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T Schulz

Publications and source records attributed to T Schulz.

At least 73 records · Page 4Linked to original sources
PubMed2001

Gross-total surgery of supratentorial low-grade gliomas under intraoperative MR guidance.

BACKGROUND AND PURPOSE: Length of survival of patients with low-grade glioma correlates with the extent of tumor resection. These tumors, however, are difficult to distinguish intraoperatively from normal brain tissue, often leading to incomplete resection. Our goal was to evaluate the effectiveness of intraoperative MR guidance in achieving gross-total resection. METHODS: We studied 12 patients with low-grade glioma who underwent surgery within a vertically open 0.5-T MR system. During surgery, localization of residual tumor tissue was guided by interactive, near real-time imaging. The amount of residual tumor tissue on MR images was evaluated at the point of the operation at which the neurosurgeon would have terminated the procedure under conventional conditions (first control) and again before closing the craniotomy. RESULTS: Significant residual tumor (more than 10% of original tumor volume) was shown in eight patients at the first control condition. The percentage of resection varied from 26% to 100% (mean, 68%) at this time. Twelve tissue samples from seven patients were obtained in areas identified as residual tumor on MR images. In 10 cases, the neuropathologic investigation confirmed the presence of residual low-grade glioma; in two cases, the borderzone of tumor was identified. In evaluating the final sets of images, we found total resection in six cases, over 90% resection in five cases, and 85% resection in one case (mean, 96%). CONCLUSION: Surgical treatment of low-grade gliomas under intraoperative MR guidance provides improved resection results with maximal patient safety.

Adult↗
PubMed2000

Nondynamic kinetic resolution of configurationally stable biaryl lactones by reduction with oxazaborolidine-activated borane: AM1 studies and experimental verification

The complete mechanistic course of the atroposelective ring opening of a lactone-bridged biaryl, dinaphth[2,1-c:1',2'-e]oxepin-3-(5H)-one (3), with a chiral oxazaborolidine-BH3 complex was calculated using the semiempirical AM1 method. The first hydride transfer to the activated carbonyl function of the adduct complexes was elaborated to be the selectivity-determining step in the postulated five-step mechanism. The calculated enantioselectivity is in good accordance with the experimental results, so that related calculations were performed on the atroposelective ring opening of a sterically strongly hindered and therefore also configurationally stable six-membered biaryl lactone, 1,3-di-tert-butyl-6H-benzo[b]naphtho[1,2-d]pyran-6-one (6f). These calculations predicted a highly (M)-selective reduction of 6f (kM/kP = 358 at -78 degrees C), which, after the smooth preparation of 6f by intramolecular biaryl coupling in high yields, was fully confirmed experimentally (kM/kP > 200 at -78 degrees C). Isolation of the intermediate hydroxy aldehyde (M)-14 at the beginning of the reaction with the same enantiomeric excess as found for the corresponding alcohol (M)-7f conclusively showed the first hydride transfer step to determine the selectivity of this process. The good agreement of computationally predicted and experimentally confirmed values proves the suitability of the AM1 method for mechanistic studies on even such complex reactions and opens a most efficient overall synthesis of sterically highly hindered biaryls, in excellent chemical (for the ring closure) and optical (for the ring cleavage) yields and for any desired axial configuration.

Journal Article↗
PubMed2000

The antiovulatory potential of progesterone antagonists correlates with a down-regulation of progesterone receptors in the hypothalamus, pituitary and ovaries.

These studies analyze the regulation of progesterone receptors (PRs) in central and peripheral tissues with the aim of further understanding mechanistically the inhibition of ovulation by progesterone antagonists (PA). Therefore, it was of interest to investigate the influence of the progesterone receptor antagonist, Onapristone (ON), on PRs in the ovary, pituitary (PT), and hypothalamus (HYP), since ON effectively inhibits ovulation in rats. For this study PMSG/hCG-primed immature and adult female rats were treated with ON. Immunohistochemistry was used for the detection of PRs. Progesterone (P4) and estradiol (E2) levels were determined by RIA. PR expression in the ovaries of immature rats was not detectable until after hCG administration. In these animals, ON caused a reduction in the staining intensity of PR in the tertiary follicles at the time when the preovulatory P4-surge was inhibited (6 h post hCG). Adult rats treated for 15 days with ON showed a decreased PR expression in PT and HYP. At this time (proestrus, 7 p.m.) the P4 and E2 levels are significantly lowered. These results suggest that after treatment with ON the expression of PR is reduced in the ovary, PT and HYP. The regulation of PR in the ovary seems to be less dependent on estrogens than on LH. Thus, it is conceivable that the reduced PR expression after ON treatment may be a result of decreased LH sensitivity in the ovary. In the pituitary and hypothalamus, PR expression is stimulated by estrogens and progesterone, and therefore the fall in the P4 and E2 levels in ON-treated animals may be responsible for the reduced PR expression in PT and HYP, and may contribute to the antiovulatory effect of ON. We therefore conclude that the mechanism of the antiovulatory potency of progesterone antagonists is based on a reduced preovulatory P4-production and PR expression in the ovary and also on the down-regulation of PR in the anterior pituitary and hypothalamus.

Animals↗
PubMed2000

Ability of xeno- and phytoestrogens to modulate expression of estrogen-sensitive genes in rat uterus: estrogenicity profiles and uterotropic activity.

The function of the uterus is regulated by female sex steroids and it is, therefore, used as the classical target organ to detect estrogenic action. Uterine response to estrogens involves the activation of a large pattern of estrogen-sensitive genes. This fact offers the opportunity to analyze the estrogenic activity of xeno- and phytoestrogens, and the mechanisms of their molecular action by a correlation of the uterotropic activity and their ability to modulate the expression of estrogen-sensitive genes. We have analyzed the expression of androgen receptor (AR), progesterone receptor (PR), estrogen receptor (ER), clusterin (CLU), complement C3 (C3), and GAPDH mRNA in the rat uterus following oral administration of ethinylestradiol (EE), bisphenol A (BPA), o,p'-DDT (DDT), p-tert-octylphenol (OCT) and daidzein (DAI). A significant stimulation of the uterine wet weight could be observed after administration of all the substances. The activity of all analyzed compounds to stimulate uterine weight was low in comparison to EE. DDT has the highest activity to stimulate uterine weight whereas BPA and DAI turned out to be less potent. The analysis of gene expression revealed a very specific profile of molecular action in response to the different compounds which cannot be detected by judging the uterotropic response alone. A dose dependent analysis revealed that C3 mRNA is already modulated at doses where no uterotropic response was detectable. Although DAI and BPA were very weak stimulators of uterine growth, these substances were able to alter the expression of AR, ER and C3 very strongly. Based on these investigations the analyzed compounds can be subdivided into distinct classes: First, compounds which exhibit a similar gene expression fingerprint as EE (e.g. OCT); second, compounds exhibiting a significant uterotropic activity, but inducing a pattern of gene expression different from EE (e.g. DDT); and third, compounds like BPA and especially DAI which exhibit a very low uterotropic activity, but nevertheless modulate the expression of estrogen-sensitive genes. These findings strongly suggest that the fingerprint of uterine gene expression is a very sensitive tool to investigate estrogenicity of natural and synthetic compounds and offers the possibility to get information in regard to the molecular mechanisms involved in the action of the respective compounds.

Animals↗
PubMed2000

Treatment with the pure antiestrogen faslodex (ICI 182780) induces tumor necrosis factor receptor 1 (TNFR1) expression in MCF-7 breast cancer cells.

Apoptosis induction by the pure antiestrogen faslodex, also known as ICI 182780 (ICI), is associated with an effective down-regulation of Bcl-2 expression in the human breast cancer cell line MCF-7. Recent observations point out that beside members of the Bcl-2 family also the TNFR1 signaling pathway may be involved in apoptosis induction by antiestrogens. In this report we have analyzed the expression of members of the TNFR1 signaling pathway during the apoptotic process induced by the pure antiestrogen faslodex and by tamoxifen (Tam) in MCF-7 breast cancer cells. Treatment with 10(-7) M ICI or 10(-7) M Tam leads to a time dependent increase of TNFR1 and TRADD steady-state mRNA levels in MCF-7 cells. In contrast, Bcl-2 expression was strongly decreased following administration of ICI but only weakly after administration of Tam. Western blot analysis and studies by the use of fluorescence microscopy and flow cytometry revealed a time dependent induction of TNFR1 protein and cell surface expression in MCF-7 cells in response to treatment with ICI. To investigate if TNFR1 is functionally involved in apoptosis induction by antiestrogens, we tested whether TNFR1 blocking antibodies can counteract the growth inhibitory action of Tam and ICI. Coincubation of MCF-7 cells with antiestrogens (ICI or Tam) and blocking TNFR1 antibodies lead to an increase in cell viability. Our results provide evidence for a cross talk between the TNFR1 signaling pathway and antiestrogens during the process of apoptosis induction in MCF-7 breast cancer cells. The superiority of the pure antiestrogen ICI to induce apoptosis in MCF-7 cells may result from its capability to modulate the induction of apoptosis via Bcl-2 as well as TNF-associated signal transduction pathways.

Antigens, CD↗
PubMed2000

Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: a quantitative model.

The lipase from Pseudomonas cepacia represents a widely applied catalyst for highly enantioselective resolution of chiral secondary alcohols. While its stereopreference is determined predominantly by the substrate structure, stereoselectivity depends on atomic details of interactions between substrate and lipase. Thirty secondary alcohols with published E values using P. cepacia lipase in hydrolysis or esterification reactions were selected, and models of their octanoic acid esters were docked to the open conformation of P. cepacia lipase. The two enantiomers of 27 substrates bound preferentially in either of two binding modes: the fast-reacting enantiomer in a productive mode and the slow-reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting enantiomers was prohibited by repulsive interactions. For the slow-reacting enantiomers in the productive binding mode, the substrate pushes the active site histidine away from its proper orientation, and the distance d(H(N epsilon) - O(alc)) between the histidine side chain and the alcohol oxygen increases, d(H(N epsilon) - O(alc)) was correlated to experimentally observed enantioselectivity: in substrates for which P. cepacia lipase has high enantioselectivity (E > 100), d(H(N epsilon) - O(alc)) is >2.2 A for slow-reacting enantiomers, thus preventing efficient catalysis of this enantiomer. In substrates of low enantioselectivity (E < 20), the distance d(H(N epsilon) - O(alc)) is less than 2.0 A, and slow- and fast-reacting enantiomers are catalyzed at similar rates. For substrates of medium enantioselectivity (20 < E < 100), d(H(N epsilon) - O(alc)) is around 2.1 A. This simple model can be applied to predict enantioselectivity of P. cepacia lipase toward a broad range of secondary alcohols.

Alcohols↗
PubMed2000

Female pseudohermaphroditism caused by caudal dysgenesis.

We report on two cases of female pseudohermaphroditism associated with anorectal, Müllerian duct, and urinary tract malformations. We suggest that this form of female pseudohermaphroditism is an extreme manifestation of the caudal type of VATER association.

Adult↗
PubMed2000

Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden: variable frequencies found in a multicenter serological study.

Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.

Adolescent↗
PubMed1999

Heartburn treatment in primary care: randomised, double blind study for 8 weeks.

OBJECTIVE: To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. DESIGN: Randomised, double blind, placebo controlled study. SETTING: 65 primary care practices in Norway. PARTICIPANTS: 483 untreated patients with complaints of heartburn >/=3 days a week, with at most grade 1 reflux oesophagitis. INTERVENTIONS: Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. MAIN OUTCOME MEASURES: Adequate control of heartburn, defined as </=1 day of the past 7 days with no more than mild heartburn, after 4 weeks of treatment. RESULTS: In the all patients treated analysis, adequate control of heartburn was achieved in 71% of patients taking omeprazole, 22% taking cisapride, and 18% taking placebo after 4 weeks of treatment (omeprazole v cisapride and placebo, P<0.0001; cisapride v placebo, non-significant). Results were comparable in patients with or without reflux oesophagitis. In patients treated with omeprazole only, symptom control was achieved significantly more often in patients positive for Helicobacter pylori. Antacid use was 2-3 times greater in patients taking cisapride or placebo than in those taking omeprazole. Relief of non-reflux symptoms did not significantly differ between the three groups. Significantly more patients taking cisapride reported adverse events than those taking omeprazole or placebo. CONCLUSIONS: Omeprazole 20 mg once daily was highly effective in relieving heartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo.

Anti-Ulcer Agents↗
PubMed1999

[Use of open MRI in head-neck surgery].

The vertical open MRI (Signa SP, 0, 5 Tesla) is ideal for interventional diagnosis and therapy. From our point of view indications in Otorhinolaryngology are biopsies of tumours which are difficult to access such as the petrous apex and the petroclival region, the parapharyngeal space and neck and the orbit. Furthermore the open MRI is useful in the surgery of paranasal sinuses, in the evaluation of tissue-resection and helpful in detection of the anatomy of delicate structures as the internal carotid artery, the skull-base and the orbit. Also navigation in open MRI is possible for example with a flash-point-system. The advantage to conventional navigation systems is the possibility of real-time-imaging, which allows detection of tissue shift occurring during the procedure. We report about our experience with ten biopsies of the petrous apex and the petroclival junction and two biopsy of the parapharyngeal space and the neck. Further experience was gained with MR guided placement of afterloading tubes into large neck metastases in three cases and microscopic surgery of paranasal sinuses in five cases. In all operative procedures an excellent resolution was found especially for soft tissue structures as for example blood vessels. With the aid of special pointer systems or artefacts by surgical instruments all relevant anatomical structures could be detected intraoperatively, concerning normal and pathologic tissue. Thus open MRI proved to be a helpful instrument in these operative procedures.

Adult↗
PubMed1999

[Brain tumor resections in an open 0.5-T MRT. 2 years' experiences from the neuroradiological viewpoint].

After two years clinical experience using an open 0.5 T-MRI, which make it possible to control all steps of a brain tumor resection, the high expense in relation to the effect is proofed. In 80 MRI-guided brain tumor resections the indication, the degree of resection, the appearance of operative induced changes, complications and clinical state are analysed. The advantage of the method consists in safety of localisation and detection especially of intra-axial cerebral tumors, recording of intraoperative invisible tumor parts and saving eloquent areas during tumor resection. To have optimal results, all over the operation time, the participation of a special experienced radiologist is necessary. The best results are shown in treatment of low grade gliomas and tumors near eloquent areas.

Astrocytoma↗
PubMed1999

Open MR imaging in spine surgery: experimental investigations and first clinical experiences.

INTRODUCTION: The latest open MRI technology allows to perform open and closed surgical procedures under real-time imaging. Before performing spinal trauma surgery preclinical examinations had to be done to evaluate the artifacts caused by the implants. METHODS: The MRT presented is a prototype developed by GE. Two vertically positioned magnetic coils are installed in an operation theater. By that means two surgeons are able to access the patient between the two coils. Numerous tests regarding the material of instruments and implants were necessary in advance. The specific size of the artifact depending on the pulse sequence and the positioning within the magnetic field had to be examined. RESULTS: The magnifying factors of the artifact in the spin echo sequence regarding titanium are between 1.7 and 3.2, depending on the direction of the magnetic vector. Regarding stainless steel they are between 8.4 and 8.5. In the gradient echo sequence the factors are between 7.5 and 7.7 for titanium and between 16.9 and 18.0 for stainless steel. The tip of an implant is imaged with an accuracy of 0 to 2 mm. Since September 1997 16 patients with unstable fractures of the thoracic and lumbar spine have been treated by dorsal instrumentation in the open MRI. Percutaneous insertion of the internal fixator has proven a successful minimally invasive procedure. The positioning of the screws in the pedicle is secure, the degree of indirect reduction of the posterior wall of the vertebral body can be imaged immediately. The diameter of the spinal canal can be determined in any plane. DISCUSSION AND CONCLUSION: The open MRI has proven useful in orthopedic and trauma surgery. The size and configuration of the artifacts caused by instruments and implants is predictable. Therefore exact positioning of the implants is achieved more easily. Dorsal instrumentation of unstable thoracolumbar fractures with a percutaneous technique has turned out safe and less traumatic under MR-imaging. Real-time imaging of soft tissue and bone in any plane improves security for the patient and allows the surgeon to work less invasively and more precisely.

Artifacts↗
PubMed1999

Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis.

Environmental and genetic factors are thought to interact in the manifestation of psoriasis, but knowledge about the involved genes and antigens is incomplete. This study has focused on the association between psoriasis and inherited variations in xenobiotic metabolism and cytokine production as two components that may influence cutaneous immune responses to foreign substances. Polymorphisms of N-acetyltransferase 2, glutathione S-transferases T1 and M1, and promoter polymorphisms of the genes encoding for tumor necrosis factor-alpha and interleukin-10 were investigated in 151 Caucasian patients with psoriasis (100 with type I and 51 with type II psoriasis) and in 123 healthy controls. Polymorphisms were detected by polymerase chain reaction-based methods, restriction enzyme analysis, and direct sequencing. There were no significant differences in the distribution of enzyme polymorphisms or point mutations at position -1082 of the interleukin-10 promoter between the psoriasis groups and the control group. The G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter (TNF alpha-238*A allele) was more common in type I psoriasis (27%) than in the controls [9.8%; odds ratio 3.4 (95% confidence interval 1.6-7.2); p = 0.0012; pcorr = 0.018]. Surprisingly, this overrepresentation of the tumor necrosis factor alpha-238*A allele was observed in male patients [4.1 (1.5-11.0); p = 0.0046; pcorr = 0.064] but not in female patients [1.8 (0.5-6.5); p = 0.5]. The G-->A polymorphism at position -308 of the tumor necrosis factor-alpha promoter was less frequent in type I psoriasis (23%) compared with controls (35.7%), although the negative association was weak [0.54 (0.3-0.97); p = 0.041; pcorr = not significant]. The distribution of the TNF alpha-238*A and TNF alpha-238*A alleles was similar in type II patients and controls. Our results suggest that male carriers of the G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter are at an increased risk to develop early-onset psoriasis.

Adolescent↗
PubMed1999

[MR-track pointer. A reusable device for localization during interventions].

PURPOSE: Development of an helpful instrument for a better planning and orientation during MR guided interventions. MATERIAL AND METHODS: We developed a reusable, sterilizable instrument that can be filled both with a solution of Gd-DTPA (1%) and with a sodium chloride solution (0.9%). The pointer has a diameter of 3 and 5 mm resp. and its length is 100-150 mm. The instrument can be combined with an interactive stereotactic tracking device. RESULTS: The MR-Track-Pointer can be fixed to the two handpieces of the integrated interactive tracking system without problems. The pointer can be seen both on T1w and T2w sequences inside and outside of the tissue. This new instrument can be interactively used for reliable planning the biopsy trajectory, planning craniotomies and identifying structures which are only visible on MR images. CONCLUSIONS: The MR-Track-Pointer is an ideal supplement for the integrated virtual tracking system. It permits a minimal invasive orientation and facilitates the exact localisation of suspect lesions in sensible regions during MR guided interventions, e.g. diagnostic biopsies and tumour resections.

Biopsy↗
PubMed1999

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell.

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.

Adult↗