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Biomedical subjects

C Riedel

Publications and source records attributed to C Riedel.

At least 19 recordsLinked to original sources

Isolation and isoenzyme characterization of Leishmania (Viannia) braziliensis from a case of human cutaneous leishmaniasis in northeast centre of the state of São Paulo.

The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.

Animals↗

Ex-vivo injection technique for implanting solid pulmonary nodules into porcine lungs for multi-slice CT.

PURPOSE: To develop a method for generating realistic pulmonary nodules that equal small pulmonary metastases and granulomas. MATERIALS AND METHODS: A total of 70 artificial lesions were introduced into 5 inflated porcine lungs inside a dedicated chest phantom by high pressure injection of a fat-wax-Lipiodol mixture and scanned with 16-slice computed tomography (CT). Image evaluation by two experienced radiologists included analysis of morphology, nodule size and density. RESULTS: The median nodule density was 78.8 Hounsfield units (HU), with 54 of 70 nodules (77.14 %) judged typical of small lung metastases. CONCLUSION: Without inducing visible damage of lung parenchyma, the injection technique produces highly realistic pulmonary nodules for morphometry or nodule detection with CT.

Animals↗

Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy.

Connective tissue turnover plays a prominent role in tumour growth and metastasis. We followed serum levels of seven connective tissue parameters in 37 patients with colorectal cancer metastatic to the liver prior to and during chemotherapy. Serum samples with episodes of tumour control (n=112) showed an increase of matrix metalloproteinase-2 (MMP-2) (P<or=0.01) and a decrease of tissue inhibitor of MMPs (TIMP-1) levels (P<or=0.01), while serum samples with episodes of tumour progression displayed the reverse pattern (P<or=0.01 and P<or=0.05, resp.). The ratio of circulating MMP-2/TIMP-1 was also significantly higher in episodes of tumour control vs tumour progression and prior to treatment (P<or=0.0001). We conclude that serum MMP-2 appears to reflect tumour resorption, while serum TIMP-1 may mirror tumour expansion.

Adult↗

Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). PATIENTS AND METHODS: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. RESULTS: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. CONCLUSION: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.

Aged↗

Comparison of macroscopic models of excitation and force propagation in the heart.

Computer aided simulations of the heart provide knowledge of phenomena, which are commonly neither visible nor measurable with current techniques. This knowledge can be applied e.g. in cardiologic diagnosis and therapy. A variety of models was created to reconstruct cardiac processes, e.g. electrical propagation and force development. In this work different macroscopic models were compared, i.e. models based on excitation-diffusion equations and cellular automata. The comparison was carried out concerning reconstruct-ability of cardiac phenomena, mathematical and biophysical foundation as well as computational expense. Particularly, the reconstruct-ability of electromechanic feedback mechanisms was examined. Perspectives for further developments and improvements of models were given.

Animals↗

Modeling force development in the sarcomere in consideration of electromechanical coupling.

Models of the cellular force development simulate the contractive behavior of the sarcomere. In conjunction with electrophysiological models they can contribute to a better comprehension of physiology and pathologies. Aim of this study is to examine the coupling of cellular electrophysiological processes and force development. For that a graphical user interface was developed to simplify the parameterization and calculation of the models as well as to present the results graphically. A feedback mechanism is introduced to pay attention to close connections between force development and intracellular processes. On basis of various tests with different boundary conditions, new force models are developed, parameterized, validated and compared with models in literature. In future studies the results will be tested in multiple cell organization.

Actins↗

Extracorporeal shock wave therapy in the treatment of lateral epicondylitis : a randomized multicenter trial.

BACKGROUND: On the basis of observational trials, numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow. However, there has been no evidence of its efficacy from well-designed randomized clinical trials. The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia. METHODS: A randomized multicenter trial with a parallel-group design was conducted. Following administration of local anesthesia, either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density (ED+) of 0.07 to 0.09 mJ/mm (2) or placebo therapy was applied on an outpatient basis. Treatment allocation was blinded for patients and for observers. The primary end point was based on the rate of success, as determined with the Roles and Maudsley score and whether additional treatment was required, twelve weeks after the intervention. Crossover was possible after assessment of the primary end point. Secondary end points were the Roles and Maudsley score, subjective pain rating, and grip strength after six and twelve weeks and after twelve months. The planned number of 272 patients was included in the study. RESULTS: The primary end point could be assessed for 90.8% of the patients. The success rate was 25.8% in the group treated with extracorporeal shock wave therapy and 25.4% in the placebo group, a difference of 0.4% with a 95% confidence interval of -10.5% to 11.3%. Similarly, there was no relevant difference between groups with regard to the secondary end points. Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention. Few side effects were reported. CONCLUSIONS: Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis. The previously reported success of this therapy appears to be attributable to inappropriate study designs. Different application protocols might improve clinical outcome. We recommend that extracorporeal shock wave therapy be applied only in high-quality clinical trials until it is proved to be effective.

Adult↗

Prolactin negatively regulates caveolin-1 gene expression in the mammary gland during lactation, via a Ras-dependent mechanism.

Caveolin-1 is a 22-kDa integral membrane protein that has been suggested to function as a negative regulator of mitogen-stimulated proliferation in a variety of cell types, including mammary epithelial cells. Because much of our insight into caveolin-1 function has come from the study of human breast tumor-derived cell lines in culture, the normal physiological regulators of caveolin-1 expression in the mammary gland remain unknown. Here, we examine caveolin-1 expression in mice at different stages of mammary gland development. We show that caveolin-1 expression is significantly down-regulated during late pregnancy and lactation. Upon weaning, mammary gland expression of caveolin-1 rapidly returns to non-pregnant "steady-state" levels. Injection of virgin mice with a battery of hormones normally up-regulated during lactation demonstrates that prolactin is the main mediator of caveolin-1 down-regulation. Virtually identical results were obtained with human mammary epithelial cells (hTERT-HME1) in culture. In addition, we demonstrate that prolactin-mediated down-regulation of caveolin-1 expression occurs at the level of transcriptional control and via a Ras-dependent mechanism. Interestingly, in the mammary gland, both mammary epithelial cells and the surrounding mammary adipocytes show prolactin-mediated down-regulation of caveolin-1. This hormone-dependent regulation of caveolin-1 expression is specific to the mammary fat pad. Finally, we employed HC11 cells, a well-established model of mammary epithelial cell differentiation, to study the possible functional effects of caveolin-1 expression. In the presence of lactogenic hormones, recombinant expression of caveolin-1 in HC11 cells dramatically suppresses the induction of the promoter activity and the synthesis of beta-casein, an established reporter of lactogenic differentiation and milk production. These findings may explain why caveolin-1 levels are normally down-regulated during lactation. This report is the first demonstration that caveolin-1 levels are down-regulated during a normal physiological event in vivo, i.e. lactation, because previous reports have only documented that down-regulation of caveolin-1 occurs during cell transformation and tumorigenesis.

Animals↗

[Prevention and therapy of diabetic foot syndrome. Preventing complications].

Selective prevention and stage-orientated treatment of the diabetic foot syndrome helps to avoid late complications. A prerequisite is good blood sugar control, early use of ACE inhibitors, CSE inhibitors and--based on the vascular situation, with consideration given to indications--platelet aggregation inhibitors. Regular inspection of the feet must be taken seriously. Every diabetic should be taught the rules of behavior in young years. The primary physician is responsible for coordinating further treatment and early referral to specialized foot clinics. In the event of an infection, specific treatment of the usually polymicrobial infection should be initiated. Long-term antibiotic treatment is not to be recommended. Wherever necessary, the calculated antibiotic therapy must be corrected on the basis of the results of antibiotic sensitivity testing of swabs taken from deep tissue (better: exudate from the floor of the wound. In the case of superinfected ulcers, wound debridement by the specialist surgeon is considered a must. Also, late stages of diabetic foot can be successfully managed in specialized centers by "foot-relieving" measures, revascularization, arthrodesis, etc.

Aged↗

Invariants for time-dependent Hamiltonian systems.

An exact invariant is derived for n-degree-of-freedom Hamiltonian systems with general time-dependent potentials. The invariant is worked out in two equivalent ways. In the first approach, we define a special Ansatz for the invariant and determine its time-dependent coefficients. In the second approach, we perform a two-step canonical transformation of the initially time-dependent Hamiltonian to a time-independent one. The invariant is found to contain a function of time f(2)(t), defined as a solution of a linear third-order differential equation whose coefficients depend in general on the explicitly known configuration space trajectory that follows from the system's time evolution. It is shown that the invariant can be interpreted as the time integral of an energy balance equation. Our result is applied to a one-dimensional, time-dependent, damped non-linear oscillator, and to a three-dimensional system of Coulomb-interacting particles that are confined in a time-dependent quadratic external potential. We finally show that our results can be used to assess the accuracy of numerical simulations of time-dependent Hamiltonian systems.

Journal Article↗

Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin.

The Na(+)/I(-) symporter (NIS) is a key plasma membrane glycoprotein that mediates active I(-) transport in the thyroid gland (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460), the first step in thyroid hormone biogenesis. Whereas relatively little is known about the mechanisms by which thyrotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS activity, post-transcriptional events have been suggested to play a role (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 3789-3793). Here we show that TSH induces de novo NIS biosynthesis and modulates the long NIS half-life ( approximately 5 days). In addition, we demonstrate that TSH is required for NIS targeting to or retention in the plasma membrane. We further show that NIS is a phosphoprotein and that TSH modulates its phosphorylation pattern. These results provide strong evidence of the major role played by post-transcriptional events in the regulation of NIS by TSH. Beyond their inherent interest, it is also of medical significance that these TSH-dependent regulatory mechanisms may be altered in the large proportion of thyroid cancers in which NIS is predominantly expressed in intracellular compartments, instead of being properly targeted to the plasma membrane.

Animals↗

Metabolic consequences of altered phosphoenolpyruvate carboxykinase activity in Corynebacterium glutamicum reveal anaplerotic regulation mechanisms in vivo.

Corynebacterium glutamicum possesses high in vivo activity of the gluconeogenic phosphoenolpyruvate carboxykinase (PEPCk) during growth on glucose, resulting together with anaplerotic carboxylation reactions in a PEP/pyruvate/oxaloacetate substrate cycle. The present study investigated the changes in intracellular fluxes and metabolite concentrations that are caused by altered PEPCk activity in L-lysine-producing C. glutamicum MH20-22B, applying a recently developed (13)C labeling-based strategy for anaplerotic flux resolution and quantification. Abolition of PEPCk activity by deletion of the respective pck gene resulted in increased intracellular concentrations of oxaloacetate L-aspartate, alpha-ketoglutarate, pyruvate, and L-lysine and in a 60% enhanced flux toward L-lysine biosynthesis, whereas increasing the PEPCk activity by pck overexpression had opposite effects. The results of the combined measurements of enzyme activities, in vivo fluxes, and metabolite concentrations were exploited to elucidate the in vivo regulation of anaplerotic reactions in C. glutamicum, and implications for the metabolic engineering of amino-acid-producing strains are discussed.

Corynebacterium↗

Journey of the iodide transporter NIS: from its molecular identification to its clinical role in cancer.

The Na+/I- symporter (NIS) is an intrinsic plasma membrane protein that mediates the active transport of I- in the thyroid, lactating mammary gland, stomach and salivary glands. The presence of NIS in the thyroid is exploited in diagnostic scintigraphic imaging and radioiodide therapy in thyroid cancer. The continued rapid progress in NIS research (aimed at the elucidation of the Na+-dependent I- transport mechanism, the analysis of NIS structure-function relations and the study of the tissue-specific regulation of NIS at all levels), holds potentially far-reaching medical applications beyond thyroid disease, in breast cancer and malignancies in other tissues.

Animals↗

CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria. 85 patients could be evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33 patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both markers were initially increased. With CEA positive patients, 143 cycles of chemotherapy were carried out, which showed the following response in the various cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53 episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive patients, 100 cycles of chemotherapy were carried out with the following results: 21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression could be excluded. Patients with an initial drop in CEA after the first cycle of chemotherapy of at least 50% of the initial level had a significantly higher probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P = 0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of 62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least 60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or CA 19-9 rise is only conditionally appropriate for recording progressions. A progression however, can be excluded with falling levels with high diagnostic accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of 79 patient episodes (99%) were correctly assessed as 'no progression'. In patients with an increased CEA and CA 19-9 the CEA determination is sufficient for the further monitoring. A confirmation of these results by multicenter trials can result in a considerable decrease of monitoring costs for palliative treatment.

Adult↗

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Aged↗

Chronic lateral epicondylitis of the elbow: A prospective study of low-energy shockwave therapy and low-energy shockwave therapy plus manual therapy of the cervical spine.

OBJECTIVE: To compare the effects of extracorporeal shockwave therapy (ESWT) alone with a combination of ESWT and manual therapy of the cervical spine in treating chronic tennis elbow. DESIGN: Prospective, matched single-blind control trial. SETTING: University hospital clinic. PATIENTS: Thirty patients with unilateral chronic tennis elbow, an unsuccessful conservative therapy during the 6 months before referral, and clinical signs of cervical dysfunction (eg, pressure pain at the C4-5 and/or C5-6 level, protraction of the head). INTERVENTIONS: Three times at weekly intervals all patients received 1000 shockwave impulses of an energy flux density of.16mJ/mm(2) at the lateral elbow. Additionally, they underwent manual therapy of the cervical spine and the cervicothoracic junction 10 times (group I). For each patient, a control matched by age (3-yr range) and gender at first conservative treatment was drawn at random from 127 patients who had undergone low-energy shockwave therapy in the same unit in the past 3 years (group II). Follow-up examinations took place at 12 weeks and at 12 months. MAIN OUTCOME MEASURES: The Roles and Maudsley outcome score at 12 months, defining an excellent or good result with no or only occasional discomfort without limitation of activity and range of motion. RESULTS: Neither group differed statistically before the study, with a poor rating for all patients (p >.05). At 12 months, there was still no significant difference, with the outcome being excellent or good in 56% in group I, and in 60% in group II (p >.05). Each group showed significant improvement compared with the respective prestudy evaluation (p <.0001). CONCLUSION: ESWT may be an effective conservative treatment method for unilateral chronic tennis elbow. The efficacy of additional cervical manual therapy for lateral epicondylitis remains questionable.

Adult↗

Weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) with folinic acid (FA) in adjuvant therapy of colon cancer.

After curative resection (R-0) of primary colon cancer or curative metastases resection, the efficacy, toxicity and compliance of a weekly 24-h infusion of high-dose 5-FU with folinic acid was examined in a prospective feasibility trial. From June 1995 to June 1997, 19 patients were included, 11 patients with UICC stage III and 8 patients with UICC stage IV colon cancer. The patients received weekly 500 mg/m2 of calcium folinic acid (Rescuvolin) as a 1-2 h-infusion on an outpatient basis following a 24-h infusion of 2,000 mg/m2 5-FU via a pump system (intermate LV5 Baxter). The adjuvant therapy was administered for 6 months. 90% of the patients received the planned 18 chemotherapy applications. The total 5-FU dose given to each patient amounted to 34.4 g/m2 in 6 months, thus corresponding to 95% of the planned 5-FU total dose. The main toxicity was diarrhea CTC toxicity grade 3 in the case of 16% of the patients. After a median follow-up of 51 months (range: 37-59 months), 82% of the patients (9 out of 11) with stage III remained free of recurrence. The 2 cases of recurrence belonged to the pN2 subgroup. In stage IV only 12% of the patients (1 out of 8) remained free of recurrence. On an adjuvant basis, a weekly 24-h infusion of high-dose 5-FU with folinic acid is accompanied by a good complicance and a high-dose intensity of 5-FU. Now it is tested within randomized phase III trials of the "Arbeitsgemeinschaft Gastroenterologische Onkologie (AGO)" of the "Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen" for UICC stage III colon cancer. Concerning stage IV, adjuvant therapy was not effective, a fact that seems to justify new drugs and new therapeutic strategies.

Adult↗

[MRI in chronic epicondylitis humeri radialis using 1.0 T equipment--contrast medium administration necessary?].

PURPOSE: Evaluation of the diagnostic value and confidence of contrast-enhanced MR imaging in patients with lateral epicondylitis in comparison to clinical diagnosis. MATERIAL AND METHODS: 42 consecutive patients with clinically proven chronic lateral epicondylitis and 10 elbow joints of healthy controls have been examined on a 1.0 T MR-unit. Criteria for inclusion in the prospective study were: persistent pain and a failed conservative therapy. The MR protocol included STIR sequence, a native, T2-weighted, fat-suppressed TSE sequence, and a Flash-2-D sequence. Also, fat-suppressed, T1-weighted SE sequences before and after administration of Gd-DTPA contrast media have been recorded. RESULTS: In 39/42 patients the STIR sequence showed an increased SI of the common extensor tendon. Increased MR signal of the lateral collateral ligament combined with a thickening and a partial rupture or a full thickness tear have been observed in 15/42 cases. A bone marrow edema at the lateral epicondilus was noticed in 6 of the studied patients and a joint effusion in 18/42 patients. After administration of contrast media we noticed an average increase of SI by about 150%. However, enhanced MR imaging did not provide additional information. CONCLUSION: In MR imaging of chronic epicondylitis administration of gadolinium-DTPA does not provide additional information.

Adult↗