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Development of the hypothalamo-pituitary-adrenocortical (HPA) axis is marked by a diminution in stress responsiveness early in the postnatal period (days 4-14 in the rat). This 'stress hyporesponsive period' (SHRP) is thought to be at least in part centrally mediated. To investigate central mechanisms underlying the SHRP, this study assessed expression of glutamic acid decarboxylase (GAD) 67 in key stress-regulatory regions in the forebrain following acute stress with or without prior maternal deprivation. This isoform of GAD is known to be induced by stress in the adult and is believed to be a major contributor to production of the inhibitory neurotransmitter GABA under stimulated conditions. Expression of GAD67 mRNA was increased in the hippocampus, central amygdala and dorsomedial hypothalamus in pups tested early in the SHRP (day 6) or after its conclusion (day 18). In contrast, restraint caused a down-regulation of GAD67 mRNA in these structures when tested later in the SHRP (day 12). GAD67 mRNA expression was not affected by prior maternal deprivation in these regions. Reduced GABA production in the hippocampus (interneurons) is consistent with enhanced HPA axis inhibition, whereas reduced amygdalar expression predicts impaired stress excitation. Expression of GAD67 mRNA in the bed nucleus of the stria terminalis (BST) was minimally affected by acute restraint or maternal deprivation during the SHRP. However, older animals showed down-regulation of basal expression following maternal deprivation and substantial GAD67 mRNA up-regulation in both deprived and non-deprived groups following acute restraint. In contrast, non-responsiveness of the BST during the SHRP suggests either that BST GABA circuits are not actively engaged by stressors during this period or that circuits regulating BST GAD67 production are not yet in place. Overall, the data implicate forebrain GABA circuits in inhibition of HPA axis activity during the SHRP.

Limbic and cortical neurocircuits profoundly influence hypothalamic-pituitary-adrenal (HPA) axis responses to stress yet have little or no direct projections to the hypothalamic paraventricular nucleus (PVN). Numerous lines of evidence suggest that the bed nucleus of the stria terminalis (BST) is well positioned to relay limbic information to the PVN. The BST comprises multiple anatomically distinct nuclei, of which some are known to receive direct limbic and/or cortical input and to heavily innervate the PVN. Our studies test the hypothesis that subregions of the BST differentially regulate HPA axis responses to acute stress. Male Sprague Dawley rats received bilateral ibotenate lesions, targeting either the principal nucleus in the posterior BST or the dorsomedial/fusiform nuclei in the anteroventral BST. Posterior BST lesions elevated plasma ACTH and corticosterone in response to acute restraint stress, increased stress-induced PVN c-fos mRNA, and elevated PVN corticotropin-releasing hormone (CRH) and parvocellular arginine vasopressin (AVP) mRNA expression relative to sham-lesion animals. In contrast, anterior BST lesions attenuated the plasma corticosterone response and decreased c-fos mRNA induction in the PVN but did not affect CRH and parvocellular AVP mRNA expression in the PVN. These data suggest that posterior BST nuclei are involved in inhibition of the HPA axis, whereas the anteroventral BST nuclei are involved in HPA axis excitation. The results indicate that the BST contains functional subdomains that play different roles in integrating and processing limbic information in response to stress and further suggest that excitatory as well as inhibitory limbic information is funneled through these important cell groups.

Objective: The aim of this study was to describe the CT and sonographic findings of hepatic visceral larva migrans of Toxocara canis., Materials and Methods: Fifty-four patients (44 men, 10 women; age range, 30-80 years; mean age, 53 years) with serologically confirmed visceral larva migrans of Toxocara canis underwent evaluation of the liver with CT (n = 25), sonography (n = 48), or both. Two radiologists used consensus for retrospective evaluation of CT and sonographic findings. Correlation between the presence and severity of hepatic abnormalities on images and the degree of peripheral eosinophilia was assessed., Results: Seventeen (68%) of 25 patients who underwent CT had single or multiple ill-defined, oval or elongated, small, low-attenuating lesions in the liver. Eighteen (38%) of 48 patients who underwent sonography had single or multiple small, poorly defined, oval or elongated, hypoechoic scattered focal lesions in the liver. In the 19 patients who underwent both CT and sonography, the two techniques had no significant difference in rate of detection of hepatic lesions (p = 0.375, McNemar test). The lesion numbers on CT and sonography showed excellent linear correlation (r = 0.844, p = 0.001) by Pearson's correlation test. An independent samples t test showed that eosinophil count and percentage in the peripheral blood were significantly higher in patients with hepatic lesions on CT and sonography than in patients without lesions., Conclusion: CT and sonographic findings of hepatic visceral larva migrans of T. canis are multiple, ill-defined, oval or elongated, small, nodular lesions scattered in the liver parenchyma. The presence of hepatic lesions on images was associated with higher peripheral eosinophil count and percentage.

The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0-895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.

Prolonged social subjugation produces physiological indices of chronic stress in rats. In the current study, we examined the impact of social stress on glutamic acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in forebrain stress circuitry, using the visible burrow system model of dominance-subordination. Subordinate male rats develop behavioral and neuroendocrine changes consistent with exposure to chronic stress, including marked loss of body weight and elevation of basal plasma corticosterone relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA expression in central stress-regulatory circuits were examined by in situ hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67 expression was decreased in the interfascicular nucleus of the BST in both the subordinate and dominant rats compared to non-burrow control rats. No changes in CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or in the hypothalamic paraventricular nucleus. Collectively, these data suggest that exposure to the visible burrow system attenuates BST GAD expression regardless of social status, whereas the enhanced physiological responses to social stress seen in subordinates may be associated with enhanced CRH expression in the oval nucleus of the BST.

Study Objectives: Cough lasting > 3 weeks has been defined as chronic cough. However, it might be more persuasive to divide cough into subacute, lasting 3 to 8 weeks, and chronic, lasting > 8 weeks. We evaluated the causes and clinical courses of subacute cough, and the value of the bronchoprovocation test and induced sputum examination (IS)., Methods: Nonsmoking patients with cough of 3 to 8 weeks duration were enrolled into the study. Patients with dyspnea, basal FEV1 of < 70% predicted, abnormal findings on a plain chest radiograph or physical examination were excluded. We prescribed an antihistamine-decongestant for patients who were suspected to have postinfectious cough or postnasal drip. If patients had positive results on a bronchoprovocation test or IS, therapy with inhaled corticosteroids was substituted according to an algorithmic approach., Results: One hundred eighty-four patients (77 men and 107 women) were evaluated; the mean age of the study group was 47.5 years. Eighty-nine of 184 patients had postinfectious cough. Cough resolved without treatment in 62 patients. Twenty-nine of 43 patients with positive bronchoprovocation test results had cough-variant asthma., Conclusions: Postinfectious cough was the most common cause of subacute cough. The spontaneous resolution of cough was frequent in patients with subacute cough. Unless asthma was strongly suspected, the performance of the bronchoprovocation test could be delayed until after empirical treatment had been administered.

Toxocariasis is one of the causes of eosinophilia in peripheral blood and provokes eosinophilic infiltration in internal organs. Extended studies on the prevalence and clinical characteristics of toxocariasis have been rare. The aim of this study is to evaluate the prevalence of toxocariasis in unknown eosinophilia and to analyze the efficacy of toxocara enzyme-linked immunosorbent assay (ELISA). We evaluated patients presenting with peripheral blood eosinophilia (>500 cells/microl or > or =10% of white blood cell count). After checking drug histories and the presence of allergic diseases and parasitic infections, specific serum IgG antibody to Toxocara canis larval antigen was measured by ELISA. Liver and lung involvement was also evaluated. One-hundred and three patients were evaluated, and the mean age was 50.9 years old. Seventy patients (68.0%) were diagnosed as having toxocariasis. The patients who had a history of raw liver eating had a higher incidence, and the patients with liver involvement had higher serum eosinophil cationic protein values. The eosinophil count was normalized in 7 of 16 treated patients and in 25 of 54 untreated patients. The mean improvement duration was 12 months. We concluded that the prevalence of toxocariasis was high in patients with unknown eosinophilia, and the toxocara ELISA was essential for evaluation of the causes of unknown eosinophilia.

Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.

Churg-Strauss syndrome (CSS) is a rare multi-system vasculitis; some cases have been reported in Korea. The aim of this study is to describe the clinical features, treatment outcome, and long-term follow-up of CSS from a single Korean medical center. Between 1995 and 2004, seventeen patients were diagnosed with CSS at the Department of Medicine of the Samsung Medical Center, Sungkyunkwan University School of Medicine. The diagnosis of CSS is based on the classification criteria of the American Collage of Rheumatology. All patients had asthma. As in other case series, the lung, peripheral nervous system, and skin were the most commonly involved organs. During the active stage of the disease, most of the patients exhibited peripheral blood eosinophilia and an elevated serum eosinophil cationic protein level. Ten patients were treated with pulses of methylprednisolone followed by tapering and cyclophosphamide, and the others were treated with corticosteroids alone. The outcomes after long-term follow-up were generally good. One patient who was refractory to initial treatment died of heart failure during the follow-up period. CSS was highly variable in its presentation and course. The manifestations may range from mild symptoms to life-threatening conditions. The outcome after long-term follow-up was as good as that of previous studies.

We report here a case with hypereosinophilia and peripheral artery occlusion. A 32-yr-old Korean woman presented to us with lower extremity swelling and pain. Angiography revealed that multiple lower extremity arteries were occlusive. The biopsy specimen showed perivascular and periadnexal dense eosinophilic infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg daily. Her skin lesion and pain were improved and the eosinophil count was dramatically decreased. After discharge, eosinophil count gradually increased again. Cyanosis and pain of her fingers recurred. She had been treated with cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis and tingling sense were progressive. The extremity arterial stenoses were slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum TNF-alpah was markedly increased. These results suggest that CD40L (a member of TNF-alpah superfamily) could play a role in the inflammatory processes when eosinophil infiltration and activation are observed. We prescribed prednisolone, cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was discharged.

Background: Angiogenesis is pivotal in the development and progression of ovarian cancer and is an ideal candidate for novel treatment approaches., Case: A case of advanced, recurrent and refractory serous carcinoma is presented that responded to bevacizumab 15 mg/m2 intravenously every 3 weeks after failing eleventh line cytotoxic chemotherapy and radiation. An objective durable response lasting at least 5 months was documented., Conclusion: Bevacizumab has activity in epithelial ovarian carcinoma and larger scale trials are indicated.

Appropriate regulatory control of the hypothalamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting 'reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such 'anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, 'anticipatory' circuits are integrated with neural pathways subserving 'reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary-adrenocortical dysfunction associated with numerous disease processes.

Background: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted., Objective: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population., Methods: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens., Results: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1)., Conclusion: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Effects of several cytokines on kinetics of Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) expression were studied on a bronchial epithelial cell line (BEAS-2B). VCAM-I was neither constitutively expressed on BEAS-2B cells nor induced by Interferon-gamma (IFN-gamma). Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta), IFN-alpha, IL-4, IL-6, IL-8 or Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). ICAM-1 was constitutively expressed on BEAS-2B cells. IFN-gamma and TNF-alpha upregulated ICAM-1 expression on these cells. The functional importance of IFN-gamma plus TNF-a upregulation of ICAM-1 expression on BEAS-2B cells was demonstrated by neutrophil-BEAS-2B cell adhesion assays. Cytokines are rapidly released and cleared in animals. Therefore, transient cytokine(s) exposure might occur on the bronchial mucosa. Brief incubation of BEAS-2B cells with IFN-gamma plus TNF-alpha led initial upregulation of ICAM-1 expression followed by a protracted downregulation. Our findings stress the importance of studying the mechanism(s) controlling the persistent increased expression of ICAM-1 after brief cytokine(s) exposure.

The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma has been proposed by earlier studies. To evaluate the possible involvement of autoimmune response against bronchial epithelial cell in the pathogenesis of nonatopic asthma, we measured circulating autoantibodies to cultured human bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent assay. We used stored serum samples form 38 age-matched healthy controls, 26 adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and 12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies to bronchial epithelial cell were significantly higher in patients with nonatopic asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that levels of circulating IgG autoantibodies to bronchial epithelial cell were increased in adult patients with nonatopic asthma. Further studies are needed to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.

There have been several reports on the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients with chronic rhinosinusitis. Whether ESS has a positive effect on the clinical course of asthma still remains controversial. There have been several subjective evaluations but few objective results. We performed a study to evaluate the effectiveness of ESS in 19 patients with asthma who underwent ESS for rhinosinusitis. The use of antiasthma medication and postoperative asthma symptoms was analyzed. Objective changes of pulmonary function tests were evaluated. There was a significant improvement in diurnal and nocturnal asthma symptoms. Improvements in asthma medication scores were also confirmed, and individual asthma symptoms (dyspnea, cough, wheezing, and sputum production) improved significantly. Despite a reduction in use of antiasthma medication after ESS, the parameters of the pulmonary function tests did not change. Both subjectively and objectively, it seems that ESS, when used to treat asthmatic patients with chronic rhinosinusitis, can play a significant role in the clinical improvement of asthma.

Background: Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD)., Objective: To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production., Materials and Methods: We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated., Results: There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner., Conclusion: These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in reducing cellular infiltration and ultimately to its anti-inflammatory property.

Background: Although there have been a few reports of occupational asthma due to cellulase in several occupational settings, this is the first case of cellulase-induced occupational asthma in an employee working in the textile industry. Its pathogenetic mechanism remains to be further clarified., Objective: It is important to alert physicians to the possibility of occupational asthma caused by cellulase in workers of the textile industry., Methods and Results: The patient had atopy and strong positive responses to cellulase extract on skin prick tests. Bronchoprovocation test showed an early asthmatic response to cellulase extract. Serum specific IgE and specific IgG4 antibodies to cellulase were detected by enzyme-linked immunosorbent assay (ELISA). In order to further characterize the allergenic component of the extract, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting studies were performed. Eight IgE binding components ranging from 6 to 97.5 kD were detected within the cellulase extract., Conclusion: These findings suggest that inhalation of cellulase can induce IgE-mediated bronchoconstrictions in employees working in the textile industry.

Although asthma is considered to be an inflammatory disease of the airways, neural mechanisms remain very important. Neural control of airways is far more complex than has been previously recognized. In addition to the classic neural pathways, the nonadrenergic, noncholinergic pathway has been described in the airways of animals and humans. Neuropeptides are present in sensory, parasympathetic, and sympathetic neurons in airways, and have been shown to have proinflammatory effects, such as increased mucus production, microvascular leakage, and smooth muscle contraction. Neuropeptides released from sensory nerves (eg, neurokinin A and substance P) mediate excitatory nonadrenergic, noncholinergic transmission, which causes bronchoconstriction and, possibly, bronchial hyperresponsiveness. Better understanding of neural mechanisms might provide a useful therapeutic approach in the future.

Purpose: Eosinophilic lung disease includes various disease entities. Each disease manifests different radiologic findings. The purpose of this review is to present the radiologic findings of the spectrum of eosinophilic lung disease., Method: We reviewed the radiologic, histologic, and clinical findings of the spectrum of eosinophilic lung disease from the previous reports and our experiences., Results: Simple pulmonary eosinophilia is characterized by transient and migrating opacities on chest radiography. Acute eosinophilic pneumonia is characterized by acute clinical symptoms and signs and rapid changes of radiographic diffuse reticular lesions. Chronic eosinophilic pneumonia, with more prolonged symptom duration, history of asthma, occurrence of relapse, and radiologic features of subpleural consolidation, can be differentiated from acute eosinophilic pneumonia. Allergic bronchopulmonary aspergillosis presents with bilateral central bronchiectasis with or without mucoid impaction. Although these diseases show specific radiographic findings, some show overlapping radiographic features. High-resolution CT enables characterization of parenchymal lesions further by showing internal and marginal features and the exact extent of the lesions. Extrapulmonary organs are involved in Churg-Strauss syndrome and idiopathic hypereosinophilic syndrome. Asthma is associated with Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and bronchocentric granulomatosis., Conclusion: Integration of clinical, laboratory, and radiologic findings enables initial and differential diagnoses of various eosinophilic lung diseases.

Background: There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma., Objective: This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histological abnormalities in asthmatics according to the severity of asthma., Methods: Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inflammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultrastructural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina., Conclusion: These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.

Salicylates and most NSAIDS in high doses cause mild to moderate temporary hearing loss, either flat or greater in the high frequencies. Hearing loss is accompanied by tinnitus and suprathreshold changes. Salicylates may or may not exacerbate hearing loss and cochlear damage induced by noise. The mechanism of salicylate ototoxicity seems to be multifactorial. Morphologic studies suggest that no permanent cochlear damage occurs with salicylate ototoxicity. Electrophysiologic, morphologic, and in vitro data conclusively demonstrate that salicylate affects outer hair cells. In addition, salicylates appear to decrease cochlear blood flow. Salicylates and NSAIDs inhibit PG-forming cyclooxygenase, and recent studies suggest that abnormal levels of arachidonic acid metabolites consisting of decreased PGs and increased LTs may mediate salicylate ototoxicity. As with salicylate, quinine ototoxicity appears to be multifactorial in origin. The mechanism includes vasoconstriction and decreases in cochlear blood flow, as measured by laser Doppler flowmetry, motion photographic studies, and histologic studies. Reversible alterations of outer hair cells also appear to play an important role, as demonstrated by histology, electron microscopy, isolated hair cell studies, and cochlear potential evaluations. Unlike with salicylate, however, the role of prostaglandins in quinine ototoxicity has not been clearly demonstrated. Also, one of quinine's principal actions, antagonism of calcium-dependent potassium channels, has yet to be investigated for its potential role in ototoxicity.