tumor cells is considered an important prognostic factor and marker of tumor progression. This phenomenon is reported for tumor entities differing as much as breast and gastrointestinal cancers. First prospective studies point to the unique opportunity of therapy monitoring utilizing follow-up bone marrow aspirations before and after adjuvant therapy. First results of these studies further indicate that currently used treatment strategies such as chemotherapy may not be efficient enough to eliminate all metastatic cells in all of the cases studied. Apart from improved tumor staging, such screening efforts may not only help to improve planning and monitoring of adjuvant therapy (which at present is only possible retrospectively) but also help to design individualized targeted biological treatment. This review summarizes the currently available data on the importance of disseminated tumor cells for the treatment of patients with breast or gastrointestinal cancer.

Bone Marrow↗
PubMed2002

[Tumor biology of primary breast cancer and minimal residual disease].

The immunocytochemical detection of isolated disseminated tumor cells (ITC) in the bone marrow of breast cancer patients, what is called minimal residual disease (MRD), has been demonstrated to be of prognostic value in all stages of the disease. In order to definitely prove the origin of these cells from the primary tumor it is necessary to identify common factors on both tumor tissue and ITC, furthermore a more detailed characterization could help to improve their prognostic impact by defining certain subgroups and possibly establish new therapeutic strategies. We examined the expression/amplification of HER2neu, CD 44 adhesion molecule and CD 31 angiogenetic factor on more than 200 primary tumor tissues by immunohistochemistry or fluorescence in situ hybridisation, resp., and found no sign. correlation with the detection of ITC. After a median follow-up of 32 months only ITC in the bone marrow were of prognostic significance. In a small number of patients we examined the expression of topoisomerase II alpha, a key enzyme of DNA replication, and its predictive value of eliminating ITC by anthracyclin based chemotherapy. No correlation with the presence of ITC before or after chemotherapy could be found, yet pat. with topoisomerase II alpha neg. tumors showed a trend to reduced disease free survival. Because of the very low number of ITC per bone marrow sample, the direct characterization of these factors on ITC stays difficult without the possibility of tumor cell enrichment or cell culture. Preliminary results on multi colour stained samples indicate that a selection of certain biological factors takes place during tumor cell dissemination.

Bone Marrow↗
PubMed2002

[Incidence and prognostic significance of disseminated tumor cells in patients with cervical cancer].

The clinical course of cervical carcinoma is widely determined by locoregional recurrence. There is increasing data, however, that haematogenic micrometastases occur early during the disease and might result in distant recurrence during follow-up. These occult disseminated tumor cells in blood, lymph nodes and bone marrow escape conventional tumor staging. Therefore, molecular and immunoytochemical techniques based on markers against human papilloma virus or cytokeratins (CK) have been applied. At present, there is only one study available on the prognostic relevance of disseminated tumor cells in bone marrow. No correlation between the bone marrow status and overall survival was observed. Still, there was a strong trend towards shorter distant disease free survival in patients with a positive bone marrow status. In view of the data on disseminated tumor cells in other tumor entities, these early results might offer new options for refined tumor staging and improved treatment options.

Bone Marrow↗
PubMed2001

Molecular markers of metastasis in breast cancer: current understanding and prospects for novel diagnosis and prevention.

The early and clinically occult spread of viable tumour cells throughout the body is increasingly considered as a hallmark of cancer progression, because recent data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumour-associated cell-membrane glycoproteins, individual carcinoma cells can be detected in cytological bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of these immunostained micrometastatic cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free period and overall survival. This screening approach might therefore be used to improve tumour staging and to guide stratification of patients for adjuvant therapy in clinical trials. Another promising clinical application is the use of these micrometastatic cells to monitor response to adjuvant therapies, which at present can be assessed only retrospectively after an extended period of clinical follow-up. This review summarises current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.

Journal Article↗
PubMed2001

The fate and prognostic value of occult metastatic cells in the bone marrow of patients with breast carcinoma between primary treatment and recurrence.

BACKGROUND: The current study examines the fate of occult metastatic cells detected in bone marrow (BM) at primary diagnosis and evaluates whether persistently positive findings support the prognostic influence of these cells in patients with Stage I--III (International Union Against Cancer) breast carcinoma. METHODS: The authors analyzed BM aspirates, at the time of primary diagnosis and after a median interval of 19 months (range, 7--67 months), from 89 patients who were free of recurrence. The presence of cytokeratin (CK) positive cells was assessed with the monoclonal anti-CK antibody A45-B/B3. Patients were observed prospectively for a median of 41 (range, 12--78) months after the first aspiration. RESULTS: At the time of primary diagnosis, 24 of 89 patients (27%) presented with occult metastatic cells in the BM. Of the same 89 patients, 25 (28%) had a positive BM finding at the time of the second BM analysis. Among those patients with an initially negative BM finding, 15 patients (17%) had occult metastatic cells at time of the second BM aspiration, whereas 10 patients (11%) had a persistently positive BM finding. Patients with a persistently negative BM status (n = 50) had a significantly better overall survival than patients with a positive BM status at the time of the second BM aspiration (n = 25), both by univariate analysis (P = 0.045, log-rank) and multivariate analysis (P = 0.034, Cox regression). CONCLUSIONS: In many patients with primary breast carcinoma, minimal residual disease can be detected by follow-up examination of the BM. This finding is prognostically relevant and provides reason to include BM monitoring in future clinical trials.

Adult↗