[A national quality program for otorhinolaryngology. Five diagnoses are described--computerization is an obstacle].
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Humans↗
Biomedical subjects
S Hellström
Publications and source records attributed to S Hellström.
Hyaluronan in human and rat muscle spindles.
Previous data on the composition of the periaxial fluid of muscle spindles have relied on indirect histochemical methods. We used a biotinylated hyaluronan-binding protein as a specific probe for the detection of hyaluronan in sections of human and rat limb muscles. Hyaluronan was identified in the axial and periaxial space of the muscle spindles as well as in the endoneurium and in the space in between individual axons. Hyaluronan was also present in the innermost layer of the spindle capsule in the A region and in all layers of the capsule in the B region.
Animals↗
Islet cell surface antibodies (ICSA) do bind to human pancreas: computerised, quantitative determination of ICSA using both pre- and postembedding immunocolloidal techniques.
Islet cell surface antibodies (ICSA) have been demonstrated significantly more often in serum of patients with IDDM and their relatives than in healthy controls, but some investigators have been unable to show binding to human islets. It has therefore been suggested that ICSA is an artefact. We have localised and quantified ICSA binding to different specimens, including human pancreas. ICSA-positive and ICSA-negative patients' serum, determined by a RIA-method, were incubated with ultrathin sections of rat insulinoma (RIN5AH) cells, stained with Goat-anti-human IgG conjugated with 10 nm gold particles. Sections were viewed in transmission electron microscopy (Mag. 30,000 x) and image analyses was used to calculate immunolabelling. To test cell specificity we used (RIN5AH-cells, rat tumour cells producing growth hormone (GH3), normal human pancreas, human insulinoma, and mice liver). Sections showed good morphology. ICSA-positive sera, with or without islet cell antibodies (ICA) gave always higher immunocolloidal labelling then ICSA-negative sera on RIN5AH sections. Thus, the colloidal gold technique could confirm the ICSA results determined with RIA. Immunolabelling was pronounced on normal human pancreas and human insulinoma cells, but none was found on GH3-cells or mice liver cells. ICSA is not an artefact but do exist and bind to human islet cells and therefore maybe can be used as a marker for IDDM immunity.
Animals↗
Specific sound-induced noradrenergic and serotonergic activation in central auditory structures.
We have studied the noradrenergic and serotonergic changes induced by white noise stimulation at 70, 90 or 110 dB SPL for 45 min, in cochlear nuclei, inferior colliculus (IC), primary auditory cortex (PAC) and as a comparison in locus coeruleus (LC) and raphe dorsalis using HPLC. Both noradrenergic and serotonergic pathways were activated in the dorsal+posteroventral cochlear nuclei (DCN+PVCN) without changes in the anteroventral cochlear nucleus (AVCN) and IC. In the DCN+PVCN the noradrenergic activation was restricted to animals exposed to 70 dB SPL whereas the increase of serotonin content was intensity-dependent. In PAC serotonergic activation was observed only after 70 dB SPL exposure. These data suggest that in physiological conditions (70 dB SPL) noradrenergic and serotonergic regulation of the processing of auditory information occurs specifically in the dorsal cochlear nucleus where the control of incoming information to higher auditory structures takes place (i.e. IC and PAC). We suggest that the serotonergic activation in the primary auditory cortex for 70 dB SPL sound stimulation could be related to the fact that low-intensity white noise stimulation could be the most plastic-demanding processing in the auditory cortex.
Acoustic Stimulation↗
The surface epithelium of recurrent infected palatine tonsils is rich in gammadelta T cells.
Using a large panel of MoAbs in quantitative morphometric analysis of immunohistochemically stained tissue sections, we compared the frequency and distribution of immune cells in palatine tonsils from patients with recurrent tonsillitis (RT) and patients with idiopathic tonsillar hypertrophy (ITH). We found that differences between the two patient groups in leucocyte populations were limited to the surface epithelium, whereas the cellular composition of interfollicular and follicular areas was similar. Most intraepithelial lymphocytes were CD8+ T cells in both groups. However, the number of intraepithelial T cells was significantly higher in RT compared with ITH. This was due to a selective increase in the number of intraepithelial CD8+ gammadelta T cells utilizing Vdelta1 and Vgamma9. In both patient groups the majority of the intraepithelial gammadelta T cells expressed Vdelta1 and Vgamma9. Subepithelially, gammadelta T cells utilizing Vgamma9 dominated over cells utilizing Vgamma8, while equal proportions expressed Vdelta1 and Vdelta2. These results suggest that cells utilizing the otherwise rare combination Vdelta1/Vgamma9 in their T cell receptors (TCR) may constitute a major gammadelta T cell population in palatine tonsils and are probably reactive to antigens specific to the tonsillar milieu. Furthermore, they indicate that preferentially this gammadelta T cell subpopulation is involved in immune reactions within the surface epithelium in RT. We speculate that gammadelta T cells are involved in clearing infectious bacteria at the tonsillar surface and in limiting inflammatory responses in the tonsils. Both local expansion and infiltration of blood cells probably contribute to the high numbers of gammadelta T cells in RT patients.
Adolescent↗
Myringotomy: a prerequisite for the development of myringosclerosis?
Streptococcus pneumoniae was inoculated into the left middle-ear cavity in two groups of rats, resulting in purulent otitis media. After 3 days, one group of infected animals and a third group of noninfected animals were subjected to left-sided myringotomy. The tympanic membranes were examined both otomicroscopically and histologically 1 and 3 months later. On otomicroscopic examination the noninfected myringotomized animals had developed extensive myringosclerotic lesions, whereas only minimal sclerotic deposits were noted in the myringotomized animals with acute otitis media (AOM). On histologic examination both the noninfected myringotomized animals and the myringotomized animals with AOM were similar in the frequency and extension of sclerotic lesions in the tympanic membrane. The nonmyringotomized rats with AOM were free of sclerotic lesions, except for minor changes found in one animal.
Acute Disease↗
Interactions between the middle ear and the inner ear: bacterial products.
The round-window membrane (RWM) is extremely thin and is the only soft-tissue barrier between the middle ear and the inner ear. Under inflammatory conditions of the middle ear the various layers of the triple-layered RWM undergo characteristic changes parallel to the changes of the middle-ear mucosa. Several studies report that bacterial products, exo- and endotoxins, from bacteria invading the middle ear may result in profound inflammatory changes in the inner ear, followed by severe damage to the inner-ear function. The present review, in which we summarized experimental and clinical observations, on bacterial products in interactions between the middle and inner ear, focused on: 1. Bacteria and bacterial products in an inflamed middle ear that may influence inner-ear function. 2. RWM structure and RWM permeability under the influence of bacteria and bacterial products. 3. Morphological and functional inner-ear effects of bacterial infection of the middle ear, and the possible mechanisms involved. 4. Future studies to be directed in this field.
Animals↗
Inhibition of the development of myringosclerosis by local administration of fenspiride, an anti-inflammatory drug.
Earlier studies have revealed a relationship between the development of myringosclerosis and oxygen-derived free radicals. The latter can be blocked by the anti-inflammatory drug fenspiride. The present study was undertaken to test the ability of fenspiride to prevent myringosclerosis from developing during healing of the tympanic membrane. Myringotomized rats were treated with either topical applications or intraperitoneal injections of fenspiride for 12 days, after which the tympanic membranes were examined by otomicroscopy and studied histologically by light microscopy. Topically applied fenspiride was found to inhibit the development of sclerotic lesions, whereas intraperitoneal injections were ineffective.
Administration, Topical↗
An animal model for external otitis.
External otitis was produced in 12 Sprague-Dawley rats by mechanical stimulation through a plastic micropipette inserted into the right external auditory canal (EAC). The EAC was later evaluated regarding the color of the skin, swelling and the presence of fluid. Within 1 day all rats developed an external otitis that was characterized by a red, swollen ear canal containing an opalescent fluid. The tympanic membrane and middle ear cavity appeared to be normal. No healed EACs were seen within the initial 10 days of follow-up and 4 of 6 rats still exhibited external otitis at day 21. Light microscopy of biopsy specimens revealed pronounced edema of the dermis of the ear canal. Mast cells were more numerous in the early phase of the otitis present, although very few inflammatory cells were found in tissues despite the marked inflammatory reaction produced. Findings show that this animal model for external otitis can be used to investigate pathogenesis as well as to test various treatment strategies.
Animals↗
Autoantibodies in relation to residual insulin secretion in children with IDDM.
To elucidate whether autoantibodies can be used to predict the intensity of autoimmune beta-cell destruction, we determined both C-peptide and autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface antibodies (ICSA) and antibodies to glutamic acid decarboxylase (GADA)). In 89 diabetic children and adolescents at diagnosis at the age of 1.2-16.6 years (mean +/- S.D., 9.0 +/- 4.5). Only 12/89 (14%) had no autoantibodies at diagnosis, while 2 patients (2%) had all 4 autoantibodies. There was a positive correlation between GADA and ICA (P < 0.01). At diagnosis 70% of the patients had GADA, most common in patients above the age of 8 years at diagnosis (P < 0.001), and with higher GAD-index in girls (P < 0.05). ICA was detected in 63%, most common in the older age groups (P = 0.04). ICSA seen in 22% of the patients as well as IAA (detected in 32%) were most common < 8 years of age (P = 0.06, P = 0.08, respectively). Children with autoantibodies had similar C-peptide levels through the follow up period as children of the same sex and age without antibodies, except for patients with ICSA alone or in combination with other autoantibodies who tended to have higher C-peptide levels. We conclude that not even combinations of autoantibodies can be used to predict beta-cell destruction in IDDM patients.
Adolescent↗
Extracellular matrix components reflect the dynamics of a healing tympanic membrane perforation--a histochemical study.
Extracellular matrix components have hitherto been sparsely studied in tissue repair processes. In this study, the distribution of hyaluronan (HYA), fibronectin, and five chondroitin sulfate glycosaminoglycans (GAGs) was analysed in healing tympanic membrane (TM) perforations of rats, at different time points, using a HYA-binding protein probe and six monoclonal antibodies (MAbs). Hyaluronan appeared, the first day, around migrating squamous epithelial and inflammatory cells in the perforation borders and close to dilated vessels at the malleus handle. Accumulated HYA persisted in the thickened perforation rim until closure of the perforation, then it slowly disappeared from the healed TM area. Fibronectin immunoreactivity occurred around proliferating cells in the perforation edge and around collagen bundles in the connective tissue. The MAbs for chondroitin sulfate GAGs rendered specific, constant immunostaining patterns throughout the healing process. Unsulfated chondroitin, chondroitin-4-sulfate and chondroitin-6-sulfate were present in small amounts in the connective tissue surrounding collagen fibres and fibroblasts. The staining for native chondroitin and dermatan sulfate was most pronounced in the epithelial layers, in particular the squamous epithelium and its keratin layer, whereas the loose connective tissue was left unstained. After closure of the TM perforations, the immunoreactivity for unsulfated chondroitin, native chondroitin and dermatan sulfate increased in the scar tissue. It is concluded that HYA is abundant in early stages of healing of TM perforations, whereas fibronectin, unsulfated chondroitin, chondroitin-4 and 6-sulfate are constantly present in small amounts during the healing process. Unsulfated chondroitin, native chondroitin and dermatan sulfate increase in the healed TM area.
Animals↗
Myringotomized mice develop myringosclerosis in the pars flaccida and not in the pars tensa.
The development of myringosclerosis has been correlated with increased production of oxygen-derived free radicals. For the present study, we used a null mutant mouse lacking extracellular superoxide dismutase to test the hypothesis that increased production of free radicals can cause the development of myringosclerosis. Null mutant mice and wild-type, control mice were myringotomized and kept in ambient air for 3 weeks. Both groups developed myringosclerosis in the pars flaccida, but not in the pars tensa. The sclerotic lesions were visible in both the light and the electron microscope but not in the otomicroscope. In particular, the localization of the sclerotic deposits was found beneath both the inner and outer epidermal epithelium. No difference concerning the extent or number of sclerotic lesions between the null mutant and the wild-type mice could be distinguished.
Animals↗
Hyaluronan in human deciduous tooth germs in the bell stage. Histochemistry and immunohistochemistry.
The primary aim of the present study was a localization of hyaluronan (HA) in human deciduous tooth germs in the bell stage. HA was compared to the content of chondroitin sulfates (CSs). HA was detected with a biotin-labeled HA-binding protein (HABP) and CS with a monoclonal antibody. As controls, enzyme digestions were carried out. Furthermore, the glycosaminoglycans were investigated histochemically with enzyme digestions followed by alcian blue staining. The investigation showed a considerable content of HA in the stellate reticulum, although CS was also found, primarily when treatment with protease was omitted. The dental papilla contained both HA and CS, while the predentin and the dentin contained only CS. The enamel did not contain any CS, but some staining with HABP was observed along the borderline between the ameloblasts and the enamel. The significance of HA in the stellate reticulum is discussed. The importance of carrying out investigations with and without protease digestions is stressed.
Antibodies, Monoclonal↗
Application of oxygen free radical scavengers to diminish the occurrence of myringosclerosis.
The present study was designed to establish whether or not an increased production of oxygen-derived free radicals is involved in the causation of myringosclerosis. Sclerotic lesions in the tympanic membrane were experimentally elicited by keeping rats with perforated tympanic membranes in an atmosphere containing roughly 40% oxygen. The animals were treated daily with a solution containing either copper zinc-superoxide dismutase plus catalase, deferoxamine, or copper sulfate plus iron chloride, applied to the traumatized area. After 1 week the extension of myringosclerotic plaques was determined otomicroscopically. The pars tensa and pars flaccida were then dissected free and prepared for light microscopic studies. The results showed that treatment with copper zinc-superoxide dismutase plus catalase and deferoxamine inhibited or reduced the development of myringosclerosis, whereas the ears treated with copper sulfate plus iron chloride appeared unaffected. Consequently, the findings support the hypothesis that the formation of oxygen free radicals contributes significantly to the development of myringosclerosis.
Animals↗
The tympanic membrane and middle ear mucosa during non-typeable Haemophilus influenzae and Haemophilus influenzae type b acute otitis media: a study in the rat.
Non-typeable Haemophilus influenzae (NTHi) and encapsulated Haemophilus influenzae type b (Hib) were inoculated into the middle ears of Sprague-Dawley rats. Tympanic membrane (TM) status was assessed otomicroscopically and specimens from various middle ear areas were prepared for light microscopy at various times during the acute phase and up to 6 months after inoculation. Irrespective of bacteria strain, acute otitis media (AOM) was present in all ears 4 days after inoculation. The Hib-infected ears showed initially a severe course of AOM, but all were otomicroscopically resolved by day 12, at which time a few NTHi-inoculated ears still exhibited middle ear effusion. The TMs infected with Hib had normalized without scar formation, whereas NTHi induced a persistent thickening of the TMs in half of all cases. The middle ear mucosa of NTHi-infected ears initially showed vigorous activity among the goblet cells, but the mucosa normalized after the acute phase. Hib, by contrast, induced prominent changes in the middle ear mucosa. Initially, no goblet cell granules or ciliated cells could be observed in the mucosa. Later on, the epithelium contained large, active goblet cells. Glands appeared beneath the mucosa which persisted as streaks of epithelial cells throughout the study period. The findings show that NTHi and Hib both induce AOM but with differing clinical courses, and affect different targets in the middle ear.
Acute Disease↗
A national framework for district nurses' uniform documentation patient records.
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Forms and Records Control↗
Abundance of intraepithelial gamma delta T cells in hypertrophic obstructive but not in chronically infected adenoids.
Using quantitative morphometric analysis of immunohistochemically stained tissue sections we compared hypertrophic obstructive adenoids (HOA, n = 10) from children without middle ear disease with chronically infected adenoids (CIA, n = 10) from children with middle ear disease. gamma delta T cell receptor (TCR)+ cells constituted the dominating T cell population in the surface epithelium of HOA, while alpha beta TCR+ cells were the dominating intraepithelial T cell population in CIA. Intraepithelially CD8+ cells dominated over CD4+ cells in both diseases. Intraepithelially B cells were not detected. The cellular composition of follicles, with B cells dominating followed by activated CD4+ alpha beta TCR+ cells, was the same in both groups. However, the number of follicles in CIA was twice as many as in HOA. In the deeper interfollicular areas granulocytes were more abundant in CIA than in HOA. The latter two findings suggest a more pronounced inflammatory response in the adenoids of patients with middle ear disease. There was no significant difference with regard to pathogenic bacterial strains colonizing the adenoid surface when comparing the two patient groups. These results suggest that in patients with HOA gamma delta TCR+ T cells help to maintain the integrity of the surface epithelium, thereby preserving its protective function. On the basis of our results we speculate that CIA have a malfunctioning defence, thereby facilitating long-standing infections deep in the adenoid. This may be the main reason for development of middle ear disease and an indication for adenoidectomy in patients with CIA.
Adenoids↗
Structural characterization of persistent tympanic membrane perforations in man.
In the present structural study the authors investigated the border of permanent tympanic membrane (TM) perforations in patients selected for myringoplasty. Furthermore, a panel of monoclonal antibody markers that recognize different epitopes within glycosaminoglycans as well as antibodies to epidermal growth factor and fibronectin were applied to the sections. In half of the specimens the epithelial junction ended at the inside of the perforation border, whereas in the other half it was located at the perforation border itself. In the junctional area the keratinocytes were covered by a thick keratin layer which protruded as a spur centripetally in order to bridge the perforation. Epidermal cells formed papillae and contained remnants of keratinocyte nuclei that showed similarities to those of the skin in inflammatory conditions. The connective tissue layer was fibrous and showed areas containing sclerotic plaques. The inner epithelium of the TM had abundant ciliae, thus supporting the concept that cells of the mucosal lining of the TM are able to differentiate in inflammatory conditions into ciliated cells and secretory cells. The immunoreactivity of hyaluronan and other glycosaminoglycans, the immunoreactivity of epidermal growth factor, and immunoreactivity of fibronectin, all of which are known to occur in healing wounds, were only scantily demonstrated; this could be one reason for the arrested healing and a reason why the natural drive to complete a mature closure is abandoned.
Biomarkers↗