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Purpose Exercise-induced laryngeal obstruction (EILO) is relatively common in young people. Treatment rests on poor evidence; however, inspiratory muscle training (IMT) has been proposed a promising strategy. We aimed to assess laryngeal outcomes shortly after IMT, and to compare self-reported symptoms with a control group 4–6 years later. Methods Two groups were retrospectively identified from the EILO-register at Haukeland University Hospital, Norway; one group had received only information and breathing advice (IBA), and another additionally IMT (IBA + IMT). At diagnosis, all participants performed continuous laryngoscopy during exercise (CLE), with findings split by glottic and supraglottic scores, and completed a questionnaire mapping exercise-related symptoms. After 2–4 weeks, the IBA + IMT-group was re-evaluated with CLE-test. After 4–6 years, both groups were re-assessed with a questionnaire. Results We identified 116 eligible patients from the EILO-register. Response rates after 4–6 years were 23/58 (40%) and 32/58 (55%) in the IBA and IBA + IMT-group, respectively. At diagnosis, both groups rated symptoms similarly, but laryngeal scores were higher in the IBA + IMT-group (P = 0.003). After 2–4 weeks, 23/32 in the IBA + IMT-group reported symptom improvements, associated with a decrease of mainly glottic scores (1.7–0.3; P Conclusion Self-reported EILO symptoms had improved after 4–6 years, irrespective of initial treatment. Full symptom resolution was rare, suggesting individual follow-up should be offered.

Objective Gradual impairment of nerve conduction is expected to be tightly associated with simultaneous gradual loss of vocal cord contractility, related to the fact that injured axons are connected to a defined number of muscle cells. In clinical studies, there is a time gap between observed adverse electromyographic (EMG) changes and examination of vocal cord function. This study evaluates the impact of intraoperative EMG changes on synchronous vocal cord contractility by simultaneous use of continuous intraoperative neuromonitoring (C-IONM) and accelerometry for registration of actual vocal cord function at a given change of EMG amplitude. Methods EMG was obtained following vagus nerve stimulation by use of C-IONM. A vocal cord accelerometer probe that could be attached to the vocal cords was developed based on a LIS3DH ultra low-power high performance three axis linear accelerometer (STMicroelectronics, Geneva, Switzerland). Accelerometer data were registered continuously together with EMG data during traction injury of the recurrent laryngeal nerve (RLN) until an amplitude depression ≤100 μV. Results Six RLN from four immature domestic pigs were studied. Vocal cord contractility assessed by vocal cord accelerometry decreased in parallel with EMG amplitude, with significant correlations ranging from 0.707 to 0.968. Conclusion Decrease of EMG amplitude during traction injury to the RLN injury is closely associated with a parallel drop in vocal cord contractility. Level of evidence NA Laryngoscope, 130:1090-1096, 2020.

Respiratory distress during exercise can be caused by exercise-induced laryngeal obstruction (EILO). The obstruction may appear at the level of the laryngeal inlet (supraglottic), similar to supraglottic collapse observed in infants with congenital laryngomalacia (CLM). This observation has encouraged surgeons to treat supraglottic EILO with procedures proven efficient for severe CLM. This article summarizes key features of the published experience related to surgical treatment of EILO. Supraglottoplasty is an irreversible procedure with potential complications. Surgery should be restricted to cases where the supraglottic laryngeal obstruction significantly affects the quality of life in patients for whom conservative treatment modalities have failed.

Patients with voice-related disorders are ideally treated by a multidisciplinary team. Acoustic voice analysis and patient-reported outcome measures are recommended parts of the clinical assessment. The present paper aims at further documenting the importance of acoustic voice analyses, maximum phonation time (MPT) and Voice Handicap Index (VHI) into clinical investigations.The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation (N = 19 various excluded)) were included consecutively at the outpatient laryngology clinic at Haukeland University Hospital. In addition, a control group of 98 healthy subjects were included.Voice samples, MPT, and the VHI scores in addition to standard clinical information were obtained. Acoustic analyses were performed from these samples determining level of jitter, shimmer and Noise-to-Harmonic ratio (NHR) as well as analyzing frequency of a prolonged vowel.Jitter, shimmer, and NHR scores correlated strongly (r ≈ 0.8; P0.001) to each other. By Analysis of Variance analyses, we have determined significant dependence on diagnostic group analyzing all the obtained acoustic scores (all P0.001). All patient groups but the dysfunctional group scored to some extent worse than the control group (mostly at P0.001). In addition, jitter scores from dysfunction group were lower than recurrent palsy group (P0.05) and shimmer scores were lower among dysfunctional than the cancer group (P0.05). Regarding NHR the cancer patients scored higher than the degenerative/inflammatory group (P0.05). The cancer group scored with longer MPT than the degenerative/inflammatory (P0.001) and recurrent palsy groups (P0.05).Among larynx disease patients acoustic and MPT analyses segregated with all determined analyses between patients and control conditions except the dysfunctional group, but also to some extent between various patient groups. VHI scores correlated to jitter, shimmer and NHR scores among cancer and degenerative/inflammatory disease patients. Acoustic analyses potentially add information useful to laryngological patient studies.

Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation.

The aim of this study is to determine to what extent the Voice Handicap Index-Norwegian (VHI-N) is scored depending on specific laryngological disease. In a multi-center study, 126 healthy subjects and 355 patients with different voice-related diseases answered the VHI-N. The VHI-N scores showed high Cronbach's alpha. Analyses of variance were performed with VHI-N dependent and specific voice-related disease as independent variable, and showed highly significant dependence by group allocation (F(7,461) = 28.0; p < 0.001). When studying post hoc analyses secondary to this ANOVA analysis, we have shown that the control group scored lower than the entire patient groups (all p < 0.001) except the dysplasia group. Aphonic patients scored higher than all the other groups (all p < 0.001) except those with spasmodic dysphonia. The cancer patient group furthermore scored lower than patient groups with recurrent palsy, dysfunctional disease or spasmodic dysphonia (all p < 0.001). In addition, patients with recurrent palsy scored higher than patients with degenerative/inflammatory disease (p < 0.001). No influences of patient age, gender, or smoking were observed in the VHI-N scores. The VHI-N is a psychometrically well-functioning instrument, also at disease-specific levels and discriminates well between health and voice diseases, as well as between different voice-related diseases. The VHI-N may be recommended to be used when monitoring voice-related disease treatment.

The current follow-up study concerning the supraglottic type of exercise-induced laryngeal obstruction (EILO) was performed to reveal the natural history of supraglottic EILO and compare the symptoms, as well as the laryngeal function in conservatively versus surgically treated patients. A questionnaire-based survey was conducted 2–5 years after EILO was diagnosed by a continuous laryngoscopy exercise (CLE) test in 94 patients with a predominantly supraglottic obstruction. Seventy-one patients had been treated conservatively and 23 with laser supraglottoplasty. The questionnaire response rate was 70 and 100% in conservatively treated (CT) and surgically treated (ST) patients, respectively. A second CLE test was performed in 14 CT and 19 ST patients. A visual analogue scale on symptom severity indicated improvements in both the groups, i.e. mean values (± standard deviations) declined from 73 (20) to 53 (26) (P

The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.

Variable obstruction to airflow at the laryngeal level may cause respiratory distress during exercise. The Continuous Laryngoscopy Exercise (CLE)-test enables direct visualization of the larynx during ongoing exercise. The aims of this study were to establish a scoring system for laryngeal obstruction as visualized during the CLE-test as well as to assess reliability and validity of this scoring system. Continuous video recording of the larynx was performed in parallel with continuous video recording of the upper part of the body, and recording of breath sounds in 80 patients and 20 symptom-negative volunteers, running on a treadmill to respiratory maximal tolerable distress or exhaustion. Each participant scored the degree of symptoms during exercise. The scoring system contains four sub-scores, each graded from 0 to 3. Two independent laryngologists, blinded to clinical data, scored the video recordings of the larynx twice. The proportion of inter- and intra-observer agreement (equal scores) for each sub-score through these four sessions varied between 70 and 100% (weighted kappa values varied from 0.49 to 1.00 correspondingly). A positive correlation was found between CLE-test sum score and symptom score (rho = 0.75, P0.001). There was a significant difference in CLE-test sum score between patients (3.34 +/- 1.34) and volunteers (0.65 +/- 0.66) (P0.001). The single CLE-test sub-score that correlated most strongly with symptom score was glottic adduction at maximal effort (rho = 0.75, P0.001). The presented scoring system is reliable and valid, and we suggest that it can be used when laryngeal function during exercise is evaluated.

A method for combined ergo-spirometry and continuous laryngeal inspection during exercise, entitled continuous laryngoscopy exercise test (CLE-test) has been developed in order to study airway obstruction at the laryngeal level during exercise. The aim of the study was to apply the CLE-test on patients experiencing respiratory distress during exercise in order to reveal the usefulness of the CLE-test both as a diagnostic tool in the selection of patients for surgery and in evaluation of treatment effects postoperatively. Until now, 81 patients with a history of exercise-induced stridor have undergone the CLE-test. Ten of these patients were selected for surgical treatment based on the severity of symptoms and their motivation for treatment. All ten patients underwent endoscopic supraglottoplasty (ES), with laser incision in both aryepiglottic folds anterior to the cuneiform cartilages and removal of the mucosa around the top of the tubercles. Each patient was examined by the CLE-test before and 3 months after surgery. Eight patients felt subjectively that their breathing capacity during exercise was improved. When pre- and postoperative ergo-spirometry evaluations were compared, increased peak oxygen consumption was observed in four out of ten patients and better maximal minute ventilation in seven out of ten. Postoperative evaluation of the laryngeal images showed less prominent aryepiglottic folds. The typical adduction of the supraglottic structures concomitant with inspiratory stridor found preoperatively was not present in any of the patients during exercise postoperatively. The ES procedure is an efficient surgical treatment for exercise-induced laryngeal supraglottic obstruction and the CLE-test eases the selection of patients for surgery and facilitates the evaluation of treatment effects.

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma (HNSCC) patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro augment their secretion of monocyte chemotactic protein-1 (MCP-1). Presently, the aims of the present work were to study whether the metabolic activity, secreted products and/or specific receptor/ligand on the surface of the F-spheroids and monocytes are necessary for stimulation of the monocyte MCP-1 secretion upon F-spheroid co-culture. Actinomycin D (1 mug/ml for 24 h) pre-treatment of the F-spheroids abolished the monocyte MCP-1 co-culture response. Co-culture of monocytes and F-spheroids separated by a semi-permeable membrane showed a decreased, but still present, monocyte MCP-1 co-culture response. Conditioned medium from F-spheroids stimulated allogenous monocytes to secrete MCP-1. The addition of glucose or galactose, but not mannose, to co-cultures partially inhibited the monocyte MCP-1 co-culture response. The addition of anti-CD14 antibody diminished the MCP-1 co-culture response. In conclusion, the monocyte MCP-1 co-culture response is dependent on metabolically active spheroids, secreted stimuli, and is augmented by direct contact with F-spheroids, possibly via lectin-like receptors and the CD14 receptor.

At diagnosis, control patients had the lowest depression levels and anxiety scores, followed by those with limited HNSCC disease and these with extended HNSCC disease. Anxiety and depression levels at diagnosis predicted prognosis via an association with extent of disease. Sense of humor, but not anxiety or depression level, predicted lower QoL and depression levels at follow-up.To study the association between anxiety score, depression level at sense of humor at diagnosis in head and neck squamous cell carcinoma (HNSCC) patients versus TNM stage, prognosis and depression level/quality of life (QOL) 6 years following diagnosis. A control group of patients with benign HN disease was also included.Male patients with newly diagnosed HNSCC (n =78) or benign HN (n =61) disease completed the following questionnaires: the Beck Depression Inventory, the Spielberger Trait Anxiety Inventory (state) and the Svebak humor questionnaire. Patients with cachexia or those aged80 years were excluded. In the HNSCC patients, TNM stage, prognosis and QOL/depression level (n =27) were determined following successful therapy.HNSCC patients reported high anxiety scores and lower depression levels than control patients, although there was overlap between the groups. N stage was associated with high anxiety scores and depression levels, whereas T stage was only associated with depression levels. Both anxiety scores and depression levels at diagnosis predicted prognosis through an association with TNM stage. Sense of humor, but not depression levels or anxiety scores, at diagnosis predicted QoL and depression levels at follow-up.

Early squamous cell carcinomas of the glottis can be treated effectively by means of surgery or external beam radiotherapy. The curability rate is about the same for both treatment modalities, but differing results have been reported regarding functional results. We selected 24 patients from a larger group of patients who had been treated for T1a glottic laryngeal cancer without the involvement of the anterior commissure. Fifteen patients were treated endoscopically and nine by radiotherapy. During a routine control videolaryngostroboscopy at an outpatient clinic, an objective and a subjective voice analysis were performed. The objective and subjective voice analyses showed no differences between the two treatment modalities. Videolaryngostroboscopy showed a significantly more pronounced glottic wave at the side that was originally affected by the tumour in the radiotherapy group. This difference disappeared when we looked at both vocal cords. Significant differences between the two treatment modalities were not found in any of the other parameters. Thus, this study shows no difference in the voice quality of patients treated by irradiation or by endoscopy. Therefore, the post-treatment voice quality is not a reason to favour radiotherapy for small T1a glottic squamous cell cancers without involvement of the anterior commissure.

Summary Objectives Patients with voice-related disorders are often treated by a multidisciplinary team including assessment by patient-reported outcome measures. The present paper aims at documenting the importance of including general health-related quality of life (HRQoL) measures to clinical investigations. Study design The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation, N = 19 various) were included consecutively at the laryngology clinic at Haukeland University Hospital. In addition, HRQoL data were included from one national group with laryngectomies (N = 105), one group with various patients formerly treated for head and neck squamous cell carcinoma (N = 96), and one population-based reference group (N = 1956). Method Obtained were the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ), the Voice Handicap Index (VHI), and the Eysenck Personality Inventory (EPI) neuroticism scores. Results By analysis of variance, we have determined significant dependence of groups analyzing the sum global QoL/health index (F = 9.47; P 0.001), the functional HRQoL sum score (F 5,2373 = 7.14, P 0.001), and the symptom sum HRQoL scores (F 7,2381 = 8.13; P 0.001). In particular, patients with recurrent palsy and laryngeal cancer had lowered HRQoL. At the index levels, in particular dyspnea scores, were scored depending on larynx disease group (F 7,2288 = 24.4; P 0.001). The VHI score correlated with the EORTC H&N35 "speech" index with a common variance of 52%. VHI scores correlated with level of neuroticism with 8% common variance ( P 0.001) and EORTC scores with 22% ( P 0.001). Conclusion In particular, among patients with voice-related disease, those with recurrent palsy and laryngeal cancer had lower HRQoL. Furthermore, the HRQoL and VHI scores were inversely tied to neuroticism.

Exercise-induced shortness of breath is not uncommon in otherwise healthy young people. Based on the presenting symptoms alone, it is challenging to distinguish exercise-induced asthma (EIA) from exercise-induced obstruction of central airways, sometimes leading to diagnostic errors and inadequate treatment. Central airway obstruction usually presents with exercise-induced inspiratory symptoms (EIIS) during ongoing exercise. EIIS tends to peak towards the end of an exercise session or immediately after its completion, contradicting symptoms of EIA typically peaking 3–15 min after the exercise has stopped. EIIS is usually associated with some form of laryngeal obstruction. Transnasal flexible laryngoscopy performed continuously throughout an incremental exercise test from rest to exhaustion or to intolerable symptoms is usually diagnostic, and also provides information that is important for further handling and treatment. Reflecting the complex anatomy and functional features of the larynx, exercise-induced laryngeal obstruction (EILO) appears to be a heterogeneous condition. Contradicting previous beliefs, recent literature suggests that laryngeal adduction in a majority of cases starts in supraglottic structures and that vocal cord adduction (VCD) most often occurs as a secondary phenomenon. However, EILO is poorly understood and more and better research is needed to unravel causal mechanisms. The evidence base for treatment of EILO is weak. Speech therapy, psychotherapy, biofeedback, muscle training, anticholinergic aerosols have all been applied, as has laser supraglottoplasty. Randomized controlled trials with well-defined and verifiable inclusion and success criteria are required to establish evidence-based treatment schemes. Electronic supplementary material The online version of this article (doi:10.1007/s00405-014-3159-3) contains supplementary material, which is available to authorized users.

Seventy newly diagnosed Caucasian male patients with head and neck squamous cell carcinomas (HNSCC) were included in the study. All patients were less than 80 years of age, with no cachexia or auto-immune disease, and they were not taking immuno-active medications. Monocytes from these patients were cultured in vitro and supplemented with autologous serum under ex vivo conditions or cultured with serum-free medium. Comparison was made to monocytes from 59 patients with benign HN diseases. Similar physical activity levels prior to testing as well as a minimum stress load were ensured in both groups. Increased monocyte supernatant levels were determined under ex vivo conditions of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, but not of interleukin-12 (IL-12) with endotoxin stimulated monocytes of HNSCC patients compared to control conditions. Increased monokine levels were not present with mononuclear cell cultures stimulated with a T-cell general stimulatory agent or with purified monocytes not specifically stimulated. With endotoxin-stimulated monocytes under in vitro conditions, an increased supernatant was shown for TNF-alpha, but not IL-6. With serum from the different patients cultured with monocytes employed from a healthy control, no difference between the groups was shown in the IL-6 and TNF-alpha response to endotoxin stimulation. The differences in IL-1 beta and TNF-alpha, but not IL-6 levels were differentiated statistically from the smoking and alcohol histories of the patients. These findings suggest that the function of monocytes in general, and thus possibly all mononuclear phagocyte system cells in HNSCC patients, are altered.

We have previously shown an increased T lymphocyte and monocyte responsiveness in peripheral blood mononuclear cells (PBMC) from patients with head and neck squamous cell carcinoma (HNSCC) compared with PBMC from control patients. This study reports T lymphocyte function of PBMC of 81 patients with HNSCC dependent on disease stage and prognosis. Males with HNSCC under 80 years of age without cachexia, with no auto-immune disease or previous cancer and on no immuno-active medication were included at the time of diagnosis of disease. The follow-up was for at least 18 months. When cells from patients with early vs late stage disease according to the T, N or T + N stage of HNSCC were compared, decreased in vitro mitogen-stimulated and spontaneous T cell proliferation was seen with increasing tumour stage. When patients were studied according to disease-specific survival, a decreased T lymphocyte mitogen-stimulated proliferation was observed to be associated with a poorer prognosis. No changes in prognosis were noticed related to decreased gamma-IFN, IL-2 or IL-4 level of the supernatants of the T lymphocyte-stimulated PBMC in vitro cultures. With stratification for disease stage, we determined that PBMC in vitro T lymphocyte-stimulated proliferation predicted outcome for the HNSCC patients. The results were similar for both laryngeal and oral cavity/pharyngeal cancers. The present investigation provides evidence to support the idea that the relationship between HNSCC and the immune system of the host may provide clinically useful information about prognosis.

Summary Background Inspiratory muscle training (IMT) has been used to treat patients with exercise-induced vocal cord dysfunction (VCD); the theoretical basis being the close relationship between the diaphragm and the posterior cricoarytenoid muscle, which is the main abductor of the larynx. Before launching a treatment protocol in patients with VCD, we aimed to substantiate this theory by performing laryngoscopy in healthy subjects during standardized IMT programs. Methods Twenty healthy volunteers at mean age 24 years were examined with video-recorded continuous transnasal flexible laryngoscopy while performing standardized training programs using a resistive loading IMT device (Respifit S). All subjects were exposed to two modes of training, that is, the resistance set to generate mouth pressures ≥80% of the maximal attainable inspiratory mouth pressure (PI max ) and 60–80% of PI max . Laryngeal movements were scored in retrospect from the video recordings by a senior laryngologist. Results At pressure settings of ≥80% of PI max , laryngeal movements could not be assessed in one subject. Abduction was observed in 10 (53%) subjects, six to a maximal extent and four to a moderate extent. At pressure settings of 60–80% of PI max , abduction was observed in 18 (90%) subjects, seven to a maximal extent and 11 to a moderate extent. Conclusions IMT can produce laryngeal abduction in healthy subjects, and training programs may conceivably contribute positively in patients suffering from laryngeal adduction during exercise. Individual response patterns varied between subjects and individualized programs seem crucial for effect. Use of high resistances seemed to be counterproductive.

Summary Objectives The main purpose of this study was to evaluate the psychometric abilities of the Norwegian version of the Voice-Related Quality of Life (V-RQOL) measure. A subsidiary goal was to examine whether the formulation of two additional questions would contribute to strengthen the test. Methods A total of 104 patients with voice disorders received the V-RQOL measure, Voice Handicap Index (VHI), and a Visual Analog Scale (VAS). Seventy-eight patients returned the forms, of which 16 were excluded because they did not meet the inclusion criteria. Analyses were carried out on 62 patients. Forty-one healthy control subjects fulfilled the V-RQOL measure, of which 36 were used in the analysis. Results The V-RQOL measure showed a strong internal consistency (Cronbach alpha=.84–.91) and a good test-retest reliability ( r =0.86–0.90). Construct validity was demonstrated with strong correlations to VHI ( r =0.91) and VAS ( r =0.78), together with a significant difference between patients and controls V-RQOL score. The two additional questions in the broadened version (V-RQOL12) had high mean scores (3.86 and 3.10) and strong item-total correlations (0.61 and 0.75), showing that these are important questions, measuring the same construct as the rest of the test. Conclusions The Norwegian version of the V-RQOL measure is a valid and reliable tool that discriminates well between voice and nonvoice patients. A broadened version of the instrument seems to strengthen the test.

Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however, there is no qualitative difference between function of TAMs and tissue macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs play an important role in the interaction with tumour cells in malignant tumours. The cells in the tumours that are the main sources of the various signal substances need to be further elucidated. The aim of this investigation was to reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence tumour cell growth and macrophage influx in tumours, respectively. Materials and methods. In order to inhibit macrophage function in F-spheroids, in some experiments the tissue fragments were initially incubated with LLME, a substance that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from untreated F-spheroids was compared to cytokine secretion from LLME-treated F-spheroids as measured by ELISA. Results. LLME did not affect the viability of F-spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and MCP-1 secretion compared with F-spheroids from tissue fragment untreated with LLME.

The results indicate that a high level of peripheral blood (PB) T-lymphocyte activation in vivo predicts impaired prognosis with and without adjustment for TNM stage in head and neck squamous cell carcinoma (HNSCC).To determine if PB T-lymphocyte activation in vivo is associated with the presence of, stage of and prognosis of HNSCC.Sixty-two patients with newly diagnosed HNSCC and 15 control patients were studied. PB T-lymphocyte activation was assessed by measuring by flow cytometry the percentage of PB T lymphocytes (CD3 + ) showing the early activation-related cell surface epitopes CD69+ or CD71+ (transferrin receptor) or the late activation epitopes CD25+ (IL-2 receptor) or HLA-DR+.There was no significant difference in expression of T-lymphocyte activation markers between HNSCC patients and control patients, or any difference dependent on TNMG stage. In HNSCC patients a high percentage of CD71+ T lymphocytes predicted worse prognosis with a relative risk (RR) of 2.38 (confidence interval (CI): 1.04-5.47). A high mean value of the early (CD69 + /CD71 + ) (RR 2.37; CI: 1.06-5.29) or late (CD25 + /HLA-DR + ) (RR 3.31; CI: 1.39-7.88) activation markers also predicted worse prognosis. Following adjustment for TNM stage, high mean value of the early activation epitopes CD71+ (RR 2.89; CI: 1.22-6.85), the mean value of CD69 + /CD71+ (RR 2.58; CI: 1.12-5.91) and CD25 + /HLA-DR+ (RR 2.75; CI: 1.14-6.62) predicted worse prognosis.

Objectives/Hypothesis: To assess the diagnostic feasibility and patient acceptance of a new developed diagnostic test for exercise induced upper airway flow limitation. Study Design: Clinical case control study including evaluation of contemporary ergo-spirometry and laryngoscopy continuously performed during exercise. Methods: Twelve nonsymptomatic controls and four young females with documented dyspnea and noisy breathing during exercise were studied. All subjects exercised to exhaustion on a treadmill while attached to a fully equipped ergo-spirometry unit and a fiberoptic laryngoscope linked to a video camera and a sound recorder. Results: The test situation was well tolerated. Two control subjects had a minor inspiratory synchronous medial motion of the aryepiglottic folds without limitation of laryngeal airflow. In the four symptomatic subjects, exercise induced inspiratory synchronous medial motion of the dorsal part of the aryepiglottic folds as well as vocal cord adduction and inspiratory stridor was demonstrated. Conclusion: The continuous laryngoscopy exercise test was easy to perform, well tolerated, and can be implemented in future diagnostic work-up programs of laryngeal dysfunction.

Monocyte fragment (F)-spheroid-stimulated and F-spheroid IL-6 and monocyte chemotactic protein (MCP)-1 secretion are related to inflammatory state, macrophage density and the TNM stage of patients with head and neck squamous cell carcinoma (HNSCC). Fragment (F)-spheroids from HNSCC patients in vitro secrete and stimulate autologous monocytes to secrete IL-6 and MCP-1. The aim of this investigation was to study this cytokine secretion in relation to other cytokines, spheroid composition and host factors.In series I (n=14) the densities of epithelial cells, fibroblasts and macrophages were determined in sections from F-spheroids and donor tissue. In series II (n=17) the TNM stage, donor inflammatory state, macrophage density and the secretion of F-spheroid- and monocyte F-spheroid-stimulated IL-6, MCP-1 and tumor necrosis factor (TNF)-alpha were determined. Epithelial cells were partly replaced by interstitial tissue during spheroid formation. Malignant (M) F-spheroids secreted more MCP-1 than benign (B) F-spheroids. No F-spheroid secreted measurable amounts of TNF-alpha. Monocytes secreted more IL-6 when co-cultured with MF- compared to BF-spheroids. Monocyte IL-6 MF- and MCP-1 MB-spheroid-stimulated secretion correlated with macrophage density. In addition, there was an association between MF- and BF-spheroid-stimulated monocyte cytokine secretion, as well as between BF- and MF-spheroid-stimulated MCP-1 secretion. An inverse relation was also noted between the erythrocyte sedimentation rate at monocyte harvest and the monocyte MCP-1 F-spheroid responses.

T-lymphocyte cell function was studied in vitro in peripheral blood mononuclear cells (PBMC) from 61 male patients with head and neck squamous cell carcinomas compared to 46 control patients. Patients older than 80 years or with reduced tumor-related performance status as measured by Karnofsky score less than 75 were excluded. In contrast to previous similar studies, control subjects ensured a minimum stress load by sampling all patients on the day of either diagnostic or therapeutic surgery. PBMC were separated by density-gradient centrifugation and subsequently cultured with autologous sera in vitro. The mitogen concanavalin A (Con A), which stimulates all T-cell clones, was employed. Findings showed that increased Con A stimulation and PBMC proliferation occurred with PBMC from cancer patients compared to that from control patients. In contrast, no differences could be detected with respect to the stimulated supernatant level of interleukin-2, interleukin-4 or interferon-gamma between the groups. These results suggest that T-lymphocytes from PBMC are generally affected by neoplastic disease through either a supporting cell or serum factor.