Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.0 mg/kg. The primary endpoint, the cumulative incidence of moderate-severe chronic GVHD at 2 years was 22.1% in the ATG group, which was significantly less than that in the non-ATG group (36.3%, P = 0.025). The ATG group had a higher incidence of immunosuppressant discontinuation, GVHD-free, relapse-free survival, and moderate-severe chronic GVHD-free, relapse-free survival at 2 years compared to the non-ATG group. The incidences of grade III-IV aGVHD and moderate-severe chronic GVHD were significantly higher in patients with high absolute lymphocyte count (ALC) before the administration of ATG, whereas relapse rate was significantly higher in patients with low ALC before ATG. In conclusion, low-dose ATG effectively suppresses chronic GVHD in unrelated PBSCT, and ALC before ATG may be a potential predictor for GVHD and relapse

高齢者の高コレステロール血症に対するProbucolの効果

The present study involved a detailed post hoc comparison of the efficacy and safety of lipid-lowering therapy in elderly hypercholesterolemic patients from the Fukuoka Atherosclerosis Trial (FAST). The FAST cohort of 246 hypercholesterolemic patients included 76 patients who were (75 years old. Patients were randomized to receive probucol (500 mg/day) or pravastatin (10 mg/day) therapy, or to a control group (diet alone), and then were followed for 2 years. In patients >75 years old, either probucol or pravastatin achieved a significant reduction of carotid intima-media thickness (IMT). In patients <75 years old, lipid-lowering therapy also achieved a significant reduction of IMT. In patients > 75 years old receiving probucol, the relative risk (95% confidence interval) of all-cause mortality was 0.15 (0.02 to 1.28) and that for major coronary events was 0.12 (0.02 to 1.04). In conclusion, probucol reduced the incidence of cardiovascular disease in elderly hypercholesterolemic patients as well as younger patients.【目的】高齢者(75歳以上)の高コレステロール血症患者に対して,積極的な脂質低下療法が頚動脈硬化の進展抑制および主要冠動脈イベントリスク低下が認められるか否かについて検討した.【方法】FASTの対象患者(246例)のうち,75歳以上(76例)と75歳未満(168例)について,脂質低下療法(ProbucolPravastain)および食事療法により,その有効性について頚動脈エコーを用いて評価した.総頚動脈の内膜中膜複合体厚(IMT)を測定し,左右6点のIMTの平均値をIMT値とした.1次エンドポイントは2年間のIMT値の変化率とし,2次エンドポイントは主要冠動脈イベントとした.【結果】Probucol群及びPravastain群では,年齢に関係なく,高齢者においても動脈硬化の進展抑制を認めた.Probuco1群における高齢者のControl群に対する各臨床イベントの相対リスク(95%信頼期間)は総死亡が0.15(0.02-1.28),総冠動脈イベント0.12(0.02-1.04)と有意な進展を認めた.一方,Pravastain群との間では,各臨床イベントの相対リスクに有意差は認められなかった.Probucol群とPravastain群との間では,各臨床イベントの相対リスクに有意差は認められなかった.【結論】75歳以上の高齢者に対してもProbucolは,頚動脈硬化の進展抑制効果が認められ,さらに主要冠動脈イベントの相対リスクの低下作用を認められる可能性が示唆された

脂質低下療法による動脈硬化症の進展抑制におけるC型肝炎ウイルス及肺炎クラミジア感染の影響

Recent experimental and epidemiological findings suggest that infectious agents may play a role in the development and progression of atherosclerosis. We previously reported that Chlamydia Pneumoniae(C.pneumoniae)infection reduces the effectiveness of lipid-lowering therapy for carotid atherosclerosis and that this microorganism may play a role in the progression of atherosclerosis. In this study, we investigated the possible association between hepatitis C virus (HCV)　infection and carotid arteriosclerosis. A total of 165 asymptomatic hypercholesterolemic patients were randomized to receive probucol(500mg/day, n=82) or pravastatin(10　mg/day, n＝83) and were followed for 2 years. The 2-year change of the maximum common carotid artery intima-media thickness (Max-IMT) was the primary endpoint, while the Max-IMT and the incidence of major cardiovascular events were secondary endpoint. All serum samples were tested for antibody to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA), and all anti-HCV-positive samples were assayed for HCV RNA. Patients without HCV infection(n=25) showed a significant reduction of Max-IMT(-10.90%)(p<O.OOO1), while a small decrease of Max-IMT was noted in the patients with HCV infection (n=25)(-0.3%). Significant differences in the reduction of serum total cholesterol and LDL cholesterol were found between patients with and without HCV infection(both p<0.OOO1). No significant difference in therapeutic effect was noted between the probucol and the pravastatin groups. After adjustment for confounding risk factors, both C. peumoniae infection and anti-HCV positivity were associated with a greater risk of an increase in Max-IMT(8.5635[1.3738-15.7532],　p<O.05, 9.5040[O.2886-18.7194], p<O.05, respectively). These findings suggest that both chronic HCV infection and C.pneumoniae infection can reduce the effectiveness of lipid-lowering therapy for carotid atherosclerosis, and that the HCV may play a role in the progression of atherosclerosis in HCV infected patients

10年間の追跡調査による沖縄県八重山地区における糖尿病有病率と罹患率及びその危険因子についての検討

To clarify the prevalence and incidence of diabetes and to evaluate which risk factors are predictive of future diabetes in the general population of Okinawa, 1,690 residents were screened in 1989 and 758 were prospectively followed-up in 1999. Of the 1,690 residents surveyed in 1989 and 1, 163 in1999, diabetes was found in 91 (5.4%) in1989 and 52 (4.5%) in 1999. Residents with diabetes were significantly older, more likely to have significantly higher levels of HbA1c, fasting glucose, serum triglyceride, ALT, BMI, systolic blood pressure, and a history of hypertension than non diabetic residents, both in 1989 and 1999. 717 residents who did not have diabetes at the 1989 screening were re-examined in 1999. Among them, 17 (incidence rate 2.4%) had developed diabetes over the ten years. Multivariate logistic regression analysis showed HbA1c, BMI, and systolic blood pressure to be independent risk factors for newly developed diabetes (p < 0.0001, odds ratio ; 28.1, p = 0.020, odds ratio ; 1.21, p = 0.039, odds ratio ; 1.04, respectively) after adjusting for age, sex, BMI, blood pressure, hystory of hypertension, HbA1c, fasting glucose, serum triglyceride, ALT, and γ GTP. Our results showed that the prevalence and incidence of diabetes are low in the general population of the Yaeyama district of Okinawa and that elevated HbA1c level, even in the normal range, is one of the best predictors of diabetes. Following BMI and systolic blood pressure is important.【目的】沖縄県八重山地区の一般住民において, 糖尿病の有病率及び10 年後の糖尿病の新規発症率とその危険因子について検討した. 【方法】1989年に1,693名，1999年に1,163 名に対し住民検診を施行した. 糖尿病の診断は, ①空腹時血糖値が126mg/dl以上② HbA1c 6.9％（国際標準値）以上③糖尿病治療中④ 75 ｇ糖負荷試験結果が糖尿病型のいずれかで診断した. 【結果】1989年に検診を受けた住民1,693名のうち計91名（5.4％）が糖尿病と診断され, 1999年は1,163 名のうち計52 名（4.5％）が糖尿病と診断されたが, 有意な経年的変化は認めなかった. 糖尿病と診断された住民は, 非糖尿病住民と比べて, 年齢, BMI, 収縮期血圧, 高血圧の病歴, 血清中性脂肪値, ALT 値が有意に高値であった, 追跡調査可能で1989 年時に非糖尿病であった717名の住民のうち, 17 名が10 年後に新規に糖尿病に罹患していた（罹患率2.4％）.糖尿病発症の独立した危険因子として, HbA1c, BMI, 収縮期血圧が抽出された（p<0.0001, odds ratio ; 28.1, p=0.020, odds ratio ; 1.21, p=0.039, odds ratio ; 1.04，respectively).【結論】沖縄県八重山地区の一般住民は, 他地域と比べ糖尿病の有病率及び罹患率が低く, HbA1c, BMI, 収縮期血圧が正常範囲内であっても危険因子になりうることが示唆された

PBMC 中の Chlamydophila pneumoniae DNA と Chlamydophila pneumoniae抗体との関連

An association has been demonstrated between Chlamydophila pneumoniae (C. pneumoniae) infection and atherosclerosis, but data on the relationship between C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) and antibodies to this organism are lacking. We investigated the C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and C. pneumoniae IgG and IgA antibodies by enzyme-linked immunosorbent assay of 168 patients with atherosclerotic diseases and 27 controls (healthy control subjects). C. pneumoniae DNA was detected for 48/168 (29%) atherosclerosis patients, IgG for 79 (47%), and IgA for 98 (58%), whereas the corresponding numbers for the controls were 11 (41%), 13 (48%), and 7 (26%). There was no significant difference of the C. pneumoniae DNA positivity rate between the atherosclerosis patients and the controls. However, the C. pneumoniae IgA-positive rate was significantly higher for carotid atherosclerosis patients who had C. pneumoniae DNA in their PBMC than for those without it (74% vs. 18%, P ＜ 0.05). Among the patients with coronary artery disease, the C. pneumoniae IgA antibody positive rate was significantly higher for the patients with DNA than for those without it (68% vs. 18%, P ＜ 0.05). Our results suggest that a high C. pneumoniae IgA antibody titer and C. pneumoniae DNA positivity are associated with an increased risk of atherosclerotic diseases due to endovascular C. pneumoniae infection.Chlamydophila pneumoniae（C. pneunomiae）感染は動脈硬化に関与しているといわれているが，末梢血中のC. pneunomiae DNA とC. pneunomiae 抗体との関連を示した報告は少ない．私共は168 例の動脈硬化性疾患群と27 例のコントロール群に対して，ELISA 法によるC. pneunomiae 抗体測定と同時に，PCR法を用いて末梢血中のC. pneunomiae DNA を測定し比較検討した.動脈硬化性疾患群において，C. pneunomiaeのDNA の検出率は48/168（29%），IgG 抗体陽性率は79/168（47%)，IgA 抗体陽性率は98/168（58%）であった．一方，コントロール群では，DNA の検出率は11/27（41%)，IgG 抗体陽性率は13/27（48%)，IgA 抗体陽性率は7/27（26%）であった．DNA の検出率は，両群に有意差は認めなかったが，末梢血中のDNA 陽性例におけるIgA 抗体陽性率は，動脈硬化性疾患群（74%）では，コントロール（18%）と比較して有意に高く（p＜ 0.05), その中の冠動脈疾患（急性冠症候群，安定狭心症，不安定狭心症）においても，コントロールと比較して有意に高かった（p ＜ 0.05）．これらの結果よりC. pneunomiae におけるIgA 抗体高値かつDNA陽性の場合は，血管内C. pneunomiae感染による動脈硬化性疾患発症の危険因子に深く関与している可能性が示唆された