[New Swedish National care process for pediatric obstructive sleep disordered breathing]. / Nytt vårdförlopp för barn med OSDB är godkänt att tas i bruk.

Obstructive sleep disordered breathing (OSDB) is a spectrum from habitual snoring and labored breathing to obstructive sleep apnea (OSA), which is common and potentially serious in children. The process contains a new question at child care centers, directed at caretakers with children at age 18 months and 3 years, concerning habitual snoring (3 times a week or more). A primary care doctor verifies the suspicion of OSDB in case of a positive answer to one of 7 additional questions or 4 status findings (e.g. tonsil hypertrophy). The process starts with the suspicion of OSDB, from the age of 18 months to 18 years, and ends when symptoms are improved after watchful waiting or upper airway surgery. National equality is a goal, with increased access to nocturnal respiratory recordings of children with comorbidities or doubtful cases. Also, with short waiting time to first visit at ORL department, and to surgery. Children with comorbidities or severe symptoms get postoperative follow-ups with a nurse after 6 months. The new ICD code for OSDB is R06.8A.

High rate of early recurrence of peritonsillar abscess among adolescents and young adults.

BACKGROUND: Peritonsillar abscess (PTA) can be treated with aspiration or incision for drainage, but a subsequent PTA can occur if tonsillectomy is not performed. Better understanding is needed of when tonsillectomy should be performed to avoid PTA recurrence. OBJECTIVE: This study investigated the recurrence rate of PTA following aspiration or incision for drainage and evaluated the risk factors for recurrence. METHODS: The medical records of 292 patients treated for PTA were reviewed. Recurrence of PTA and elective or quinsy tonsillectomy were the primary endpoints. A Cox proportional hazards regression model for PTA recurrence was constructed with sex, age, and PTA history as predictors. RESULTS: Young age was the only significant predictor of PTA recurrence. Patients aged 15 to 24 years had a 30-day recurrence rate of 15.5% and a total recurrence rate of 26.6%. The total recurrence rate among patients over 30 years of age was significantly less at 4.0% (Fisher's exact test, p < .05). CONCLUSION AND SIGNIFICANCE: Based on our results, tonsillectomy should be considered for PTA patients between 15 and 25 years of age and, to effectively avoid future recurrence of PTA, should be performed urgently.

High prevalence of pharyngeal bacterial pathogens among healthy adolescents and young adults.

The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.

Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants.

The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs within the balance organs of mammalian inner ears. This low-level renewal of vestibular HCs exists during normal conditions and it is further enhanced after trauma-induced loss of these HCs. The main process for renewal of HCs within mammalian vestibular epithelia is a conversion/transdifferentiation of existing supporting cells (SCs) into replacement HCs.In earlier studies using long-term organ cultures of postnatal rat macula utriculi, HC loss induced by gentamicin resulted in an initial substantial decline in HC density followed by a significant increase in the proportion of HCs to SCs indicating the production of replacement HCs. In the present study, using the same model of ototoxic damage to study renewal of vestibular HCs, we focus on the ultrastructural characteristics of SCs undergoing transdifferentiation into new HCs. Our objective was to search for morphological signs of SC plasticity during this process. In the utricular epithelia, we observed immature HCs, which appear to be SCs transdifferentiating into HCs. These bridge SCs have unique morphological features characterized by formation of foot processes, basal accumulation of mitochondria, and an increased amount of connections with nearby SCs. No gap junctions were observed on these transitional cells. The tight junction seals were morphologically intact in both control and gentamicin-exposed explants. Anat Rec, 303:506-515, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients.

OBJECTIVES: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function. METHODS: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography. RESULTS: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 ± 23 vs. 25 ± 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 ± 8 vs. 2 ± 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 ± 8 vs. 3 ± 3%, P = .05). CONCLUSION: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea. LEVEL OF EVIDENCE: NA.

Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea.

BACKGROUND: The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. METHODS: Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. RESULTS: Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 ± 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 ± 10% desmin-abnormal muscle fibres vs. 22 ± 6% in patients without swallowing dysfunction, p = 0.002. CONCLUSION: Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea.

BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea. METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea. RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 × 10-3 axons/µm2; P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 ± 4.2% vs 4.8 ± 2.4%; P = .02). CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

Tonsillectomy in adults with obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: To study whether tonsillectomy is effective on obstructive sleep apnea (OSA) in adults with large tonsils. STUDY DESIGN: A multicenter prospective interventional study. METHODS: The study comprised 28 patients with OSA, an apnea-hypopnea index of > 10, large tonsils (Friedman tonsil size 3 and 4), and age 18 to 59 years. They were derived from 41 consecutive males and females with large tonsils referred for a suspicion of sleep apnea to the ear, nose, and throat departments in Umeå, Skellefteå, and Sunderbyn in northern Sweden. The primary outcome was the apnea-hypopnea index, measured with polygraphic sleep apnea recordings 6 months after surgery. Secondary outcomes included daytime sleepiness, as measured with the Epworth Sleepiness Scale, and swallowing function, using video-fluoroscopy. RESULTS: The apnea-hypopnea index was reduced from a mean of 40 units per hour (95% confidence interval [CI] 28-51) to seven units per hour (95% CI 3-11), P < 0.001, at the 6-month follow-up after surgery. The apnea-hypopnea index was reduced in all patients and 18 (64%) were cured. The Epworth Sleepiness Scale was reduced from a mean of 11 (95% CI 8-13) to 6.0 (95% CI 4-7), P < 0.001. A swallowing dysfunction was found in seven of eight investigated patients before surgery. Of those, swallowing function improved in five patients after surgery, whereas no one deteriorated. CONCLUSION: Tonsillectomy may be effective treatment for adult patients with OSA and large tonsils. Tonsillectomy may be suggested for adults with OSA and large tonsils. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2859-2862, 2016.

Bacterial flora and the epidemiology of staphylococcus aureus in the nose among patients with symptomatic nasal septal perforations.

Conclusions Patients with symptomatic perforations of the nasal septum had a high prevalence of S. aureus in the nasal mucosa. Pulsed field gel electrophoresis (PFGE) analysis revealed a high genetic heterogeneity of S. aureus among both patients and controls. This indicates that presence of different strains of S. aureus can maintain a chronic inflammation in symptomatic nasal septal perforations. Objective The purpose of this study was to investigate the microbial flora around nasal septal perforations in patients having severe symptoms regarding bleeding, obstruction, and crustation associated with their perforation. Methods Twenty-five patients with untreated symptomatic nasal septal perforations were included. For culture, swabs around the perforations were collected. Bacteria were identified with standard laboratory techniques including a MALDI-TOF mass spectrometer. Epidemiological analysis was done using PFGE protocols. Bacteriological data were compared with data from a healthy control group. Results Staphylococcus aureus was present in the mucosa surrounding the nasal perforation significantly more often (p < 0.0001) in the patients (88%) compared to a control group (13%). Corynebacterium spp. and Propionibacterium spp. were significantly more frequently identified in the control group. The PFGE analysis of S. aureus strains revealed a high genetic heterogeneity and no specific S. aureus genotypes were associated with septal perforation.

Unique expression of cytoskeletal proteins in human soft palate muscles.

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for ß-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, ß-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants.

We have studied aminoglycoside-induced vestibular hair-cell renewal using long-term culture of utricular macula explants from 4-day-old rats. Explanted utricles were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro (DIV), and then recovering in unsupplemented medium. Utricles were harvested at specified time points from the 2nd through the 28th DIV. The cellular events that occurred within hair cell epithelia during the culture period were documented from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) with the assistance of morphometric software. Ultrastructural observations were made from selected specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four days after gentamicin exposure, the density of HCs was 11% of the number of HCs observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was 61% of the number of HCs observed in the control group explant specimens. Simultaneously with this increase in HCs there was a corresponding decline in the number of SCs within the epithelium. The proportion of HCs in relation to SCs increased significantly in the gentamicin-exposed explant group during the 5th to the 28th DIV period of culture. There were no significant differences in the volume estimations of the gentamicin-exposed and the control group explants during the observed period of culture. Morphological observations showed that gentamicin exposure induced extensive loss of HCs within the epithelial layer, which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11 days after gentamicin exposure) a pseudostratified epithelium with multiple layers of disorganized cells was observed. At 21 DIV new HCs were observed that also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs with several layers of SCs located more basally characterized the gentamicin-exposed epithelium. No mitoses were observed within the epithelial layer of any explants. Our conclusion is that direct transdifferentiation of SCs into HCs was the only process contributing to the renewal of HCs after gentamicin exposure in these explants of vestibular inner ear epithelia obtained from the labyrinths of 4-day-old rats.

Effects of Radiofrequency versus sham surgery of the soft palate on daytime sleepiness.

OBJECTIVES/HYPOTHESIS: To evaluate the effect of radiofrequency surgery of the soft palate on daytime sleepiness in snoring men with mild or no sleep apnea. STUDY DESIGN: Randomized controlled trial. METHODS: Thirty-five men were recruited from consecutive patients referred to the Ear, Nose, and Throat Clinic due to snoring and complaints of daytime sleepiness. The inclusion criteria were an apnea-hypopnea index (AHI) of ≤ 15, male gender, and age 18 to 65 years. Patients were randomized to either radiofrequency or sham surgery of the soft palate. All but one chose and received the option of three treatments. All patients participated in a follow-up, including an overnight sleep apnea recording and questionnaires 12 months after the last treatment. The primary outcome was daytime sleepiness measured with the Epworth Sleepiness Scale (ESS) and other questionnaires. Secondary outcomes were effects on the AHI and subjective snoring. RESULTS: Thirty-two of 35 patients-19 of 20 patients in the radiofrequency surgery group and 13 of 15 patients in the sham surgery group-completed the study. No differences between the two groups in relation to the ESS or AHI were found at follow-up. CONCLUSION: Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring, or apnea frequency in snoring men with mild or no sleep apnea 1 year after surgery. LEVEL OF EVIDENCE: 1b. Laryngoscope 124:2422-2426, 2014.

The microbial flora in the nasal septum area prone to perforation.

To explore the colonizing bacterial flora of the nasal septum area, that is mostly afflicted by perforations, 101 healthy police students had swab samples taken from that location. The described culture strategy recovered positive cultures from 95% of the test subjects and from 60% with more than one organism. In total, 191 bacterial isolates were classified according to colony morphology, Gram-stain and a panel of standard laboratory techniques. A part of the bacteria was identified to species-level by biochemical methods and by sequencing of the 16S rRNA gene. The predominant finding was Gram-positive irregular rods - 65 presumptive Corynebacterium isolates, both lipophilic and non-lipophilic, and 37 anaerobic Propionibacterium isolates. The second largest bacterial group was Gram-positive catalase-positive cocci, of which 13 isolates were identified as Staphylococcus aureus and 53 as coagulase-negative staphylococci. The few potential airway pathogens included Streptococcus pneumonia (n = 1) and Moraxella catarrhalis (n = 3) isolates. The bacterial flora colonizing the nasal septum mainly consists of Gram-positive bacteria. Although of low virulence, the microbial flora may impact on occlusion treatment of nasal septum perforations with silicone obturators.

Morphological and morphometric characteristics of vestibular hair cells and support cells in long term cultures of rat utricle explants.

A method for long term culture of utricular macula explants is demonstrated to be stable and reproducible over a period of 28 days in vitro (DIV). This culture system for four-day-old rat utricular maculae is potentially suitable for studies of hair cell loss, repair and regeneration processes as they occur in post-natal mammalian inner ear sensory epithelia. The cellular events that occur within utricular macula hair cell epithelia during 28 days of culture are documented from serial sections. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) and the assistance of morphometric computer software. Ultrastructural observations were made with transmission electron microscopy (TEM) for describing the changes in the fine detailed morphological characteristics that occurred in the explants related to time in vitro. After 2 DIV the density of HCs was 77%, at 21 DIV it was 69%, and at 28 DIV it was 52% of HCs present at explantation. Between 2 DIV and 28 DIV there was a 1.7% decrease of the vestibular macula HC density per DIV. The corresponding decrease of SC density within the utricular explants was less than 1% per DIV. The overall morphology of the epithelia, i.e. relationship of HCs to SCs, was well preserved during the first two weeks in culture. After this time a slight deterioration of the epithelia was observed and although type I and type II HCs were identified by TEM observations, these two HC types could no longer be distinguished from one another by LM observations. In preparations cultured for 21 DIV, SC nuclei were located more apical and further away from the basal membrane compared to their position in macula explants fixed immediately after dissection. The loss of cells that occurred was probably due to expulsion from the apical (i.e. luminal) surface of the sensory epithelia, but no lesions of the apical lining or ruptures of the basal membrane were observed. There were no significant changes in the volume of the vestibular HC comprising macular epithelium during the observation period of 28 DIV.

Treatment of nasal septal perforations with a custom-made prosthesis.

We present the fabrication and clinical use of a custom-made nasal septal silicone button that can be inserted transnasally into a perforation of the nasal septum by the physician as an office procedure, or by the patients themselves in their home. Questionnaire and retrospective chart review were used to evaluate the efficacy of this prosthesis as treatment of disturbing symptoms from nasal septal perforation. The study included 41 patients (27 women) with a nasal septal perforation. The follow-up time ranged from 1 to 9 years. Symptoms investigated were nasal obstruction, crusting, feeling of dryness, pain, epistaxis, and whistling from the nose. The degree of experienced symptoms was estimated on a VAS-scale. The questionnaire was answered by 37 of the 41 patients. Fourteen patients were still using their button at the follow-up. Treatment with the prosthesis greatly diminished all the investigated symptoms. Also, use of the silicone button resulted in an improved quality of life. No case of infection was noted in connection with use of the silicone prosthesis.

Lack of plasminogen does not alter the early inflammatory response following a tympanic membrane perforation: a study in plasminogen-deficient mice.

CONCLUSIONS: The results of the present study show that the early inflammatory response in plasminogen (plg)-deficient mice is not altered compared to that in wild-type (wt) mice. Therefore the chronicity of the perforation in the long-term healing experiment cannot be explained by an impairment of the early inflammatory response, but rather by an impairment in activation of the inflammatory cells. These findings give further insight into the mechanisms resulting in a clinically seen chronic tympanic membrane (TM) perforation and thus possible therapeutic strategies to replace today's conventional surgical treatment of these perforations. OBJECTIVES: Plg has been shown to play an essential role in the healing of TM perforations. In plg-deficient mice a completely arrested healing reaction was seen, resulting in a chronic TM perforation. The mechanisms involved seem to be an abundant neutrophil recruitment, an accumulation of macrophages, an arrested keratinocyte migration, and a massive deposition of fibrin along the TM tissue. However, the exact functional role of plg in the early inflammatory response during healing of TM perforation remains unclear. This study aimed to evaluate the early inflammatory response, mainly the occurrence of macrophages and neutrophils, during the first 48 h following a perforation in the pars tensa (PT) of the TM, in mice lacking the plasminogen gene compared to the corresponding response in wt mice. MATERIALS AND METHODS: The TMs were perforated in 45 plg-deficient and 39 wt mice. Otomicroscopic evaluation was performed at 3, 6, 9, 12, 18, 24, and 48 h after the perforation was made. Mice were harvested at all time points and prepared for morphology including immunohistochemistry (IHC). IHC was performed with antibodies targeting macrophages, neutrophils, T and B cells, cytokeratin, and fibrin(ogen). Morphometry was performed regarding the volume percentage of TM tissue occupied by the different inflammatory cells. RESULTS: Perforation of the TM resulted in early otomicroscopic changes of the pars flaccida (PF) in both genotypes. Infiltration of inflammatory cells to PF and the presence of edema occurred as early as 6 h after the perforation was made, in both plg-deficient and wt mice. Morphometry did not reveal any significant differences between the genotypes concerning the occurrence of inflammatory cells. In contrast to the PF, the PT showed only sparse reactions during the experimental period. Furthermore, the migration pattern of keratinocytes did not differ between the genotypes throughout the experimental period.

Physical findings in the upper airways related to obstructive sleep apnea in men and women.

UNLABELLED: CONCLUSIONS, There are gender differences when it comes to the risk factors for sleep apnea. Large tonsils, a high tongue and a wide uvula are risk factors for sleep apnea in men, while large tonsils and a retrognathic mandible are risk factors in women. Upper airway abnormalities including mandibular retrognathia are, however, unable to predict sleep apnea among snorers being investigated for suspected sleep apnea. OBJECTIVES: To identify gender-specific risk factors for obstructive sleep apnea and the diagnostic performance from physical upper airway examinations among snoring men and women investigated because of suspected sleep apnea. PATIENTS AND METHODS: The dimensions of the uvula, tonsils, velopharynx and tongue, and nasal septal deviation, mandibular position, neck circumference, weight, and height were systematically scored in 801 consecutive snoring patients (596 men and 205 women), who had been referred for a primary sleep apnea recording. RESULTS: In men, large tonsils, a high tongue, and a wide uvula were independent factors associated with an apnea-hypopnea index of >15. In women, large tonsils and mandibular retrognathia were independent factors associated with an apnea-hypopnea index of >15. The positive predictive values for upper airway abnormalities ranged between 0.20 and 0.25 in men and between 0.09 and 0.15 in women.

Prediction and risk of dysphagia after uvulopalatopharyngoplasty and uvulopalatoplasty.

OBJECTIVE: To test the hypothesis that preoperative asymptomatic pharyngeal swallowing dysfunction predisposes for the development of symptoms of dysphagia after uvulopalatopharyngoplasty (UPPP) and uvulopalatoplasty (UPP). MATERIAL AND METHODS: A total of 42 patients who snored were scheduled to undergo UPPP (n = 20) or UPP (n = 22). UPP was performed using either a CO2 laser or a conventional steel scalpel. Preoperatively and 1 year postoperatively all patients were examined videoradiographically to assess pharyngeal swallowing function. They also completed a questionnaire pre- and postoperatively concerning their snoring problems and swallowing function as well as the outcome of surgery. RESULTS: Preoperatively, 7 (17%) patients reported dysphagia. Pharyngeal swallowing dysfunction was demonstrated in 6/7 patients with preoperative dysphagia while pharyngeal swallowing dysfunction was evident preoperatively in 18/35 non-dysphagic patients. Of the 35 patients without preoperative dysphagia, 10 (29%/) developed dysphagia after surgery. There was no significant risk of development of postoperative dysphagia for patients with compared to patients without preoperative pharyngeal swallowing dysfunction. Only one of the seven patients with preoperative dysphagia experienced worsening of the problem. A total of 93% of the patients reported a decrease in snoring and 95% reported a decrease in daytime sleepiness. CONCLUSIONS: Preoperative pharyngeal swallowing dysfunction was not proven to predict the development of dysphagia after UPPP or UPP. The surgical method did not influence the frequency of postoperatively acquired dysphagia. The results do not indicate that patients with preoperative dysphagia should be excluded from treatment with UPPP or UPP.

Unique antitumour effects of L-2,4 diaminobutyric acid on cultured hepatoma cells.

A single hepatoma cell line was grown in vitro and incubated with L-2,4 diaminobutyric acid (DAB), a non-metabolizable amino acid, under various conditions. The tumour cells were irreversibly damaged by incubation for 8 hours with 8 mmol/L of DAB. The tumour cell-destroying effect of DAB was dose- and time-dependent with no effect at a DAB concentration of 1.6 mmol/L. The presence of N-methyl alpha-aminoisobutyric acid (a specific substrate of amino acid transport system A) in the incubation medium abrogated the tumour cell destructive effect of DAB in a dose-dependent fashion. The presence of non-physiological amino acids in the incubation medium per se was not the cause of tumour cell destruction, since inclusion of alpha-amino-isobutyric acid and N-methyl alpha-aminoisobutyric acid in the incubation medium did not influence the viability of hepatoma cells. We conclude that the tumour cell destructive effect of DAB was the result of a huge and unlimited uptake of DAB energized by the Na(+)-gradient and that this uptake was not subjected to the law of saturation kinetics. This was combined with a tumour cell energy crisis in attempts to restore the Na(+)-gradient.

Spontaneous hair-cell renewal following gentamicin exposure in postnatal rat utricular explants.

We have established an in vitro model of long-time culture of 4-day-old rat utricular maculae to study aminoglycoside-induced vestibular hair-cell renewal in the mammalian inner ear. The explanted maculae were cultured for up to 28 days on the surface of a membrane insert system. In an initial series of experiments utricles were exposed to 1 mM of gentamicin for 48 h and then allowed to recover in unsupplemented medium or in medium supplemented with the anti-mitotic drug aphidicolin. In a parallel control series, explants were not exposed to gentamicin. Utricles were harvested at specified time points from the second through the 28th day in vitro. Whole-mount utricles were stained with phalloidin-fluorescein isothiocyanate and their stereociliary bundles visualized and counted. In a second experimental series 2'-bromo-5'deoxyuridine labeling was used to confirm the antimitotic efficacy of aphidicolin. Loss of hair-cell stereociliary bundles was nearly complete 3 days after exposure to gentamicin, with the density of stereociliary bundles only 3-4% of their original density. Renewal of hair-cell bundles was abundant (i.e. 15x increase) in cultures in unsupplemented medium, with a peak of stereociliary bundle renewal reached after 21 days in vitro. A limited amount of hair-cell renewal also occurred in the presence of the anti-mitotic drug, aphidicolin. These results suggest that spontaneous renewal of hair-cell stereociliary bundles following gentamicin damage in utricular explants predominantly follows a pathway that includes mitotic events, but that a small portion of the hair-cell stereociliary bundle renewal does not require mitotic activity.