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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

At least 91 records · Page 5Linked to original sources
PubMed1998

Tumor cell-specific transgene expression prevents liver toxicity of the adeno-HSVtk/GCV approach.

Treatment of colorectal liver metastases with the HSVtk/GCV approach and adenoviral vectors is highly toxic. We present a nontoxic alternative using the cell type-specific CEA promoter instead of the widely used hCMV immediate-early promoter to drive tk gene expression in the context of a recombinant adenovirus. Analysis of CEA promoter-dependent tk gene expression showed significant activity of this promoter in several human and rat tumor-derived cell lines but not in rat primary hepatocytes and in mouse liver, whereas the CMV promoter was highly active in all cell types and tissues investigated. CEA promoter-dependent tk gene expression was sufficient to kill 100% of cancer cells in vitro, even if less than 10% were infected by the adenoviral vector, indicating a significant bystander effect. Moreover, treatment of subcutaneous tumors in SCID mice with Ad.CEA-tk led to a several-fold reduction of tumor growth, and tail vein injection of a high dose of Ad.CEA-tk caused no side-effects in the liver. The CMV promoter was more potent than the CEA promoter in mediating GCV sensitivity to cancer cells in vitro and in vivo, but even a 20-fold reduction of the dose of Ad.CMV-tk did not prevent its liver cell toxicity after systemic application to mice and still resulted in the death of all animals within 4 days after the start of GCV treatment. These results indicate that restriction of tk gene expression to tumor cells in the liver prevents systemic toxicity. Moreover, the CEA promoter is a safe and efficient tool for tumor cell-specific expression of suicide genes in the liver.

Adenoviridae↗
PubMed1998

[Digital mammography: experiences in its clinical application].

TARGET: In 1989 in the Cantonal Hospital of Lucerne conventional film-screen mammography was replaced by digital mammography. With the support of a retrospective study, it was checked whether or not digital mammography represents an equally valid diagnostic procedure in daily routine. METHODS: 1204 patients were examined using digital mammography. A reevaluation of these patients was carried out using clinical and radiological routine controls. Additionally a radiological and histological examination was performed in 127 cases in which excisional biopsies had been done, paying particular attention to detail perception. RESULTS: The sensitivity of digital mammography achieved a total of 85%, whereas the accuracy was 81%. With additional use of ultrasound and galactography the sensitivity attained 91%. By reevaluation the sensitivity amounted to 87%, the accuracy remaining at 81%. The positive predictive value was especially high with 76% and 77%. CONCLUSION: Digital mammography offers satisfactory diagnostic performance.

Biopsy↗
PubMed1998

The endolymphatic sac receives antigenetic information from the organs of the mucosa-associated lymphatic system.

The endolymphatic sac holds the entire arrangement of immunocompetent cells and functions as an immunological potent control organ for the inner ear. The evidence of secretory immunoglobulin A and other features of lymphocyte subtypes characterizes the endolymphatic sac as an organ of the mucosa-associated lymphatic system (MALT). In this system a permanent recirculation of sensitized memory lymphocytes from one organ to the other has been demonstrated experimentally as serving to dispose memory lymphocytes after renewed antigenetic stimulus. The aim of this study was to prove the possible recirculation of antigen-sensitized lymphocytes to the endolymphatic sac after antigenic stimulus of another part of the mucosa-associated lymphatic system. The results are evidence that the endolymphatic sac is provided with immunocompetent cells which derive from the lymphatic tissue of the nasopharynx. While the origin of immunocompetent cells in the endolymphatic sac still remains uncertain, this study underlines the role of lympho-epithelial tissue of the nasopharynx as a possible cell source for the endolymphatic sac. The results might explain the altered or disturbed function of the endolymphatic sac as a possible cause of certain inner ear diseases.

Animals↗
PubMed1998

Time resolving ionization monitor for microsecond radiation impulses.

The current induced in the outer circuit of a fast response ionization chamber exposed to pulsed radiation consists of two components, a fast one induced by free electrons and a slow one induced by ions. The fast electron component may be used for the representation of the shape of the ionizing pulse. In order to avoid interference with the slow ion current, the latter has to be removed from the signal. This is achieved by deriving a voltage course from the chamber signal which fits the shape of the ion component and subtracting this from the entire signal. The function of the electronic circuit used for this purpose is described. Some considerations about the time resolution of the chamber gas are to be found in the appendix.

Electronics↗
PubMed1998

Nonlinear mechanics of the organ of Corti caused by Deiters cells.

Though the organ of Corti (OC) has been an object of experimental and theoretical hearing research, open questions remain concerning the processing of acoustic signals by the cochlea where the OC is located. Today there is extensive knowledge about single parts of the organ but a lack of understanding as to how these elements act together. One of the reasons for this is the missing analysis of the mechanics of the OC in three dimensions. In order to fill this gap, we have analyzed a short section (0.06 mm) of the basilar membrane including the OC and evaluated its nonlinear finite element model numerically. The Deiters cells are idealized as thin elastic beams with a comparably low modulus of elasticity of actin. Therefore, they show nonlinear mechanical behavior generating additional frequency components with two-tone stimulation.

Basilar Membrane↗
PubMed1998

Growth behavior of the 2 f1-f2 distortion product otoacoustic emission in tinnitus.

High-resolution hearing threshold and 2 f1-f2 distortion product otoacoustic emission (DP) were measured with the same in-the-ear sound probe and same calibration at 51 frequencies between 500 and 8000 Hz in 39 sensorineural hearing loss ears associated with tinnitus. Using a primary tone setting L1 = 0.4L2 + 39 that accounts for the nonlinear interaction of the two primary tones at the DP generation site at f2, DPs were elicited in a wide range from L2 = 65 to 20 dB SPL. We failed to find a uniform DP behavior in the 39 tinnitus ears tested. Seventeen of them behaved like impaired ears without tinnitus. In these ears a linearized DP growth was observed where the DP level decreased and the slope of the DP I/O functions steepened with increasing hearing loss and as a result both the DP level and the DP slope strongly correlated with hearing threshold. The other population, 22 tinnitus ears, exhibited a poor or even inverse relationship between DP level and hearing threshold, i.e., displayed an increase of DP level with increasing hearing loss. Despite the severe hearing loss but due to the high level, DPs could be recorded well in the frequency range that corresponded to the appearance of the tinnitus. The DP slope, however, increased with increasing hearing loss and, therefore, did still correlate with hearing threshold revealing pathological alteration. The data suggest that the DP level alone is hardly capable of assessing hearing impairment in tinnitus ears and may even be misleading. Thus just the DP slope seems to be the only reliable indicator of cochlear malfunction around the tinnitus frequency. The observed nonuniform DP behavior suggests different cochlear impairments in tinnitus ears. In those ears where the DP level decreases and the slope of the I/O functions increases with hearing loss, cochlear sensitivity and tuning are supposed to be diminished. In those ears where the DP level increases with increasing hearing loss, a reinforced mechanical distortion is hypothetized to be generated by cochlear hyperactivity that can be the source of both the abnormally high DP level and the tinnitus.

Adult↗
PubMed1998

The level and growth behavior of the 2 f1-f2 distortion product otoacoustic emission and its relationship to auditory sensitivity in normal hearing and cochlear hearing loss.

The 2 f1-f2 distortion product otoacoustic emission (DP) was measured in 20 normal hearing subjects and 15 patients with moderate cochlear hearing loss and compared to the pure-tone hearing threshold, measured with the same probe system at the f2 frequencies. DPs were elicited over a wide primary tone level range between L2 = 20 and 65 dB SPL. With decreasing L2, the L1-L2 primary tone level difference was continuously increased according to L1 = 0.4L2 + 39 dB, to account for differences of the primary tone responses at the f2 place. Above 1.5 kHz, DPs were measurable with that paradigm on average within 10 dB of the average hearing threshold in both subject groups. The growth of the DP was compressive in normal hearing subjects, with strong saturation at moderate primary tone levels. In cases of cochlear impairment, reductions of the DP level were greatest at lowest, but smallest at highest stimulus levels, such that the growth of the DP became linearized. The correlation of the DP level to the hearing threshold was found to depend on the stimulus level. Maximal correlations were found in impaired ears at moderate primary tone levels around L2 = 45 dB SPL, but at lowest stimulus levels in normal hearing (L2 = 25 dB SPL). At these levels, 17/20 impaired ears and 14/15 normally hearing ears showed statistically significant correlations. It is concluded that for a clinical application and prediction of the hearing threshold, DPs should be measured not only at high, but also at lower primary tone levels.

Adolescent↗
PubMed1998

Effect of hyperbaric oxygen therapy in comparison to conventional or placebo therapy or no treatment in idiopathic sudden hearing loss, acoustic trauma, noise-induced hearing loss and tinnitus. A literature survey.

With the published clinical data to hand on the therapeutic results of patients with idiopathic sudden hearing loss, acoustic trauma or noise-induced hearing loss, it may be confirmed that 65% of those polypragmatically treated patients demonstrated a hearing improvement of 19 +/- 4 dB. In 35% of the cases, no hearing improvement was detected independent of the drugs administered. This corresponds to the results obtained from placebo-treated patients who demonstrated a hearing improvement of 20 +/- 2 dB in 61% of cases and no hearing gain in 39% of cases (fig. 1). A different set of results was obtained from patients with a hearing loss who were treated either with prednisolone or placebo. The percentage of patients who achieved normal hearing again in the placebo-treated group amounted to 31% and 38% and in the verum-treated group 50% and 78%. It may be concluded that a placebo therapy is equally effective to that of all nonsteroidal drugs. Problems arise when comparing non-treated patients since information on spontaneous remission rates differs greatly in the references, i.e. between 25-68% for spontaneous full remissions and 47-89% for spontaneous partial remissions. From a statistical view, 35% and 39% of patients experienced no success with nonsteroidal drugs or placebo, respectively. These patients can still be helped with HBO therapy. 18 patients only underwent primary HBO therapy. In all other 50 studies evaluated here with a total of 4, 109 patients suffering from idiopathic sudden hearing loss, acoustic trauma or noise-induced hearing loss and/or tinnitus, HBO therapy was administered as a secondary therapy, i.e. following unsuccessful conventional therapy. If the onset of affliction was more than 2 weeks but no longer than 6 weeks, one half of the cases showed a marked hearing gain (in at least 3 frequencies of more than 20 dB), one-third showed a moderate improvement (10-20 dB) and 13% showed no hearing improvement at all (fig. 2). 4% no longer experienced tinnitus, 81.3% observed an intensity decrease and 1.2% an intensity increase of their tinnitus condition. 13.5% remained unchanged (fig. 2). If HBO therapy was administered at a later stage, but still within 3 months following onset of affliction, 13% showed a definite improvement in hearing, 25% a moderate improvement and 62% no improvement at all. 7% no longer suffered from tinnitus, 44% reported an intensity decrease, a similar percentage noticed no change and 5% a temporary deterioration of their tinnitus condition. If the onset of affliction was longer than 3 months up to several years, no hearing improvement can be expected in the majority of patients (fig. 3); however, one third of the cases reported an intensity decrease of tinnitus, 60-62% reported no change and 4-7% noticed a temporary intensity increase (fig. 4). In conclusion, it may be deduced that HBO therapy is recommended and warranted in those patients with idiopathic sudden deafness, acoustic trauma or noise-induced hearing loss within 3 months after onset of disorder.

Clinical Trials as Topic↗
PubMed1998

Delayed facial palsy following uneventful middle ear surgery: a herpes simplex virus type 1 reactivation?

In rare cases, a facial palsy appears a few days after uneventful middle ear surgery. The reason for this delayed palsy is unclear. One hypothesis is that it results from a reactivation of herpes simplex virus type 1 (HSV-1) in the geniculate ganglion of the facial nerve. From 1987 to 1996, in the course of over 1,800 middle ear operations, we observed 7 ipsilateral delayed facial palsies and investigated 5 of them using immunologic and virologic methods, including the polymerase chain reaction (PCR). We could detect HSV-1 genome with the nested primer PCR in the tongue swabs of 4 of the 5 examined patients with delayed facial palsy. The immunologic changes in these palsies are also compatible with a reactivation of HSV-1. We conclude that minimal stimulation of the facial nerve during middle ear surgery could result in a reactivation of HSV-1 in the geniculate ganglion, which may in turn lead to a facial palsy.

Adult↗
PubMed1998

[Surgical treatment of bone metastases in breast carcinoma].

The operative treatment of skeletal metastases takes only a small part of the total of traumatology and orthopaedic treatments. They should taken within the scope of an interdisciplinary treatment plan and mean a palliative step. The pathological fracture is, especially such of the spinal column and the long bones an absolute indication for stabilisation. The prophylactic stabilisation has priority by patients with osteolyses, because essential benefits. 48 operative steps in all has been taken between 1995 and 1997 in the "Zentrum für Orthopädie, Unfall- und Wiederherstellungschirurgie" of the Klinikum Suhl.

Bone Neoplasms↗
PubMed1997

Induction of an inner-ear-specific autoreactive T-cell line for the diagnostic evaluation of an autoimmune disease of the inner ear.

Different patterns of sensorineural hearing loss with a potential improvement in auditory function following immunosuppressive therapy might be caused by an isolated autoimmune disease of the inner ear. Because of the lack of well-defined detection methods 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. Previous studies found evidence that this entity might be cellular mediated. By heterologeous immunization of inbred Lewis rats with inner-ear tissue, an autoreactive inner-ear-specific T-cell line was established. After passive transfer of these cells, a labyrinthitis was induced in recipient animals. The experimental design can serve as an animal model for a cellular-mediated autoimmune disease of the inner ear. Further studies have to split the cochlear proteins and to identify the protein with the strongest autoimmunological potency. After biotechnical production of this protein, a clinical test to diagnose an autoimmune disease of the inner ear in man should be possible.

Animals↗
PubMed1997

Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells.

The pathogenesis and etiology of Hodgkin's disease, a common human malignant lymphoma, is still unresolved. As a unique characteristic, we have identified constitutive activation of the transcription factor nuclear factor (NF)-kappaB p50-RelA in Hodgkin/Reed-Sternberg (H/RS) cells, which discriminates these neoplastic cells from most cell types studied to date. In contrast to other lymphoid and nonlymphoid cell lines tested, proliferation of H/RS cells depended on activated NF-kappaB. Furthermore, constitutive NF-kappaB p50-RelA prevented Hodgkin's lymphoma cells from undergoing apoptosis under stress conditions. Consistent with this dual function, Hodgkin's lymphoma cells depleted of constitutive nuclear NF-kappaB revealed strongly impaired tumor growth in severe combined immunodeficient mice. Our findings identify NF-kappaB as an important component for understanding the pathogenesis of Hodgkin's disease and for developing new therapeutic strategies against it.

Animals↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin.

Base Sequence↗
PubMed1997

Herpes simplex virus antibodies in the perilymph of patients with Menière disease.

OBJECTIVE: To evaluate the presence of IgG antibodies directed to herpes simplex virus (HSV) in the perilymph of patients with Menière disease. DESIGN: Antibodies to HSV, Epstein-Barr virus, cytomegalovirus, and measles virus were analyzed in serum and perilymph samples by enzyme-linked immunosorbent assay. Total IgG and albumin in serum and perilymph samples were measured by nephelometer analysis. The relation of specific antivirus IgG in the perilymph vs the serum was expressed as an index. PATIENTS: Perilymph and serum samples from 7 patients with long-standing, disabling Menière disease were collected during therapeutic vestibulotomy. Perilymph and serum samples from 7 patients with otosclerosis and 2 recipients of cochlear implants were used as controls. RESULTS: Compared with the corresponding serum sample, the perilymph from the patients with Menière disease disclosed a higher level of specific anti-HSV IgG. An elevated level of specific anti-measles virus IgG in the perilymph was detected in patients with otosclerosis. Patients of all groups showed no variation of specific anti-Epstein Barr virus IgG and anti-cytomegalovirus IgG in the serum or in the perilymph. CONCLUSIONS: Our results show the presence of HSV IgG in the perilymph of patients with Menière disease and support the hypothesis that HSV may play an important role in the etiopathogenesis of Menière disease.

Antibodies, Viral↗
PubMed1997

Experiences with the Montgomery Salivary Bypass Tube (MSBT)

Patients with hypopharyngeal and cervical esophageal strictures and fistulas caused by advanced malignancy, ingestion of caustic material, or following surgery or radiation therapy often suffer from marked dysphagia. In such cases the implantation of a Montgomery Salivary Bypass Tube (MSBT) can be an effective therapeutic option to bridge the fistulous tract or bypass a stenosis. Being able to eat and drink without the need for intravenous supplementation or nasogastric or gastrostomy tube feeding in general greatly improves the patient's quality of life. Since 1981 we have successfully inserted the MSBT in 44 cases suffering from dysphagia of different etiology. Our experiences with the indications for implantation, insertion techniques, and postoperative results are presented. Three selected cases of progressive dysphagia in which the MSBT is demonstrated to be the treatment of choice are described in more detail. In one case, a tracheoesophageal fistula and in another a stricture of the upper esophageal sphincter (UES) were bypassed so that oral intake of soft food became possible again. The third patient suffered from a disturbance of the esophageal motility after resection of a Hippel-Lindau tumor in the spinal cord and syringe drainage; even swallowing saliva was impeded. After insertion of a MSBT, uncomplicated soft food intake became possible again.

Adult↗