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Tobias Schilling

Publications and source records attributed to Tobias Schilling.

11 recordsLinked to original sources
PubMed2006

Localization of hyperfunctioning parathyroid glands by selective venous sampling in reoperation for primary or secondary hyperparathyroidism.

BACKGROUND: Localization of hyperfunctioning parathyroid glands in patients with previous cervical operations is not always successful with noninvasive methods such as ultrasound, sestamibi scan, or magnetic resonance imaging. The aim of our study was to evaluate the results of selective venous sampling (SVS) of intact parathyroid hormone (PTH) in patients undergoing surgery for primary (75%) or secondary (25%) hyperparathyroidism (HPT). METHODS: Between January 2000 and January 2006, SVS for PTH was performed in 51 consecutive patients with persistent or recurrent HPT or patients with previous cervical explorations. The results of SVS were compared with those of noninvasive localization studies. RESULTS: Successful surgical treatment was achieved in 47 of 51 patients (92%). SVS had a sensitivity of 83.3% for the correct localization of a parathyroid adenoma (79.5%) or hyperplastic parathyroid glands (91.6%). False-positive or indeterminate results of SVS were found in 6% and 2%, respectively, of the patients. Ultrasound detected enlarged parathyroid glands with a sensitivity of 33.3%, and sestamibi scan with a sensitivity of 57.1%. CONCLUSIONS: Compared with noninvasive localization studies, SVS for PTH yielded the best results for recurrent or persistent HPT and for patients with previous neck explorations. SVS is strongly recommended in reoperative surgery for HPT with indeterminate results of noninvasive methods.

Adult↗
PubMed2006

Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma.

Inhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors. Addition of the respective specific ligands further increased apoptosis, indicating that COX-2 inhibition induced the expression of functional death receptors. Overexpression of a dominant-negative Fas-associated death domain mutant reduced COX-2 inhibitor-mediated apoptosis. Furthermore, our findings showed a link between COX-2 inhibition and the mitochondrial apoptosis pathway. COX-2 inhibition led to a rapid down-regulation of myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the Bcl-2 family, followed by translocation of Bax to mitochondria and cytochrome c release from mitochondria. Consequently, overexpression of Mcl-1 led to inhibition of COX-2 inhibitor-mediated apoptosis. Furthermore, blocking endogenous Mcl-1 function using a small-interfering RNA approach enhanced COX-2 inhibitor-mediated apoptosis. It is of clinical importance that celecoxib acted synergistically with chemotherapeutic drugs in the induction of apoptosis in HCC cells. The clinical relevance of these results is further substantiated by the finding that COX-2 inhibitors did not sensitize primary human hepatocytes toward chemotherapy-induced apoptosis. In conclusion, COX-2 inhibition engages different apoptosis pathways in HCC cells stimulating death receptor signaling, activation of caspases, and apoptosis originating from mitochondria.

Apoptosis↗
PubMed2006

Thyroid carcinoma.

PURPOSE OF REVIEW: Diagnostic methods and treatment options for differentiated and medullary thyroid carcinoma are continuously influenced by new trends and techniques. Our review therefore displays the most recent clinical practices for diagnosis and operative treatment of differentiated and medullary thyroid carcinoma. RECENT FINDINGS: Among the new diagnostic methods, high-resolution ultrasonography plays an important role for both the evaluation of thyroid nodules and the detection of enlarged suspicious cervical lymph nodes. The results of ultrasound will definitely influence operative decisions. A second step to diagnose medullary thyroid carcinoma is calcitonin measurement before surgery, which is sensitive and specific enough to detect medullary thyroid carcinoma in patients with thyroid nodules. Surgical treatment for differentiated or medullary thyroid carcinoma mostly consists of total or near-total thyroidectomy. An additional central or lateral modified-radical neck dissection might help to reduce local recurrence, especially in medullary carcinoma, but still does not influence significantly the survival rates. Monitoring of the recurrent laryngeal nerve during surgery is used increasingly. According to the newest literature, however, compared with visual identification of the laryngeal nerve, it cannot be considered as superior. SUMMARY: Diagnosis and treatment of thyroid carcinoma are still subjected to changes and the different options of surgical treatment in particular will be continuously discussed in the future.

Biomarkers↗
PubMed2006

Testing for anti-p53 antibodies increases the diagnostic sensitivity of conventional tumor markers.

The aim of this study was to determine whether anti-p53 antibodies are of clinical significance as a serological marker in the diagnosis and monitoring of malignancies. A total of 1874 serum samples from 591 patients with various types of cancer, esophageal, gastric, colorectal, pancreatic, hepatocellular, breast, and urogenital cancer, and 436 control individuals were analyzed by immunoblot for antibodies against p53. The anti-p53 antibody test was correlated with expression of conventional tumor markers, survival and the clinicopathological features of malignant disease. Anti-p53 antibodies were found in 23.4% (138/591) of the sera of patients with malignant disease (range 11.5-34%). The detection of anti-p53 serum antibodies had a specificity of 100% for malignancy (p<0.0001). The overall sensitivity of measuring established tumor markers was 62.9% (372/591). The elevation of conventional tumor markers and the presence of anti-p53 antibodies in the sera of patients with malignant disease turned out to be an independent variable (p<0.05). Combination of established tumor markers with the anti-p53 antibody test led to an increase in diagnostic sensitivity of 8% (49/591) (p<0.01). Thus, the independence of anti-p53 antibodies from established tumor markers allows the serological detection of additional tumor patients. Kaplan-Meier analysis revealed a trend toward a poorer prognosis in hepatocellular carcinoma and breast cancer patients who were anti-p53 serum positive. In conclusion, testing for anti-p53 antibodies can increase the diagnostic sensitivity when used in combination with measurement of conventional tumor markers. This increase is achieved without a parallel decrease in specificity.

Adult↗
PubMed2005

TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria.

TP63, an important epithelial developmental gene, has significant homology to p53. Unlike p53, the expression of p63 is regulated by two different promoters resulting in proteins with opposite functions: the full-length transcriptionally active TAp63 and the dominant-negative DeltaNp63. We investigated the downstream mechanisms by which TAp63alpha elicits apoptosis. TAp63alpha directly transactivates the CD95 gene via the p53 binding site in the first intron resulting in upregulation of a functional CD95 death receptor. Stimulation and blocking experiments of the CD95, TNF-R and TRAIL-R death receptor systems revealed that TAp63alpha can trigger expression of each of these death receptors. Furthermore, our findings demonstrate a link between TAp63alpha and the mitochondrial apoptosis pathway. TAp63alpha upregulates expression of proapoptotic Bcl-2 family members like Bax and BCL2L11 and the expression of RAD9, DAP3 and APAF1. Of clinical relevance is the fact that TAp63alpha is induced by many chemotherapeutic drugs and that inhibiting TAp63 function leads to chemoresistance. Thus, beyond its importance in development and differentiation, we describe an important role for TAp63alpha in the induction of apoptosis and chemosensitivity.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Impact of intraoperative parathyroid hormone levels on surgical results in patients with renal hyperparathyroidism.

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.

Adolescent↗
PubMed2004

[Endocrinology--I].

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗
PubMed2004

[Thyroid hormones and the function of the vascular endothelium].

Numerous clinical studies point towards connections between cardiovascular morbidity and mortality and disorders of the thyroid function. This does not only apply to clinically manifest functional disorders, but also to their subclinical stages. The present review discusses in detail some of the most important endothelial changes, open questions and future developments.

Arteriosclerosis↗
PubMed2003

[Osteoporosis and cardiovascular disease--two sides of the same coin?].

BACKGROUND: Osteoporosis and cardiovascular disease have numerous epidemiologic changes, health economic consequences, and molecular mechanisms in common, which are highlighted in this short review. EPIDEMIOLOGY AND CLINICAL STUDIES: The incidence of osteoporosis and cardiovascular disease is increasing in western societies, and genetic background, nutrition and psychologic factors play important roles in the pathogenesis of both diseases. The presence of a decreased bone mass or osteoporotic vertebral fractures are associated with an increased cardiovascular mortality. Calcaneal bone loss of 1 SD (standard deviation) as measured by osteodensitometry is associated with a 1.31 times increased risk for the occurrence of stroke. MOLECULAR MECHANISMS: The observed increase in interleukin-6 and tumor necrosis factor serum concentrations during the menopause contributes to osteoporotic bone loss and is associated with arteriosclerosis. Furthermore, the presence of hydroxyapatite in arteriosclerotic plaques supports the notion of common pathogenetic mechanisms for both, osteoporosis and arteriosclerosis. Osteopontin, bone GLA protein and bone morphogenetic protein-2, which have first been isolated from the organic bone matrix, are also present in arteriosclerotic plaques. 1,25-dihydroxycholecalciferol potently stimulates bone matrix mineralization and is also a negative regulator of the renin-angiotensin system; therefore vitamin D(3) deficiency in addition to bone metabolism also affects blood pressure. Osteoporosis and arteriosclerosis develop in mice lacking the osteoprotegerin gene and also in klotho gene knockout mice. CONCLUSION: Diagnosis of osteopenia, osteoporosis and osteoporotic vertebral or hip fractures indicates the presence of an increased cardiovascular risk which needs to be addressed by the physician who cares for patients with osteoporosis. The experimental finding of an osteoanabolic effect of statins supports the possibility of common pathogenetic disturbances which may be responsible for the simultaneous and frequent manifestation of osteoporosis and arteriosclerosis in elderly patients.

Animals↗
PubMed2003

Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin-releasing peptide RT-PCR.

Despite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT-PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20-PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP-PCR. In 16 of 61 nodes (26%) each PCR-system detected disseminated tumor cells in histologically tumor-free lymph nodes. Disseminated tumor cells were detected with CK20-PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20-PCR, compared to 1 of 8 samples with preproGRP-PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor-free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates.

Adult↗