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Biomedical subjects

A Lutz

Publications and source records attributed to A Lutz.

At least 19 recordsLinked to original sources

Bone mineral density and quantitative ultrasound in adults with cystic fibrosis.

OBJECTIVE: With increasing life span osteoporosis becomes a more recognized problem in patients with cystic fibrosis (CF). The aim of this cross-sectional study in 75 adult patients with CF (mean age 25.3 years) was to assess the prevalence of low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and, for the first time, by quantitative ultrasound (QUS), and to identify predicting factors. DESIGN AND METHODS: Bone status was assessed at the lumbar spine (L2-L4) and the femoral neck by DEXA, and at the calcaneus by QUS (stiffness index). These data were correlated with a variety of clinical and anthropomorphic variables. Biochemical markers of bone turnover such as osteocalcin, bone-specific alkaline phosphatase, crosslinks in urine, 25-hydroxy vitamin D (25-OH vitamin D), parathyroid hormone, calcium and free testosterone were determined by standard assays. RESULTS: The mean BMD T score (+/-s.e.m.) was -1.4+/-0.17 at the lumbar spine, and -0.54+/-0.16 at the femoral neck. The mean T score of the calcaneal stiffness index was -0.83+/-0.19. Based on a lumbar spine T score <-2.5 by DEXA, 27% of the patients had osteoporosis. Multiple regression analysis showed that the forced expiratory volume in one second (FEV1) and the use of oral glucocorticoids were independent predictors of low lumbar spine BMD, whereas body mass index (BMI) and the use of oral glucocorticoids were independent predictors of low femoral neck BMD. The stiffness index correlated moderately with BMD (0.49-0.62, P<0.0001). QUS had a sensitivity and specificity of only 57% and 89% respectively for diagnosing 'osteoporosis' (based on a femoral neck T score <-2.5 by DEXA). Positive and negative predictive values were 36% and 95% respectively. CONCLUSIONS: Low BMD is frequent in adults with CF and is most strongly correlated with disease severity (BMI, FEV1) and the use of glucocorticoids. Calcaneal QUS might help to screen out patients with a normal BMD, but sensitivity and specificity were not sufficiently high to replace DEXA in these patients.

Absorptiometry, Photon↗

Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony.

The quantification of phase synchrony between neuronal signals is of crucial importance for the study of large-scale interactions in the brain. Two methods have been used to date in neuroscience, based on two distinct approaches which permit a direct estimation of the instantaneous phase of a signal [Phys. Rev. Lett. 81 (1998) 3291; Human Brain Mapping 8 (1999) 194]. The phase is either estimated by using the analytic concept of Hilbert transform or, alternatively, by convolution with a complex wavelet. In both methods the stability of the instantaneous phase over a window of time requires quantification by means of various statistical dependence parameters (standard deviation, Shannon entropy or mutual information). The purpose of this paper is to conduct a direct comparison between these two methods on three signal sets: (1) neural models; (2) intracranial signals from epileptic patients; and (3) scalp EEG recordings. Levels of synchrony that can be considered as reliable are estimated by using the technique of surrogate data. Our results demonstrate that the differences between the methods are minor, and we conclude that they are fundamentally equivalent for the study of neuroelectrical signals. This offers a common language and framework that can be used for future research in the area of synchronization.

Brain↗

Expression of collagenase-3 (MMP-13) in c-fos-induced osteosarcomas and chondrosarcomas is restricted to a subset of cells of the osteo-/chondrogenic lineage.

The interstitial collagenases have been suggested to play a critical role in bone formation, remodeling, and cancerogenesis. We have previously shown that during mouse development expression of collagenase-3 (MMP-13) is restricted to bone and cartilage (Gack et al., 1995; Tuckermann et al., 2000) and is affected in mice with altered c-Fos and Cbfa-1 expression (Gack et al., 1994; Porte et al., 1999). In this study, using immunohistochemistry (IHC) and in situ hybridization (ISH) techniques, we have identified cells of the osteoblastic lineage to be the origin of strongly enhanced levels of MMP-13 transcripts in c-fos-induced osteosarcomas. Expression in these cells is further increased in c-fos/c-jun double transgenic mice and paralleled by Cbfa-1 expression. Similarly, in spontaneous and radiation-induced osteosarcomas, both c-Fos and MMP-13 proteins are detectable, suggesting that overexpression of both genes is a characteristic feature of osteosarcomas of different origin. We also observed high levels of MMP-13 in c-Fos-induced chondrosarcomas. In osteoblast-like cells and in cells of late chondrocyte differentiation such as hypertrophic chondrocytes, high levels of MMP-13 transcripts were found. In contrast, in anaplastic areas of the tumors representing highly proliferating chondrocytes, no MMP-13 expression is detectable, suggesting that in addition to Fos/AP-1, bone-specific transcription factors are responsible for restricted expression of collagenase-3/MMP-13 in a specific subset of cells of bone and cartilage in physiology and pathology.

Animals↗

Implementation of a cone-beam reconstruction algorithm for the single-circle source orbit with embedded misalignment correction using homogeneous coordinates.

We present an efficient implementation of an approximate cone-beam image reconstruction algorithm for application in tomography, which accounts for scanner mechanical misalignment. The implementation is based on the algorithm proposed by Feldkamp et al. and is directed at circular scan paths. The algorithm has been developed for the purpose of reconstructing volume data from projections acquired in an experimental x-ray micro-tomography (microCT) scanner. To mathematically model misalignment we use matrix notation with homogeneous coordinates to describe the scanner geometry, its misalignment, and the acquisition process. For convenience analysis is carried out for x-ray CT scanners, but it is applicable to any tomographic modality, where two-dimensional projection acquisition in cone beam geometry takes place, e.g., single photon emission computerized tomography. We derive an algorithm assuming misalignment errors to be small enough to weight and filter original projections and to embed compensation for misalignment in the backprojection. We verify the algorithm on simulations of virtual phantoms and scans of a physical multidisk (Defrise) phantom.

Algorithms↗

How enduring were the inequalities among European immigrant groups in the United States?

A long-standing and unresolved issue in the study of racial and ethnic groups concerns the persistence of initial inequalities among groups. Recently it has surfaced again in the study of U.S. immigrant groups, in George Borjas's (1994) claim that the human capital differences among early-twentieth-century immigrant groups are reflected in the relative socioeconomic achievements of their third generations. Reexamining this claim, we find that Borjas's analysis hinges on a series of problematic decisions, such as his inclusion of non-European groups as well as his failure to take ethnically mixed ancestry into account and to compensate for the weak correspondence in eastern Europe between ethnic ancestry and the national frontiers of the early 1900s. We replicate a portion of his analysis, correcting for these problems. Our results reveal no correspondence between the literacy of the first generation and the educational attainment of the third among European groups. Borjas's analysis seems to go farthest astray in including non-Europeans, especially Mexicans, because of the more systematic legal and social liabilities suffered by these groups.

Adolescent↗

Adrenocortical function in patients with macrometastases of the adrenal gland.

OBJECTIVE: Metastases of the adrenal gland are a frequent finding in patients with malignant tumors like bronchogenic carcinoma or breast cancer. Only limited and conflicting data on adrenocortical function in these patients are available. DESIGN: Cross-sectional study. METHODS: We investigated the impact of adrenal macrometastases on adrenocortical function in a series of 28 tumor patients using the ACTH(1-24) stimulation test and dexamethasone suppression test. Seven normal controls (Con), eleven patients without adrenal metastases (No Met), eight patients with unilateral (Uni Met) and nine patients with bilateral adrenal metastases (Bil Met) were investigated. RESULTS: The prevalence of adrenal insufficiency was low in our study population, with only two of nine patients with bilateral metastases having subclinical adrenocortical insufficiency. In the remaining patients with uni- or bilateral metastases, baseline and stimulated cortisol concentrations were higher than in controls and cancer patients without metastases (baseline cortisol (in nmol/l): Con: 307+/-33.2 vs Uni Met: 440+/-53.5, and Bil Met: 637.6+/-92.1, P=0.04 by ANOVA; cortisol 60 min after ACTH(1-24): Con: 794.6+/-41.2 vs Uni Met: 990.8+/-92.9, and Bil Met: 1151.4+/-155.5, P=0.03 by ANOVA). Simultaneously, baseline and stimulated serum aldosterone concentrations were significantly blunted in the tumor groups. CONCLUSIONS: Adrenal insufficiency is infrequent and develops only in patients with bilateral metastases. However, the majority of patients have activation of the hypothalamic-pituitary-adrenal axis despite adrenal metastases with strongly elevated cortisol concentrations.

Adrenal Cortex↗

[Micro-CT. Technology and application for assessing bone structure].

The strength and fracture resistance of bone is determined by the structure of the trabecular network and the cortical shell. While standard 2D techniques like histomorphometry are inadequate to assess the 3D nature of the trabecular network, isotropic 3D datasets of this network can be acquired with the new imaging modality of microCT. However, so far the quantitative analysis of the generated datasets, in particular the extraction of appropriate parameters describing the bone structure, has not been finally solved. In this article we describe the technology and applications of microCT systems relevant in the field of osteology. The most important technical features of current microCT systems in this context are: 1. A spatial resolution down to 5-10 microns can be achieved. 2. The maximum sample size is related to the desired resolution by a factor of approximately 1000, that is, a resolution of 10 microns limits the maximum sample size to approximately 1 cm. 3. Scan times for microCT systems vary between minutes and hours. Currently five areas for the application of microCT systems in osteology can be identified: 1. The search of parameters characterizing the 3D trabecular structure. 2. The application of finite element models to determine the biochemical competence of the structural parameters. 3. The use of microCT in preclinical trials to study drug effects in small animals. 4. The validation of analysis methods used in high-resolution in-vivo imaging systems. 5. The 3D quantification of modeling and remodeling processes.

Adult↗

A neural network model of general olfactory coding in the insect antennal lobe.

A central problem in olfaction is understanding how the quality of olfactory stimuli is encoded in the insect antennal lobe (or in the analogously structured vertebrate olfactory bulb) for perceptual processing in the mushroom bodies of the insect protocerebrum (or in the vertebrate olfactory cortex). In the study reported here, a relatively simple neural network model, inspired by our current knowledge of the insect antennal lobes, is used to investigate how each of several features and elements of the network, such as synapse strengths, feedback circuits and the steepness of neural activation functions, influences the formation of an olfactory code in neurons that project from the antennal lobes to the mushroom bodies (or from mitral cells to olfactory cortex). An optimal code in these projection neurons (PNs) should minimize potential errors by the mushroom bodies in misidentifying the quality of an odor across a range of concentrations while maximizing the ability of the mushroom bodies to resolve odors of different quality. Simulation studies demonstrate that the network is able to produce codes independent or virtually independent of concentration over a given range. The extent of this range is moderately dependent on a parameter that characterizes how long it takes for the voltage in an activated neuron to decay back to its resting potential, strongly dependent on the strength of excitatory feedback by the PNs onto antennal lobe intrinsic neurons (INs), and overwhelmingly dependent on the slope of the activation function that transforms the voltage of depolarized neurons into the rate at which spikes are produced. Although the code in the PNs is degraded by large variations in the concentration of odor stimuli, good performance levels are maintained when the complexity of stimuli, as measured by the number of component odorants, is doubled. When excitatory feedback from the PNs to the INs is strong, the activity in the PNs undergoes transitions from initial states to stimulus-specific equilibrium states that are maintained once the stimulus is removed. When this PN-IN feedback is weak the PNs are more likely to relax back to a stimulus-independent equilibrium state, in which case the code is not maintained beyond the application of the stimulus. Thus, for the architecture simulated here, strong feedback from the PNs onto the INs, together with step-like neuronal activation functions, could well be important in producing easily discriminable odor quality codes that are invariant over several orders of magnitude in stimulus concentration.

Animals↗

[What are you doing when you are doing nothing? ERP components without a cognitive task].

Two experiments, an "active" and a "passive" oddball-paradigm (1. phase) with visual and auditive stimuli were performed. In both, two stimuli with a probability of 0.7/0.3 were presented. The oddball-sequence was replaced in the 2. phase without knowledge of the subjects by a sequence, in which only targets were presented. One group of the subjects has got an active task (counting the rare stimulus), the other group was told to view the stimuli passively. The rare stimulus in the oddball-sequence evoked a larger parietal P3, the auditive stimulation additionally a larger fronto-central N1 and the visual stimulation a larger central P2. The non-expected change into the 2. phase resulted in a reverse of the ERP-lateralization between 150-300 ms: Before the change of the probability the amplitudes were more negative left than right, thereafter more negative right than left. All components and effects in the active task maintained without task, but they decreased. The differences were larger with the visual stimuli. These results suggest, that the passive paradigm could be applied to patients with motoric deficits. From a theoretical point of view these results lead to certain difficulties in the interpretation of the functional importance of the P3. It can be explained better by the context-closure theory (Desmedt, 1980; Verleger, 1988) than by the context-updating theory (Donchin, 1981).

Adult↗

An ocular model of Adenovirus type 5 infection in the rabbit.

Adenoviruses are a common cause of viral eye disease in humans. Recently, new antiviral drugs have been developed, which possess promising anti-adenovirus activity. In order to test these drugs, an ocular model of adenovirus infection was developed in 10 Hollander rabbits following topical, intrastromal and subconjunctival inoculation with a standard laboratory serotype (Adenovirus type 5 from The American Type Culture Collection). Clinical signs of infection-conjunctivitis, keratitis, corneal edema, subepithelial opacities, anterior chamber reaction and iritis-were evaluated. Adenovirus was isolated from the eye several days after inoculation and intra-epithelial viral replication was detected using the replica-technique. Reproducible ocular infection was clinically demonstrated in all rabbits.

Adenine↗

Instrument development in the measurement of unsupported arm exercise endurance in normal adult subjects.

Many daily activities, from basic grooming to employment tasks, require adequate unsupported arm endurance (UAE). We developed an electromechanical device to measure UAE endurance. The purpose of this study was to standardize the instrument for two rates of arm motion, moderate and slow, in 18 normal adult subjects (FEVI = 3.7L +/- .78, FVC = 4.2L +/- .74, FEV1/FVC = 1.1 +/- .08). Exercise endurance limits, and the following metabolic, ventilatory, and sensation responses were determined at rest prior to exercise and at end-exercise limits for both rates of UAE:minute ventilation (Ve), tidal volume (VT), respiratory rate (RR), duty cycle (Ti/Ttot), oxygen uptake (VO2), carbon dioxide production (VCO2), inspiratory flow (VT/Ti), heart rate (HR), and visual analog scale measurements (VAS) of dyspnea (D), respiratory effort (RE), and arm fatigue (AF). Significance increases from baseline rest were shown at the endurance limits for both rates of UAE in: VO2, VCO2, Ve, VT, RR, VT/Ti, HR, VAS-D, VAS-RE, and VAS-AF. There were no changes in Ti/Ttot and SaO2 with UAE. Peak VO2, RR, Ve, VT/Ti, and VAS-D with moderate exercise were significantly greater than slow UAE; and there was a trend increase in peak HR for moderate as opposed to slow rate UAE. Despite these differences, the endurance time between the two rates of UAE were similar. These data provide standards against which UAE in COPD can be evaluated.

Adult↗

Immunogenicity of a mammalian cell-derived recombinant human growth hormone preparation during long-term treatment.

The development of anti-human growth hormone (anti-hGH) and anti-host-cell protein antibodies to recombinant hGH (rhGH) of mammalian cell origin was determined in 395 children (304 GH deficiency; 91 Turner syndrome) undergoing long-term treatment (up to 54 months) for growth disorders. In all patients, blood samples were obtained prior to and every 2-3 months during treatment, and analyzed at a central laboratory for anti-hGH antibodies by RIA and antibodies to host-cell antigens by ELISA. During the first 24 months of treatment, 9 (3%) of the 304 patients with GH deficiency developed antibodies to rhGH for longer than 3 months. However, persistent antibodies were seen in only 2 patients, both of whom had proven hGH-N gene defects. In the remaining 7 (2%) anti-rhGH-antibody-positive patients, antibody concentrations showed a tendency to increase for 3-12 months, irrespective of the time of onset of measurable concentrations, and declined thereafter. In these patients, binding capacities were between 0.01 and 0.1 mg/l, and binding affinities were between 7 x 10(8) and 8 x 10(9) l/mol. Height velocity was unaffected in these children. None of the 91 patients with Turner syndrome developed persistent anti-hGH antibodies. Further, no child developed antibodies to host-cell antigens during treatment with rhGH of mammalian cell origin.

Adolescent↗

New ether oxime derivatives of erythromycin A. A structure-activity relationship study.

The discovery of roxithromycin is the result of a rational and scientific process, based on the fact that at least one reason for erythromycin A's resorption variability after oral administration was its instability in the gastric juice. This instability is due to the reactivity of the ketone in position 9 in acidic medium and one chemical approach was to mask it by an oxime function. Both stereoisomers of this oxime were isolated. Direct O-alkylation of this oxime allowed access to various ether oxime derivatives and of the latter the E stereoisomers were more interesting than the Z ones. The choice of the nature of the oxime substitution was made according to the lipophilic or hydrophilic character of the aliphatic ether chain and these alterations were mainly carried out by introducing heteroatoms into this chain. These different derivatives were classified in 5 groups according to the chemical nature of the chain: Aliphatic, aromatic and nitrogen-, oxygen- and sulfur-containing chains. Two classes, those containing a nitrogen or an oxygen in the ether side chains, showed differential in vitro/in vivo antibiotic activities, with improved bioavailability. Some preliminary pharmacokinetic data confirmed this improvement and led to the selection of five candidates, from which roxithromycin emerged as the best compound.

Animals↗

A new microclip for vascular occlusion. Technical note.

A new microclip for use on blood vessels 300 mu to 1 mm in diameter is described. This clip is suitable for either temporary or permanent occlusion and has been used in experimental applications. Potential clinical applications are described.

Surgical Instruments↗

[Cefotaxime, syn isomer of a new methoxyimino cephalosporin with unusual activity (author's transl)].

Cefotaxime, the - syn - derivative of 7 - [(2-(2-amino-4-4-thiazolyl)-2-methoxyimino) acetamido] cephalosporanic acid, is a new semisynthetic cephalosporin. In in vitro studies, it was 80 times more active than the - anti - derivative against beta-lactamase-producing strains of Gram-negative bacteria. The range of inhibitory concentrations of cefotaxime against Gram-negative bacteria, including Haemophilus influenzae, susceptible or resistant to penicillins and cephalosporins was from 0.01 to 0.1 micrograms/ml. This activity was consistently higher than that observed with cephalothin, cephaloridine, cephalexin, and cefazolin. Nevertheless, some strains of Enterobacter cloacae were resistant. Cefotaxime showed very similar activity to that of ampicillin against group A streptococci and Streptococcus pneumoniae.

Cefotaxime↗