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Biomedical subjects

H Zeitler

Publications and source records attributed to H Zeitler.

At least 19 recordsLinked to original sources

Application of the "-Omic-" technologies in phytomedicine.

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.

Drug Synergism↗

[The modified Bonn Malmö protocol (MBMP) in the treatment of acquired haemophilia A].

BACKGROUND AND OBJECTIVE: Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance. PATIENTS AND METHODS: Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented. RESULTS: In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%. CONCLUSION: Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.

Aged↗

Elevated serum concentrations of soluble adhesion molecules in coronary artery disease and acute myocardial infarction.

OBJECTIVES: Adhesion molecules are involved in a number of chronic conditions and diseases like rheumatoid arthritis, tumor growth and wound repair. Soluble adhesion molecules (SAM) play an important role in angiogenesis which is a common aspect of the conditions mentioned above and atherosclerosis. The aim of the present study was to assess the prevalence and the impact of elevated soluble adhesive molecule plasma concentrations in patients with atherosclerosis. DESIGN AND SUBJECTS: In this study, we measured the soluble forms of intercellular adhesive molecule (sICAM), endothelial adhesive molecule (sELAM) and vascular adhesive molecule (sVCAM) using a sandwich ELISA technique in plasma of patients with acute myocardial infarction (AMI), coronary heart disease (CHD) and in healthy subjects (HS). RESULTS: Patients suffering from CHD and AMI showed significant higher plasma concentrations of sICAM (p <0. 05 and p <0.005), sELAM (p <0.01 and p <0.001) and sVCAM (p <0.001 and p <0.005) than HS. In patients with fatal outcome of myocardial infarction the plasma concentrations of sICAM, sELAM and sVCAM were significantly elevated compared to surviving patients (p <0.005; p <0.005; p <0.05). In patients undergoing thrombolytic therapy there were no significant differences of plasma adhesive molecule concentrations. The levels of SAM were not related to other risk factors like diabetes, nicotin abuse, hyperlipidemia, hypertension and a familiary history of cardiovascular disease. CONCLUSIONS: Elevated levels of SAMs are found in patients with coronary heart disease. High SAM levels in plasma seem to be a prognostic factor in acute myocardial infarction. This effect is independent from other concomitant risk factors. Our results suggest that SAMs are involved both in acute phase of myocardial infarction and chronic process of atherosclerosis. It seems that similiar to other chronic inflammatory diseases, atherosclerosis seems to be modulated by soluble forms of adhesive molecules.

Adult↗

[MR enteroclysis for nuclear spin tomographic diagnosis of inflammatory bowel diseases with contrast enhancement].

PURPOSE: To evaluate MRI for effectiveness in assessment of intra- and extramural changes in the small intestine. METHODS: 40 patients with known or suspected small bowel disease underwent MR imaging immediately after conventional enteroclysis with barium and a mixture of methyl cellulose and gadolinium-DTPA. RESULTS: In 6 of 24 patients with no pathological findings in conventional enteroclysis, intraabdominal pathology such as thickening of the intestinal wall and an abscess were identified. In the remaining patients, MRI showed good correlation with conventionally obtained data and provided important additional information regarding extraluminal involvement such as enlargement of mesenterial lymph nodes and fistulas as well as abscesses. CONCLUSIONS: MRI, carried out using this technique, provides important additional information regarding intra- and extraluminal changes with good image quality.

Adolescent↗

[Doubtful mammographic findings: the value of negative MR mammography for tumor exclusion].

PURPOSE: To determine whether the addition of MR mammography (MRM) is useful in excluding malignant lesions and how reliable negative MRM findings are. METHODS: Amongst 694 MRM's, those originally regarded as normal were retrospectively reappraised. 239 female patients were involved. In all these patients there were clinical, sonographic and/or mammographic findings which were not entirely normal but there was no urgent indication for histological clarification. In 46 patients there were, however, histological examinations since the patients themselves insisted on it. In the remaining patients there was clinical, sonographic, mammographic and/or MRM follow-up after 12 to 18 months. RESULTS: In 95.4% (200/239) a carcinoma could be excluded by means of MRM, in 7 patients a carcinoma in situ and in two patients an invasive carcinoma was demonstrated histologically which had not been demonstrated by MRM. Even in retrospect, no abnormality could be found. CONCLUSION: Because of the only moderate sensitivity of MRM in the recognition of carcinoma in situ, doubtful lesions which can be localised, should be biopsied by a stereotactic method. In cases where evaluation is difficult on clinical, sonographic and mammographic findings, MRM is of value in excluding tumours, particularly in patients with increased carcinoma risk.

Adolescent↗

MRI of breast cancer: influence of chemotherapy on sensitivity.

MR mammography (MRM) seems to be a sensitive method for detection of breast cancer. The effect of cytotoxic agents on the dynamics of contrast medium uptake in primary breast carcinoma or recurrent disease is not known. This study addresses this question and evaluates MRM as a method of monitoring therapeutic success. A total of 13 patients (age range 34-62 years) with histologically confirmed breast cancer were investigated. The patients received neoadjuvant intravenous (iv) chemotherapy. MRM and interpretation of the dynamic measurements were performed in a standardized manner after positioning the patient in a double breast coil. A gradient echo sequence (Flash 3D, TE 5 ms, TR 12 ms, flip angle 25 degrees) was acquired before and 1, 2, 3 and 8 min after intravenous injection of Gd-DTPA 0.15 mmol kg-1 body weight. A T2 weighted SE sequence (TE 103 ms, TR 6900 ms, 4 mm, field of view 350 mm) was also obtained. MRM was performed prior to histological evaluation and after chemotherapy. All cases of malignancy were correctly diagnosed with MRM. Based on MR findings, eight patients were classified as "responders" and the remaining as "non-responders". In the "responders" a flattening of the Gd-DTPA uptake curve after the first cycle of chemotherapy of complete absence of Gd-DTPA uptake after the fourth cycle was observed. The change in Gd-DTPA uptake behaviour led to an underestimation of the extent of tumour in two patients and false negative findings in four patients. MRM provides information regarding response to therapy following the first cycle. MRM does not provide information regarding invasive tumour tissue in "responders".

Adult↗

Cell-cycle arrest in G0/G1 phase of growth factor-induced endothelial cell proliferation by various calcium channel blockers.

Calcium channel blockers cause antiproliferative effects on various cells in culture. Since angioneogenesis is a crucial step in the development of tumor growth, we examined the influence of different calcium channel blockers on human umbilical arterial endothelial cell (HUAEC) growth. Cell growth was measured by cell count, by [3H]thymidine incorporation, and by a 5-bromo-2-deoxyuridine (BrdU-incorporation immunofluorescence assay. Cell-cycle analysis was performed by flow cytometric analysis. Nifedipine, isradipine, diltiazem, and verapamil dose-dependently inhibited the basic fibroblast growth factor (bFGF)-induced [3H]thymidine incorporation. Fifty micromolars of nifedipine, isradipine, diltiazem, and verapamil completely inhibited bFGF-induced proliferation of HUAEC. Ten micromolars of each calcium channel blocker abolished the bFGF-induced increase in cell count. Five micromolars of isradipine completely blocked the bFGF-induced BrdU incorporation. Stimulation of HUAEC with bFGF (50 ng/ml) for 24 h caused a 2-fold increase in cells that entered S and G2+M phase in comparison with control cells. Five micromolars of isradipine abolished this effect completely. We conclude that calcium channel blockers are able to inhibit cell proliferation by a cell-cycle arrest in G0/G1 phase.

Calcium Channel Blockers↗

[The value of MR-mammography at 1.5 tesla in the differential diagnosis of non-puerperal mastitis and inflammatory breast carcinoma].

PURPOSE: The distinction between mastitis and inflammatory breast carcinoma is an important one. Current methods of evaluation including mammography, ultrasound and clinical examination do not enable this distinction. Dynamic magnetic resonance mammography (MRM) is a study with potential in this regard. MATERIAL AND METHODS: 12 patients, in whom clinical examination, mammography and ultrasound could not distinguish between both diseases, were reviewed retrospectively by means of MRM using a 1.5 T Siemens Magnetom SP and a circular mamma coil. We used dynamic 3-D gradient echo sequences with a duration of one minute. RESULTS: At present MRM cannot definitely distinguish between mastitis and inflammatory carcinoma, 80% of the inflammatory carcinomas were found to enhance more than 100% in the first minute, compared to 43% for mastitis. No other differences were seen. CONCLUSION: MRM proved useful in the follow-up of treated mastitis to demonstrate the success of antibiotic treatment of mastitis and to diagnose a histologically unconfirmed inflammatory carcinoma by means of a different follow-up.

Adenocarcinoma↗

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure.

We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.

Administration, Oral↗

Reverse transcriptase-polymerase chain reaction (RT-PCR): a sensitive method to examine basic fibroblast growth factor-induced expression of the early growth response gene-1 (egr-1) in human umbilical arterial endothelial cells.

Immediate-early genes are expressed upon growth and differentiation in a large variety of cells and species. In the present study we investigated the effect of basic fibroblast growth factor (bFGF) on early growth response gene-1 (egr-1)-mRNA expression in human umbilical arterial endothelial cells (HUAEC). The detection of this gene in HUAEC was performed by Northern blotting and by reverse transcriptase-polymerase chain reaction (RT-PCR). For RT-PCR specific primers for egr-1 and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) were constructed and PCR conditions were optimized. bFGF induced a time- and concentration-dependent increase of egr-1 expression. Maximal expression occurred within 30 min of stimulation with bFGF at a concentration of 50-100 ng ml-1. RT-PCR gave highly reproducible and specific results. The comparison of both methods showed comparable results but a higher sensitivity for RT-PCR in detecting the egr-1 mRNA. RT-PCR is an excellent method for detecting the expression of egr-1 mRNA in HUAEC.

Base Sequence↗

[Dynamic arthro-CT in the diagnosis of recurrent shoulder dislocations].

"Dynamic" double contrast arthro-CT in internal and external rotation was performed on 42 patients with recurrent subluxation of the shoulder. The differential distribution of contrast and air caused by the rotation resulted in optimal demonstration of the capsulo-labrale components responsible for joint stability. In 22 patients there appeared to be an indication for arthroscopy; this confirmed the previous findings. In all cases the anterior part of the capsule and the middle and lower labrum were seen best during internal rotation. In this way all the 15 anterior capsule lesions could be seen, as well as 16 out of 17 Bankart lesions; it also showed one lesion of the middle labrum which had been masked by a haemarthrosis during external rotation. The study also defined lesions of the upper labrum caused by a different pathological mechanism which was present in 7 patients (6 Andrews and 1 S.L.A.P. lesion). These and 2 posterior labrum tears could be diagnosed during external rotation. Sensitivity for lesions of the anterior labrum was 95%.

Adolescent↗