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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

At least 577 records · Page 32Linked to original sources

Opiate levels in hair.

By means of radioimmunoassay-technique, hair samples of users, drug related fatalities, carcinoma patients receiving morphine and of experimental guinea pigs receiving codeine were investigated for opiates. The RIA-investigations require a minimum of material; our routine procedures need only 50 mg of hair. No correlation existed between administered doses of opiates and their concentrations in hair of both human and experimental animals. By sectioning the hair, the approximate period of drug use in man could be detected. However, these findings could not be confirmed by the animal experiments. The growth rate of the hair, diffusion and adhesion processes may influence the transport of drugs along the hair. External contaminations and washing procedures were shown to increase or diminish the drug concentration of the samples.

Animals↗

The determination of drugs and their substitutes in human hairs.

In recent years it has become possible to detect organic pharmaceuticals and drugs in a few milligrams of a person's hair, using modern analytical methods (RIA, GC/MS, GC), whether this person has taken narcotics and other drugs in past times. With the aid of hair analysis it is possible to examine the drug career of a drug addict for up to 1 year, and sometimes for a longer time. This is mostly of great importance in criminalistics and forensic medicine, in the criminal retrospective examination of addicts.

Forensic Medicine↗

[Nuclear magnetic resonance tomography of meniscus lesions].

In magnetic resonance imaging (MR) the use of suitable surface coils combined with high resolution makes it possible to obtain differentiated information on the condition of the menisci. In particular, the course and extent of cracks, degenerative changes, and the attachment zones of the menisci can be assessed. This paper describes MR and clinical findings in 58 patients and compares them with those in seven healthy subjects.

Humans↗

Genetic analysis of the Rhizobium meliloti exoYFQ operon: ExoY is homologous to sugar transferases and ExoQ represents a transmembrane protein.

The nucleotide sequence of a 4.8-kb ClaI-EcoRI DNA fragment of megaplasmid 2 of Rhizobium meliloti Rm2011 involved in succinoglucan (EPS I) synthesis and nodule infection was determined. Four open reading frames (ORFs) were identified on this fragment. A mutational analysis revealed that these ORFs represent genes that were termed exoX, exoY, exoF, and exoQ. The locations of transposon insertions in these exo genes were determined at the nucleotide level. Plasmid integration mutagenesis revealed that the genes exoY, exoF, and exoQ are organized in an operon. The exoX gene running in opposite direction forms a monocistronic transcriptional unit. The exoX gene was shown to negatively influence the amount of EPS I synthesized. The exoY gene is coding for a membrane associated protein homologous to the C-terminal part of the Xanthomonas campestris glucosyltransferase GumD and the Salmonella typhimurium galactose transferase RfbP. ExoF, a probable periplasmatic protein, is nearly identical to the protein encoded by ORF1 of Rhizobium sp. strain NGR234. ExoQ is most probably a membrane associated protein as deduced by its hydrophobic structural features. All three genes of the exoYFQ operon were shown to be essential for succinoglucan synthesis and nodule infection.

Amino Acid Sequence↗

Analysis of the Rhizobium meliloti genes exoU, exoV, exoW, exoT, and exoI involved in exopolysaccharide biosynthesis and nodule invasion: exoU and exoW probably encode glucosyltransferases.

Sequence analysis of a 5.780-kb DNA fragment originating from megaplasmid 2 of Rhizobium meliloti 2011 involved in biosynthesis of exopolysaccharide I (EPS I) and invasion of alfalfa nodules revealed the presence of five exo genes designated exoU, exoV, exoW, exoT, and exoI. ExoT resembled transmembrane proteins, whereas ExoI displayed a characteristic signal peptide. Sequence comparisons with several polysaccharide-polymerizing enzymes of both prokaryotic and eukaryotic origin indicated that exoW and exoU encode glucosyltransferases. Moreover, ExoV displayed weak homologies to the ExoO, ExoA, ExoL, and ExoM proteins of R. meliloti, which are also discussed as glucosyltransferases. Using exo-lacZ transcription fusions in connection with plasmid integration mutagenesis, promoters were identified in front of exoI, exoT, exoW, exoV, and exoU.R. meliloti 2011 strains with mutations in exoT, exoW, exoV, and exoU produced no detectable EPS I and were unable to infect alfalfa nodules, whereas exoI mutants synthesized a reduced amount of EPS I and did infect alfalfa nodules.

Amino Acid Sequence↗

Molecular analysis of the Rhizobium meliloti mucR gene regulating the biosynthesis of the exopolysaccharides succinoglycan and galactoglucan.

The Rhizobium meliloti Tn5 mutant Rm3131, producing galactoglucan (EPS II) instead of succinoglycan (EPS I), was complemented by a 3.6-kb EcoRI-fragment of the Rhizobium meliloti genome. Sequencing of this fragment revealed six open reading frames (ORFs). The ORF found to be affected in the mutant Rm3131 codes for a putative protein of 15.7 kDa and forms a monocistronic transcriptional unit. Further genetic analysis revealed that the gene mutated in Rm3131 is identical to the previously described R. meliloti mucR gene (H. Zhan, S.B. Levery, C. C. Lee, and J.A. Leigh, 1989, Proc. Natl. Acad. Sci. USA 86:3055-3059). By hybridization it was shown that a mucR homologous gene is present in several rhizobacteria. The deduced amino acid sequence of MucR showed nearly 80% identity to the Agrobacterium tumefaciens Ros protein, a negative regulator of vir genes and necessary for succinoglycan production. MucR contains like Ros a putative zinc finger sequence of the C2H2 type. Transcriptional fusions of genes for EPS I and EPS II synthesis, the so-called exo and exp genes, with the marker gene lacZ were used to delineate the role of mucR for exo and exp gene expression. It was found that exp genes are negatively regulated by MucR on the transcriptional level, whereas a posttranscriptional regulation by MucR is assumed for exo genes. Furthermore, mucR is negatively regulating its own transcription.

Amino Acid Sequence↗

Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells.

The glutamatergic synapses between inner hair cells and afferent neurons seem to be involved in pathophysiological conditions of the cochlea. The excessive release of glutamate from inner hair cells during noise trauma and ischemia affects the afferent neurons. It is possible that in tinnitus outer hair cell or inner hair cell dysfunction or damage leads to an altered spontaneous release of glutamate from inner hair cells. Thus, the pharmacological modulation of glutamatergic neurotransmission could be of great value in the therapy of certain inner ear diseases. Recently, it has been discovered that the spasmolytic drug memantine has antiglutamatergic properties. As a possible drug for inner ear diseases, we were interested in the action of memantine on the neurotransmission of inner hair cells. With the aid of microiontophoretic techniques we were able to show a strong depressing effect on spontaneous activity as well as on glutamate-induced activity. This effect seems to be mediated by a blockade of N-methyl-D-aspartate (NMDA) receptors as memantine showed a strong inhibiting effect on NMDA-induced activity but not on AMPA-induced activity. These results recommend memantine for the treatment of inner ear diseases, e.g. especially tinnitus.

Animals↗

Alpha B-crystallin in the mammalian inner ear.

To study the distribution of alpha B-crystallin, formalin-fixed preparations of the inner ear of the rat, cynomolgus monkey, rhesus monkey and human were stained immunohistochemically for alpha B-crystallin. In all cochleae investigated, intense staining for alpha B-crystallin was found in the inner and outer pillars as well as in the cells of Hensen and Claudius. In the primate inner ear, alpha B-crystallin was also present in the polygonal epithelial cells of Reissner's membrane, the interdental cells and some fibrocytes of the spiral limbus, epithelial cells of the outer spiral sulcus and the Schwann cells of the 8th nerve. In the primate stria vascularis, alpha B-crystallin was mainly seen in the basal cell layer and the adjacent cells of the connective tissue layer. alpha B-crystallin was found to be present in a large variety of cells in the inner ear surrounding the scala media.

Aged↗

A rat T-cell line that mediates autoimmune disease of the inner ear in the Lewis rat.

In various patterns of sensorineural hearing loss including Ménière's disease, which may show improvement in auditory function following immunosuppressive therapy, an isolated autoimmune disease of the inner ear has been postulated. Because of the lack of well-defined diagnostic criteria to identify autoimmune processes within the inner ear and the fact that the human inner ear is one of the few organs of the body not amenable to diagnostic biopsy, there has been great interest in developing animal models that mimic these clinical entities. Previous studies have found evidence that this process might be cell mediated and that the endolymphatic sac functions as an immunodefensive organ for the inner ear. By heterologous immunization of inbred Lewis rats with inner ear tissue, an autoreactive inner-ear-specific T helper cell line was established. After passive transfer of these cells a labyrinthitis was induced in recipient animals. Immunohistochemically, T helper cells were first identified in the cochlea suggesting that this cell type might carry the autoantigenic epitope. Autoantibodies against inner ear tissue were demonstrated in animals with histologically evident labyrinthitis. We conclude that this experimental design can serve as an animal model for cell-mediated autoimmune disease of the inner ear and could be used to explain the etiology of certain types of sensorineural hearing loss such as Ménière's disease. With this approach the identification of the causative autoantigen should be possible and will lead to the development of appropriate clinical tests to diagnose autoimmune diseases of the inner ear in humans.

Animals↗

3D-finite element model of the human cochlea including fluid-structure couplings.

The propagation of acoustic waves in the inner ear in vivo could not be quantified completely yet. This is in particular true in conjunction with the micromechanical structures of the organ of Corti, though these data are important for the explanation and discussion of clinical measurements like otoacoustic emissions and auditory brainstem responses. To access these problems a three-dimensional mechanical model of the cochlea including the fluid-structure couplings is developed and evaluated numerically by finite elements. Although the complex cochlear partition is covered by passive mechanical elements, the results fit early experiments (1928), which studied the wave propagation in the cochlea with fresh human cadavers [G. von Békésy: Experiments in Hearing. New York, McGraw-Hill, 1960]. Additionally it is now easy to calculate the mechanical input impedance of the cochlea. These results agree with recent experiments [S.N. Merchant et al.: Hear Res 1996;97:30-45].

Biomechanical Phenomena↗

Active nonlinear mechanics of the organ of Corti including the stereocilia-tectorial membrane complex.

There is a large amount of knowledge about the different components of the organ of Corti (OC), but little is known about how these components act together in vivo. To clarify the complex mechanical behavior of the OC, anatomic results are carefully analyzed and used to develop a finite element model of a short section of OC, which includes 8 outer hair cells (OHC) and their supporting structures. The modal analysis shows the frequency-dependent phase reversal of the radial stereocilia displacement. The transient computation confirms the amplification of OC displacements when the ability of the OHC to contract and elongate is considered. The inclusion of a nonlinear function describing the mechanoelectrical transduction in OHC amplifies and distorts the displacement of the OC when it is stimulated by a sinusoidal input pressure function. These results are in agreement with other psychoacoustic, electrophysiologic and otoacoustic measurements.

Biomechanical Phenomena↗

Confirmation of G. von Békésy's theory of paradoxical wave propagation along the cochlear partition by means of bone-conducted auditory brainstem responses.

In order to investigate the propagation time of the traveling wave in the cochlea after bone-conduction stimulation of the inner ear, bone-conducted auditory brainstem responses (ABRs) were recorded in 6 normally hearing subjects after masking the basal cochlear region using high-pass filtered noise. As in air-conducted ABRs, Jewett V wave latency is delayed corresponding to the propagation time of the traveling wave front traversing the desynchronized hair cell region. These results support the theory of paradoxical wave propagation proposed by von Békésy in 1952, who postulated that wave motion always starts from the stiffest part of the basilar membrane, independent of the location of the vibrating force. In addition, we also found a latency delay of the Jewett V wave of bone-conducted ABRs in 8 patients with high-frequency hearing loss which corresponded to the severity of their hearing impairment.

Adolescent↗

Diagnostic procedures for detection of lymph node metastases in cancer of the larynx.

Squamous cell carcinoma is the most common malignant neoplasm of the larynx. One of the most important influences on prognosis is the presence of metastases to the cervical lymph nodes. Accurate determination of lymph node involvement is therefore a prerequisite for individualized therapy in patients with squamous cell carcinoma of the larynx. Clinical palpation of the neck is not very accurate and the role of imaging techniques such as ultrasound, ultrasound-guided fine needle aspiration cytology, color Doppler ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography is being applied in order to improve upon the results of clinical investigation alone. According to our investigations and review of the literature, the accuracy of computed tomography scanning (84.9%) and magnetic resonance imaging (85%) was superior to palpation (69.7%) and ultrasound (72.7%). Ultrasound-guided fine needle aspiration cytology showed an accuracy of 89% and was in the same range with positron emission tomography (90.5%).

Biopsy, Needle↗

Comparison of the TEMPO+ ear-level speech processor and the cis pro+ body-worn processor in adult MED-EL cochlear implant users.

A study was conducted to compare the new MED-EL TEMPO+ ear-level speech processor with the CIS PRO+ body-worn processor in the COMBI 40/COMBI 40+ implant system. Speech tests were performed in 46 experienced subjects in two test sessions approximately 4 weeks apart. Subjects were switched over from the CIS PRO+ to the TEMPO+ in the first session and used only the TEMPO+ in the time between the two sessions. Speech tests included monosyllabic word tests and sentence tests via the telephone. An adaptive noise method was used to adjust each subject's scores to approximately 50%. Additionally, subjects had to complete a questionnaire based on their 4 weeks of experience with the TEMPO+. The speech test results showed a statistically significant improvement in the monosyllabic word scores with the TEMPO+. In addition, in the second session, subjects showed a significant improvement when using the telephone with the TEMPO+, indicating some learning in this task. In the questionnaire, the vast majority of subjects found that the TEMPO+ allows equal or better speech understanding and rated the sound quality of the TEMPO+ higher. All these objective and subjective results indicate the superiority of the TEMPO+ and are mainly attributed to a new coding strategy called CIS+ and its implementation in the TEMPO+. In other words, based on the results of this study, it appears that after switching over from the CIS PRO+ to the TEMPO+, subjects are able to maintain or even improve their own speech understanding capability.

Adult↗

High-resolution three-dimensional magnetic resonance imaging of the vestibular labyrinth in patients with atypical and intractable benign positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is a most common cause of dizziness and usually a self-limited disease, although a small percentage of patients suffer from a permanent form and do not respond to any treatment. This persistent form of BPPV is thought to have a different underlying pathophysiology than the generally accepted canalolithiasis theory. We investigated 5 patients who did not respond to physical treatment, presented with an atypical concomitant nystagmus or both with high-resolution three-dimensional magnetic resonance imaging of the inner ear. This method provides an excellent imaging of the inner ear fluid spaces. In all 5 patients, we found structural changes such as fractures or filling defects in the semicircular canals which we did not find in control groups. One patient clinically presented with the symptoms of a 'heavy cupula'. Whereas crosssections through the ampullary region and the adjoining utricle showed no abnormalities, there were significant structural changes in the semicircular canals, which are able to provide an explanation for the symptoms of a heavy cupula.

Adult↗

Magnetic resonance imaging and high-resolution computed tomography in the otospongiotic phase of otosclerosis.

Otosclerosis very often leads to severe hearing loss in a chronic progressive manner. In the first phase of the disease, otospongiosis causes an inflammatory osteolytic process in the osseous labyrinthine capsule. In the cases reported here, this osteolytic process was pronounced in the osseous capsule of the cochlea. High-resolution CT and MRI showed the precise localization and stage of this inflammatory-osteolytic process in the petrous bone, while scintigraphy confirmed the diagnosis.

Adult↗

Meningitis following cochlear implantation: pathomechanisms, clinical symptoms, conservative and surgical treatments.

Pneumococcal otogenic meningitis is a rare postsurgical complication that can develop following stapedectomy or after cochlear implantation. The bacterial infection can be fatal in some instances. A recent increase in the incidence of otogenic meningitis among cochlear implant wearers is of concern. The majority of meningitis cases are associated with a 2-component electrode manufactured by one cochlear implant company. The device with the added 'positioner' component has been withdrawn from the market (FDA Public Health Web Notification: Cochlear Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29, 2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent to otitis media and symptoms have developed from less than 24 h up to a few years after implantation. The purpose of this paper is to review and discuss the pathogenesis, pathology/bacteriology and to elaborate on some clinical features of otogenic meningitis in implanted children and adults. Essential aspects of surgery, electrode design, and cochleostomy seal are discussed. Conclusions are drawn from the available data and recommendations are made for good practice in cochlear implantation and follow-up.

Acute Disease↗

Noise-induced cochlear hypoxia is intensity dependent, correlates with hearing loss and precedes reduction of cochlear blood flow.

Anesthetized and artificially ventilated guinea pigs were exposed to broad-band noise of 95, 101, 106 or 115 dB SPL for 30 min and studied for 180 min after cessation of noise. The partial pressure of oxygen (pO2) in the perilymph, the cochlear blood flow (CoBF) and auditory-evoked potentials were continuously recorded. Arterial blood pressure, electrocardiogram, inspiratory and expiratory gas levels, arterial blood gas levels and acid-base status were kept stable to exclude influences of these parameters on cochlear parameters. Exposure to 95 dB SPL did not affect perilymphatic pO2 or CoBF. Cochlear microphonics (CMs) were reduced, but compound action potentials of the auditory nerve (CAPs) and auditory brainstem potentials (ABRs) increased after exposure to this low-level noise. Perilymphatic pO2 decreased during exposure to 101 dB SPL and then further decreased during the subsequent 60 min after cessation of the noise. CoBF did not change significantly during and 30 min after noise but then paralleled the decline of perilymphatic pO2. However, both parameters showed a clear indication of recovery in the second and third hours after noise. At 101 dB SPL, CMs were again reduced immediately, CAPs were unaltered and ABRs again increased. Exposure to 106 and to 115 dB SPL resulted in a decrease in both perilymphatic pO2 and CoBF; this decrease began during the exposure but became progressively worse after the noise. Hearing loss was observed immediately with exposure and showed no signs of further deterioration after cessation. The observed time courses of changes are important. They reveal that hearing loss and cochlear hypoxia precede reduction in CoBF due to noise exposure. The potential mechanisms underlying these effects are discussed.

Animals↗