重组活化基因1缺陷鼠和正常小鼠急性细菌性鼻窦炎模型的比较研究

目的　探讨C5 7BL/ 6J 重组活化基因 1(recombinantactivegene 1,Rag1)敲除鼠 (简称Rag1小鼠 )和C5 7BL/ 6 (C5 7)小鼠急性细菌性鼻窦炎的自然感染过程及二者之间的差别。方法　Rag1缺乏鼠和C5 7小鼠各 10只 ,采用鼻孔内接种肺炎链球菌T5 9,另外 4只接种大豆肉汤作对照。分别于接种2d(各 2只 )、5d(各 4只 )、10d(各 2只 )、14d(各 2只 )处死动物 ,对照组于第 5天处死。处死前作鼻腔灌洗培养 ,头颅石蜡包埋 ,连续切片 ,Luna染色 ,计算机辅助光镜观察 ,计算窦腔内中性粒细胞集落所占窦腔的百分率和每平方毫米窦腔黏膜中浸润的多形核白细胞数。结果　接种 5dRag1小鼠和C5 7小鼠窦腔感染均达到高峰 ,窦腔中白细胞集落和黏膜中白细胞数均明显高于对照组 (P <0 0 5 ) ,10d后C5 7小鼠窦腔感染逐渐减轻 ,14d后基本控制 ,而Rag1小鼠感染持续存在 ,与C5 7比较差异有显著性(P <0 0 5 ) ,14d后鼻灌洗液中仍培养出肺炎链球菌。结论　采用肺炎链球菌T5 9鼻内接种法成功地诱导出Rag1和C5 72种小鼠急性鼻窦炎 ,肺炎链球菌在C5 7小鼠鼻腔鼻窦内的感染可被完全、自主、快速控制 ,但Rag1小鼠则不能完全控制这种感染 ,并有演变成慢性炎症的倾向 ,提示T和B淋巴细胞依赖性免疫功能在清除细菌感染中起着关键的作用 ,基因敲除     

Bactrim reduces the inflammatory response in a murine model of acute rhinosinusitis

OBJECTIVE: To determine whether treatment with an antibiotic (trimethoprim-sulfamethoxazole) reduced the inflammatory response in a murine form of Streptococcus pneumoniae-induced rhinosinusitis. DESIGN: We randomized 18 C57BL/6 mice to either treatment with intraperitoneal trimethoprim-sulfamethoxazole (Bactrim, 30 mg/kg) or no treatment (control). After 2 days, we inoculated all C57BL/6 mice intranasally with a Bactrim-susceptible strain of Streptococcus pneumoniae, ATCC 49619, suspended in Trypticase soy broth. At day 5 after bacterial inoculation, we sacrificed the mice and prepared histopathologic sections of their sinuses after culturing their nasal cavities by lavage. SETTING: Animal care facility at a tertiary, academic institution. METHODS: The histopathologic sections of the sinuses were examined in a blind manner for the percent of sinus cavity area occupied by neutrophil clusters, and for the number of neutrophils per square millimeter of sinus mucosa. RESULTS: The Bactrim group had a significantly smaller sinus area occupied by neutrophil clusters (1.58% +/- 1.13 vs 4.38% +/- 3.41; P < 0.05), significantly fewer neutrophils infiltrating the mucosa (58.81 +/- 29.63/mm2 vs 105.85 +/- 48.49/mm2; P < 0.05), and significantly less growth of Streptococcus pneumoniae colonies in the intranasal cultures (8 few and 1 moderate vs 3 few, 3 moderate, and 1 many; P = 0.05) compared to the control group. CONCLUSION: In our murine model of acute rhinosinusitis, Bactrim decreased the number of neutrophil clusters in the sinus cavities, the number of neutrophils infiltrating the sinus mucosa, and the growth of Streptococcus pneumoniae. We propose that our murine model can be used for the study of the pathophysiology and treatment of acute rhinosinusitis.     

Effect of genetic background on the response to bacterial sinusitis in mice

OBJECTIVE: To study the importance of ongoing allergen exposure and TH1/TH2 genetic background in augmented bacterial and inflammatory responses in allergic and infected mice. DESIGN: BALB/c and C57BL/6 mice were made allergic to ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated intranasally with Streptococcus pneumoniae. The numbers of bacteria and inflammatory cells in the sinuses were determined, and nasal responsiveness to histamine was assessed. RESULTS: Infected BALB/c and C57BL/6 mice that received ongoing ovalbumin challenge following intraperitoneal sensitization showed significantly greater bacterial load and phagocyte level compared with the infected-only mice. Differences were diminished after the allergen challenge was stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number of bacteria 28 days after infection. CONCLUSIONS: Ongoing allergic reaction augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less allergic inflammation and bacterial load compared with allergic and infected BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c mice, which favor a TH2 response, were less able to clear infection than C57BL/6 mice, which favor a TH1 response. Inflammation and bacterial load are affected by genetic background of mice and ongoing allergen stimulation.     

C57Bl/6 and BALB/c mice have similar neutrophil response to acute Streptococcus pneumoniae sinus infections

BACKGROUND: Previous investigations have shown that mice with a tendency toward a T(H)1 or T(H)2 lymphocyte response manifest different reactions to inoculation with the parasite Leishmania major. BALB/c mice (with a tendency for a T(H)2 response) showed evidence of systemic infection, whereas C57Bl/6 mice (with a tendency for a T(H)1 response) showed only a local reaction. OBJECTIVE: To investigate whether BALB/c and C57Bl/6 mice respond differently to acute bacterial infection of the sinuses. METHODS: We inoculated the nasal cavities of C57Bl/6 and BALB/c mice with Streptococcus pneumoniae (type ATCC59), or with broth as a control. The mice were humanely killed 2, 5, 10, and 14 days after inoculation. Their heads were fixed, decalcified, and embedded in paraffin blocks. Sections were stained with hematoxylin and eosin, and the degree of inflammation was quantified by the number of neutrophils per square millimeter of the sinus mucosa and the percentage of the sinus cavity occupied by neutrophil clusters. RESULTS: Both groups of mice showed evidence of inflammation that was significantly greater than controls (P =.01), with no difference between groups. There was a correlation between the number of neutrophils per square millimeter in the sinus mucosa and the percentage of neutrophil clusters (C57Bl/6 mice, r = 0.37, P<.001; BALB/c mice, r = 0.20, P<.001). In the infected mice, the number of infiltrating neutrophils was significantly greater (P<.001) in anatomically lower (dependent) areas of the sinuses compared with the upper areas. CONCLUSION: Unlike leishmaniasis, acute bacterial sinusitis is not affected by the tendency of the host to favor either a T(H)1 or T(H)2 response.     

Evaluation of importance of Toll-like receptor 4 in acute Streptococcus pneumoniae sinusitis in mice

OBJECTIVES: To investigate the effect of RC-527, a synthetic toll-like receptor 4 (TLR4) agonist, on stimulating the immune response before acute Streptococcus pneumoniae sinusitis in a mouse model, and to determine the importance of TLR4 in modulating the response to S. pneumoniae. Toll-like receptor 4 agonists have been shown to induce protective innate immune responses when administered before some bacterial or viral challenges in mice. DESIGN: We intranasally inoculated BALB/c, TLR4 complex-deficient C3H/HeJ, and wild-type C3H/HeOuJ mice with S. pneumoniae 24 hours after treatment with 10 or 1 microg of RC-527 or vehicle. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were quantified at postinoculation days 2, 5, and 14. MAIN OUTCOME MEASURE: Immune response induced by RC-527. RESULTS: Treatment with RC-527 induced an immune response through TLR4, as demonstrated by recruitment of phagocytes in uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. The immune response was also demonstrated by a significant increase of CD3+, CD4+, and CD8+ T cells in infected and uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. However, the enhancement of the immune response induced by the TLR4 agonist showed a limited effect on bacterial clearance. CONCLUSIONS: Our studies in mice suggest that stimulation of TLR4 plays a minor role in the overall response to S. pneumoniae infection of the upper airway, and stimulating this receptor before infection does not significantly enhance the immune response of immunocompetent mice to clear S. pneumoniae infection.     

小鼠变应性鼻炎合并急性细菌性鼻窦炎的初步研究

目的 探讨变应性鼻炎动物模型合并急性细菌性鼻窦炎的方法.方法 清洁级C57BL6/J小鼠40只,随机分为4组:A组(卵清蛋白+肺炎链球菌);B组(卵清蛋白+生理盐水);C组[磷酸盐缓冲溶液(phosphate buffered solution,PBS)+肺炎链球菌];D组(PBS+生理盐水),每组各10只.①实验第1～9天,A组和B组每天腹腔注射200μl 10%卵清蛋白,第10～17天A、B组用6%卵清蛋白鼻腔局部激发建立变应性鼻炎模型,C组和D组用等量PBS替代,步骤同前;②于实验第13天A组和C组鼻腔接种肺炎链球菌ATCC 49619 200μl;B组和D组用等量生理盐水代替.接种后第6天处死动物,处死前各组动物行内眦静脉采血,以间接酶联免疫吸附试验检测血清白介素5水平.取鼻面骨,石蜡包埋,连续切片,行HE染色和0.5%甲苯胺蓝染色,计算机辅助显微镜下观察肥大细胞脱颗粒情况,并计算每平方毫米鼻窦黏膜中多形核中性粒细胞和嗜酸粒细胞的数量.结果 A组和B组分别有9只和8只动物变应性鼻炎建模成功,鼻部症状、黏膜水肿和黏膜下微血管明显扩张,C组症状轻微,D组无任何症状.A组鼻窦黏膜多形核中性粒细胞密度(-x±s)为(139.3±26.5)个/mm2,高于B组(70.7±16.7)个/mm2、C组(63.0±14.7)个/mm2和D组(40.2±14.1)个/mm2(P值均＜0.01);A组和B组嗜酸粒细胞密度和白介素5水平(-x±s)分别为(134.6±25.5)个/mm2、(48.2±13.9)pg/ml和(116.2±25.2)个/mm2、(40.8±7.8)pg/ml,均高于C组(16.7±2.7)个/mm2、(23.9±8.7)pg/ml(P值均＜0.05)和D组(13.4±4.9)个/mm2、(24.6±6.5)pg/ml(P值均＜0.05).结论 变应性鼻炎合并细菌性鼻窦炎造模成功.     

Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice

OBJECTIVES: To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. DESIGN: Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. INTERVENTIONS: For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. RESULTS: Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). CONCLUSIONS: Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.     

Histological and immunological observations of bacterial and allergic chronic rhinosinusitis in the mouse

BACKGROUND: The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS). METHODS: A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid. RESULTS: Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 +/- 2.33 versus 1.37 +/- 0.86; p < 0.01). CONCLUSION: Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.     

Developing a mouse model of acute bacterial rhinosinusitis

The objective of this study is to establish a mouse model of acute bacterial rhinosinusitis. 179 healthy male BALB/c mice were divided into four groups in this randomized and controlled study. Sponge slivers impregnated with methicillin-resistant Staphylococcus aureus (MRSA COL) suspension were inserted into the right nasal cavities for group A; sponge slivers impregnated with sterile saline were inserted into the right nasal cavities for group B; group C mice were inoculated with MRSA COL suspension in right nasal cavities; group D was control group without any treatment. Mice were killed on days 1, 4, 7 and 14, respectively. Nasal lavage fluid was prepared for microbiological culture. Histological examinations of nasal specimens were performed to observe the severity of inflammatory reaction. Acute bacterial rhinosinusitis was induced in all group A mice. Less severe inflammation was seen in partial group B mice compared with that in group A mice (P ≤ 0.05). No inflammatory reaction was found in group C and D mice. In conclusion, a mouse model of acute bacterial rhinosinusitis has been developed successfully using an easier, less invasive and potentially more reversible technique than those used in previous studies.     

Intranasal infection of ICR mice with herpes simplex virus type 1

Intranasal inoculation of mice with herpes simplex virus (HSV) provides a model of human herpetic infection through a natural route of inoculation. Five-week-old male ICR mice were infected intranasally with various strains of herpes simplex virus type 1 (HSV-1), and the fundamental aspects of the pathogenicity of this virus were studied. Six virus strains examined showed variance in their virulence determined by lethal dose 50 (LD50) for mice. Four of the strains were revealed to be virulent, and two were shown to be attenuated. The relative degree of virulence among these strains corresponded well to that shown by intraperitoneal inoculation. When mice were inoculated with a virulent virus strain (F), virus multiplication was shown clearly in several organs tested, such as the lung, brain, olfactory bulb, trigeminal ganglion, spinal cord and adrenal gland. Viremia was also demonstrated. On the other hand, in mice inoculated with an attenuated virus strain (-GCr), virus was recovered only from the lung and adrenal gland and in much less amount than in the respective organs of mice infected with the virulent strain. No viremia was demonstrated. These data strongly suggest that the lethal effect of HSV-1 on mice is dependent upon whether or not significant virus multiplication occurs in the central nervous system, which is the critical target organ of HSV. Preinoculation of mice with an attenuated strain via the intranasal route suppressed the lethal effect of subsequent infection with any of the virulent strains by the same route of inoculation, although this protection phenomenon was not so pronounced when the virulent UNO-1A strain was used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacology of Sinupret. Recent results on the rational for the Sinupret compound

The herbal medicinal product Sinupret has been successfully used for the treatment of sinusitis for 70 years. In Germany the product is established as a standard in the therapy of sinusitis. The most recent pharmacodynamic findings resulted from close scientific cooperation with Pontus Stierna and co-workers from the Karolinska Institute in Stockholm: Mice were infected intranasally with Streptococcus pneumoniae to induce bacterial rhinosinusitis. Animals were randomized to treatment with ampicillin, dexamethasone, Sinupret, or sham treatment. All groups receiving active treatment showed a reduction in bacterial growth after 4 days and a significant reduction of bacterial growth after 8 days. Similar results were observed regarding histopathology. Initial findings in a sinusitis model in the New Zealand White rabbit confirmed the results observed in the aforementioned studies in mice. Understanding of the pharmacological profile of Sinupret supports the knowledge about the clinical efficacy of this herbal medicinal product.     

Management of complicated acute sinusitis in the setting of concurrent COVID-19

PurposeIntraorbital and intracranial complications of acute bacterial rhinosinusitis require timely medical and surgical treatment to prevent the development of long-term neurologic sequelae. The era of Coronavirus Disease-2019 (COVID-19) has complicated the management of complicated acute rhinosinusitis, especially when patients have concurrent acute sinusitis and COVID-19 infection. This case series aims to highlight the clinical course of pediatric patients at a single tertiary pediatric hospital with concurrent complicated bacterial rhinosinusitis and COVID-19.Materials and methodsA search of pediatric patients treated for COVID-19 and complications from acute sinusitis was performed using billing records for the year 2020–2021 at a single pediatric tertiary hospital. Data regarding presentation, management, microbiology, and hospital course was collected for review.ResultsA total of 6 patients with complicated bacterial sinusitis in the setting of COVID-19 infection were included. All patients were initially managed with medical therapy, consisting of systemic antibiotics, but 3 of these patients ultimately required surgical intervention. Cultures from the cohort grew Staphylococcus aureus, streptococcus intermedius, streptococcus constellatus or Prevotella species. All patients experienced clinical improvements and were eventually discharged home with oral antibiotics.ConclusionCOVID-19 continues to be an unusual disease especially for the pediatric population. Concurrent complicated acute rhinosinusitis and COVID-19 appear to have higher rates of surgical requirement in the pediatric population. COVID-19 safety precautions have influenced management practices for patients with severe bacterial rhinologic infections. While there may be an association between complicated bacterial rhinosinusitis and COVID-19 infection, further research is necessary to determine a true correlation.     

Symptoms and clinical and radiological signs predicting the presence of pathogenic bacteria in acute rhinosinusitis

A minority of patients with upper respiratory tract infections (URTI) have a bacterial infection and may benefit from antibiotherapy. In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions, resolution of symptoms was significantly improved by antibiotic treatment. The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria. Detailed clinical histories were obtained and medical examinations performed in 265 patients (138 females, 127 males; mean age 35 years) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae and M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Azithromycin (500 mg/day for 3 days; n = 133) or placebo (n = 132) were randomly given to all patients in a double-blind manner. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge (p < 0.003), facial pain (p < 0.032) and radiologically determined maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening > 10 mm) (p < 0.001). This best predictive model had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. In the group of patients with positive bacterial cultures, resolution of symptoms at Day 7 was observed in 73% of patients treated with azithromycin and in 47% of patients in the placebo group (p < 0.007). We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria.     

Electrophysiological characteristics of inferior colliculus neurons in mutant mice with hereditary absence of cochlear outer hair cells

One strain of homozygous Kit^W-v mice (formerly known as W^v/W^v) lack 98% of the cochlear outer hair cells (OHCs) from birth. Inner hair cells (IHCs) and supporting cells develop normally. Thus, this strain is an attractive model to study the effect of complete OHC absence on central frequency representation. Frequency threshold curves were recorded along the tonotopic axis of inferior colliculus (IC) in mutant and control mice of the genetic background strain (C57BL/6J) and a different outbred strain (NMRI/wild mouse hybrids) known to be free of any cochlear pathology. The average threshold level of neurons in the mutants was 100 dB sound pressure level, 60 dB higher than in C57BL/6J and NMRI mice. Their tuning curves lacked the sharply tuned tip. In the C57BL/6J mice, although younger than four months, abnormal tuning curves were found for about 30% of the neurons, especially in the high frequency range. No abnormal tuning curves were found in the NMRI mice. The bandwidth of the tuning curves, measured at 10 dB above threshold, was on average 1.27 octaves in mutants, 0.62 octaves in C57BL/6J mice, and 0.34 octaves in NMRI mice. The range for the high cut-off frequency of the tuning curves at 10 dB above threshold was 6.4–61.1 kHz in the NMRI and 7–59.5 kHz in C57BL/6J. In the mutants, the range was limited to 11.1–41.7 kHz. The tonotopic gradient based on the cut-off frequency was less steep in the IC of the mutants than in both control groups.     

小鼠急性细菌性鼻及鼻窦炎模型

目的建立小鼠急性细菌性鼻及鼻窦炎模型。方法 179只BALB/c/小鼠,随机分为4组。A、B组BALB/c小鼠右侧鼻腔中塞入棉条。A组,以耐甲氧西林金黄色葡萄球菌（methicillin resistant Staphylococcus aureus,MRSA）COL菌悬液浸润棉条;B组,以无菌生理盐水浸润棉条;C组,只在小鼠鼻腔中滴入MRSA COL菌悬液;D组,对照组。动物分别于1、4、7、14 d处死。对鼻部组织做细菌培养和病理切片研究。死亡的3只小鼠（A组）未计人数据统计中。结果 A组小鼠全部诱导出急性细菌性鼻及鼻窦炎,B组小鼠可诱导出鼻腔炎症反应。炎症程度经统计学分析,A、B组有明显统计学差异。C、D组小鼠没有出现炎症反应。结论以植入膨胀海绵并滴入菌液的方式成功建立小鼠急性细菌性鼻及鼻窦炎模型。     

Influence of genotype and age on acute acoustic trauma and recovery in CBA/Ca and C57BL/6J mice.

Two inbred strains of mice, CBA/Ca (with a moderate auditory impairment starting late in life) and C57BL/6J (with a progressive auditory degeneration starting during young adulthood), were exposed to a 120 dB SPL broadband noise (2-7 kHz) for 5 min at the age of 1, 3, or 6 months. Compound and permanent threshold shifts (CTS and PTS) were determined by auditory brainstem response during the first day (CTS) and 1 month (PTS) after exposure. With increasing age, susceptibility to CTS at middle frequencies (8 and 12.5 kHz) decreased in CBA mice, yet was retained in C57 mice. C57 mice were more severely affected by CTS than age-matched CBA mice. Noise-induced CTS was positively correlated to pre-exposure thresholds in C57 mice and to PTS over all ages and strains. The amount of recovery from CTS to PTS was, however, independent of age and strain. There was only a 2% risk of classifying CBA mice as C57 mice by pre-exposure thresholds at high frequency, while there was about 40% risk by CTS. The results indicate that genetic predisposition can affect susceptibility to auditory degeneration and noise impairment in a systematic manner, allowing the identification of susceptible individuals by pre-exposure audiometric examination, especially at high frequencies.     

Aging and the auditory brainstem response in mice with severe or minimal presbycusis

Threshold, latency, and amplitude of the auditory brainstem response (ABR) were obtained with filtered noise pips in young and aging C57BL/6J mice (to 16-months), which undergo severe progressive age-related sensorineural hearing loss (presbycusis) and CBA/J mice (to 19-months), which show only mild loss late in life. Aging per se (CBA mice) is not associated with significant changes in ABR parameters. Presbycusis, in aging C57 mice, is associated with increased thresholds; there is a trend toward increased latencies, but only when threshold elevations are substantial. Amplitudes of early waves, but not late waves, decrease greatly in aging C57 mice. In young C57 mice, amplitudes of early ABR waves vary monotonically with intensity, while amplitudes of later waves (IV and V) have a relatively flat, or even nonmonotonic, relationship to intensity; in older C57 mice, all waves have monotonie intensity functions. ABR parameters are not affected by gender in either strain. The mouse models can help to clarify some inconsistencies in the human literature on aging and the ABR.     

Microbiology of recurrent acute rhinosinusitis

OBJECTIVE: We undertook to evaluate the microbiology of recurrent acute rhinosinusitis. METHODS: Repeated aspirations of maxillary sinus secretions by endoscopy were performed in eight patients over a period of 98 to 185 days. RESULTS: Bacteria were recovered for all 25 aspirates. A total of 31 isolates-14 Streptococcus pneumoniae, 11 Haemophilus influenzae, 5 Moraxella catarrhalis, and 1 Staphylococcus aureus-were recovered. The organism persisted in consecutive cultures in 13 instances and were eliminated in 8, and new organisms emerged in 6 instances. An increase in antimicrobial resistance was noted in 5 instances (3 in S. pneumoniae and 2 H. influenzae). CONCLUSIONS: This study illustrates the microbial dynamics of recurrent acute rhinosinusitis, with the changes in microbial findings and increased bacterial resistance that occurs over time.     

Prolonged exposure to an augmented acoustic environment ameliorates age-related auditory changes in C57BL/6J and DBA/2J mice.

The effects of exposure to an augmented acoustic environment (AAE) on auditory function were evaluated in mouse strains that exhibit high-frequency hearing loss beginning during young adulthood (the C57BL/6J strain [C57]) or around the time of weaning/ adolescence (the DBA/2J strain [DBA]). Beginning at age 25 days, mice were exposed 12 h every night to a 70 dB SPL broad-band noise AAE. The AAE was maintained until age 14 months in C57 mice and 9 months in DBA mice. Control mice were age-matched and maintained under normal vivarium acoustic conditions. The auditory brainstem response (ABR), acoustic startle response amplitude, and prepulse inhibition (PPI) were used to assess the auditory system. Exposure to the AAE resulted in improved auditory performance in both strains (better PPI, lower ABR thresholds, bigger startle amplitudes).