Kiyoshi Kitamoto

Increased release of myeloperoxidase in vitro from neutrophils of patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis

Summary: In order to elucidate the role of neutrophils in the pathogenesis of MPO‐specific anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) related glomerulonephritis (GN), MPO release, beta‐glucuronidase (BGL) release, superoxide anion (O2−) production from the neutrophils of patients with MPO‐ANCA related GN were measured. the effect of plasma on MPO release from neutrophils was also studied in patients with MPO‐ANCA related GN. Neutrophils and plasma were obtained from patients with MPO‐ANCA related GN, GN unrelated to MPO‐ANCA and healthy controls. MPO release from the neutrophils of patients with MPO‐ANCA related GN was higher than that of controls significantly. This was also higher than that in patients with GN unrelated to MPG‐ANCA, but this was not statistically significant. Superoxide anion production from neutrophils of patients with MPO‐ANCA related GN was significantly higher than that in patients with GN unrelated MPO‐ANCA, However, BGL release was not significantly different among three groups. Furthermore, MPO release and O2− production increased in parallel with clinical activity of MPO‐ANCA related GN. Neutrophils of patients with MPO‐ANCA related GN showed to be significantly more sensitive to FMLP on MPO release than those in the other two groups. However, plasma from MPO‐ANCA related GN increased the sensitivity to FMLP on MPO release, but not BGL release, in neutrophils obtained from healthy controls, whereas it suppressed MPO release from neutrophils with MPO‐ANCA related GN. This suggests that in patients with MPO‐ANCA related GN MPO can be highly released from activated neutrophils and that the plasma of patients with MPO‐ANCA contains factor(s) which modulate reactivity of neutrophils.

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Flexible treatments for intimal hyperplasia after angioplasty are still needed. The aim of this study was to demonstrate the long-term effects of vascular photodynamic therapy with talaporfin sodium on intimal hyperplasia following interventional injury. Intimal hyperplasia was induced by balloon distension injury to the carotid artery in 31 rabbits. Talaporfin, 5.0 mg/kg, was delivered systemically immediately after balloon injury. The injury site was irradiated with a diode laser light of wavelength 664 nm using a fluence of 50 J/cm2 after 30 min. At day 3 and weeks 3, 6, 9, 15, and 25 after photodynamic therapy, the treated artery of each rabbit was excised and examined immunohistochemically. Thirty minutes after talaporfin administration, drug fluorescence was found only in the balloon-injured carotid artery wall. At 3 days, no smooth muscle cells were seen in the media of the photodynamic therapy-treated arterial segments. Intimal hyperplasia developed progressively in the balloon-injured and untreated segments; however, in the segments treated with photodynamic therapy, intimal hyperplasia was markedly suppressed until 25 weeks and the media was repopulated by smooth muscle cells without macrophages. Vascular photodynamic therapy with talaporfin may be used to inhibit restenosis after vascular intervention.

Guanabenz, an antihypertensive centrally acting α2-Agonist, suppresses morning elevations in aggregation of human platelets

To determine whether the antihypertensive agent guanabenz affects the circadian rhythm in the hemorheologic properties of the platelet, we evaluated the aggregability of platelets collected from 11 healthy subjects in the morning and the evening after the oral administration of this agent, daily for 2 weeks. We analyzed platelet aggregation by the turbidimetric method. In an in vitro study, guanabenz, 10 nM-100 μM, did not affect platelet aggregation, whereas epinephrine induced platelet aggregation at an EC50 of 1.5 μM. The healthy volunteers demonstrated a diurnal variation in platelet aggregability that was high in the morning and low in the evening (66 ± 10% and 56 ± 11% respectively, of the percent platelet aggregation induced by epinephrine). The same variation was seen with the platelet aggregation induced by adenosine diphosphate (ADP) (62 ± 8% [morning] vs. 51 ± 7% [evening]). After the administration of guanabenz, platelet aggregability was significantly reduced in the morning compared with that before drug administration, when platelet aggregation was induced by epinephrine (49 ± 9%, p < 0.05) or ADP (48 ± 7%, p < 0.05), although the plasma levels of catecholamine were unchanged. A suppressive effect of guanabenz on platelet aggregability was observed in the evening, as the platelets were stimulated by epinephrine (38 ± 9%, p < 0.05), but not by ADP (49 ± 5%). Findings suggest that guanabenz mainly suppressed the morning enhancement in platelet aggregability, which contributes to the formation of intravascular thrombi. Thus, in addition to its antihypertensive actions, guanabenz may help to reduce the risk of vascular accidents, which frequently occur in the morning.

Clinical Characterization of Acute Renal Failure in Multiple Organ Dysfunction Syndrome

BackgroundAcute renal failure frequently occurs as a complication of multiple organ dysfunction syndrome (MODS). Various forms of therapy for MODS, including endotoxin absorption and anticytokine therapy, have been attempted.MethodsWe retrospectively studied the pathophysiologic characteristics of acute renal failure in 152 MODS patients examined in our department over the past 5 years. The diagnosis of MODS was based on the criteria of the Japanese Association for Critical Care Medicine. The diagnosis of systemic inflammatory response syndrome (SIRS) and sepsis was conducted in accordance with the definition proposed at the 1992 Consensus Conference of the American College of Chest Physicians/ Society of Critical Care Medicine.ResultsAcute renal failure occurred as a complication of secondary MODS with a high frequency of 76.3% (116/152 patients). Significant associations have been found between the respective frequencies of acute renal failure and disseminated intravascular coagulation occurring as complications of SIRS. An increase in the number of cases undergoing continuous hemodiafiltration was noted, in an attempt to improve the survival rate of MODS complicated with acute renal failure.ConclusionAcute renal failure seen in secondary MODS is thought to be derived from a pathogenesis differing from that of conventional intrinsic acute renal failure, such as ischemic and nephrotoxic forms. Acute renal failure associated with secondary MODS appears to be a disease entity that arises as a sequela of SIRS, similar to disseminated intravascular coagulation.

Report of a case of successful pregnancy and delivery on maintenance hemodialysis

血液透析患者では, 月経の不順等により妊娠の機会が少なく, また, 妊娠しても母体の危険性の増大, 胎児の発育不全, 出血傾向の増大, 母児ともの栄養障害等の理由から妊娠分娩は禁忌とされてきた. しかし近年, 透析技術の進歩に伴い, 1971年Confortiniの世界最初の透析患者における妊娠, 分娩の成功例の報告以来, 本邦でも, 我々が文献的に検索しえたものだけで12例の報告がみられた. 今回我々も, 透析歴約7年, 32歳, の妊娠分娩に成功したので報告する.当院では, 14週より透析及び妊娠の管理を行い, BUN 60mg/dl以下, Cr 6mg/dl以下を目標に減ヘパリン透析を行った. ドライウェイトは収縮期血圧が100mmHg以下にならないことを最低条件とし, 羊水量及び胎児体重の推定により決定した. 妊娠32週2日, 帝王切開により無事女児を分娩した. Apgar score 9点, 全身状態良好で, 体重1454gであった. 発育は順調で, 生後60日3360gで退院, 現在4か月, 体重5450gで異常は見られていない. 本例の分娩成功の原因は, 1. 患者本人が透析を十分理解し, 非妊時より自己管理が良く, 2. 家族の協力が得られ, 3. 産婦人科, 小児科医の協力が得られたことなどが考えられる. また, 妊娠継続のためには, BUN 60mg/dl以下, Cr 6mg/dl以下, Ht 30%以上の状態の確保が必要とされているが, 本邦の報告例13例を検討すると, 生児を得るためには, 妊娠30週以上, 胎児体重1000gまで妊娠を継続する必要があると考えられた.今後, 妊娠分娩を希望する透析患者が増加すると考えられるが, 安易に妊娠を継続するのではなく, 決して安全ではないことを本人及び家族と十分話し合い, 産婦人科及び小児科医の協力を得ることが必要であると思われた.

Three cases of acute renal failure associated with minimal change nephrotic syndrome

腎生検にて微小変化型ネフローゼ症候群と診断し,経過中に急性腎不全を合併した3例について報告した.年令は23, 54, 72才ですべて男性.急性腎不全発症に関連すると思われる薬物の使用はなかった. 3例とも高度の低蛋白血症を認めていた. 2例は透析導入後,短期間で透析を離脱できた.急性腎不全の発症機序は,微小変化型ネフロ一ゼ症候群の突然発症的な大量蛋白尿による急激な低蛋白血症のために,腎血流量の減少とともに尿細管腔蛋白円柱と腎間質浮腫による尿細管閉塞を生じ,急性腎不全をきたしたと推察された.急性腎不全は微小変化型ネフロ一ゼ症候群の重大な合併症のひとつであり,本症候群の治療・管理には,充分に注意が必要である.

A case report of myocardial infarction in a patient with systemic lupus erythematosus with marked atherosclerotic lesions demonstrated by autopsy

症例は39才,男性. 28才時に全身性エリテマトーデスの診断にて,以後ステロイド療法が施行された. 34才時,胸痛が出現し急性心筋梗塞と診断された. 36才時に言語障害と右不全麻痺が出現し,脳梗塞を合併した. 39才時,二度目の心筋梗塞発作で死亡した.剖検上,全身の著しい動脈硬化性病変を認め,特に冠状動脈と中大脳動脈に器質化血栓を伴うアテローム性動脈硬化症が認められた.全身性エリテマトーデス症例における動脈硬化促進因子については,全身性エリテマトーデス固有の血管炎・血栓をきたしやすい病態,ステロイド長期投与の影響の他に,高血圧,高脂血症,大量喫煙などの多様な因子の存在も重要な役割を果たしていると考えられた.

A case report of blood coagulation in the dialyzer associated with heparin-induced thrombocytopenia

ヘパリンの副作用により血小板減少症を来すことがまれにあり, 血栓症やDICを起こすことが知られている. 我々は, 透析中に抗凝固薬として使用したヘパリンがヘパリン依存性の血小板減少症を来した症例を経験した.症例は78歳の男性で呼吸困難を主訴とし来院. 慢性腎不全の診断で, 入院当日より血液透析を開始した. 抗凝固薬としてヘパリンを使用したが, 第19病日目より透析回路内に凝固が生じた. このため, ヘパリンの増量, チクロピジンの投与, ダイアライザーの変更等を行ったが効果は認められなかった. 検査所見上, 透析中の血小板数の経時的低下およびPF4とβ-TGの著明な上昇が認められた. そこで, チクロピジンと血小板凝集抑制の作用機序の異なるアスピリンを投与したところ, PF4とβ-TGの上昇および血小板数の低下は認められなくなり, 回路内の凝固も生じなくなった.また正常者platelet rich plasmaと患者platelet poor plasmaの混合液にヘパリンを添加すると血小板凝集能の亢進が認められた. このことは本症例では抗凝固薬として使用したヘパリンが血小板凝集能の亢進を来し回路内に凝固が生じ, この過程に対してアスピリン投与が有効であったことを示している.

Clinical studies on rapidly progressive end stage renal failure in patients with lupus nephritis.

最近我々が経験した,母疾患であるSLEの発症と同時に,あるいは腎症が発現してから数年以上経過してから,急速に腎不全が進行して末期腎不全に陥つたループス腎炎(RPLN) 11例の臨床所見と検査所見の特徴について検討した.その結果,発症時から腎機能の低下が著しく, 1ヵ月以内に死亡した3例(Group I, hyperacute RPLN)と,約1ヵ月間のネフローゼ症候を経過してRPLNへ進行し,約1ヵ月後に腎外症状により死亡した3例(Group II, acute RPLN),および持続性蛋白尿ないし血尿の時期を1～3年経過した後に,短期間のネフローゼ症候を経てRPLNに進行した5例(Group III, accelerated RPLN)の3群に分類された.組織学的には,全例管内性増殖性病変と同時に,半月体形成腎炎の像を呈し,さらにGroup Iの3例は細動脈のフィブリノイド型血管炎を伴つていた.検査所見上,血清補体の著明な低下,血中免疫複合体(CIC)レベルの上昇および中～大分子量サイズのIC活性の存在,凝固線溶亢進状態との共通した特徴を示した.このような急激な経過をとらないようにするためには,検査所見の特徴から早期に本病型を診断し, SLEの免疫学的活動性を充分に抑制することが最も重要である.不幸にしてこのような状態を生じた場合には免疫抑制療法に抗凝固線溶療法を併用し,かつ適切な時期に透析治療を導入することが臨床上極めて重要と思われた.