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Biomedical subjects

Thomas Schulz

Publications and source records attributed to Thomas Schulz.

16 recordsLinked to original sources

[Efficient diagnosis of pathological fractures].

Pathological fractures are defined as fractures, which appear at diseased and mechanically weakened bones due to systemic or local processes. Their frequency is below 5%. This study demonstrates typical results and diagnostic criteria of pathological fractures. It will be shown, how diagnostic analysis is supposed to be performed to recognize pathological fractures. Based just on the X-ray image, diagnostic algorithms should provide all tools required for the radiologist to create a final diagnosis or to refer to other appropriate imaging modalities followed by a correct diagnosis and, if necessary, to allow interdisciplinary causal therapies.

Diagnosis, Differential↗

Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme--a quantitative radiological analysis.

Patients with supratentorial high-grade glioma underwent surgery within a vertically open 0.5-T magnetic resonance (MR) system to evaluate the efficacy of intraoperative MR guidance in achieving gross-total resection. For 31 patients, preoperative clinical data and MR findings were consistent with the putative diagnosis of a high-grade glioma, in 23 cases in eloquent regions. Tumor resections were carried out within a 0.5-T MR SIGNA SP/i (GE Medical Systems, USA). The resection of the lesion was carried out using fully MR compatible neurosurgical equipment and was stopped at the point when the operation was considered complete by the surgeon viewing the operation field with the microscope. We repeated imaging to determine the residual tumor volume only visible with MRI. Areas of tissue that were abnormal on these images were localized in the bed of resection by using interactive MR guidance. The procedure of resection, imaging control and interactive image guidance was repeated where necessary. Almost all tissue with abnormal characteristics was resected, with the exception of tissue localized in eloquent brain areas. The diagnosis of glioblastoma was confirmed in all 31 cases. When comparing the tumor volume before resection and at the point where the neurosurgeon would otherwise have terminated surgery ("first control"), residual tumor tissue was detectable in 29/31 patients; the mean residual tumor volume was 30.7 +/- 24%. After repeated resections under interactive image guidance the mean residual tumor volume was 15.1%. At this step we found tumor remnants only in 20/31 patients. The perioperative morbidity (12.9%) was low. Twenty-seven patients underwent sufficient postoperative radiotherapy. We found a significant difference (log(rank)p = 0.0037) in the mean survival times of the two groups with complete resection (n = 10, median survival time 537 days) and incomplete resection (n = 17, median survival time 237 days). The resection of primary glioblastoma multiforme under intraoperative MR guidance as demonstrated is a possibility to achieve a more complete removal of the tumor than with conventional techniques. In our small but homogeneous patient group we found an increase in the median survival time in patients with MRI for complete tumor resection, and the overall surgical morbidity was low.

Adult↗

MR Imaging-guided percutaneous procedures in children.

Magnetic resonance imaging (MRI)-guided therapeutic interventions in children are very rare. In comparison to other imaging techniques, it is very unusual for MRI to be used for diagnostic percutaneous interventions despite its imaging benefits. We provide a brief description of available MRI systems and instruments and use clinical examples to present and discuss typical indications for percutaneous procedures while showing possibilities for percutaneous therapeutic interventions.

Biopsy↗

Interventional and intraoperative MR: review and update of techniques and clinical experience.

The concept of interventional magnetic resonance imaging (MRI) is based on the integration of diagnostic and therapeutic procedures, favored by the combination of the excellent morphological and functional imaging characteristics of MRI. The spectrum of MRI-assisted interventions ranges from biopsies and intraoperative guidance to thermal ablation modalities and vascular interventions. The most relevant recently published experimental and clinical results are discussed. In the future, interventional MRI is expected to play an important role in interventional radiology, minimal invasive therapy and guidance of surgical procedures. However, the associated high costs require a careful evaluation of its potentials in order to ensure cost-effective medical care.

Biopsy, Needle↗

[Therapy-related hematologic neoplasias after breast cancer. Epidemiologic, etiologic and cytogenetic aspects and new risk factors according to published data and own results].

BACKGROUND: Breast cancer is the most frequent solid tumor in women. The incidence is increasing. In Germany, about 45,000 women are newly diagnosed each year. The general strategy aims for the best local control of the tumor by surgery and radiotherapy. This strategy is supplemented by systemic adjuvant chemotherapy and/or anti-hormonal therapy. The following substances have shown their efficacy in clinical trials: alkylating agents, antimetabolites, anthracyclines, topoisomerase inhibitors, platinum derivatives, and taxanes. Due to intensified treatment schedules remission rates and overall survival could be significantly improved. On the other hand, the long-term toxicity of this antineoplastic therapy is an increasing problem. SECONDARY LEUKEMIAS: Therapy-associated secondary leukemias frequently occur after treatment for malignant lymphomas and multiple myelomas. However, they can also be observed after antineoplastic therapy of solid tumors such as cancers of the breast, lung, testicles and ovaries and sarcomas. The highest risk for secondary leukemias has been attributed to concurrent radiochemotherapy. Therapy-associated hematologic neoplasias are a severe medical problem due to the high incidence of breast cancer and the dismal outcome of secondary leukemias, which occur in 0.3-5% of patients receiving antineoplastic therapy. RISK FACTORS: The delineation of new individual risk factors is urgently required to improve the safety of modern breast cancer treatment, which includes intensive combined radiochemotherapy. Candidate mechanisms could be polymorphisms in DNA repair and/or xenobiotic-metabolizing enzymes. Preliminary data suggest that the resulting deficiencies in xenobiotic-metabolizing enzymes such as glutathione S-transferases increase the risk for therapy-induced hematologic neoplasias in patients with breast cancer.

Acute Disease↗

Secondary leukaemia after cure for locally advanced NSCLC: alkylating type secondary leukaemia after induction therapy with docetaxel and carboplatin for NSCLC IIIB.

Specific cytogenetic alterations in t-MDS and t-AML are associated with different chemotherapeutic agents, such as loss of chromosomal material from #5 and #7 with alkylators. No data have been published on secondary leukemias following the taxane docetaxel. We report a patient, who being in long-term remission after docetaxel-based induction chemotherapy with docetaxel and carboplatin, surgery and adjuvant radiotherapy for non-small cell lung cancer stage IIIB, developed a t-MDS and subsequently a t-AML 40 months after start of therapy. The t-MDS was characterised by a complex aberrant karyotype including monosomy #13 and partial monosomies of #5 and #7. This is the first report in the literature of t-MDS after docetaxel chemo-radiotherapy, implicating a possible association of docetaxel with alkylator type t-MDS and t-AML. The case will be discussed in the context of a review of the current literature.

Acute Disease↗

Establishment of a mouse xenograft model for mycosis fungoides.

Mycosis fungoides (MF) is the most frequent variant of cutaneous T-cell lymphomas (CTCLs). MF primarily involves the skin initially with patches and plaques. In later stages, cutaneous tumors develop and tumor cells may spread to lymph nodes and finally to visceral sites. Here, we describe an animal model for MF in immune-deficient nude mice, using the CTCL cell line MyLa. Subcutaneous transplantation of MyLa cells leads to the formation of cutaneous tumors in 80% of the mice (50/60 total). Spread of tumor cells to visceral sites was detected by immunohistochemistry and polymerase chain reaction (PCR)-based detection of specific T-cell receptor-gamma rearrangement. MyLa cells were found circulating in the blood, lymph nodes, and in blood vessels of heart, kidney, lung, and liver. In lung and liver tissue, tumor cells presented perivascular invasion, but no large secondary tumors developed. The nude mouse model described here will be a valuable test system for new therapeutic approaches for the treatment of MF and opens the unique opportunity to study the disease in vivo.

Animals↗

Surgical impact of computerized 3D CT-based visualizations in living donor liver transplantation.

For living donor liver transplantation (LDLT), accurate diagnostic evaluation is essential. Problems arise in assessment of the vascular, bile duct anatomy, liver graft volume, and vascular territories involved. Requirements for the realization of decision-support and enhanced precision in the planning of surgery in LDLT engineering fields are a three-dimensional (3D) visualization system that improves anatomic assessment, allows for interactive surgery planning, and acts as an intraoperative guide. Thirteen LDLT candidates and three LDLT recipients were assessed by "multislice" computer-tomographic examinations. Image processing for 3D visualization included segmentation and calculation of centre lines. A hierarchical mathematical model representing the vascular and biliary tree was created, which allowed calculation of individual vascular territories. Precision of 3D computed tomography (CT)-based visualizations was superior to diagnostic modalities used currently. In addition to detection of decisive anatomic variants, computerized interactive insertion of splitting lines allowed for better planning of the surgical approach and image-guided surgery. 3D CT-based visualization in LDLT facilitates diagnostic evaluation with high accuracy. Multiple examinations, especially with regard to invasive diagnostics, may be avoided. Surgical strategy was directly influenced by the detection of vascular and biliary variants.

Contrast Media↗

MLV/HIV-pseudotyped vectors: a new treatment option for cutaneous T cell lymphomas.

Cutaneous T cell lymphomas (CTCLs) are lymphoproliferative disorders involving the skin. Malignant cells have a CD4+ T-helper phenotype and are found in early stages of the disease in plaques and cutaneous tumors. MLV/HIV-pseudotyped retroviral vectors target gene transfer to CD4-positive T cells and are therefore well suited to be specific delivery vehicles to treat CTCLs. We established a mouse xenograft model for CTCL and generated MLV/HIV-pseudotyped vectors encoding the herpes simplex virus thymidine kinase (HSV-TK), a well-known suicide gene, to prove the efficacy of MLV/HIV vectors in CTCL treatment. Vector particles were intratumorally injected into CTCL nude mouse xenografts. Mice were systemically treated with ganciclovir (GCV) and the tumor tissue was analyzed. A significant delay in tumor growth was observed for HSV-TK-transduced and GCV-treated tumors. GFP expression could be detected exclusively in CD4+ cells of tumors after transduction with GFP-encoding control vectors. The data demonstrate a cell-specific in vivo gene delivery via MLV/HIV-pseudotyped vectors and open new avenues for the treatment of CTCL in humans.

Animals↗

[Clinical use of interventional MR imaging].

The integration of diagnostic and therapeutic procedures by MRI is based on the combination of excellent morphologic and functional imaging. The spectrum of MR-guided interventions includes biopsies, thermal ablation procedures, vascular applications, and intraoperative MRI. In all these applications, different scientific groups have obtained convincing results in basic developments as well as in clinical use. Interventional MRI (iMRI) is expected to attain an important role in interventional radiology, minimal invasive therapy, and monitoring of surgical procedures.

Biopsy↗

[Intraoperative use of an open mid-field MR scanner in the surgical treatment of cerebral gliomas].

The aim of the present study was to evaluate the effectiveness of intraoperative MRI guidance in achieving more gross-total resection in case of primary brain tumors. We studied 12 patients with low-grade glioma and 19 patients with high-grade glioma who underwent surgery within a vertically open 0.5 T MR system. After initial imaging, the resection was stopped at the point in which the neurosurgeon considered the resection complete by viewing the operation field. At this time, intraoperative MRI was repeated ("first control") to identify any residual tumor. Areas of tumor-suspected tissue were localized and resected, with the exception of tissue adjacent to eloquent areas. Final imaging was carried out before closing the craniotomy. Comparison of "first control" and final imaging revealed a decrease of residual tumor volume from 32% to 4.3% in low-grade gliomas, and from 29% to 10% in high-grade gliomas. Intraoperative MRI allows a clear optimization of microsurgical resection of both low-grade and high-grade gliomas.

Brain Neoplasms↗

[MR-guided laser-induced thermo-ablation of liver tumors: clinical experiences and therapy control concepts].

Minimally-invasive, laser-induced interstitial thermotherapy (LITT) of solid tumors represents a valid alternative to surgical procedures such as tumor resections. Within the framework of a palliative study on 16 patients, a total of 25 metastases in the liver were treated in an open MR system (0.5 T). The intraoperative scanner design allows patient-based navigation, decisive for a safe applicator positioning, as well as temperature monitoring and direct inspection of the therapy result, without need for patient transfer or repositioning. Although the MR thermometry applied in the open scanner assisted LITT monitoring, the current accuracy of temperature data was not sufficient to serve automatic irradiation control. Therefore, an experimental monitoring and control system was developed in a closed MR scanner (1.5 T) featuring a calibrated MR thermometry. The system provides also an interface to the laser system, allowing the automatic off/on switching of the laser power according to preoperatively defined control criteria. The basic functionality of the automatic laser control was successfully demonstrated with laser ablation experiments of liver samples using irradiation parameters close to typical clinical values.

Body Temperature↗

Human embryonic stem cell lines derived from discarded embryos.

Human pluripotent embryonic stem (ES) cells have important potential in regenerative medicine and as models for human preimplantation development; however, debate continues over whether embryos should be destroyed to produce human ES cells. We have derived four ES cell lines on mouse embryonic fibroblast cells in medium supplemented with basic fibroblast growth factor, human recombinant leukemia inhibitory factor, and fetal bovine serum. The source of these cell lines was poor-quality embryos that in the course of routine clinical practice would have been discarded. After continuous proliferation in vitro for more than 12 months, these ES cell lines maintained their developmental potential to form trophoblast and somatic cells, including cardiac muscle and neuronal tissue.

Animals↗

MR-guided percutaneous core biopsy of small breast lesions: first experience with a vertically open 0.5T scanner.

PURPOSE: The growing use of highly sensitive but only moderate specific breast MRI requires the development of both minimal-invasive as well as precise biopsy systems. The aim of the study was to prove the accuracy and feasibility of a biopsy procedure carried out in prone position in a vertically opened MR imager. MATERIALS AND METHODS: The biopsies were carried out in 21 women with lesions visible on MRI alone using an open breast coil with an integrated biopsy device. A 14 G coaxial needle was placed under near real-time MRI-guidance. After the tip of this needle was verified in contact with the lesion, we used a non MR-compatible, but MR-safe biopsy gun with a 16 G canula to take four to eight cores. RESULTS: We found eight malignant and 12 benign lesions. In one patient the procedure was not successful. In case of malignancy, the operation confirmed the diagnosis in all cases. The 12/21 patients with benign lesions have been followed without evidence of lesions growth over eight to 28 months. CONCLUSION: The described procedure allows MRI-guided minimal invasive core biopsy of small breast lesions (five to 17 mm) with a high degree of accuracy.

Adult↗

Tissue concentrations and induction of a hepatic monooxygenase in male Wistar rats after repeated doses of defined polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDDs and PCDFs) mixtures.

Two groups of male Wistar rats were treated 16 times (every 3rd day) subcutaneously with a defined mixture of polychlorinated dibenzo-p-dioxins (PCDDs) or of polychlorinated dibenzofurans (PCDFs). These mixtures contained no measurable amount of 2,3,7,8-TCDD. Each single dose was calculated to contain either 57 ng I-TEq (international 2,3,7,8-T4CDD toxicity equivalencies)/kg body weight of the PCDD mixture or 39 ng I-TEq/kg body weight of the PCDF mixture. Both mixtures contained a large excess of non-2,3,7,8-substituted congeners. The activities of ethoxyresorufin O-deethylase (EROD) in liver microsomes were correlated with the corresponding concentrations of PCDDs or PCDFs in hepatic tissue. Data were compared with results obtained after single injections of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-T4CDD). As expected, a complex kinetic situation resulted, because of the different tissue distributions and elimination half-lives of the various congeners: (1) 2,3,7,8-substituted PCDDs: the time course of the concentrations in liver and adipose tissue was similar for all congeners, the levels increased during the treatment period and decreased after treatment. Tissue concentrations of all 2,3,7,8-substituted PCDDs were considerably higher in liver than in adipose tissue. The liver/adipose tissue concentration ratios increased with the degree of chlorination. The ratio of 1,2,3,7,8-P5CDD was much lower than those of all other 2,3,7,8-substituted congeners. (2) 2,3,7,8-substituted PCDFs: 1,2,3,7,8-P5CDF was rapidly eliminated from liver and adipose tissue while 2,3,4,7,8-P5CDF largely persisted after the treatment period in both tissues. 2,3,7,8-T4CDF was eliminated even more rapidly than 1,2,3,7,8-P5CDF and could not be detected after treatment in both tissues. Time courses of the concentrations of 2,3,4,7,8-P5CDF, H6CDFs, H7CDFs and OCDF in liver and adipose tissue were similar: the levels of all congeners increased during the treatment period but no clear-cut decrease was observed within 34 days after the last treatment. Tissue concentrations of all 2,3,7,8-substituted PCDFs were higher in liver than in adipose tissue. The liver/adipose tissue concentration ratios increased with the degree of chlorination. The ratios of 2,3,7,8-T4CDF and 1,2,3,7,8-P5CDF were much lower than those of all other 2,3,7,8-substituted congeners. (3) non-2,3,7,8-substituted PCDDs and PCDFs: a number of non-2,3,7,8-substituted PCDD and PCDF congeners were found in both tissues in concentrations below 1 ng/g. In adipose tissue nearly all congeners were found during the treatment period showing a decrease after the treatment. In liver samples, many higher chlorinated PCDF congeners (with >4 chlorine atoms) could be detected. Most of those substituted in three of the four 2, 3, 7 and 8-positions persisted after treatment. In contrast, only one 1,4,6,9-substituted isomer of each PCDD homologue group was found during treatment with high recoveries after the third injection, but a rapid decline occurred already during the treatment period. (4) EROD activity: a good linear relationship (when using a double-log plot) between the EROD activities and the hepatic concentrations (ng I-TEq/g tissue) was found both in the PCDD-treated (r2= 85.8%) and in the PCDF-treated group (r2=87.3%). A similar correlation (r2=95.6%) was observed in rats treated with 2,3,7,8-TCDD alone (concentration range in liver tissue: 0.2 to 9.7 ng/g wet weight). The concentration-response curves for both the PCDD and PCDF mixtures run parallel to the curve for 2,3,7,8-T4CDD. However, the inductive potency of the PCDD or PCDF mixture was approximately 3-fold or 4-fold lower, respectively, compared with the inductive potency of 2,3,7,8-T4CDD. Thus, the I-TE factors overestimated the potency of the mixtures in the concentration range tested and taking EROD induction as an end point.

Adipose Tissue↗

Increased risk for therapy-associated hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1.

The most serious long-term complications of anti-tumor therapy are secondary malignancies. Parameters which might allow an estimation of the individual risk to develop a therapy-induced neoplasia are urgently needed. We examined whether the genotypes of the glutathione S-transferases (GST) M1 and T1, which metabolize various cytostatic drugs, as well as reactive oxygen species, influence the risk for secondary neoplasia. In a retrospective study, we analyzed peripheral blood lymphocyte or bone marrow DNA samples from 213 patients with acute myeloid leukemia (AML) and 128 with myelodysplastic syndromes (MDS) 44 of whom suffered from therapy-associated AML/MDS. The control group consisted of 239 healthy individuals with comparable composition as to race and sex. GSTM1 and GSTT1 were analyzed by multiplex PCR. Comparison between patients and control group revealed a significant (P=0.0003) overrepresentation of combined deletions of both GSTM1 and GSTT1 (double null genotype) in the group of patients with AML/MDS secondary to chemo- and/or radiotherapy of a carcinoma of the breast. In this group, 55% of the patients displayed the double null genotype as compared with 8.8% in the control group. We conclude that patients with carcinoma of the breast and inheritance of a combined gene deletion of GSTM1 and GSTT1 might bear an increased risk to develop a secondary therapy-induced hematologic neoplasia. An insufficient detoxification of cytostatic drugs such as cyclophosphamide is suggested to represent the underlying pathomechanism.

Adult↗