骨髄移植の実際と問題点 : 自験例を中心に

同種骨髄移植は,造血器悪性腫瘍,再生不良性貧血などの疾患に対する根治療法として,最近10余年にわたり著しくその成績を向上させてきた.しかし,いま解決されねばならない問題点も多く,ここに白血病の2症例を提示し,その実際と問題点について述べる.症例1は急性単球性白血病の12歳の女性.分割放射線全身照射とhigh-dose Ara-Cにて前処置を行い,HLAの一致した姉より骨髄移植を施行した.移植後の回復は順調であり,合併症もほぼ認められなかった.症例2は慢性骨髄性白血病急性転化の25歳の女性.high-dose busulfanとcyclophosphamideにて前処置を行い,HLAの一致した弟より,移植を施行した,移植後,血液学的回復は良好であった.GVHDは軽度でIPは認められなかったが,day 30以降に重度の肝内胆汁うっ滞型肝細胞障害を呈した.その後全身状態は改善していったが,day 90の骨髄染色体検査にて再発を認めた.前処置の選択,GVHD,IP,種々の感染症の予防等の問題点は,基礎的,臨床的な研究の成果により,かなり改善が認められてきている.しかし,急性白血病再発例や,慢性骨髄性白血病急性転化例に対する対策や再発予防といった点が,今後の課題となる.Allogeneic bone marrow transplantation (BMT) for hematological malignancies has remarkably improved during the last decade. In spite of recent progress, however, many problems remain unsolved in the clinical treatise and in basic research. In this paper, BMT are described practically in two patients with hematological malignancies, and their problems at the present time are also discussed. The first patient (12-year-old female) with acute monocytic leukemia was pretreated by fractionated total body irradiation and high-dose cytosine arabinoside in her first remission. BMT was performed utilizing the marrow cells from a HLA-identical sibling. After severe marrow suppression, granulocytes and platelets reached 500/μl at day 32 and 20,000/μl at day 20, respectively. On day 90, no serious complications had been observed. The second patient (25-year-old female) with a second blastic crisis in Ph1-positive chronic myelogenous leukemia was pretreated with high-dose busulfan and cyclophosphamide and received BMT from her HLA-identical brother. After severe marrow suppression, granulocytes and platelets recovered at day 23 and at day 70, respectively. Graft-versus-host disease (GVHD) was minimal (grade I) and no interstitial pneumonitis (IP) was observed in this patient. Severe intrahepatic cholestasis, however, appeared after day 30. Although her general condition improved slowly around in day 90, metaphasic Ph1-positive blasts were found in the patient\u27s bone marrow, indicating a relapse of leukemia. The following problems are left to be solved in the BMT for acute or chronic leukemia. First is the selection of the best conditioning regimen for pretreatment of BMT, for which no appropriate standard has been available. Second, complications should be prevented, such as bacterial and fungal infections, GVHD, IP, and so on. For these purposes, new prophylaxes for viral infection and for GVHD will be required. Third, the contributions of basic and clinical research should be introduced into BMT extensively. More this to just after research such as work on suppression of the residual leukemic clone, on prolongation of the disease-free survival state, and on the appropriate therapeutical regimen for relapsed cases with acute leukemia or with blastic crisis of chronic myelogenous leukemia

Recurrence of Atrial Fibrillation within Three Months after Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation : Analysis Using an External Loop Recorder with Auto-trigger Function

Pulmonary vein isolation (PVI) via catheter ablation has been shown to be a highly effective option for patients with symptomatic paroxysmal atrial brillation (AF). The recurrence of AF within 3 months after PVI is not considered a failure of the ablation procedure because early recurrence of AF is not always associated with late recurrence. We examined the usefulness of an external loop recorder with auto-trigger function (ELR-AUTO) to detect AF following PVI to characterize early recurrence and determine the implication of AF within 3 months after PVI. The study included 53 consecutive patients with symptomatic paroxysmal AF (age, 61.6 ± 12.6 years ; 77％ male) who underwent PVI, and were fitted with an ELR-AUTO for 7 ± 2 days within 3 months after PVI. Of the 33 patients(62.2％) who did not have AF within the 3-month period, only 1 patient had AF recurrence at 12 months. Seven of 20 patients (35％) who experienced AF within 3 months had symptomatic AF recurrence at 12 months. The sensitivity, specificity, positive predictive value, and negative predictive value of early AF recurrence for late recurrence was 87.5％, 71.1％, 35.0％, and 96.9％, respectively. Thus, AF recurrence detected by ELR-AUTO within 3 months after PVI can predict late AF recurrence. Freedom from AF in the firrst 3 months following ablation significantly predicts long-term freedom from AF. An ELR-AUTO is useful for detecting symptomatic and asymptomatic AF

Larval pufferfish protected by maternal tetrodotoxin

Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin. All species of the genus Takifugu accumulate TTX in the liver and ovaries, although the tissue(s) in which it is localized can differ among species. TTX is the major defense strategy the pufferfish appears to use against predators. TTX is also used as a male-attracting pheromone during spawning. Here we demonstrate an additional (and unexpected) use of maternal TTX in the early larval stages of the Takifugu pufferfish. Predation experiments demonstrated that juveniles of all the species of fish used as predators ingested pufferfish larvae, but spat them out promptly. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) analysis revealed that the pufferfish larvae contain a small quantity of TTX, which is not enough to be lethal to the predators. Immunohistochemical analysis with anti-TTX monoclonal antibody revealed that the TTX is primarily localized in the body surface of the larvae as a layer of protection. Our study showed the female parent of the Takifugu pufferfish vertically transfers TTX to the larvae through its accumulation in the ovaries, and subsequent localization on the body surface of the larvae