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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 55 records · Page 3Linked to original sources

Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.

Adult↗

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗

Restoration of pinch grip in ulnar nerve paralysis: extensor carpi radialis longus to adductor pollicis and abductor pollicis longus to first dorsal interosseus tendon transfers.

A double tendon transfer was used to restore thumb pinch in nine consecutive patients. The extensor carpi radialis longus was transferred to the adductor pollicis tendon and one slip of the abductor pollicis longus was transferred to the first dorsal interosseus tendon. The patients were followed for 6 (range, 2-10) years and there were no instances of transfer rupture. Selective recruitment of the motors of the transfers was possible in all cases. Their amplitude was considered adequate for all the cases of adductor transfers but was limited in all of the first dorsal interosseus ones. Key pinch was 73% (range, 41-104%), the pulp-to-pulp pinch was 72% (range, 50-95%) and the power grip was 73% (range, 35-91%) of the opposite hand. The force of thumb adduction was 63% (range, 27-132%) and of index finger abduction was 58% (range, 21-104%) of the unaffected side.

Adult↗

[Medical care research based on family doctor routine data--are interface-communicated treatment data feasible?].

AIMS OF THE STUDY: As part of an ongoing project on the utilisation of generic drugs in general practice we aimed at determining whether the transfer of prescriptions and patient characteristics from doctors' computerized medical records via the BDT (Behandlungsdatenträger) interface was feasible, and whether these data are suitable for research in pharmacoepidemiology. METHODS: All 1,395 general practitioners from 6 regions in Germany were invited to participate in the 'generics project'; 232 (17 %) agreed. The 17 software companies whose systems were used by the participating practices were asked to grant access to the BDT interface. For a prescription survey, doctors were supposed to export BDT files from two 3-month periods each in 2000 and 2001. Data were anonymised and relevant information extracted with a special programme. RESULTS: So far, BDT data are available from 79 practices. They are suitable for practice- and patient-related prescribing analyses. By filter modifications, additional information (such as diagnoses, referrals, clinical findings or accounting codes) can be obtained. The procedure was well accepted if doctors and practice staff were assisted by computer experts. Some difficulties, however, were encountered in obtaining access to the BDT-interface from the software companies. Lack of standardisation of the BDT interface required additional conditioning of the data. CONCLUSION: The BDT interface offers an opportunity to export computerised patient records without the requirement of additional documentation. If routine data are more readily available for health services research, a standardised data structure and open access must be assured e. g. by centralised certification via the Federal statutory health organisation.

Data Collection↗

[Dose reduction through gridless technique in digital full-field mammography].

PURPOSE: To determine the role of the scatter grid in digital full-field mammography with respect to image quality and dose and to compare the experimental results with initial clinical experience. MATERIALS AND METHODS: A phantom consisting of 205 fields that enclose gold dots of different thickness and size (CD-Mam phantom, Medical Department, Nijmegen, Netherlands) was used for digital full-field mammography with the conventional grid module and a special gridless module. Four different breast thicknesses were simulated using Plexiglas as scatter material. First, the phantom was exposed at the parameter and dose settings automatically selected in each experimental setup (with and without grid). Subsequently, the phantom was exposed at the different simulated breast thicknesses using the gridless module in combination with the parameters automatically selected for the grid module. This was followed by a series of phantom mammograms obtained with the experimental setup reversed. The 16 mammograms were evaluated by 3 readers and the results compared considering breast thickness, radiation dose, and quality. The gridless module was used for preoperative labeling in 16 patients for comparison of mammograms obtained with and without a grid. RESULTS: For the same entrance dose used in routine mammography, digital mammography without grid is superior to digital mammography with grid when performed on simulated thin breasts (Plexiglas less than 3 cm), with no difference found when performed on simulated large breasts. The advantages of gridless mammography are more pronounced at a markedly reduced entrance dose (identical parenchymal dose without and with grid using the dose automatically selected for the gridless module). This tendency is confirmed by the initial clinical comparison. CONCLUSION: Gridless digital full-field mammography has the potential to reduce the dose further, in addition to already known mechanisms of dose reduction. However, the gridless system must be adjusted (markedly higher "switch-off dose" at the detector) to achieve an overall dose reduction since gridless mammography is inferior to grid mammography for identical doses at the detector plane.

Artifacts↗

[Sacroiliitis in children with spondyloarthropathy: therapeutic effect of CT-Guided intra-articular corticosteroid injection].

PURPOSE: The prospective investigation of the therapeutic effect of CT-guided intra-articular corticosteroid injection into inflammatory sacroiliac (SI) joints compared to conventional treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) in children with juvenile spondyloarthropathy (jSpA) and the determination of the role of dynamic magnetic resonance imaging (MRI) in establishing the indication and monitoring the therapy. MATERIALS AND METHODS: The study comprises 89 children with known jSpA who were diagnosed by MRI to have a unilateral or bilateral sacroiliitis. Therapy with NSAIDS was initiated or continued in all 89 patients. Four weeks after the diagnostic MRI, two groups were distinguished according to the clinical response to NSAIDS, with group 1 consisting of 33 responders and group 2 of 56 non-responders. The patients of group 2 were treated with CT-guided intra-articular corticosteroid injection (low-dose injection) while the therapy with NSAIDS was continued. A total of 83 SI joints were punctured without complications, 27 bilaterally and 29 unilaterally. The indication for the intervention was based on inflammatory activity as determined by MRI. The therapy was monitored by clinical follow-up every 8 to 12 weeks over a period of 20 months. Follow-up by dynamic MRI was performed in all 56 children of group 2 and in 15 of the 33 children of group 1 within 8 +/- 4 months of the initial examination. RESULTS: A total of 87.5% of the children in group 2 showed a statistically significant decrease in their subjective complaints from 6.9 +/- 3.4 to 1.8 +/- 1.7 (p < 0.05) as measured on a visual analog scale (VAS from 0 to 10). Improvement was seen as early as 1.5 +/- 1.0 weeks after the intervention and lasted for a mean of 12 +/- 6 months. The children in group 1 already showed similar improvement of the VAS from 6.8 +/- 3.2 to 1.5 +/- 1.4 (p < 0.05) during the initial four weeks of NSAIDS therapy, with the improvement lasting for the 20-month observation period. The follow-up dynamic MRI (0.1 mmol/kg body weight) during therapy showed a statistically significant lower contrast-enhancement in both groups (group 1: 117 +/- 43 % versus 38 +/- 24 %, p < 0.05; group 2: 127 +/- 59 % versus 38 +/- 22 %, p < 0.05). One third of the patients of group 2 showed progression of joint destruction despite absence of subjective complaints. CONCLUSION: CT-guided intra-articular corticosteroid injection has proven an effective, symptomatic, and uncomplicated therapy of acute sacroiliitis in patients with jSpA. Dynamic MRI has a role in establishing the indication for intervention but its role for any follow-up is restricted to cases with inconclusive clinical response.

Adolescent↗

[Functional MRI of the pelvic floor: postpartum changes of primiparous women after spontaneous vaginal delivery].

PURPOSE: Detection of morphological and functional changes of the pelvic floor with functional MRI in primiparous women after spontaneous vaginal delivery. METHODS AND MATERIALS: The study comprises 26 primiparous women after vaginal delivery and a control group of 41 healthy asymptomatic nulliparous volunteers. MRI was performed on a 1.5 T system in supine position with vagina and rectum opacified with Sonogel. The static images consisted of sagittal and axial T 2 -weighted SE sequences and functional images of true FISP sequences in midsagittal and axial planes acquired with the patient at rest, straining and during defecation. Evaluation of morphometric parameters included pelvimetry, thickness of the puborectal muscle and width of the urogenital hiatus as well as position and movement of the pelvic organs relative to the pubococcygeal reference line. RESULTS: The configuration of the bony pelvis did not differ for both groups. The puborectal muscle was significantly thinner in the study group (0.8 cm vs 0.6 cm). The functional images showed no significant differences between both groups at rest but a significantly increased incidence in the descent of the bladder neck, vaginal fornix and anorectal junction in the study group during straining. In addition, the primiparous women had more prominent rectoceles (0.6 cm vs 1.5 cm). CONCLUSION: Static imaging alone fails to demonstrate relevant pelvic floor changes and a functional method is necessary to evaluate the interactions of the pelvic organs regarding organ descent. Functional MRI of the pelvic floor is an excellent method to reveal the significant changes of the pelvic floor after vaginal birth without exposing the uterus to radiation.

Adult↗

Feedback on the motion of a single atom in an optical cavity.

We demonstrate feedback on the motion of a single neutral atom trapped in the light field of a high-finesse cavity. Information on the atomic motion is obtained from the transmittance of the cavity. This is used to implement a feedback loop in analog electronics that influences the atom's motion by controlling the optical dipole force exerted by the same light that is used to observe the atom. In spite of intrinsic limitations, the time the atom stays within the cavity could be extended by almost 30% beyond that of a comparable constant-intensity dipole trap.

Journal Article↗

Circulatory arrest and renal function in open-heart surgery on infants.

This study was designed to evaluate the impact of circulatory arrest on renal function in open-heart surgery on infants. Renal function was described by diuresis, urine/plasma creatinine ratio, creatinine clearance, urinary albumin, and N-acetyl-beta-D-glucosaminidase measurements. Seven patients who underwent circulatory arrest (group 1) were compared with 37 patients operated on with cardiopulmonary bypass without circulatory arrest (group 2). In group 1, bypass time was 164 minutes and the lowest body temperature was 25.6 degrees C (median), compared with 106 minutes and 31.3 degrees C in group 2 (p < 0.05). Although diuresis and creatinine clearance revealed no differences between the groups, urine measurements, which had normal values before cardiopulmonary bypass, increased during reperfusion to 58.6 (range 16.2-75.5) mg gCrea(-1) albumin and to 14.8 (range 1.6-21.8) U gCrea(-1) N-acetyl-beta-D-glucosaminidase in group 1, compared with 8.1 (range 0-127.7) mg gCrea(-1) and 1.9 (range 0-47.8) U gCrea(-1) in group 2 (p < 0.05). Thus, deep hypothermic circulatory arrest (DHCA) subjected the kidney to ischemia reperfusion injury. Although the findings are mild and do not indicate severe ischemic renal damage, potential renal damage by DHCA should be taken into account when planning surgical procedures for congenital heart disease patients with additional risks of acute renal failure.

Acute Kidney Injury↗

Optical kaleidoscope using a single atom.

A new method to track the motion of a single particle in the field of a high-finesse optical resonator is analyzed. It exploits sets of near-degenerate higher-order Gaussian cavity modes, whose symmetry is broken by the position dependent phase shifts induced by the particle. Observation of the spatial intensity distribution outside the cavity allows direct determination of the particle's position. This is demonstrated by numerically generating a realistic atomic trajectory using a semiclassical simulation and comparing it to the reconstructed path. The path reconstruction itself requires no knowledge about the forces on the particle. Experimental realization strategies are discussed.

Journal Article↗

Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging. A report from the Standardization Group of the European Society of Contact Dermatitis based upon the HIRELADO European community project.

This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

Humans↗

Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT).

We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT. At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP). Patients were evaluated for hematologic, cytogenetic and molecular response, survival and toxicity. In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses. Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response. Two of five patients had transient reductions in WBC and blasts, and three patients achieved a sustained hematologic response (>4 weeks). Cytogenetic analysis in these patients revealed numerical and/or structural responses. In CML chronic phase, STI-571 induced complete hematologic responses in all patients and major cytogenetic responses in 61% of patients with a complete cytogenetic response rate of 46%. This report indicates that STI-571 is a safe and effective drug in heavily pretreated patients. No apparent additional side-effects were noted in this patient cohort. The high rate of complete hematologic and complete cytogenetic responses in CP patients is remarkable, as intensive treatment approaches plus IFN-alpha failed to be efficient in achieving long-term stabilization of CML in this patient cohort.

Adult↗

[Detection of tibial condylar fractures using 3D imaging with a mobile image amplifier (Siemens ISO-C-3D): Comparison with plain films and spiral CT].

PURPOSE: To analyze a prototype mobile C-arm 3D image amplifier in the detection and classification of experimental tibial condylar fractures with multiplanar reconstructions (MPR). METHOD: Human knee specimens (n = 22) with tibial condylar fractures were examined with a prototype C-arm (ISO-C-3D, Siemens AG), plain films (CR) and spiral CT (CT). The motorized C-arm provides fluoroscopic images during a 190 degrees orbital rotation computing a 119 mm data cube. From these 3D data sets MP reconstructions were obtained. All images were evaluated by four independent readers for the detection and assessment of fracture lines. All fractures were classified according to the Müller AO classification. To confirm the results, the specimens were finally surgically dissected. RESULTS: 97 % of the tibial condylar fractures were easily seen and correctly classified according to the Müller AO classification on MP reconstruction of the ISO-C-3D. There is no significant difference between ISO-C and CT in detection and correct classification of fractures, but ISO-CD-3D is significant by better than CR. CONCLUSION: The evaluation of fractures with the ISO-C is better than with plain films alone and comparable to CT scans. The three-dimensional reconstruction of the ISO-C can provide important information which cannot be obtained from plain films. The ISO-C-3D may be useful in planning operative reconstructions and evaluating surgical results in orthopaedic surgery of the limbs.

Humans↗

[Studies on image quality, high contrast resolution and dose for the axial skeleton and limbs with a new, dedicated CT system (ISO-C-3 D)].

PURPOSE: Evaluation of 3D-CT imaging of the axial skeleton and different joints of the lower and upper extremities with a new dedicated CT system (ISO-C-3D) based on a mobile isocentric C-arm image amplifier. MATERIAL AND METHODS: 27 cadaveric specimes of different joints of the lower and upper extremities and of the spinal column were examined with 3D-CT imaging (ISO-C-3D). All images were evaluated by 3 radiologists for image quality using a semiquantitative score (score value 1: poor quality; score value 4: excellent quality). In addition, dose measurements and measurements of high contrast resolution were performed in comparison to conventional and low-dose spiral CT using a high contrast phantom (Catphan, Phantom Laboratories). RESULTS: Adequate image quality (mean score values 3 - 4) could be achieved with an applied dose comparable to low-dose CT in smaller joints such as wrist, elbow, ankle and knee. A remarkably inferior image quality resulted in imaging of the hip, lumbar and thoracic spine (mean score values 2 - 3) in spite of almost doubling the dose (dose increased by 85 percent). The image quality of shoulder examinations was insufficient (mean score value 1). Phantom studies showed a high-contrast resolution comparable to helical CT in the xy-axis (9 lp/cm). CONCLUSION: Preliminary results show, that image quality of C-arm-based CT-imaging (ISO-C-3D) seems to be adequate in smaller joints. ISO-C-3D images of the hip and axial skeleton show a decreased image quality, which does not seem to be sufficient for diagnosing subtle fractures.

Arm↗

[Image quality and detection of pathology by ultrasound: comparison of B-mode ultrasound with photopic imaging and tissue harmonic imaging alone and in combination].

PURPOSE: To determine the accuracy of photopic imaging (PI) in detecting pathology by ultrasound (US) and to assess the image quality in direct comparison with conventional B-mode ultrasound and tissue harmonic imaging (THI). MATERIAL AND METHODS: Fifty-two patients underwent US examination, among them 29 patients for abdominal assessment and 23 for otolaryngological assessment. A total of 208 freeze frames, 52 B-mode scans each with and without THI and 52 B-mode scans each with and without PI, were assessed by three readers, who determined the presence of pathology on a scale of 1 (definitely abnormal) to 5 (definitely normal). All 52 patients underwent US follow-up within six weeks. The results were confirmed by CT in 30 patients and by histology in five cases. Image quality and different color encodings of each technique were rated on a ranking scale of 1 (optimal) to 4 (poor). The different US techniques were compared in terms of image quality, diagnostic accuracy, and color encoding using McNemar's test and ROC analysis. RESULTS: The results for image quality were as follows: B-scan 3.9; THI 1.9; PI 2.8; and THI plus PI 1.5 (each p < 0.05). The following AUCs (Area under Curve, presence of pathology) were calculated: 0.925, 0.990, and 0.990 for B-mode US, THI, and PI, respectively (not significant), and 0.994 for THI plus PI (significant compared to B-mode scan). The different color encodings were rated as follows: reddish brown 1.6, gray 1.9, blue 3.1, and green 3.6 (each p < 0.05). CONCLUSION: For ultrasound examinations, PI in combination with THI improves the image quality and conspicuity of pathology.

Abdomen↗

[Ultrasound at the bedside: does a portable ultrasound device save time?].

AIM: To prospectively determine whether the use of a portable ultrasound device results in a detectable reduction of the time required for acute ultrasound (US) assessment at the bedside. MATERIALS AND METHODS: A total of 125 patients underwent US at the bedside, among them 68 for abdominal assessment, 12 patients for chest or soft-tissue evaluation, and 45 patients with vascular disease. Five different US systems equipped with 3.5 MHz and 7.5 MHz wide-band transducers were compared in terms of overall examination time including transport, setting up and disassembling, switching on and off as well as initializing the device (but without writing of the report). The following ultrasound systems were used: the portable SonoSite 180 (SonoSite, Germany) as well as the mobile units Masters/Gateway 2000 (Diasonics, USA), Tosbee (Toshiba, Japan), PowerVision 7000 (Toshiba, Japan), and SONOLINE Elegra (Siemens AG, Germany). RESULTS: The portable ultrasound device significantly reduced the examination time per patient to a mean 16 +/- 4 min from 26 +/- 5 min for the mobile units (p < 0.05). This result was predominantly affected by the time required for switching on and initializing the device as well as the duration of positioning at the bedside and to a lesser extent by elevator waiting time. CONCLUSION: The overall time required for performing an ultrasound examination at the bedside can be considerably reduced if a portable device is used instead of a mobile system.

Abdomen, Acute↗

Cardiovascular effects of beta-blockers with and without intrinsic sympathomimetic activity. A comparison between celiprolol and metoprolol.

BACKGROUND: Celiprolol, a newer beta-blocking agent, has been reported to have vasodilatory capacity which may be due to partial beta-2-receptor agonistic activity or to alpha-receptor antagonistic or central sympathoinhibitory effects. METHODS: To more critically assess the physiologic effects of celiprolol, we measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF), blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP), and during a cold pressor test (CPT). Responses were compared with those seen with metoprolol and with placebo, i.e. each subject was studied three times. RESULTS: Celiprolol did not alter resting levels of hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In contrast, metoprolol produced significant decreases of FBF and HR, and increases of forearm vascular resistance and BP, but had also no effect on responses to the applied stress tests. CONCLUSIONS: The lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial beta-2-receptor agonistic effect and does not seem to be due to a central or reflex action or to an alpha-blocking effect. Both beta-blockers do not impair fundamental neural mechanisms involved in circulatory homeostasis.

Adrenergic beta-Antagonists↗

BCR-ABL as a target for novel therapeutic interventions.

The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of protein tyrosine kinase activity, antisense strategies and immunomodulation.

Animals↗