Estrogen as a guardian of auditory health: Tsp1-CD47 axis regulation and noise-induced hearing loss.

OBJECTIVES: This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. METHODS: An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. RESULTS: After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)-CD47 axis in OVX rats was discovered and verified. CONCLUSIONS: OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1-CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

Brusatol attenuated proliferation and invasion induced by KRAS in differentiated thyroid cancer through inhibiting Nrf2.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) can be developed from differentiated thyroid cancer, and this dedifferentiated transformation leads to poor prognosis and high mortality. The role of Nrf2 in the dedifferentiation of differentiated thyroid cancer (DTC) induced by KRAS remains unclear. METHODS AND MATERIALS: In this study, two DTC cell lines, BCPAP and WRO, were used to evaluate the function of Nrf2 in the dedifferentiation caused by wild-type KRAS (KRAS-WT) and G12V point mutation KRAS (KRAS-G12V). RESULTS: The overexpression of KRAS-WT and KRAS-G12V increased the proliferative and invasive ability of BCPAP and WRO cells. Aggressive morphology was observed in KRAS-WT and KRAS-G12V overexpressed WRO cells. These results suggested that overexpression of KRAS-WT or KRAS-G12V may induce dedifferentiation in DTC cells. The expression of Nrf2 was increased by KRAS-WT and KRAS-G12V in DTC cells. In addition, compared with normal thyroid tissues, the expression of Nrf2 protein was considerably higher in thyroid cancer tissues on immunohistochemistry (IHC) staining, and the increased expression of Nrf2 indicated a poor prognosis of thyroid cancer. These results indicated that Nrf2 is the KRAS downstream molecule in thyroid cancer. Functional studies showed that the Nrf2 inhibitor Brusatol counteracted the proliferative and invasive abilities induced by KRAS-WT and KRAS-G12V in BCPAP and WRO cells. In addition, the xenograft assay further confirmed that Brusatol inhibits tumor growth induced by KRAS-WT and KRAS-G12V. CONCLUSION: Collectively, this study suggests that Nrf2 could be a promising therapeutic target in KRAS-mediated dedifferentiation of thyroid cancer.

Effect of wearing an N95 respirator on the internal nasal valve and the association with external nasal anatomy - a cohort study.

OBJECTIVES: To determine whether: the N95 respirator affects nasal valve patency; placement on the bony vault improves patency; and external nasal anatomy affects the outcome. METHODS: A prospective study with 50 participants was conducted. Nasal patency was measured by the minimal cross-sectional area via acoustic rhinometry, and using the Nasal Obstruction Symptom Evaluation survey, before and after wearing the N95 respirator and after adjustment. RESULTS: The minimal cross-sectional area was narrowed by 27 per cent when wearing the N95 respirator (p < 0.001), and improved by 9.2 per cent after adjustment (p = 0.003). The total Nasal Obstruction Symptom Evaluation score increased from 10.2 to 25.4 after donning the N95 respirator (p < 0.001), and decreased from 25.4 to 15.6 after adjustment (p < 0.001). There was no correlation with external nasal anatomy parameters. CONCLUSION: Wearing the N95 respirator causes narrowing of the nasal valve, and adjustment onto the bony vault improves symptoms. The findings were not affected by external nasal anatomy.

Perceptions and experiences of post-irradiation swallowing difficulties in nasopharyngeal cancer survivors.

This study aimed to explore the perceptions and experiences of swallowing difficulties in irradiated survivors of nasopharyngeal carcinoma (NPC). Qualitative semi-structured interviews were conducted with 60 post-irradiation NPC patients after they had answered a set of self-report questions. The interviews were transcribed verbatim for analysis. Results of the self-report data showed that in response to a global question 'Do you have any swallowing difficulties?' eight-five per cent of the respondents reported a certain degree of difficulty. The qualitative interview findings, however, suggested that this figure might have been underestimated. Patient interpretations of swallowing difficulties had excluded part of the symptoms. Some respondents who claimed to have no difficulty swallowing, in fact, were suffering from oral retention of food bolus, regurgitation of food or liquids through the nose, and/or even choking. The risk of aspiration was generally neglected. Informants' concerns focused more on the threat of cancer recurrence, thus paid less attention to the radiation-induced swallowing complication. Respondents did not possess sufficient knowledge to judge their swallowing abilities at a general level. This study suggests ways to enhance patient-provider communication and health education to improve patient knowledge.

Efficacy of a Comprehensive Dysphagia Intervention Program Tailored for the Residents of Nursing Homes.

Oropharyngeal dysphagia is a widespread condition in older people and thus poses a serious health threat to the residents of nursing homes. The management of dysphagia relies mainly on compensatory strategies, such as diet and environmental modification. This study investigated the efficacy of an intervention program using a single-arm interventional study design. Twenty-two participants from nursing homes were included and had an average of 26 hours of intervention, including oromotor exercises, orosensory stimulation and exercises to target dysphagia and caregiver training. Four of the 22 participants exhibited improvement in functional oral intake scale (FOIS) but was not statistically significant as a group. All oromotor function parameters, including the range, strength, and coordination of movements, significantly improved. These results indicate that this intervention program could potentially improve the oromotor function, which were translated into functional improvements in some participants' recommended diets. The validity of this study could be improved further by using standardized swallowing and feeding assessment methods or an instrumental swallowing assessment.

Psychometric properties of the Chinese (Cantonese) Tinnitus Handicap Inventory.

OBJECTIVES: To establish the reliability and validity of the Chinese (Cantonese) version of the Tinnitus Handicap Inventory to measure the self-perceived handicapping effect and severity of the condition in patients with chronic tinnitus. DESIGN: Cross-sectional psychometric validation study. SETTING: Audiology clinics in a hospital setting. PARTICIPANTS: Subjects were 114 adult Chinese who attended the audiology clinics with a complaint of tinnitus. MAIN OUTCOME MEASURES: Test-retest and internal consistency reliability; construct validity. RESULTS: The Chinese version of the Tinnitus Handicap Inventory and its subscales showed good internal consistency reliabilities (alpha = 0.72-0.94) that are comparable to those of the original version. High correlations were observed between the Tinnitus Handicap Inventory and psychological distress, tinnitus-related problem ratings and severity ratings. Factor analysis showed that the Chinese version of the Tinnitus Handicap Inventory has a unifactorial structure. A high degree of test-retest reliability was observed (intraclass correlation coefficient = 0.88). CONCLUSIONS: The results suggest that the Chinese (Cantonese) version of the Tinnitus Handicap Inventory is a reliable and valid measure of general tinnitus-related distress that can be used in clinical settings to quantify the impact of tinnitus on daily life.

Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.

Adult croup.

Adult croup is a distinct disease entity that probably represents a heterogeneous clinical syndrome. Three cases of adult laryngotracheitis characterized by upper airway infection and progression to airway obstruction are illustrated. Close observation and prompt decisions regarding airway intervention are critical in effective management, and complete resolution is expected.

The influence of verapamil on the gastric effects of stress in rats.

The influence of verapamil on stress- or bethanechol-induced gastric effects was investigated in rats. Intraperitoneally injected verapamil (1, 2 or 4 mg/kg), given 30 min beforehand, dose-dependently prevented gastric glandular ulceration, mast cell degranulation and the increased stomach wall contractions evoked by restraint at 4 degrees C for 1 h. Gastric acid secretion, as well as ulceration in both the forestomach and glandular segment, produced by subcutaneously-injected bethanechol (3.2 mg/kg) were also inhibited. It is concluded that decreased amine release from the mast cells, stomach wall relaxation and reduced gastric acid were responsible for the ulcer-antagonising effects of the calcium-entry blocker. The possible antiulcer actions of verapamil are discussed in the light of present knowledge regarding calcium involvement in the various mechanisms thought to contribute to the pathophysiology of stress ulceration in rat stomachs.

Polyotia--a rare external ear anomaly.

A rare case of polyotia in a 7-year old boy associated with first arch syndrome is reported. The accessory auricle formed a well defined helix and conchal bowl located anterior to a normal auricle and an atretic external auditory meatus. Surgical resection and reconstruction resulted in a good cosmetic outcome.

Nasal foreign bodies in children.

This study investigates the pattern of pediatric nasal foreign body impaction and its management in a metropolitan area. Data was obtained from 147 children presenting to the Accident and Emergency Department over a 4-year period. The majority of foreign bodies were toys and household products. Complications which occurred, such as ingestion of the foreign body or epistaxis were usually related to attempts at removal. Fourteen cases of local complications resulted from button battery impaction. Most of these patients can successfully be managed without complication if correct procedures are adopted.

A double-blind comparative study of ofloxacin otic drops versus neomycin-polymyxin B-hydrocortisone otic drops in the medical treatment of chronic suppurative otitis media.

Active chronic suppurative otitis media poses a management problem when patients are being considered for surgical treatment. Topical antibiotics have demonstrated varying degrees of success in the management of discharging ears. The introduction of quinolones has revived interest in these topical agents. This double-blind study compares two antibiotics, namely ofloxacin and neomycin-polymyxin B, with similar in vitro sensitivities to Gram positive and Gram negative organisms. Fifty-two patients were selected randomly and the results show that ofloxacin eardrops have marginal benefits in symptomatic improvement (89 per cent versus 79 per cent, p = 0.27) and bacterial eradication (81 per cent versus 75 per cent, p = 0.81) in active chronic suppurative otitis media. Significantly fewer patients (seven per cent versus 29 per cent, p = 0.04) in the ofloxacin group had active disease at the end of the two-week treatment. We recommend the use of ofloxacin eardrops in managing active chronic suppurative otitis media since it has high clinical efficacy, contains no steroid component and has no demonstrated risk of ototoxicity.

Flexible nasopharyngoscopy for fish bone removal from the pharynx.

The use of flexible nasopharyngoscopy with biopsy forceps for the removal of fish bones found in the oropharynx and hypopharynx is described. One hundred and sixty-eight patients with ingested fish bones in the upper aero-digestive tract were studied over a 12-month period. Of these, 73 per cent were removed per-orally, or by indirect laryngoscopy. Fifteen per cent were removed using the fibreoptic nasopharyngoscope. Twelve per cent required a general anaesthetic and rigid oesophagoscopy for removal of fish bones at or below the level of the cricopharyngeus muscle. The technique has proven to be quick, well tolerated and low in morbidity. It is invaluable in patients in whom indirect laryngoscopy is unsatisfactory.

Nasal manifestation of extranodal Rosai-Dorfman disease--diagnosis and management.

Two cases of Rosai-Dorfman disease with polypoid nasal infiltration mimicking nasal tuberculosis and malignant lymphoma are reported. This rare benign disease was first described by Rosai and Dorfman in 1969 and is characterized by histiocytic proliferation. It is seldom considered in the differential diagnosis of granulomatous diseases due to its rarity and histological similarity to other diseases. Extranodal manifestations of this disease are uncommon. Although no specific treatment can guarantee a sustained remission of this disease, surgery for loco-regional lesions can result in long-term symptomatic control and restoration of function. Both patients underwent endoscopic resection of the nasal polypoid lesions and have subsequently been free of recurrence. Loco-regional infiltration of the nasal cavity by Rosai-Dorfman disease is effectively managed by endoscopic resection.

Ingested foreign bodies--a contemporary management approach.

A prospective study of all foreign body complaints presenting through our Accident and Emergency Department was conducted in a population where the condition is endemic. All patients were managed by otolaryngologists. Six hundred and eight patients were attended to yielding 179 foreign bodies. Making use of modern equipment and a practical approach, the requirement for examination under general anesthesia was 6.3 per cent. In this series there was a complication rate of 0.5 per cent.

Prevalence of otitis media with effusion in multicultural schools in Hong Kong.

The prevalence of otitis media with effusion (OME) in Asia has only been studied in a limited fashion. This preliminary study forms part of a larger study aiming to establish the prevalence of OME in Hong Kong. One hundred and seventy-seven children (from multicultural schools) between the ages of five and 6.03 years were screened for OME otoscopy and tympanometry. Nine positive screens (5.1 per cent) were obtained for OME. Within this mixed ethnic group, Chinese children had a significantly lower point prevalence (1.3 per cent) than Caucasian children (9.5 per cent) (p < 0.05). Although the point prevalence from this mixed ethnic group of children was significantly higher (p < 0.05) than that of local Chinese school children (1.95 per cent) by the same group of investigators, the point prevalence in the ethnic Chinese children was comparable. The reason for the lower prevalence of OME in the Chinese population needs further research.

Anorectal anomalies: a review of 49 cases.

A series of forty-nine cases of anorectal anomalies treated in the Department of Surgery, Singapore General Hospital, is reviewed. The incidence of ano-rectal malformation in the Singapore population is estimated to be one in 11,500 live births. There is a significant male preponderence with a ratio of 7 to 3. Supralevator lesions accounted for 55% of the cases and of this group, 31% had associated congenital anomalies. In contrast only 11% of the low anomalies had other congenital defects. All patients were treated surgically either by anoplasty for the low lesions or staged rectoplasty for the intermediate and high lesions. The results of surgery for the low anomalies were uniformly good. In the group with high anomalies 7 cases had a good results, 21 had a fair result with occasional soiling only, and 2 cases had a poor result with frank incontinence.

Surgical revascularisation for diffuse CAD--an experience in 116 cases.

There were 94 male and 22 female, age ranges 32 to 71 years with a mean age of 54 years. All of them had angina pectoris and strong positive stress test inspite of maximum medical treatment. All had severe triple vessel disease including (12 (10%) had critical left main stem lesion, 68 (52%) were diabetic and hypertensive, 51 (44%) had myocardial infarct with 16 (14%) of them showing global hypokinesia of ejection fraction 30%. The average grafts per patient was 3.8 Seventy-nine patients (68%) and RCA endarterectomy; 19 (16%) had right and left coronary endarterectomy and 18 (15%) had left coronary artery endarterectomy. One-hundred and three (86%) were reconstructed with saphenous vein graft. 13 (12%) with IMA grafts. There was no operative mortality. Two hospital deaths and two late deaths occurred in those patients who had very poor left ventricular function. The perioperative infarct rate was 2.7%. All patients were followed-up regularly at 2 weeks, 3 months, 6 months, postoperatively. The mean follow-up was 18 months ranging 10 to 43 months. Clinically over 95% are free from angina pectoris with improved effort tolerance. We conclude that endarterectomy with patch angioplasty is an effective and safe procedure in treating Diffuse Coronary Artery Disease which cannot be treated by bypass alone. The incidence of Diffuse Coronary Artery Disease is likely to increase in the future as the percutaneous balloon angioplasty is becoming more widely practised and Re-do CABG patient would come to surgery at a more advanced state of the disease.

Coronary artery bypass in patients with impaired left ventricular function.

Myocardial revascularisation in patients with severe left ventricular dysfunction has been shown to improve survival. This report analyses the efficacy of myocardial revascularisation in this subset of patients with coronary artery disease manifesting severe left ventricular dysfunction on the basis of left ventricular ejection fraction (LVEF). Twenty-two consecutive patients with coronary artery disease complicated by severe left ventricular dysfunction underwent aorta-coronary bypass electively at Singapore General Hospital for the 3 year period ending February 1989. Twenty-one patients have angina +/- congestive heart failure refractory to medical therapy. One patient had congestive heart failure and objective evidence of ischaemia confirmed by preoperative thallium stress test. Nineteen (82.6%) patients had triple-vessel coronary artery disease. The mean LVEF for the series was 25% with the range from 10-13%. The duration of follow up was 6 months to 3 years (mean 24 months) with follow up survival data on 100% of patients. The hospital mortality was 9% (2/22) and there were 3 late deaths. Of the 17 survivors available for direct assessment, 12 reported improvement in their symptoms and 3 are completely asymptomatic. These preliminary results indicate that myocardial revascularisation can be performed in patients with severe LV dysfunction at an acceptable risk and that operation results in improvement in survival expectation and symptoms compared with medical therapy.