The Ossicle Bank of the University Medical Centre (UMCU), The Netherlands.
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Bone Banks↗
Biomedical subjects
J E Veldman
Publications and source records attributed to J E Veldman.
['Surgery by the red-haired barbarians'; Dutch physicians in Japan, 1600-1870].
Approximately 400 years ago, Dutch physicians laid the foundations for Western medicine in Japan. Around 1860, Dutch naval surgeons, trainees of the College of Army Surgeons in Utrecht, were to become the founders of the Medical Faculties at the Universities of Nagasaki, Tokyo and Osaka. The earlier Deshima-settlement surgeons Engelbert Kaempfer and Philipp Franz von Siebold played a highly important role in our knowledge of Japan during the 18th and 19th centuries.
Faculty, Medical↗
Fluoride therapy for cochlear otosclerosis? an audiometric and computerized tomography evaluation.
The progress of sensorineural hearing loss (SNHL) in patients with cochlear otosclerosis was compared for 19 patients treated with fluoride for 1-5 years and 22 untreated controls. CT scans of eight patients before and after fluoride treatment were evaluated visually. Fluoride therapy arrested the progression of SNHL in the low (250, 500 and 1,000 Hz) (p < 0.001) and high (2 and 4 kHz) (p = 0.008) frequencies. It seemed to be more effective for the higher frequencies in cases with an initial SNHL of < 50 dB. Fluoride administration for 4 years did not seem to be superior to a shorter treatment period (1-2 years). For six patients followed up after discontinuing fluoride therapy there was minimal deterioration in SNHL. There was no clear relationship between the size and site of otospongiotic lesions on CT and the severity of SNHL. Follow-up with CT evaluation did not provide reliable information as to the efficacy of fluoride therapy.
Adult↗
Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea.
Numerous studies investigating cisplatin ototoxicity in animals have been performed, but it is difficult to derive a clear dose-effect relation from these studies. The degree of cisplatin-induced ototoxicity depends on a multitude of factors. Many parameters, such as dose, mode of administration, dosage schedule and concomitant administration of protective additives, vary among the published studies. Therefore, we performed a basic dose-effect study on cisplatin ototoxicity in the guinea pig. Albino guinea pigs were treated with cisplatin at daily doses of either 0.7, 1.0, 1.25, 1.5 or 2.0 mg/kg for 8 consecutive days. Electrocochleography was performed on day 10 after which the cochleas were removed and processed for histological examination. The electrophysiological results showed a marked transition from almost no ototoxic effect to a large effect between a daily dose of 1.25 and 1.5 mg/kg (Stengs et al., 1998). Outer hair cell (OHC) counts corresponded well with the electrophysiological results. At daily doses of 0.7, 1.0 and 1.25 mg/kg no statistically significant OHC loss was observed, whereas OHC loss averaged 60% and 65% in the basal turns at daily doses of 1. 5 and 2.0 mg/kg, respectively. Morphological changes in the stria vascularis were present only in cochleas from animals treated with cisplatin doses of 1.0, 1.25 and 1.5 mg/kg/day. Cochleas from animals treated with a daily cisplatin dose of 2.0 mg/kg for 8 consecutive days showed an endolymphatic hydrops. The present study shows that cisplatin, administered at a daily dose of 1.5 mg/kg for 8 consecutive days, provides a degree of OHC loss that is well suited to study the effects of putative protective agents and possible hair cell recovery.
Animals↗
Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?
Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infrequently, recovery of hearing has been described in animals and humans. Stengs et al. (1997) treated guinea pigs with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days and subsequently studied cochlear function after survival times varying from 1 day to 16 weeks. Spontaneous improvement of the hair cell-related potentials (cochlear microphonics and summating potentials) was observed starting 2 weeks after cessation of treatment. In the present study we examined light microscopically the cochleas used in the study of Stengs et al. (1997). One day after cessation of cisplatin administration outer hair cell (OHC) loss in the basal cochlear turn averaged 66%. In the 1-week survival group, OHC counts were similar to those of the 1-day survival group. In the 4-week survival group, however, a relatively small loss of OHCs was found in the basal cochlear turn; OHC loss averaged only 15%. A similar loss was found after 8 weeks. In the 16-week survival group, OHC loss in the basal turn increased to 48%, but this was not statistically significant. Our histological observations are in line with the electrophysiological data from the same animals. Our findings suggest that OHCs recover from cisplatin-induced damage 1-4 weeks after treatment. However, the results do not allow a conclusion as to whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs.
Animals↗
Histological effects of co-administration of an ACTH((4-9)) analogue, ORG 2766, on cisplatin ototoxicity in the albino guinea pig.
Cisplatin is one of the most potent antineoplastic drugs presently known, but its therapeutic efficacy is seriously limited by several side effects such as ototoxicity. Several compounds that are known for their nephroprotective effects also seem to reduce the incidence and severity of cisplatin-induced ototoxicity. Hamers et al. (1994) and De Groot et al. (1997) investigated the possibly protective effect of concomitant administration of the ACTH((4-9)) analogue ORG 2766 upon cisplatin ototoxicity in guinea pigs. Animals were treated with cisplatin at a daily dose of 2.0 mg/kg for 8 consecutive days and ORG 2766 at a daily dose of 75 mcg/kg for 9 days. Concomitant administration of cisplatin plus ORG 2766 resulted in a bimodal distribution of the electrophysiological data (compound action potential and cochlear microphonics amplitudes) and the histological data (outer hair cell (OHC) counts). It was surmised that this dichotomy might occur at a certain cisplatin dose. We investigated whether this protective effect of ORG 2766 could be enhanced by reducing the daily dose of cisplatin while maintaining the same dose of ORG 2766. Thirty-six animals were treated with daily i.p. injections of cisplatin at a dose of 1.0 mg/kg (n=18) or 1.5 mg/kg (n=18) for 8 consecutive days. When comparing the mean OHC counts of the different experimental groups, treatment with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days resulted in a considerable loss of OHCs, which was significantly reduced after co-administration of ORG 2766. Co-treatment with ORG 2766 did not result in a change in the volume of the scala media. The present results are in agreement with the electrophysiological results published earlier (Stengs et al., 1998b).
Adrenocorticotropic Hormone↗
Experimental autoimmune inner ear disease: an electrocochleographic and histophysiologic study.
Systemic immunization with swine inner ear antigens in complete Freund's adjuvant induces functional disturbances in the cochlea. Morphometric data indicate that an endolymphatic hydrops develops within 2 weeks. It diminishes 6 weeks after immunization. A progressive decrease in the compound action potential amplitude is observed from 2 to 6 weeks after immunization. Enhancement of the amplitude of the summating potential is present without a clear overall correlation to the presence of endolymphatic hydrops. The amplitude of the cochlear microphonics shows no significant changes after immunization. Western blot analysis of the sera performed 2 and 6 weeks after immunization shows enhanced reactivity at 68, 50, 45, and 27 kd molecular weights, as compared to controls. The same spectrum of cross-reacting antibodies is believed to be instrumental in immune-mediated sensorineural hearing loss in patients. Apparently, cross-reacting antibodies and released mediators disturb cochlear homeostasis, resulting in the observed changes in the electrophysiological responses. However, these changes are not clearly related to structural changes at the light and electron microscopic levels.
Animals↗
Induction of endolymphatic hydrops in the guinea pig by perisaccular deposition of sepharose beads carrying and not carrying immune complexes.
We tried to induce endolymphatic hydrops in guinea pig cochleas by unilateral, perisaccular deposition of sepharose beads carrying immune complexes. Controls consisted of the deposition of sepharose beads without immune complexes and the contralateral, untreated ear. The effects of the treatment were studied by light microscopy and electrophysiological recordings of the gross cochlear potentials 1, 2, and 6 weeks after treatment. Each condition included six animals. Analysis of variance of the morphometric data concerning the ears treated with deposition of the beads showed a statistically significant difference (P = 0.04) between the degree of hydrops found for the beads with immune complexes and for those without. The difference between the treated ears and the contralateral untreated ears was significant (P = 0.01) for the beads with immune complexes and not significant (P = 0.8) for those without immune complexes while there was no significant effect of post-treatment time interval. Analysis of variance of the electrophysiological data, collected in response to tone bursts at the apex of the cochlea, showed no significant differences between the results for the beads with and without immune complexes. Therefore these results were pooled. One week after treatment the pooled results for the compound action potential showed a small decrease in amplitude, just significant at 2 kHz, but not at 4 and 8 kHz. This decrease disappeared completely after 6 weeks. The pooled results for the negative summating potential (SP) showed a significant increase in magnitude at all frequencies decreasing with post-treatment interval. The cochlear microphonics did not demonstrate any change in amplitude after treatment. The results indicate that deposition of sepharose beads with immune complexes induces endolymphatic hydrops. Also, deposition of the sepharose beads itself may have induced hydrops together with enhancement of the SP. SP enhancement may be related to the development of endolymphatic hydrops rather than to the presence of hydrops as such. This may be based on pressure build-up while hydrops develops.
Action Potentials↗
Revision surgery for chronic otitis media: a learning experience. Report on 389 cases with a long-term follow-up.
The objective of this study was to evaluate, during a long-term follow-up period, the results of revision surgery for chronic otitis media with or without cholesteatoma. Intact canal wall and canal wall down procedures were performed. The surgical history of every patient was assessed before the operation. A dry, relatively safe, and disease-free ear was created in 90% of the reoperated ears (N = 389). The recurrence rate of cholesteatoma was 5% for the total group. Reperforations of the tympanic membrane occurred in 10%, and persistent or recurrent otorrhea was present in 10% of cases. The functional hearing results were quite satisfactory. A residual air-bone gap of < or =30 dB was reached in 70.3% of the cases after revision tympanoplasty only (N = 41). Revision mastoidectomy with revision tympanoplasty as a one-stage procedure led subsequently, in 76% of intact canal wall procedures (N = 113) and 55% of canal wall down procedures (N = 98), to a residual air-bone gap of < or =30 dB.
Adolescent↗
Immune-mediated sensorineural hearing loss with or without endolymphatic hydrops: a clinical and experimental approach.
Since 1979, when McCabe first described a pattern of bilateral sensorineural hearing loss (SNHL) characterized by a rapid progression over days to weeks, the postulated autoimmune basis of this disease remains unknown. Various attempts have been made to develop the best assays that will clinically confirm the diagnosis and will help identify those patients who may respond to immunosuppressive therapy. The Western blot assay has now been widely applied by different research groups. It has been suggested that antibody to the 68-kD protein is most closely associated with this disorder. Recent analyses suggest that the protein of interest is probably a heatshock protein (hsp 70) with this molecular weight. This disease pattern of rapidly progressive bilateral SNHL presents itself clinically as a different disease than endolymphatic hydrops with fluctuating SNHL, and it is most often associated with vertigo and roaring tinnitus. Meniere's disease may be also immune-mediated, but lacks an autoimmune basis. Its etiopathogenesis is different. A critical review of our own Western blot analyses from patients with either idiopathic rapidly progressive SNHL (N = 33), sudden deafness (N = 53), or other SNHL forms (N = 71) is presented. Immuno-suppressive treatment responses were evaluated. A new concept of immune-mediated endolymphatic hydrops was also further developed on the basis of recent experimental data and earlier clinical observations in order to focus on another aspect of this most intriguing inner-ear disease.
Animals↗
[More than 10 years of revision-cleaning and revision-reconstructive ear surgery in chronic otitis media; good long-term results].
OBJECTIVE: To describe the long-term results of revision surgery in patients with chronic otitis media. SETTING: University Hospital, Utrecht, the Netherlands. METHODS: A personal series of 323 revision mastoidectomies and (or) revision tympanoplasties was evaluated. Surgery was performed between 1981-1995 with a follow-up of one (minimal) to 14 years (maximal). Anatomical and functional results of various subgroups were compared. RESULTS: A preoperative incidence of cholesteatoma of 34% (n = 99) dropped after revision surgery to 11% residual/recurrent cholesteatomas (n = 9). A dry, safe and disease-free ear with a closed tympanic membrane was obtained in nearly 90% of the cases. However, in 5% (n = 10) without pre-existent cholesteatoma (n = 199), a cholesteatoma developed de novo after revision surgery. A residual air-bone hearing gap < or = 30 dB resulted in 79% of the patients after revision tympanoplasty only (n = 27). Revision mastoidectomy with revision tympanoplasty in open (n = 91) and closed (n = 92) procedures lead to a residual air-bone gap < or = 30 dB in 56% of the open cases (n = 91) and in 73% of the closed cases (before the operation the figures were 37% and 55% respectively). CONCLUSION: Revision mastoid surgery and (or) revision tympanoplasty can be quite rewarding and successful.
Adolescent↗
Demonstration of intermediate filament proteins in the guinea pig vestibular labyrinth by a new, high-resolution cryotechnique.
In order to establish the more precise localization of IFPs in the vestibular labyrinth we have developed an immunohistochemical method using semithin cryosections from guinea pig inner ear. The vestibular end organs were fixed by intralabyrinthine perfusion with formaldehyde and glutaraldehyde. Microdissection was performed, followed by decalcification in EDTA. After specimen embedding in gelatin, semithin cryosections (1 micron) were prepared. Prior to the immunohistochemical staining, a new antigen-unmasking treatment was performed. Monoclonal antibodies for cytokeratins (Cks), vimentin, neurofilament protein (NF), and glial fibrillary acidic protein (GFAP) were used and visualized with an indirect ABC method. In the guinea pig vestibular labyrinth, Cks8, 18 and 19 were present. Vimentin and NF were stained positively, GFAP negatively. These results are in accordance with our previous results in the human vestibular labyrinth except for Ck7. The high-resolution cryotechnique in combination with a new antigen-unmasking method may yield more, and more detailed information about the localization of IFPs in the vestibular region.
Animals↗
The effect of nimodipine on cochlear potentials and Na+/K(+)-ATPase activity in normal and hydropic cochleas of the albino guinea pig.
In experimental endolymphatic hydrops (EEH) a decrease in the endocochlear potential (EP) has been reported and is thought to be due to decreased activity of the enzyme Na+/K(+)-ATPase in the stria vascularis. By stimulating Na+/K(+)-ATPase, the EP, and thereby cochlear function as a whole, might be restored. On the other hand, stimulation of stria vascularis Na+/K(+)-ATPase might result in excessive production of endolymph and thus produce or augment hydrops. In this study we have investigated the effect of intraperitoneally applied nimodipine on cochlear potentials and on Na+/K(+)-ATPase activity in the stria vascularis, both in normal cochleas (control) and in cochleas with EEH. Nimodipine is an L-type Ca(2+)-channel blocking agent with Na+/K(+)-ATPase stimulating properties at concentrations as low as 1.5 nM. The compound action potential (CAP), evoked by 2,4 and 8 kHz tone bursts was found to be depressed in the EEH ears with and without nimodipine treatment, and in the nimodipine treated control ears. Statistical analysis (ANOVA) showed that the effects of EEH and nimodipine on the CAP were additive. The negative summating potential (SP), measured extracochlearly at the apex, in response to 4 and 8 kHz tone bursts was significantly enhanced in the EEH ears. Nimodipine treatment did not affect the SP, neither in the control, nor in the EEH ears. Cytochemically, Na+/K(+)-ATPase activity appeared to be decreased in the oedematous stria vascularis of hydropic cochleas. No effect of nimodipine on Na+/K(+)-ATPase activity could be established ultracytochemically, neither in the controls nor in the EEH ears. In the lower turns of some of the nimodipine treated control cochleas a mild hydrops was seen during light-microscopic evaluation. Although it was not possible to prove a stimulatory effect of nimodipine on the enzyme Na+/K(+)-ATPase cytochemically, the finding of mild endolymphatic hydrops in nimodipine treated control ears suggests (a history of) increased endolymph production. This hydrops might be responsible for the depression of the CAP in the nimodipine treated ears.
Animals↗
[Donor selection and preservation methods for the prevention of transmission of AIDS and Creutzfeldt-Jakob disease via allogeneic transplants in ear surgery].
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Acquired Immunodeficiency Syndrome↗
Structure and composition of stereocilia cross-links in normal and hydropic cochleas of the guinea pig.
Structure and composition of stereocilia cross-links were investigated cytochemically in normal and hydropic cochleas of the guinea pig. The electron-dense markers colloidal thorium and cationized ferritin were used for visualization. Side links as well as tip links were visualized using both markers. Cationized ferritin allowed a better visualization of the delicate cross-link substructure than did colloidal thorium. Following digestion with neuraminidase, cross-link reactivity for colloidal thorium was virtually abolished. However, the basic structure of the cross-links could still be observed as a result of routine post-fixation and contrast staining. In both 3- and 6-month hydropic cochleas glycocalyx reactivity of the stereocilia appeared to be unaltered, provided that stereocilia were still present. However, loss of cross-links of the outer hair cells - resulting in disarrangement of the stereociliary bundles - was observed in hydropic cochleas. Our results suggest that cross-links are a separate morphological and cytochemical entity, which is different from the glycocalyx. Furthermore, loss of stereocilia cross-links, with concomitant disarrangement of the outer hair cell stereociliary bundle, appears to be one of the early pathological features of surgically induced endolymphatic hydrops, which might be responsible for permanent sensorineural hearing loss.
Animals↗
Diagnostic and therapeutic dilemmas in rapidly progressive sensorineural hearing loss and sudden deafness. A reappraisal of immune reactivity in inner ear disorders.
Sera from 76 patients with a clinical diagnosis of idiopathic rapidly progressive sensorineural hearing loss (SNHL) (n = 15), sudden deafness (n = 31) and with other etiologies of their hearing loss (n = 30) were analysed by western blot assay. Seventy-three percent of the cases with rapidly progressive SNHL had cross-reacting antibodies (27, 45, 50, 68 kD). The overall response to immunoprogressive therapy was effective in only 50% of cases. Sixty-five percent of the patients with sudden deafness also had cross-reacting antibodies (27, 45, 50, 80 kD). In these cases steroid therapy was more effective in re-establishing the hearing than no treatment, regardless of the western blot outcome. Spontaneous recovery occurred in approx. 50% of cases, but only in those with a positive assay. The antigenic epitopes detected with immunoblotting were not cochlea specific; they were also found in protein extracts of other organs (cranial nerves, kidney, brain).
Autoimmune Diseases↗
Cell membrane polarity of the epithelial cells in the endolymphatic sac of the guinea pig.
The epithelial cells of the endolymphatic sac (ES) were studied in order to characterize their glycocalyx composition. Colloidal thorium and cationized ferritin were used as electron-dense markers to visualize the glycocalyx as well as the basement membrane. In addition, enzymatic digestions were performed to identify the reactive components of the glycocalyx responsible for colloidal thorium labeling. The results indicate that the glycocalyx of the ES epithelial lining is very rich in sialic acid. Furthermore, a marked polarity in glycocalyx reactivity is present between the apical and basolateral membranes, whereas difference in glycocalyx reactivity between the light and the dark cells are not obvious. We speculate that the specific composition and the apparent polarity of the ES epithelial cell glycocalyx are of importance to the equilibrium of electrolytes in the ES lumen.
Animals↗
Expression of intermediate filament proteins in the adult human vestibular labyrinth.
The immunohistochemical detection of intermediate filament proteins, cytoskeletal constituents that allow the characterization of tissues, was investigated in frozen sections of the chemically fixed, nondecalcified, adult human vestibular labyrinth. Cytokeratins (CKs) were detected in all epithelia (including the sensory epithelia), although substantial differences in the degree of staining between individual cells occurred. The expression of CKs 7, 8, 18, and 19 as detected with our subunit-specific monoclonal antibodies in the vestibular epithelia is typical of "simple" epithelia and is identical to the CK subtypes found in the human cochlea. Although immunostaining for CK 7 was very weak and was limited to certain vestibular wall cells, the other CKs demonstrated a pronounced and rather uniform distribution throughout the different epithelia. All epithelia (including the sensory epithelia) displayed expression of vimentin, thus demonstrating co-expression with CKs. Vimentin was also present in the subepithelial connective tissue fibroblasts and mesothelial lining of the vestibular labyrinth. Neurofilament proteins were detected in all neuronal structures. The intense staining for CKs in the maculae and cristae implies that these sensory organs are rigid structures, a finding that may possibly be of importance in the mechanoelectrical transduction process for the sense of equilibrium.
Aged↗