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Biomedical subjects

H Schüller

Publications and source records attributed to H Schüller.

At least 19 recordsLinked to original sources

Expression of ABC-1 transporter is elevated in human glioma cells under irradiation and temozolomide treatment.

OBJECTIVE: Chemo-therapeutic treatment of glioma patients has minor success. Little is known about mechanisms of a pronounced resistance of gliomas towards actual therapies, yet. ABC-1 belongs to the group of transporters known to be involved in the export of hydrophobic substances and vascular regulation. This study investigates an effect of both temozolomide (TMZ) treatment and/or irradiation on the expression of the ABC-1 transporter in human U87-MG glioma cells. MATERIAL AND METHODS: In parallel experiments U87-MG cells underwent either irradiation (RT), chemo-treatment (CT) using TMZ, and combined chemo/radiation-treatment (CT/RT). After each treatment the cells were incubated either 2 or 24 hours at 37 degrees C and counted before protein analysis using Western-Blot technique. RESULTS AND CONCLUSIONS: An exponential growth of cellular density was observed for both untreated and irradiated cells being, however, about 2-times slower in irradiated compared to untreated cells. In contrast the density increase of chemo-treated cells as well as that of cells, which underwent the combined CT/RT treatment was of linear nature. ABC-1 expression was detected in untreated as well as treated cells. Increasing cell density and all kinds of treatment resulted in a considerably enhanced ABC-1 expression. CT treatment resulted in highly up-regulated ABC-1 expression especially in non-confluent cultures compared to untreated cells. Irradiation had a comparable or even higher inducible effect on the ABC-1 expression rates depending, however, on cell density. The highest expression rates were observed in cultures with high cellular density 2 hours after application of the combined treatment. Strong up-regulation of ABC-1 expression under both irradiation and chemo-treatment might be a clue to multidrug and irradiation cross-resistance mechanisms of malignant glioma cells converting the ABC-1 transporter into an attractive pharmacological target for a clinical breakthrough in the therapy of malignant gliomas.

ATP-Binding Cassette Transporters↗

Malignant thymoma: current status of classification and multimodality treatment.

Classification, understanding of the pathophysiology, and treatment options of thymoma have changed during recent years. It is hoped that novel strategies will lead to a survival benefit in these patients. It has become clear that patients with thymoma are best treated with multimodality therapy. In this review, a pathologist, an immunologist, a surgeon, a radiotherapist, a pneumologist, and oncologists discuss the current status of classification and strategies for the treatment of patients with thymoma.

Clinical Trials as Topic↗

Magnetic resonance imaging analysis of anterior and posterior eye segment displacement during ocular gaze shifts.

PURPOSE: To determine the relationship between movements of the posterior and anterior eye segments during arbitrary gaze shifts and to obtain information for monitoring fixation during radiotherapy for ocular diseases. METHODS: We examined eye movements of ten emmetropic volunteers in a 1.5 T magnetic resonance system. Using a T2-weighted ultrafast turbo-spin echo sequence (UTSE), the eyes were examined within 21 seconds. Sagittal and transversal eye slices were obtained in five passages in five gaze directions (straight ahead, 15 degrees above, 15 degrees below, 15 degrees right and 15 degrees left of the primary position). Displacement of the posterior eye segment was analyzed in relation to the movement of the anterior segment in all directions. RESULTS: The relationship between the movements of the anterior and posterior eye segment was 1:0.8 (+/- 0.06 SD) during horizontal gaze shifts and 1:1.16 (+/- 0.11 SD) during vertical gaze shifts. CONCLUSIONS: Magnetic resonance imaging showed that the relationship between anterior and posterior eye segments was different during horizontal and vertical eye movements, indicating the presence of more than one center of rotation. Compared to the anterior eye segment, there was less displacement of the posterior eye segment during horizontal eye movements and more displacement during vertical eye movements.

Adult↗

[1H-MR Spectroscopy of brain tumors in the course of radiation therapy: Use of fast spectroscopic imaging and single-voxel spectroscopy for diagnosing recurrence].

PURPOSE: To improve differential diagnosis of residual or recurrent tumor vs. tissue necrosis in the course of radiation therapy of neurosurgically-treated brain tumors by application of fast (1)H-MR spectroscopic imaging in combination with single-voxel spectroscopy (SVS). METHODS: 54 patients after with malignant brain tumor (44 cases of glioblastoma, 10 other high-grade gliomas) were examined post-surgically in a total of 140 proton MRS examinations in the course of radiotherapy and in follow-up controls. Fast SI acquisition was performed as single-slice or double-slice TSI sequence with 32 x 32 phase encodings within 11 or 15 minutes, respectively. SVS with TR/TE 2000/272 ms yielded relative metabolite ratios, and in 15 patients the time courses of the absolute concentrations of brain metabolites were also determined. RESULTS: In the group of 44 patients that could be tracked by MRS until therapy completion, TSI localized in 23 patients a persistent or newly arisen distinct choline accumulation indicating residual or recurrent tumor after radiation therapy. In all these cases MRS diagnosis was confirmed histologically or by short-term follow-up. However, in 6 of 15 patients showing a normal choline pattern in the TSI acquisition, tumor recurrence appeared within three months. SVS provided early recognition of recurrent tumor when detecting characteristic alterations of metabolite concentrations oin therapy follow-up. CONCLUSION: TSI and SVS represent complementary MRS techniques and are able to diagnose tumor recurrence early and unambiguously in cases where focal choline accumulation is detected.

Adult↗

External beam radiotherapy for age-related macular degeneration causes transient objective changes in tear-film function.

PURPOSE: Dry-eye symptoms have been described as possible radiation side effects after external beam radiotherapy for age-related macular degeneration. We therefore investigated tear-film function before and after treatment. METHODS: Thirty-nine patients with no apparent history of dry-eye symptoms were treated with a 6 MV linear accelerator using a 2x2 cm lateral field angled 10 degrees posteriorly. A total dose of 20 Gy, divided into 10 fractions of 2 Gy and administered 3 times a week, was delivered. Before and 1, 3, and 6 months after radiotherapy, tear secretion was measured by means of tear-film fluorophotometry. The fellow eyes served as controls. RESULTS: At baseline, mean tear secretion as measured by tear-film fluorophotometry was 7.15 microl/min in the eyes receiving radiation and 5.89 microl/min in the control eyes. No statistically significant differences were found between the two eyes at baseline (signed rank test). One month after treatment, again no significant differences could be found between the two eyes; 3 months after radiation, however, tear secretion was significantly lower in the irradiated eyes than in the fellow eyes (P=0.0017). Six months after treatment this effect could no longer be detected. CONCLUSION: External beam radiotherapy using 20 Gy in 10 fractions and a 2x2 cm lateral field causes a statistically significant difference in tear secretion 3 months after radiation. This effect seems to be transient, as it had disappeared in later follow-up examinations.

Dose Fractionation, Radiation↗

Radiotherapy for age-related macular degeneration: is there a benefit for classic CNV?

AIM: To evaluate the efficacy of radiotherapy in the treatment of subfoveal classic and occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD) under strict fixation control. METHODS: Twenty-seven eyes of 27 patients with subfoveal CNV as a result of AMD were treated with a total dose of 20 Gy in 10 fractions (10 well-defined, 17 occult). Fixation monitoring was achieved by installing a TV camera with an attached fixation light 3 cm from the cornea of the eye being treated. Visual acuity and fluorescein angiography were obtained before and 6 months after treatment. Fifteen eyes of 15 patients served as controls (4 well-defined, 11 occult). RESULTS: After 6 months the treated group showed an average decrease in visual acuity of 27%; the control group experienced a decrease of 31%. Membrane size increased by 56% in the treated group and by 28% in the control group. There was no statistically significant difference. Within the subgroup analysis, however, patients with classic CNV suffered significantly less visual loss than in the control group. CONCLUSION: Radiation therapy under optimized treatment conditions by fixation monitoring failed to control further growth in membrane size in both classic and occult CNV. Regarding visual acuity, however, patients with classic CNV seem to benefit from radiation treatment compared to the natural course.

Adolescent↗

Combipolar sensing in dual chamber pacing: is there still a need for bipolar leads in the atrium?

Bipolar leads have been shown to provide superior sensing conditions compared to unipolar leads as bipolar sensing is less susceptible to interference. However, the mechanical long-term integrity and longevity of bipolar leads is inferior to that of unipolar leads. A prospective randomized, multicenter study was performed to investigate a new atrial detection configuration called combipolar sensing. This new sensing concept is designed for the use of conventional unipolar leads in the atrium and the ventricle. While the atrial stimulation is unipolar, atrial sensing is accomplished in a bipolar way using the ventricular lead tip as the indifferent electrode. A modified dual chamber pacemaker provided with this sensing concept was implanted in 26 patients. At predischarge and at the 1- and 3-month follow-ups no significant differences in atrial sensing thresholds and P wave amplitudes were found between the unipolar and the combipolar sensing configuration at rest or during provocation. Myopotential inhibition could be demonstrated in 22 patients during unipolar sensing at sensitivity settings as "low" as 2 mV. In contrast, during combipolar sensing it could only be demonstrated in one patient once and only at the highest atrial sensitivity of 0.5 mV. Combipolar atrial sensing is feasible under normal conditions and during provocation. Myopotential interference is negligible. Thus, combipolar sensing offers comparable atrial sensing to bipolar without the disadvantages of a bipolar lead.

Adolescent↗

Threshold tracking pacing based on beat by beat evoked response detection: clinical benefits and potential problems.

Continuous monitoring of pacemaker stimulation thresholds and automatic adjustment of pacemaker outputs were among the longstanding goals of the pacing community. The first clinically successful implementation of threshold tracking pacing was the Autocapture feature which has accomplished automatic ventricular capture verification for every single stimulus by monitoring the Evoked Response (ER) signal resulting from myocardial depolarization. The Autocapture feature not only decreases energy consumption by keeping the stimulation output slightly above the actual threshold, but also increases patient safety by access to high-output back-up pulses if there is loss of capture. Furthermore, it provides valuable documentation of stimulation thresholds over time and serves as a valuable research tool. Current limitations for its widespread use include the requirements for implantation of bipolar low polarization leads and unipolar pacing in the ventricle. Fusion/pseudofusion beats with resultant insufficient or even non-existent ER signal amplitudes followed by unnecessary delivery of back-up pulses and a possible increase in pacemaker output is not an uncommon observation unique to the Autocapture feature. The recent incorporation of the Autocapture algorithm in dual chamber pacemakers has been challenging because of more frequent occurrence of fusion/pseudofusion beats in the presence of normal AV conduction. Along with a review of the previously published studies and our clinical experience, this article discusses the clinical advantages and potential problems of Autocapture.

Algorithms↗

Radiotherapy for age related macular degeneration causes transient lens transparency changes.

AIM: Evaluation of potential side effects of photon radiotherapy on the transparency of the lens. METHODS: The anterior segments of 14 phakic eyes from patients suffering from subfoveal neovascularisation as a result of age related macular degeneration (AMD) were documented by Scheimpflug photography (Topcon SL-45, Kodak Tmax 400) before the start of radiotherapy as well as 6 and 12 months afterwards. All negatives were evaluated by microdensitometry, and peak heights for distinct layers of the lens were used for statistical comparison. External beam radiotherapy (6 MeV photons) consisted of a total dose of 20 Gy, delivered as 10 fractions of 2 Gy. RESULTS: Six and 12 months following irradiation statistical comparison of the ratios in density change of lenses from irradiated versus non-irradiated fellow eyes revealed statistically significant (p</=0.05) loss of transparency of layers 5 and 7 of the nuclear region. In layer 1 (capsuloepithelial complex) the changes were close to significance. At the 12 month examination, however, all of these significant changes had disappeared. CONCLUSION: Six months following radiotherapy for AMD, both the anterior capsuloepithelial region and the nuclear layers showed precataractous changes. As most of these significant differences had disappeared after 12 months, it is obvious that these findings reflect acute radiation damage to the lens epithelial cells and an ionising effect on the proteins of the lens nucleus. Long term studies will have to be carried out to demonstrate whether or not this acute radiation damage, which is expressed as a transient increase in light scattering of some layers of the lens, actually does lead to permanent transparency changes, thus reflecting radiation cataractogenesis, and if so, after what time interval and to what extent cataract occurs.

Aged↗

Magnetic resonance imaging to detect bone marrow metastases in the initial staging of small cell lung carcinoma and breast carcinoma.

BACKGROUND: Bone marrow is a common site of metastases in patients with small cell lung carcinoma (SCLC) and female breast carcinoma (FBC). Metastatic bone marrow involvement is found in approximately 50% of SCLC patients and up to 85% of FBC patients at autopsy. Initial staging procedures detect malignant bone marrow lesions in only 2-30% of patients with these tumors. This study was performed to assess whether MRI can improve the detection rate of bone marrow metastases in tumors with a high incidence of skeletal involvement. METHODS: Fifty-two patients with histologically verified SCLC (25 with limited stage disease and 27 with extensive stage disease) and 33 women with FBC were entered into a prospective study. The MRI protocol was comprised of coronal slices in the pelvic region and sagittal slices of the whole spine utilizing a T1-weighted spin echo sequence with a field of view of 50 cm. All patients underwent initial routine diagnostic staging procedures including bone scintigraphy, unilateral crest biopsy, and plain film radiography of suspicious skeletal areas. RESULTS: Only in two SCLC patients, MRI was positive in 25 cases. All SCLC patients with bone marrow lesions histologically verified, diagnosed by crest biopsy (six patients) or by bone scan (seven patients) had the correct diagnosis of metastases by MRI. In addition MRI revealed hypointense bone marrow foci in 14 cases. In contrast, 28 of 33 FBC patients examined during the initial staging procedure showed no evidence of bone marrow involvement. MRI was not superior compared with bone scintigraphy in FBC patients. CONCLUSIONS: The staging results obtained in SCLC and FBC patients are different, although both tumors have a high incidence of bone marrow metastases. It may be assumed that the biologic behavior of these tumors is reflected by the initial bone marrow involvement. Because of its superiority compared with biopsy and bone scan, the authors believe MRI should become an integral part of the initial staging procedures in patients with SCLC. When staging patients with FBC, MRI should be applied only in clinically indicated cases.

Bone Marrow Neoplasms↗

X-ray diagnosis of impacted upper canines in panoramic radiographs and computed tomographs.

Ten orthodontists were asked to diagnose the number of impacted upper canines and the number of resorbed lateral and/or central incisor roots in 30 panoramic radiographs (P1) from 30 patients. In order to objectify these diagnoses, transversal CT images of all 30 patients were examined in addition. Addition of the recordings in the 30 patients revealed that the 10 orthodontists had diagnosed 350 impacted/displaced canines. On comparison of the P1 and CT results, the latter revealed that, in fact, 390 canines were impacted or displaced, not just 350. Addition of the recordings further showed that, based on P1, the investigators had diagnosed 73 resorptions in the 1,200 incisors examined. However, the CT showed 160 resorptions; this corresponds to a sensitivity value of 45.6%. The CT showed 1,040 incisors with no resorptions, whereas the investigators diagnosed only 925 teeth as not resorbed in the P1. The specificity was thus 88.9%. These results show that, due to their low reliability, panoramic radiographs are not an appropriate means of diagnosing resorptions in front teeth in connection with impacted canines.

Adolescent↗

Low-energy epicardial pacing in children: the benefit of autocapture.

BACKGROUND: Permanent cardiac pacing in children results commonly in augmented energy consumption because of the high pacing rates and the ample stimulation safety margin applied in children. Cardiovascular anatomy and limited venous access sometimes preclude the otherwise preferred endocardial approach. In this multicenter patient series, we studied the feasibility, safety, and energy saving obtained by a combination of steroid-eluting epicardial leads with autocapture devices capable of ongoing adjustment of the stimulation output to the prevailing threshold. METHODS: Autocapture devices (Pacesetter Microny SR+/- and Regency SR+/-; Pacesetter, Solna, Sweden) and steroid-eluting epicardial pacing leads (Medtronic CapSure Epi 10366; Medtronic, Inc, Minneapolis, MN) were implanted in 14 children. Thresholds, telemetry data, evoked response, and polarization signals were obtained at discharge and follow-up, and battery service life was calculated. RESULTS: During a median follow-up of 6.5 months, autocapture pacing was applied in 12 of 14 children. The automatically adjusted pulse amplitude of autocapture devices demonstrated low-energy pacing with no significant changes between discharge and 6 months follow-up (1.1 +/- 0.3 versus 0.9 +/- 0.3 V). Autocapture-programmed pacemakers had calculated life spans of 7.8 +/- 1.4 years (Microny) and 21.0 +/- 1.6 years (Regency). No adverse effects were noted. CONCLUSIONS: Autocapture-controlled pacing with bipolar epicardial pacing leads is feasible and safe in children. Autocapture programming results in substantial energy savings and extends battery life markedly.

Child↗

Recombinant human thyrotropin in thyroid cancer and hypopituitarism due to sella metastasis.

We present a patient with thyroid cancer and hypopituitarism who required recombinant human thyrotropin (rhTSH) for 131I scanning with respect to subsequent therapy. The thyroid cancer had been unknown until central neurological symptoms developed, leading to the diagnosis of a huge metastasis to the sella that was the only manifestation of metastatic spread. The failure to generate endogenous thyrotropin (TSH) was overcome by the use of rhTSH for performing a 131I test. Unfortunately, the 131I uptake was not sufficient for therapy. This subject is the first reported case who required the application of rhTSH due to a single thyroid cancer metastasis in the sella region with secondary failure to generate endogenous TSH.

Aged↗

Assessment of the space for the lower wisdom teeth. Panoramic radiography in comparison with computed tomography.

From 13 patients a computed tomograph (CT-scan) and a panoramic radiograph (Orthophos, program 1, P1) were examined with respect to the spatial conditions of the lower wisdom teeth. In the panoramic radiograph the available space for the third molars of the lower jaw was determined by calculating the ratio (Q) of 2 distances: the mesiodistal crown diameter and the retromolar space. In the axial CT 3 different positions of the third molar were distinguished: third molar located anterior to the ramus mandibulae = sufficient space, partially within the ramus = restricted space, totally within the ramus = deficient space. These positions were compared with the findings in the panoramic radiograph, firstly in relation to the ramus and secondly in relation to a line (L) perpendicular to the occlusal plane at the intersection of the anterior border of the ramus and the crista temporalis. Furthermore, the mesial rotation of the third molar was measured and the relation of the bony structures surrounding the teeth were described. Comparison of the CT results with the quotients of the P1 showed that, for those wisdom teeth molars with an available space above 50% to under 100%, any of the 3 CT gradings was found. Assessing the projection of the ramus over the third molar as seen in the P1, 60% of the P1- and CT-results corresponded. The relation between the line L and the third molar showed coincidence in 76% of all cases. These results and the mesial rotation of the wisdom teeth as well as their different relation to the bony environment are possibly important factors concerning their eruption prognosis. The three-dimensional CT-scan gives new possibilities for further investigations of third-molar problems.

Adolescent↗