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PubMed1996

Olfaction and the homing ability of pigeons in the southeastern United States.

The importance of atmospheric odors for homing pigeon navigation was tested using birds from a loft located in Savannah, GA, in the southeastern United States. When released from a familiar training site, control pigeons and pigeons given intranasal injections of zinc sulfate to produce anosmia both displayed good homeward orientation and homed quickly. When released from three unfamiliar release sites, in contrast, control birds tended to orient southeast, while zinc sulfate-treated birds were more likely to fly northwest. More importantly, while the majority of control pigeons returned to the home loft, few of the zinc sulfate-treated birds returned. The good performance of both groups from the familiar site indicates that zinc sulfate treatment does not impair the general motor ability or motivation of homing pigeons. Therefore, the observed impairment in homing success of the zinc sulfate-treated pigeons from the unfamiliar locations presumably reflects an impaired ability to use atmospheric odors to navigate home. As such, the data support the hypothesis that successful homing pigeon navigation is based on the perception of atmospheric odors and that olfactory navigation is the primary mechanism used by pigeons over a broad range of geographic areas to approximate their relative position with respect to home from unfamiliar locations.

Animals↗
PubMed1997

Sensation of smell does not determine nutritional status in patients with cystic fibrosis.

Poor nutritional status in patients with cystic fibrosis (CF) is associated with increased mortality. Patients with CF often have a decreased sensation of smell secondary to recurrent sinus infections or sinus surgery; in other CF populations, a decreased sensation of smell has been associated with poor nutritional status. We hypothesized that a decreased sensation of smell would be associated with worse nutritional status in patients with CF. We studied 50 (26 F and 24 M) of 58 consecutive patients with CF (86%) aged 14-53 years (28 +/- 8; mean +/- SD) who attended the University of Washington Medical Center from June 1994 to March 1995 and who agreed to participate. Demographic information was obtained, and nutritional status was assessed by ideal body weight, arm muscle area, arm fat area, pancreatic sufficiency, insulin-requiring diabetes, vitamins A and E levels, albumin, iron, iron binding capacity, ferritin, cholesterol, and zinc levels. Objective sensation of small was examined (Sensonics, Philadelphia, PA), a sinus compacted tomogram (CT) was performed, and a questionnaire for prior sinus symptoms, sinus surgery, medications, and subjective sensation of smell was administered. Twenty-seven of 49 subjects (55%) had an objective decrease in sensation of smell, 23/50 (46%) had had prior sinus surgery. 46/50 (92%) were pancreatic insufficient, and 8/50 (16%) were insulin-requiring diabetics. Weight for height ranged from the 38th to 157th percentile (100 +/- 18; mean +/- SD). Arm muscle area ranged from the < 5th to the 75th percentile (25 +/- 23; mean +/- SD). Arm fat area ranged from the < 5th to the 95th percentile (45 +/- 39; mean +/- SD). Sinus CT scans were abnormal in all patients (100%). Patients with anosmia were more likely to have had sinus surgery, but their nutritional status was no different from that of patients with a normal sensation of smell. We conclude that decreased sensation of smell is common in patients with CF, especially those with prior sinus surgery. Subjective sensation of smell and sinus CT scans were unreliable indicators of a decreased objective sensation of smell. In this pilot study, no association was found between sensation of smell and nutritional status.

Adolescent↗
PubMed2001

Loss of olfaction in de novo and treated Parkinson's disease: possible implications for early diagnosis.

Olfactory dysfunction is a common finding in patients with Parkinson's disease (PD). As most studies reported on odor identification in more advanced and treated PD, we administered an odor detection, discrimination, and identification test to a heterogeneous, partly de novo, group of patients. Forty-one non-demented PD patients, 24 of whom had untreated early PD, and 18 healthy controls, were examined. Odor identification and discrimination data were corrected for odor detection scores. PD patients scored significantly lower on all olfactory tests. Interestingly, the subgroup of de novo patients with early PD also showed significant olfactory disturbances compared with healthy subjects. Within the PD group, using multiple regression analysis, we found a significant, negative correlation between odor discrimination measures and disease The present study is the first to describe decreased performance of PD patients on odor discrimination, in addition to the already well-established deficits in odor detection and identification. Furthermore, odor discrimination measures were related to disease severity, possibly indicating that at least some aspects of olfactory dysfunction in PD may be secondary to ongoing degenerative processes in PD. As significant olfactory impairments were found in early, de novo PD, olfactory tests may be useful in the early diagnosis of PD.

Adult↗
PubMed1996

Genetic and molecular studies of olfaction in Drosophila.

Drosophila melanogaster, an insect amenable to convenient molecular and genetic manipulation, has a highly sensitive olfactory system. A number of Drosophila olfactory mutants have been isolated and characterized. The smellblind mutant has a defect affecting a voltage-gated Na+ channel. The norpA mutant, defective in a phospholipase C, has a reduced response to odorants in one type of olfactory organ, providing genetic evidence for use of the inositol-1,4,5-trisphosphate signal transduction pathway in olfaction. Since the norpA gene is also required for phototransduction, this work demonstrates overlap in the molecular genetic basis of vision and olfaction. Interestingly, genetic analysis indicates that some olfactory information flows through a pathway which does not depend on norpA. Some mutants, such as ptg, acj6 and Sco, show odorant specificity, in the sense that some odorant responses are greatly reduced, whereas others are little affected, if at all. Some, but not all, mutations affect both larval and adult olfactory responses. Two tightly-linked Drosophila genes encode homologues of moth pheromone-binding proteins (PBPs). Genetic analysis may help determine whether PBPs facilitate transit of pheromones to or from olfactory receptor neurons. Information from Drosophila could be useful in designing means of controlling mosquitoes. It may also be possible to study olfactory genes, such as those encoding PBPs, from other insects by mutating them, introducing them into Drosophila and analysing their function in vivo.

Amino Acid Sequence↗
PubMed1991

Measurement precision of an olfactory perception threshold test for use in field studies.

Changes in olfactory function have been associated with workplace exposure to a variety of substances. In the workplace, smell can be particularly important, since it is commonly used to detect potentially hazardous situations or as an indicator of mask cartridge breakthrough. Sensitive quantitative measures of olfactory loss would be useful in epidemiological studies and workplace surveillance. The objective of the present study was to determine the reproducibility of an olfactory perception threshold test and variations with age, gender, and smoking status. The test was a standard olfactory kit (Olfactolab No. 11), including 18 serial dilutions of PM-carbinol, with an equal number of blanks. The forced choice method was used, with both tester and subject blinded as to which bottle contained the odorant. Olfactory perception threshold was recorded when the subject identified the same dilution three times. To assess reproducibility, testing was repeated four times over a period of 4 weeks, on the same weekday and the same time of day. Subjects (n = 63) ranged in age from 20 to 60 years (mean age: 39.7 +/- 12.5 years), 47.6% were women, 29.5% currently smoked, and 27.9% were former smokers. Results showed no inter-week differences in olfactory perception threshold (Analysis of variance for repeated measures: F = 0.59; p much greater than 0.05). Inter-class correlation for assessment of agreement of continuous variables was 0.76. Inter-week concordance of hyposmia showed fair to good agreement (0.55 greater than or equal to kappa less than or equal to 0.66). Three-way analysis of variance (ANOVA) revealed significant differences with respect to age category (F = 7.36; p less than 0.001) and current smoking status (F = 4.54; p less than 0.05), but not for gender (F = 2.32; p greater than 0.05). The multiple regression model with age and smoking as independent variables was highly significant (F = 13.03; p less than 0.001), explaining 28% of the variance; olfactory threshold increased 0.47 ds/year (t = 4.01; p less than 0.001) and 0.27 ds/cigarettes/day (t = 2.46; p less than 0.05). The findings of this study indicate that this test is reproducible and sensitive to expected changes with age and smoking status. It corresponds well to criteria for testing in the field and should be considered for studies characterizing olfactory functions and sensory loss among working populations.

Adult↗
PubMed1983

The syndrome of anosmia with hypogonadotropic hypogonadism: a genetic study of 18 new families and a review.

Among 18 NIH probands with anosmia and hypogonadotropic hypogonadism (AHH), seven had affected relatives and three had consanguineous parents. Both sexes were equally affected and parents were phenotypically normal. Parental age was not increased. Cleft lip and palate occurred in both eugonadal and hypogonadal persons, a previously reported association that may represent variable expression of AHH. Diabetes mellitus, usually insulin-dependent, was frequent in probands and their families. Other common traits included obesity, cryptorchidism, and hearing loss. All probands were chromosomally normal. The frequency of some dermatoglyphic traits of probands differed from normal, but no trait was unique to AHH. Segregation analysis of our proband sibships was consistent with a hypothesis of autosomal-recessive inheritance with variable expression. However, genetic heterogeneity was apparent when previous reports of familial AHH were surveyed. An X-linked or male sex-limited autosomal-dominant form with unilateral renal agenesis, mental retardation, and hypotelorism has been observed. The infrequent reports of direct male-to-male transmission limit characterization of an autosomal-dominant form of AHH. Our phenotypic analysis suggests that the traits of mental retardation, renal anomalies, hypotelorism, diabetes, and hearing loss may help to distinguish various forms of AHH, whereas cryptorchidism, clefts, and obesity appear in several types of families. At present, genetic counseling is dependent upon establishing inheritance pattern after examination for the known associated anomalies.

Chromosome Banding↗
PubMed1983

A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism.

We describe a large, three generation kindred in which 16 individuals were affected with alopecia, hyposmia or anosmia, conductive deafness associated with protruding ears, microtia, and/or atresia of the external auditory canal, hypogonadotropic hypogonadism due to LH/FSH deficiency, and a greater than normal tendency to dental caries. Variable manifestations include mild facial asymmetry, mental retardation, congenital heart defect, and cleft palate. This seems to be a previously undescribed pleiotropic autosomal dominant trait with variable expressivity. The manifestations can be explained on the basis of involvement of the ectoderm and neuroectoderm of the first and second branchial arches, of Rathke's pouch, and of the diencephalon.

Abnormalities, Multiple↗
PubMed1986

Characteristic craniofacial appearance and brachytelephalangy in a mother and son with Kallman syndrome in the son.

We report on a mother and son with a similar facies characterized by a square forehead, small nose, telecanthus, and thin upper lip. They both had a similar metacarpal-phalangeal profile characterized by marked brachytelephalangy. They were both short in comparison to other family members, and the son had hypogonadotropic-hypogonadism and anosmia. We favor the hypothesis of a single autosomal dominant gene with variable expression of the hypogonadism and anosmia, although there are alternative explanations for the combination.

Adolescent↗
PubMed1987

Estimating frequency of Kallmann syndrome among hypogonadic and among anosmic patients.

The frequency of Kallmann syndrome (hypogonadotropic hypogonadism and anosmia, HHA) was estimated in patients presenting with hypogonadism and patients with anosmia. Of 791 hypogonadal males 19 had HHA. The frequency of HHA was about 1:25 (n = 8/189) in outpatients questioned about their sense of smell, about 1:50 (n = 11/579) in patients whose blood samples were sent to us for chromosome analysis, and about 1:30 (n = 19/605) in males with hypogonadism and 46,XY chromosomes. The relation of patients with HHA to those with Klinefelter syndrome was 1:10 (n = 19/186). From 24 patients presenting with anosmia we found 1 hitherto undiagnosed case of HHA. The mean age at diagnosis was 24.8 and 24.9 years in our cases and cases from literature, respectively. These data provide evidence that Kallmann syndrome is not infrequent and that most patients remain undiagnosed until the third decade of life. Earlier diagnosis is emphasized by questioning each hypogonadal patient about his sense of smell because therapeutic success seems to be age dependent.

Adolescent↗
PubMed1989

Male infant with ichthyosis, Kallmann syndrome, chondrodysplasia punctata, and an Xp chromosome deletion.

We report on a male infant with X-linked ichthyosis, X-linked Kallmann syndrome, and X-linked recessive chondrodysplasia punctata (CPXR). Chromosome analysis showed a terminal deletion with a breakpoint at Xp22.31, inherited maternally. This patient confirms the localization of XLI, XLK, and CPXR to this region of the X chromosome and represents an example of a "contiguous gene syndrome." A comparison of the manifestations of patients with CPXR, warfarin embryopathy, and vitamin K epoxide reductase deficiency shows a remarkable similarity. However, vitamin K epoxide reductase deficiency does not appear to be the cause of CPXR. We propose that CPXR may be due to a defect in a vitamin K-dependent bone protein such as vitamin K-dependent bone carboxylase, osteocalcin, or matrix Gla protein.

Chondrodysplasia Punctata↗
PubMed1990

Chromosome abnormality in Kallmann syndrome.

We report on an individual with Kallman syndrome (KS) and a balanced de novo translocation (7;12)(q22,q24). None of 6 full sibs, 3 half-sibs, or parents have KS or this chromosome translocation. This is the only known report of KS with a chromosome abnormality. This may represent a spurious association or genetic heterogeneity vis-a-vis the reported linkage of KS to the steroid sulphatase gene on the X chromosome. The pathophysiology and genetics of KS are discussed.

Adult↗
PubMed2001

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Aged↗
PubMed2004

Idiopathic hyposmia as a preclinical sign of Parkinson's disease.

Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n = 40) and normosmic (n = 38) individuals for a 2-year clinical follow-up evaluation and sequential single-photon emission computed tomography (SPECT), using [123I]beta-CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow-up of the remaining 283 relatives. Two years from baseline, 10% of the individuals with idiopathic hyposmia, who also had strongly reduced [123I]beta-CIT binding at baseline, had developed clinical PD as opposed to none of the other relatives in the cohort. In the remaining nonparkinsonian hyposmic relatives, the average rate of decline in dopamine transporter binding was significantly higher than in the normosmic relatives. These results indicate that idiopathic olfactory dysfunction is associated with an increased risk of developing PD of at least 10%.

Aged↗
PubMed1986

A new syndrome of anosmia, ichthyosis, hypogonadism, and various neurological manifestations with deficiency of steroid sulfatase and arylsulfatase C.

We describe a family consisting of 3 affected men with congenital ichthyosis, anosmia, hypogonadism, nystagmus with decreased visual acuity, strabismus, hypopigmentation of the iris, and mirror movements of the hands and feet. Two of them had limitation of ocular movement and unilateral renal agenesis or hypoplasia. The condition appears to be inherited as an X-linked recessive trait. Clinical, pathological, and biochemical evaluations were compatible with a diagnosis of X-linked ichthyosis. Steroid sulfatase and arylsulfatase C activities in leukocytes and fibroblasts were markedly diminished in the affected patients. Their hypogonadism was due to decreased luteinizing hormone-releasing hormone secretion (hypogonadotropic). Hyposecretion of antidiuretic hormone was also recognized. Chromosome analysis of leukocytes and skin fibroblasts revealed a normal 46,XY male karyotype in all of the patients.

Adolescent↗