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Biomedical subjects

M Fuchs

Publications and source records attributed to M Fuchs.

At least 55 records · Page 3Linked to original sources

Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.

The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly, p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.

Animals↗

[Radiologic imaging of thoracic trauma].

Blunt trauma to the chest results from the transfer of kinetic energy to the human body. It may cause a wide range of mostly life-threatening injuries, including fractures of the thoracic skeleton, disintegration of the pleural space, contusion or laceration of pulmonary parenchyma and damage to the mediastinal structures. For a systematic approach it may be helpful to follow an organ-based evaluation of thoracic trauma. However, it should be borne in mind that subtle injuries may be associated with serious complications. Trauma to the chest may affect different anatomic compartments at the same time, requiring an extending diagnostic approach. Conventional radiography plays a major role in diagnosing thoracic trauma, complemented by ultrasound examination of the pleura and abdomen. It is well documented that CT scanning represents a major technological improvement for assessment of thoracic trauma. With the advent of fast helical CT scanning this method becomes more applicable for severely traumatized patients and potentially replaces other time-consuming procedures. State-of-the-art imaging of both projection and cross-sectional techniques provides useful information for immediate and appropriate treatment mandatory in patients with thoracic trauma.

Accidents, Traffic↗

Exposure of the surgeon to radiation during surgery.

Exposure to radiation over many years increases the incidence of cataracts and promotes the development of carcinoma of the thyroid gland. A prospective study of 24 operative procedures involving minimal invasive techniques and fluoroscopic guidance was undertaken in order to measure the radiation exposure to the primary surgeon. The study was conducted during 8 K-wire osteosyntheses in fractures of the distal radius, 8 closed interlocking intramedullary nailings in fractures of the femur and 8 internal fixator procedures, with or without posterior autogenic transpedicular bone grafting, in fractures of the lumbar spine. Radiation was monitored with the use of high sensitive thermoluminescent dosimeters. Fluoroscopy was necessary during the procedures, with exposure times ranging from 55 s to 12 min 35 s. The radiation dose received per procedure ranged from 0.6-259.3 microSv and was well within the dose limits set by German law.

Fluoroscopy↗

Rotational instability and integrity of the interosseous membrane in cadaveric ulnar shaft fractures.

The stability of isolated ulnar shaft fractures required further investigation because no data were available for fractures in the middle third or on the effect on rotational stability. Ten intact cadaveric arms were used to study the pathomechanics of fractures of the middle ulna. In all of them a transverse osteotomy was performed (A), then in five of them, an additional osteotomy was done in order to create a third fragment (B). The interosseous membrane was subsequently divided for 2 cm on either side of the osteotomy (A-->C, C-->D). On radiographs the displacement was recorded in pronation and supination, and the rotational displacement was calculated. Rotational instability occurred in all fractures studied, even in the so-called stable ones. Also, dissection of the interosseous membrane was not followed by a displacement of more than 50%, and shortening of the ulna should also be considered in fractures with less than 50% displacement as a sign of instability.

Adult↗

Degradation of and intraosseous reactions to biodegradable poly-L-lactide screws: a study in minipigs.

In 20 minipigs an osteotomy of the lumbar spine was done at L3 and fixed with resorbable implants (plate and screws) made of poly-L-lactide. For 24 months postoperatively the cancellous bone surrounding the screws was examined histologically. Specimens from the body of lumbar spine L2 and L4, carrying the screws, were fixed in a series of ethanol immersions and then embedded in methylmethacrylate. Longitudinal and transverse sections were cut with a microtome at 4-5 microns and stained by the Masson-Goldner and Giemsa method for light microscopy. Our investigation confirmed a long degradation period of poly-L-lactide and little inflammatory reaction within the bone during the whole period of observation. For poly-L-lactide the degradation time exceeded the longest follow-up time in this study, 24 months. Polymorphonuclear granulocytes and mononuclear round cells were scarce in all follow-up groups. Osteolytic changes or the emergence of seroma was not observed. Textured bone was evident early close to a thin fibrous capsule surrounding the screws. The remodelling of the bone close to the screws ensues by the formation of osteons.

Absorbable Implants↗

Improving source reconstructions by combining bioelectric and biomagnetic data.

OBJECTIVES: A framework for combining bioelectric and biomagnetic data is presented. The data are transformed to signal-to-noise ratios and reconstruction algorithms utilizing a new regularization approach are introduced. METHODS: Extensive simulations are carried out for 19 different EEG and MEG montages with radial and tangential test dipoles at different eccentricities and noise levels. The methods are verified by real SEP/SEF measurements. A common realistic volume conductor is used and the less well known in vivo conductivities are matched by calibration to the magnetic data. Single equivalent dipole fits as well as spatio-temporal source models are presented for single and combined modality evaluations and overlaid to anatomic MR images. RESULTS: Normalized sensitivity and dipole resolution profiles of the different EEG/MEG acquisition systems are derived from the simulated data. The methods and simulations are verified by simultaneously measured somatosensory data. CONCLUSIONS: Superior spatial resolution of the combined data studies is revealed, which is due to the complementary nature of both modalities and the increased number of sensors. A better understanding of the underlying neuronal processes can be achieved, since an improved differentiation between quasi-tangential and quasi-radial sources is possible.

Brain Mapping↗

Factors affecting length of stay and need for rehabilitation after hip and knee arthroplasty.

The purpose of this study was to determine the factors that predict the length of stay on a surgical service after total hip or knee arthroplasty and the factors that predict whether a patient will require admission to a rehabilitation unit before he or she is ready to return home. The authors reviewed the records of all patients admitted to the Albany Medical Center for elective total hip or total knee arthroplasty in 1995. The study looked for correlations of patients' age, sex, marital status, body mass index, and comorbid illnesses with length of stay on the surgical service and need for inpatient rehabilitation. The only factor that correlated with length of stay on the surgical unit was age. The factors that correlated with the need for inpatient rehabilitation were age and diabetes mellitus.

Age Factors↗

Differential expression of MAM-subfamily protein tyrosine phosphatases during mouse development.

The MAM-subfamily of type II transmembrane protein tyrosine phosphatases (PTPases) currently comprises the enzymes PTPkappa, PTPmu and PCP2. In an effort to elucidate the individual physiological roles of these closely related proteins we performed a detailed analysis of their mRNA transcript distributions at different stages of mouse embryogenesis and postnatal brain development. Our in situ hybridization studies revealed distinct and complementary expression patterns of PTPkappa, PTPmu and PCP2 transcripts. Based on our results and previous reports we discuss MAM-PTPases as a new class of morphoregulatory molecules.

Amino Acid Sequence↗

Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and FEM, indicating the high spatial accuracy of this technique in individual head models.

Adult↗

Gastrointestinal pH profiles in patients with inflammatory bowel disease.

BACKGROUND: 5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating. AIM: To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen. METHODS: Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn's disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease). RESULTS: The median gastric pH values in the patient groups (Crohn's disease 2.4, range 1.5-4.1; ulcerative colitis 1.95, range 1.55-4.4) were significantly higher than those observed in the controls (1.55, range 0.95-2.6). In the small bowel and colonic segments, all the pH values of Crohn's disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission. CONCLUSIONS: The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.

Adult↗

Glycosylation of Asn-632 and Asn-651 is important for functional expression of endothelin-converting enzyme-1.

It has been shown previously that N-glycosylation of Asn-144 and/or Asn-627 is important for functional expression of neutral endopeptidase-24.11 (NEP). All glycosylation sites of NEP are conserved within endothelin-converting enzyme-1 (ECE-1). In the present study we investigated the importance of proper glycosylation for the biologic function of ECE-1. We show that the double mutation of Asn-632 and Asn-651 leads to expression of an enzymatically inactive ECE-1 protein. In contrast, the single mutation of either Asn-632 or Asn-651 did not alter the enzymatic activity of ECE-1b.

Animals↗

An improved boundary element method for realistic volume-conductor modeling.

An improved boundary element method (BEM) with a virtual triangle refinement using the vertex normals, an optimized auto solid angle approximation, and a weighted isolated problem approach is presented. The performance of this new approach is compared to analytically solvable spherical shell models and highly refined reference BEM models for tangentially and radially oriented dipoles at different eccentricities. The lead fields of several electroencephalography (EEG) and magnetoencephalography (MEG) setups are analyzed by singular-value decompositions for realistically shaped volume-conductor models. Dipole mislocalizations due to simplified volume-conductor models are investigated for EEG and MEG examinations for points on a three dimensional (3-D) grid with 10-mm spacing inside the conductor and all principal dipole orientations. The applicability of the BEM in view of the computational effort is tested with a standard workstation. Finally, an application of the new method to epileptic spike data is studied and the results are compared to the spherical-shells approximation.

Body Fluid Compartments↗

[Radiation dosage of the surgery from intraoperative roentgen procedures: risks and dose management in the operating room].

A prospective study of 24 operative procedures with fluoroscopic guidance was undertaken to measure the radiation exposure of the primary surgeon. The dose received per procedure ranged from 0.6 to 259.3 microSv and was well within the government guidelines. An in vitro study during lateral fluoroscopy proved the position of the surgeon close to the image converter was irradiated with less scatter.

Body Burden↗

Immunoassay for thyroxine (T4) in serum using capillary electrophoresis and micromachined devices.

As part of our ongoing effort to develop electrophoretic assay technology for clinical diagnostics, we describe a competitive immunoassay for the determination of serum thyroxine (T4) based on electrophoresis and laser induced fluorescence (LIF). Measurements of total T4 are useful for the clinical evaluation of thyroid function. A fluorescein thyroxine conjugate was utilized in conjunction with a polyclonal antibody preparation as assay reagents. Capillary electrophoresis (CE) conditions tolerant of the direct injection of serum without extraction or other sample preparation steps were developed and used for quantitation of total T4 in serum. We have been exploring the use of micromachined devices with arrays of channels for high assay throughput. Our assay protocol was carried in a microchip format. The results illustrate that gains in speed can be additionally achieved, with the electrophoretic separation of free from bound labelled T4 being performed in about 15 s for serum samples.

Electrophoresis, Capillary↗

Fast visual evoked potential input into human area V5.

Studies of the human visual cortex have demonstrated that an area for motion processing (V5) is located in the lateral occipito-temporal cortex. To study the timing of arrival of signals in V5 we recorded multi-channel visual evoked potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis which was computed on a grand average of 10 subjects, and on five individual subjects, respectively. We demonstrate an early VEP component with onset before 30 ms and with a peak around 45 ms, located in the vicinity of V5. This early component was independent of a second activity, which started around 50 ms and peaked around 70 ms, and was located within the striate cortex (V1). These results provide further evidence for a very fast input to V5 before activation of V1.

Adult↗

Endothelin-1 potently stimulates chloride secretion and inhibits Na(+)-glucose absorption in human intestine in vitro.

1. Serosally added synthetic endothelin-1 (ET-1) increased short-circuit current (Isc) across isolated muscle-stripped human colonic mucosa in vitro. Bumetanide inhibited Isc responses, indicating that ET-1 stimulates electrogenic Cl- secretion. 2. In isolated human jejunal mucosa, ET-1 exhibited a concentration-dependent dual action. At low concentrations it induced rapid increases in Isc and these were inhibited by bumetanide. At a higher concentration (0.1 microM), ET-1 provoked a drastic and progressive decrease in Isc below the baseline value. 3. Pretreatment with phlorizin or omission of glucose from the Krebs-Ringer solution at the apical (luminal) side of the jejunal mucosa prevented the decreases in Isc evoked by ET-1, suggesting that the peptide inhibits the glucose-coupled electrogenic Na+ absorption. Indeed, flux experiments with D-[14C]glucose demonstrated that ET-1 decreases jejunal glucose absorption by approximately 80% within 30 min. 4. Electron microprobe analyses of cryosections of human jejunum showed that ET-1 (0.1 microM) evokes a significant decrease in intracellular Na+ concentrations of villus (not crypt) epithelial cells, suggesting that the peptide attenuates apical Na(+)-glucose entry by reducing the activity of the Na(+)-glucose cotransporter, SGLT1. 5. In the presence of tetrodotoxin (TTX), ET-1-induced Cl- secretion was significantly reduced, in both human jejunal and colonic mucosa. However, the inhibitory effect on jejunal Na(+)-glucose absorption was not affected by TTX. 6. ET-1 increases electrogenic Cl- secretion across human intestinal mucosa in vitro. This effect is mediated in part via the activation of enteric nerves. Responses of the human jejunal mucosa to high ET-1 concentrations exhibit a second component, namely the rapid inhibition of electrogenic Na(+)-glucose absorption, which might be mediated by an inhibition of the transport activity of SGLT1. This effect is independent from neuronal mediators. Our results suggest different cellular action sites for ET-1 in human small and large intestine.

Absorption↗

[Saving the extremity by massive transfusion in grade III open femoral fracture with vascular lesion. A case report].

The major problems in the treatment of open fractures with high blood loss are hypothermia acidosis and coagulopathy. By improving the standards of polytrauma management and using massive transfusion systems, which should help to avoid those complications, the indication for primary limb salvage under hypovolemic shock conditions is greatly increased. The following case of an grade 3 open fracture of the femur with severe soft-tissue damage, including vascular lesions, with consecutive massive transfusion, should demonstrate that the cardiac-respiratory system can still be stabilized, even if a surgical solution seems impossible.

Adult↗