Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Hiroshi Hamamatsu university, school of medicine, Associate Professor, 医学部, 助教授 (40178330)
KANAYAMA Naohiro Hamamatsu university, school of medicine, Professor, 医学部, 教授 (70204550)
小林 隆夫 浜松医科大学, 医学部, 助教授 (20107808)
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Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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Research Abstract |
We classified AFE patients into two groups. One is the established AFE group : fetal materials are found in maternal pulmonary vessels at autopsy. Another is the potential AFE group who fills with modified Benson's criteria. 1) currently pregnant or within 12 hours after delivery, 2) one or more of the following to require medical treatment severely, a) cardiac arrest b) large amount of bleeding after delivery within 2 hours (more than 1500ml except for atonic bleeding), c) disseminated intravascular coagulation, d) respiratory distress, 3) absence of other medical explanations for clinical course. We discovered specific fetal antigens, Sialyl Tn (STN) and Zinc coproporphyrin1 (Zn-CP1), which present in meconium and developed quantitative methods to determine fetal antigen leakage into maternal circulation. One hundred thirty five patients, 20 with established AFE and in 115 with potential AFE, were recruited from institutions all over the world including Japan. These patients were ava
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ilable to evaluate the STN and Zn-CP1 level in serum. The cut-off points in serum were provided 46.0U/ml(STN) and 1.6pmol/ml (Zn-CP1), respectively, as mean plus 2SD. The serum levels of STN and Zn-CP1 in 135 patients with AFE showed higher concentrations than those in control(STN:163.4±229.1U/ml [established AFE], 70.5±198.5 [potential AFE]vs. 29.5±8.8U/ml [control], Zn-CP1:30.2±26.7pmol/ml[established AFE], 84.0±193.9 [potential AFE] vs. 0.50±0.54pmol/ml[control]). Positive rate of STN in patients with AFE, established AFE and potential AFE was 84.6% and 18.5% respectively. Meanwhile positivity of Zn-CP1 was 75.0% and 57.0%, respectively. The findings of AFE in lung sections were divided 2 types. One was that the structure of the lung tissues were almost normal when the patients died within 1 day. This cause of death was the dysfunction of pulmonary ventilated system and circulation, because the embolus and fibrin deposite could be found out intra pulmonary vessels. Second was that the structure of the lung tissues were almost destroyed similar to adult respiratoly distress syndrome when the patients died after a few days. The leukocytes in the region of pulmonaty vasculature, where the TKH-2 immunostaining was positive, were mainly composed of neutrophils. Using a monoclonal antibody against neutrophil elastase, this region showed strong staining for neutrophils. It is conceivable that the activated neutrophils-derived hypercytokinemia may result in the cause of death of AFE after a few days. In concern of this result, the inflammatory cytokine IL-8 was measured in the patients with AFE. IL-8 in the died patients was significant higher than in the survived patients. We suggest when the values of IL-8 are indicated over 400pg/ml, the prognosis of AFE patients is poor. An updated analysis, preterm labor and pre-eclampsia was approved more in the patients with AFE compared with the other complication. The appearance of AFE was occurred frequently in both multipara and inducted delivery. The pregnant women with multipara and the complications of preterm labor and pre-eclampsia should not be inducted easily without the medical indication. The registration system of AFE was started from August 2003 officially in the society of Japan obstetrics and gynecology. The registration of the patients with AFE are rapidly increasing. Less
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