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PubMed1985

Antigonadal actions of olfactory and light deprivation. I. Effects of blindness combined with olfactory bulb deafferentation, transection of vomeronasal nerves, or bulbectomy.

Olfactory bulbectomy is known to potentiate the antigonadal effects of light deprivation. However, the physiological interpretation of the effects of bulbar ablation is complex, since it simultaneously implies sequelae like: a) the loss of olfactory sensitivity (anosmia), b) the suppression of the accessory olfactory system (AOS), and c) the suppression of nonsensorial functions of the bulbs. To study the participation of these three mechanisms in the effects of bulbectomy + light deprivation, we compared, in 28-day-old male rats, the effects of olfactory bulb deafferentation (peripheral anosmia) with those induced by either olfactory bulbectomy or blocking the AOS, alone or associated with blindness. As compared to the intact or blinded animals, both blinded deafferented (EA) and blinded bulbectomized (EB) rats showed various reductions in weights of body, testes, accessory sexual glands, and prostates; serum testosterone levels were also depressed. Testes of EA rats showed various degrees of alterations in spermatogenesis. The only difference between EA and EB groups was in the pituitary weight, significantly lower in EA rats.

Animals↗
PubMed1996

Luteinizing hormone-releasing hormone and innervation pathways in human prenatal nasal submucosa: factors of importance in evaluating Kallmann's syndrome.

A previous study has demonstrated that luteinizing hormone-releasing hormone (LHRH) is localized in the human bilateral vomeronasal organs in the nasal septum during a 4-week period of intrauterine life (22). The purpose of the present study was to elucidate the location of LHRH-expressing cells outside the vomeronasal organs, with special emphasis on the submucosa of the medial wall and roof of the nasal cavity. An additional aim was to study the innervation pathways in the same regions. Both regions can be affected in Kallmann's syndrome, which is characterized by hypogonadotropic hypogonadism (lack of LHRH) and often associated with anosmia. Histological sections of craniofacial regions (49 normal human fetuses, 6-19 weeks) were examined by immunohistochemical techniques for LHRH and for neuronal tissue (protein gene product 9.5, PGP 9.5). LHRH reactions were only seen in the septal submucosa extending from the vomeronasal organs to the olfactory bulb. There was a close spatiotemporal association between the occurrence of LHRH and neuronal tissue. From the rhino-olfactory epithelium separate nerve tissue extended to the olfactory bulb. It is suggested that the medial region of the nasal placode giving rise to the septal wall is always affected in Kallmann's syndrome, and in cases in which the phenotypic features are associated with anosmia, also the more lateral part of the nasal placode, from which the rhino-olfactory region originates, is affected.

Cell Movement↗
PubMed2001

Olfactory function in patients with olfactory groove meningioma.

OBJECTIVES: Olfactory meningiomas are rare benign tumours and represent about 12% of all basal meningiomas. Anosmia is thought to be among the first symptoms, even though patients often present with headaches or visual problems. However, so far no detailed psychophysical tests of olfactory function have been performed in a large number of those patients. METHODS: Twelve patients (five men, seven women; mean age 52 years) with olfactory meningiomas were examined. In all patients extensive preoperative and postoperative lateralised olfactory testing was performed using the "Sniffin' Sticks" test battery, a psychometric testing tool. In eight cases the meningioma was lateralised (five left, three right), in four patients a bilateral meningioma was found. In addition to a detailed ear, nose, and throat examination MRI was performed in all patients. RESULTS: In preoperative testing six patients were found to be anosmic on the side of the tumour, two were hyposmic. Four patients were normosmic. Postoperative investigations showed lateralised anosmia in four patients on the operated side, three were normosmic on the contralateral side and one hyposmic. The remaining eight patients were completely anosmic postoperatively. CONCLUSIONS: (1) Contrary to expectations, olfactory testing seems to be of little help in detecting olfactory meningiomas. (2) The likelihood of normal postoperative olfactory function contralateral to the tumour was high when the tumour was less than 3 cm in diameter and preoperative normosmia had been established. (3) Preservation of olfactory function ipsilateral to the tumour seems to be extremely difficult, irrespective of tumour size or surgical approach.

Adult↗
PubMed2006

Olfaction in neurodegenerative disorder.

There has been gradual increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (IPD) and Alzheimer-type dementia. It is an intriguing observation that a premonitory sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed sense of smell. In this review of aging, IPD, parkinsonian syndromes, tremor, Alzheimer's disease (AD), motor neuron disease (MND), Huntington's chorea (HC) and inherited ataxia, the following observations are made: (1) olfactory senescence starts at about the age of 36 years in both sexes and accelerates with advancing years, involving pleasant odours preferentially; (2) olfactory dysfunction is near-universal, early and often severe in IPD and AD developing before any movement or cognitive disorder; (3) normal smell identification in IPD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; (4) anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; (5) subjects with hyposmia and one ApoE4 allele have an approximate 5-fold increased risk of later AD; (6) impaired sense of smell may be seen in some patients at 50% risk of parkinsonism, and possibly in patients with unexplained hyposmia; (7) smell testing in HC and MND where abnormality may be found is not likely to be of clinical value, and (8) biopsy of olfactory nasal neurons reveals non-specific changes in IPD and AD and at present will not aid diagnosis.

Aging↗
PubMed1985

The nose after laryngectomy.

Previous studies of nasal function after laryngectomy have suggested that patients must accept complete and irreversible anosmia as an inevitable consequence of the operation, and that this is due to interruption of a poorly defined neuronal interaction between larynx and nose. In this study nasal function was investigated in 23 laryngectomees and 10 patients about to undergo laryngectomy. Scanning electron microscopy showed a more densely ciliated nasal epithelium in the laryngectomees compared with the preoperative controls, and nasal mucociliary transport, measured by saccharine clearance, was significantly faster (P less than 0.01) in laryngectomees. Olfactory acuity, as determined by the threshold for detection of insufflated pyridine vapour, was normal in laryngectomees. Some laryngectomees did have a relatively normal sense of smell; these were shown to be those who had discovered a technique of sniffing using buccopharyngeal rather than respiratory musculature. These findings have obvious implications for the rehabilitation of laryngectomees, many of whom may otherwise have to contend with distressing anosmia as well as the other physical and psychological consequences of the operation.

Adult↗
PubMed2002

Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism.

GnRH treatment is successful in inducing virilization and spermatogenesis in men with idiopathic hypogonadotropic hypogonadism (IHH). However, a small subset of IHH men, poorly characterized to date, fail to reach a normal testicular volume (TV) and produce sperm on this therapy. To determine predictors of outcome in terms of TV and sperm count, we studied 76 IHH men (38% with anosmia) undergoing GnRH therapy for 12-24 months. The population was stratified according to the baseline degree of prior pubertal development: absent (group 1, n = 52), partial (group 2, n = 18), or complete (adult onset HH; group 3, n = 6). Cryptorchidism was recorded in 40% of group 1, 5% of group 2, and none in group 3. Pulsatile GnRH therapy was initiated at 5-25 ng/kg per pulse sc and titrated to attain normal adult male testosterone (T) levels. LH, FSH, T, and inhibin B (I(B)) levels were measured serially, and maximum sperm count was recorded. A longitudinal mixed effects model was used to determine predictors of final TV. LH (97%) and T (93%) levels were normalized in the majority of IHH men. Groups 2 and 3 achieved a normal adult testicular size (92%), FSH (96%), I(B) levels (93%), and sperm in their ejaculate (100%). However, given their prior complete puberty and thus primed gonadotropes and testes, group 3 responded faster, normalizing androgen production by 2 months and completing spermatogenesis by 6 months. In contrast, group 1 failed to normalize TV (11 +/- 0.4 ml) and I(B) levels (92 +/- 6 pg/ml) by 24 months, despite normalization of their FSH levels (11 +/- 2 IU/liter). Similarly, sperm counts of group 1 plateaued well below the normal range (median of 3 x 10(6)/ml) with 18% remaining azoospermic. The independent predictors of outcome of long-term GnRH therapy were: 1) the presence of some prior pubertal development (positive predictor; group effect (beta) = 4.3; P = 0.003); 2) a baseline I(B) less than 60 pg/ml (negative predictor; beta = -3.7; P = 0.009); and 3) prior cryptorchidism (negative predictor; beta = -1.8; P = 0.05). Notably, anosmia was not an independent predictor of outcome when adjusted for other baseline variables. Our conclusions are: 1) pulsatile GnRH therapy in IHH men is very successful in inducing androgen production and spermatogenesis; 2) normalization of the LH-Leydig cell-T axis is achieved more uniformly than the FSH-Sertoli cell-I(B) axis during GnRH therapy; and 3) favorable predictors for achieving an adult testicular size and consequently optimizing spermatogenesis are prior history of sexual maturation, a baseline I(B) greater than 60 pg/ml, and absence of cryptorchidism.

Adolescent↗
PubMed2007

A mutation in the fibroblast growth factor receptor 1 gene causes fully penetrant normosmic isolated hypogonadotropic hypogonadism.

CONTEXT: Kallmann syndrome (KS) consists of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia/hyposmia. Currently, the fibroblast growth factor receptor 1 (FGFR1) gene is the only known autosomal dominant cause of KS, which is also associated with synkinesia, midfacial defects, and dental agenesis. OBJECTIVE: Mutations in FGFR1 typically demonstrate reduced penetrance, variable expressivity, and until recently have been exclusively identified in families with anosmia. The purpose of this study was to determine whether FGFR1 mutations were present in a unique family with autosomal dominant, fully penetrant, normosmic IHH. DESIGN: The study is a review of detailed clinical findings, dynamic endocrine studies, and performance of a molecular analysis of the FGFR1 gene. SETTING: The study was carried out in an academic medical center. PATIENTS: All four affected individuals have complete IHH with full penetrance but no anosmia/hyposmia, and they have none of the FGFR1-associated anomalies. In addition, no other family member has anosmia. Inverventions: Interventions included detailed phenotype characterization including history, physical exam, smell testing, dynamic pituitary testing, brain imaging, and molecular analysis. MAIN OUTCOME MEASURES: Outcome was measured by the determination of the severity of IHH, olfactory function, and sequence of the FGFR1 gene. RESULTS: The same heterozygous nonsense mutation, Arg622X, was present in all four affected members, but not in three unaffected members or 100 controls. The mutation is predicted to encode a truncated protein or result in nonsense-mediated decay. CONCLUSIONS: Our findings indicate that mutations in the FGFR1 gene can cause normosmic, fully penetrant, complete IHH with little or no variable expressivity, and without the other FGFR1-associated anomalies typically found in KS.

Adolescent↗
PubMed1998

Homing pigeons use olfactory cues for navigation in england

Although the use of olfactory cues in pigeon navigation is well established, the generality of olfactory navigation remains uncertain because of apparent variability in results gained by different researchers in different regions. We report the results of the first experiments investigating the effect of anosmia on homing pigeons reared in a previously uninvestigated region, southern England. In series 1, experienced birds showed little effect of anosmia induced with zinc sulphate at unfamiliar sites 30 km and 39 km from the loft, but treated birds were significantly poorer than controls at homing from an unfamiliar site 66 km distant (and in pooled results). In series 2, naive (untrained) birds, both control and zinc-sulphate-treated, showed poor homing abilities and initial orientation from sites 25 km, 36 km and 39 km from the loft. Nevertheless, in pooled results, controls showed significantly better homeward orientation than anosmic birds and were significantly more likely to home on the day of release. The most likely explanation for our results is that pigeons are able to use olfactory navigation in southern England, but that for some reason the olfactory map is relatively weak.

Journal Article↗
PubMedDate not supplied

Clinical evaluation in isolated hypogonadotrophic hypogonadism (Kallmann syndrome).

OBJECTIVE: To describe the clinical features, laboratory investigation and treatment of Kallmann syndrome. DESIGN: A retrospective study of patients treated in the Endocrine Clinic of the Royal Children's Hospital and St Vincent's Hospital, Melbourne, between 1984 and 1996. RESULTS: Eleven males and 5 females with Kallmann syndrome are described. Their ages at presentation ranged from one week to 21 years. Presenting symptoms were micropenis, small testes, anosmia and delayed puberty. Fifty-six percent (9/16) had a family history of either anosmia or infertility. The features of Kallmann syndrome are variable. We have described unilateral renal aplasia, coloboma of iris, deafness, midline anomalies, oculomotor apraxia and Moebius anomalad as features that were associated with Kallmann syndrome in our group of subjects. One patient diagnosed as having X-linked Kallmann syndrome has previously been shown to have a specific mutation in an intronic sequence adjacent to exon 6. Most patients showed low serum levels of basal gonadotrophins, testosterone or oestrogen, and had a poor response to LHRH stimulation, but two patients showed a pubertal response to LHRH stimulation, and may have a variant form of Kallmann syndrome. Treatment given to these patients included exogenous testosterone or oestrogen for induction of puberty, with appropriate pubertal progress occurring in each patient. CONCLUSION: The manifestations of Kallmann syndrome vary, depending upon the degree of LHRH deficiency. Therapy should combine exogenous sex hormone replacement and psychological support, with long-term follow-up to ensure maintenance of normal sexual function, normal bone mass and psychosocial outcome, with fertility induction when indicated.

Adolescent↗
PubMed2004

New insights in the genetics of isolated hypogonadotropic hypogonadism.

Isolated gonadotropic deficiency or isolated hypogonadotropic hypogonadism is defined as a low sexual hormone secretion by the gonads associated with low LH and FSH plasma levels. Kallmann syndrome is defined as a congenital isolated gonadotropic deficiency associated with anosmia whereas the phenotype of the idiopathic form is limited to the gonadotropic axis. For several years, it has been known that mutations of the KAL-1 gene or loss-of-function mutations of GnRH receptor did not explain all familial cases of isolated gonadotropic deficiency with or without anosmia. Thus the existence of other genes playing a major role in the physiology of the gonadotropic axis was highly suggested. In 2003, fibroblast growth factor receptor 1 (FGFR1) and GPR54 were shown to be two of these genes. FGFR1 loss-of-function mutations were reported in Kallmann syndrome whereas inactivating mutations of GPR54 were described in the idiopathic form of the gonadotropic deficiency. These genetic studies have opened up a new chapter in the physiology and the pharmacology of the gonadotropic axis.

Animals↗
PubMed1992

Successful treatment of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia.

A 51-year-old male was admitted because of eyelid edema and anosmia, which developed in 1985. He showed bilateral cervical lymphadenopathy, with nodes larger than 2 x 2 cm, and remarkable eyelid edema. Anemia, hyperimmunoglobulinemia with hypo-albuminemia (no M-protein) and liver dysfunction were found. Bone marrow, renal function, urine analysis and LDH level were normal. Cervical lymph node biopsy showed interfollicular proliferation of plasma cells without any malignant appearance. On day 3 of oral prednisolone (PD), anosmia abruptly improved from day 7, eyelid swelling, cervical lymphadenopathy and gammopathy subsided gradually. Since PD was tapered off, no relapse has been observed thus far.

Castleman Disease↗
PubMedDate not supplied

Nasal lavage cytometry in the diagnosis of nonallergic rhinitis with eosinophilia syndrome (NARES).

The nonallergic rhinitis with eosinophilia syndrome (NARES) is a type of chronic rhinitis, characterized by intense (> 20%) eosinophilia of the nasal secretions. In this study, screening for NARES in 81 patients with nonallergic chronic rhinitis was performed using a modified nasal lavage cytometric method. Twenty-one of the 81 investigated individuals (25.9%) showed nasal eosinophilia greater than 20%, therefore being diagnosed as having NARES. No statistical difference in total serum IgE concentration (Prist Pharmacia) was observed between the NARES subjects and those with other forms of chronic rhinitis, confirming the seemingly nonallergic nature of NARES. In 28.6% of these cases the presence of anosmia was detected: in 19.0% of cases with NARES (all subjects complaining of long-lasting symptoms and suffering from anosmia), nasal polyposis coexisted. Our results confirm that nasal lavage cytometry may represent a useful clinical tool in the diagnosis of chronic rhinitis.

Adult↗
PubMed1995

Bulbar morphology and expression of bulbar dopamine and parvalbumin in experimentally-induced anosmic rats.

Morphological study was carried out in rats with olfactory dysfunction induced by deafferentation of serotonergic fibers in the olfactory bulb. With a computer capable of area measurements, olfactory bulbs of the anosmic rats were found to be decreased in size to 61% of control bulbs, and all bulbar layers were involved in the bulbar shrinkage. Given areas of each bulbar layer in control bulbs to be 100%, percentages of each bulbar layer in the anosmic rats were 23% in the olfactory nerve layer, 54% in the glomerular layer, 63% in the external plexiform layer, 83% in the internal plexiform layer and 81% in the granule cell layer. Dopamine-and parvalbumin-containing neurons were examined immunohistochemically in the experimentally-induced anosmic rats. As a result, immunoreactive neurons for these two chemical substances were significantly decreased in number (dopamine, 33% of control value; parvalbumin, 46% of control value). The present study, using an animal model of anosmia, provided quantitative data on the bulbar atrophy and showed effects of anosmia on expression of dopamine and parvalbumin in the bulb.

Animals↗
PubMed1995

[Improvement of olfactory disturbance by endoscopic endonasal surgery for chronic sinusitis].

Olfactory disturbance is the one of the most important symptoms of chronic sinusitis. In the present study, we followed up the postoperative clinical course of olfactory disturbance in patients who underwent surgery for chronic sinusitis. Ninety patients with severe olfactory disturbance or anosmia who underwent endoscopic endonasal surgery for chronic sinusitis with severe olfactory disturbance or anosmia in the preceding three-year period were enrolled in this study. We obtained a high postoperative improvement rate of 78.8%. We compared and examined our cases' postoperative clinical course concerning their olfactory disturbance and various factors in other patients before and after surgery, and obtained the following results: a) Young patients, 30 years old or under at the time of surgery, showed significantly higher rates of improvement than patients who were 50 years old or more at the time of surgery. b) Even though revision surgery was performed, the improvement rates were almost the same as after the initial surgery. c) Although the Alinamin intravenous olfaction test is regarded as an olfaction threshold test, we have seen quite a few cases in which improvement was achieved despite the absence of a preoperative response to the Alinamin intravenous olfaction test. d) There was no clear correlation between the presence of preoperative lesions of the ethmoid sinus and the olfactory cleft and the improvement rates. e) The cases with unsatisfactory results concerning the paranasal sinuses and nasal cavity--those accompanied by postoperative adhesions of the olfactory cleft, recurrence of polyps, etc.,--showed significantly lower improvement rates than cases with satisfactory postoperative results. During surgery in patients with severe olfactory disturbance, we conclude that it is particularly important to adequately clean the lesions of the olfactory cleft and the anterior and posterior ethmoid sinus endoscopically. This ensures leaving clear the olfactory cleft.

Adult↗
PubMed1976

A female case of Kallmann's syndrome.

A case of 20-year-old woman with hypogonadotropic hypogonadism and anosmia is reported, since very few female cases of Kallmann's syndrome have been reported so far in Japan. Three uncles on the father's side had no children. Height was 168 cm, and arm span 165 cm. The olfactory test revealed complete anosmia. Bone age was 13 year. Chromosome was 46 XX and normal karyotype. Basal levels of serum FSH, LH and estrogens (E1, E2 and E3) were low. Serum FSH and LH levels rose slightly only after LH-RH administration, and did not increase in clomiphene test. Plasma estrogens did not increase after daily injection of 150 IU of HMG for 3 successive days. The response of serum GH to arginine infusion was normal, while that to insulin-induced hypoglycemia was poor.

Adult↗
PubMed1999

Smell diskettes as screening test of olfaction.

A screening test of olfaction was developed with reusable diskettes as applicators of 8 different odorants. Using a questionnaire with illustrations, the test was designed as a triple forced multiple choice test resulting in a score of 0 to 8 correct answers. To validate the test, 102 volunteers with normal olfaction, as well as 22 patients with subjective hyposmia or anosmia, were tested. To compare the developed test with an already validated method, the same persons also performed the sniffin' sticks screening test. The results indicate that the screening test with smell diskettes recognizes patients with normal olfaction and consistently distinguishes them from patients with hyposmia or anosmia.

Adolescent↗
PubMed2000

[A case of Kallmann syndrome: diagnostic usefulness of cranial magnetic resonance imaging].

We report a case of Kallmann syndrome in which the cranial magnetic resonance imaging (MRI) findings of the olfactory tract were useful in making the diagnosis. A 20-year-old male who complained of delayed puberty was referred to our hospital in November 1998. He presented with hypogonadism and anosmia. The plasma levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were low. Pituitary and Leydig cell functions were normal by the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test, respectively. The karyotype was normal (46, XY). The smell test showed anosmia. After administration of hCG, a good response of plasma testosterone level and masculinization were recognized. Cranial MRI findings revealed an absence of olfactory bulbs and hypoplastic olfactory sulci. These MRI findings are characteristic of Kallmann syndrome and allowed us to confirm our diagnosis, in addition to classically used endocrinological and olfactory examination.

Adult↗