Combining olfactory test and motion analysis sensors in Parkinson's disease preclinical diagnosis: a pilot study.

OBJECTIVES: Preclinical diagnosis of Parkinson's disease (PD) is nowadays a topic of interest as the neuropathological process could begin years before the appearance of motor symptoms. Several symptoms, among them hyposmia, could precede motor features in PD. In the preclinical phase of PD, a subclinical reduction in motor skills is highly likely. In this pilot study, we investigate a step-by-step method to achieve preclinical PD diagnosis. MATERIAL AND METHODS: We used the IOIT (Italian Olfactory Identification Test) to screen a population of healthy subjects. We identified 20 subjects with idiopathic hyposmia. Hyposmic subjects underwent an evaluation of motor skills, at baseline and after 1 year, using motion analysis sensors previously created by us. RESULTS: One subject showed significant worsening in motor measurements. In this subject, we further conducted a dopaminergic challenge test monitored with the same sensors and, finally, he underwent [123 I]-FP/CIT (DaTscan) SPECT brain imaging. The results show that he is probably affected by preclinical PD. CONCLUSIONS: Our pilot study suggests that the combined use of an olfactory test and motor sensors for motion analysis could be useful for a screening of healthy subjects to identify those at a high risk of developing PD.

Analysis of voice in patients with untreated active acromegaly.

BACKGROUND: Voice changes are common clinical findings of acromegaly, although scanty data are available so far. OBJECTIVE: To analyze features and quantify changes of voice in patients with untreated active acromegaly. DESIGN AND METHODS: This was a pilot case-control study. Voice was analyzed using the Multi Dimensional Voice Program software, which generates 33 parameters related to fundamental frequency (F0), micro-perturbation of F0 and amplitude, noise, tremor, voice breaks and irregularities, and diplophony. PATIENTS: Thirteen consecutive patients (8 women, 5 men, mean age 48+/-9 yr) with active acromegaly, at first diagnosis, and 13 sex- and age-matched normal subjects (controls). RESULTS: Patients with untreated active acromegaly had mean values of parameters related to F0 significantly lower than those of controls, although mostly remaining in the normal range. Most acromegalic patients had micro-perturbation of F0, as indicated by higher mean of absolute or percentage jitter values than those of controls; micro-perturbation of amplitude was a common feature of voice in most acromegalic men. Noise-related parameters were also affected by acromegaly, being higher in male acromegalic patients than in controls and acromegalic women. On the contrary, parameters related to tremors, voice breaks, voice irregularities and diplophony did not differ in acromegalic patients and controls. CONCLUSIONS: Patients with untreated active acromegaly had low-pitched voice characterized by lowering F0 and increased values related to noise, micro perturbation of frequency, and amplitude.

Possible association between thyroid autoimmunity and Menière's disease.

Various aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear-vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66.7% TPO-Ab and 33.3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66.7% TPO-Ab and 33.3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0.0001 versus group A and group B) had significant autoantibody levels (68.4% TPO-Ab; 15.8% TPO-Ab + TR-Ab; 10.5% Tg-Ab; 5.2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.

Fiberoptic endoscopic evaluation of swallowing (FEES): proposal for informed consent.

Fiberoptic endoscopic evaluation of swallowing (FEES) is now a first choice method for studying swallowing disorders on account of the various advantages it offers: easy to use, very well tolerated, allows bedside examination and is economic. Nevertheless, this diagnostic procedure is not without risks, the most probable consequences of which include discomfort, gagging and/or vomiting, vasovagal syncope, epistaxis, mucosal perforation, adverse reactions to topical anaesthetics and laryngospasm. The risks involved with FEES stress the importance of informing the patient of these; this is an important aspect in medicine that necessarily and immediately implies receiving the patient's so-called "informed consent". Informed consent should be obtained not only by means of specific printed forms but also after the patient has had an interview with the physician who will be performing the procedure and who will offer information according to the personal clinical, psychological, cultural and linguistic situation of the patient and in keeping with the type of procedure proposed. In the case of FEES, as with other invasive or non-invasive diagnostic procedures, therefore, routine written and signed consent, together with a patient/physician interview should fulfil what is known as "complete information". In this report, a specific form for informed consent to FEES procedures, is proposed.

Swallowing disorders: proposal of a method for forensic medicine assessment.

For a correct classification of dysphagia, morphologic instrumental investigations capable of analysing the anatomical structures of the digestive tract, are undoubtedly essential, but the most important investigations are the functional investigations, such as videofluoroscopy, fiberoptic endoscopic evaluation of swallowing, oro-pharyngo-oesophageal scintigraphy, manometry and pH-metry. Results of these examinations enable us to identify, in patients with dysphagia, the extent of permanent damage, as a consequence of injury to the structures designated to swallowing, must be such that it at least minimally impairs and decreases the relative function, but to a degree that can be detected and, in some manner, measured. From a legal point of view, alterations in swallowing, caused by damage to structures belonging to the respiratory-digestive tract, can be found in crimes against persons and particularly in those involving body injury. In the case of civil, but also in private or social insurance proceedings, it is necessary to distinguish which parameters are to be used as reference for evaluating and quantifying the injury in terms of reimbursement. With the introduction of complete biological well-being, injury is considered as an impairment of the worth and right to enjoy psychological-physical integrity as a quality of life. The criteria currently used internationally take into account the conception of psychological-physical efficiency; nevertheless, in Italian forensic medicine, there is no table that offers a thorough quantification of swallowing modifications, if one excludes oesophageal disorders. Herewith, an evaluation table, dividing oro-pharyngo-oesophageal dysphagia into five, progressively serious classes, is proposed.

Clinical applications of oro-pharyngo-oesophageal scintigraphy in the study of dysphagia.

The diagnostic approach to patients with dysphagia is well established and relies mainly on videofluoroscopy and endoscopy. Oro-pharyngo-oesophageal scintigraphy permits both a functional and a semi-quantitative study of the various stages of swallowing. Moreover, by means of this investigation, it is possible to estimate the amount of inhaled bolus. Oro-pharyngo-oesophageal scintigraphy with 99mTc-nanocolloid has been found to be easy to use, economical, well tolerated and, supplying precise indications regarding the extent of the swallowing disorder, then permits a better clinical definition of the patient. The limitations of swallowing scintigraphy are: poor definition in visualizing anatomic structures and low specificity when used as the only diagnostic test. Scintigraphy plays an important role in the diagnosis and follow-up of dysphagia, and its use, together with other diagnostic techniques, increases diagnostic accuracy. In this study, the role of oro-pharyngo-oesophageal scintigraphy has been analysed in patients with post-surgical, neurological and oesophageal dysphagia.

Paradoxical vocal cord dysfunction: clinical experience and personal considerations.

Paradoxical vocal cord dysfunction is a nosographic entity that remains to be fully elucidated as far as concerns criteria required for diagnosis and underlying aetiopathogenesis. The disorder manifests with repeated episodes of acute dyspnoea associated with a series of symptoms that may include hoarseness, globus, chest pain and "shortness of breath". A retrospective analysis of cases with acute dyspnoea referred to our Department between June 2004 and June 2005 revealed 3 patients with paradoxical vocal cord dysfunction. In 2 of these 3 cases, concomitant psychiatric morbidity was observed and the third also presented gastro-oesophageal reflux. In one patient, the episodes of dyspnoea were triggered by inspiration of irritating substances. Diagnosis of the condition requires a high level of suspicion, which is confirmed by a laryngoscopic investigation that demonstrates hyperadduction of the true vocal cords and a reduction of at least 50% in the breathing space. From a therapeutic point of view, patients with paradoxical vocal cord dysfunction require, in our opinion, a multidisciplinary approach; in fact, only a team comprising otorhinolaryngologists, phoniatricians, pulmonologists, neurologists, allergologists, psychotherapists and speech therapists is capable of defining the appropriate treatment according to the clinical and psychological characteristics of each individual patient. Our results with speech therapy, focused on respiratory and speech retraining, are reported.

The endoscopic evaluation of the oral phase of swallowing (Oral-FEES, O-FEES): a pilot study of the clinical use of a new procedure.

Oral FEES (O-FEES) is an endoscopic procedure conceived to directly visualise the oral phase of swallowing. In the perspective of clinical use, the feasibility, safety and acceptability of O-FEES has been evaluated. Subsequently, the procedure was compared with the radiological gold standard. The acceptability of O-FEES was compared to that of FEES using a 10 point questionnaire submitted to a sample of 52 outpatients complaining of swallowing disorders. Repeated measure analysis of variance (rm-ANOVA) models were used to test the mean difference of acceptability in the same subjects after FEES and O-FEES. Subsequently, another sample of 8 male outpatients underwent a simultaneous O-FEES and videofluoroscopic study (VFSS). The inter-rater reliability using 10 radiological landmarks, compared to O-FEES, was blindly determined between two raters. Inter-rater agreement between the two judges for O-FEES and VFSS scores was assessed with the single score intra-class correlation coefficient (ICC). Differences between FEES and O-FEES answers for each question and among all the items considered overall were statistically significant (rm-ANOVA; F-statistic p < 0.001). The inter-rater agreement concerning endoscopic and radiological evaluations between the two raters showed strong values of intra-class correlation coefficient (ICC) (95% confidence interval): 0.875 (0.373-0.979) and 0.921 (0.542-0.986), respectively. The Bland-Altman test showed a bias of -0.24 (95% limits of agreement; -1.77 to +1.19), which suggests that both methods produced almost identical results. In clinical practice and compared with FEES, O-FEES is a well tolerated and safe procedure. Compared with the radiological gold standard, O-FEES offers reliable information about oral preparation and oral propulsion of the bolus.

Stabilometric findings in patients affected by organic dysphonia before and after phonomicrosurgery.

The purpose of this study is to understand if there is any alteration in the posture of patients affected by organic dysphonia and describe possible postural modifications after phonomicrosurgery on the vocal folds. Forty subjects (22 males, 18 females; mean age 32.6 ± 7.5 years) suffering from organic dysphonia (15 cases of polyps, 11 submucosal retention cysts, 10 bilateral fibrous vocal fold nodules and 4 bilateral Reinke's oedema) were examined by open-eye and closed-eye posturography while breathing spontaneously before surgery, 24 hours after surgery and after 6 months. The variables taken into account were: the coordinates of the centre of pressure on both frontal and sagittal planes, length and surface of the track, mean velocity of the oscillations and relative standard deviations, spectral analysis of oscillation frequency, statokinesigram and stabilogram values. No characteristic pathological pattern was seen in basal stabilometry in any of the subgroups (polyps, cysts, Reinke's oedema). Only the subgroup of patients with fibrous vocal fold nodules (8/10; 80%) showed a slight forward shift from the centre of gravity when analysed in both open-eye and closed-eye posturography. A comparison performed within the same subgroup using open-eye and closed-eye posturography before and after surgery revealed no significant difference in any of the parameters being studied. The use of static stabilometry in this study demonstrates the absence of characteristic postural alterations in patients affected by organic dysphonia and also excludes that simple removal of the vocal fold lesion can change posture.

Comparison between videofluoroscopy, fiberoptic endoscopy and scintigraphy for diagnosis of oro-pharyngeal dysphagia.

The purpose of this study was to compare videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngo- oesophageal scintigraphy (OPES) with regards to premature spillage, post-swallowing residue and aspiration to assess the reliability of these tests for detection of oro-pharyngeal dysphagia. Sixty patients affected with dysphagia of various origin were enrolled in the study and submitted to VFS, FEES and OPES using a liquid and semi-solid bolus. As a reference, we used VFS. Both the FEES and the OPES showed good sensitivity with high overall values (≥ 80% and ≥ 90% respectively). The comparison between FEES vs VFS concerning drop before swallowing showed good specificity (84.4% for semi-solids and 86.7% for liquids). In the case of post-swallowing residue, FEES vs VFS revealed good overall validity (75% for semi-solids) with specificity and sensitivity well balanced for the semi-solids. OPES vs. VFS demonstrated good sensitivity (88.6%) and overall validity (76.7%) for liquids. The analysis of FEES vs. VFS for aspiration showed that the overall validity was low (≤ 65%). On the other hand, OPES demonstrated appreciable overall validity (71.7%). VFS, FEES and OPES are capable of detecting oro-pharyngeal dysphagia. FEES gave significant results in the evaluation of post-swallowing residues.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

Inflammatory mediators and eosinophilia in atopic and non-atopic patients with nasal polyposis.

Nasal polyps are characterized by eosinophilic infiltration and presence of inflammatory mediators, such as total IgE, eosinophil cationic protein (ECP) and cytokines. The role of atopy in nasal polyp pathogenesis is still unclear. Therefore, we evaluated serum IgE levels, nasal mucus concentrations of ECP and cytokines and the number of infiltrating eosinophils in nasal tissue of polyps from atopic and non-atopic patients. Samples were obtained from a randomized population of 31 patients with nasal polyposis having endonasal sinus surgery and of 13 control subjects undergone corrective surgery of the nasal septum. On the basis of medical history of allergy, positive skin-prick tests and total IgE levels, patients with polyposis were divided in atopic (n = 13) and non-atopic (n = 18) patients. We determined levels of IgE in blood, ECP and cytokines (IL-4, IL-6, IL-8, IFN-gamma and IL-2) in nasal mucus, and number of infiltrating eosinophils in nasal tissue. The concentrations of total IgE, ECP, IL-4 and IL-8 and eosinophilia were significantly higher in all patients with nasal polyps compared with controls. Inside, all patients with nasal polyposis showed lower levels of IL-6, IFN-gamma and IL-2 compared with controls. The atopic patients showed significant differences when compared with non-atopic patients for the higher concentrations of total IgE (698.80+/-322.24 vs. 279.63+/-234.11; P < 0.0001) and IL-8 (1437.2 pg/ml+/-1250.7 vs. 605.5 pg/ml+/-481.1; P < 0.015). These findings suggest that inflammation still remains the major factor in the etiology of nasal polyposis and show different levels of inflammatory mediators into atopic and non-atopic patients.

The value of oropharyngoesophageal scintigraphy in the management of aspiration into the tracheobronchial tree in neurological patients.

AIM: Dysphagia and bolus aspiration are two of the most frequent and invalidating symptoms of various neurological diseases. Swallowing disorders often lead to tracheobronchial aspiration with consequent pneumonia episodes. Aspiration pneumonia per se constitutes the most frequent cause of death in these patients, with mortality rate ranging from 20% to 62%. Oropharyngoesophageal scintigraphy (OPES) permits functional quantitative assessment of the different stages of swallowing, together with the detection and quantitative measurement of bolus aspiration. In this work, we analyzed the role of OPES in patients with different neurological conditions to evaluate swallowing and to detect and quantify bolus aspiration. MATERIAL AND METHODS: We enrolled 43 neurological patients (25 women and 18 men, mean age 67.3±12.4 yr) complaining of dysphagia with suspected inhalation. All patients underwent OPES with (99m)Tc-nanocolloid using a liquid bolus first, followed by a semi-solid bolus. We evaluated the following parameters: Oral, Pharyngeal and Esophageal Transit Time, Oro-Pharyngeal Retention Index, Esophageal Emptying Rate, and Aspiration Rate (% AR). RESULTS: OPES detected some airway aspiration in 26/43 patients. 19 patients had tracheal aspiration (with a mean 18.1% AR) and the remaining 7 patients had bilateral broncho-pulmonary aspiration (mean 44.9% AR). CONCLUSIONS: OPES is a feasible, repeatable and noninvasive method that allows quantitative assessment of bolus aspiration into the tracheobronchial tract, thus representing a useful and accurate tool to guide the most appropriate treatment and to monitor response to therapy in neurological patients with dysphagia.

Mucus of the human olfactory epithelium contains the insulin-like growth factor-I system which is altered in some neurodegenerative diseases.

Growth factors are believed to be involved in the mitotic regulation of the animal olfactory epithelium (OE). We investigated mucus covering the human OE area to see if it contained the insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) and to examine their behaviour in neurodegenerative diseases. Thirty patients with idiopathic late onset cerebellar ataxia (ILOCA), Parkinson's disease, and amyotrophic lateral sclerosis (ALS) and 30 age- and sex-matched healthy subjects were studied. In 10 controls, we also analyzed the mucus of the respiratory mucosa of the nose and tears. We detected IGF-I in the mucus covering the OE and Western ligand blot analysis (WLB) showed IGFBPs with an apparent Mr of 41, 500/38,500, 34,000 and 24,000, which were immunoprecipitated by specific antisera to IGFBP-3, -2 and -4, respectively. Their levels were higher than those observed in the respiratory mucosa of the nose or in tears. Mucus of the OE of the patients contained significantly reduced levels of IGF-I in comparison with those of controls. The intensity of all the IGFBPs-related bands were reduced in the ILOCA, while the remaining patients had a loss in the amounts of IGFBP-3. Plasma IGF-I and IGFBPs levels were similar in patients and controls. In conclusion, our data show that mucus covering the human OE contains IGF-I and IGFBPs, suggesting that these factors have a role in the activity of the OE. The amounts are reduced in the patients' mucus, possibly reflecting a dysfunction of the OE itself.

Homing experiments on pigeons subjected to bilateral destruction of the paratympanic organ

The paratympanic organ (PO) in birds is a specialised sensory organ whose function is still unknown. G. Vitali, who first described the PO from observations of the behaviour of PO-lesioned pigeons, proposed that this organ was needed to maintain normal wing muscle function and called it the 'organ of flight'. This interpretation has since been disputed. To solve this controversy and to test whether the PO is involved in flight and navigation, we performed release tests on homing pigeons subjected to bilateral destruction of this organ. No impairment of either flight or navigation was observed in the lesioned pigeons.

Cytokine secretion in nasal mucus of normal subjects and patients with allergic rhinitis.

Allergic rhinitis is regulated by the local production and release of several cytokines. The levels of Th2 cytokines IL-4, IL-6, IL-10 and the Th1 cytokine IFN-gamma were studied in nasal mucus from 30 subjects with allergic rhinitis and 45 non-atopic healthy controls. In this study a sampling technique for collecting nasal mucus, well tolerated by the subjects and with a minimal stimulation of the mucosa, was performed. The cytokine concentrations in nasal mucus samples were detected and quantitated by a new paramagnetic particle-based immunofluorescent assay system more sensitive than the conventional ELISA techniques. The new technique showed reliable values of the measured parameters. The nasal mucus from allergic patients contained significantly higher concentrations of IL-4 (25.5 +/- 3.6 pg/ml; P < 0.001) and IL-10 (1300 +/- 190 pg/ml; P < 0.05) compared to the nasal mucus from control subjects (15.2 +/- 2.3 and 532 +/- 28 pg/ml, respectively, for IL-4 and IL-10). No significant modification in IFN-gamma levels of allergic patients was found when compared to control group (respectively, 19.9 +/- 3.3 vs. 25.7 +/- 5.1 pg/ml; P > 0.05). Moreover, the allergic patients showed lower levels of IL-6 concentrations in the nasal mucus compared to control subjects (64.8 +/- 9.1 vs. 129.0 +/- 18.1 pg/ml; P = 0.0099). These data can be interpreted by the hypothesis that in response to environmental allergens there is a preferential Th2 polarity by activated CD4+ T cells and that the cytokines IL-6 and IL-10 have, respectively, an important anti-inflammatory and counterregulatory action in the pathogenesis of allergic rhinitis.

Ultracytochemical localization of the NADPH-d activity in the human nasal respiratory mucosa in vasomotor rhinitis.

OBJECTIVES: Description of the ultrastructural localization of nitric oxide synthase in the blood vessels of the nasal respiratory mucosa in patients with vasomotor rhinitis. STUDY DESIGN: This research was conducted on seven patients--men and women, ages 20 to 45 years--suffering from vasomotor rhinitis and who had undergone surgical therapy for reduction of the inferior turbinates. METHODS: To study the ultrastructural localization of nitric oxide synthase, NADPH-diaphorase cytochemistry was employed. Samples of the nasal mucosa were obtained from inferior turbinates. RESULTS: The endothelial cells of the arterioles, capillaries, venules and cavernous sinuses revealed a distribution of the enzymatic activity similar to that found in unaffected subjects. A strong enzymatic activity was recognized in the smooth muscle cells of the cavernous sinuses. The smooth muscle cells of arterioles and venules were generally found to be negative to enzymatic reaction. CONCLUSIONS: This study suggests that the vascular disorders of the vasomotor rhinitis depend, at least in part, from nitric oxide synthase induction in the smooth muscle cells of the cavernous sinuses.

Menière's disease: role of antibodies against basement membrane antigens.

Recently, high levels of anti-collagen II (CII) antibodies have been found in a significant percentage of patients with Menière's disease (MD). An immune response against other collagens (C) present in the basal membranes has also been suggested by the presence of anti-CIV and anti-laminin antibodies in a number of instances of progressive systemic sclerosis (PSS) and Raynaud's phenomenon (RP). The aim of the present study was to measure the levels and frequency of anti-CI, -CII, -CIV, -CV, and anti-laminin antibodies by enzyme-linked immunosorbent assay (ELISA) in 45 patients affected by MD, 24 patients with PSS, 24 patients with RP, and 25 normal subjects. Immunoglobulin G (IgG) anti-CII antibodies were detected in 15.5% of MD sera, and 6.6% of MD sera were positive on CV, 11.1% were positive on laminin, 4.4% were positive on CI, and 4.4% were positive on CIV. A low incidence of anti-CI, -CII, -CIV, -CV, and antilaminin antibodies was found. Positive sera did not react on immunoblot with peptides obtained by cyanogen bromide (CNBr) digestion of CII. These results contrast with those of Yoo, et al.; differences in the washing procedure used and in the ethnic background of the patients may explain this divergence. Our results would seem to indicate that autoimmune responses do not play a role in the pathogenesis of MD.

Distribution of 3-nitrotyrosine in the nasal polyps of atopic patients.

OBJECTIVE: To investigate whether formation of nitrotyrosine in the nasal polyps of atopic patients occurs. STUDY DESIGN: A nonrandomized, retrospective, controlled qualitative and quantitative study. METHODS: Nasal polyp tissue samples were acquired from 12 atopic patients. Control fragments of nasal mucosa were taken from 10 patients undergoing corrective surgery of the nasal septum. For routine histologic examinations, hematoxylin-eosin staining was used. Low-magnification microscopy was designed to yield pathologic characteristics and high magnification to quantify the number of eosinophils in the subepithelial connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical method. RESULTS: Hematoxylin-eosin staining revealed presence of numerous eosinophils in the epithelium and in the subepithelial connective tissue. All polyps were characterized by epithelial damage. Nitrotyrosine was present in the eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet cells, glands, and vessels were found to be negative. No significant differences concerning the localization of nitrotyrosine were recognized among the examined nasal polyps. CONCLUSIONS: Nitrotyrosine immunohistochemical staining in nasal-polyp tissues suggested the existence of progressive epithelium injury caused by peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to be precisely established. The lack of nitrotyrosine in glands and blood vessels indicated that peroxynitrite does not have a significant role in the vascular and glandular dysfunction of nasal polyps.

Kartagener's syndrome and rheumatoid arthritis: an unusual association.

We report the case of a 66-year-old caucasian woman affected by Kartagener's syndrome (KS), a genetically transmitted disorder characterised by situs viscerum inversus, bronchiectasis and sinusitis, who also developed rheumatoid arthritis (RA). The impaired mucociliary function typical of KS caused recurrent paranasal sinus and lung infections, as shown by CT scans of the sinuses and chest. The coexistence of KS and RA in our patient was probably accidental. Given the small number of patients in whom an association of the two disorders has been described, it is impossible to establish whether KS might play a role in the pathogenesis of RA.