Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.

BACKGROUND: Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). PATIENTS AND METHODS: CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. RESULTS: The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. CONCLUSIONS: This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM(+)) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.

BACKGROUND: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. METHODS: LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. RESULTS: In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. CONCLUSIONS: GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo.

Extraventricular neurocytoma of the spinal cord in a dog.

Central neurocytoma is a rare, prognostically favorable neuronal tumor of the human central nervous system, typically located intraventricularly near the foramen of Monro. Extraventricular cerebral neurocytomas and spinal tumors have also been reported. To date, however, neurocytomas have not been documented in domestic animal species. In this report, we describe a spinal cord tumor in a dog. The microscopic examination revealed tumor cells forming loosely packed clusters in some areas and palisades in other areas. In addition, they showed fine fibrillary neuropil-like areas of different sizes, sometimes resembling the "rosettes" of pineocytomas, as well as ependymoma-like perivascular pseudorosettes. The tumor cells had scant eosinophilic cytoplasm, with perinuclear halos, closely resembling the appearance of oligodendroglioma. Immunohistochemical staining showed expression of synaptophysin and neuron-specific enolase by tumor cells and pronounced in fibrillary areas. On the basis of histomorphology and immunohistochemical reactivity, the present tumor was diagnosed as extraventricular neurocytoma.

Functionally distinct monomers and trimers produced by a viral oncoprotein.

While the process of homo-oligomer formation and disassembly into subunits represents a common strategy to regulate protein activity, reports of proteins in which the subunit and homo-oligomer perform independent functions are scarce. Tumorigenesis induced by the adenovirus E4-ORF1 oncoprotein depends on its binding to a select group of cellular PDZ proteins, including MUPP1, MAGI-1, ZO-2 and Dlg1. We report here that in cells E4-ORF1 exists as both a monomer and trimer and that monomers specifically bind and sequester MUPP1, MAGI-1 and ZO-2 within insoluble complexes whereas trimers specifically bind Dlg1 and promote its translocation to the plasma membrane. This work exposes a novel strategy wherein the oligomerization state of a protein not only determines the capacity to bind separate related targets but also couples the interactions to different functional consequences.

Spontaneous and experimental glycoprotein storage disease of goats induced by Ipomoea carnea subsp fistulosa (Convolvulaceae).

Spontaneous and experimental poisoning with the swainsonine-containing and calystegine-containing plant Ipomoea carnea subsp fistulosa is described. Three of 8 goats presenting with emaciation, weakness, symmetrical ataxia, posterior paresis, proprioceptive deficits, abnormal posture, abnormal postural reaction, and muscle hypertonia were necropsied. I fistulosa was suspected to be the cause of the neurologic disease in all cases. An experiment was conducted to confirm the diagnosis using 12 goats and diets containing 3 different concentrations of the plant. All goats fed I fistulosa developed neurological signs that were similar to those observed in the spontaneous intoxication. Muscle atrophy and pallor were the only macroscopic changes observed in spontaneous and in experimental intoxication. Histological lesions of spontaneous and experimental animals were similar. The most prominent lesion was cytoplasmic vacuolation in neurons of the central and the autonomous nervous system, pancreatic acinar cells, hepatocytes, Kupffer cells, follicular epithelial cells of the thyroid gland, and macrophages of the lymphatic tissues. Neuronal necrosis, axonal spheroids formation, and astrogliosis were additionally observed in the brain. Ultrastructurally, the cytoplasmic vacuoles consisted of distended lysosomes surrounded by a single-layered membrane. Nonreduced end-rests or sequence of alpha-Man, alpha-Glc, beta(1-4)-GlcNAc, and NeuNAc on lysosomal membrane were revealed by lectin histochemistry. Samples of plants used in the experimental trial contained swainsonine and calystegine and their intermediary derivate. We conclude that I fistulosa induces a glycoprotein storage disease primarily based on the inhibition of the lysosomal alpha-mannosidase by the alkaloid swainsonine.

Cognitive processing in headache associated with sexual activity.

Cognitive processing in headache associated with sexual Cognitive processing as measured by event-related potentials (ERP) in patients suffering from the explosive subtype of headache associated with sexual activity (HSA type 2) was investigated. Visual ERP were measured in 24 patients with HSA type 2 outside the headache period. The differences of the first and the second part of measurement were evaluated separately to determine the amount of cognitive habituation. Twenty-four sex- and age-matched healthy subjects and 24 patients with migraine without aura served as controls. A missing increase of P3 latency during the second part of the measurement was found in 79% of patients with HSA type 2 and in 75% with migraine, but only in 17% of the healthy controls (P < 0.001). The P3 amplitude was increased during the second part in 71% of patients with HSA type 2 and in 79% with migraine, but only in 33% of the healthy controls (P = 0.02). Mean P3 latency was decreased and mean P3 amplitude was increased during the second part of the measurement in HSA type 2 and in migraine but not in the healthy control group. Patients with HSA type 2 have a loss of cognitive habituation as measured by ERP. This specific information processing is very similar to that in migraine observed in previous studies.

Headache associated with sexual activity: demography, clinical features, and comorbidity.

OBJECTIVE: S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). METHODS: Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. RESULTS: The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). CONCLUSION: Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

[Bilateral vestibular loss. Diagnosis and follow-up]. / Der beidseitige Vestibularisausfall. Diagnostik und Krankheitsverlauf.

BACKGROUND: Atypical symptom in patients with bilateral vestibular loss is head movement-induced oscillopsia. The paucity of precise complaints in many patients is surprising. Therefore, bilateral loss of vestibular function is often undiagnosed. PATIENTS: We report on the long-term follow-up in 29 patients. They were monitored for 2-7 years (mean: 4.5 years). RESULTS: Of the 29 patients 16 described oscillopsia. All symptomatic patients had acute bilateral vestibular loss.Patients described that their symptoms improved over a period of 1-2 years. Improvement was not age dependent. CONCLUSIONS: Otoneurologists should be aware of the particular clinical symptoms in bilateral vestibular loss. Regarding clinical features, compensation of bilateral vestibular loss seems to be unlikely only based on central compensatory eye movement reflexes. More likely perceptual adaptations and restriction of head movement are responsible for subjective improvement.

Evidence of infectious diseases in harbour porpoises (Phocoena phocoena) hunted in the waters of Greenland and by-caught in the German North Sea and Baltic Sea.

The pathological, microbiological and serological findings in harbour porpoises hunted in Greenlandic waters were compared with the findings in animals accidentally caught in fishing gear in the German North Sea and Baltic Sea. The body condition of the Greenlandic animals was good, whereas nine of 23 German harbour porpoises were moderately to markedly emaciated. Both groups were infested with parasites. In the Greenlandic animals parasitism of the aural peribullar cavity with Stenurus minor, of the liver and pancreas with Orthosplanchnus mironovi, of the lungs with Halocercus species and of the subcutaneous and mammary tissue with Crassicauda species was generally associated with a mild inflammatory response. No diseases associated with bacteria were identified in any of the Greenlandic harbour porpoises. In the porpoises from the German North Sea and Baltic Sea, parasites were present in the aural peribullar cavity (S minor), liver (Campula oblonga), first and second gastric compartment (Anisakis simplex) and in the lungs (Pseudalius inflexus and Torynurus convolutus). Moderate to marked pulmonary parasitism and suppurative pneumonia, not observed in the Greenlandic porpoises, were present in 11 and 10, respectively, of the 23 German porpoises. The suppurative pneumonia was attributed to bacterial infection with beta-haemolytic streptococci and Escherichia coil var haemolytica. Four Greenlandic and 10 German porpoises had positive porpoise morbillivirus-specific antibody titres suggesting that the virus was circulating in both populations.

Post-mortem findings in harbour porpoises (Phocoena phocoena) from the German North and Baltic Seas.

Between 1991 and 1996, necropsies were performed on 445 harbour porpoises (Phocoena phocoena), in various states of preservation, stranded on German coasts or accidentally caught by German fishermen. The animals originated from the North and Baltic Seas, and 133 were considered suitable for histopathological, immunohistochemical and microbiological examination. Most of the lesions in these 133 porpoises were caused by parasites, in particular in the respiratory tract, two-thirds of the animals exhibiting pneumonia associated with the parasites. Pneumonia was considered to be the cause of death in 46% of the stranded subadult and adult animals. The findings gave no evidence of any epidemic due to bacterial or viral infection. Bacteriological examination suggested that pneumonia was mainly caused by secondary bacterial infection and not by parasitic infestation alone. Beta-haemolytic streptococci were considered to be the main infectious agents. Morbillivirus antigen was not detected immunohistochemically.

[Pseudoemissions and false positive findings in measurement of transiently evoked otoacoustic emissions (TEOAE)]. / Pseudoemissionen und falsch positive Befunde in der Messung transitorisch evozierter otoakustischer Emissionen (TEOAE)1.

BACKGROUND: Recording procedure of transiently evoked otoacoustic emissions is an important part of diagnostics in pediatric audiology. As a rule of thumb measurable TEOAE excludes more than slight hearing impairment. Nevertheless any interpretation of these measurements in a clinical setting must consider supposed false positive findings (so called pseudoemissions) and real false positive findings in cases of profound hearing loss with reproducible TEOAE and missing auditory evoked potentials. PATIENTS AND METHODS: TEOAE recordings in 512 patients were evaluated for recording procedure failure. Possible types of recording procedure failure were divided into failures conditioned by the patients and stimulus or probe dependent failures. In case of insufficient test procedure and absent TEOAE recording procedure was improved and repeated. RESULTS: In 2 patients with severe to profound hearing loss we discovered reproducible TEOAE whereas auditory evoked potentials were missing. As a stimulus and probe dependent recording procedure failure we saw reproducible pseudoemissions in 3 other patients with profound hearing loss. CONCLUSIONS: These results indicate that conclusions concerning hearing ability on the base of TEOAE should keep in mind possible pseudoemissions as a result of recording procedure failure. Reported cases with absent auditory evoked potentials and reproducible TEOAE showed that TEOAE recordings in these cases indicate substantially preserved outer hair-cell function independent of profound hearing loss.

[Surgery of the external auditory canal in familial bilateral auditory canal atresia]. / Die Chirurgie des äusseren Gehörgangs bei familiärer bilateraler Gehörgangsatresie.

BACKGROUND: Inherited isolated bilateral atresia of the external auditory canal is rare. Ear canal surgery procedure is difficult. METHODS: Basing on a case report of a family with inherited isolated bilateral atresia of the external auditory canal in 4 cases the way of preoperative diagnostics including human genetics and our surgical concept is described. RESULTS: Resulting clinical findings showed complete epithelialization of the ear canal and ear drum with slight conductive hearing loss. CONCLUSIONS: Canaloplasty in atresia can be easily and successfully accomplished by our modified technique.

Distribution of Borna disease virus in the brain of rats infected with an obesity-inducing virus strain.

Experimental infection of Lewis rats with Borna disease virus (BDV), a nonsegmented, single-stranded RNA virus, usually causes an immune-mediated biphasic neurobehavioral disorder. Such animals develop a persistent infection of the CNS with viral antigen expression in all brain regions and a disseminated nonpurulent meningoencephalitis. Interestingly, intracerebral infection of Lewis rats with a BDV-variant (BDV-ob) causes a rapid increase of body weight with the development of an obesity syndrome without obvious neurological signs. The obese phenotype is correlated with a characteristic distribution of inflammatory lesions and BDV-antigen in the rat brain. Infiltration with mononuclear immune cells and viral antigen expression are restricted to the septum, hippocampus, amygdala and ventromedian tuberal hypothalamus. Therefore, infection with the obesity-inducing BDV-ob results most likely in neuroendocrine dysregulations leading to the development of an obesity syndrome. This might be due to the restriction of viral antigen expression and inflammatory lesions to brain areas which are involved in the regulation of body weight and food intake. The BDV-induced obesity syndrome represents a model for the study of immune-mediated neuroendocrine disorders caused by viral infections of the CNS.

Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs.

OBJECTIVE: To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner. ANIMALS: 20 clinically normal, 8- to 12-month-old male Beagles. PROCEDURE: All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed. RESULTS: One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium X phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules. CONCLUSIONS AND CLINICAL RELEVANCE: Pamidronate disodium is a potentially useful drug to reduce CCF-induced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs.

[Surgical treatment of auditory canal exostoses]. / Die operative Behandlung von Gehörgangsexostosen.

BACKGROUND: Although complications of surgical removal of external auditory canal exostoses are rare, reported surgical complications include tympanic membrane perforation, postoperative hearing loss, canal stenosis, and facial nerve injuries. PATIENTS AND METHODS: We report on our experience in exostosis surgery, consisting of 59 procedures in 48 patients. Preoperative and postoperative complaints and findings, intraoperative complications, and audiologic results are described and discussed. There has been a minimum of one year of follow-up in every case. RESULTS: Postoperative canal stenosis was seen in 2 cases of preoperative severe persistent external otitis. Temporary threshold shift was recorded in 6 patients. Persistent sensorineural hearing loss occurred in 4 patients. Six of the 10 patients with temporary or persistent hearing loss had already shown preoperative sensorineural hearing loss. Intraoperatively tympanic membrane perforation occurred in 3 cases, accidental opening of the mastoid in 1 case. CONCLUSIONS: Exostosis surgery should be reserved for uninfected ear canals. Meatal skin preservation without circular meatal flap incision is recommended to avoid postoperative canal stenosis. Especially in cases of preexisting sensorineural hearing loss, attention should be focused on the intraoperative noise reduction by tympanic membrane protection and pauses of noise exposition.

Thymic cysts in harbor porpoises (Phocoena phocoena) from the German North Sea, Baltic Sea, and waters of Greenland.

Thymic cysts have not been previously reported in harbor porpoises (Phocoena phocoena). Two hundred forty stranded or "by-caught" harbor porpoises originating from the German North Sea and Baltic Sea and 14 animals from the waters of Greenland were necropsied. Thymuses of 78 porpoises of the North Sea and Baltic Sea were considered suitable for histopathologic examination based on the extent of postmortem autolysis. Immunohistochemistry using an anti-cytokeratin antibody was employed to demonstrate thymic epithelial structures in selected cases. Thymic macrocysts were rare and were only found in animals > or =7 years of age. Thymic microcysts, lined by a single cytokeratin-positive cell layer, were common in involuting thymuses, and the prevalence increased with advancing age. Thymic cysts might have arisen from degenerating Hassall's corpuscles or condensed epithelial reticulum. Thymuses were easily identified macroscopically in most adult healthy harbor porpoises, suggesting that physiological thymic involution proceeds slowly in this species.

Expression of major histocompatibility complex class II antigen in neoplastic cells of canine cutaneous histiocytoma.

Forty five cases of canine cutaneous histiocytoma (CCH) were examined by immunohistology for expression and distribution of major histocompatibility complex (MHC) class II antigen in neoplastic cells. In addition, expression of lysozyme and calprotectin (leucocyte protein L1) in neoplastic cells was investigated. Furthermore, B and T lymphocytes were demonstrated by antibodies against the CD3 antigen, IgG, and IgM. Neoplastic cells showed two staining patterns for MHC class II antigen: focal juxtanuclear cytoplasmic staining and/or rim-like staining along the cell periphery. In 24 cases, a predominant or exclusive focal juxtanuclear cytoplasmic MHC class II antigen reaction in neoplastic cells, and the presence of few diffusely distributed infiltrating CD3 antigen-positive T lymphocytes were observed. Tumors with numerous neoplastic cells exhibiting staining for MHC class II antigen along the cell periphery (n = 21) showed increased inflammatory alterations, represented by disseminated and nodular infiltrations of mainly CD3 antigen-positive T cells. B cells, plasma cells, exudate macrophages, and neutrophils were rarely seen disseminated between neoplastic cells whereas their number increased within focal inflammatory infiltrates. The focal cytoplasmic reaction for MHC class II antigen in neoplastic cells might represent newly synthesized MHC class II molecules stored in vesicles, whereas staining of the cell periphery might occur due to accumulation of MHC class II molecules along the plasma membrane. The increasing expression of MHC class II molecules on the cell surface might be the decisive factor for onset and progression of tumor regression. However, the exact mechanism of priming and activation of T cells by neoplastic cells and the nature of the presented antigen are not yet known.

[Cochlear implant for non-deaf patients?]. / Cochlear-Implant-Versorgung bei nicht tauben Patienten?

BACKGROUND: Cochlear implants have proven to be the method of choice for postlingually deafened adults. The great success of this application requires discussion of the degree in which the indication for cochlear implantation should be expanded to include patients with residual hearing. METHOD AND PATIENTS: Following an initial discussion of the term deafness, we present the preoperative and postoperative results in five patients with residual hearing. These patients achieve a certain degree of speech recognition with their well fitted hearing aids. However, their aided speech intelligibility did not exceed 30% with the standardized Freiburg monosyllabic word test at 70 dB. In each case the worse hearing ear was treated with a cochlear implant. Speech discrimination in silence and noise are compared with the results of a group of postlingually deafened cochlear implant patients. RESULTS: The five patients are very satisfied with the cochlear implant and use the telephone to communicate with unknown partners. They score 100% in the standardized four-syllable number test above 55 dB and they document a loss of speech discrimination between 0 and 25% within the open-set monosyllabic word test. The mean increase of best monosyllable intelligibility by the cochlear implant over the hearing aids is 65%. Using the innsbruck sentence test the patients score 100% at 70 dB; with the Göttingen sentence test, the mean result is 75%. Their mean results in noise are also very good, 76% at 10 dBS/N and 57% at 5 dBS/N respectively. None of these patients use the hearing aid on the untreated, better hearing ear. CONCLUSION: A multichannel cochlear implant lead to a significant improvement of speech comprehension in these patients with residual hearing. We can successfully implant patients with minimal benefit of their well fitted hearing aids. Our group is too small to be able to define general selection criteria. For the time being we use as an audiological indication a open-set monosyllabic word intelligibility of not more than 30% at 70 dB with well fitted hearing aids.

[Objective criteria for expert assessment of vestibular vertigo]. / Objektive Kriterien für die Begutachtung des vestibulären Schwindels.

BACKGROUND: Even for experienced examiners quantitative and objective medicolegal assessment of vestibular vertigo is difficult. Current medicolegal opinions place disproportionate emphasis of subjective symptoms. METHODS: Based on parameters from spontaneous and provoked vestibular nystagmus with Frenzel's glasses, objective criterias for adequate medicolegal assessment of vestibular disorders are presented. Diagrams in tabular form for unilateral and bilateral vestibular dysfunction and benign peripheral positional vertigo allow assessment of reduction in earning capacity. CONCLUSIONS: The widespread use of subjective criteria in the medicolegal evaluation of vestibular complaints should not be accepted. The qualified ENT specialist is able to evaluate vestibular deficits using objective and reproducible methods.