Odor and chemesthesis from brief exposures to TXIB.

UNLABELLED: An experiment explored ability of subjects to detect vapors of the plasticizer TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate) and ethanol via olfaction and via ocular and nasal chemesthesis, i.e. chemically stimulated feel. Testing, tailored to the sensitivity of each subject, produced psychometric functions for individuals. Olfactory detection of TXIB began at concentrations below 1 ppb (v/v), with 50% correct detection at 1.2 ppb. (Comparable detection for ethanol occurred almost two orders of magnitude higher.) Chemesthetic detection of TXIB began at about 500 ppb, with 50% correct detection at 2.1 ppm for the eye and 4.6 ppm for the nose, both close to saturated vapor concentration. (Comparable detection for ethanol occurred essentially three orders of magnitude higher.) Suggestions that TXIB plays a role in generation of irritative symptoms at concentrations in the range of parts-per-billion need to reckon with a conservatively estimated 200-fold gap between the levels putatively 'responsible' for the symptoms and those even minimally detectable via chemesthesis. Neither the variable of exposure duration nor that of mixing offers a likely explanation. Inclusion of ethanol in the study allowed comparisons pertinent to issues of variability in human chemoreception. An interpretation of the psychometric functions for individuals across materials and perceptual continua led to the conclusion that use of concentration as the metric of detection in olfaction inflates individual differences. PRACTICAL IMPLICATIONS: This study indicated that the plasticizer TXIB could contribute odor at concentrations in the range of parts-per-billion, but could hardly contribute sensory irritation per se, as alleged in reports of some field studies where TXIB has existed amongst many other organic compounds.

Orbital response indicates nasal pungency: analysis of biomechanical strain on the skin.

Stimulation of the human nasal passage with pungent vapor elicits motor responses in a zone around the eye. This investigation addressed whether quantification of such responses, particularly activity of the orbicularis oculi muscle, could yield a sensitive index of nasal pungency. We placed an array of small, high-contrast targets just beneath the lower eyelid and videotaped their movement to capture deformation of the skin atop the orbicularis oculi during 3 s stimulation with pungent concentrations of ethyl acetate. Eleven subjects participated. Analysis of the movements served to determine mechanical strain, which yielded a single index that we termed 'maximum strain'. This increased with concentration of the vapor and with time during and just after stimulation. Comparison with psychophysical data showed that the strain became evident at concentrations just detectable as pungent. Maximum strain measured on the skin shows promise as an objective index of pungency.

Subjective and objective assessments in patients with seasonal allergic rhinitis: effects of therapy with mometasone furoate nasal spray.

BACKGROUND: Efficacy of topical nasal steroid therapy for allergic rhinitis is usually evaluated by patient and clinician assessments of subjective symptom changes in diaries and at clinical interviews. OBJECTIVE: We sought to complement the subjective measures with objective measures of nasal cytology, biochemistry, and function. METHODS: In this double-blind, randomized study patients with seasonal allergic rhinitis (SAR) 12 years of age or older received 200 microg mometasone furoate nasal spray (n = 80) or placebo spray (n = 41) once daily for 2 weeks. Subjective assessments by clinician and patient comprised symptom/sign scores and overall therapeutic response evaluations. Objective measures included nasal cytology, nasal biochemistry, nasal airway resistance (NAR), mucociliary clearance, and olfactory functions. RESULTS: Mometasone furoate produced a significantly greater decrease than placebo in subjective measures of SAR for total symptom score (-46% vs -30%, p < 0.05), total nasal score (-47% vs -30%, p < 0.024), individual nasal symptom scores, and overall therapeutic response. The objective measures of eosinophil, basophil, and neutrophil counts and mucociliary clearance were significantly better in mometasone furoate- than in placebo-treated patients. Similarly, within-treatment statistically significant improvements were produced by mometasone furoate but not by placebo sprays for levels of eosinophilic cationic protein, tryptase and albumin, NAR, and odor identification. Significant positive correlations were found between NAR and nasal stuffiness and between eosinophils, basophils, and neutrophils and both eosinophilic cationic protein and albumin. CONCLUSION: Subjective measures of SAR were significantly improved in the mometasone furoate group by comparison with placebo-treated patients. Objective assessments supported the subjective findings because within-treatment measures were frequently significantly improved after mometasone furoate treatment but not after placebo treatment.

Prevalence and assessment of qualitative olfactory dysfunction in different age groups.

The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.

Smell impairment. Can it be reversed?

Patients who have lost the sense of smell usually come to a doctor on their own, reporting loss of the sense of taste. Inflammation (often due to allergy), viral infection, and head trauma are common causes of olfactory disturbance. History taking may provide clues to these and other problems (eg, toxin exposure, congenital dysosmia). Workup should not begin until a standardized test has been given that established impairment of the sense of smell. The only truly reversible cause is inflammation, which is confirmed when smell returns after a course of corticosteroid. Sinus computed tomography is necessary to view the olfactory cleft; lack of obstruction indicates that smell impairment is nonreversible. Patients deserve an explanation for their disorder and a prognosis. If restoration of their sense of smell is unlikely, patients should be cautioned to take steps to ensure safety in regard to such dangers as gas leaks, smoke, and spoiled foods.

Histamine levels and nasal cytology in children with chronic otitis media and rhinitis.

OBJECTIVE: Nasal and middle ear diseases are frequent health problems for young children. In some of these patients, allergic reactions may be contributing factors. The objective of this study was to determine whether the histamine level in nasal mucosal scrapings may be used as a marker for this subset of children. METHODS: A total of 50 children, aged 2 through 7 years, was categorized into five groups of ten subjects as: normal, allergic rhinitis, nonallergic rhinitis, allergic with otitis media and nonallergic with otitis media by history, physical examination, allergy skin testing, nasal cytology, and tympanometry. Nasal mucosal scrapings were obtained using the Rhino-probe technique. Eosinophils, basophilic cells, neutrophils, and bacteria in nasal cytograms were quantified. Histamine levels were measured by radioimmunoassay, the values normalized to the total protein content assayed by enzyme-linked immunoassay, and expressed in pcg/micrograms of total protein. RESULTS: The mean histamine level for each group was: normal = 0.20, allergic rhinitis = 10.14, nonallergic rhinitis = 0.13, allergic with otitis media = 5.34, nonallergic with otitis media = 0.24 pcg/micrograms of total protein. Mean levels of histamine were statistically significantly higher in the allergic groups than in the nonallergic and normal groups (P < .05). Allergic groups had significantly more eosinophils and basophilic cells in the nasal cytograms than the nonallergic groups. By contrast, the cytograms of children with nonallergic rhinitis and nonallergic otitis had significantly more neutrophils than the normal and allergic groups. CONCLUSION: We conclude that measuring histamine in nasal mucosal scrapings could be useful in the evaluation of young children with rhinitis and otitis and in determining which patients may have allergic disease.

Oronasal reconstruction with local mucoperiosteal and free latissimus dorsi flaps.

We describe the use of maxillary sinus mucoperiosteum as a pedicled flap to reconstruct the floor of the nose following resection of cancer involving the palate, buccal mucosa, and mandible. Complete inferior turbinectomy allows access to the roof of the maxillary sinus to harvest the mucoperiosteum as a vascularized flap pedicled under the remaining middle turbinate. A free latissimus dorsi myocutaneous flap suspended from the floor of the orbit and nasal septum is then used to obliterate the maxillary sinus, reconstruct the palate, and support the floor of the nose. A reconstruction employing this combination of flaps is presented, including postoperative endoscopic intranasal photography and magnetic resonance imaging. Despite the elevated level of the floor of the nose and the absence of the inferior turbinates, rhinomanometry performed 3 months postoperatively demonstrates adequate nasal airflow with normal responses to nasal decongestants.

The rhinologic evaluation of Alzheimer's disease.

Olfactory dysfunction is currently not listed among the NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease. There is a large amount of psychophysical and neuropathologic evidence to suggest that patients with Alzheimer's type dementia have olfactory system abnormalities. The rhinologic status of this group has not been characterized. The authors examined 21 Alzheimer's patients and 21 age-matched controls to determine whether 1. the Alzheimer's group, in fact, had a diminished sense of smell, and whether 2. rhinologic factors were responsible for this nasal dysfunction. The findings support a neurologically mediated phenomenon as the cause for significant impairment in olfactory function in patients with probable Alzheimer's disease.

Rapid detection of respiratory syncytial virus in nasopharyngeal specimens obtained with the rhinoprobe scraper.

We compared the Rhinoprobe scraping technique for collection of superficial nasal mucosa epithelial cells and rapid detection of respiratory syncytial virus by immunofluorescence with paired, swab-collected specimens for virus culture from 1,257 infants and children with acute respiratory infections. Compared with viral culture as the reference test, the sensitivity, specificity, and accuracy of the immunofluorescence test were 83.6, 93.6, and 91.3%, respectively. We found the Rhinoprobe method safe, easy to use, and helpful in obtaining large quantities of epithelial cells for detection of respiratory syncytial virus and other respiratory viruses.

Peroxidase-antiperoxidase assay for rapid detection of respiratory syncytial virus in nasal epithelial specimens from infants and children.

A peroxidase-antiperoxidase (PAP) assay for the rapid detection of respiratory syncytial virus was compared with the indirect immunofluorescence method and with viral culture. Nasal epithelial specimens from 147 infants and children with acute respiratory infections were obtained and evaluated for the presence of respiratory syncytial virus antigens. Sensitivity, specificity, and accuracy by PAP were 91.7, 84.8, and 87.1%, respectively, and 87.0, 88.5, and 88.0%, respectively, by immunofluorescence compared with viral culture. The PAP assay was found to be as accurate as the indirect immunofluorescence method and more convenient to perform, since the color reaction and cell morphology were more easily observable by light microscopy. A new specimen collection method is reported; gentle scraping of the superficial nasal mucosa by the Rhino-probe method provided sufficient numbers of epithelial cells to perform multiple assays.

Normal nasal cytology in infancy.

Nasal cytology in the first year of life has rarely been utilized diagnostically because of an early report that nasal eosinophilia is a common finding in normal young infants. Using an improved sampling technique with a flexible nasal probe, we obtained nasal mucosal specimens for histologic examination from 22 healthy infants and five infants with upper respiratory tract infections. None of the healthy infants had nasal eosinophilia and no adverse effects were noted during the sampling procedure. We concluded that the present sampling technique is as safe and effective in infants as in children and adults and that the majority of healthy young infants do not have nasal eosinophilia.

Surgery for nasal obstruction--evaluation by rhinomanometry.

Nasal obstruction is predominantly a subjective patient complaint. The physical examination of the nose for nasal obstruction is a subjective evaluation as well. While the history and physical examination are reasonable diagnostic indicators, an objective means of evaluation is needed. Rhinomanometry measures nasal obstruction objectively and reliably. Thirty-six patients with nasal obstruction were evaluated by rhinomanometry before and after nasal surgery. The results are reported here. Rhinomanometry confirms the effectiveness of intranasal surgery. Using rhinomanometry, various techniques of intranasal surgery are evaluated, and several interesting observations are made.

Distribution of specific ventilation in cystic fibrosis.

Continuous distributions of specific tidal ventilation were recovered from nitrogen washouts in 29 patients with cystic fibrosis and 22 normal subjects along with other pulmonary parameters to assess the utility of the recovered distribution in describing the progress of the disease. Normal subjects showed predominantly unimodal distributions of a pattern showing a small amount of ventilation going to units with high specific ventilation. Multimodal distributions were the rule in the cystic population with only subjects with normal pulmonary function having unimodal distribution.

The in vitro effect of levamisole on lymphocyte proliferation, polymorphonuclear leucocyte chemotaxis, basophil histamine release and platelet serotonin release in patients with atopic dermatitis.

The in vitro effect of levamisole (LMS) on lymphocyte, neutrophil, basophil and platelet function was investigated in patients with severe atopic dermatitis and hyperimmunoglobulinaemia E. Lymphocyte stimulation by several concentrations of PHA, con A and PWM, polymorphonuclear leukocyte chemotaxis and basophil histamine release were unaffected by LMS (10 micrograms/ml). Platelet serotonin release induced by iodipamide was decreased in patient and control groups by LMS but release induced by methacholine, epinephrine and thrombin was not.

Continuous distributions of specific ventilation recovered from inert gas washout.

We describe a new technique for recovering continuous distributions of ventilation (V) as a function of tidal ventilation/volume ratio (V/V0) from the nitrogen washout. The analysis yields a continuous distribution of V as a function of V/V0 represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: a) the distributions of young, normal subjects were narrow and unimodal with a mean ln standard deviation of 0.56 plus or minus 0.13; b) those of subjects over age 40 were broader (ln SD 0.86 plus or minus 0.19) with more poorly ventilated units; c) patients with pulmonary disease of all descriptions showed enlarged dead space; d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and e) patients with obstructive lung diseases fell into several classes, three of which are illustrated. These results suggest that our approach is well suited for clinical investigation.

Distribution of red and white blood cells in alveolar walls.

Dog lungs were perfused with blood and rapidly frozen with liquid Freon gas at various pulmonary artery and venous pressures. The numbers of red and white blood cells per mm-2 of alveolar wall were counted in lung sections and, in addition, the proportion (by area) of the wall occupied by the cells was measured by point counting. The number and proportional area of the red blood cells rapidly increased as perfusing pressure was raised. These findings are consistent with earlier observations of capillary recruitment and distension. An unexpected observation was the large number of leukocytes in the capillaries especially at low perfusing pressures. For example when arterial exceeded alveolar pressure by 5 cmH2O (as occurs near the apex of the upright human lung), there were about 5,000 red cells and 4,000 white cells per mm-2 of alveolar wall. As perfusing pressure was increased, the number of leukocytes paradoxically decreased in zone 3 but remained constant in zone 2. Most of the white cells were mononuclear cells. These results suggest that the lung behaves as a mechanical sieve for large cells and that the number of trapped cells depends on the capillary pressure.