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Early expression of the KAL gene during embryonic development of the chick.

The human KAL gene is responsible for the X chromosome-linked Kallmann syndrome, which consists of the association of hypogonadotropic hypogonadism and anosmia. The human and chicken KAL genes have been isolated. Using in situ hybridization, we studied KAL gene expression during development of the chick. We have previously reported that, from embryonic day 8, the expression is almost restricted to definite neuronal populations in the central nervous system, most of which still express the gene after hatching. Here we report that the KAL gene is also expressed during early embryonic development (days 2-8) in various endodermal, mesodermal, and neurectodermal derivatives. In most endodermal and mesodermal derivatives, the expression is transient and precedes cell differentiation. In contrast, the expression in the nervous system concerns postmitotic central neuroblastic populations, most of which still express the gene after differentiation. In accordance with such a spatio-temporal pattern of expression, we suggest that the KAL gene is involved both in morphogenetic events and in neuronal late differentiation. In addition, the absence of detectable expression of the KAL gene either in the embryonic olfactory epithelium or in the surrounding nasal mesenchyme reinforces the hypothesis that Kallmann's syndrome results from a central olfactory target cell defect.

Animals↗

Deletions of the steroid sulphatase gene in "classical" X-linked ichthyosis and in X-linked ichthyosis associated with Kallmann syndrome.

We have studied 16 men, from 10 unrelated Italian families, affected by steroid suphatase (STS) deficiency, which is the basic defect of X-linked ichthyosis (XLI). The patients' clinical diagnoses were of either isolated ichthyosis or ichthyosis associated with Kallmann syndrome (KS) (hypogonadotropic hypogonadism and anosmia). DNA from patients and their relatives was analysed by Southern blotting followed by hydridization with an STS cDNA probe. None of the patients affected by either XLI or XLI/KS showed any hybridization signal, thus revealing a deletion in the STS gene. We suggest that a gene deletion may be the most common molecular defect involved in XLI and that the syndrome XLI/KS may be due to a deletion of both the STS and the KS loci.

Chromosome Deletion↗

Familial cerebellar ataxia with hypogonadism.

A brother and sister with congenital cerebellar ataxia, anosmia, oligophrenia, hypogonadism and anomalies of amino acid distribution are reported. Ties between the different symptoms are difficult to establish. It seems to be a new syndrome rather than a new disease. Once more these associations emphasize the need for metabolic and biochemical research in heredodegenerative diseases. The evolution of the disease in these cases might make it possible to classify and locate it more accurately.

Adult↗

A case of Foster Kennedy syndrome without frontal lobe or anterior cranial fossa involvement.

Foster Kennedy syndrome is a very rare syndrome which includes ipsilateral optic atrophy and central scotoma, anosmia, contralateral papilledema, and, occasionally, ipsilateral proptosis. A large frontal lobe, olfactory groove, or medial third sphenoidal wing tumor, usually a meningioma, creates this syndrome. In this report, the author presents a case of metastatic cerebral tumor with Foster Kennedy syndrome but without frontal lobe or anterior cranial fossa involvement.

Biopsy↗

Sinonasal polyposis: investigation by direct coronal CT.

To demonstrate the typical clinical and CT features of sinonasal polyposis, we reviewed the clinical records and preoperative direct coronal CT scans of 35 patients with surgically proven disease. Symptoms included progressive nasal stuffiness (100%), rhinorrhea (69%), facial pain (60%), headache (43%) and anosmia (17%). We found associations with rhinitis (46%), asthma (29%) and aspirin sensitivity (9%). Coronal CT features included polypoid masses in the nasal cavity (91%), partial or complete pansinus opacification (90%), enlargement of infundibula (89%), bony attenuation of the ethmoid trabeculae (63%) and nasal septum (37%), opacified ethmoid sinuses with convex lateral walls (51%) and air-fluid levels (43%). The latter feature correlated with symptoms and signs of acute sinusitis in only 40% of patients. Recognition of sinonasal polyposis is important to the endoscopic surgeon since it can be the most troubling sinonasal inflammatory disease to manage due to its aggressive nature and tendency to recur despite appropriate treatment.

Diagnosis, Differential↗

Comparison of the sensitivity of C57BL/6J and AKR/J mice to airborne molecules of isovaleric acid and amyl acetate.

Wysocki et al. (1977) have previously compared the abilities of several inbred strains of mice to avoid odorized drinks after odor-aversion conditioning and have proposed C57BL/6 mice as an animal model to study the specific anosmia to isovaleric acid. We have compared the olfactory performances of C57BL/6J mice and AKR/J mice using one-bottle and two-bottle tests to study the latencies of contacts with odorized or control drinks after odor-aversion conditioning. In both inbred strains, sensitivities to airborne molecules of amyl acetate (control odor) or isovaleric acid are demonstrated. Differences in behavioral strategies are suggested but the results are consistent with the hypothesis of a selective hyposmia to isovaleric acid in C57BL/6J mice.

Animals↗

The basal interhemispheric approach for acute anterior communicating aneurysms.

We reviewed the surgical outcome in 85 patients with ruptured anterior communicating artery (ACoA) aneurysms, who were operated on within 72 hours of onset via a basal interhemispheric (BIH) approach (Group 1, N = 48), or an anterior interhemispheric (AIH) approach (Group 2, N = 37). The age, sex ratio and pre-operative grade (Gr) were similar for both groups. The outcome at the time of discharge was as follows for group 1: excellent or good 88%; fair, 6%; vegetative state, 2% and death 4%. For group 2, it was: excellent or good 78%; fair, 16%; vegetative state, 3%; and death, 3%. A significant correlation between admission grade and outcome was found in both groups. The outcome in group 1 was better than in group 2 for patients with a Glasgow Outcome Scale (GOS) better than fair (p < 0.07). No patient in group 1 had postoperative anosmia, but nine patients in group 2 became anosmic. The total number of complications was also significantly less in group 1. Our overall mortality rate was 4%. In conclusion, the BIH approach was more beneficial for treating acute ACoA aneurysm.

Adult↗

Olfactory dysfunction in the Shy-Drager syndrome.

The aetiology of the Shy-Drager syndrome (multiple system atrophy) is unknown. We reported previously a preliminary association between environmental-occupational risk factors and Shy-Drager syndrome. To further investigate this relationship, we evaluated olfactory function in eight patients in different stages of disease. When the eight patients' olfactory function was compared with 203 age- and sex-matched controls using a self-administered olfactory test, seven scored below the 39th percentile of this population. Five of the eight patients had total anosmia or microsmia. Additional studies will be required to elucidate the significance of this abnormal clinical observation.

Aged↗

Odor-guided behavior in mammals.

The odor-guided behaviors selected for presentation in this paper encompass the major areas of animal behavior, and illustrate the important principal that complex relations exist between odor-guided behaviors, hormonal state, and experiential factors. Clearly, experiences with odors at several life stages results in profound influences upon later behaviors, including those related to eating, mating, fighting, and nesting. Interestingly, only brief social encounters are needed in rats to induce such phenomena as ultrasonic calling to conspecific estrous females or their odors, preferences for estrous over non-estrous odors, and the short-term modification of feeding behaviors. Although the mechanisms behind these intriguing phenomena are poorly understood, it is noteworthy that rats can learn relatively complex concepts on the basis of odors, rivaling even the ability of our own species to learn analogous tasks by visual cues. Despite the fact that close relationships can be demonstrated between odor-guided behaviors and variables such as endocrine state and sexual experience, caution is warranted in assuming that simple causal relations exist between such variables. In normally cycling women, for example, the correlation between olfactory sensitivity and plasma levels of estradiol during the menstrual cycle is relatively high; however, attenuation of the cyclical estradiol fluctuations by oral contraceptives does not eliminate the olfactory fluctuations, suggesting the relation is not causal. In house mice, social experience can override hormonal factors in their odor-guided urine marking and submissive behaviors. Thus, even though androgen titer usually correlates with such measures, a mouse made subordinant in a social encounter will not exhibit scent marking even when its circulating testosterone is maintained at a high level by a silastic implant. Further reason for caution comes from studies that suggest olfactory input influences the endocrine systems of sexually experienced and sexually inexperienced animals in different ways. For example, in sexually experienced male rats, anosmia decreases testosterone and estradiol levels and increases corticosterone levels, whereas in sexually inexperienced ones it has no significant influence on the levels of these steroids. Taken together, such observations suggest that the causal bases of a number of the odor-guided behaviors described in this paper are complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Diagnosis of X-recessive Kallmann syndrome in early infancy. Evidence of hypoplastic rhinencephalon.

A 3-month-old infant presented with hypogonadism, a small penis and bilateral cryptorchidism. He showed an insufficient response of luteotropic hormone (LH) and follicle stimulating hormone (FSH) to luteotropic hormone releasing hormone (LHRH) and of testosterone to human chorionic gonadotropin. The maternal uncle had hypogonadism and anosmia and also showed an impaired LH and FSH response to LHRH. MRI examination showed hypoplasia of the rhinencephalon in both cases. These findings in the son and brother of the clinically unaffected mother suggest X-linked recessive inheritance.

Adult↗

Superficial siderosis of the central nervous system.

Two patients with superficial siderosis of the central nervous system are reported. Both developed progressive deafness over many years; one with associated anosmia and partial seizures; the other with progressive ataxia and diplopia. The cerebrospinal fluid was xanthochromic in one and the protein was raised in both. Magnetic resonance imaging revealed a hypodense rim around the eighth cranial nerve, cerebellum, brain stem and spinal cord. Despite extensive investigations the cause of the superficial siderosis in both patients remains undetermined.

Adult↗

Coincidental visualization of an atypical bronchial carcinoid on Tc-99m-sestamibi scan in Kallmann's syndrome.

We report a case of an atypical bronchial carcinoid showing sestamibi uptake. A 27-year-old man with Kallmann's syndrome and hyperparathyroidism had parathyroid scintigraphy with 99mTc-sestamibi. A focal uptake was observed on the right perihilar region, and this right perihilar mass was demonstrated on computed tomography and proved histologically to be an atypical bronchial carcinoid tumor. Factors which may explain the tumoral avidity for sestamibi are increased blood flow, transmembrane potentials of plasma and mitochondrial membranes and the relative number of mitochondria present in the cells of this carcinoid tumor. The importance of this case is the coincidence of an atypical carcinoid in a patient with significant failure of secondary sexual characteristics, right renal agenesis and bilateral anosmia associated with Kallmann's syndrome.

Adult↗

Genetics of hypogonadotropic hypogonadism.

Determining the physiologic influences that modulate GnRH secretion, the prime initiator of reproductive function in the human, is fundamental not only to our understanding of the rare condition of congenital idiopathic hypogonadotropic hypogonadism (IHH), but also common disorders such as constitutional delay of puberty and hypothalamic amenorrhea. IHH is characterized by low levels of sex steroids and gonadotropins, normal findings on radiographic imaging of the hypothalamic-pituitary regions, and normal baseline and reserve testing of the remainder of the hypothalamic-pituitary axes. Failure of the normal pattern of episodic GnRH secretion results in delay of puberty and infertility. IHH is characterized by rich clinical and genetic heterogeneity, variable modes of inheritance, and association with other anomalies. To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing). As these mutations account for less than 20% of all IHH cases, discovery of additional gene mutations will continue to advance our understanding of this intriguing syndrome.

Aspartic Acid Endopeptidases↗

Idiopathic hypogonadotrophic hypogonadism associated with arachnoid cyst of the middle fossa and forebrain anomalies: presentation of an unusual case.

We report a 22-yr-old male patient with hypogonadotrophic hypogonadism (HH) associated with a giant middle fossa arachnoid cyst (AC) diagnosed by magnetic resonance imaging (MRI). He presented with pubertal and growth delay. He also had learning disabilities and anosmia. Laboratory investigation revealed pre-pubertal levels of testosterone and normal results of the combined test of anterior pituitary function, except for in GnRH acute and prolonged test. Cranial MRI showed an AC in left middle fossa with expansion to suprasellar cisterna and several abnormalities like left temporal lobe hypoplasia, left optic tract and bilateral olfactory bulb hypoplasia and left hypothalamic hypoplasia.

Adult↗

[Olfactory dysfunctions. Epidemiology and therapy in Germany, Austria and Switzerland].

INTRODUCTION: Olfactory dysfunction has been reported to affect more than 200,000 patients a year in the USA. The aim of this survey was to obtain comparable epidemiological data and treatment information on olfactory dysfunction in German speaking countries. METHODS: Questionnaires were sent to all otorhinolaryngology departments in Germany, Austria and Switzerland; 52% of hospitals completed the survey. RESULTS: An average of 46 patients with olfactory dysfunction were treated per hospital every month. Hyp- and anosmia were most commonly caused by inflammatory diseases of the nose/paranasal sinuses (53%), respiratory dysfunction (19%), or postviral conditions (11%). Steroids were used most frequently for pharmacological treatment (topically 82%; orally 65%). Approximately one third of the clinics used B vitamins, or zinc; 80% of the hospitals performed surgery to treat underlying diseases. Acupuncture and smell training was used by approximately 20%. CONCLUSION: A total of 79,000 patients per year are treated for olfactory dysfunction in German hospitals. The vast majority of these disorders (72%) is caused by sinunasal diseases. The quality control of therapeutic strategies is urgently needed.

Austria↗

[Paraneoplastic limbic encephalitis].

We report on a 69-year old male patient who presented with vague depressive symptoms and loss of weight accompanied by lack of appetite, ageusia and anosmia. The patient died of bronchial pneumonia, and neuropathological examination revealed a so-called limbic encephalitis. The paraneoplastic origin of this case was later confirmed by discovery of a clinically inapparent, indolently growing small cell lung cancer. This case illustrates the difficult clinical diagnosis of paraneoplastic limbic encephalitis and the need for a close cooperation of pathologists and neuropathologists in the clarification of such cases.

Aged↗

Idiopathic hypertrophic cranial pachymeningitis associated with an orbital pseudotumor.

We report a case of idiopathic hypertrophic cranial pachymeningitis (IHCP) associated with an orbital pseudotumor and granulocytic thyroiditis of unknown origin. The patient suffered from progressive and finally complete loss of visual acuity, as well as from multiple cranial nerve dysfunctions. Medical treatment and radiation therapy were not beneficial. As reported in the literature, the CT and MRI findings of IHCP were non-specific; thus, diagnosis had to be made by exclusion and open biopsy was required. An inflammatory pseudotumor of the orbit is rarely found in patients with IHCP. Thyroiditis has not yet been reported in the context of IHCP. The patient also suffered from anosmia, which is an unusual feature of IHCP.

Autoimmune Diseases↗

[Adult Refsum disease. A retinal dystrophy with therapeutic options].

Adult Refsum disease is one of the few forms of tapetoretinal degenerations accessible for therapy. The disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety tissues. Beside tapetoretinal degeneration, additional symptoms are chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, skeletal malformations, and cardiac abnormalities. A diet low in phytanic acid leads to an amelioration of polyneuropathy and ataxia and slows or even stops the other manifestations. This beneficial effect of dietary precautions requires the need to get hold of as much patients as possible but better all of them. The ophthalmologist plays a crucial role to this end because of the early manifestation of the tapetoretinal degeneration. A delay of 11 years between the appearance of first symptoms and the diagnosis of Refsum disease, as reported in the literature, is not acceptable.

Adult↗