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J Mester

Publications and source records attributed to J Mester.

At least 37 records · Page 2Linked to original sources

[Onco-PET: lesion detection by monitor versus standardized film documentation].

AIM: Lesion detection and localization of 2-[18F]fluoro-2-deoxy-D-glucose (F-18-FDG) Onco-PET-Investigations are usually performed on-line at the computer display. The aim of the present study was to evaluate the clinical efficacy of a standardized film documentation as an alternative approach. METHODS: 100 Onco-PET-investigations without attenuation correction were analyzed with regard to number and localization of lesions suspicious of malignancy. A standardized documentation on film was developed including 1. transversal slices of the brain, 2. coronal slices and maximum-intensity-projections (MIPs) of the head/neck region and 3. of the trunk and 4. MIPs of the legs. These transparencies were analyzed at the light box. An additional analysis on the computer display was performed slice by slice in coronal, transversal and sagittal directions for the whole body. RESULTS: A total of 315 lesions were detected in 100 patients. In 96/100 patients the two modalities agreed both in number and localization of tumor-suspicious lesions. 7 lesions in the legs of 3 patients didn't show when interpreting the films (MIPs only). In 2/100 patients additional analysis on the computer display caused a change in the localization of 9/315 lesions. 8 of these were located in the legs. When adding coronal slices for the documentation of the lower extremities all the lesions were shown. Moreover, all lesions were localized correctly except one clinically non-relevant change of localization out of a total of 322 lesions. CONCLUSION: The newly developed standardized documentation supports the concept of film reading and reporting of onco-PET investigations, restricting an additional on-line analysis to rare cases only. Furthermore, the intention of the "Arbeitsgemeinschaft Standardisierung" (work group standardisation) are met, i.e. to ease analysis of follow-up studies acquired at different places.

Documentation↗

Quantitative salivary gland scintigraphy.

OBJECTIVE: Uptake of 99mTc-pertechnetate in salivary glands reflects intact salivary gland parenchyma. However, no standardized protocol for an accurate quantification of parenchymal function has been established so far. METHODS: In this paper we report on a validated acquisition protocol supplying a normal database for standardized quantitative salivary gland scintigraphy. RESULTS: The major advantage of salivary gland scintigraphy, as compared to other imaging modalities, is that both parenchymal function and excretion fraction of all four major salivary glands (i.e., parotid and submandibular glands) can be simultaneously quantified with a single intravenous injection. CONCLUSION: Quantitative salivary gland scintigraphy is demonstrated to be a suitable imaging modality for research applications in evaluating the effects of radioprotective drugs on salivary glands. Salivary gland scintigraphy is easy to perform, reproducible and well-tolerated by the patient.

Adolescent↗

Clinical value of 24-hour delayed imaging in somatostatin receptor scintigraphy for meningioma.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful in patients suspected of having meningiomas. Delayed imaging is regularly performed up to 24 h postinjection. However, this procedure is time consuming and expensive. Therefore, we investigated whether 24-h imaging may be omitted in these patients. METHODS: After clinical examination and standard MRI, 71 patients were suspected of having 92 meningioma lesions. Before surgery, all patients underwent SRS after intravenous injection of 200 MBq (5.4 mCi) 111In-octreotide. Planar whole-body images were obtained at 10 min and 1, 4 and 24 h, and SPECT was performed at 4 and 24 h. Results of SRS in all lesions were evaluated with respect to histology and time of image acquisition. RESULTS: SRS yielded 58 true-positive, 20 true-negative and 14 false-negative results, with the false-negatives all less than 5 mL (2.3+/-2.1 mL) in volume. In 52 of 58 true-positive lesions (89.7%), diagnosis could be established by 4-h imaging without further information by 24-h imaging. In 10 of the 52 lesions, SPECT was necessary to confirm planar findings. Imaging at 24 h was necessary in only 6 of 58 true-positive lesions (10.3%): 3 patients who had intracranial relapse of meningioma (volume < 5 mL) and 3 who had spinal meningioma. Thus, a diagnosis of intracranial meningioma could be established in 52 of 55 lesions (95%) using a 4-h imaging protocol. CONCLUSION: With a 4-h acquisition protocol that includes SPECT imaging, SRS yields sufficient information in patients suspected of having intracranial meningiomas. Delayed imaging at 24 h is recommended only for patients who have small meningiomas (volume < 5 mL), spinal localizations or negative SRS at 4 h.

Adolescent↗

Quality assurance in PET: evaluation of the clinical relevance of detector defects.

UNLABELLED: Defective detector blocks in PET may cause serious image artifacts. To estimate the influence of malfunctioning detectors on image quality, a method is described for transferring the actual detector defect onto previously acquired scans. METHODS: Consequences of detector defects of varying types and extensions were simulated in phantom studies as well as in clinical 18F-fluorodeoxyglucose investigations. First, a condition frame was obtained by dividing the sinogram of a blank measurement, obtained with rod sources on the defective PET camera, by the sinogram of a reference blank acquired before the appearance of the defect. Second, the sinogram of a previously acquired typical patient study was multiplied by the condition frame and reconstructed. Thereafter, images from corrupted sinograms were compared visually with their originals. For repairing defective sinograms, linear interpolation and the constrained Fourier space method were tested. RESULTS: The effects of detector defects can be simulated accurately in patient studies. The correction methods applied are especially helpful in cases of (a) several neighboring defective detectors and small study objects, (b) small hot artifacts and (c) several nonadjacent defective detectors. Linear interpolation is faster than the constrained Fourier space method; it is more widely applicable and provides similar results. CONCLUSION: The proposed approach allows specific evaluation of clinical consequences of detector defects. This technique simplifies the decision as to whether a planned patient study can be performed or must be postponed. Even in cases of serious detector problems, sinogram repair may help eliminate image artifacts and minimize the loss of image quality.

Artifacts↗

Radioprotection of salivary glands by amifostine in high-dose radioiodine treatment. Results of a double-blinded, placebo-controlled study in patients with differentiated thyroid cancer.

BACKGROUND AND PURPOSE: Parenchymal impairment of salivary glands following high-dose radioiodine treatment is a well-known side effect in general caused by free radicals. Therefore, the radioprotective effect of the radical scavenger amifostine was evaluated prospectively in patients receiving high-dose radioiodine treatment. PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed in 50 patients with differentiated thyroid cancer prior to and 3 months after high-dose radioiodine treatment with either 3 GBq 131I (n = 21) or 6 GBq 131I (n = 29) in a double-blinded, placebo-controlled study. Twenty-five patients treated with 500 mg/m2 amifostine intravenously prior to high-dose radioiodine treatment were compared to 25 control patients receiving physiological saline solution. Xerostomia was graded according to WHO-criteria. RESULTS: In 25 control patients high-dose radioiodine treatment significantly (p < 0.001) reduced parenchymal function of parotid and submandibular glands by 40.2 +/- 14.1% and 39.9 +/- 15.3%, respectively. Nine out of these 25 patients developed Grade I and 2 Grade II xerostomia. In contrast, in 25 amifostine-treated patients there was no significant (p = 0.691) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage of salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

Effect of attenuation correction on lesion detectability in FDG PET of breast cancer.

UNLABELLED: The aim of this study was to compare the visual analysis of attenuation-corrected and noncorrected 18F-fluoro-2-deoxy-D-glucose (FDG) PET images in patients with primary or metastatic breast cancer using standardized film documentation and to evaluate the influence of attenuation correction on lesion detectability. METHODS: Standard FDG PET of the breasts and of the axillary regions was performed on 28 women with breast cancer. Transmission scans were acquired for attenuation correction after administration of FDG. Transverse and coronal slices and maximum intensity projections both with and without attenuation correction were documented in a standardized manner on film. Noncorrected images were displayed with an upper threshold of five times the mean activity in normal lung tissue. Attenuation-corrected images were documented with an upper threshold of a standardized uptake value of five. Two independent nuclear medicine physicians, who were unaware of the results of clinical investigation, other imaging modalities and histopathologic findings, interpreted the images visually, noncorrected images first. RESULTS: One hundred eighty-four of 189 lesions in 28 of 28 patients were found on attenuation-corrected and noncorrected images. Seventeen lesions were found in the breasts of 12 patients. In 18 patients, 31 axillary lesions were found. Moreover, 141 lesions representing distant metastases were detected in 18 patients. Attenuation-corrected images showed the same lesions in all patients but 2, in whom 5 of 189 small pulmonary lesions (2.6%) were not detected. Iterative reconstruction did not improve detectability of these lesions on attenuation-corrected images. These lesions were confirmed by CT, which revealed diameters of <1 cm. CONCLUSION: Attenuation correction by transmission measurement after injection may impair lesion detectability in PET for staging of breast cancer patients. When using the image modalities described, noncorrected PET images should be considered in image analysis.

Axilla↗

Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response.

A plasmid expression system encoding murine IFN-alpha4 and complexed with a protective interactive noncondensing polymeric (PINC) delivery system was used for in vivo immunotherapy treatment of an immunogenic murine renal cell carcinoma, Renca, and a nonimmunogenic mammary adenocarcinoma, TS/A. Mice bearing established tumors were treated with IFN-alpha/polyvinylpyrrolidone (PVP) expression complexes via direct intratumoral injection. Up to 100% inhibition of tumor growth was observed in the treated mice. By using an optimal dose of 96 and 48 microg of formulated IFN-alpha plasmid for the treatment of Renca and TS/A, respectively, 30% (Renca) and 10% (TS/A) of the treated animals remained tumor free. Inhibition of tumor growth was dependent on activation of the immune system. The antitumor activity elicited by IFN-alpha gene therapy was abrogated when mice were selectively depleted of CD8+ T cells. By contrast, depletion of CD4+ T cells resulted in enhanced tumor rejection following IFN-alpha/PVP treatments. Finally, mice that remained tumor free following IFN-alpha gene therapy displayed immune resistance to a subsequent tumor challenge. These data provide evidence that IFN-alpha gene therapy can be used to induce an efficient antitumor response in vivo.

Adenocarcinoma↗

Structure, synthesis, and molecular cloning of dermaseptins B, a family of skin peptide antibiotics.

Analysis of antimicrobial activities that are present in the skin secretions of the South American frog Phyllomedusa bicolor revealed six polycationic (lysine-rich) and amphipathic alpha-helical peptides, 24-33 residues long, termed dermaseptins B1 to B6, respectively. Prepro-dermaseptins B all contain an almost identical signal peptide, which is followed by a conserved acidic propiece, a processing signal Lys-Arg, and a dermaseptin progenitor sequence. The 22-residue signal peptide plus the first 3 residues of the acidic propiece are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes. The 25-residue amino-terminal region of prepro-dermaseptins B shares 50% identity with the corresponding region of precursors for D-amino acid containing opioid peptides or for antimicrobial peptides originating from the skin of distantly related frog species. The remarkable similarity found between prepro-proteins that encode end products with strikingly different sequences, conformations, biological activities and modes of action suggests that the corresponding genes have evolved through dissemination of a conserved "secretory cassette" exon.

Amino Acid Sequence↗

Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

PURPOSE: Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT. PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria. RESULTS: Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients. CONCLUSION: Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

[Chest X ray: routine indication in the follow-up of differentiated thyroid cancer?].

AIM: This retrospective study sought to elucidate whether routine chest x-ray is still useful for detection of pulmonary metastases in low risk patients despite the high sensitivity of the tumor marker thyroglobulin. METHOD: The hospital files of 609 patients with well-differentiated thyroid cancer were analysed. Pulmonary formation of metastases was diagnosed in 50 patients. The thyroglobulin value at the time of diagnosis was compared with the chest x-ray findings and, if present, additional diagnostic information such as Iodine-131 whole body scintigraphy (WBS) and thorax CT. RESULTS: The sensitivity of the chest x-ray to detect pulmonary metastases was at 52% lower than that of WBS (64%), thorax CT (82%) and thyroglobulin during suppression therapy (86%). Among the patients with papillary carcinoma stage I and II (UICC 1987), only 1 patient developed pulmonary metastases during follow up. In this low risk group of patients, detection of lung metastases exclusively by chest x-ray, without elevation of thyroglobulin level is extremely rare (calculated probability 1/4000) and associated with considerable costs. CONCLUSION: Routine, life long chest x-ray in low risk patients without a suspected recurrence (e.g. positive thyroglobulin) needs to be reconsidered.

Carcinoma, Papillary↗

[Carving and ski technique--aspects of biological regulation].

Based on theoretical calculations the effects of skis with great sidecuts on the biological regulation are shown. Of main interest is the overload of the biological system by unexpectedly catching an edge. The calculations show that a great sidecut using the same edge ankle causes a greater lateral deviation compared to a normal ski. The correction of unexpected incidents is done by reflex mechanisms. Remarkable consequences for the reflex time can be calculated for the various sidecuts only. It can be concluded that problems in using carving skis mainly occur in combining high velocities and/or weak movement experiences.

Acceleration↗

[Implementation and indications for quantitative sialoscintigraphy].

BACKGROUND: Since its introduction in 1965 salivary gland scintigraphy has been an established method to simultaneously investigate excretion function in major salivary glands. In order to elucidate parenchymal function of salivary glands, several authors described various quantitative and semiquantitative methods. However, no standardized protocol for quantitative salivary gland scintigraphy has been established so far. METHODS: Therefore, in this paper we report on a standardized and validated acquisition protocol for salivary gland scintigraphy using 99mTc-pertechnetate. RESULTS: A normal data base for both parenchymal and excretion function is given in detail. In addition, the diagnostic value of salivary gland scintigraphy is reviewed in various clinical settings, such as mild parenchymal damage in beginning Sjögren's syndrome, proof of functional obstruction in sialolithiasis with and without parenchymal damage, and parenchymal damage following radioiodine treatment. In a second part, applications of salivary gland scintigraphy in current clinical research are described, and radiation protection of salivary glands in rabbits and patients treated with high doses of I-131 are discussed. CONCLUSIONS: Salivary gland scintigraphy is a study that is easily performed and well tolerated by the patient. It yields quantitative parameters for parenchymal function and excretion fraction.

Animals↗

Effects of olomoucine, a selective inhibitor of cyclin-dependent kinases, on cell cycle progression in human cancer cell lines.

We have studied the effects of olomoucine, a selective inhibitor of cdk2, cdc2 and MAP kinase, on the rate of proliferation and the cell cycle progression in human cancer cells in culture. Olomoucine inhibited the growth of the KB 3-1, MDA-MB-231 and Evsa-T cell lines in a concentration-dependent manner, with EC50 values of 45, 75 and 85 microM, respectively. Incubation of exponentially growing KB 3-1 cells in the presence of olomoucine led to an increased proportion of cells in G1 phase after 24 h or more of incubation. Olomoucine failed to rapidly affect the phosphorylation of the Rb tumor-supressor gene product. However, [3H]thymidine incorporation into the cell DNA was rapidly inhibited. We show that this inhibition is due, at least in part, to the diminution of thymidine entry into the cells. Surprisingly, all these cell lines, when synchronized at the G1/S interface and relaxed in the presence of olomoucine, progressed unhindered through the S phase. Under these conditions, the G2 phase transit was markedly retarded but not prevented. Insufficient permeability of the cell membrane to olomoucine may explain the low activity of the drug.

Cell Cycle↗

Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers.

Oxaliplatin, classical [5-fluorouracil (5-FU)] and non-classical (AG337) thymidylate synthase inhibitors have shown promising activity in the treatment of cancer. This study investigates the cytotoxic effects of oxaliplatin in combination with 5-FU and AG337 in cultured human colon (HT29, CaCo2), breast (MCF-7, MDA-MB-231) and ovarian (2008) cancer cell lines, and their derived counterparts selected for their resistance to 5-FU (HT29-5-FU), doxorubicin (MCF-7mdr) or cisplatin (2008C13). Therapeutic experiments were conducted in mice bearing colon-HT29 xenografts and in the GR hormone-independent mammary carcinoma model. In vitro, oxaliplatin shows potent cytotoxic activity in colon (IC50 from 2.1 +/- 1.1 to 5.9 +/- 1.7 microM), ovarian (IC50 = 10 +/- 1.6 microM) and breast cancer cells (IC50 from 7.4 +/- 2.7 to 17.9 +/- 7.1 microM). Oxaliplatin was a potent inhibitor of DNA synthesis and bound to cellular DNA. Surprisingly, the overall amount of oxaliplatin DNA binding was significantly inferior to that induced by isocytotoxic concentrations of cisplatin in HT29 (p=0.026). In vitro, synergistic antiproliferative effects were observed when oxaliplatin was added to 5-FU and AG337. Those synergistic effects of combinations were maintained in colon HT29-5-FU cancer cells. In vivo, 5-FU increased significantly the antitumor activity of oxaliplatin in HT29 xenografts (p=0.0036), and similarly 5-FU and AG337 increased the activity of oxaliplatin in the GR tumor model (p=0.0012). These data may encourage further clinical investigation of oxaliplatin in combination with classical and non-classical thymidylate synthase inhibitors in the treatment of human cancers.

Antimetabolites, Antineoplastic↗

[Peptide-like substances in sheep amniotic fluid which regulate proliferation of BP-A31 cells].

Cell proliferation and differentiation of developing fetus is influenced by hormones as well as insulin-like growth factors and their binding proteins contained in amniotic fluid. Our purpose was to study the actual mitogenic activity of proteins and peptides present in the sheep amniotic fluid. The cell cycle regulatory activity was estimated by using mouse fibroblasts BP-A31 as target cells. The whole amniotic fluid was inactive. However, after removal of small molecules on Sephadex G-10, the fraction eluted in the void volume (M(r) > or = 0.7 kDa) was able to induce the cell division cycle in a significant proportion of quiescent fibroblasts (Fig. 1, fraction A; Fig. 2). By further gel chromatography of this active fraction at acidic condition on Sephadex G-50, two components with mitogenic activity were separated. One component was eluted immediately after the void volume of the column, the other one was coeluted with 125I-IGF-I (Fig. 3). The functional characteristics of mitogenic signal of both components (sensitivity to mitogenic effectors) were similar to those of IGF-I and insulin (Fig. 4). We suppose that a component with higher molecular weight eluted in the vicinity of the void volume of Sephadex G-50 represents probably IGFBPs or other similar proteins.

Amniotic Fluid↗

Direct inhibition of the expression of cyclin D1 gene by sodium butyrate.

In the mouse fibroblasts BP-A31 as well as in the human epidermoid carcinoma cells KB-3-1, both cyclin D1 mRNA and protein contents decreased rapidly during incubation with sodium butyrate. The decrease of cyclin D1 mRNA was not prevented by cycloheximide indicating that protein synthesis is not required for the inhibition of the expression of cyclin D1 gene by sodium butyrate. The 973 bp region upstream of the human cyclin D1 gene conferred inhibition of the expression of an indicator gene in transiently transfected cells. An 11 base-pair segment situated within this region, with a strong homology to the butyrate-response consensus element identified in butyrate-inducible promoters, also caused an inhibition of transcription under these conditions, indicating that cyclin D1 expression is inhibited by butyrate at the transcriptional level.

Animals↗