Shigemi Sakamoto

Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: a prospective randomized study

BACKGROUND/AIMS Although ursodeoxycholic acid is effective for the treatment of primary biliary cirrhosis, some patients do not respond to this treatment. The objective of the present study was to investigate the effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. METHODS Twenty-two patients with primary biliary cirrhosis treated with ursodeoxycholic acid (600 mg/day) for 30 months were randomly assigned to two groups: group 1, colchicine (1 mg/day) and ursodeoxycholic acid (n = 10); group 2, ursodeoxycholic acid alone (n = 12). RESULTS In group 1, there were significant decreases in mean serum levels of alkaline phosphatase, total bilirubin, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, and IgM, and these changes were more remarkable in those who responded poorly to ursodeoxycholic acid. In contrast, there were no significant changes in those values in group 2. CONCLUSIONS Additional administration of colchicine to ursodeoxycholic acid may be beneficial for patients with primary biliary cirrhosis, especially those who respond poorly to ursodeoxycholic acid. It is necessary, however, to further confirm the efficacy of colchicine by examining histological changes and following the patients for longer periods.

Severe chronic active hepatitis induced by UFTR containing tegafur and uracil.

SummaryA 77-year-old female patient developed severe hepatic injury after the administration of UFTR, which contains tegafur and uracil, for postoperative chemotherapy of colon cancer. Liver damage was recognized 10 months after its administration. Serum markers for viral hepatitis and various autoantibodies were negative. The wedged biopsied liver specimen revealed advanced chronic active hepatitis with periportal confluent necrosis, marked intralobular spotty necrosis, and significant proliferation of pseudo-bile ductules. Although the cessation of the drug and conservative therapies improved hepatic function, an accidental readministration of UFTR caused her severe hepatic damage again. These findings suggest that liver injury in the present case was caused by UFTR. Histological findings were unique. Although tegafur is known to worsen hepatic function when given to patients with liver cirrhosis, UFTR may also cause severe hepatic injury in those without preexisting liver disease.

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and αβ‐receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, γ‐globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.

Case Report: A Variant Alkaline Phosphatase-Producing Gastric Carcinoma with Super Bone Scan

in English) 4. Uchida T, Shikata T, Shimizu S, Takimoto Y, Iino S, Suzuki H, Oda T, Hirano K, Sugiura M: Gonadotropin and alkaline phosphatase producing occult gastric carcinoma with widespread metastasis of generalized bone. Cancer 48:140 ± 150,

Flow Cytometric Method to Detect Lymphocyte Transformation in Drug-Allergic Hepatic Injury

Flow cytometric methods for the analysis ofincorporated bromodeoxyuridine are extremely rapid andsimple. We investigated whether these methods wereuseful for detecting drugallergic hepatic injury in 18 patients with drug-allergic hepatic injury,18 healthy controls, and 9 nonallergic patientsreceiving drugs. Peripheral blood mononuclear cells werestimulated with drug solutions. Incorporation ofbromodeoxyuridine was detected after labeling with FITC, andS-phase cells were counted by flow cytometry.Percentages of S-phase cells in drug-stimulated cultureminus those in spontaneous cultures were less than 1% in both healthy controls and nonallergic patientsreceiving drugs. Taking 1% as the upper limit, 13patients (72%) were judged as positive. After the invitro addition of interleukin-2, two patients among five who had been judged as negative werejudged as positive. Lymphocyte transformation test byflow cytometry may be useful in the diagnosis ofdrug-allergic hepatic injury.

Case Report: Gastric Adenocarcinoma Producing Neuron-Specific Enolase

Enolase s (2-phospho-D-glyce rate hydro-lyase , EC 4.2.1.11) are glycolytic enzymes that convert 2-phosphoglyc erate to phosphoenolpyruvate . They are dimers composed of three immunological ly distinct subunits a , b , and g (1, 2). The g g and a g -enolase s are expressed preferentially in neurons and neuroendocrine cells (3, 4), and neuron-spe ci® c enolase (NSE) has often been used to refer to the g g -enolase or g -subunit itse lf (5). Tumors with neuroendocrine characte ristics, including small cell carcinoma of the lung and neuroblastoma contain high concentrations of NSE (6, 7). A majority of patients bearing such tumors have high serum NSE leve ls (8 ± 10) . Although neuroendocrine granule s were often demonstrable ultrastructural ly in gastric endocrine tumors (11± 14) and a part of a solid carcinomao of the stomach (15) , gastric adenocarcinoma with high serum NSE leve ls has not been reported. Described in this article is an autopsy case of gastric adenocarcinoma with high serum NSE leve ls. NSE was detected in the carcinoma cells by immunohistoche mistry, which was conside red to result in elevated serum NSE leve ls.

[A case of lupoid hepatitis, factor XI deficiency and Hashimoto's disease with circulating anticoagulant].

ルポイド肝炎に先天性第XI因子欠乏症と橋本病を合併し,経過中に循環抗凝血素が出現したと考えられる症例を経験した.症例は69才,女性.鼻出血の止血困難を主訴とし,肝機能異常,全血凝固時間と活性化部分卜ロンボプラスチン時間(APTT)の延長,甲状腺機能低下,各種自己抗体陽性所見が認められた.第XI因子活性は4.8%と著明な低値を示した.入院後, LE細胞陽性化に続いて肝胆道系酵素の上昇,内因系凝固因子活性の低下が観察され,循環抗凝血素の存在が確認された.プレドニゾロン投与後循環抗凝血素は消失したが,第XI因子活性低値は持続した,娘に第XI因子活性の低値が観察されたことから,第XI因子欠乏症は先天性であると考えられた.

A young female case of myxedema associated with atrophic gastritis (type A) with remarkable hypergastrinemia

症例は29才の女性で, 26才頃より耐寒性が低下し,皮膚が粗〓で便秘傾向であつた. 27才より無月経となり,甲状腺の精査を勧められ入院となつた.体温は35.2°C,甲状腺腫はなく,腋毛・恥毛は希薄であつた.心臓超音波断層検査で著明な心膜液の貯留を認め,甲状腺機能検査では, T3 3.5ng/dl, T4 0.3μg/dl, TSH 218μU/ml,基礎代謝率-56.5%であり,粘液水腫と診断された.一方,血清gastrinは6830pg/mlと正常の約70倍の高値を示し,末梢血で小球性低色素性貧血を認め,血清ビタミンB12は正常で,悪性貧血は伴つていなかつた.胃液検査では, basal acid output (BAO) 0.27mEq/h, maximum acid output (MAO) 0.28mEq/hと無酸症を呈し,胃底腺領域の生検所見は,萎縮性胃炎の像を呈していた.また,経口的胃内酸負荷では, gastrinは急速に低下したため,本例における高gastrin血症は,萎縮性胃炎に伴う負のフィードバックによると考えられた.本例では,抗甲状腺自己抗体が陰性であるが,一般に特発性甲状腺機能低下症は橋本病が成因と考えられ,一方type A萎縮性胃炎では,抗胃壁細胞抗体が陽性のことが多く,その進展に自己免疫現象の関与が唱えられている.悪性貧血も橋本病などの自己免疫疾患との合併が多く,その本体が萎縮性胃炎に伴うビタミソB12の吸収障害であることから,本例は,甲状腺疾患と胃病変の関連を考えるうえで示唆にとむ1例と考えられた.

A case of metronidazole-induced liver injury.

Metronidazoleによると考えられる薬物性肝障害の1例を経験したので,臨床経過を中心に報告した。症例は35歳の男性で夫人が膣トリコモナス症に罹患したため,Metronidazoleの投与をうけた.内服開始後13日目に発熱,腹痛が出現し,肝機能障害の指摘をうけた.白血球増加,著明な好酸球増加がみられ,リンパ球刺激試験を実施したところ,Metronidazoleが陽性であったことから,本例は,Metronidazoleによる薬物性肝障害と診断された.肝生検組織像では,小葉中心性の肝細胞壊死および細胞浸潤を認めた.Metronidazoleは,抗トリコモナス薬として広く使用されているが,その副作用として肝障害の報告はなく,本例がその最初の報告であると思われる.