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At least 451 records · Page 25Linked to original sources
PubMed2003

Anosmin-1 immunoreactivity during embryogenesis in a primitive eutherian mammal.

Kallmann syndrome is hypogonadotropic hypogonadism coupled with anosmia. A morphological study found that the endocrine disorder in X-linked Kallmann syndrome is due to failed migration of gonadotropin releasing-hormone (GnRH) neurons from the olfactory placode to the brain during development. Anosmia results from agenesis of the olfactory bulbs and tracts. The gene responsible for the X-linked form of Kallmann syndrome, KAL-1, has been characterized. The orthologues of KAL-1 have been isolated in the chick and the zebrafish, but still await identification in rodents. In the present study, we used polyclonal and monoclonal antibodies to the human KAL-1 encoded protein, anosmin-1, in a primitive mammal, the Asian musk shrew. Musk shrews are insectivores and are therefore evolutionarily closer to primates than rodents. By immunoblot analysis of musk shrew tissues, a band of the expected apparent molecular mass (95 kDa) was detected in several structures of the central nervous system, but not in liver or muscle, which is consistent with the gene expression pattern previously reported in the chick. By immunohistochemical analysis, anosmin-1 was detected in the developing olfactory epithelium, the olfactory, vomeronasal and terminalis nerves, the olfactory bulbs, the cerebellum and the cerebral cortex and in several other regions of the brain, during musk shrew embryogenesis. Furthermore, migrating gonadotropin releasing-hormone (GnRH)-immunoreactive neurons were seen in close association with anosmin-1-immunoreactive fibers. Assuming that the protein is present at the surface of these fibers, we suggest a possible direct role of anosmin-1 in the migration of GnRH neurons in this species.

Animals↗
PubMed1989

Electro-olfactogram (EOG) in olfactometry.

The electro-olfactogram (EOG) is a potential originated in olfactory epithelium evoked by odorous stimulation, which has been demonstrated and termed by Ottoson (1959). In order to ascertain the clinical application of EOG, we attempted to record similar potentials in human subjects. In some preliminary experiments using rabbits, it was quite easy to produce Ottoson's findings. In human subjects, however, there were sometimes great technical difficulties owing to the hidden anatomical position of the olfactory epithelium. Then we utilized Olympus selfoscope endoscopy for placing and retaining the electrode to the olfactory portion precisely and safely, with a tube for sending airborne odor. As results, we succeeded in recording negative spike discharge similar to Ottoson's findings. We examined a total of 27 nasal cavities in 22 patients with peripheral olfactory disorders and 11 nasal cavities in 12 patients with central olfactory disorders. The positive EOG rate in patients with peripheral or central olfactory disorders was 28 and 69%, respectively. Moreover, the positive rate was decreased in proportion to the degree of olfactory disorders in chronic rhinosinusitis. No positive EOG was observed in anosmic nasal cavities, while it was 68% in normal persons and resulted in an equal value to anosmia group caused by the damage of central olfactory pathway. From these results, it is considered that the positive EOG study is the only method which provides objective finding for the differential diagnosis of anosmia caused by disorders of olfactory epithelium or disorders of central olfactory tract.

Chronic Disease↗
PubMed1993

Contributions of olfaction to maternal aggression in laboratory rats (Rattus norvegicus): effects of peripheral deafferentation of the primary olfactory system.

We examined the effects in postpartum female rats (Rattus norvegicus) of olfactory deafferentation by intranasal ZnSO4 on maternal aggression and retention of aggression 24 hr after pups are removed. When females were tested with pups, effects of deafferentation depended on postpartum interval; anosmia failed to reduce aggression on Lactation Day 3 (L3), but anosmia was associated with moderate reductions on L8-L12. We propose that postpartum aggression is stimulated initially by hormonal factors associated with late pregnancy but later is supported by exteroceptive stimulation. After removal of pups, although aggression scores were lower across treatment conditions, anosmic females had shorter latencies to attack and tended to elicit more submissive behavior from intruders. Data suggest that odor cues from conspecifics normally inhibit aggression by females, but this inhibition is reduced during lactation.

Administration, Intranasal↗
PubMed2002

The olfactory receptor gene superfamily of the mouse.

Olfactory receptor (OR) genes are the largest gene superfamily in vertebrates. We have identified the mouse OR genes from the nearly complete Celera mouse genome by a comprehensive data mining strategy. We found 1,296 mouse OR genes (including 20% pseudogenes), which can be classified into 228 families. OR genes are distributed in 27 clusters on all mouse chromosomes except 12 and Y. One OR gene cluster matches a known locus mediating a specific anosmia, indicating the anosmia may be due directly to the loss of receptors. A large number of apparently functional 'fish-like' Class I OR genes in the mouse genome may have important roles in mammalian olfaction. Human ORs cover a similar 'receptor space' as the mouse ORs, suggesting that the human olfactory system has retained the ability to recognize a broad spectrum of chemicals even though humans have lost nearly two-thirds of the OR genes as compared to mice.

Animals↗
PubMed1998

Contiguous gene syndrome due to deletion of the first three exons of the Kallmann gene and complete deletion of the steroid sulphatase gene.

OBJECTIVE: Large terminal or interstitial deletions of the 22.3 region on the short arm of the X chromosome cause contiguous gene syndromes. Kallmann syndrome (hypogonadotrophic hypogonadism with anosmia or hyposmia) associated with X-linked ichthyosis, due to a contiguous gene syndrome, is an uncommon finding. Genetic defects have been demonstrated in the Xp22.3 region, explaining the presence of one or both entities in affected individuals. In this report we describe the molecular findings of a patient with Kallmann syndrome and X-linked ichthyosis. PATIENT: A 20-year-old subject with hypogonadism, anosmia and generalized ichthyosis was studied endocrinologically, biochemically and molecularly. MEASUREMENTS: Levels of LH, FSH, GH, testosterone, oestradiol and cortisol were determined basally and after specific stimulation tests. Enzymatic activity of steroid sulphatase was measured in leucocytes. Polymerase chain reaction of the 14 exons of the Kallmann gene and of the 5' and 3' extremes of the steroid sulphatase gene was performed in genomic DNA. RESULTS: A partial deletion from exon 1 to exon 3 of the Kallmann gene, as well as a complete deletion of the steroid sulphatase gene were observed. CONCLUSIONS: A patient bearing a contiguous gene syndrome with partial deletion of the Kallmann syndrome gene and complete deletion of the steroid sulphatase gene is described. This is the first time a mutation in the conserved cysteine-rich N-terminal region which corresponds to the whey acidic protein motif of the Kallmann gene has been characterized, thus demonstrating the importance of this specific region for the function of the gene.

Adult↗
PubMedDate not supplied

[Kallmann De Morsier syndrome: FGF-signaling insufficiency?].

Kallmann syndrome (KAL) associates hypogonadotropic hypogonadism and anosmia, i.e. a deficiency of the sense of smell. Anosmia is related to the absence or the hypoplasia of the olfactory bulbs. Hypogonadism is due to GnRH deficiency, and is likely to result from the failed embryonic migration of GnRH-synthesizing neurons. These cells normally migrate from the olfactory epithelium to the forebrain along the olfactory nerve pathway. Kallmann syndrome is genetically heterogeneous. The gene responsible for the X-chromosome linked form of the disease, KAL-1, has been identified in 1991. KAL1 encodes a ~95 kDa glycoprotein of unknown function, which is present locally in various extracellular matrices during the period of organogenesis. The recent finding that FGFR1 mutations are involved in an autosomal dominant form of Kallmann syndrome (KAL-2), combined to the analysis of mutant mouse embryos that no longer express Fgfr1 in the telencephalon, suggests that the disease results from a deficiency in FGF-signaling at the earliest stage of olfactory bulb morphogenesis. We propose that the role of the KAL1 gene product, the extracellular matrix protein anosmin-1, is to enhance FGF-signaling, and suggest that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X-inactivation) explains the higher prevalence of the disease in males.

Biomedical Research↗
PubMed1995

[Sense of smell].

About two million Americans suffer from anosmia. Most result from nasal obstruction, head injuries, and viral infections. Brain disorders like epileptic seizures, tumours, and dementia can distort can distort the sense of smell. Anosmia adversely affects patient well-being. Patients cannot detect spoiled food, gas leakage, or dangerous smoke. They are unable to distinguish flavour and smell the springtime or the ocean. Many products as soaps, cat litter, toilet paper, etc. are perfumed because consumers will more readily buy a product that smells nice than one that has no smell at all. Historically, the importance of odors was very different. The ancient Romans loved exotic aromas during their banquets and orgies. In the Middle Ages the church did not like fragrances. The French revolution of 1789 brought a revolution of deodorization to Europe. Today, fragrance companies' increasing sales are an indication of the power of odor.

Humans↗
PubMed1999

Recovery of olfactory function after an anterior craniofacial approach.

We assessed recovery of olfactory function in five consecutive patients who underwent surgical resection of midline skull base tumors using an anterior craniofacial approach in which the cribriform plate was mobilized with the dura. Olfactory function was evaluated before and after surgery using an intravenous olfactory test with prosultiamine and also a standard olfactory acuity test. Before surgery, one patient showed anosmia attributable to obstruction of the nasal cavity and olfactory cleft, and four patients showed normal olfactory function. After surgery, one patient was irreversibly anosmic, probably because of intradural dissection of the olfactory tracts. The other four patients, including the patient showing anosmia preoperatively, reported subjective recovery of olfaction 3 to 8 weeks after surgery. Intravenous and standard olfactory acuity tests indicated recovery of olfaction to the normal range in three patients and decreased olfactory function in one. With careful preservation of the olfactory system and of the integrity of the nasal cavity, olfactory function was found to recover after skull base resections via the anterior craniofacial approach.

Journal Article↗
PubMed1998

Return of olfaction after gross total resection of an olfactory groove meningioma: case report.

Patients with olfactory, groove meningiomas may present with anostnia, Surgery in patients with intact olfaction can also lead to anosmia when the olfactory nerves are sacrified. Olfaction can be preserved by using the prerional approach and microsurgical technique. To our knowledge; however, the recovery of olfaction after resection of an olfactory groove meningroma has not been reported. We therefore describe a patient who presented with anosmia whose evaluation revealed a large olfactory groove meningioma. She underwent a bifrontal approach for microsurgical gross bilateral excision of the tumor. At her 6-month follow-up examination, her olfaction, as measured by formal testing, had recovered.

Case Reports↗
PubMed1977

Clinical testing of olfaction reassessed.

Odours in current use for testing olfaction (e.g., peppermint, camphor) cause considerable trigeminal nerve stimulation; this would render them relatively inefficacious in the detection of lesions of the main olfactory pathway. Musks and floral odours are considered to be relatively 'pure' olfactory stimulants, acting virtually exclusively via the first cranial nerve. These odours have been compared with standard odours in a group of patients whose olfactory pathways had been damaged by frontal tumours, surgical operation, head injury, multiple sclerosis and miscellaneous causes. Hyposmia or anosmia was detected more frequently and more reliably by musks and floral odours in all groups of patients; a number of patients had gross deficits of odour description without hyposmia or anosmia. Two-thirds of an unselected group of patients with multiple sclerosis had olfactory abnormalities. A substantial improvement in the rate of detection of organic lesions affecting the olfactory pathway can be achieved by substituting odours such as musk ketone, exaltolide, linalyl acetate and coumarin for those in current use.

Humans↗
PubMed1994

Olfactory function in patients with hypogonadotropic hypogonadism: an all-or-none phenomenon?

Hypogonadotropic hypogonadism (HH) refers to an endocrine defect of hypothalamic origin resulting in gonadal hypoplasia and frequently associated with anosmia or severely impaired olfactory function (Kallmann's syndrome). This apparently results from a disruption in the migration of neurons from the olfactory placode to the bulb and hypothalamus early in development, and so provides a unique opportunity to investigate olfactory function in human subjects with congenitally incomplete peripheral systems. Olfactory performance in 37 HH patients and 37 age-matched controls was compared using a modified version of the Munich Olfaction Test. This test is based on the sniff-bottle method and includes tests of (i) odor quality discrimination, (ii) intensity discrimination, (iii) detection thresholds, and (iv) recognition, hedonic evaluation and identification ability. The patients could be divided into two distinct groups differing significantly on all four subtests and showing no overlap in performance: 20 anosmics, conforming to Kallmann's syndrome, and 17 apparent normosmics whose performance was slightly poorer, but not significantly different to that of the controls. The unexpected failure to find a continuum of olfactory dysfunction now raises the question whether HH with or without anosmia represents two syndromes with distinct etiologies, or rather reflects the ability of the olfactory system to function well despite morphological impairment.

Adult↗
PubMed1998

Olfactory and intranasal trigeminal event-related potentials in anosmic patients.

The aim of this study was to investigate the usefulness of chemosensory event-related potentials (CSERPs) in response to both olfactory and intranasal trigeminal stimulation in the diagnosis of anosmia. Forty-four patients participated. Gaseous CO2 was used for trigeminal stimulation, vanillin and H2S were used as olfactory stimulants. Event-related potentials to olfactory stimuli could not be obtained in any of the anosmic patients, indicating the complete loss of the sense of smell. However, all patients responded to stimulation of the trigeminal nerve with CO2. These data clearly demonstrate the clinical significance of CSERPs in the assessment of anosmia.

Adolescent↗
PubMed2002

Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract.

OBJECTIVES/HYPOTHESIS: The study aimed to investigate the potential therapeutic effects of alpha-lipoic acid in olfactory loss following infections of the upper respiratory tract. Possible mechanisms of actions include the release of nerve growth factor and antioxidative effects, both of which may be helpful in the regeneration of olfactory receptor neurons. STUDY DESIGN: Unblinded, prospective clinical trial. METHODS: A total of 23 patients participated (13 women, 10 men; mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range, 4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic acid was used orally at a dose of 600 mg/day; it was prescribed for an average period of 4.5 months. Olfactory function was assessed using olfactory tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. RESULTS: Seven patients (30%) showed no change in olfactory function. Two patients (9%) exhibited a moderate decrease in olfactory function; in contrast, six patients (26%) showed moderate and eight patients (35%) remarkable increase in olfactory function. Two of the 4 patients with functional anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall, this resulted in a significant improvement in olfactory function following treatment (P =.002). At the end of treatment parosmias were less frequent (22%) than at the beginning of therapy (48%). Interestingly, recovery of olfactory function appeared to be more pronounced in younger patients than in patients above the age of 60 years (P =.018). CONCLUSIONS: The results indicate that alpha-lipoic acid may be helpful in patients with olfactory loss after upper respiratory tract infection. However, to judge the true potential of this treatment, the outcome of double-blind, placebo-controlled studies in large groups of patients must be awaited, especially when considering the relatively high rate of spontaneous recovery in olfactory loss after upper respiratory tract infection.

Adult↗
PubMed2004

Prevalence of olfactory dysfunction: the skövde population-based study.

OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Therefore, the objectives were to investigate the prevalence of olfactory dysfunction in an adult Swedish population and to relate dysfunction to age, gender, diabetes mellitus, nasal polyps, and smoking habits. STUDY DESIGN: Cross-sectional, population-based epidemiological study. METHODS: A random sample of 1900 adult inhabitants, who were stratified for age and gender, was drawn from the municipal population register of Skövde, Sweden. Subjects were called to clinical visits that included questions about olfaction, diabetes, and smoking habits. Examination was performed with a smell identification test and nasal endoscopy. RESULTS: In all, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of olfactory dysfunction was 19.1%, composed of 13.3% with hyposmia and 5.8% with anosmia. A logistic regression analysis showed a significant relationship between impaired olfaction and aging, male gender, and nasal polyps, but not diabetes or smoking. In an analysis of a group composed entirely of individuals with anosmia, diabetes mellitus and nasal polyps were found to be risk factors, and gender and smoking were not. CONCLUSION: The sample size of the population-based study was adequate, with a good fit to the entire population, which suggests that it was representative for the Swedish population. Prevalence data for various types of olfactory dysfunction could be given with reasonable precision, and suggested risk factors analyzed. The lack of a statistically significant relationship between olfactory dysfunction and smoking may be controversial.

Aged↗
PubMed2005

Comparison of diagnostic findings using different olfactory test methods.

OBJECTIVE: To quantify discrepancies in the diagnosis of olfactory function that might exist when comparing results obtained from centers using different methods of olfactory testing. STUDY DESIGN: Prospective study of 50 healthy adult volunteers and 25 adult patients with olfactory complaints. METHODS: Two test methods, the Connecticut Chemosensory Clinical Research Center (CCCRC) test widely used in the United States, and the Jet Stream Olfactometer (JSO) test used in Japan, were used to measure and categorize the diagnostic level of olfactory function (normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, anosmia). Olfactory function was measured separately for each nostril. RESULTS: There was a significant correlation (rs = 0.788, P < .01, n = 150 nostrils) between diagnostic categories assigned by the CCCRC and JSO test methods. Diagnostic categories were identical for 66.7% of the nostrils tested, and in only 7.3% of the cases did the results differ by more than one category. For the anosmic and normosmic categories, test results were in agreement 91.7% of the time, whereas for the hyposmic categories (mild, moderate, and severe) results were in agreement only 22.2% of the time. CONCLUSIONS: Our results demonstrate that when comparing clinical or research data obtained from centers using different olfactory test methods, subjects with diagnoses of anosmia or normosmia may be more reliably compared than those with different levels of hyposmia.

Adolescent↗
PubMedDate not supplied

Familial Kallmann syndrome with unilateral renal aplasia.

On the basis of studies in two brothers and their double first cousin, the Kallmann syndrome (KS) is discussed as an X-linked syndrome of anosmic hypogonadotropic hypogonadism. The anosmia is thought to represent agenesis or hypoplasia of the olfactory lobes, the mildest form of the alobar holoprosencephaly developmental field defect; this is supported by the finding of hypotelorism in two of the patients and their mother. The endocrine defect is thought to represent a hypothalamic abnormality of the luteinizing hormone releasing hormone; borderline normal intelligence may represent another pleio-tropic CNS manifestation of the KS gene. All three affected males had unilateral renal aplasia, associated in one with ipsilateral absence of the testis. The presence of at least two developmental field defects (involving the CNS and urogenital system) makes it likely that the KS is a true multiple congenital anomaly syndrome; this is supported by the finding of additional, mostly minor, anomalies reported by other investigators. Heterozygous females may also show manifestations of anosmia, hypogonadism, possibly even internal genital malformation; however, genetic heterogeneity of anosmic hypogonadism is possible, and for the time being it is probably better to designate sporadic female cases of anosmic hypogonadism as examples of the olfacto-genital syndrome of DeMorsier. Linkage studies are urgently needed to clear up the question of genetic heterogeneity and to help develop empiric recurrence risk figures in anosmic hypogonadism.

Adult↗
PubMed1987

Kallmann syndrome associated with choanal atresia.

Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. A previously unreported association of Kallmann syndrome and choanal atresia in a family is reported. The mechanism of the embryopathic association of hypogonadotropic hypogonadism, anosmia, and choanal atresia is though to be due to a single developmental field defect in the region of the median forebrain and associated structures. An irregular autosomal dominant mode of inheritance is suspected.

Adult↗
PubMed1977

Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds.

Animals↗