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Expression of interleukins in patients with nasal polyposis.

OBJECTIVE: To correlate the levels of interleukins 1beta, 3, 4, and 5 before and after surgery and compare the levels between patients with and without recurrence of nasal polyposis. STUDY DESIGN AND SETTING: Thirty-nine patients with NP were selected, 13 of them allergic and 26 nonallergic. A control group of 11 individuals was also studied. The concentrations of interleukins were measured by enzyme-linked immunosorbent assay. RESULTS: There was a higher incidence of NP after the fourth decade of life and among men. The clinical symptoms were similar in both groups of patients with nasal polyposis and characterized by nasal obstruction and anosmia. A significant reduction of all interleukins studied was observed after surgical treatment. CONCLUSION: Levels of interleukins 1beta, 3, 4, and 5 were significantly reduced after surgery and the levels of interleukins 1beta and 5 were significantly lower in patients without recurrence of nasal polyposis after surgery when compared to those with recurrence.

Adolescent↗

Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau mutation).

The objective of this clinical-pathologic study was to identify biomarkers for a pallidopontonigral degeneration (PPND) kindred of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K tau mutation. Five affected subjects, one at-risk who later became symptomatic, and one at-risk asymptomatic mutation carrier, had abnormal (18)fluorodeoxyglucose PET demonstrating asymmetric temporal lobe hypometabolism. All except the asymptomatic mutation carrier had abnormal brain MRI. Parkinsonism, myoclonus, anosmia, insomnia, speech, and autonomic dysfunction were identified. Autopsy of six affected subjects showed frontotemporal degeneration with extensive tauopathy. Further studies of FTDP-17 patients are needed to replicate these findings.

Adult↗

Electrophysiological and behavioral phenotype of insulin receptor defective mice.

The olfactory bulb expresses one of the highest levels of insulin found in the brain. A high level of expression of the concomitant insulin receptor (IR) kinase is also retained in this brain region, even in the adult. We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein. Phosphorylation also induces current suppression of the Kv1.3-contributed current in cultured olfactory bulb neurons (OBNs) of rodents. In order to explore the behavioral importance of this kinase-induced modulation of the channel for the olfactory ability of the animal, mice with a targeted-gene deletion of the insulin receptor were electrophysiologically and behaviorally characterized. Mice heterozygous for the insulin receptor kinase (IR+/-) gene performed the same as wild-type (+/+) mice when challenged with a traditional, non-learning-based task to test gross anosmia. There was also no significant difference across the two genotypes in tests designed to measure exploratory behavior or in a battery of systems physiology experiments designed to assess metabolic energy usage (locomotion, ingestive behaviors, weight, oxygen consumption, and respiratory quotient). Object memory recognition tests suggest that IR+/- mice have an impairment in recognition of familiarized objects; IR+/- mice demonstrate poor performance for both short-term (1 h) and long-term (24 h) memory tests in comparison to that of wild-type mice. Electrophysiological experiments indicate that mitral cell neurons cultured from both heterozygous and homozygous-null mice (IR+/- and IR-/-) have an decreased peak current amplitude compared with that recorded for wild-type (+/+) animals matched for days in vitro (DIV). These data indicate that the loss of one allele of the IR kinase gene modifies the electrical phenotype of the mitral cell neurons in the olfactory bulb without a change in gross olfactory ability. Given our findings that there are no significant changes in metabolic balance of the IR (+/-) mice but some impairment in memory retention, future experiments testing for specific olfactory behaviors or functional deficits in IR-/+ mice models of diabetes will need to either be tasks that do not require learning or will require a different model (such as diet-induced diabetes) that may evoke a stronger phenotype.

Animals↗

Neuroenteric cyst of the anterior cranial fossa: case report and review of the literature.

A case of intradural neuroenteric cyst located in the anterior cranial fossa is presented. The cyst caused anosmia and progressive personality changes in an elderly woman. The patient underwent bifrontal craniotomy with evacuation of cyst contents and removal of the cyst wall. Incidence, classification, histopathology, and histogenesis of neuroenteric cysts are discussed with review of the literature.

Aged↗

Ontogeny of GnRH and olfactory neuronal systems in man: novel insights from the investigation of inherited forms of Kallmann's syndrome.

GnRH embryonic neuronal fate is determined by discreet spatio-temporal expression patterns and interactions of axonal guidance and cell adhesion molecules and extracellular matrix proteins. Expression of several transcription factors, locally derived growth factors and neurotransmitters influence GnRH ontogeny and rostral forebrain specification. In man, disrupted GnRH neuronal ontogeny can be caused by several monogenic disorders leading to isolated hypogonadotrophic hypogonadism (IHH); these include mutations within KAL-1, GnRH-R, and FGFR1. Mutations in KAL-1 and its encoded protein anosmin-1, causes X-linked Kallmann's syndrome (XKS) characterized by IHH, anosmia, synkinesis, and unilateral renal agenesis. Anosmin-1 has an obligate functional interaction with membrane associated heparan sulphate proteoglycans (HSPG) and FGFR-1 (KAL-2) whose mutations lead to the autosomal dominant form of KS (AKS). FGFR1 and anosmin-1 may interact via a HSPG dependent mechanism raising the possibility of interaction between two single gene defects cause similar phenotypic abnormalities.

Animals↗

Androstadienone odor thresholds in adolescents.

A sex-related difference in olfactory sensitivity to androstenone has been reported to occur during adolescence. More males than females exhibited anosmia to androstenone, or an increase in androstenone threshold with age. The current study addressed the question whether similar, sexually dimorphic effects of aging over puberty can also be found for androstadienone. A total of 102 subjects participated (36 females, 66 males). Similar to previous investigations, subjects were divided into a group of 47 individuals with a mean age of 13.3 years, defined as pre/peri-pubertal, and a group of 55 subjects with a mean age of 17.1 years, defined as post-pubertal. All subjects underwent tests for verbal abilities, general olfactory function, and measurements of androstadienone thresholds. The study provided the following major results: (1) Male subjects exhibited higher androstadienone sensitivity in the pre/peri-pubertal group as compared to the post-pubertal group. This difference was not observed in female subjects. Correspondingly, a negative correlation between age and androstadienone sensitivity was found for male subjects, but not for female subjects. (2) In contrast to this sex-specific change of the androstadienone odor threshold, verbal skills and odor identification abilities increased with age in all subjects regardless of their sex. In conclusion, the present observations confirm previous research on sex-differentiated effects of aging during puberty on sensitivity towards odorous steroids. While the underlying causes are unknown, it may be hypothesized that the decreased sensitivity could result from the increased endogenous levels of androstadienone in male subjects. Future studies should include both steroid and non-steroid odorants to further explore these age-related changes.

Adolescent↗

[Nasal polyposis: postoperative long term results (5 years) after endoscopic sinus surgery].

The purpose of this study is to evaluate the results after endoscopic sinus surgery in cases of nasal polyposis. We include 54 patients with diffuse nasal polyposis suffering from nasal obstruction. An endoscopic sinus surgery under general anesthesia with excision of the polyposis was performed. There were no complications. The patients were followed closely and treated with local and systemic steroids. After 5 years, the 75% of these patients were free of nasal symptoms and in the 67% the mucosa appeared normal. We also review the influence of some factors (ASA triad, anosmia, allergy...) in the recurrence of the disease.

Adult↗

Magnetic resonance imaging of the brain in idiopathic hypogonadotropic hypogonadism.

Magnetic resonance imaging (MRI) of the pituitary, hypothalamus and olfactory sulci was performed in 40 patients with idiopathic hypogonadotropic hypogonadism (IHH). Twelve of these patients had an impaired sense of smell (Kallmann's syndrome). Sagittal and coronal imaging revealed no morphological abnormalities in the hypothalamic-pituitary region. On axial imaging rudimentary, hypoplastic or aplastic olfactory sulci were found in eight cases. All patients with olfactory sulcal abnormalities had associated hyposmia (one case) or anosmia (seven cases). Structural defects identifiable on MRI were present only in 20 per cent of patients with IHH.

Adult↗

A case of complete hypogonadotropic hypogonadism with a mutation in the gonadotropin-releasing hormone receptor gene.

OBJECTIVE: To screen for mutations in the GnRH receptor gene in a case of complete hypogonadotropic hypogonadism (HH) with GnRH resistance. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A male patient with the complete form of HH without anosmia. INTERVENTION(S): Physical examination and laboratory and genetic studies. MAIN OUTCOME MEASURE(S): Gonadotropins at the basal state and after GnRH administration and GnRH receptor DNA sequencing. RESULT(S): A novel missense mutation, localized in the first amino acid of the extracellular loop found in the heterozygous state, and another mutation, Arg(139)His (R139H), located in the conserved aspartate-arginine-serine motif at the junction of the third transmembrane and second intracellular loop of the GnRH receptor, were identified in the homozygous state. Pedigree studies reveal that both parents were heterozygous for R139H, while the mother carried the missense mutation at codon 1(M1T). CONCLUSION(S): GnRH receptor mutations may account for a larger proportion of cases of HH than previously thought. The phenotypic spectrum of HH seems to vary, and this heterogeneity may be related, at least in part, to the degree of impaired biological activity of the mutated GnRH receptor caused by the allelic type of mutations.

Adult↗

Kallmann syndrome and associated malformation of the uterus.

Kallmann syndrome is a rare combination of hypogonadotropic hypogonadism due to hypothalamic insufficiency and anosmia. In both patients treated at our institution for infertility, a malformation of the uterus was noted: one patient had a unicornuate uterus, the other a uterus with a fundal hypoplasia and tubes of approximately 9 cm. It is not clear if the malformation is in association with Kallmann syndrome or purely coincidental. Given the known association of other malformations with Kallmann syndrome, we suppose that probably an underlying genetic defect having to do with organogenesis is the cause of the uterine malformations.

Adult↗

Hypogonadotropic hypogonadism: retrospective analysis of 19 cases.

OBJECTIVES: To survey the clinical data of patients with isolated gonadotropin deficiency. METHODS: We retrospectively surveyed the medical records of 19 patients with isolated gonadotropin deficiency aged 16-31 years (mean: 20 years). The major complaint was primary amenorrhea in 100% of the patients, with 42.1% of them also reporting absence of secondary sex traits, and 10% reporting anosmia or hyposmia. Seventy-four percent of the patients had been submitted to hormonal replacement therapy. RESULTS: Bone densitometry was determined in 5 patients and revealed lumbar spine osteopenia in 3 patients and femoral osteopenia in 1. An association with urologic malformations was detected in 10.5% of cases and an association with gynecologic malformations was detected in 31.6%. CONCLUSIONS: Isolated gonadotropin deficiency can be easily diagnosed but requires early estrogen replacement therapy because of a higher risk of osteopenia and consequently of osteoporosis. Concomitant urogenital malformations are frequent and should be investigated.

Adolescent↗

Callosal disconnection syndrome in a left-handed patient due to infarction of the total length of the corpus callosum.

We report on a left-handed patient with an ischemic infarction affecting exclusively the total length of the corpus callosum. This lesion clinically correlated with an almost complete callosal disconnection syndrome as described in callosotomy subjects, including unilateral verbal anosmia, hemialexia, unilateral ideomotor apraxia, unilateral agraphia, unilateral tactile anomia, unilateral constructional apraxia, lack of somesthetic transfer and dissociative phenomena. Despite the patient's left-handedness, his pattern of deficits was similar to the disconnection syndrome found in right-handers. Our report focusses on motor dominance and praxis. We followed-up the improvement in left apraxia and investigated the ability to initiate and learn a new visuo-motor skill. The results permit two tentative assumptions: (1) that the improvement in left apraxia was due to a compensatory increase in ipsilateral proximal muscle control, and (2) that motor dominance, i.e. the competence to initiate and learn a new movement pattern, was hemispherically dissociable from manual dominance in the sense of praxis control.

Apraxias↗

[Malignant triton tumor of the sinonasal tract].

INTRODUCTION: The combination of a malignant peripheral nerve sheath tumor with rhabdomyosarcomatous elements has been termed Malignant Triton Tumor (MTT). This tumor was first reported in 1932 and the prognosis was poor. Involvement of the sinonasal tract is rare with only 10 case reports. CASE: We report the case of a 80-year-old woman who presented an obstruction of the right nasal fossa which developed over several years without anosmia. She consulted because of recurrent epistaxis. The CT-scan revealed a tumor occupying the right ethmoid the right maxillary sinus and the homolateral nasal fossa. Resection was achieved via an extended mediofacial route. The histological diagnosis was low-grade schwannosarcoma with a discretely extended rhabdomyosarcomatous component, i.e. MTT. No complementary treatment was given. Eight months later, the tumor relapsed with cerebral involvement. Despite new surgery with two teams, a neurosurgical and a radiotherapy team, the tumor relapsed at the ethmoid-nasal level. After five years, the patient is alive with local progression without metastasis. DISCUSSION: MTT of the sinonasal tract is a rare disease that clinicians should be aware of and that must be included in the differential diagnosis of malignant lesions involving the sinonasal tract. Most of the reported cases involving localizations other than the ethmoidonasal cavities, are associated with von Recklinhausen neurofibromatosis and occurr in young subjects (mean age 35 years). There have however been sporadic cases, mainly in older women or after radiotherapy. The prognosis is somewhat better for ethmoidonasal localizations.

Aged↗

[Long-term functional and aesthetic sequelae after complex facial trauma associated with a mild brain injury].

INTRODUCTION: Most victims of complex facial trauma will have permanent sequelae. The goal of our work was to evaluate, by means of a retrospective study, the long-term sequelae in these patients. MATERIAL AND METHOD: 102 victims of complex facial trauma were treated in our department between 1995 and 2000. Twenty-four could be re-examined in 2006 in order to evaluate their long-term sequelae. All the patients suffered a mild brain injury. RESULTS: The overall satisfaction rate was good (19/24), but all patients presented either functional or aesthetic sequelae. The major functional sequelae were dental lost (17/24), sensory impairment of the trigeminal nerve (15/24), partial or complete loss of vision (10/24), pain (10/24), hypo- or anosmia (9/24), stenosis of the lacrimal ducts (8/24) and symptomatic deviation of the nasal septum (7/24). The main esthetic sequelae were facial scarring (23/24), facial asymmetry (13/24), dystopia of the eyeball (11/24) and modification of the aspect of the nose (10/24). DISCUSSION: The prognosis of severe facial trauma is highly dependent on the quality of the initial pluridisciplinary care. Secondary revision procedures are technically more difficult and only enable partial resolution of persisting sequelae. Thus, primary single-course surgical procedures should be a priority, recognizing that complete recovery is almost always illusory.

Adolescent↗

Neuropeptides in hypothalamic neuronal disorders.

A few examples of hypothalamic, peptidergic disorders leading to clinical signs and symptoms are presented in this review. Increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) and decreased activity of the vasopressin neurons in the biological clock and of the thyroxine-releasing hormone (TRH) neurons in the PVN contribute to the signs and symptoms of depression. In men, the central nucleus of the bed nucleus of the stria terminalis (BSTc) is about twice as large and contains twice as many somatostatin neurons as in women. In transsexuals this sex difference is reversed, pointing to a role of this structure in gender. Luteinizing hormone-releasing hormone (LHRH) neurons are formed in the fetal olfactory placade and migrate along the terminal nerve fibers into the hypothalamus. In Kallmann's syndrome the migration process of the LHRH (gonadotropin-releasing hormone) neurons is aborted, which explains the joint occurrence of hypogonadotropic hypogonadism and anosmia in this syndrome. In postmenopausal women, the neurons of the infundibular nucleus hypertrophy and become hyperactive because of the disappearance of the estrogen feedback and contain hyperactive peptidergic neurons. Climacteric flushes may be caused by hyperactivity of the neurokinin-B or LHRH neurons in this nucleus. The hypocretin (orexin) neurons in the perifornical area are involved in sleep. In narcolepsy with cataplexy, a loss of these neurons, probably due to an autoimmune process, is found. Obese subjects with a mutation in the gene that encodes for leptin, the preproghrelin gene, or the alpha-melanocyte-stimulating hormone (alpha-MSH) gene have been described. Decreased numbers and activity of the oxytocin neurons in the PVN may be responsible for the absence of satiety in Prader-Willi syndrome. Moreover, a glucocorticoid receptor polymorphism is associated with obesitas and dysregulation of the hypothalamus-pituitary-adrenal axis. In contrast, two single nucleotide polymorphisms (SNPs) of the AGRP gene have been associated with anorexia nervosa.

Animals↗

Subcranial fronto-orbito-nasal approach for ethmoidal cancers surgical techniques and results.

BACKGROUND: The authors report their experience with the subfronto-orbito-nasal approach (SFON) for the treatment of 30 patients suffering from ethmoidal cancers over the past 3 years. The advantages and pitfalls of this technique are described and compared with other classic approaches. METHODS: Among 156 patients suffering from ethmoidal cancers and treated between January 1984 and January 1998, 30 patients were operated on using the SFON approach during the past 3 years. There were 27 males and 3 females, ranging in age from 15 to 77 years. Histologic composition of the lesions was as follows: 15 adenocarcinomas, 6 esthesioneuroblastomas, 3 melanomas, 2 epidermoid carcinomas, 1 nondifferentiated carcinoma, 1 neuroendocrine carcinoma, 1 villous carcinoma, and 1 cystic adenoid carcinoma (cylindroma). According to the authors' classification, 7% were T1, 6% T2, 22% T3, 38.5% T4a, and 26.5% T4b. All patients were operated on through a SFON approach, followed by removal of the tumor and reconstruction of the skull base with a pericranial flap. RESULTS: Since the mean follow-up was of short duration (12 months, ranging from 3 to 29 months), significant carcinologic results could not be obtained. However, a detailed analysis of the surgical procedure was performed. No patient died or had major complications related to the SFON approach. One cerebrospinal fluid (CSF) fistula and four oculomotricity dysfunctions were observed. Definitive anosmia was reported in all cases. CONCLUSION: The advantages of the procedure include a wide exposure of the anterior skull base through a limited approach, the possibility of modifying the approach according to the size and location of the lesion, total resection of tumors, simplified skull base reconstruction technique, and reduction of postoperative confusion and hospital stay.

Adolescent↗

Flavor-illness aversions: potentiation of odor by taste is disrupted by application of novocaine into amygdala.

Taste and odor have different properties in toxiphobic conditioning. When each is used alone, taste becomes aversive when followed by immediate or delayed poison, while odor becomes aversive only if followed by immediate poison. However, if odor and taste are presented as a compound and followed by delayed poison, then odor does become aversive when tested alone. It is as if taste has potentiated the odor signal. Several experiments assessed the role of the amygdala in this potentiation effect by anesthetizing the amygdala with 10% novocaine. Novocaine applied 30 min before presentation (Pre-CS) of an odor-taste compound disrupted the potentiated odor aversion but not the taste aversion. In contrast, novocaine applied 1 min after the compound odor-taste or 1 min prior to LiCl poison did not dissociate odor and taste aversions; both odor and taste aversions were facilitated. Novocaine applied 30 min before an odor alone also disrupted an odor aversion induced by immediate LiCl. But identical treatment did not disrupt odor avoidance conditioned by immediate foot-shock, suggesting that amygdala anesthesia does not simply produce anosmia. Pre-CS novocaine treatment also disrupted flavor neophobia prior to conditioning. The results suggest that novocaine applied to the amygdala disrupts the integration of odor with taste and illness during toxiphobic conditioning.

Amygdala↗

Increased olfactory sensitivity in first episode psychosis and the effect of neuroleptic treatment on olfactory sensitivity in schizophrenia.

Olfactory sensitivity to two odorants, isoamyl acetate and androstenone, was assessed in 19 male schizophrenic patients and 10 control subjects. Tests were performed during a drug-free period and 2-3 weeks after initiation of neuroleptic drug therapy. Olfactory sensitivity in schizophrenic patients was significantly impaired during the drug-free period and neuroleptic treatment further reduced olfactory sensitivity in these patients. The same olfactory tests were administered to 22 first-episode-psychosis patients, 12 first-episode-schizophrenia and 10 brief-psychotic-disorder patients, as well as to 20 age-matched control subjects. The first-episode-psychosis patients had significantly higher sensitivity to isoamyl acetate and to androstenone, but the incidence of anosmia to androstenone was not higher in the first episode patient group as compared to the control group. We conclude that olfactory dysfunction in schizophrenic patients, and possibly other forms of psychosis, is mainly due to long-term effects of commonly used neuroleptic drugs.

Acute Disease↗