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Biomedical subjects

Joachim Müller

Publications and source records attributed to Joachim Müller.

11 recordsLinked to original sources

Kinetic analysis of semisynthetic peroxidase enzymes containing a covalent DNA-heme adduct as the cofactor.

The reconstitution of apo enzymes with DNA oligonucleotide-modified heme (protoporphyrin IX) cofactors has been employed as a tool to produce artificial enzymes that can be specifically immobilized at the solid surfaces. To this end, covalent heme-DNA adducts were synthesized and subsequently used in the reconstitution of apo myoglobin (aMb) and apo horseradish peroxidase (aHRP). The reconstitution produced catalytically active enzymes that contained one or two DNA oligomers coupled to the enzyme in the close proximity to the active site. Kinetic studies of these DNA-enzyme conjugates, carried out with two substrates, ABTS and Amplex Red, showed a remarkable increase in peroxidase activity of the DNA-Mb enzymes while a decrease in enzymatic activity was observed for the DNA-HRP enzymes. All DNA-enzyme conjugates were capable of specific binding to a solid support containing complementary DNA oligomers as capture probes. Kinetic analysis of the enzymes immobilized by the DNA-directed immobilization method revealed that the enzymes remained active after hybridization to the capture oligomers. The programmable binding properties enabled by DNA hybridization make such semisynthetic enzyme conjugates useful for a broad range of applications, particularly in biocatalysis, electrochemical sensing, and as building blocks for biomaterials.

Animals↗

In vitro effects of thiazolides on Giardia lamblia WB clone C6 cultured axenically and in coculture with Caco2 cells.

The thiazolides represent a novel class of anti-infective drugs, with the nitrothiazole nitazoxanide [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide] (NTZ) as the parent compound. NTZ exhibits a broad spectrum of activities against a wide variety of helminths, protozoa, and enteric bacteria infecting animals and humans. In vivo, NTZ is rapidly deacetylated to tizoxanide (TIZ), which exhibits similar activities. We have here comparatively investigated the in vitro effects of NTZ, TIZ, a number of other modified thiazolides, and metronidazole (MTZ) on Giardia lamblia trophozoites grown under axenic culture conditions and in coculture with the human cancer colon cell line Caco2. The modifications of the thiazolides included, on one hand, the replacement of the nitro group on the thiazole ring with a bromide, and, on the other hand, the differential positioning of methyl groups on the benzene ring. Of seven compounds with a bromo instead of a nitro group, only one, RM4820, showed moderate inhibition of Giardia proliferation in axenic culture, but not in coculture with Caco2 cells, with a 50% inhibitory concentration (IC50) of 18.8 microM; in comparison, NTZ and tizoxanide had IC50s of 2.4 microM, and MTZ had an IC50 of 7.8 microM. Moreover, the methylation or carboxylation of the benzene ring at position 3 resulted in a significant decrease of activity, and methylation at position 5 completely abrogated the antiparasitic effect of the nitrothiazole compound. Trophozoites treated with NTZ showed distinct lesions on the ventral disk as soon as 2 to 3 h after treatment, whereas treatment with metronidazole resulted in severe damage to the dorsal surface membrane at later time points.

Animals↗

Usefulness of tissue Doppler imaging for estimation of left ventricular filling pressures in patients with systolic and diastolic heart failure.

The diagnostic usefulness of the mitral E/E' ratio (derived from tissue Doppler imaging) as an estimate of left ventricular filling pressures was studied in 28 patients with diastolic heart failure (defined by heart failure signs and symptoms but with preserved ejection fraction) and in 46 patients with systolic heart failure (heart failure signs and symptoms and reduced ejection fraction). E/E' was reflective of filling pressures in subjects with diastolic and systolic heart failure and may be of special use in ruling out elevated filling pressures in subjects with suspected diastolic heart failure.

Aged↗

Music perception in cochlear implant users: an event-related potential study.

OBJECTIVE: Compare the processing of music-syntactic irregularities and physical oddballs between cochlear implant (CI) users and matched controls. METHODS: Musical chord sequences were presented, some of which contained functionally irregular chords, or a chord with an instrumental timbre that deviated from the standard timbre. RESULTS: In both controls and CI users, functionally irregular chords elicited early (around 200 ms) and late (around 500 ms) negative electric brain responses (early right anterior negativity,ERAN and N5). Amplitudes of effects depended on the degree of music-syntactic irregularity in both groups; effects elicited in CI users were distinctly smaller than in controls. Physically deviant chords elicited a timbre-mismatch negativity (MMN) and a P3 in both groups, again with smaller amplitudes in CI users. CONCLUSIONS: ERAN and N5 (as well as timbre-MMN and P3), can be elicited in CI users. Although amplitudes of effects were considerably smaller in the CI group, the presence of MMN and ERAN indicates that neural mechanisms of both physical and music-syntactic irregularity-detection were active in this group.

Acoustic Stimulation↗

Analysis of ceiling effects occurring with speech recognition tests in adult cochlear-implanted patients.

This article presents a simple method of analysing speech test scores which are biased through ceiling effects. Eighty postlingually deafened adults implanted with a MED-EL COMBI 40/40+ cochlear implant (CI) were administered a numbers test and a sentence test at initial device activation and at 1, 3, 6, 12 and 24 months thereafter. As a measure for speech recognition performance, the number of patients who scored at the 'ceiling level' (i.e. at least 95% correct answers) was counted at each test interval. Results showed a quick increase in this number soon after device activation as well as a continuous improvement over time (numbers test: 1 month: 51%; 6 months: 73%; 24 months: 88%; sentence test: 1 month: 33%; 6 months: 49%; 24 months: 64%). The new method allows for the detection of speech recognition progress in CI patient samples even at late test intervals, where improvement curves based on averaged scores are usually assuming a flat shape.

Adult↗

Introduction of polyethylene terephthalate mesh (KoSa hochfest) for abdominal hernia repair: an animal experimental study.

BACKGROUND: Nowadays the surgical treatment of abdominal hernias includes the use of synthetic meshes in most cases. Due to chronic foreign body reactions, however, the most commonly used polypropylene meshes can lead to material hardening and recurrent hernias. As a proven cruciate ligament replacement polyethylene terephthalate (KoSa hochfest showed only little foreign body reactions and provided excellent clinical outcomes. In an animal trial it was therefore tested as mesh implant for hernia treatment and compared with Prolene. MATERIAL AND METHOD: The study was carried out in 12 mini-pigs. 10 x 10 cm of the musculofascial abdominal layer was resected, the peritoneum was preserved. A 15 x 15 cm synthetic mesh was implanted in sublay-technique (either KoSa hochfest, Telos GmbH, Marburg, Germany or Prolene, Ethicon, Norderstedt, Germany), mainly to test for chronic foreign body reactions. An independent pathologist tested the mesh size and foreign body reaction at 2 and 6 months, analysing the number of foreign body giant cells. RESULTS: No significant differences in mesh size were observed, neither between the compared groups nor with respect to the time periods. Compared to KoSa hochfest the foreign body reaction was significantly stronger in the Prolene implants, both at 2 and at 6 months (number of foreign body giant cells at 2 months: Prolene/KoSa hochfest: 2.2 +/- 0.4/0.8 +/- 0.2, at 6 months: 4.6 +/- 1.3/1.1 +/- 0.5). In contrast to KoSa hochfest, Prolene still showed significant foreign body reactions at 6 months as well as calcifications of all samples. CONCLUSION: The animal trials revealed that due to its high biocompatibility and little foreign body reaction KoSa hochfest is a promising implant for the treatment of hernias.

Animals↗

Deep electrode insertion in cochlear implants: apical morphology, electrodes and speech perception results.

Morphological examination of the human temporal bone in the apical region supports the benefits of deep electrode insertion. Initiation of spikes on peripheral processes close to the basilar membrane would provide improved channel selectivity during electrical stimulation but recruiting of nerve fibres requires a higher current. A clinical study was performed on 10 users of the MED-EL COMBI 40 + implant to evaluate the effect of the insertion depth of the cochlear implant electrode on speech perception. All subjects were implanted with the standard COMBI 40 + electrode with an insertion depth of > 30 mm. Acute speech tests were carried out in which stimulation was restricted to the apical, middle and basal regions of the cochlea in turn, and using electrode arrangements in which contacts were either distributed over the whole length of the cochlea or concentrated at the basal end, thus mimicking an insertion depth of approximately 20 mm only. The results showed that stimulation of the apical region of the cochlea supports a significant degree of speech understanding, and that distributing the contacts over the whole length of the cochlea improves speech perception in quiet and in noise.

Adult↗

Speech understanding in quiet and noise in bilateral users of the MED-EL COMBI 40/40+ cochlear implant system.

OBJECTIVE: The purpose of the study was to investigate speech understanding in quiet and noise in subjects bilaterally implanted with multi-channel cochlear implants. DESIGN: Nine adults bilaterally implanted with MED-EL implants were included in the study. The subjects were tested in three conditions: with both implants, with the right implant only, and with the left implant only. Speech tests included monosyllables in quiet and sentences in noise (10 dB signal to noise ratio). Speech was presented from the front, and noise was presented from either 90 degrees or 270 degrees azimuth. RESULTS: All subjects reported benefit from bilateral stimulation. Speech scores for all subjects were higher with bilateral than with unilateral stimulation. The average score across subjects for sentence understanding was 31.1 percentage points higher with both cochlear implants compared with the cochlear implant ipsilateral to the noise, and 10.7 percentage points higher with both cochlear implants compared with the cochlear implant contralateral to the noise. The average score for recognition of monosyllabic words was 18.7 percentage points higher with both cochlear implants than with one cochlear implant. All of these differences in average scores were significant at the 5% level. CONCLUSIONS: Bilateral cochlear implantation provides a significant benefit in speech understanding in both quiet and noise.

Acoustic Stimulation↗

Speech reception thresholds obtained in a symmetrical four-loudspeaker arrangement from bilateral users of MED-EL cochlear implants.

OBJECTIVE: The purpose of the study was to investigate speech reception in noise in subjects who had undergone bilateral implantation with multichannel cochlear implants. METHODS: Nine adults with bilateral MED-EL implants were included in the study. The subjects were tested using both implants and the better implant only. Tests were performed in a symmetrical setup, which ideally eliminates any head shadow effect. Speech tests included sentences in quiet and at various signal-to-noise ratios. From the results, the gain in signal-to-noise ratios at the speech reception threshold was determined. RESULTS: All subjects showed a substantial gain in signal-to-noise ratios of approximately 4 dB on average. In addition, the gain in signal-to-noise ratios was essentially stable for as long as 4.4 years. CONCLUSIONS: The results indicate that bilateral cochlear implant users are able to binaurally process speech.

Acoustic Stimulation↗