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Biomedical subjects

S Hellström

Publications and source records attributed to S Hellström.

At least 127 records · Page 7Linked to original sources

Impaired hearing following instillation of hydrocortisone into the middle ear. Preliminary report from an animal study.

The effect of cortisone on the inner ear function was investigated. A suspension of 2% hydrocortisone in sterile water was instilled into the middle ear in the round window niche area of healthy rats. The hearing for eight frequencies was determined by auditory brainstem response (ABR) measurements. After 5 days of daily local application, ABR thresholds impaired in the high-frequency range 12 to 31.5 kHz. The impaired ABR thresholds remained unchanged throughout 3 weeks of observation, indicating irreversible damage to the inner ear. It is also noteworthy that hydrocortisone delayed healing of the perforated tympanic membrane.

Animals↗

DL-propranolol inhibits the vascular changes in the rat carotid body induced by long-term hypoxia.

Two groups of rats were exposed to hypoxia (10% O2) for 1 and 3 weeks with or without daily injections of DL-propranolol (0.66 mg.kg-1 ip). The structure of the carotid body was analyzed by light microscopical morphometry and the catecholamine content was assayed by high performance liquid chromatography. Exposure to hypoxia induced enlargement of the carotid body due to enhanced vascularity and hypertrophy of glomic and interstitial tissues. The dopamine and norepinephrine content were increased at both 1 and 3 weeks of hypoxia and reached levels 40-50 times those of the controls. The DL-propranolol treatment abolished the vasodilatory effect of hypoxia within the first week but did not prevent the other structural changes or the rise in catecholamine content. The data suggest that 1. the vasodilation elicited by long-term hypoxia may be controlled by beta-adrenoceptors and 2. the structural and biochemical events occurring in rat carotid body during long-term hypoxia do not influence each other and thus seem to be controlled by different mechanisms.

Animals↗

Paraganglia of the rat recurrent laryngeal nerve after long-term hypoxia: a morphometric and biochemical study.

Paraganglia of the recurrent laryngeal nerve of rats exposed to hypoxia (10 +/- 0.5% O2) for 3 weeks became enlarged in volume by 2.6-fold. The volume densities of blood vessel lumen and endothelial cells were unchanged. The enlargement of the paraganglia was mainly attributed to hypertrophy of the dense-cored vesicle-containing cell. Concerning the profile diameter of the vesicle, a unimodal distribution of dense-cored vesicle cells was found in both control and hypoxic paraganglia. The vesicle diameter increased by about 19%, whereas the numerical density of dense-cored vesicles and the vesicle volume density were unaltered after hypoxia. Recurrent laryngeal nerves assayed by a sensitive high performance liquid chromatography technique contained an average of 1.9 pmol dopamine and 1.3 pmol norepinephrine. Exposure to 2 weeks of hypoxia increased the dopamine level to 4.9 pmol, whereas the norepinephrine content was unchanged. It is suggested from this study that the catecholamines determined are housed in the paraganglia of the recurrent laryngeal nerve.

Animals↗

Paraganglia of the superior laryngeal nerve of the rat.

Paraganglia were consistently found at the bifurcation of the superior laryngeal nerve of the rat. Ultrastructurally the paraganglionic cells resembled the type I and type II cells of the carotid body. The dense-cored vesiculated type I cell was found most frequently, whereas the type II cell represented 10-25% of the cell population. The volume density of the dense-cored vesicles was found to be 3.5 +/- 0.5, which is about half as much as that found in the recurrent laryngeal nerve and about twice of that found in the carotid body. A total of 24,634 dense-cored vesicles were measured, and the mean diameter was calculated to be 113.8 +/- 4.9 nm. Based on the median vesicle profile diameter, only one type of dense-cored vesicle cell was found.

Animals↗

Hyaluronan in the middle ear of the rat. The normal distribution of hyaluronan and the clearance of exogenously administered hyaluronan from the middle ear.

The content of hyaluronan (HA), a common connective tissue component, was determined in well defined areas of the rat middle ear. The HA concentration in the pars flaccida of the tympanic membrane was considerably greater than in the pars tensa and areas on the medial wall of the middle ear cavity. The fate of exogenous HA introduced into the middle ear was also studied in rats. Tritium-labelled HA disappeared through the Eustachian tube (ET) and was followed by analysis of the nasopharyngeal secretion. The radioactivity in the secretion reached a peak at 3 h and decreased to almost zero within 12 h, indicating that most of the HA was removed. By autoradiography and direct analysis of the HA concentration and molecular weight distribution the fate of HA after obstruction of the ET was followed. Radioactive HA was confined to the middle ear and no uptake into surrounding tissues could be traced by autoradiography 4 days after application. The amount of HA that could be recovered from the middle ear was constant for up to 6 days. Analysis of the molecular weight distribution of the deposited HA indicated only slow degradation during these 6 days.

Animals↗

Consequences of using hyaluronan-coated tympanostomy tubes.

The effects of hyaluronan-coated polyethylene tympanostomy tubes on the tympanic membrane structure were investigated and compared with non-coated polyethylene tubes without the coating. The tubes were inserted into the tympanic membrane (TM) and removed 3 weeks later. After 3 weeks the tubes were reinserted. This tube insertion and removal and reinsertion sequence was repeated 4 times and the tympanic membrane structure was examined histologically at 3 weeks and 12 weeks later. The study did not reveal any differences regarding the thickness and light microscopical appearance when comparing the TMs with the hyaluronan-coated tubes to those with the non-coated polyethylene tubes. However, the present way of evaluating the effects of different tube materials may be too crude. In future experiments aimed at elucidating the effects of different surface coatings of tympanostomy tubes other experimental designs must be employed, e.g. fewer tube insertion sequences and less traumatizing extractions.

Animals↗

Hyaluronan and healing of tympanic membrane perforations. An experimental study.

Hyaluronan, an extracellular high molecular weight polysaccharide, was applied onto experimentally performed tympanic membrane (TM) perforations in the rat. The hyaluronan-treated perforations closed faster than the untreated controls and showed less scar tissue. Initially the perforation became covered by a sheet of keratin and hyaluronan, which appeared to relax and orientate the retracted collagen fibres at the margin of the perforation. The hypertrophic stratified keratinizing squamous epithelium advanced within the hyaluronan-keratin cover and closed the perforation ahead of an approaching connective tissue. Three months after the closure, the hyaluronan-treated TMs appeared transparent in comparison to the opaque untreated controls. In histological sections the hyaluronan-treated TM was comparably thin and an organized collagen fibre layer was discernible. Hyaluronan of various concentrations (0.75, 1.0, 1.75 and 1.9%) and molecular weights (4 x 10(6) and 6 x 10(6)) were tested. The healing rate and degree of scar tissue was dependent on the concentration, but not on the molecular weight of the hyaluronan. Hyaluronan, at the higher concentration, healed the perforations faster and produced a less opaque TM than hyaluronan at low concentration. The number of applications of hyaluronan also influenced the healing rate; fewer applications resulted in a reduced rate. However, the quality of the healed TM was influenced to a lesser extent by the number of hyaluronan applications. Even single applications caused less scar tissue in comparison with untreated TMs. It is inferred from the study that hyaluronan, exogenously applied, might be valuable also in the clinical situation to enhance the healing of different types of TM perforation.

Animals↗

Reversible changes in inner ear function following hyaluronan application in the middle ear.

A safety study regarding the potential ototoxicity of 1.9% hyaluronan was performed in 20 rats. In all animals the middle ear was completely filled with hyaluronan three times at 2-day intervals between the administrations. Inner ear function was evaluated by computerized auditory brainstem response (ABR) measurements. ABR recordings were performed prior to exposure, after myringotomy (but prior to administration of hyaluronan), 5 days after the last administration (n = 15; these animals were then sacrificed for analysis of the middle ear), one month and 3 months later (n = 5). The hearing thresholds were improved in animals 5 days after the last administration of hyaluronan at 6-8 kHz, whereas the hearing thresholds were impaired at 12 and 20 kHz. After one month, ABR thresholds were even better than precontrol levels at 2, 4 and 6 kHz, whereas at all other frequencies the ABR threshold was normal. Three months after hyaluronan exposure, all ABR thresholds were normal, but viscous material was present in the middle ear in 3 of 5 animals. It is concluded that hyaluronan causes reversible changes in inner ear function but lacks ototoxic adverse effects.

Animals↗

Hyaluronan applied to the middle ear mucosa prior to fixation improves the morphological quality.

In a previous study, it was noted that immersion-fixed middle ear mucosa appeared better preserved if treated with hyaluronan (hyaluronic acid, HA) prior to fixation. The present study showed that HA instilled into the middle ear caused the epithelial cells to emerge more brilliant--when stained with toluidine blue--but did not hinder minor autolytic changes from occurring. The precise molecular or biochemical event or events that cause the brilliance are not known at present. HA did not cause any severe structural alterations of the mucosa.

Animals↗

The antihypertensive drug DL-propranolol inhibits the vascular changes in rat carotid body during long-term hypoxia.

Rats were exposed to hypoxia (10% O2) for 1 and 3 weeks with or without daily injections of DL-propranolol (0.66 mg/kg i.p.). The structure of the carotid bodies was analyzed by light microscopical morphometry. Hypoxia induced enlargement of the carotid body due to enhanced vascularity and hypertrophy of glomic and interstitial tissues. The contents of dopamine and norepinephrine multiplied. Propranolol abolished the vasodilatory effect of hypoxia within the first week but did not prevent the other structural changes and the rise in catecholamine content. The data suggest that 1) the vaso-dilation elicited by long-term hypoxia may be controlled by beta-adrenoceptors; 2) the structural and biochemical events occurring in rat carotid body during long-term hypoxia seem to be controlled by different mechanisms.

Animals↗

Catecholamines of endoneurial laryngeal paraganglia in the rat.

The catecholamines in the recurrent and superior laryngeal nerves of the rat were assayed by high performance liquid chromatography. The nerves were shown to contain high levels of dopamine (1.9 +/- 0.6 and 2.3 +/- 0.4 pmol, respectively) and noradrenaline (1.3 +/- 0.3 and 0.9 +/- 0.2 pmol, respectively). No adrenaline could be detected in any of the nerves. Reserpine markedly depleted the stores of these amines in both nerves. A significant increase in dopamine level was seen in the superior laryngeal nerve after treatment with a monoaminoxidase inhibitor, but not in the recurrent laryngeal nerve. The high levels of dopamine detected are presumably derived from endoneurial paraganglia which were demonstrated by glyoxylic acid-induced fluorescence. The source of noradrenaline is less evident, but noradrenaline is probably stored in both endoneurial paraganglia and in sympathetic nerve endings.

Animals↗

Fiber composition of the recurrent laryngeal nerve after experimental vagotomy and sympathectomy. A qualitative study by light and electron microscopy.

A qualitative study of the nerve fiber composition of the recurrent laryngeal nerve of the rat was performed by light and electron microscopy. Various surgical denervation procedures were employed to determine the origin of the variously sized myelinated fibers and the unmyelinated axons present within the nerve. After extracranial vagotomy all myelinated fibers degenerated, whereas some unmyelinated axons remained intact. Intracranial vagotomy on the other hand revealed that about 70% of the small (1.5-4.0 micron) myelinated fibers were unaffected, as were many unmyelinated axons. After sympathectomy, both kinds degenerated but normal unmyelinated axons could be found. Thus, the majority of the small myelinated fibers are afferent sensory fibers whose cell bodies are located in the vagal ganglia at the base of the skull. The medium and large myelinated fibers represent efferent neurons originating from the brain stem. The unmyelinated fibers emanate from at least three different sites, viz. the brain stem, the sensory vagal ganglia and finally the ganglia of the cervical sympathetic nerve trunk.

Animals↗

The vascular supply of the rat tympanic membrane.

The vascular supply of the rat tympanic membrane (TM) was studied by means of otomicroscopy, angiography, acrylic casts, and light microscopy. The branches of the external carotid artery in the external auditory meatus were found to vascularize 1) the pars flaccida, 2) the manubrial part of the pars tensa, and 3) the junction between the fibrocartilaginous ring of the TM and the tympanic sulcus of the temporal bone. The TM vessels of areas 1 and 2 were found beneath the squamous epithelium, close to mast cells and nerve bundles. Vessels originating from the tympanic cavity (also probably emanating from the external carotid artery) supplied the periphery of the pars tensa with minute branches, localized immediately beneath the tympanal epithelium. The portion of the pars tensa between the manubrial part and the periphery lacked a vascular system. Upon mechanical stimulation (gentle pressure on the handle of the malleus), the normally visible vessels dilated and minute branches appeared. This dilation may be caused, at least partly, by a release of vasoactive substances from mast cells and/or nerves in its vicinity. Even under mechanical stimulation, a large portion of the pars tensa seemed to be devoid of vessels. The nutrition of this part may be served by diffusion, with nutrients originating from the vessels in the tympanal rim and along the handle of the malleus. The architecture of the attachment of the fibrocartilaginous ring to the bony sulcus of the temporal bone is quite unique. Thus, the flow in the dense vascular network between these structures may be affected by an altered tension in the pars tensa.

Angiography↗

Evaluation of inner ear damage during conditions with middle ear effusion by use of brainstem audiometry.

The method of auditory evoked brainstem responses (AEBR) was applied on an animal model with two types of well defined middle ear effusions--serous otitis media (SOM) and purulent otitis media (POM). The animals with SOM exhibited fairly normal interpeak latencies but a considerably increased auditory threshold. In contrast, POM mainly affected the latencies of the brainstem evoked potential but also caused a slight increase of the auditory threshold. The results indicate that SOM chiefly causes a conductive hearing loss, while POM also affects the neural circuit.

Animals↗

Pharmacological characterization of receptors on blood vessels in the tympanic membrane involved in otitis media.

Acetylcholine dropped onto the meatal surface of the tympanic membrane evoked vasodilatation and a vascular leakage to the middle ear cavity. The vasoreactions were atropine-resistant. Substance P and vasoactive intestinal polypeptide (VIP) injected intravenously caused a marked vascular leakage and VIP also vasodilatation. These blood vessel changes seem to be regulated by the parasympathetic nerves as they were inhibited by vagotomy. Constriction of the tympanic membrane vessels was mediated through alpha-receptors.

Animals↗

Exogenous hyaluronic acid (Healon) accelerates the healing of experimental myringotomies.

Topical application of hyaluronic acid (Healon) onto the borders of rat tympanic membrane perforations accelerated the rate of wound healing. The closure time was roughly 60% of that of the untreated perforations. Epithelial cells fused with opposing cells slightly in advance of supporting connective tissue and thus bridged the remaining gap. It seems as if hyaluronic acid, topically applied, can serve as a supporting and orienting matrix for the proliferating squamous epithelium.

Administration, Topical↗

Tympanostomy tubes prevent the development of experimentally induced purulent otitis media.

Cleavage of the soft palate will cause purulent otitis media bilaterally in 100% of experimental animals (the rat) within 2 weeks. In this model a tympanostomy tube was inserted unilaterally. At 2, 7, and 21 days after the surgery the middle ear status was mapped in the otomicroscope and microbiological samples collected from the middle ear cavities and the nasopharynx. All intact ears became infected and developed purulent otitis media. Most of the tubulated ears exhibited normal middle ear cavities and remained culture negative. The few ventilated ears which were infected, however, showed a lower bacterial count than the corresponding intact ear. Thus in this model the insertion of a tympanostomy tube prevents the purulent otitis media from occurring.

Animals↗