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Biomedical subjects

S Hellström

Publications and source records attributed to S Hellström.

At least 109 records · Page 6Linked to original sources

Structural changes in the round window membrane following exposure to Escherichia coli lipopolysaccharide and hydrocortisone.

The present study focused on structural changes of the round window membrane (RWM) from agents that evoke transient or permanent impairment of the auditory brainstem response when applied into the RW niche. Escherichia coli (E. coli) lipopolysaccharide (LPS) in sterile water (SW) and a 2% suspension of hydrocortisone (CORT), micronized in SW, were instilled into the round window (RW) niche of Sprague-Dawley rats. The morphology of the RWM was analyzed 3 to 21 days after instillation of either substance. Both substances caused minor structural alterations at the light microscopic level. The RWM showed a slight thickening and an invasion of inflammatory cells. At the ultrastructural level, the CORT-treated specimens showed an increased epithelial height and numerous microvilli, whereas the epithelium of the LPS-treated specimens was extended and contained few microvilli resembling those in the normal RWM. We postulate that the RWM may undergo dynamic structural changes when exposed to various agents. The structural alterations per se can influence the passage of substances from the middle ear to the inner ear.

Animals↗

The role of liver and kidneys in the removal of circulating hyaluronan. An experimental study in the rat.

The concentration of circulating hyaluronan was determined in rats after either the liver or the kidneys had been excluded from the systemic circulation. Both conditions caused an increase of the serum levels of hyaluronan. However, the rate of increase was more rapid in the animals with ligated hepatic vessels compared to those with ligated renal vessels. This in vivo investigation indicates that in the rat both kidney and liver systems are important for the removal of hyaluronan from the blood.

Animals↗

Bronchial epithelium in humans recently recovering from respiratory infections caused by influenza or mycoplasma.

Sixty three bronchial mucosal biopsies were collected from 12 patients recovering from respiratory infections with influenza virus (n = 8) and Mycoplasma (n = 4). The bronchoscopy was performed within 1-6 wks from the onset of symptoms. Of the 63 biopsies prepared for light microscopy, 27 biopsies from the influenza patients and 10 from the Mycoplasia patients were further analysed at the light and electron microscope level. The epithelium and the underlying stroma was analysed morphometrically and the results were compared to those of 39 biopsies from 27 healthy subjects. A slightly raised bronchial reactivity was noted in two patients. In the influenza patients the epithelial height was greater compared to that of the healthy subjects and subepithelial lymphocytosis was noted. Areas with damaged epithelium, epithelium shedding, and occasionally a thickened basement membrane, considered typical for asthma, occurred in both infected groups, and in the biopsies of the healthy subjects.

Adult↗

Structural characterization of bronchial mucosal biopsies from healthy volunteers: a light and electron microscopical study.

Bronchial mucosal biopsies were collected by flexible fibreoptic bronchoscopy (FFB) from normal healthy volunteers. The volunteers were not receiving any medication and had been free from respiratory infection for at least five weeks prior to the bronchoscopy. Biopsies with a minimum of 115 microns of undamaged perpendicularly sectioned epithelium were investigated by light and transmission electron microscopy. The height of the epithelium varied between 22-62.5 microns, with a median value of 41.5 microns. The volume density of the various epithelial cells in relation to the total epithelium was 61% for the ciliated and non-ciliated, non-secretory luminal cells, 6% for the goblet cells and 32% for the basal cells. The width of the lamina reticularis of the basement membrane ranged between 3-17.5 microns, with a median value of 8.5 microns. Blood vessels occupied 2.8% of the subepithelial tissue. Only a few inflammatory cells were seen in the connective tissue, volume density occupied by lymphocytes and polymorphonuclear granulocytes, 0.6% and 0.2% respectively. This study shows that structural damage is a common finding in biopsies collected by FFB. Mechanical damage of bronchial biopsies caused by the forceps should be considered before alterations in the epithelium are attributed to pulmonary disease.

Adult↗

Catecholamines in the carotid body are unaffected by hypercapnia.

In contrast to the increased content of dopamine and norepinephrine in rat carotid body during hypoxia (10% O2 in nitrogen) for 3 and 21 days, hypercapnia (8% CO2 in air) for 21 days failed to alter the catecholamine concentrations. DOPAC content was elevated in hypoxia whereas there were no significant changes in hypercapnia. This finding supports the view that the mechanisms of peripheral chemoreception differ, at least partly, in hypoxia and hypercapnia.

3,4-Dihydroxyphenylacetic Acid↗

Neuropeptides in intact and denervated tympanic membranes. An immunohistofluorescence study in the rat.

The distribution and origin of peptide-containing and sympathetic nerve fibers were studied in the tympanic membrane of rats with intact innervation, and in rats following sympathectomy, vagotomy, or capsaicin treatment. Nerve fibers showing substance-P-like immunoreactivity (SP-LI), calcitonin gene-related peptide (CGRP)-LI, vasoactive intestinal polypeptide (VIP)-LI, enkephalin-LI, neuropeptide Y (NPY)-LI and tyrosine hydroxylase (TH)-LI were detected along blood vessels in the pars flaccida, the external auditory canal and in the fibrocartilaginous ring of the pars tensa. In the pars flaccida there were numerous fibers demonstrating SP-LI and CGRP-LI, while there were few such fibers in the pars tensa. In both portions of the tympanic membrane these fibers were present within and beneath the keratinized stratified squamous epithelium. In the pars flaccida, nerve fibers showing SP-LI and CGRP-LI were also seen near mast cells. Sympathectomy led to a loss of nerve fibers showing TH-LI and NPY-LI, whereas the other peptide-containing nerve fibers remained unaffected. Vagotomy did not reduce the immunoreactivity for any of the neuropeptides studied. Capsaicin treatment caused a reduction in nerve fibers displaying SP-LI and CGRP-LI. The abundance of nerve fibers showing SP-LI and CGRP-LI in the keratinized squamous epithelium indicates that the tympanic membrane is richly supplied with sensory nerves. The localization of nerve fibers exhibiting these latter substances in the vicinity of mast cells in the pars flaccida suggests that this part of the tympanic membrane is a site where neurogenic inflammation occurs.

Animals↗

Sympathectomy provides evidence of dopamine storage in rat laryngeal nerve paraganglia.

Catecholamine content in the recurrent and superior laryngeal nerves (RLN and SLN) of the rat was analysed by high-performance liquid chromatography after surgical and chemical sympathectomy. Sympathectomy induced by repeated injections of guanethidine did not lead to any change in the dopamine (DA) level, whereas the noradrenaline (NA) content decreased by 68% and 64% respectively in the RLN and SLN. Surgical excision of the superior cervical ganglion (SCG) did not alter the level of DA in the SLN, but caused a 60% decrease of DA in the RLN. Removal of SCG did not affect the NA levels either in the RLN or in the SLN, unless it was combined with extirpation of the middle cervical ganglion, which induced a decrease in NA in both nerves. The results indicate that much of the DA in the laryngeal nerves is stored outside the sympathetic nerve fibres, probably in the small organs earlier characterized as endoneurial paraganglia.

Animals↗

Hydrocortisone applied into the round window niche causes electrophysiological dysfunction of the inner ear.

A suspension of 2% hydrocortisone, micronized in sterile water, was instilled through a perforation in the tympanic membrane into the round window (RW) niche of 9 healthy rats once a day for 5 consecutive days. Three animals were used as controls, and were exposed to sterile water only instilled into the RW niche. Auditory brainstem response (ABR) thresholds were determined for eight frequencies: 2, 4, 6, 8, 12, 16, 20 and 31.5 kHz. Hydrocortisone caused impaired ABR thresholds in the frequency range of 12-31.5 kHz after 5 days of instillation. The impaired thresholds remained unchanged for 2 months, indicating irreversible electrophysiological changes in the inner ear. No morphological damage could be detected in the cochlea by means of light microscopy or transmission electron microscopy. However, hydrocortisone delayed the healing of the perforated tympanic membrane.

Animals↗

Functional changes in the inner ear in renal insufficiency. An experimental study in the rat.

In acute uremia the auditory brainstem response thresholds in the rat (n = 10) became primarily affected in the low-frequency area. As time elapsed in uremia, even the high-frequency thresholds became impaired. In most animals the latencies for wave 2 at the threshold level increased during the first 48 h concomitant with the impairment of thresholds. After 72 h of uremia, the latencies were shortened as compared with the control values.

Animals↗

Frequency-specific auditory brainstem response analysis of young normal, aged normal and aged alcohol-addicted rats.

Normative data for frequency-specific (+/- 100 Hz) auditory brainstem response (ABR) thresholds were determined in 60 normal healthy 3-month-old, 5 normal 22-month-old and 6 alcohol-addicted 22-month-old Sprague Dawley rats. The highest degree of auditory sensitivity was in the range of 12-20 kHz. These frequencies showed significant mean differences between the 3-month-old and the old normal rats. In contrast, alcohol-addicted old rats did not reveal any significant threshold changes as compared with either normal old or 3-month-old rats.

Aging↗

Hyaluronan in experimental serous and purulent otitis media.

The concentration of hyaluronan (hyaluronic acid; sodium hyaluronate; HA), a major component of connective tissue, was analyzed by a specific radioassay in tissue samples from normal rat middle ears and in tissue and effusions from middle ears affected by experimentally induced otitis media. In normal ears the pars flaccida of the tympanic membrane contained a considerably higher concentration of HA (60 to 200 micrograms/g) than the pars tensa and areas of the medial wall (2 to 7 micrograms/g). In purulent otitis media the pars flaccida contained less HA than in normal ears. The HA concentrations were lower in purulent (3 to 40 micrograms/mL) than in serous (20 to 190 micrograms/mL) effusions. The weight average molecular weight of HA in serous fluid was high (greater than 10(6] and comparable to that in lymph. It is inferred from the study that the subepithelial tissue and its matrix components, eg, HA, must be considered when attempting to understand the function of the middle ear normally and in otitis media.

Animals↗

Structure of the round window membrane.

In the present study the literature on the round window membrane (RWM) structure was reviewed and the rat used as an animal model to elucidate structural alterations of the RWM occurring during serous (SOM) and purulent (POM) otitis media. In SOM the RWM was about the same thickness as that of the control, whereas in POM it increased about 5-fold. The structural changes in POM were mainly confined to the epithelium facing the middle ear cavity. The normal flat epithelium was transformed into a pseudostratified epithelium with both ciliated and goblet cells. Light microscopy revealed only minor changes in the RWM structure during SOM. However, ultrastructurally, the connective tissue layer exhibited dense accumulations of collagen and elastic fibres which were not observed in either normal or the POM ears. The study showed that different inflammatory conditions of the middle ear cause different structural alterations of the RWM. To what extent these changes also influence differently the permeability of the RWM remains to be elucidated. Obviously ultrastructural studies are needed to be able to characterize the structural changes which appear in the RWM in a diseased ear.

Animals↗

Toxic effects on inner ear of noxious agents passing through the round window membrane.

The effects on inner ear of Xylocain, EMLA, phenol, endotoxin and hydrocortisone were analysed before treatment and 24 h-6 months after instillation of each drug into the round window (RW) niche, where the substance was left. Inner ear function was determined by repeated auditory brainstem recordings (ABR). All cochleae were analysed morphologically at the light microscopic level. Hydrocortisone, Xylocain and endotoxin caused functional changes without morphological correlates, even at long-term follow-up. In contrast, phenol and EMLA caused both functional impairment and graded morphological damage to the organ of Corti in the basal coil. Outer hair cells (OHC) were more vulnerable than inner hair cells (IHC).

Anesthetics, Local↗

A rat model for bacterial otitis media.

Rat middle ear was exposed to challenge with viable pneumococci, type 3 and 6A, and the course of changes in the middle ear was observed by otomicroscopy and analysis of bacterial samples from blood, nasopharynx and middle ear effusions. Microscopical examination of changes in the middle ear mucosa during and after the acute infection was also made. Depending on the type and concentration of pneumococci, three different results were observed: otitis media with purulent effusion, otitis media with serous effusion, or no reaction at all. The mortality rate was low and most animals recovered within 10 days without postinfectional changes visible by otomicroscopy. The microscopical examination of the middle ear mucosa revealed distinct changes. Inoculation of rat middle ear with pneumococci causes a self-limiting infection that closely resembles acute otitis media in the human. Thus the rat would seem to be a suitable animal model for the study of bacterial otitis media.

Acute Disease↗

Non-specific secretory supersensitivity in rat parotid gland following neonatal sympathetic denervation.

Newborn rats were surgically sympathectomized by extirpation of the left superior cervical ganglion. After 9 weeks the parotid glands of both sides were used for secretory studies. Isoprenaline, dopamine, and the dibutyryl analogue of cAMP (DBcAMP) caused an increase in amylase release, which was significantly higher in the denervated glands. Also carbamylcholine was more effective in the denervated gland; the concentration-response curve was shifted to the left, and the maximal output of amylase was increased. Neonatal sympathetic denervation induces supersensitivity for both adrenergic and cholinergic agonists as well as for DBcAMP. This may be due to compensatory mechanisms involving both up-regulation of receptors as well as amplification of the intracellular mediation.

Adrenergic Fibers↗

Hyaluronan improves the healing of experimental tympanic membrane perforations. A comparison of preparations with different rheologic properties.

Preparations of hyaluronan at various concentrations and molecular weights were topically applied to experimental tympanic membrane (TM), perforations in the rat and their ability to improve the healing pattern was elucidated. The perforation occupied the upper posterior quadrant of the TM. Alterations in healing rate and quality of the healed TM were examined by otomicroscopy and in histologic sections. Hyaluronan enhanced the healing rate and resulted in less opacity and structural alteration of the scar area. Closure time for the TM perforation was correlated to the concentration of hyaluronan but not to its molecular weight or viscosity. Improved scar quality was obtained in the presence of hyaluronan irrespective of its rheologic properties. Hyaluronan improved the restoration of the fibrous connective tissue layer. Treatment of TM perforation in man with hyaluronan at high concentrations should be considered as an alternative to myringoplasty.

Administration, Topical↗

Structural effects of the topical lidocaine-prilocaine anesthetic Emla on the tympanic membrane.

A eutectic mixture of two anesthetic solutions is that of lidocaine and prilocaine, which is available commercially as Emla (eutectic mixture of local anesthetics). This solution is commonly used in clinics in superficial skin surgery and when inserting intravenous catheters, and we also wanted to determine its surface effects when applied onto the tympanic membranes (TM) of rats and guinea pigs as animal models. The animals were observed by otomicroscopy for 2 weeks up to 5 months after administrations of the anesthetic solution. Tissue specimens were then obtained for light microscopy and fine structural analysis. The application of Emla caused minor structural changes to the rat TM, but hardly any alterations to that of the guinea pig. The changes displayed were an overall increased thickness, with typical submucosal edema but only slight epithelial reaction. In comparison with previous results with lidocaine, phenol and Bonain's solution, Emla seemed to be harmless to the structure of the TM. However, the efficacy of Emla as a topical TM anesthetic remains to be proved in future clinical trials.

Anesthetics, Local↗