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PubMed1991

Migration of LHRH-immunoreactive neurons from the olfactory placode rationalizes olfacto-hormonal relationships.

Nerve cells that express luteinizing hormone-releasing hormone (LHRH), essential for reproductive functions, originate in the epithelium of the medial olfactory placode. While the peripheral origin of this physiologically important brain peptide is surprising, associations between olfactory and reproductive systems are well documented in behavioral studies of pheromones and in clinical studies of disorders including hypogonadotropic hypogonadism with anosmia or olfactory-genital dysplasia. Mechanisms underlying this migration include a close association with neural cell adhesion molecules (NCAM), but are likely also to involve other physical and chemical factors.

Animals↗
PubMed1991

Sexual pheromones in the domestic sheep: importance and limits in the regulation of reproductive physiology.

In mammals, primer pheromones are considered as the most important signals involved in socio-sexual stimulation of the reproductive processes. In the domestic sheep, male-female interactions induce changes in the pulsatile rhythm of the LH secretion in both sexes which influences reproductive endocrinology. In the female, the odor of the ram's fleece induces LH secretion and ovulation. The acid sub fraction of the methylene chloride extract under C16 and diols appear to contain the active components. An interspecific action has been observed, as male goat's hair extract is similarly active. In the male, although the receptive female is the most effective to stimulate LH release, no pheromonal action has been demonstrated. In the female, lesions of the vomeronasal system do not eliminate the endocrine response to pheromonal stimulation. Furthermore, in both sexes, anosmia does not impair the response to direct interaction with the sexual partner. In domestic sheep, the existence of primer pheromones has been demonstrated, but other sensory cues could replace olfaction during socio-sexual interactions interfering with the control of reproductive endocrinology.

Animals↗
PubMed2004

Hypogonadotropic hypogonadism in a female with the Johnson-McMillin syndrome.

A case of hypogonadotropic hypogonadism associated with the Johnson-McMillin syndrome is presented. This is a rare, autosomal dominant disorder, characterized by variable degrees of alopecia and anosmia, conductive hearing loss, and increased dental caries. Until now hypogonadotropic hypogonadism has only been observed in affected men. Ovulation can be induced with gonadotropins and conception can be obtained, but because prenatal diagnosis is not as yet possible, oocyte donation should be offered as an alternative for procreation.

Abnormalities, Multiple↗
PubMedDate not supplied

Two consecutive cases of cerebrospinal fluid rhinorrhea after septoplasty operation.

Our aim in this work is to define the importance of anatomical knowledge in septoplasty operation and to prevent complications. Septoplasty is one of the most common operations in otorhinolaryngology to treat the nasal obstruction caused by septal deviation. During and after septoplasty, there are some recorded complications, such as hemorrhage, hematoma, septal abscess, septal perforation, saddle nose, infection, anosmia, visual disturbances, cavernous sinus thrombosis, meningitis, pneumoencephalos, subarachnoid hemorrhage, subdural empyma, brain abscess, periorbital emphysema, toxic shock syndrome, and cerebrospinal fluid (CSF) rhinorrhea. Some of the complications are rare, but their results are life threatening. We report a rare complication of septoplasty CSF rhinorrhea. Two consecutive cases of CSF fistulas after septoplasty operation are presented. Both of the cases were treated endoscopically. The possible mechanisms and different treatment options are discussed. Prevention of the CSF fistula in septoplasty is more important than its treatment. Realizing the anatomic variations and gentle manipulation at the ethmoid roof is essential.

Adult↗
PubMed2006

GnRH receptor and GPR54 inactivation in isolated gonadotropic deficiency.

Isolated hypogonadotropic hypogonadism (IHH) is defined by a complete or partial impaired secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In the regulation of the gonadotropic axis, the gonadotropin-releasing hormone (GnRH) and its receptor have evolved as a central element in fetal life, at puberty, and for reproduction in adulthood. GnRH resistance due to GnRH receptor (GnRHR) germ-line mutations was the first genetic alteration identified in patients with IHH. GnRHR mutated receptors are associated with impaired GnRH binding, intracellular trafficking or ligand-induced signal transduction, leading to various degrees of LH and FSH deficiency. Loss-of-function mutations of the GnRH receptor account for 50% of familial cases of IHH without anosmia. In 2003, mutations of GPR54 were identified in patients with IHH, opening a new pathway in the physiological regulation of puberty and reproduction. Kisspeptins, which are the natural ligands of GPR54, are potent stimulators of the LH and FSH secretion via the control of GnRH secretion or modulation of the pituitary response to GnRH stimulation. Genotype-phenotype correlations in IHH due to GnRHR and GPR54 mutations indicate that similar mutations may lead to a variable phenotype and suggest that the pituitary might have its own pubertal maturation independent from GnRH. These two causes of IHH result in a more quantitative than qualitative defect of the gonadotropic axis activation. Molecular genetics of IHH has led to a major breakthrough in the neuroendocrine regulation of the gonadotropic axis. New insights into the understanding of the initiation of puberty and in the therapeutic management of defects of the gonadotropic axis have emerged from these studies.

Animals↗
PubMed2004

Disinhibition of maternal behavior following neurotoxic lesions of the hypothalamus in primigravid rats.

Virgin female rats do not respond maternally to foster pups due to an endogenous neural circuit that actively inhibits the display of maternal behavior. Once pregnant, primigravid rats will continue to avoid foster pups until just prior to or at parturition. Anosmia or lesions of the olfactory tract, medial amygdala, and areas of the hypothalamus will stimulate virgin females to display maternal behavior rapidly, but little is known of the effect of these lesions in primigravid rats. The objective of the present study was to determine if neurotoxic lesions of the dorsomedial (DMH) and ventromedial nuclei (VMH) of the hypothalamus will advance the onset of maternal behavior in primigravid rats. Nulliparous Sprague-Dawley female rats were mated and then on day 8 of gestation bilaterally infused with N-methyl-d-aspartic acid (NMDA; 8 microg/0.2 microl/side) or vehicle directed toward either the DMH or VMH. Beginning on day 15 of gestation until parturition, females were tested daily for maternal responsiveness. DMH and VMH lesions significantly advanced the onset of maternal behavior (5-6 days vs. 0-1 day before parturition) in first-time pregnant rats. These results indicate that the DMH and VMH are involved in the regulation of maternal behavior and may be part of an endogenous neural circuit that inhibits maternal behavior during pregnancy.

Animals↗
PubMed2006

[Choanal stenosis: a rare complication of radiotherapy for nasopharyngeal carcinoma].

Choanal stenosis is usually a congenital anomaly in children. Acquired choanal stenosis after radiotherapy for nasopharyngeal carcinoma is a very rare pathology; only two publications report seven cases in the literature. We describe the clinical history, preoperative evaluation, surgical treatment and outcome of a case of acquired choanal stenosis after radiotherapy. The patient, a 56-year-old woman, presented with a history of nasopharyngeal carcinoma (T2- NO-MO) one year before that had been successful treated with radiotherapy (68 Gy). At the end of radiotherapy, she complained of complete nasal obstruction, anosmia and hearing loss due to a bilateral serous otitis media. Bilateral complete choanal stenosis was confirmed by endoscopy and CT scan. Functional endoscopic surgery was performed, and nasal stents were left in place for 3 weeks. One year after, the patient have good airflow, and a patent nasopharynx without choanal stenosis. In conclusion, choanal stenosis is an unusual complication of radiotherapy that can be successfully treated with transnasal endoscopic resection.

Carcinoma↗
PubMed2006

Clinical and molecular characterization of a large sample of patients with hypogonadotropic hypogonadism.

OBJECTIVE: To characterize the phenotype, modes of inheritance, karyotype, and molecular basis of patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Review of medical records, karyotyping, and collation of gene mutation analysis. SETTING: University molecular reproductive endocrinology laboratory. PATIENT(S): Patients with IHH. INTERVENTION(S): Review of medical records, laboratory studies, and molecular studies. MAIN OUTCOME MEASURE(S): Sense of smell, severity of IHH (complete vs. incomplete), associated anomalies, karyotype, mutation analysis, and genotype/phenotype correlations were studied. RESULT(S): Of 315 patients with IHH, 6.3% had one or more affected relatives. Autosomal recessive inheritance was likely in most of these familial cases, but autosomal-dominant and X-linked recessive inheritance patterns were likely in some families. Complete IHH was more commonly found in males (62%), whereas incomplete IHH was more commonly observed in females (54.3%). Anosmia was present in 31.3% of males and 27.9% of females. The karyotype was normal in all 19 females tested, but was abnormal in 3 of 57 (5.3%) of males tested. Although cryptorchidism did not differ among those who were anosmic vs. normosmic, it was approximately four times more common in patients with complete IHH than incomplete IHH (15.3% vs. 3.9%). Approximately 10% of the IHH patients tested had mutations in either the GNRHR or KAL1 gene. CONCLUSION(S): Idiopathic hypogonadotropic hypogonadism is a heterogeneous disorder affecting fertility, in which the number of familial cases is probably underestimated. Further study of genes that regulate hypothalamic-pituitary development and function will likely reveal important information regarding the development of normal puberty in humans.

Adolescent↗
PubMed2004

Endoscope assisted removal of cementoossifying fibroma in the paranasal sinuses in a five-year-old girl.

We report a five-year-old girl with a sinonasal cementoossifying fibroma with CT findings that reveal the invasion of all paranasal sinuses and the remodeling of facial bones. It was possibly a congenital lesion and caused a slowly progressive nasal obstruction and anosmia. Tumor removal with transnasal endoscopic approach was applied and total removal of the mass was accomplished. It was found out to be the cementoossifying fibroma of the paranasal sinuses when the results of the pathological examinations were obtained.

Child, Preschool↗
PubMed2004

Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria): Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis.

BACKGROUND: The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined. OBJECTIVE: We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria). METHODS: We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria. RESULTS: The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05). CONCLUSION: Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.

Adult↗
PubMed2006

Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization followed by daily aspirin therapy is effective add-on treatment for patients with aspirin-exacerbated respiratory disease. Prior studies used 650 mg of aspirin twice daily, but studies at lower dosages were inconclusive. OBJECTIVE: We sought to determine the optimal daily dosage of aspirin treatment. METHODS: We studied 137 patients who had undergone successful aspirin desensitization and randomized them into 2 groups, 650 mg twice daily versus 325 mg twice daily. After 1 month, patients either increased or decreased their dosage based on their symptom control and continued that dosage for the remainder of the year. RESULTS: Patients taking either 650 mg twice daily or 325 mg twice daily showed significant improvements in number of sinus infections, sinus operations, and hospitalizations for asthma (all P < .0001). Anosmia, nasal/sinus symptoms, and asthma symptoms also improved in both groups (all P < .03). Systemic corticosteroid dosages decreased by 3- and 4-fold in the 325 mg twice daily and 650 mg twice daily groups, respectively. Of the 137 patients, 32 had adverse effects from or discontinued aspirin therapy: 14 (44%) of 32 from the group randomized to taking 650 mg twice daily and 18 (56%) of 32 from the group randomized to 325 mg twice daily. The most common adverse effect was dyspepsia. CONCLUSION: Both dosages were efficacious, and side effects occurred in both groups at similar frequencies. Some patients initially taking 325 mg twice daily required an increase to 650 mg twice daily for optimal symptom control. CLINICAL IMPLICATIONS: We recommend that patients begin daily aspirin therapy with 650 mg twice daily and subsequently decrease to the lowest effective dosage (usually 325 mg twice daily).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Pneumosinus dilatans frontalis: two case reports.

INTRODUCTION: Pneumosinus dilatans was described first in 1898 by Meyes. Up to now only 60 cases have been published worldwide dealing mainly with young men between 20 and 30 years of age. The aetiology remains unknown. Whilst frontal sinuses are affected most often other sinuses can also be involved. The expansion of the pneumosinus is not only an aesthetic problem but may also have functional consequences. There may be a bulging of the roof of the orbit with consequent global displacement, ocular alterations and ptosis. Other features are headache and anosmia. PATIENTS: Two male patients with a pneumosinus dilatans of the frontal sinus are presented. They were 22 and 25 years old. The main complaints were aesthetic disfigurement. Treatment consisted of craniofacial repair of the malformation. RESULTS: While one patient was lost to follow-up, the other still is happy and has a stable aesthetic long-term result.

Adult↗
PubMed2006

Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).

Kallmann syndrome characterised by hypogonadotropic hypogonadism (HH) and anosmia is genetically heterogeneous with X-linked, autosomal dominant and autosomal recessive forms. The autosomal dominant form due to loss of function mutation in the fibroblast growth factor receptor 1 (FGFR1) accounts for about 10% of cases. We report here three paediatric cases of Kallmann syndrome with unusual phenotype in two unrelated patients with severe ear anomalies (hypoplasia or agenesis of external ear) associated with classical features, such as cleft palate, dental agenesis, syndactylia, micropenis and cryptorchidism. We found de novo mutation in these two patients (Cys178Ser and Arg622Gly, respectively), and one inherited Arg622Gln mutation with intrafamilial variable phenotype. These genotype-phenotype correlations indicate that paediatric phenotypic expression of FGFR1 loss of function mutations is highly variable, the severity of the oro-facial malformations at birth does not predict gonadotropic function at the puberty and that de novo mutations of FGFR1 are relatively frequent.

Adolescent↗
PubMed2005

The olfactory bulbectomised rat as a model of depression.

Bilateral olfactory bulbectomy results in changes in behavior, and in the endocrine, immune and neurotransmitter systems, that simulates many of those seen in patients with major depression. The olfactory system in the rat forms a part of the limbic region in which the amygdala and hippocampus contribute to the emotional and memory components of behavior. However, the loss of olfaction alone, which results from bulbectomy, is not the major factor that contributes to the behavioral abnormalities as peripherally induced anosmia does not cause the same behavioral changes. Thus it would appear that bulbectomy causes a major dysfunction of the cortical-hippocampal-amygdala circuit that underlies the behavioral and other changes. These neuroanatomical areas also seem to be dysfunctional in the patient with major depression. Chronic, but not acute, administration of antidepressants largely corrects most the behavioral, endocrine, immune and neurotransmitter changes that occur following bulbectomy. Thus the olfactory bulbectomized rat is not only a model for detecting antidepressant activity but also one for exploring the inter-relationships between these systems that are also dysfunctional in patients with major depression.

Animals↗
PubMed2006

Olfactory stimulation with scent of lavender oil affects autonomic neurotransmission and blood pressure in rats.

Previously, we observed that olfactory stimulation with scent of lavender oil (SLVO) suppressed sympathetic nerve activities and elevated gastric vagal (parasympathetic) nerve activity (GVNA), decreased plasma glycerol concentration and body temperature, and enhanced appetite in rats. Here, we further showed that olfactory stimulation with SLVO lowered renal sympathetic nerve activity (RSNA) and blood pressure (BP) and elevated GVNA in urethane-anesthetized rats. Olfactory stimulation with linalool, a component of lavender oil, also elicited decreases in RSNA and BP and an increase in GVNA in urethane-anesthetized rats. Anosmia induced by pretreatment of the nasal cavity by application of ZnSO4 eliminated the effects of both SLVO and scent of linalool on RSNA, GVNA and BP. Furthermore, intracerebroventricular administration of thioperamide, a histaminergic H3-antagonist, abolished the suppression of RSNA and BP as well as the elevation of GVNA mediated by both SLVO and scent of linalool. Finally, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) eliminated RSNA and BP suppression and the elevation of GVNA due to SLVO or linalool. Thus, it was concluded that scent of lavender oil and its active component, linalool, affects autonomic neurotransmission and reduces blood pressure through the central histaminergic nervous system and the SCN.

Animals↗
PubMed2006

Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats.

Rodent models of cognitive aging routinely use spatial performance on the water maze to characterize medial temporal lobe integrity. Water maze performance is dependent upon this system and, as in the aged human population, individual differences in learning abilities are reliably observed among spatially characterized aged rats. However, unlike human aging in which cognitive deficits rarely occur in isolation, few non-spatial learning deficits have been identified in association with spatial impairment among aged rats. In this study, a subset of male aged Fischer 344 rats was impaired both in water maze and odor discrimination tasks, whereas other aged cohorts performed on par with young adult rats in both settings. The odor discrimination learning deficits were reliable across multiple problems. Moreover, these deficits were not a consequence of anosmia and were specific to olfactory learning, as cognitively impaired aged rats performed normally on an analogous non-olfactory discrimination task. These are among the first data to describe an aging model in which individual variability among aged rat cognition occurs across two independent behavioral domains.

Aging↗
PubMed2003

The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect.

The Coolidge effect is a phenomenon in which males show renewed sexual interest in a novel female following copulation to satiety with another female. In golden hamsters, this phenomenon depends on the ability to recognize conspecifics using chemosensory cues processed through the main olfactory system. Here we tested whether olfactory targets in the hippocampal system support this natural form of recognition memory. Male hamsters received ibotenic acid lesions of the perirhinal-entorhinal cortex (PR-ENT) or hippocampus (H) and were allowed to copulate to satiety with a female conspecific, then were presented with two anesthetized females, the familiar mate and an unfamiliar female that copulated with another male. Sham-operated and H-lesioned subjects preferentially investigated the novel female, indicating intact recognition of individual identity. By contrast, PR-ENT-lesioned males failed to discriminate familiar and novel females, and this deficit could not be attributed to abnormal copulatory behavior during mating. All subjects were able to detect and discriminate between female odors when presented in isolation during a habituation-discrimination test, indicating that behavioral deficits shown by PR-ENT males were not due to anosmia or a general investigatory deficit. Thus, the perirhinal-entorhinal cortex, but not the hippocampus, is critical for the recognition of familiar conspecifics in this naturalistic situation. This study reveals an essential role for the perirhinal-entorhinal cortex, but not the hippocampus, in a natural form of recognition memory within the social behavior of hamsters. The findings show a strikingly similar pattern to the effects of selective damage to the same brain regions on performance in standard recognition memory tasks by rats and monkeys. Therefore, the present data extend our understanding of the differential role of structures of the hippocampal memory system, showing continuity across species and between formal laboratory tests and the function of memory in natural social behavior.

Animals↗
PubMed2006

Refsum's disease may mimic familial Guillain Barre syndrome.

Refsum's disease is a rare autosomal recessive disorder with clinical features including retinitis pigmentosa, anosmia, deafness, chronic sensory-motor neuropathy, ataxia and the accumulation of phytanic acid in blood plasma and body tissues. We report the occurrence of Refsum's disease in two sisters, both presenting with acute demyelinating polyneuropathy mimicking the familial Guillain Barre syndrome. Thus, when GBS is suspected, particularly in cases of familial recurrence as well as in atypical cases of acute polyneuropathy, the diagnosis of Refsum's disease should be considered, looking for other features of the disease and, if appropriate, testing plasma phytanic acid levels.

Adult↗