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AIDSが誘因となった播種性非定型感染症にて腸閉塞をきたした1例を経験した. 症例は48歳の男性. 主訴は腹痛と嘔吐であった. 開腹既往歴なし. 1996年カリニ肺炎にてAIDS発症, その後サイトメガロ網膜炎, 陰部ヘルペス, 頸部リンパ節腫脹を伴う播種性非定型抗酸菌感染症を発症し当院外来にて加療中であった. 2000年に左下腹部痛を主訴に当院を受診した. 身体所見上左下腹部圧痛を認め, 諸検査にて腸閉塞と診断され, 入院した. 入院3日後症状増悪し緊急開腹手術を施行した. 開腹所見にて, 横行結腸と癒着しarch を形成する上部空腸腸間膜リンパ節の著明な腫大を認め, 空腸が陥入し腸閉塞となっていた. Archを解除し陥入する小腸を引き出したところ, 腸管の色調は著明に改善を認めたために腸切除を行うことなく手術を終了した. 術後25日目に退院したが, 術後123日目にAIDSの増悪にて死亡した. AIDSが誘因となった腸閉塞は本邦でも今後増加する可能性があり, 文献的考察を加え報告する.

Objective: The purpose of this study was to examine the changes in trimethadione (TMO) metabolism over seven stages from neonates to elderly adults. Methods: The subjects were divided into seven groups according to age: neonates (

肝予備能評価法として我々が用いているtrimethadione (TMO) 負荷試験が, 肝硬変例における肝障害についての臨床的な重症度の評価に有効か否かを判定するために, Child-Pugh基準 (Pugh score) と対比して検討した.TMO経口投与4時間後のTMOと, その唯一の代謝物dimethadione (DMO) の血中濃度比 (DMO/TMO値) は, 臨床的な肝障害重症度を判定するPughscoreによる分類のA群0.33±0.07, B群0.26±0.10, C群0.11±0.06で, 各群間に有意差を認めた (p

肝ミクロゾーム分画で代謝される抗てんかん薬のtrimethadione (TMO)を用いた負荷試験が,肝のいかなる組織形態学所見を反映しているか検討した.対象は肝硬変(LC) 16例,慢性肝炎(CH)と肝線維症の各2例の20例である.術前の肝CT像より算出した肝容積と肝組織の光学顕微鏡所見の画像解析により肝実質比(実質/実質+間質)や単位体積あたりの細胞数を求めた.それらの指標より肝実質量(肝容積×実質比),肝細胞量(肝容積×単位体積あたりの肝細胞数),肝実質細胞総量(肝容積×実質比×単位体積あたりの細胞数)を算出した.TMO負荷試験値と肝実質量や肝細胞量とは,それぞれ高い相関(r=0.771, r=0.809; p

It has been reported that caffeine (CA) metabolism in humans is catalyzed by cytochrome P450(CYP)1A2. Recently, we reported that human CYP3A4 and 2C, but not 1A2, contribute to trimethadione (TMO) N-demethylation in the human liver. In this study we simultaneously administered two indicators, CA (2 mg/kg) and TMO (4 mg/kg), which have different patterns of metabolism, to patients with cholelithiasis (control) or cirrhosis. The serum levels of CA and TMO, and their individual metabolites, were determined by high-performance liquid chromatography and gas chromatography, respectively. The metabolism of CA and TMO was significantly inhibited in patients with cirrhosis as compared with controls. The ratios of serum paraxanthine (PX)/CA and DMO/TMO at 4 h after administration of the two probe drugs were also significantly decreased in patients with cirrhosis. The PX/CA ratios of the smoking patients with cirrhosis were higher than those of non-smokers. No differences in serum DMO/TMO ratios were observed between the smokers and non-smokers. These results suggest that different estimations of hepatic oxidizing capacity, catalysed mainly by CYP2C and 3A4, are possible in humans.

肝硬変併存肝癌例の耐術評価に用いられている肝機能検査が, いかなる肝の形態的所見を反映しているか, 画像解析装置を用いて検討した. 肝硬変併存肝癌16例の肝実質の数か所から得た組織切片から単位体積あたりの肝細胞数と肝実質比を測定した. それにCT像から求めた肝容積とを組み合わせて肝細胞量や肝実質量および肝細胞総量を算出して形態的所見の定量化を試みた. さらに, これらの指標とICG負荷試験値 (ICGR15) や一般肝機能検査値とを比較検討した. ICGR15と, 実質比や単位体積あたりの細胞数および細胞量とは, r=-0.506 (p

The trimethadione (TMO) tolerance test, an estimation based on serum dimethadione (DMO)/TMO ratio (DMO is the only metabolite of TMO) was used to quantitatively confirm the functional hepatic parenchyma after hepatectomy. Hepatic functional reserve was confirmed to be improved when measured by TMO tolerance test after transarterial embolization(TAE)for ruptured case of hepatocellular carcinoma. The patient well tolerated hepatectomy. Accordingly, activation of hepatic functional reserve with TAE was tried on 3 patients who were diagnosed inoperable because of decreased hepatic functional reserve. In these patients, DMO/TMO ratios also increased after TAE and were considered operable. Hepatectomies were carried out and all 3 patients well tolerated the surgery. Histological examination of resected hepatic specimens revealed the regenerative nests at the sites where TAE did not affected. TMO tolerance test was able to evaluate the improvement in hepatic functional reserve, based on the hepatic parenchyma lregeneration. Thus, this test can be applied to evaluate the hepatic functional reserve in cases with decreased hepatic functional reserve.

肝細胞癌手術の術前と術後に, リピオドール-抗癌剤懸濁液動注療法 (L-TAI) をおこなった, 絶対的非治癒切除例を除く肝切除耐術例34例の予後規定因子を検討した.そのうち11例 (32%) に再発を認めた.その無再発生存率は, 1年, 91%, 3年, 68%, 5年, 45%であった.L-TAIによる80%以上の腫瘍内壊死, 腫瘍径5cm以下, 組織学的被膜浸潤なし (fc-inf (-)) そして組織学的門脈侵襲なし (vp (-)) などの各因子は, 有意に予後に良い影響を与えた.被膜浸潤の有無にかかわらず, 3cm以下の腫瘍の5年無再発生存率は100%であった, さらにfc-inf (-) 例やfc-inf (+) 例のそれぞれにおいて, 壊死率の高いほど, また腫瘍径が小さいほど, 再発までの期間は延長した.

Pre-operative evaluation of the quantity of functional remnant hepatic parenchyma after hepatectomy was carried out to predict the optimal amount of hepatic resection using the trimethadione (TMO) tolerance test. This test is an estimate based on serum diamethadione (DMO)/TMO ratio (DMO is the only metabolite of TMO) 4 h after oral administration of TMO, and computed tomography (CT) scans of the liver in patients with hepatocellular carcinoma (HCC). The percentage of remnant hepatic parenchyma was calculated pre-operatively from the remaining non-cancerous portion and the whole hepatic parenchyma, excluding the HCC portion, using the CT scans. Presumptive remnant DMO/TMO ratio was calculated by multiplying the percentage of remnant hepatic parenchyma and pre-operative serum DMO/TMO ratio in 45 patients with HCC undergoing resection. The presumptive remnant DMO/TMO ratios were 0.31 +/- 0.10 (mean +/- s.d.) in 42 patients who survived hepatectomy and 0.13 +/- 0.02 (below 0.15) in the three patients who died from postoperative hepatic failure. Of these surviving patients, two patients who had the presumptive remnant DMO/TMO ratios under 0.15 developed postoperative severe complications. Thus, hepatectomy may not be indicated in patients where presumptive remnant DMO/TMO ratio is 0.15 and lower. These findings suggest that pre-operative measurement of presumptive remnant DMO/TMO ratio, when obtained with the CT of the liver and TMO tolerance test, is useful for prediction of the quantity of functional remnant hepatic parenchyma after hepatectomy in patients with chronic liver disease.

Pharmacokinetic interactions between caffeine 2 mg/kg and trimethadione 4 mg/kg were evaluated in 10 healthy volunteers. Whether administered alone or together, the total body clearance (CL), the apparent volume of distribution (Vd) and half-life (t1/2) of caffeine and trimethadione were the same, however, there was a weak correlation between the CL of caffeine and trimethadione [alone: r = 0.51 (P < 0.05); coadministered: r = 0.56 (P < 0.05)]. There were also weak correlations between the CL of trimethadione and the area under the serum concentration-time curves (AUC) of theobromine (r = -0.61, P < 0.05), paraxanthine (r = -0.69, P < 0.05) and theophylline (r = -0.60, P < 0.05), when the two drugs were administered alone. After combined administration, the correlation between the CL of trimethadione and the AUCs of the metabolites of caffeine were as follows: theobromine r = -0.63 (P < 0.05); paraxanthine r = -0.68 (P < 0.05); theophylline r = -0.65 (P < 0.05). These findings suggest that caffeine and trimethadione metabolism in healthy subjects is mediated by only in part by a form(s) of P450 enzymes involved.

Absorption, magnetic circular dichroism (MCD) and emission spectra as well as preparations of the aluminum(III) complexes of 5,10,15,20-tetraphenylporphin (TPP) and 2,3,7,8,12,13,17,18-octaethylporphin (OEP) are presented. On the basis of the spectral observations, the molecular parameters to describe the lowest (π,π*) excited states of a typical metal porphyrin with only minor perturbation by the incorporated tervalent metal ion were determined. The orbital angular momenta in the excited states were evaluated from the MCD spectra as follows: TPPAlCl, Λz=3.0 h in Q00 band, Λz=±0.61 h Ti in B band and OEPAlCl, Λz=±0.61 h Ti in Q00 band, Λz=0.557 h in band. A Davydov splitting of the Soret band observed for the μ-oxo dimer was interpreted in terms of the exciton coupling between two parallel porphyrin chromophores.

RES機能の診断に応用するために肝のシンチグラフィー用試薬99mTc-フチン酸を用いたRES機能総量の測定法について薬物動力学的解析による基礎的検討を行った.99mTc-フチン酸静注後の循環血中のγ線量の減衰はα相とβ相からなる二相性を示し,2-コンパートメントオープンモデルで解析された.β値は肝切除群や肝障害群そしてDIC群などに関係なくほぼ一定であった.そこで静注直後に出現する分布相(α相)の消失速度定数であるα値をもってRES機能総量の値とした.肝切除モデルの検討では,RES機能は肝切除後の残存肝容積に近似した変動を示した.またDICモデルや急性肝障害モデルにおけるRES機能は低下した.また慢性肝障害モデルでは脾のフチン酸の取り込みは増加したが,全身のRES機能は低下した.本測定法は,臨床例におけるRES機能の診断に応用可能と思われた.