Biomedical subjects
Publications and source records attributed to E H Huizing.
Differential diagnosis of granulomatous lesions of the nasal mucosa is difficult. One of the possible causes is an infection with Leishmania braziliensis as reported in this case. Therefore leishmaniasis should be included in the differential diagnosis of granulomatous lesions of the nasal mucosa in patients who have travelled to endemic areas.
Calcitonin gene-related peptide (CGRP) is one of the neuropeptides that is released in the human nasal mucosa after trigeminal nerve stimulation. We investigated the in vitro effect of CGRP on the ciliary beat frequency (CBF) of human upper respiratory cilia. Ciliated epithelium of freshly removed adenoidal tissues was used in all experiments. CBF was measured using a computerized photo-electric method. The results showed that CGRP exerted a significant dose-dependent stimulation on CBF in concentrations of 10(-9)-10(-6) M (n = 10), with a maximum of 23%. Our findings indicate that CGRP in vivo may help to protect the airway epithelium by directly stimulating ciliary beat.
Thirty-four patients suffering from chronic otorrhoea were tested for delayed type contact allergy. Patch testing showed a relevant positive reaction in 19 patients (56%). The most frequent allergens were aminoglycosides with neomycin and framycetin as major offenders. Other antimicrobial agents (clioquinol, polymyxin B), cream bases (lanolin) and corticosteroids (tixocortol) were less common allergens encountered. These results indicate that it is almost obligatory to perform patch testing in any patient with long-standing otitis which does not respond to local therapy. Scoring of the patch tests has to be extended to 7 days, as notably the aminoglycosides and corticosteroids only become positive after such a long interval. Because of the high risk of sensitization, topical preparations containing neomycin and framycetin should not be used routinely. We recommend the use of either a topical antiseptic or a topical antibiotic with low allergenic potential for the initial treatment of otorrhoea.
On stimulation of trigeminal nerve endings, neuropeptides are released into the nasal mucosa. Among these neuropeptides is substance P(SP). In this study, we determined the effect in vitro of SP, as well as SP together with thiorphan, a blocker of the SP-degrading enzyme neutral endopeptidase, on the ciliary beat frequency (CBF) of the human upper respiratory tract. Ciliated epithelium of human adenoid tissue was used in the experiments. The CBF was measured by means of a computer-assisted photoelectric method. Substance P(10(-8) to 10(-5) mol/L, n = 7) showed a small but statistically significant dose-dependent decrease in CBF. On perfusion with SP (10(-8)) to 10(-5) mol/L, n = 8) in combination with thiorphan, no statistically significant effect was found. We conclude that SP does not have a direct effect on ciliary activity to such an extent that it will affect mucociliary transport in vivo.
Diminished mucociliary transport can occur in a type-I (Ig-E mediated) allergic reaction. We determined the effects of the allergy mediators prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) on the ciliary beat frequency (CBF) of human upper respiratory cilia in vitro. Human adenoid tissue was used as the source for ciliated epithelium. CBF was measured by a computerized photo-electric method. PGD2 (10(-8)-10(-5) M, n = 7) showed no statistically significant effect on CBF. PGE2 (10(-9)-10(-6) M, n = 10) caused a significant dose-dependent stimulation, with a maximum of 37% (ANOVA, p < 0.001). Thus prostaglandins D2 and E2 do not exert a direct negative influence on ciliary activity, which could account for a decrease in mucociliary transport. The stimulating effect of PGE2 may be relevant in promoting mucociliary clearance in vivo.
The aim of this study was to explore the usefulness of two different in vitro models for studying the function of human upper respiratory cilia, i.e. cell suspension cultures of human upper airway epithelium, and ciliated adenoid epithelium. Ciliary beat frequency (CBF) and signal consistency (SC), as parameters of ciliary function, were measured by a computerized photo-electrical method. Measurements after one week revealed that CBF of ciliated aggregates from cell suspension cultures had deteriorated to a mean of 5.8 Hz. In the subsequent period, it remained at this rather low and non-physiological level. SC decreased too, although not as dramatically. These results indicate that ciliated aggregates from cell suspension cultures cannot be used for human ciliary function experiments in vitro. On the other hand, in ciliated adenoid epithelium, CBF remained constant for a period of 5 h, although SC decreased after 30 min. Because of this result and the fact that ciliated adenoid epithelium is easily obtainable, we regard this material as suitable for studying human ciliary beat in vitro.
Some authors consider the interdomal ligament to be an important structure of nasal tip support, whereas in other studies of lobular anatomy such a ligament is not mentioned at all. To clarify this question, we performed an anatomical investigation, which included macroscopical dissection and histological sectioning of 14 human cadaveric noses. Our anatomical study failed to reveal the presence of an actual ligament in the interdomal area.
BACKGROUND: At least half of the cases of profound deafness of early onset are caused by genetic factors, but few of the genetic defects have been identified. This is particularly true of the most common hereditary forms of deafness, which occur in the absence of any associated syndrome. METHODS: We studied a large Indonesian family in which hearing loss was inherited in an autosomal dominant pattern. The hearing loss first affects the high frequencies during the teens or 20s and becomes profound within 10 years. To locate the responsible gene, we performed genetic-linkage analysis, using microsatellite markers distributed over the entire genome. We then performed linkage analyses in an American family and a Dutch family with similar patterns of hereditary hearing loss. RESULTS: In the extended Indonesian family, a gene linked to deafness mapped to chromosome 1p, with a multipoint lod score of more than 7. In the American family, deafness was linked to the same locus on chromosome 1p, with a multipoint lod score of more than 5. In the Dutch family, however, this locus was ruled out. The flanking markers D1S255 and D1S211 defined a region of 6 cM on chromosome 1p that is likely to contain the gene associated with deafness in the first two families. CONCLUSIONS: In some families with early-onset autosomal dominant hearing loss, the responsible gene is on chromosome 1p.
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.
The effects of cocaine and lidocaine on ciliary beat frequency and ciliary beat harmony were studied in biopsy specimens of normal human nasal mucosa. Cocaine was investigated in increasing concentrations (0.875%, 1.75%, 3.5%, and 7%) in five samples; lidocaine (0.125%, 0.25%, 0.5%, 1%, and 2%), in four samples. Ciliary beat was recorded photoelectrically and the signal was analyzed. Cocaine was found to decrease ciliary beat frequency and ciliary beat harmony at concentrations of 1.75% and higher. Partially reversible ciliostasis was seen at 7%. Lidocaine was found to decrease ciliary beat frequency and ciliary beat harmony at concentrations of 0.25% and higher. Irreversible ciliostasis was seen at 2%. Cocaine and lidocaine affected ciliary beat frequency and ciliary beat harmony in the same way.
Decreased mucociliary transport can occur in patients with type I (IgE-mediated) allergic rhinitis or allergic asthma. This study investigated if the allergic mediators histamine and leukotriene C4 (LTC4) could interfere with ciliary beat frequency (CBF) of in vitro human upper respiratory cilia and eventually result in decreased mucociliary transport. Ciliated epithelium of human adenoid tissue was used in the experiments and CBF was determined using a computer-assisted photoelectric method. Histamine in concentrations of 10(-6) - 10(-3) M (n = 12) and LTC4 as 10(-9) - 10(-6) M solutions (n = 10) showed no statistically significant dose-dependent effect on CBF in vitro.
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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.
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.
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.
Autoimmune reactivity against corneal antigens is described in two patients with Cogan's syndrome, a nonsyphilitic deep interstitial keratitis with vestibuloauditory symptoms. In both cases corneal antibodies were found at the beginning or during an exacerbation of the disease. After administration of high doses of corticosteroids the corneal antibodies diminished. Interstitial keratitis can generally be controlled by local or systemic corticosteroids. The effect of corticosteroid therapy on the audiovestibular symptoms is variable. The possibility of an autoimmune pathogenesis of Cogan's syndrome is discussed.
The movement of normal human nasal cilia was analyzed. Ciliary beat was recorded by means of a phase-contrast microscope equipped with a photodetector. The electrical signal was analyzed as follows: i) a power spectrum was calculated in order to measure ciliary beat frequency (CBF), ii) the beat cycles were averaged and the standard deviation of the waveform was computed to determine signal consistency (SC), and iii) the ratio of the duration of the smooth to that of the steep part of the cycles was measured. This was done under three different conditions: 1) normal or "initial", 2) after induction of "function loss", and 3) after "salbutamol stimulation". At "function loss," the cilia beat slower and with less harmony. CBF decreased from an average of 9.0 Hz in the "initial" condition to 5.8 Hz. SC decreased from an average of 5.7 to 1.9. After "salbutamol stimulation", average CBF was partially restored to 7.7 Hz, while average SC increased to 4.4. These findings indicate that in ciliary function studies, SC, as a measure for ciliary beat harmony, may be introduced alongside CBF as a second valuable parameter. In this study we were not able to identify different phases in the signal that might be used as a third parameter to indicate the effective and the recovery stroke.
The endo- and perilymphatic glycocalyx of the cochlear epithelia were investigated ultrastructurally in normal and hydropic cochleas using the electron-dense markers cationized ferritin and colloidal thorium. In the normal cochleas all epithelial surfaces showed reactivity with both markers. Using cationized ferritin, no regional differences in reactivity could be demonstrated. With colloidal thorium, however, the apical membranes of the outer hair cells reacted more intensely than either the basolateral membranes or the membranes of the supporting cells of the organ of Corti. Cationized ferritin reactivity was not affected by digestion with either neuraminidase or hyaluronidase. In contrast, colloidal thorium reactivity of the endolymphatic surfaces was greatly reduced after neuraminidase digestion. Reactivity of the cell membranes lining the perilymphatic compartments of the cochlea was less affected by neuraminidase digestion, except for the basolateral membranes of the sensory and supporting cells of the organ of Corti, which demonstrated a greatly reduced reactivity. These findings indicate that the glycocalyx of the epithelial surfaces lining the endolymphatic compartment has a high content of sialic acid. The differences that are observed in normal cochleas in regard to colloidal thorium reactivity between the apical membranes of the outer hair cells and the membranes of the Deiters' cells, could not be demonstrated in hydropic cochleas. This probably contributes to the early functional changes in outer hair cells observed in experimental hydrops.