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M Hultcrantz

Publications and source records attributed to M Hultcrantz.

At least 19 recordsLinked to original sources
PubMed2006

Estrogen and hearing: a summary of recent investigations.

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turner's syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the male's hum-like call. If estrogen receptor beta is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, alpha and beta, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.

Aging↗
PubMed2003

Effect of estrogen and antiestrogens on the estrogen receptor content in the cochlea of ovariectomized rats.

Older women in the normal population tend to develop less severe hearing loss as compared to males in the same age. In Turner syndrome (45,X), estrogen deficiency is one of the predominant problems. Ear and hearing problems are common among these patients. Does estrogen have an impact on the hearing organ? Twenty-four rats were ovariectomized and treated with vehicle (controls), estradiol or selective estrogen receptor modulators such as tamoxifen and ICI182780, in order to study the effects on the estrogen receptor levels and distribution in the inner ear. The cochleas were stained immunohistochemically using antibodies against estrogen receptor alpha and beta. No major difference in estrogen receptor content in the cochleas was observed among groups. There was however a potential down regulation of estrogen receptor alpha in the marginal cells of stria vascularis in the rats that were substituted with ICI182780 (pure antiestrogen) as compared to those given estradiol or tamoxifen. When investigating the tissues with light microscopy no change in inner ear anatomy could be observed.

Animals↗
PubMed2003

Ear and hearing problems in Turner's syndrome.

OBJECTIVES: To report hearing results in Swedish women with Turner's syndrome (TS), describe the recommendations of the Otologic Section of the Swedish Turner Academy for handling these patients and discuss the effect of estrogen on hearing in animals. MATERIAL AND METHODS: Audiometric and karyotype tests were performed in 325 Swedish women with TS. A questionnaire was completed by 143 females with TS. Immunohistochemical staining of inner ear specimens was undertaken using antibodies against estrogen receptors in both human fetuses with TS and middle-aged women. Temporal bones obtained from various animal species were also studied immunohistochemically. RESULTS: A total of 61% of the women had suffered from otitis media. A senorineural dip in hearing could be observed as early as the age of 6 years, progressed over time and was related to karyotype. The results of the questionnaire revealed that hearing impairment was rated as the fourth most serious problem associated with TS. The immunohistochemical study confirmed that estrogen receptors are present in the inner ear of humans. The animal experiments showed that estrogen receptors were present at almost equal amounts in rats, mice, TS mice, beta knockout mice and ovariectomized rats and at the same localization as in the human inner ear. CONCLUSIONS: Both the senorineural dip in hearing and the karyotype can be used to predict the future course of hearing problems in TS patients. Estrogen may have an effect on hearing loss in TS patients but this phenomenon requires further investigation.

Adolescent↗
PubMed2002

Estrogen receptors alpha and beta in the inner ear of the 'Turner mouse' and an estrogen receptor beta knockout mouse.

Estrogen receptors have earlier been shown in the normal mouse, rat and human inner ear. If estrogens are important in normal hearing and development of presbyacusis in the normal population is not known. However it is known that patients with Turner syndrome, where a lack of estrogens is one of the main characteristics, commonly develop an early presbyacusis. A 'Turner mouse' has been developed, as a model for the ear problems in Turner syndrome, and it shows otitis media and a premature aging of the hearing. Estrogen receptors exist in an alpha and a beta form. In this study inner ear tissue, from the Turner mouse and an estrogen receptor beta knockout mouse (betaERKO), was investigated regarding estrogen receptor alpha and beta using immunohistochemistry. Results show that the Turner mouse has the same pattern of inner ear labeling, both concerning the estrogen receptor alpha and beta, as that of a normal CBA/Ca mouse, with positive staining in the organ of Corti and spiral ganglion. The betaERKO mice show close to normal inner ear morphology and positive estrogen receptor alpha immunostaining at the same locations as the CBA/Ca mouse.

Animals↗
PubMed2001

A study of inflammatory mediators in the human tympanosclerotic middle ear.

OBJECTIVE: To analyze immunocompetent cells as well as 2 factors involved in inflammation and also thought to be involved in bone remodeling-interleukin 6 (IL-6) and inducible nitric oxide synthase in the human middle ear, including the tympanic membrane. DESIGN: Biopsy specimens were obtained from the human middle ear and tympanic membrane during surgery. Using an immunohistochemical technique, the expression of macrophages, T cells, B cells, IL-6, and inducible nitric oxide synthase were analyzed. MATERIALS: Nine biopsy specimens from tympanic membranes in children having a transtympanic ventilation tube inserted as a treatment for secretory otitis media and 11 biopsy specimens from tympanosclerotic plaques from patients with chronic otitis media and tympanosclerosis. RESULTS: More positively stained specimens showing macrophages, B cells, and IL-6 were seen in the biopsy specimens from children with secretory otitis media compared with the biopsy specimens from patients with chronic otitis media and tympanosclerosis. The biopsy specimens from patients with chronic otitis media and tympanosclerosis more often showed positive stainings for inducible nitric oxide synthase than the biopsy specimens from children with secretory otitis media. The presence of IL-6 and inducible nitric oxide synthase was shown by staining to be mostly in the surface cells, while macrophages and B cells were stained deeper in the tissues, in connective tissue, or around sclerotic lesions. CONCLUSIONS: The 2 patient groups differed in antigen presentation so that macrophages, B cells, and IL-6 were labeled more frequently in patients with secretory otitis media, that is, an early phase of the disease. Inducible nitric oxide synthase was seen more frequently in the patients with already established tympanosclerosis in a later phase of the disease.

B-Lymphocytes↗
PubMed2001

Detection and localization of interleukin-6 in the rat middle ear during experimental acute otitis media, using mRNA in situ hybridization and immunohistochemistry.

OBJECTIVE: Otitis media is one of the most common diseases among children. A well-known sequela of acute, chronic, and secretory otitis media is tympanosclerosis. With the exception of surgery, there is no causal treatment available for this condition, which may cause hearing disabilities. This study aimed to describe the localization of interleukin (IL)-6 mRNA and its gene product in the rat middle ear during pneumococcal otitis media. IL-6 is known to be involved in inflammatory and bone remodeling processes. METHODS: Using an experimental model of pneumococcal acute otitis media, the expression of interleukin IL-6, was analyzed. Sprague-Dawley rats were sacrificed at different time points varying from 1 h to 6 days intervals after inoculation. The middle ears were analyzed by messenger RNA in situ hybridization, and by immunohistochemistry with cell-type specific antibodies directed against IL-6. RESULTS: Transcripts of IL-6 were observed only on day 1 post-inoculation, whereas the final gene product was observed at all intervals after inoculation. IL-6 was localized in the bony part of the bulla nearest to the mucosa, around mucosal vessels, and in the ciliae of the mucosal epithelium. The results demonstrated that IL-6 was synthesized locally as early as 1 h after bacterial middle ear challenge, and that although transcription could not be detected after 24 h, the cytokine product persisted for at least 5 days after the infection was introduced. CONCLUSIONS: IL-6 was shown to be produced early in the inflammatory process during induced pneumococcal otitis media in the rat. No production was seen after 24 h although the protein remained in the tissue for at least 5 days. IL-6 could initiate a differentiation of macrophages to osteoclasts and thereby participate in a bone remodeling process leading to tympanosclerosis development.

Acute Disease↗
PubMed2001

Estrogen receptors in the normal adult and developing human inner ear and in Turner's syndrome.

The influence of estrogens, the female sex hormone, on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The presence of estrogen receptors alpha and beta has earlier been shown in the inner ear of mice and rats. The aim of this study was to map possible estrogen receptors in the human inner ear. Inner ear tissue from human adults, aborted human normal fetuses and fetuses with Turner's syndrome were collected. Paraffin embedded sections of adult and fetal inner ears were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptor alpha containing cells were found in the adult human inner ear only in the spiral ganglion, and estrogen receptor beta in the stria vascularis solely. The human fetal inner ear tissue from both normal and Turner fetuses showed a very weak staining of estrogen receptor alpha in the spiral ganglion cells, but no specific labeling of the Kölliker's organ of Corti at 13, 14 and 18 weeks of age. No staining of estrogen receptor beta was seen in the fetal inner ear.

Adult↗
PubMed2001

Na,K-ATPase expression in the mouse cochlea is not dependent on the mineralocorticoid receptor.

This study was performed in order to test the hypothesis that the mineralocorticoid hormone stimulates the expression of Na,K-ATPase in the cochlea of the mouse. Immunohistochemistry was used to investigate the distribution of the mineralocorticoid receptor (MR) in the cochlea of the C57Bl/J6 mouse at different ages between gestational day 19 and postnatal day 30, and the occurrence and distribution of Na,K-ATPase in the inner ear of a mouse with a null mutation of the MR. Adult patterns of staining for MR were found as early as on gestational day 19 in the cochlea, with small changes thereafter. MR was detected in the same structures in the cochlea as Na,K-ATPase in earlier studies, where the amount of Na,K-ATPase increased after postnatal day 4. Thus there is latency between the increase of MR and the increase of Na,K-ATPase. In the cochlea of the MR deficient mouse, antibody labelling of Na,K-ATPase showed no significant difference as compared to the control wild type mouse. The hypothesis that mineralocorticoid hormone alone via MR stimulates the formation of Na,K-ATPase in the inner ear could not be confirmed by this study, and other regulating mechanisms must be considered.

Animals↗
PubMed2001

Cochlear distribution of Na,K-ATPase and corticosteroid receptors in two mouse strains with congenital hearing disorders.

As corticosteroid hormones, via their receptors, and Na,K-ATPase are thought to be involved in the regulation of endolymph production, two mouse models were used to investigate whether degeneration of the stria vascularis (SV) and disturbed endolymph composition are correlated with changes in the amounts and distribution of corticosteroid receptors and Na,K-ATPase in the cochlea. Both the shaker-2 mouse and the newly discovered mix mouse are deaf at birth and show vestibular dysfunction. In both mouse strains, the SV is degenerated and endolymph production is severely disturbed. In the shaker-2 mouse, using the C57Bl mouse as a normal control, immunohistochemical staining of mineralo- and glucocorticoid receptors (MR and GR) and the Na,K-ATPase subunits alpha1, alpha3 and beta1 showed a weaker reaction in all structures of the cochlea. The inner ear morphology of the mix mouse is described and compared to that of asymptomatic littermates. Immunostaining of MR, GR and the different Na,K-ATPase subunits in this mouse was considerably weaker in the SV, while staining intensities were normal in the remaining cochlea. The reduced corticosteroid receptor levels may lead to a reduction in Na,K-ATPase expression in the same tissues, although this conclusion should be treated with caution. The conclusion that reduced Na,K-ATPase levels in both mouse strains may be an important mechanism of the disturbed endolymph production is less controversial.

Animals↗
PubMed2001

Recommendations for the diagnosis and management of Turner syndrome.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

Adolescent↗
PubMed2000

Characterization of hearing in an X,0 'Turner mouse'.

Turner's syndrome is due to total (45,X) or partial (mosaicism) loss of one X-chromosome. The main features are short stature, ovarian dysgenesis with no estrogen production and infertility. In addition to ear and hearing disorders, middle ear problems including acute/serous otitis media and chronic middle ear disease are frequent. Sensorineural hearing loss is often seen with a dip in the mid-frequencies and also an early high frequency loss. In this study, middle-and inner-ear pathology was characterized using physiological and morphological techniques in a 'Turner mouse' that has been generated with the chromosomal aberration X,0. Otitis media was found in some of these X,0 animals, a symptom that is seldom found in control animals. The auditory brainstem responses (ABR) of the Turner mouse showed a progressive hearing loss in the high frequency region that exceeded the normal age-related hearing loss of control mice and increased latencies of the first ABR wave. Outer hair cell loss was apparent in the cochlear basal turn of Turner mice. Decreases in the amplitude of distortion product otoacoustic emissions were correlated with the loss of ABR threshold sensitivity. These results indicate that hearing problems in the Turner mouse seems to be of cochlear origin with an eighth nerve component. This Turner mouse model appears to have ear and hearing problems quite similar to humans and can therefore be used as a model to determine the auditory pathology underlying this syndrome.

Animals↗
PubMed2000

Labeling of the glucocorticoid receptor and Na,K-ATPase in a rat otitis media model.

HYPOTHESIS: Glucocorticoid hormones exert an influence on the inflammatory response of the middle ear during acute otitis media. Rats with experimentally induced purulent otitis media were given either glucocorticoid hormones in excess or a glucocorticoid hormone blocker that deprived the animals of the hormone. BACKGROUND: Acute otitis media is a common inflammatory disease among children. Streptococcus pneumoniae is the most usual causative agent. The standard treatment today is phenoxymethylpenicillin. The role of glucocorticoid hormones in inflammatory reactions in the middle ear has been widely debated. METHODS: In an otitis media model, a suspension of pneumococci was inoculated into the bulla of the rat, after the animals were pretreated with either a dose of corticosteroid hormones or the glucocorticoid receptor blocking agent RU 486. Rats with induction of otitis media only, but no pretreatment, were used as control subjects, as were the left control-operated ears of all rats. The inflammatory response in the inner ear and in the middle ear was evaluated. The presence of glucocorticoid receptors and the enzyme Na,K-ATPase was investigated with immunohistochemistry. RESULTS: The inflammatory response in the animals with untreated otitis media and in the group with otitis media in rats pretreated with the receptor blocker was much more extensive than in the group of animals pretreated with corticosteroids. In the corticosteroid-treated group, the tympanic membrane and the mucous membrane of the middle ear were less edematous, but the middle ear cavity contained more pus. Only a few lymphocytes were found in the inner ears of these rats. When the inner ear was labeled with antibodies against glucocorticoid receptors, there seemed to be no difference between the labeling patterns in the three groups. This was also the case for antibody labeling against Na,K-ATPase. CONCLUSION: The present results indicate that the reaction in the middle ear mucous membrane is more pronounced in rats that had been pretreated with the hormone receptor blocking drug. An increase of corticosteroid hormone levels during the inflammatory process seem to diminish the reaction in the tympanic membrane and the middle ear mucosa. Neither the hormone receptor blocking drug nor the steroid hormones change the content of glucocorticoid receptors and Na,K-ATPase in the inner ear in the otitis media rat model.

Acute Disease↗
PubMed1999

Mapping of estrogen receptors alpha and beta in the inner ear of mouse and rat.

The sex hormone estrogen is classically known to influence growth, differentiation and function of peripheral tissues of both the female and male reproductive tract, mediated through the estrogen receptors alpha and beta. The influence of estrogens on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The aim of this study was to map eventual estrogen receptors in the inner ear in mouse and rat. Paraffin embedded sections of mouse and rat inner ear were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptors alpha and beta containing cells were found in the inner ear, showing a unique distribution pattern, both in the auditory pathways and in the water/ion regulating areas. The presence of estrogen receptors indicates that estrogens may have an effect on the inner ear and hearing functions.

Animals↗
PubMed1999

An immunohistochemical study of inducible nitric oxide synthase in the rat middle ear, with reference to tympanosclerosis.

Tympanosclerosis and myringosclerosis are well-known sequelae after acute and chronic otitis media and are also often seen after treatment of secretory otitis media with ventilation tubes. They sometimes cause serious hearing disability. There is no successful treatment for these conditions. There might be factors triggering an immunological or autoimmune chain reaction, which leads to tympanosclerosis. Intervention with the aim of abolishing this type of response might be possible if an interruption of the chain reaction can be found. Nitric oxide is a radical molecule with the ability to kill pathogens and is produced by the enzyme nitric oxide synthase. Expression of inducible nitric oxide synthase (iNOS) was analysed immunohistochemically in a rat model of acute otitis media. In rats sacrificed at days 3 and 6 after inoculation. iNOS was also strongly expressed in the middle ear mucosa and in the tympanic membrane as well as in the inner ear. In control specimens as well as in infected ones. iNOS was expressed in the tissue of the external ear canal. In rats sacrificed at day 10 and after 3 months, iNOS was expressed at the same locations, although less frequently. These data indicate that iNOS expression is induced during acute otitis media and suggest that nitric oxide may be important in the host defence against ear infections.

Acute Disease↗
PubMed1999

Infiltration of immunocompetent cells in the middle ear during acute otitis media: a temporal study.

HYPOTHESIS: The inflammatory response to acute otitis media (AOM) is a chain reaction involving, among others, macrophages, B lymphocytes, and T lymphocytes that vary in number on different days during the infection. The response is thought to eventually contribute to tympanosclerosis (TS). BACKGROUND: In humans, TS and myringosclerosis (MS) are obscure sequelae of chronic otitis media. MS is also commonly seen in children who have had acute purulent otitis media or secretory otitis media or after treatment with ventilation tubes in the tympanic membrane (TM). It causes hearing disability, especially if the ossicles or the inner ear are affected. No successful treatment is available. This study was performed to evaluate the inflammatory stages that may lead to TS or MS. METHODS: Sprague Dawley rats were exposed to a Pneumococcus type 3 solution into the middle ear. Groups of rats were killed at 3, 6, and 10 days after inoculation. Sections from the TM specimen were stained immunohistochemically according to the avidin-biotin method. Antibodies used were directed against macrophages, T cells, and B cells. Positive cells were counted and a mean value was estimated for each slide and section for each antibody in each rat. RESULTS: Results showed that macrophages, T cells, and B cells were presented time-dependently in the acute inflammatory response in AOM. At day 3, dendritic cells, macrophages, T cells, B cells, and other major histocompatibility complex (MHC)-restricted cells were richly expressed in the whole submucosal layer and especially in the annulus fibrosus. At day 6, the amount of all positive cells decreased except for B cells and other MHC-restricted cells, which slightly increased in number. At day 10, all of the cells were lower in number than at days 3 and 6. Macrophages and possible T cells could be detected in the TM, which has not been observed earlier. Large osteoclastlike cells were present close to the bone. CONCLUSIONS: Macrophages were the first cells to invade the tissue after AOM induction. Some cells were found in the TM. Large osteoclastlike cells could be seen adjacent to the bone in the submucosa. T cells and B cells were seen in the submucosa.

Acute Disease↗
PubMed1999

[The medical faculty in Vienna during the nineteenth century].

To understand the enormous cultural dominans of Vienna during the 19-teenth century it is necessary to know some of the long history of the Habsburg empire. It was created as early as 1276. The Vienna medical faculty got its first strong position during the middle of the 18-teenth century. Vienna became the political and cultural centre as capital of the empire. From all parts of the many cultural country the intelligentsia came to the city. The development in all fields of culture: music, literature, art, and architecture was impressing. After the revolution in 1848 the medical faculty changed its policy and the so called second Vienna School was established. The pathologist Carl von Rokitansky played a decisive role both as administrator and as scientist. Many famous doctors and scientists gave the medical faculty a world-wide reputation and pupils from all over the world found Vienna to be a medical Mecca. In many medical specialities Vienna took the leading position. At the same time the faculty became a centre for bitter priority fights. One of the reasons for that was the vast collection of representatives from different nationalities and ethnic groups. The era of greatness began to diminish when it got to its end when the Austrian-Hungarian double monarchy fell into pieces in 1916 and disappeared definitely in 1938 after the German annexation.

Austria↗