Patients with chronic renal failure often have hypertension, but the cause of hypertension, other than an excess of body fluid, is not well known. We hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are stimulated by uremic toxins in patients with chronic renal failure. To investigate whether RVLM neurons are sensitive to uremic toxins, such as uric acid, indoxyl sulfate, or methylguanidine, we examined changes in the membrane potentials (MPs) of bulbospinal RVLM neurons of Wister rats using the whole-cell patch-clamp technique during superfusion with these toxins. A brainstem-spinal cord preparation that preserved the sympathetic nervous system was used for the experiments. During uric acid, indoxyl sulfate, or methylguanidine superfusion, almost all the RVLM neurons were depolarized. To examine the transporters for these toxins on RVLM neurons, histological examinations were performed. The uric acid-, indoxyl sulfate-, and methylguanidine-depolarized RVLM neurons showed the presence of urate transporter 1 (URAT 1), organic anion transporter (OAT)1 or OAT3, and organic cation transporter (OCT)3, respectively. Furthermore, the toxin-induced activities of the RVLM neurons were suppressed by the addition of an anti-oxidation drug (VAS2870, an NAD(P)H oxidase inhibitor), and a histological examination revealed the presence of NAD(P)H oxidase (nox)2 and nox4 in these RVLM neurons. The present results show that uric acid, indoxyl sulfate, and methylguanidine directly stimulate bulbospinal RVLM neurons via specific transporters on these neurons and by producing oxidative stress. These uremic toxins may cause hypertension by activating RVLM neurons.

新鮮凍結血漿（Fresh Frozen Plasma：FFP）の投与によりアナフィラキシー様反応を来し，検索の結果，抗C4抗体（IgGクラス）が関与した可能性が示唆された症例を経験した．さらに本例では輸血後にトリプターゼ値上昇，好酸球増多がありIgE値が高く，好酸球・好塩基球・肥満細胞の脱顆粒により生じたmediatorによるアナフィラキシー様反応を起こした可能性も示唆された． 症例は79歳男性，胃癌と胆石症のため，胃全摘および胆嚢摘出術が施行された．手術中の総出血量が1,282ml，縫合部に出血傾向を認めたため，術後に照射赤血球濃厚液（Red Cell Concentrates：RCC）4単位を輸血し，その後FFP4単位の輸血を施行した．2本目のFFP投与開始30分後に蕁麻疹が出現したため直ちに輸血を中止し，電解質輸液に置換した．さらに頻脈と酸素飽和度（SpO2）の低下を認めたため，酸素マスクを装着し全身管理を行いながら経過観察した．翌朝にはSpO2は96％まで回復し，全身状態も改善した． 輸血で認められるアナフィラキシーの原因は完全には解明されておらず成因を特定することは困難な場合が多いが，本例は原因の検索を行うことにより発生機序が推定された例と考えられ，ここに報告した．

輸血により急性呼吸障害が生じ，当初，輸血関連急性肺障害（transfusion-related acute lung injury：TRALI）を疑ったが，精査の結果輸血関連循環過負荷（transfusion-associated circulatory overload：TACO）と診断された症例を経験した．症例は75歳男性，自宅にてタール便を認め当院の救急外来を受診，Hb4.3g/dlであったため照射赤血球濃厚液（Red Cell Concentrates：RCC）6単位の輸血を施行した．輸血開始3時間後に呼吸苦が出現，酸素飽和度（SpO2）が88％に低下した．酸素マスクを装着したが呼吸状態は改善せず，胸部X線検査で肺水腫の像を認めた．輸血開始から5時間後に挿管し，人工呼吸にしたところSpO2は99～100％に安定したため輸血を続行し，約13時間後にRCCの輸血を終了し，Hb値は7.8g/dlに回復した．輸血後の心エコー検査で駆出率は31.31％に低下，NT-proBNPは9,200pg/mlに上昇しており心不全状態であった．輸血3製剤の検索で，抗顆粒球抗体および抗HLA抗体は全製剤陰性，患者血清中の抗体は，抗顆粒球，抗HLA，抗血漿蛋白抗体は全て陰性，また先天性の欠損蛋白もなくTRALIは否定された．TRALIとTACOは呼吸困難や肺水腫などの症候が共通し，両者が共存する可能性もあることから鑑別診断が非常に困難である場合が多い．本症例では定型的なTACOの経過をとっていた．

鉄の需要が供給を上回る状態が続くと，貧血のない鉄欠乏に陥り，さらに進行すると，鉄欠乏性貧血となる．鉄欠乏の進行により組織鉄欠乏を来し，舌乳頭萎縮や食道の襞形成，匙状爪などを呈するに至る．また異食症など特異な症状も見られる．鉄欠乏や鉄過剰にいたる経過をもっとも鋭敏にとらえる指標は，血清フェリチンである．日本人女性では約半数が何らかの鉄欠乏状態にあり，鉄欠乏性貧血は女性の10％程度の頻度でみられる．鉄欠乏克服の戦略として，鉄摂取への食事指導，鉄補助食品の使用，鉄添加食品の導入があげられる．

A patient with Richter's syndrome developed rapid generalized lymph node enlargement with a decrease of peripheral blood lymphocytes after recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy for neutropenia induced by chemotherapy. The lymphadenopathy subsided spontaneously following discontinuation of rhG-CSF medication. Reinstitution of rhG-CSF therapy was followed by the same response as during initial therapy. Histopathologically, the lesions were characteristic of diffuse large cell lymphoma (DLL) with no evidence of myeloid cell involvement. No spontaneous contraction of enlarged lymph nodes followed withdrawal of the second course, but the enlargement subsided with chemotherapy. The patient died of myocardial infarction. All residual tumors examined post mortem presented microscopic features of small lymphocytic lymphoma (SLL), and G-CSF receptor was demonstrated on these neoplastic cells by Northern blot hybridization analysis. This observation indicates that some B cell malignancies may retain G-CSF receptor and respond to G-CSF.

目的：最近，近赤外線分光画像計測法が，非観血的に血中ヘモグロビン量を測定可能であることで注目されている．今回我々は，本法が，将来献血前の血中ヘモグロビン値測定に利用しうるか否かについて予備的検討を行った．方法：近赤外線分光画像計測器は，シスメックス株式会社製のアストリムを使用した．同一献血者で，このアストリムで測定した血中ヘモグロビン値と，従来の採血血液を用いて測定した血中ヘモグロビン値を比較した．対象：4群合計258名で，第1群43名は献血ルーム（室温22°C）で測定した．第2群73名は移動採血車1（気温26°C）で測定した．第3群86名は移動採血車2（気温24°C）で測定した．第4群56名は移動採血車3（気温12°C）で測定した．成績：4群合計258名の平均では，アストリムで測定した血中ヘモグロビン値と，従来の採血した血液を用いて測定した血中ヘモグロビン値との間には有意差はなく，相関係数は0.65であった．各群毎に検討すると，気温または室温が20°C以上の第1群から第3群では両者の測定値間には有意差はなかった．この3群合計202例で，観血的測定法と非観血的測定法で共にカットオフ値を12.5g/dlとした場合，献血可否判定の一致度の検定でκ係数が0.65となり，可否判定は実質的に一致していた．気温が12°Cであった第4群では，両者の測定値間に有意差を認めた．第1群から第3群の202例のROC解析では，アストリムで測定した血中ヘモグロビン値が14.6g/dl以上ですべて献血可となり，11.4g/dl以下ですべて献血不可と判定された．これを実際の測定値で検討すると，202例中100例でアストリムで献血可否判定ができ，誤判定は1例のみであった．結論：アストリムで測定した血中ヘモグロビン値と，従来の採血血液を用いて測定した血中ヘモグロビン値との間には良好な相関関係があり，気温が20°C以上であれば献血可否判定は実質的に一致した．気温が低いと両者の測定値間の相関関係が悪化した．ROC解析で検討すると，約半数の例で，非観血的に献血可否判定ができた．すなわち，気温または室温に配慮して，非観血的血中ヘモグロビン値測定法と直接採血法を併用して献血の可否を判定すれば，事前採血に伴う献血者と採血側の負担を減らすことができると考えられた．

遺伝子組換え活性型血液凝固第VII因子製剤(rFVIIa)の使用成績調査について, 5年間の長期有効性および安全性に関する中間解析結果をまとめた. 先天性および後天性血友病患者102例1,580出血エピソードが報告された. 全出血エピソードの中で12時間以内に止血効果が認められた, 著効あるいは有効と評価された出血エピソードの割合(有効率)は69.6%であった. また, 8時間以内に止血効果が認められた著効の割合は, 既報の臨床成績(31.2%)のほぼ2倍(60.9%)であった. 全出血エピソードのうち, 3つの要件(初回投与量90 mg/kg以上, 出血から初回投与までの時間3時間以内, 平均投与間隔3時間以内)を全て満たした群(推奨治療条件群)の有効率は82.4%で, その他の群(非推奨治療条件群)の有効率44.4%に比し有意に高かった. しかし, 推奨治療条件を満たした治療エピソードは全体の約40%に過ぎず, rFVIIaの有効性をさらに高めるためには3つの要件を満たすことの重要性が示唆された. 安全性について, 副作用は20例42件が報告された. 重篤な副作用は3例4件報告されたが, いずれも本剤との明らかな関連性は認められなかった.

We administered recombinant human interleukin-la (ILla). the common mediator of inflammation process, to C,,B1/6 male mice (0.5 pg, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 f 9 x 104/mm3) compared with the control mice injected with heated IL-la (101 k 11 x 104/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-18treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-lB by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-la stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-la (0.5 pg) injection, monitored by colony assay

患者は34歳,女性.既往歴として24歳時にFisher症候群を発症していた.今回,感冒後に複視で発症し歩行困難となり入院, Fisher症候群の再発と診断された.血漿交換療法により神経症状は改善し,血清中の抗GQlb抗体も低下した.しかし発症7カ月後も抗GQlb抗体は陰性化しておらず,軽度の複視の遷延化と関連している可能性が示唆された.

We evaluated the effect of repeated apheresis on storage iron status in 82 males and 138 females. Storage iron was calculated according to the formula proposed by the National Health and Nutrition Examination Survey (NHANES) as previously described. Calculated storage iron after repeated apheresis was 362±282mg in male donors and 128±176mg in females. These values were significantly lower than those in normal subjects and 400-ml repeated whole blood donors. A total of 12.2% of males and 45.7% of females were in negative iron balance before donation. The high prevalence of storage iron deficiencfy may be due to residual blood in the circuit or other factors.

A 26-year-old woman was admitted to our hospital for lumbago on November 29, 1995. The white blood cell count was 6,500/microliter with 26.5% myeloblasts and the bone marrow was hyperplastic due to myeloblasts. Myeloblasts were negative for myeloperoxidase and positive for alpha-naphthyl butylate esterase, CD11a (89%), CD11b (38%), CD11c (92%), CD33 (91%) and HLA-DR (58%). Chromosomal abnormalities were recognized: 46, XX, t(9;11) (p22;q23), 45, XX, -7, t(9;11) (p22;q23) and 47, XX, +19, t(9;11) (p22;q23). Acute myeloblastic leukemia (M5a) was diagnosed. Disseminated intravascular coagulation was also present. The patient received induction therapy and achieved remission on January 9, 1996, but myeloblasts increased to 3.6% in bone marrow despite consolidation therapy. Low doses of cytarabine (AraC) and etoposide were instituted on March 7, granulocyte colony-stimulating factor (G-CSF) was started on March 15, and pronounced skin infiltration developed on March 18. The patient received reinduction therapy from April 16 and administration of G-CSF was combined for 2 days, and a marked increment of myeloblasts in the peripheral blood was observed. After discontinuation of G-CSF, myeloblasts decreased and skin infiltration disappeared. However, the patient died of cerebral infiltration on June 30. The response of myeloblasts to G-CSF by in vitro liquid culture was noteworthy. The present case stresses the requirement for great caution to be exercised in the use of G-CSF in patients receiving low dose AraC.

We describe a 44‐year‐old man with non‐Hodgkin's lymphoma receiving granulocyte colony‐stimulating factor (G‐CSF) who developed an acute arterial thrombosis. The removed thrombus contained large amounts of platelet aggregation. A rapid increase of platelets and increased adenosine diphosphate (ADP)‐ and collagen‐induced platelet aggregation were observed at the time of the thrombotic event. A challenge test of G‐CSF showed an increase in the platelet count and an augmentation of ADP‐ and collagen‐induced platelet aggregation. In the use of G‐CSF, patients who produce a rapid increase in platelet levels could be at greater risk for thrombotic events and need to be followed‐up carefully.

We evaluated the effect of repeated 400ml whole blood donation on storage iron status in 26 males and 196 females. Iron status was estimated from hemoglobin concentration, transferrin saturation and serum ferritin. Storage iron was calculated according to the formula proposed by the National Health and Nutrition Examination Survey (NHANES). Calculated storage iron after repeated donation of 400ml was 806±174mg in male donors and 292±248mg in females. Levels after 400ml donation decreased to 606mg in males and to 92mg in females. Among females, 20.5% were in negative iron balance before donation, increasing to 37.7% after donation. However, no significant decrease in storage iron by repeated blood donation was recognized, when standards for blood collection were strictly complied with.

A 34-year-old man was admitted to our hospital for a headache in March, 1995. The patient's hemoglobin was 7.5 g/dl, platelet count was 1.8 x 10(4)/microliter and white blood cell (WBC) count was 12,400/microliters with 99% myeloblasts. Myeloblasts were agranular or hypogranular but electron microscopy revealed microgranules in cytoplasm, and a few faggots were observed. The bone marrow was hyperplastic due to myeloblasts and chromosomal abnormality was recognized: 46, XY, t(15; 17) (q22; q12). PML-RAR alpha with intron 3 breakpoint of the PML locus, and rearrangements of the T-cell receptor beta and gamma genes were detected. These cells were positive for CD2 (63%), CD8 (47%), CD13 (87%) and CD33 (99%). Microgranular variant type of acute promyelocytic leukemia (APL) was diagnosed. Disseminated intravascular coagulation (DIC) was also present. The patient was treated with enocitabine, daunorubicin, 6-mercaptopurine, dalteparin sodium, anti-thrombin III concentrates and gabexate mesilate with prophylactic frozen transfusions of fresh plasma and platelet transfusions for 5 days, but WBC count did not decrease and DIC did not improve. The patient died of cerebral hemorrhage 7 days after diagnosis of APL. APL with CD8 expression has never been reported. We suggest that therapy should be modified in this type of APL and conclusions concerning the most appropriate therapeutic strategy will depend on the results of treatment of similar cases in the future.

A 56-year-old woman developed mixed warm and cold antibody type autoimmune hemolytic anemia (mixed AIHA) associated with systemic lupus erythematosus. The patient was admitted to our hospital for acrocyanosis and shortness of breath. High fever and jaundice were observed. Urinalysis revealed protein and hemoglobin, and the sediment contained granular and hyaline casts. Her erythrocytes agglutinated markedly at room temperature. Her hemoglobin was 5.6 g/dl and reticulocyts were 19.3%. Total bilirubin, GOT and LDH were elevated, while haptoglobin and complements were abnormally reduced. Polyclonal increase of immunoglobulin, ANA and anti-Sm antibody were detected. The direct antiglobulin test was positive; IgG1, IgG3 and C3d were detected on the red cell surface. The cold agglutinin (CA) titer was 4096, showing anti-I blood group specificity, and was still active at 30 degrees C. Upon administration of prednisolone gradual increase of hemoglobin and decrease of reticulocytes were observed, indicating the healing of hemolysis. CA disappeared but the direct antiglobulin test remained positive. Mixed AIHA has been defined as the presence of both warm and cold antibodies. In addition, the presence of symptoms of cold agglutinin disease, or low-titer and high thermal amplitude CA might be necessary for the diagnosis of mixed AIHA.

We describe a 69-year-old man who developed chylothorax after a 9-year remission of malignant lymphoma. The patient was admitted to our hospital and received exploratory laparotomy for ileus in February 1986. Bulky masses in the posterior mediastinum and the retroperitoneum, and also a jejunal tumor were observed. Fibrosis of the liver was also observed. The jejunal tumor was removed and histological findings revealed diffuse large B-cell malignant lymphoma. He was treated by combination chemotherapy and remission was achieved. He was discharged in June and remained in remission, but was readmitted for right pleural effusion in October 1994. Effusion was chylous and the chylomicron level was estimated to be 181 mg/dl. Liver cirrhosis also developed but there was no chylous ascites. Chylorrhea disappeared after continuous aspiration, but recurred in December. Continuous aspiration was ineffective, therefore 10 KE of OK-432 was administered twice into the pleural cavity, and chylorrhea again disappeared. No findings suggestive of malignant lymphoma were not detected by computerized tomography and gallium scintigram. He was discharged in March 1995 and chylothorax has not recurred since. These findings suggest that the fragility of the thoracic duct which had been infiltrated by malignant lymphoma might increase, resulting in rupture, even if in remission.

This report describes an intermediate state between the human T-cell lymphotropic virus type I (HTLV-I) healthy carrier and adult T-cell Leukemia (ATL) who developed acute myeloblastic leukemia (AML, FAB subtype M2). The polyclonal integration of HTLV-I proviral DNA was demonstrated in the peripheral blood lymphoid cells, whereas AML cells had no HTLV-I proviral DNA. The patient achieved remission after combination chemotherapy but cells with lobulated nuclei persist at a low level and the polyclonal integration of HTLV-I proviral DNA is still demonstrated. We suggest that the patients with the integration of HTLV-I proviral DNA might develop secondary neoplasms more frequently than healthy carriers and this case stresses the need to exercise caution with these patients. The relationship between HTLV-I and AML is briefly discussed.