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79 歳男性.発熱,咳嗽で発症し,鼻閉の既往,空洞を伴う両下肺の浸潤影,顕微鏡的血尿,急速進行する腎機能障害およびPR3-ANCA 高値を示し,Wegener 肉芽腫症( WG) と診断された.一時シクロフォスファミド併用を含む,高用量副腎ステロイド療法が開始され,臨床および検査所見は改善した.ステロイド薬は漸減され,3 ヶ月後にはC-ANCA は陰性化した.WG は寛解していたが,8 ヶ月後に胸部下行大動脈瘤形成を認め,その1 ヶ月後に突然大喀血し,死亡した.動脈瘤形成は疾患活動性とは関連なく,経過中注意深い観察の継続を要する., A 79-year-old man was admitted because of fever andcough. He had been diagnosed with Wegener's granulomatosis(WG) on the basis of 10-year history of stuffy nose,pulmonary infiltrates with cavity formation, rapidly progressedrenal dysfunction with microscopic hematuria, andhigh level of PR3-ANCA. He was treated with high dose ofglucocorticoid( GC) temporarily in combination with cyclophosphamide,accordingly, the clinical manifestation and thelaboratory results had been recovering. The dose of GC wastapered down, and 3 months after the initiation of therapy,C-ANCA testing was negative. Despite remission was obtained,8 months after, chest computed tomography (CT)scan showed aneurysm formation on the descending aorta.One month after that, the patient had an abrupt onset ofcoughing up a massive amount of blood, and died. Aneurysmformation may develop independently of disease activityin WG and may be unpredictable, so that a carefulobservation whether aneurysm is formed should be continuouslyconsidered in the follow-up during the entire course.

35歳男性.入院約6週前より喀痰,咳嗽出現.数日前に左上肺空洞影指摘,喀痰中抗酸菌(3+)検出され入院.INH,RFP,PZA 及びEB による標準化学療法が開始された.咳嗽,呼吸困難,両肺野狭窄音聴取及び多量排菌持続し,気管支鏡所見上気管〜両側主気管支に隆起性潰瘍病変を認め,気管支結核を確定.高度の呼吸器症状遷延のため中等量のステロイド点滴投与を開始し,症状ならびに気道粘膜病変は改善した.高率に気管・気管支瘢痕収縮へ移行しうる気道粘膜像であったが,中等量の全身ステロイド療法により回避された.気道瘢痕狭窄回避のため,気管支結核活動性病変には中等量以上の全身ステロイド療法を考慮すべきと考えられた., A 35-year-old man admitted to the hospital because of acavitary lesion in the lung and acid-fast bacilli (AFB) (3+) in a sputum specimen, a polymerase-chain-reaction ofwhich revealed positive for M. tuberculosis. He had beenwell until approximately 6 weeks before admission, whenproductive cough developed. He also had temperature of upto 38 ℃, hoarseness, and shortness of breath couple of daysbefore. Intractable cough, dyspnea, wheeze in both lungfields, and numerous AFB in a sputum sustained, despiteprompt introduction of conventional chemotherapy containingINH, rifampicin, pyrazinamide, and ethambutol. Diagnosisof EBTB was confirmed by fibroptic bronchoscopy,which revealed granulomatous ulceration in the mucosa oftrachea and both main bronchi. Accordingly, intravenousmedium-dose methylprednisolone was administered, resultingrelief from serious respiratory manifestation and avoidanceof cicatricial stenosis of trachea and bronchi. This outcomesuggested that the current early intervention withglucocorticoid should be considered in serious active lesionof tracheal and bronchial mucosa in patients with EBTB.

Background:Bronchial asthma is considered to be a chronic airway inflammatory disease, and inhaledcorticosteroids play a central role in controlling airway inflammation. In some patients, however, it is difficultto control symptoms despite the use of moderate to high doses of inhaled corticosteroids. Long-actinginhaled b2-agonists have recently become available and reconsidered as a controller.Objectives:To examine whether combination of an inhaled corticosteroid and an oral b2-agonist can improvesymptoms in patients with moderate bronchial asthma whose airway obstructive symptoms cannotbe relieved sufficiently by inhaled corticosteroids alone.Methods:Of outpatients in our hospital with moderate bronchial asthma (step 3) given beclomethasoneat a daily dose of 800 mg, whose peak expiratory flow rate in the early morning was 70 % or less of the predictedvalue, 12 patients were enrolled in the study who showed at least 12.5 % improvement in the forcedexpiratory volume in one second (FEV1.0) after inhalation of 20 mg procaterol (Meptin Air from OtsukaPharma. Co.) for 15 minutes. Procaterol tablets (Meptin tablets, 50 mg from Otsuka Pharma. Co.) were administeredin the morning and before bed for 4 weeks, and change in the peak expiratory flow rate, subjectivesymptoms, respiratory function, and the number of puffs of the b2-agonist were evaluated.Results:The peak expiratory flow rate, FEV1.0, forced vital capacity (% FVC),and airway hyperresponsivenessimproved after coadministration of oral procaterol and beclomethasone.Conclusions:The oral b2-agonist in combination with an inhaled corticosteroid might improve asthmasymptoms better than inhaled corticosteroids alone.

The efficacy of a lymph node cell proliferation assay in the guinea pig as a first stage screening method of predicting sensitizing potentials of chemicals was studied by using several haptens. Animals were sensitized by a single 24-hr occlusive patch (24 cp), intradermal injection (id) and a combination of id and 24 cp, at a concentration used for guinea pig conventional contact hypersensitivity assay methods. Control animals were treated with vehicle(s) only. Suspensions of the lymph node cells (LNC) were individually prepared and cultured with [3H]methyl thymidine ([1H]TdR). [1H]TdR incorporation was measured and a stimulation index (SI) was calculated as a ratio of the mean [3H]TdR incorporation in sensitized animals and the mean [3H]TdR incorporation in control animals. LNC sensitized by 24 cp with 2,4-dinitrochlorobenzene proliferated maximally and significantly at day 5, whereas this occurred at day 7 after id sensitization. Significant LNC proliferation and high SI values were obtained successively by a combination of 24 cp and id. Moreover, strongly sensitizing chemicals increased significant LNC proliferation (SI > 2.0); weakly to moderately sensitizing chemicals also induced significant LNC proliferation (SI = 1.3 1.7). On the other hand, a primary irritant, sodium dodecyl sulfate, failed to encourage LNC proliferation (SI ≈ 1.0).

A new method for delayed contact hypersensitivity assay of chemical compounds in guinea pigs, a short-period method (14 days) with a high detection sensitivity, has been developed. The new method was as follows; a combination of a Freund's complete adjuvant (FCA, undiluted) intradermal injection and a 24-h occlusive patch on a guinea pig was performed 2x at an interval of 4 days and challenged by non-occlusive topical application 11 days after the first sensitization (with benzyl alcohol during test development). Acanthosis and spongiosis in the epidermis and mononuclear cell infiltration into the dermis were observed histopathologically at the skin reaction site. This newly developed method (adjuvant and 24-h occlusive patch 2x test: AP2 test) could equally and/or better detect the allergenicities of 6 other chemical compounds (bromostyrol, citronellal, benzyl salicylate, p-aminobenzoic acid ethyl ester, p-phenylenediamine and formaldehyde) as compared with the cumulative contact enhancement test (CCET) and the guinea pig maximization test (GPMT).

Simple and efficient ex vivo/in vitro screening systems for contact allergens are developed for alternative to conventional animal tests. We have previously proposed an ex vivo/in vitro proliferation assay as a first stage screening method with advantages over existing alternatives, using lymph node cells (LNC) from sensitized guinea pigs of the Hartley strain. In this study, we have first confirmed, by histochemical analysis using in vivo bromodeoxyuridine (BrdU) and pyronin staining, that the ex vivo/in vitro LNC proliferation reflects in vivo response of lymph nodes to contact allergens. Furthermore, to improve the LNC assay, we then have investigated several experimental conditions for their influences on the LNC assay, demonstrating that, (1) the subscapular and the cervical LNC responded highly to contact allergens, (2) among three cervical lymph nodes the superficial dorsal cervical lymph nodes were the most reactive, (3) several vehicles alone used for animal sensitization exhibited little influence on the LNC proliferation, (4) employment of stimulation index offset the inter-batch fluctuation of the LNC proliferation in the control animals as baseline proliferation. Under optimized experimental conditions as above, experimentally determined stimulation indexes of several contact allergens correlated well with their sensitizing potential estimated by conventional animal tests. Therefore, the ex vivo/in vitro LNC proliferation assay should be a simple and efficient alternative to conventional guinea pig testings including the guinea pig maximization test (GPMT).

The enhancement effect of cyclophosphamide on the delayed contact hypersensitivity reaction of chemical compounds was studied in Hartley albino guinea pigs. A series of assay procedures, combining the AP2 test (adjuvant and 24-h occlusive patch 2x test, as previously reported) with intraperitoneal cyclophosphamide administration, were examined. The newly developed method was as follows; cyclophosphamide 200 mg/kg intraperitoneal administration 3 days before the 1st sensitization of the AP2 test (cyclophosphamide, adjuvant and 24-h occlusive patch 2x test: CAP2 test). Comparing the CAP2 test with the AP2 test, the cumulative contact enhancement test (CCET) and the guinea pig maximization test (GPMT), the CAP2 test equally and/or better enabled the detection of allergenicities not only of strong allergens such as bromostyrol, citronellal, p-phenylenediamine and formaldehyde, but also of weak allergens such as benzyl salicylate and p-aminobenzoic acid ethyl ester. Acanthosis and spongiosis in the epidermis and mononuclear cell infiltration into the dermis at the skin reaction site were histopathologically observed. Cyclophosphamide effectively enhanced the delayed contact hypersensitivity reaction of weak allergens.

We report a case of a middle-aged man who suffered a cerebral infarction resulting from dissection of a vertebral artery associated with morning blood pressure surge. A 56-year-old man was transferred to our hospital with dizziness and vomiting in the early morning on a cold day in winter. He reported that he had been standing in front of the sink after bathing when he suddenly felt dizzy and fell down. He did not lose consciousness, and by the time he reached the hospital by ambulance, his dizziness had subsided, but he complained of severe headache and vomited 3 times. On admission, he was alert, and there were no neurological or radiological abnormalities (CT, MR angiography) in the brain. However, infarction in the left cerebellar hemisphere was detected by brain MRI on the 5th day of hospitalization. String sign of the left vertebral artery was noted by angiography, confirming the diagnosis of dissection of the left vertebral artery. Ambulatory blood pressure monitoring was performed after discharge. Although the mean 24-h blood pressure was in the normal range, a marked morning blood pressure rise was observed. We speculated that the acute rise of blood pressure in the early morning might have contributed to the dissection of the vertebral artery.