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Background Dietary fatty acids can affect chronic intestinal inflammation and have been reported to be associated with the development of ulcerative colitis (UC), mainly in Europe and the United States. The association of dietary intake of fatty acids and the risk for UC was investigated in Japan, where dietary habits lead to lower meat and higher fish consumption than in Western countries. Methods A multicenter case-control study of 83 newly diagnosed patients with UC and 128 age- and sex-matched control patients in the hospital was conducted from 2008 to 2014. Dietary fatty acid intake in the preceding 1 month and 1 year were examined using a self-administered diet history questionnaire that was developed for Japanese people. Results About 92% of patients had experienced the first symptoms of UC within the preceding 11 months. Regarding dietary habits in the preceding year, the risk for UC was significantly decreased in patients who consumed n-6/n-3 polyunsaturated fatty acids at a ratio of ≥5.2 (odds ratio [OR] = 0.26; 95% confidence interval [CI], 0.10-0.68). Conversely, an increased risk for UC was observed in the highest tertiles of consumption of docosahexaenoic acid (OR = 7.22; 95% CI, 2.09-24.95), eicosapentaenoic acid (OR = 6.91; 95% CI, 1.88-25.44), and docosapentaenoic acid (OR = 4.83; 95% CI, 1.56-14.95). Conclusions The ratio of n-6/n-3 polyunsaturated fatty acid intake was associated with a decreased risk for UC development. However, high intakes of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid may increase the risk for UC development.

AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis.This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment.Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug.AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis.EA Pharma and Kissei Pharmaceutical.For the Japanese translation of the abstract see Supplementary Materials section.

SUMMARY 1. Production of nitric oxide (NO) is implicated in the pathogenesis of inflammatory bowel disease. However, the cells responsible for the production of NO in situ in the human colon remain unknown. 2. Surgical samples from 12 patients with ulcerative colitis, eight patients with Crohn’s disease and 10 controls were studied. Possible generation of NO was visualized by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity in human colon. Immunohistological staining for various NO synthase (NOS) isoforms (endothelial, neuronal and inducible), nitrotyrosine and interleukin-2 was also performed. 3. Reduced NADPH diaphorase activity was not found in lamina propria mononuclear cells, but was found in colonic epithelium, endothelium and myenteric neurons and their processes. 4. The NADPH-diaphorase activity positive processes were significantly less common in colon from patients with Crohn’s disease compared with control colon. 5. Endothelial NOS was constitutively expressed on colonic endothelium. 6. Neuronal NOS was constitutively expressed on myenteric neurons. 7. Expression of inducible NOS (iNOS) was increased in the epithelium and endothelium of the colon of patients with ulcerative colitis. 8. No correlation was found between expression of iNOS and NADPH diaphorase activity. 9. Nitrotyrosine was expressed by lamina propria leucocytes, but not by epithelium. 10. Interleukin-2 was expressed on both leucocytes and myenteric neurons. 11. Colonic epithelium, endothelium and myenteric neurons synthesize NO. Myenteric neurons were principally responsible for NO production and NO may act as a neurotransmitter in the enteric nervous system.

当科にて現在まで経験した腸管ベーチェット病9例および単純性潰瘍4例について臨床的に検討した. 性別は男性11例, 女性2例である. 初発年齢は11歳から58歳, 平均36歳である. 診断の内訳は完全型ベーチェット病1例, 不全型ベーチェット病3例, ベーチェット病疑いが9例であり, 疑い症例のうち消化管病変以外のべーチェット病症状を認めない症例は4例である. 初期診断はクローン病4例 (うち1例は虫垂炎, 他の1例は腸結核も疑われる), ベーチェット病3例, 大腸癌2例, 若年性関節リウマチ1例, 膠原病1例, 単純性潰瘍1例, 不明1例である. 完全型および不全型ベーチェット病では2例で腸管切除が行われ, 頻回の入院歴がある. ベーチェット病疑い5例のうち2例で腸管切除が行われているが, 単純性潰瘍4例では1例が大腸癌の疑いにて腸管切除が行われているほか手術および入院の既往はなく, 臨床的に腸管ベーチェット病と異なる経過であった.

We report results of a retrospective chart review to evaluate factors predicting short-term outcome of patients with ulcerative colitis treated by corticosteroids. Between January 1992 and December 1997, we treated 71 patients with ulcerative colitis (44 with severe and 27 with moderately severe disease). Forty-nine patients were treated by conventional prednisolone therapy and 22 patients by steroid pulse therapy. There were no differences in clinical or endoscopic improvement between the two treatments. Clinical examination showed that 41 patients entered remission, 17 patients improved, and 13 patients did not respond. Endoscopically, 26 patients entered remission, 30 patients improved, and 15 patients did not respond. Extent of disease, type of disease (first attack, relapsing, or chronic active type), and endoscopic findings were factors useful in predicting short-term outcome of medical treatment.

Objective: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. Methods: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. Results: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. Conclusion: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis.

外来にて経過観察中に再燃をきたした潰瘍性大腸炎中等症6例に対して,ステロイド・パルス療法を行った.対象は男性5例,女性1例であり.左側大腸炎型4例,全大腸炎型2例である,年齢は25歳から49歳で,平均34歳である.パルス療法としては,1日量としてmethyl-prednisolonelgを補液に混じて点滴静注した.3日間連日点滴した後4日間休薬し,上記7日間を1コースとして,3例に1コース,3例に2コースのステロイド・パルス療法を行った.その結果,臨床的に緩解3例,有効1例,無効2例であり,有効および緩解例4例において入院が回避された.

SUMMARY 1. Phenotypical heterogeneity of macrophages infiltrating the colonic mucosa of patients with ulcerative colitis has been shown in many reports. The functional diversity of macrophages in inflamed colonic mucosa remains unclear. 2. Intestinal macrophages have been characterized by immunohistochemical staining and their ability to generate free oxygen radicals in inflamed and non-inflamed mucosa. 3. No correlation was found between RFD1 (activated dendritic cells), RFD7 (tissue macrophages) or RFD9 (epithelioid cells, giant cells in association with granuloma) positivity and either CD68 or human histocompatibility complex class II antigen (HLA-DR) positivity. The proportions of RFD7- and RFD9-positive cells were significantly increased in inflamed colonic mucosa. Nitroblue tetrazolium-reducing mononuclear cells were CD68 or RFD7 positive but they were rarely positive for HLA-DR and RFD1. 4. These results suggest that nitroblue tetrazolium-reducing macrophages are (scavenger) macrophages.

80歳,男性.水様性下痢を初発症状とし,その後血便が出現し当科を受診した.大腸内視鏡検査(以下CF)にて全大腸炎型潰瘍性大腸炎(以下UC)と診断した.本例は肝硬変,肝細胞癌,膝関節症,側弯症を合併していたため副作用を考慮してステロイドパルス療法を行った.Hydrocortisone sodium succinateを1日1g点滴静注し,3日間を1コースとして計4コース施行した.パルス療法施行後,臨床症状の改善と内視鏡的緩解を認めた,高齢者はさまざまな合併症を伴っていることが多いため,全身状態と副作用とを考慮した治療法が要求され,パルス療法は高齢者UCの治療法の1つとして位置づけるべきと考えられた.

クローン病の実験モデルである2,4,6-trinitrobenzene sulfonic acid(TNBS)大腸炎を作成し,塩酸Azelastine(AZ)を投与して病変粘膜局所における免疫担当細胞の動態を免疫組織化学的に検討した.TNBS大腸炎群の潰瘍形成部ではICAM-1,Mac-1陽性の単核球の強い浸潤があり,隣接した粘膜固有層にはICAM-1陽性の血管内皮細胞とLFA-1,Mac-1陽性の単核球の増加がみられた.AZ投与群では,潰瘍形成を示したのは5例中1例のみであった.肉眼的に炎症のない粘膜においては,TNBS大腸炎群に比べICAM-1の発現とLFA-1,Mac-1陽性細胞は軽度に認められるのみであった.IgG,IgE含有細胞および好酸球数も有意に低下していた(p

A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC). From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI. A total of 195 patients with UC who underwent colorectal surgery were enrolled. SSI was diagnosed in 38 (19.5 %) patients, in the form of incisional infection in 23 (11.8 %), organ/space infection in 16 (8.2 %), and both in 1 (0.5 %). There were no significant risk factors associated with an increased risk of development of incisional SSI. An American Society of Anesthesiologists physical status of ≥ 3 was indicated as the only significant risk factor for organ/space SSI (P = 0.02) compared with other factors, such as a neutrophil count of >100 × 102/mm3, albumin level of

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.

クローン病に対する内科的緩解維持療法の有用性についてretrospectiveに検討した.対象は緩解期クローン病60例であり, 男性39例, 女性21例である.罹患範囲別には大腸型11例, 小腸型20例, 小腸大腸型29例である.栄養療法, 薬物療法およびこれらの併用療法による緩解維持効果に関して検討した.観察期間は214日から3,365日であり, 平均2,873日である.性別および罹患範囲別に有意な累積緩解率の差はみられなかった.合併症を有する症例では, 有意に累積緩解率が低下した.治療法別の累積緩解率では有意差は認められなかったが, 罹患範囲別に小腸大腸型においては併用療法が栄養療法に比して有効である傾向が認められた.

SUMMARY In this study the effect of K-76. a sesquiterpcne compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochcmical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotcin concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.

The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease.

The effect of stress on the activity and level of mRNA of spermidine/spermine N 1 -acetyltransferase (SAT), a polyamine degradation rate-limiting enzyme, was studied in Ehrlich ascites tumor cells. When the cells were treated with sodium arsenite or ethanol for 1 h at 37°C, the activity of SAT increased time- and dose-dependently. Total RNA was isolated from cells treated with stress, and the relative abundance of the SAT mRNA was measured by Northern blot analysis. The amount was comparable to those in control cells. In stress-treated cells, the biological half-life of the enzyme was 48–55 min, but 27–30 min in control cells. When cells were treated with arsenite in the presence of cycloheximide, enzyme activity did not increase. In those cells, half-life of the enzyme was shorter than in the cells treated with arsenite alone. This suggests that stress-treatment of cells enhanced SAT activity posttranslationally and that some factor(s) which was synthesized de novo during the treatment of arsenite is involved in the stabilization of the enzyme.

Crohn病102症例中肛門病変合併は30例(29.4%)にみられた.本症における消化管,あるいは全身的症状の出現以前における肛門病変の出現は7例(23.3%)であり,このうち大腸型Crohn病の5例中4例は肛門周囲膿瘍・痔瘻に至っている.肛門病変の種類別頻度は,肛門周囲膿瘍23例(76.6%),skin tag 6例(20%),直腸腔瘻3例(10%)である.Crohn病の腸管病変別の頻度は小腸型14例(47%),小腸・大腸型6例(20%),大腸型10例(33%)であり,これらのうち大腸病変を含有する場合においては肛門病変は53.3%を占めた.内科的治療と肛門病変との関連性は認められないが,Crohn病発症の早期の段階のdisease activityの高い時期に出現する傾向が強く,初期の治療の重要性が示唆された.

One hundred and twenty-one ulcerative colitis patients diagnosed during the period of 1984 to 1988 were examined endoscopically on repeated occasions. Forty-six patients had total colitis, 56 had left-sided colitis, 15 had proctitis, and 4 were postoperative patients. When classified according to their macroscopic findings, 28 of the patients had the polyposis type of this disease, 88 had the atrophic type, and 5 had the mixed type. Longitudinal ulcers were found in 9 patients, occuring usually in the sigmoid colon. There was no pathological evidence of ischemic changes in these 9 patients. Mucosal bridges were found in 13 of the patients with total colitis, occurring somewhere from the cecum to the rectum. The mucosal bridges tended to be present during the mildly active stage of the disease. Red spots, which sometimes looked like vascular spiders, were found in 10 patients. The spots tended to appear before the disease went into the inactive stage. Histological observation showed regenerating vessels, sometimes with intramucosal bleeding; therefore the spots seemed to be intractable changes.

患者の受容性を向上させるためPEGの服用量を2Lよりもさらに減量するための改良を試みた.すなわち,PEG併用法においてPEG服用開始後の排便回数が4回あった時点で服用を中止するという方法(PEG変法)をretrospective studyより設定し,100人の患者に本方法を行いPEG併用法を行った100人と比較検討した.その結果,服用量はPEG併用法の2000mlに対して1710±280ml(1000-2000m1)と有意(p

当科にて昭和61年3月より平成1年2月までの期間に臨床的に検討しえた小児潰瘍性大腸炎9症例 (発症年齢 : 11歳から14歳までの男子6名女子3名, 平均12.4歳) について検討した。初発症状, 既往歴, 家族歴に特異的な事象は認められなかった.罹患範囲は全大腸炎型5例, 左側大腸炎型3例, 直腸炎型1例であった.臨床経過は再燃・緩解型が6例, 現時点での初回発作型は2例, 慢性持続型が1例である.9症例をまとめた結果, (1) 罹患範囲としては全大腸炎型が過半数を占め, 重症度別には重症例が少ない傾向を認めた, (2) 病型は再燃緩解型が67%であり, 頻度的に成人型と変わりはなかった. (3) 再燃緩解型は, 投薬の漸減中に再燃を起こしやすい傾向にあった. (4) betamethazone (リンデロン ®) 坐薬の併用が緩解維持に有効と考えられた. (5) salazosulfapyridine (サラゾピリン ®) の緩解維持効果は確認できなかった. (6) 再燃時のsteroidhormone投与開始量としては30mg/dayが有効と考えられた.

Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2-microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase.

Salicylazosulphapyridine and corticosteroids are the only remedies for inflammatory bowel disease currently in clinical use. They do not, however, necessarily bring about satisfactory therapeutic benefits, so that new agents are needed. In this study, we evaluated the effect of bucillamine, a new antirheumatic agent, in experimental rat colitis induced by trinitrobenzene sulfonic acid enema. Wistar rats were given vehicle alone (n = 16) or treated with 50 (n = 20) or 150 (n = 20) mg/kg of bucillamine daily for three weeks after induction of colitis. Conventional histological sections of the colon stained by haematoxylin and eosin were prepared and observed under a light microscope to determine colonic damage scores. The determinations were significantly lower in the group treated with 50 mg/kg of bucillamine and tended to be lower in the group treated with 150 mg/kg of bucillamine than in the untreated group, which implied that the experimentally induced colonic inflammatory changes and ulcerations were alleviated by bucillamine. Blood tests showed no abnormal values at the end of the treatment. The present observations suggest that bucillamine should be developed further as a possible therapy for inflammatory bowel disease.

Studies of the T-cell-receptor repertoire and oligoclonal expansion of lamina propria T cells in patients with Crohn's disease suggest restricted antigen processing in this disease. We examined HPLC elution profiles of HLA-DR-bound peptides isolated from human intestine. Surgical samples of colon and ileum were obtained from patients with ulcerative colitis, patients with Crohn's disease, and normal colon from patients undergoing colon carcinoma treatment as controls. Specimens were homogenized and HLA-DR molecules were isolated using anti-HLA-DR antibody-coupled immunoaffinity chromatography. HLA-DR-bound peptides were dissociated from the HLA-DR groove by acid treatment, isolated, and analyzed by reversed-phase HPLC. HPLC elution profiles of HLA-DR-bound peptides were similar in patients with ulcerative colitis and controls. Large peaks were found in patients with Crohn's disease, but the retention times of these peaks differed among individuals. Elution profiles of HLA-DR bound peptides suggest that specific antigen presentation might occur in patients with Crohn's disease, although the specific antigens appear to differ between patients.

Primary sclerosing cholangitis is often accompanied by inflammatory bowel disease in western countries. However, the incidence of primary sclerosing cholangitis in patients with ulcerative colitis appears to be much lower in Japan.Between 1980 and 1998, a total of 402 patients with ulcerative colitis were seen in our department. The patients were evaluated by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography when persisting abnormalities of biochemical findings suggested the presence of hepatobiliary diseases.Of the 402 patients with ulcerative colitis, 3 patients with primary sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had left-sided colitis while 2 had total colitis. Magnetic resonance cholangiopancreatography was done in 2 of these 3 patients and demonstrated diagnostic features of primary sclerosing cholangitis. All 3 patients had intra- and extrahepatic involvement by primary sclerosing cholangitis. One male patient died due to progressive hepatic failure. The other male patient was treated with ursodeoxycholic acid, but serum alkaline phosphatase level remained above the normal range. The female patient maintained normal serum alkaline phosphatase levels without specific medication.Magnetic resonance cholangiopancreatography is the most safe and convincing tool for the diagnosis of coexistent primary sclerosing cholangitis in the patients with ulcerative colitis.

Background: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. Methods and Results: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. Conclusions: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.

OBJECTIVE: The pathogenesis of Crohn’s disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC). METHODS: We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12). RESULTS: In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC. CONCLUSIONS: The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.

body tomograph SET2400W (Shimadzu Co, Japan), with an intrinsic spatial resolution of 3·9 mm. The figure shows PET images of the subject lying supine. Correction of tissue attenuation was made after emission acquisition (postinjection transmission) using a needle Ge/Ga source. We found that F-FDG uptake was increased in the soleus and gastrocemius muscles—those most exercised in endurance running. Lesser accumulations of F-FDG in other muscles including those of the thighs were also noted. These images indicate that PET can identify muscles used in physical activity. The amount of radioactivity required for imaging can probably be reduced to less than 40 MBq, corresponding to a whole body radiation dose of around 0·5 mSv, equivalent to half the exposure of an abdominal radiograph. PET mapping of muscle activity may provide useful information for sports and rehabilitation medicine.

The production of reactive oxygen species may have an important role in the pathogenesis of inflammatory bowel disease, yet the cells responsible in colonic mucosa have not been clearly defined. We studied 28 patients with ulcerative colitis and 13 controls to determine the cells generating reactive oxygen species, using a combined method for determining nitroblue tetrazolium reducing activity and immunohistochemical characterization. In contrast to the proportion of EBM11-positive cells (tissue macrophages), which did not increase in inflamed mucosa, the proportions of PMN-13F6 positive cells, CD11b-positive cells, and eosinophils were significantly increased in inflamed mucosa. PMN-13F6 positive cell and eosinophil counts were significantly correlated with CD11b positivity. Eosinophils, however, showed a stronger correlation with CD11b positivity than PMN-13F6-positive cells. The majority of CD11b-positive cells were eosinophils. Although some nitroblue tetrazolium reducing leukocytes were positively stained with EBM11 or PMN-13F6, eosinophils were the major subset of nitroblue tetrazolium reducing leukocytes. Recruitment and activation of eosinophils may play an important role in the pathogenesis of ulcerative colitis.

BACKGROUND: Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known about their functional activity in vascular endothelium. METHODS: We studied in situ nitroblue tetrazolium reducing activity and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in the same biopsy specimen in controls and patients with ulcerative colitis (UC). RESULTS: VCAM-1 expression was negative in mucosal vessels. E-selectin-positive vessels were significantly increased in endoscopically active colitis compared with normal mucosa. ICAM-1-positive vessels were consistently found in normal, quiescent UC and active UC. CD31-positive vessels were not significantly increased in quiescent UC and active UC compared with control. Only E-selectin significantly correlated with the histologic grade of inflammation. Nitroblue tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue tetrazolium reduction was mainly seen in the large mucosal vessels, but capillaries showing nitroblue tetrazolium reduction were rarely positive for E-selectin. CONCLUSIONS: Phenotypic and functional activation of vascular endothelium might be involved in the recruitment of leukocytes and tissue destruction of inflamed colonic mucosa.

To identify which cells generate superoxide, inflamed human mucosa was tested with nitro-blue tetrazolium as a probe, because it is reduced by strong reducing agents to form insoluble blue formazan, which then precipitates in tissues. Biopsy specimens from control subjects and patients with ulcerative colitis were studied. The specimens were organ cultured with bubbling air or nitrogen, and inhibition of the reduction by catalase (a hydrogen peroxide scavenger), para-benzoquinone (a tissue permeable superoxide scavenger), or superoxide dismutase (a superoxide scavenger) was assayed. The dye was reduced by epithelial cells, vascular endothelium, and infiltrating mononuclear cells of the mucosa. Its reduction by vascular endothelium and infiltrating mononuclear cells was greater in inflamed mucosa. The reduction by vascular endothelium and infiltrating mononuclear cells was inhibited in cultures with nitrogen saturation or with 1 mM para-benzoquinone. The vascular endothelium seems to produce superoxide in the inflamed mucosa, which would exacerbate tissue injury in ulcerative colitis.

5年以上経過追求しえた潰瘍性大腸炎46例について臨床的検討を加えるとともに,当科にて術後経過追求しえた手術例8例についての残存直腸のmanagementを中心に検討した.長期経過例46例は全大炎型24例,左側大腸炎型15例,直腸炎型7例であり,重症例のうち77%が全大腸炎型である.これら46例について難治性および非難治性症例に分けて検討した.難治例は46例中21例,45.6%であり,男女比は難治例2:1,非難治例0.8:1である.長期経過例の内視鏡的経過についての検討では,難治例では経過にともない粘膜の萎縮像や炎症性ポリポーシスを呈する症例が多く認められた.また,難治例においては直腸が治療に反応するにもかかわらず,その口側大腸に活動性の潰瘍性あるいはびらん性病変が残存する傾向にあった.手術例8例は術前すべて全大腸炎型であり,慢性持続型3例,再燃緩解型5例であった.術後の内科的治療としては,salicylazosulphapyridine 3-4gを基本とし,残存直腸の活動性病変ならびに再燃病変にはbetamethasone座薬1-2mgの併用療法を行った.

潰瘍性大腸炎 (ulcerative colitis : UC) を長期経過例も含めて臨床的な面から難治性の要因を分析し, 難治性UCとしてのcriteriaを設けることを試みた. 5年間以上にわたって追求し得たUCでは頻回再燃例や厳密な内科的治療に奏効せず, 活動期間が遷延したり, より重症化する傾向が得られた. これらの症例は, (1) 慢性持続型, (2) 再燃後6カ月以上活動期にある例, (3) 頻回に再燃をくり返す例, のいずれかに相当するものであり, これらを総括して難治性UCとした. その結果, 難治性UCでは26%において罹患範囲が進展し, 再燃の頻度は発症後の5年以内において高く, その後低下する傾向を示した. 活動期間は発症後5年以内では年当りに占める割合は低いが, 6年から15年間では逆に高くなった. 難治性UCの中で, とくに3回以上再燃し, かつその都度重症化し, 6カ月以上活動期にある場合は相対的手術適応と考えた.

当教室で外科的治療が行われた潰瘍性大腸炎15例を対象に検討を加えた. 発症時年齢は平均29. 7歳であり, 男性11例, 女性4例であった. 罹患部位別では全大腸炎型12例, 左側大腸炎型3例, 重症度別分類では重症8例, 中等症7例であった. 合併症は白内障, 両側大腿骨頭壊死, 静脈血栓症, 痔疾患などがみられた. 手術適応は, 緊急手術が5例 (大出血3例, 穿孔1例, 中毒性巨大結腸症1例) であり, 準緊急手術が1例, 待期手術が9例であった. 手術術式は, 結腸全摘・回腸直腸吻合術7例, 結腸全摘・回腸瘻造設術5例, 大腸全摘・回腸瘻造設術2例, 盲腸瘻造設術1例であった. 術後は12例においてほぼ満足した社会生活を営んでいた.

抗生物質に起因する非偽膜性出血性腸炎は, 抗生物質投与2～3日後に突発的に腹痛, 下痢, 下血を生じ, 炎症所見を伴う.症状の割に理学的所見は軽度といえる.起因薬剤としては合成ペニシリンが大半を占め, 基礎疾患, 投与方法, 投与量に一定の傾向はない.診断には大腸内視鏡検査が有用で, かつ大腸全域の観察が肝要である.病変部にはびまん性のerosion, 出血がみられるが, 非偽膜性で, 主病巣の近傍の粘膜の散在性のerosionや出血斑などは特徴的といえる.本症は腸内細菌のなかでも嫌気性菌のClostridium difficileのenterotoxinにより粘膜を障害するとする偽膜性大腸炎と同じ病態生理に基づくとするものや, Klebsiella oxytocaに発生因子を求める考え方などがある.

患者は68歳女性,腹痛を主訴に来院し,注腸透視にて上行結腸に約2cm大の表面平滑で境界明瞭な腫瘤陰影を認め,大腸内視鏡検査では同部にやや黄色調を呈する可動性に富む軟かい有茎性ポリープを認めた。診断と治療の目的に内視鏡的ポリペクトミーを行った.摘出標本の大きさは1.7×1.5×1.5cmで,病理組織学的には粘膜下に発生した脂肪腫であった.大腸脂肪腫は近年増加傾向にあるが,内視鏡的ポリペクトミーにより摘出例は本例を含め23例に過ぎない.内視鏡的ポリペクトミーは本症の診断と今後の治療法として有用と考える.