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Biomedical subjects

M Fuchs

Publications and source records attributed to M Fuchs.

At least 37 records · Page 2Linked to original sources

Quantitative determination of free intracellular amino acids in single human polymorphonuclear leucocytes. Recent developments in sample preparation and high-performance liquid chromatography.

The described procedure allows quantitative, highly precise and reproducible analysis of free amino acid concentrations in single polymorphonuclear leucocytes (PMLs). This method is superior to previously described procedures with regard to sample size, PML separation, sample preparation and stability, as well as the chosen fluorescence high-performance liquid chromatography procedure, and can satisfy the high demands for ultra-sensitive and comprehensive amino acid analysis, especially for the continuous surveillance of severe diseases and organ dysfunction.

Amino Acids↗

Complex feedback regulation of bile acid synthesis in the hamster: the role of newly synthesized cholesterol.

Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol. After interruption of the enterohepatic circulation, physiological and double-physiological doses of conjugated cholate (25 or 50 micromol/100 g. h) or of unconjugated deoxycholate (6 or 12 micromol) were infused intraduodenally for 54 hours and compared with controls. De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation. Directly after depletion of the bile acid pool (6-9 hours) at nearly physiological conditions, chenodeoxycholate synthesis was significantly reduced by cholate and deoxycholate by up to 45% to 51%, whereas cholate formation decreased by approximately 22% during deoxycholate. This short-term effect was mainly mediated by reduced synthesis from preformed cholesterol. After long-term bile depletion (30-54 hours), bile acid synthesis returned to control levels during 25 micromol of cholate and of both deoxycholate doses. In contrast, only 50 micromol of cholate prevented derepression of bile acid synthesis. This long-term effect was mainly attributed to a diminished formation from de novo cholesterol exceeding the reduced synthesis from preformed cholesterol. In summary, short- and long-term regulation of bile acid synthesis in hamsters differs with respect to availabilities of preformed and de novo cholesterol.

Amino Acids↗

[Iatrogenic Cushing syndrome and mutatio tarda caused by dexamethasone containing nose drops].

Nasal steroid drops can produce iatrogenic Cushing's syndrome if the recommended dose is exceeded. We now report a 19-year-old male patient for whom dexamethasone nasal drops were prescribed because of nasal obstruction. He had been using these drops for more than 5 years, with a daily dexamethasone dose of 0.7-1.0 mg. It is likely that significant amounts of dexamethasone were swallowed and absorbed by the patient's gastrointestinal tract. As a consequence, the patient developed Cushing's syndrome with panhypopituitarism, growth retardation, osteoporosis and hypertension. A boyish size of the larynx resulted in a fundamental speaking frequency of a child. After discontinuing the intranasal use of the of dexamethasone and adjusting doses of hydrocortisone over 3.5 months a normalization of endocrine function occurred with the beginning of puberty and normal sexual changes. These findings show that the use of nasal steroid drops particularly in children should be limited to a short period and drugs with a low absorption dose employed.

Administration, Intranasal↗

[Measuring intraoperative radiation exposure of the trauma surgeon. Measuring eye, thyroid gland and hand with highly sensitive thermoluminescent detectors].

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. Radiation was monitored with the use of high sensitive thermoluminescent dosimeters. At the spots of dosimetry (eyes, thyroid gland, hand and genitals under lead apron) the dose was uniformly low and ranged from 0.6 muSv at the eyes to 259.3 muSv at the hand. The dose is determined by the duration of fluoroscopy and the amount of scattered rays, which in turn depends on the volume being x-rayed. On the basis of our results there is no likelihood of exceeding the limits of safety regulations even in a very busy operative environment, although a statistically increased incidence of thyroid cancer or a radiation-induced glaucoma is present. In vitro measurements with irradiation of a phantom resulted in the following recommendations: 1) fluoroscopy should be performed using the magnification-mechanism of the x-ray apparatus, 2) during lateral fluoroscopy the primary surgeon should be positioned close to the image intensifier. At least the surgeon should be familiar with the technique of closed reduction and instrumentation to reduce the duration of fluoroscopy which proved to be the most important factor for the amount of the radiation exposure.

Eye↗

Using at least 5x10(6)/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and use of antibiotics after transplantation.

For autologous stem cell transplantation, it is common practice to infuse at least 2 x 10(6)/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5 x 10(6)/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin's and non-Hodgkin's lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 x 10(6)/kg (range 0.64-25.9 x 10(6)/kg). Haematopoietic recovery to a neutrophil count >0.5 x 10(9)/l took a median of 10 (range 5-16) days from transplant. When comparing patients receiving at least 5 x 10(6)/kg and 2-5 x 10(6)/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 x 10(9)/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 x 10(6)/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 x 10(6)/kg particularly in patients with a good stem cell mobilisation capacity.

Adolescent↗

A second unrelated bone marrow transplant: successful quantitative monitoring of mixed chimerism using a highly discriminative PCR-STR system.

A second bone marrow transplant (BMT) might be considered as an option in patients with leukaemia with graft failure after BMT. We report the successful treatment of a patient with graft failure by a second stem cell transplant from another unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. In addition to this, a penta PCR-STR system was tested and shown to be sensitive for monitoring of marrow engraftment. The conditioning regimen for the first transplantation consisted of busulfan and cyclophosphamide while anti-thymocyte globulin and CY were used for the second BMT. The patient successfully engrafted at day +11 after second BMT.

Adult↗

[Risk of injuries in snow boarding].

Survey of a group of injured snowboarders and analysis of their sustained injuries and risk factors in comparison to experience level and equipment. 55% of all injuries occurred within the first 7 days of learning how to ride the snowboard. The affected body region of 36% of all injuries and 53% of the severe injuries was the wrist. The primary mechanism of injury was through low-velocity falls on hard or icy snow, essentially a loss of balance with backward fall onto out-stretched arms leading to hyperextension and trauma to the wrist.

Accidental Falls↗

Linear and nonlinear current density reconstructions.

Minimum norm algorithms for EEG source reconstruction are studied in view of their spatial resolution, regularization, and lead-field normalization properties, and their computational efforts. Two classes of minimum norm solutions are examined: linear least squares methods and nonlinear L1-norm approaches. Two special cases of linear algorithms, the well known Minimum Norm Least Squares and an implementation with Laplacian smoothness constraints, are compared to two nonlinear algorithms comprising sparse and standard L1-norm methods. In a signal-to-noise-ratio framework, two of the methods allow automatic determination of the optimum regularization parameter. Compensation methods for the different depth dependencies of all approaches by lead-field normalization are discussed. Simulations with tangentially and radially oriented test dipoles at two different noise levels are performed to reveal and compare the properties of all approaches. Finally, cortically constrained versions of the algorithms are applied to two epileptic spike data sets and compared to results of single equivalent dipole fits and spatiotemporal source models.

Algorithms↗

Detection of bovine herpesvirus type 1 in blood from naturally infected cattle by using a sensitive PCR that discriminates between wild-type virus and virus lacking glycoprotein E.

In the present study, we report for the first time on the detection of bovine herpesvirus type 1 (BHV-1) in whole-blood samples derived from naturally infected cattle. Sensitive PCR assays specific for glycoprotein B (gB), gC, and gE of BHV-1 allow the detection of one BHV-1 DNA copy in 10(5) to 10(7) peripheral blood leukocytes (PBLs). The incidence of BHV-1-positive PBLs in naturally infected cattle appears to be quite high (92.2% positive PBLs among all samples tested), although in most cases only between 10(-5) and 10(-7) positive leukocytes were present. The results demonstrate that the viral DNA is detectable not only in the peripheral blood of acutely infected animals but, more importantly, also in the peripheral blood of subclinically infected cattle. The gE-specific PCR described in the report allows discrimination between wild-type (WT) virus-infected and vaccinated animals, which is of importance for control programs that use the recently introduced vaccination strategy with a gE-negative virus. The results further show that doubtful serological results can be verified or falsified and that individual animals can be monitored for the presence or absence of WT BHV-1 or gE-negative virus in cattle herds. The PCR protocols allow the detection of BHV-1 prior to seroconversion or in BHV-1-seronegative cattle. Finally, the results indicate the simultaneous presence of WT and gE-negative vaccine virus in the PBLs of several cattle. Therefore, investigations of viremia in naturally and experimentally infected cattle and on the identification of infected cell types of bovine PBLs can be now performed.

Animals↗

[Prediction of the onset of voice mutation in singers of professional Boys' choirs: investigation of members of the Thomaner choir, Leipzig].

Die phoniatrische Betreuung der kindlichen Singstimme während des Stimmwechsels erscheint gerade bei Sängern in Knabenchören mit hoher stimmlicher Belastung wichtig. Die vorliegende Studie sucht nach Methoden, den Eintrittszeitpunkt der Mutation vorherzusagen und das Vorliegen einer Mutation differentialdiagnostisch von hyperfunktionellen Stimmstörungen oder entzündlichen Erkrankungen des Stimmorganes zu trennen. Dazu wurden 36 Knaben des Leipziger Thomanerchores im Sinne einer Longitudinalstudie alle 3 Monate über 3,5 Jahre bis zum hörbaren Einsetzen der Mutation untersucht. Es erfolgte die Bestimmung von zehn stimmlichen und acht stimmunabhängigen Parametern, die erstmals in solch umfassender Form auf ihre prädiktive Aussagekraft geprüft wurden. Die statistische Auswertung wies besonders den Serumtestosteronspiegel und die Wachstumsrate als Grössen aus, die mit dem Prämutationsverlauf korrelieren und eine konkrete Vorhersage ermöglichen. Das Vorliegen einer Mutation kann ausserdem durch den Verlauf der mittleren ungespannten Sprechstimmlage und unter Hinzuziehung des Genitalstatus bestätigt werden. Durch die exakte und prädiktive Bestimmung des Mutationsbeginnes können Erkrankungen des Stimmapparates vermieden werden, die aus dem intensiven Singen in der Mutation resultieren. Weiterhin geben die Ergebnisse dem Chorleiter wertvolle Informationen für die Planung der Besetzung seiner Knabenstimmen.

Adolescent↗

Sterol carrier protein 2 participates in hypersecretion of biliary cholesterol during gallstone formation in genetically gallstone-susceptible mice.

In inbred mice, susceptibility to cholesterol gallstone disease is conferred by Lith genes, which in part promote hypersecretion of cholesterol into bile in response to a high-fat/cholesterol/cholic acid (lithogenic) diet. Because cytosolic sterol carrier protein 2 (SCP2) is believed to participate in cellular cholesterol trafficking and is elevated in the liver cytosol of cholesterol gallstone patients, we defined the hepatic expression of SCP2 during cholesterol gallstone formation in gallstone-susceptible C57L and gallstone-resistant AKR mice fed the lithogenic diet. Steady-state cytosolic SCP2 levels in C57L, but not AKR mice increased as a function of time and were correlated positively with biliary cholesterol hypersecretion, cholesterol saturation indices of gall-bladder biles and the appearance of liquid and solid cholesterol crystals leading to gallstone formation. Steady-state mRNA levels increased co-ordinately, consistent with regulation of SCP2 expression at the transcriptional level. Our results suggest that overexpression of SCP2 contributes to biliary cholesterol hypersecretion and the pathogenesis of gallstones in genetically susceptible mice. Because of the different chromosomal localizations of the Lith and Scp2 genes, we postulate that Lith genes control SCP2 expression indirectly.

Animals↗

[Food allergies].

Food allergy must have an immunological background. Till recently it was restricted only to the IgE mechanism, today we include also non-atopical reactions (in particular type III and IV according to Coombs and Gell). We speak of probable and possible food allergies. By differential diagnosis we must differentiate food allergies from food intolerance (e.g. enzyme deficiencies), food aversions (psychic factor) as well as toxic and pharmacological effects. There are more than 10% undesirable reactions in humans after ingestion of food but only every fifth (some 2% of the population have food allergies. The diagnosis is based above all on the case-history, subsequent elimination and exposure tests and examination by allergological tests, or examination of specific immunoglobulins E (IgE). The diagnosis is not always unequivocal--it is influenced among others by a different specificity and sensitivity of food antigens (allergens). The manifestations of food allergy are found at the site of action (mouth, GIT) or are systemic (respiration, cardiovascular system, skin etc.). A special type of food allergy is the oral alimentary syndrome, i.e. food allergy crossed with pollen hypersensitivity, described in the great majority of subjects sensitive to pollen. Food allergy has its specific age-conditioned and geographical features. In childhood sensitivity to the protein of cows milk, egg white but also soya or flour predominates, with advancing age allergies to nuts, fruit, vegetables, spices, cheese, sea foods increase. Food allergy can be a very early allergy (manifested already in infant age) but it is one of the few allergies which can also recede (incl. laboratory tests). Treatment is dietetic, the period of dietetic treatment depends on the type of food and the patient's age, not infrequently it must be lifelong. If diet does not suffice, preventive medication is used (sodium cromoglycate) or symptomatic (antihistamine preparations, corticosteroids, external agents etc.), in some countries specific immunotherapy is being tested.

Food Hypersensitivity↗

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↗