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Background The number of patients with type 2 diabetes is drastically increasing worldwide. It is a serious health problem in Japan as well. Lifestyle interventions can reduce progression from impaired glucose tolerance to type 2 diabetes, and glycemic control has been shown to improve postprandial plasma glucose levels. Moreover, several studies have suggested that continuous interventions (combined diet and exercise) can improve the plasma glucose level and reduce dosage of hypoglycemic agents. Although many interventional studies of lifestyle education for persons with diabetes in hospitals have been reported, only a few have been clinic-based studies employing an evidence-based lifestyle education program. This article describes the design of a cluster randomized controlled trial of the effectiveness of lifestyle education for patients with type 2 diabetes in clinics by registered dietitians. Methods/Design In Japan, general practitioners generally have their own medical clinics to provide medical care for outpatients in the community, including those with type 2 diabetes. With the collaboration of such general practitioners, the study patients were enrolled in the present study. Twenty general practitioners were randomly allocated to each provide patients for entry into either an intervention group (10) or a control group (10). In total, 200 participants will be included in the study. The intervention group will receive intensive education on lifestyle improvement related to type 2 diabetes by registered dietitians in clinics. Lifestyle education will be conducted several times during the study period. The control group will receive information on dietary intake and standard advice on glycemic control by registered dietitians. The primary endpoint is the change from the baseline value of HbA1c at 6 months. Data on health behavior and related issues will be gathered continuously over a 6-month period. Discussion This is the first study to evaluate lifestyle education in clinics by a cluster randomization trial in Japan. The proposed study will provide practical information about the usefulness of the intensive lifestyle improvement education program in primary care settings. The study was started in September 2007 and entry of subjects was completed in December 2010. Data on the effect evaluation will be available in 2011. Trial Registration UMIN000004049

To assess the state of thrombosis and fibrinolysis, we measured the plasma concentrations of fibrinopeptide A (FPA), fibrinopeptide Bβ15-42 (FPBβ15-42), D-dimer, protein C (PC) activity and antigen, and antithrombin III (AT III) in 17 patients of cardioembolic stroke. Patient group had significantly high concentrations of FPA and FPBβ15-42, and significantly low concentrations of PC and AT III compared with healthy control group (p

Background The prevalence of type 2 diabetes is rising worldwide, as has been the global mean fasting plasma glucose level. This study aimed to evaluate the effectiveness of a structured individual-based lifestyle education (SILE) program to reduce the hemoglobin A1c (HbA1c) level in type 2 diabetes patients delivered by registered dietitians in primary care clinical settings. Methods This was a 6-month prospective cluster randomized controlled trial in a primary care setting with randomization at the practice level. Twenty general practitioners in 20 clinics in Kanagawa prefecture, Japan, were involved. 193 adults (51% men, mean age 61.3 years) with type 2 diabetes and HbA1c ≥6.5% who received treatment in medical clinics were the participants. A SILE program was implemented through 4 sessions with trained registered dietitians during the 6-month study period. Results were compared with those of a control group who received usual care. The primary endpoint was the change in HbA1c levels at 6 months from baseline. Secondary endpoints were the changes at 6 months from baseline in fasting plasma glucose, lipid profile, blood pressure, BMI, energy, and nutrient intakes (whole day and each meal). Intention-to-treat analysis was conducted. Mixed-effects linear models were used to examine the effects of the treatment. Results The mean change at 6 months from baseline in HbA1c was a 0.7% decrease in the intervention group (n = 100) and a 0.2% decrease in the control group (n = 93) (difference −0.5%, 95%CI: -0.2% to −0.8%, p = 0.004). After adjusting for baseline values and other factors, the difference was still significant (p = 0.003 ~ 0.011). The intervention group had a significantly greater decrease in mean energy intake at dinner compared with the control group and a greater increase in mean vegetable intake for the whole day, breakfast, and lunch as shown in crude and adjusted models. A tendency toward improvement was observed in the other secondary endpoints but the improvement was not statistically significant. These results were confirmed by several sensitivity analyses. Conclusions The SILE program that was provided in primary care settings for patients with type 2 diabetes resulted in greater improvement in HbA1c levels than usual diabetes care and education. Trial registration http://UMIN000004049

The polymerase chain reaction (PCR) method was used to determine the presence and amount of human T lymphotropic virus type I (HTLV-I) proviral DNA in central nervous system (CNS) tissue obtained at autopsy from 6 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 1 patient with adult T-cell leukemia (ATL) and CNS infiltration of leukemic cells, and 9 control subjects with other neurological disorders. HTLV-I pX and env but not pol DNA were detected in CNS tissue from 5 of 6 patients with HAM/TSP. The ATL samples were positive for pX, env, and pol DNA by PCR. None of the control samples was consistently positive for HTLV-I by PCR, but all showed positive bands on beta-globin PCR. Quantitative PCR combined with histological studies showed no correlation between HTLV-I proviral DNA amounts and extent of perivascular mononuclear cell infiltration in the HAM/TSP CNS. Also, the amounts of pX and probably env DNA were greater in the HAM/TSP samples than in the ATL sample, although the extent of mononuclear cell infiltration was far less in the HAM/TSP samples than in the ATL sample. Therefore, in addition to infiltrating mononuclear cells, constituent cells of the CNS may harbor the HTLV-I genome, at least in the pX and env regions, in patients with HAM/TSP.

Intravenous (i.v.) injection of 0.1 mg/kg of ADP within one second in 13 rats caused a prompt drop in platelet count to 55.1 plus or minus 3.2% of the preinjection value with a statistical significance (p less than 0.01) at 30 seconds after the injection. At that time, mean arterial pressure and arterial PO2 decreased, while central venous pressure increased. Heart rate decreased with an appearance of sinus bradycardia and variable A-V block. Various respiratory effects such as shallow or slow respiration or apnea appeared. Such changes showed a tendency to recovery within 3 minutes. Splenectomy did not prevent these changes in 6 rats. In 6 thrombocytopenic and leukopenic rats treated with busulfan, these changes did not appear. Intra-arterial injection of the same amount of ADP induced almost no response. When ADP was injected twice 20 seconds apart in 10 rats, the second injection resulted in no effects or slight responses. In contrast, when 10 rats were injected twice 180 seconds apart, both the first and second injections showed the same effects on platelets and cardiopulmonary functions. The results suggests that the effects observed following I.V. ADP are probably due to transient obstruction of coronary and pulmonary microvessels by platelet aggregates. Reduced response following two successive injections may be due either to the reduced platelet count or to a refractory state induced by the first injection. ADP is probably rapidly metabolized in systemic microvascular beds.

Antiplatelet effects by combination therapy with aspirin and ticlopidine were investigated in comparison with single aspirin or ticlopidine therapy in 62 patients with cerebral thrombosis and transient ischemic attack. The 14, 21 and 27 patients were given orally 300mg aspirin, 200mg ticlopidine and 81mg aspirin with 100mg ticlopidine, respectively. Aspirin inhibited platelet aggregation (PA) to ADP and arachidonic acid (AA) but not to PAF, while ticlopidine inhibited PA to ADP and PAF but not to AA. In contrast, aspirin with ticlopidine inhibited PA to all the 3 agonists. Aspirin decreased plasma thromboxane (TX) B2 but not plasma β-thromboglobulin (βTG) or platelet factor (PF) 4, while ticlopidine decreased βTG and PF 4 but not TXB2. In contrast, aspirin with ticlopidine decreased TXB2 as well as βTG and PF 4. Platelet survival and lysis remained unaltered after aspirin or ticlopidine alone, whereas platelet survival was longer and percent platelet lysis was lower in 4 patients treated with both aspirin and ticlopidine than in 3 non-treated patients. Hemorrhagic complications were observed in 2, 3 and 8 patients treated with aspirin, ticlopidine and both, respectively. The results above indicate that combination therapy with aspirin and ticlopidine is a potential antithrombotic strategy, although further investigaton appeared necessary to determine optimal doses for minimizing hemorrhagic complications.

A 50-year-old, right-handed, male showed cortical deafness and Wernicke's aphasia after 14 hours' duration of atrial paroxysmal tachicardia.Neuroradiological study by 90Tm brain scan revealed hot lesions in the temporal area bilaterally and CT scan showed that a low-density area occupied in the both temporal gyri and insulas. The basal ganglia and thalamus (including medial geniculate bodies) were spared bilaterally.1) Pure tone audiometry revealed a bilateral mild hearing loss but the thresholds were unstable.2) Bekesy audiometry showed a temporary threshold shift bilaterally.3) Speech audiometry revealed lower discrimination rate than 25% bilaterally.4) Discrimination rate of musical instruments was remarkably low. Perception of rhythm and melody was markedly impaired.5) Sound localization for warble tone was well preserved.6) Auditory Brain Stem Response by click sounds was normal.7) Wave forms of the middle latency response were almost normal.However, thresholds of the slow vertex response were abnormally high in both ears. Thus, auditory pathway in the peripheral apparatus and brain stem appeared to be almost intact, but functionally, cortical or subcortical lesions were suspected bilaterally, Sensory aphasia was coincident. Other six cases of cortical deafness or auditory agnosia in the literature were reviewed, and the clinical findings and auditory disorders of these seven cases were remarkably similar to those of the case reported herein. In conclusion, we consinered that “auditory agnosia due to bitemporal lesions” for these cases was the better term “cortical deafness.”

Lumi-aggregometerを用いて血小板より放出されるATP量を求め, 虚血性脳血管障害におけるATP放出能と凝集能との関係ならびに抗血小板剤の効果について検討した.抗血小板剤未投与の脳血栓症, TIAのATP放出量はそれぞれ3.88±2.24μM, 4.97±4.11μMであった.最大凝集率 (M%) はそれぞれ66.3±11.1%, 77.1±11.6%, 最大凝集までの時間 (Tm) はそれぞれ288.5±86.9sec, 301.8±78.8sec, 解離率 (D%) はそれぞれ, 6.2±11.5%, 3.4±5.1%であった.これらの値は, 健康成人ならびにASA (0.3～0.7g/日), ticlopidine100mg/日または200mg/日の治療群と比べ有意 (p

Currently we developed a new in vitro test of hemostasis, the filter bleeding time (FBT), which is based on progressive decrease of flow rate of citrated blood through a disk filter of Woven Dacron under controlled pressure as platelet aggregates occlude the filter. FBT is defined as the time when the blood drop rate has fallen to less than 1/30sec. There was a high correlation (r=-0.91) between FBT and platelet count below 105/μl in dogs made thrombocytopenia by estradiol. There was a significant correlation (r=0.65) between FBT and Ivy Bleeding Time (IBT) in 59 patients referred because of a suspected bleeding disorder. FBT was prolonged in 3 of 3 patients with Glanzmann's thrombasthenia, 5 of 6 with von Willebrand disease and normal in 6 of 6 with hemophilia. FBT was more sensitive than IBT in detecting abnormal platelet aggregation in response to collagen, epinephrine or arachidonate. A monoclonal platelet antibody (HP1-1D), which is a specific antibody for platelet membrane glycoprotein IIb and IIIa, increased FBT in a dose dependent manner. FBT was prolonged by adding 0.1μM prostaglandin I2 and an ADP scavenge system, CP/CPK/ATP but not by adding thromboxane synthetase inhibitor, UK-37, 248 or UK-38, 485. Thromboxane synthetase inhibitors had, however, a synergistic effect on FBT when added with CP/CPK/ATP. Oral ticlopidine 250mg b. i. d. for 7 days increased FBT as well as IBT and Template bleeding time. Additional increase in FBT and skin bleeding times was produced by simultenous taking of 650mg aspirin b. i. d. for 7 days.FBT was significantly shorter in smokers than in non-smokers. It is suggested from these observations that FBT is a useful test of platelet function and has certain advantages over skin bleeding time methods.

Recently ethanol intoxication has been recognized as a risk factor of cerebral thrombosis in the young adults.The purpose of this study is to elucidate the effects of ethanol on blood coagulability, fibrinolytic activity, platelet aggregability, blood viscosity, and serum protein and lipids. Each comparative study was made before and after the oral administration of beer in nine young, healthy male volunteers. Beer was taken in the total amount of 1899ml containing about 4.5% ethanol (total ethanol volume: about 85g) over 3 hours.The results of this study were as follows:(1) Elevated hepaplastintest (p

A variety of platelet function tests were performed in patients with four forms of obstructive cerebrovascular disease (CVD); transient ischemic attacks (TIA), reversible ischemic neurological deficit (RIND), cerebral infarct, and cerebral embolism of cardiac source in rheumatic valvular heart disease (RVHD). Platelet studies included platelet aggregation induced by ADP and ristocetin, spontaneous platelet aggregation, von Willebrand factor (VIII:vWF), platelet aggregation enhancing factor (PAEF), and percentage of large platelets (megathrombocytes). Serial testing was carried out in acute stroke patients. The effect of aspirin therapy was also evaluated. A clear difference in results was observed between patients with cardiogenic embolism and those with other forms of CVD. In patients with TIA, RIND, and cerebral infarct, platelet aggregation, both induced and spontaneous, was enhanced along with elevation of plasma VIII:vWF and PAEF, and increased percentage of megathrombocytes. In patients with cardiogenic embolism, however, these studies were negative except for percent megathrombocytes. This value was increased in the embolic patients with RVHD in comparison with non-embolic patients with RVHD. Increase in platelet aggregation to ADP and percent megathrombocytes developed slowly over a week following stroke. Induced and spontaneous platelet aggregation, and percent megathrombocytes could be normalized with 600 mg aspirin p.o. These studies suggest that a systemic increase of hyperaggregable platelets and of plasma activators of platelet function exists in thrombotic CVD and may be related to its pathogenesis, while local hemodynamic factors may be more important in the thrombogenesis of cardiogenic embolism.

症例は37才,男性.幼少より小柄で,また四肢の不随意運動を認めていた. 11才頃より両側眼瞼下垂,次第に外眼筋麻痺,難聴が出現した.姉および兄は,外眼筋麻痺,難聴,知能低下,やせを呈し, 40才前後で死亡しており同様疾患の可能性があるほか,同胞8名中4名に腎障害がみられた.入院時現症では,やせ著明,網膜色素変性,外性器発育不良を認め,神経学的には,知能低下,外眼筋麻痺,難聴,近位筋優位の筋萎縮,筋力低下,深部反射低下,舞踏病様不随意運動を認めた.心電図上,不完全右脚ブロック.髄液タンパクの軽度上昇,頭部CTで白質の広範な低吸収域および大脳萎縮を,また,表面筋電図上,舞踏病様不随意運動を確認した.左腓骨筋生検ではragged-red fiberを認め,電顕像でクリスタル様封入体を有する異常ミトコンドリアの集積を認めた.ホルモン検査ではLH, FSHの高値, testosteroneの低値を認め,各種負荷試験結果は原発性性腺機能低下症に一致した.以上より本症例は多彩な合併症を有するKearns-Shy症候群と診断された.合併症として原発性性腺機能低下症, CT異常はまれながら記載がみられたが,舞踏病様不随意運動についてはこれまでに報告がなく,極めてまれである.

身体半側萎縮症と部分てんかんを合併したpachygyriaの1例を報告する.症例は34才,女.小児期より軽い跛行が出現し,左上下肢が右側に比し細く短いのを自覚していた.昭和50年より時々左身体抑制発作が出現.昭和58年2月妊娠中に同発作が頻回となり,突然左姿勢発作が出現し,てんかん重積状態となつたため入院.臨床所見として左身体半側萎縮を認めた.頭部CT,および脳血管撮影において,右Sylvius裂・弁蓋部の形成不全とともに,右prefrontalよりprecentral regionにかけて皮質・脳回の肥厚を認め,頭部dynamic CTにて肥厚部が皮質と同様の時間-吸収値曲線を示すことから他の健常な皮質と同質と推測し,同部位に限局したpachygyriaと診断した.また,身体の萎縮側で皮膚温低下.発汗低下.指尖容積脈波上中枢性の細動脈反応の低下があり,筋生検ではtype II atrophyを認めた.従来, pachygyriaの生前診断は困難とされていたが,近年CT技法の発達に伴い数例の報告がみられるようになり,本症例の如く頭部dynamic CTをも用いることで診断は可能となつた.合併症については,部分てんかんの責任病巣はpachygyriaの部位と一致した.本症例のtype II atrophyはpachygyriaによる錐体路起始部の障害と関連があると考えられ,一方,自律神経障害を介しpachygyriaが半側萎縮症の成因となつた可能性が示唆された.本症は,形態的な奇形であるpachygyriaに対応する機能障害を呈した貴重な症例と考えられる.

60～79歳までの101名 (男55名, 女46名) の脳卒中後遺症のリハビリテーション (リハ) を行った. 発症より入院までの期間は平均2.8カ月, 入院期間は平均5.6カ月であった. 入院時及び退院時に Brunnstrom stage の分類に従って麻痺側の機能を分類した. 退院時の運動障害の予後として上肢を廃用手, 補助手, 実用手の3段階に, 下肢を歩行不能, 介助～監視, 独歩の3段階に分類してリハの効果を判定した. 全例にCTスキャンを施行し, 第一群 (内包・基底核・視床) 33例, 第二群 (皮質・皮質下広汎) 33例, 第三群 (皮質・皮質下限局性) 15例, 第四群 (病巣不詳) 20例であった. 臨床症状, 精神機能並びに心理検査を施行し, リハの阻害因子について病巣との関連を検討し, 次の様な結果を得た.1) 第一群～第四群まで入院時上下肢の Brunnstrom stage (Br. stage) と退院時 Br. stage に変化がみられなかった. すなわち, 入院後に著しい麻痺の回復はみられなかった.2) 重度の麻痺である Br. stage (退院時) 3以下のものは, 第一群に比べ第二群の方が, 上下肢共に有意 (p

The following are the clinical and autopsy findings in a 63-year-old woman with myelopathy associated with the human T-cell lymphotropic virus Type I (HTLV-I). HTLV-I antibody was positive in both the serum and cerebrospinal fluid (CSF). In the lower thoracic region, demyelination and the loss of axons were accompanied by a proliferation of astrocytes, and gliosis was found in the lateral columns. Perivascular and parenchymal infiltrations of macrophages, lymphocytes, and plasma cells were also observed, but neither viral inclusion bodies nor atypical lymphocytes were found.

Three cases with the occurrence of asterixis during the administration of L-dopa were reported. Liver and metabolic functions were normal in all the patients. Upon the appearance of asterixis no other involuntary movements probably resulting from an excess administration of L-dopa were observed. Asterixis occurred accompanied by clinical symptoms such as hallucination and a mild clouding of consciousness by insomnia. Because of its reversal with drug withdrawal, asterixis seemed to be L-dopa-related. The biochemical basis of asterixis is not known but may involve the dopaminergic or serotonergic system.

脳塞栓症を生じて入院した特発性心筋症 (ICM) 8症例について臨床的検討を加えた.ICMの病型の内訳は拡張型3例, 肥大型4例, 肥大型閉塞性1例で, 肥大型の多いことが従来の報告と異なっていた.肥大型も心房細動や心不全を合併する病期になると拡張型と同様に塞栓症を併発しやすくなると考えられた.ICMによる脳塞栓症の特徴は右内頚動脈系に多く, 頻回に再発をくり返し, 意識障害はないか軽度なことであった.凝血学的には血小板放出因子 (β-TG, PF4) の増加と血液粘度の上昇が高率に認められ, 心腔内の血流異常や血栓形成との関連が示唆された.ICMによる脳塞栓症の再発予防に抗血小板剤療法は有効とは云い難く, 抗凝固療法が試みられるべぎである.

Despite the efforts of many workers, the cause and therapy has not been clarified. We carried out the therapeutic trial of thyrotropin releasing hormone (TRH) for amyotrophic lateral sclerosis (ALS) from January, 1979 to January, 1983. There were 16 subjects. The patients were given a low dose (0.5-2 mg) of TRH intravenously or intramusculary. Mild to moderate improvement was found in 9 (56%) of 16 patients. TRH has been reported to have the activating effects on the pyramidal tract, brainstem motor nuclei, and motoneuron in the spinal cord as a neurotransmitter or neuromodulator. We thought such action of TRH to be useful to the therapy of ALS.

Platelets have been known to be an important factor in thrombogenesis. In an early stage of thrombosis, platelets adhere to exposed subendothelial collagen eliciting release of ADP and aggregate each other. ADP seems to be a very important substance in platelet thrombosis. In this experiment ADP was injected into the vein in 7 control Wistar rats and 6 spontaneously hypertensive rats (SHR). SHR were administered with 0.1% NaCl as drinking water over a period of 10 weeks and the blood pressure showed to be 200mmHg or above.ADP 1mg/kg was injected rapidly into the jugular vein of the anesthetized rats. Blood samples were collected from carotid cannula before and 30sec, 3, 10, 20 and 30min after the injection. EKG and respiration were monitered and recorded continuously. 51Cr-labeled platelets were infused in 2 rats. They were sacrificed 1min after ADP injection and the organs were studied for the radioactivity and the histological observation. In control animals, platelet count decreased immediately after the ADP injection. Variable A-V block, premature beats and apnea developed immediately after the injection and subsided by 1min. Arterial hypotension and rise in the central venous pressure were also observed for a period of 10min and gradually subsided. In the analysis of platelet radioactivity, platelets were revealed to accummulate unproportionally in the lungs. Histological examination revealed platelet thrombi in the pulmonary microvas-culature.In SHR rats, decrease in platelet count and heart rate, degree of arrhythmia, apnea, systemic hypotension and elevation in central venous pressure after ADP injection were less than in control rats. In the platelet volume study, the mode related volume was at 2.7μ3 in SHRs as compared with the mode of 2.4μ3 in controls. The volume distribution curve in SHR shifted to the left indicating a relative increase in smaller platelets in the population.In summery, ADP injected into the central vein produced platelet aggregation which were trapped in the pulmonary microvasculature causing pulmonary thromboembolism. Arrhythmia and respiratory distress seems to be due to transient pulmonary thromboembolism. These changes were less severe in SHRs. These results would suggest that hypertension and/or possible association of the vascular change cause different attitude of platelets to ADP.

サルコイド・ポリニューロパチーはサルコイドーシスの神経学的合併症の中でも比較的まれである.さらにサルコイド・ポリニューロパチーと考えられる症例の末梢神経組織内に肉芽腫性病変を証明したとの報告は極めてまれなので若干の文献的考察を加えて報告する.症例は四肢末梢のしびれ感を呈した53才,女性で末梢神経組織内にサルコイド病変が認められた.その所見として腓腹神経横断面では肉芽腫性血管炎を示し縦断面ではepineurial spaceに肉芽組織がみられた.髄鞘・軸索の変化は軽度であつた.電顕では末梢神経組織内の血管基底膜の変化が観察された.なお本症例でプレドニゾロンによる治療を試みたが末梢神経症状の改善は明らかでなかつた.

血小板ADP凝集の記録方法として,血小板浮遊液の濁度変化による透過光線の変化を経時的に測定する方法が最も広く用いられている.本法により血小板ADP凝集の強さを定量的に表現しようと試みた.すなわち,ADPにより最大の凝集を示した時の血小板浮遊液のoptical density (OD)と血小板を除いた血漿自身のODの比をもつて凝集の強さを百分率変化として表現した.実験には10例の症状の安定した患者ならびに健康者を用い,同一個体から日を変えて3回採取した検体にて,血小板ADP凝集の強さの再現性,濃度一反応関係,個体差を二元配置法にて推計学的に検討した.用いたADPは最終濃度10-6, 3×10-6,10-5モルである.各濃度のADPによる反応の10例の平均値で,再現性は危険率1%以下で認められた.個体差も危険率1%以下で各濃度による反応に認められた.3濃度間の濃度一反応関係は,一次性,二次性ともに認められた(P〈0.01).この原因として,血小板ADP凝集の強さに上限があり,二次性を構成する最終濃度10-5モルADPを除いてADP凝集の強さの濃度一反応関係をあらわすと, Y=358.382+64.324X(X=ADP log Concentation)なる一次式であらわせた.

When an activity of respiratory center in brain is depressed by high O2 pressure in blood, CO2 pressure in blood increases and respiratory acidosis appears in some patients especially with chronic respiratory diseases. Resipratory acidosis induces disturance of consciousness and the phenomenon is called as CO2 narcosis. The authors reported 2 cases of CO2 narcosis under an inhalation with high concentration of oxygen in O2-tent. The 1st case: 60 years old male was suffered from chronic cor pulmonale during 8 years. He was taken in O2-tent because he had infection of respiratory tract and showed dyspnea. Under the inhalation with air containing 50% of oxygen, he showed sopor 6 hr later. At that time, his PaO2 was 72 mmHg, PaCO2 was 75 mmHg and pH of blood was 7.34. The 2nd case : 70 years old female was suffered from pulmonary emphysema during 6-7 years. She was taken in O2-tent because she had infection of respiratory tract and showed dyspnea. Under the inhalation with air containing 50% of oxygen, she showed somnolence 22 hr later. Her PaO2 was 68 mmHg, PaCO2 was 96 mmHg and pH of blood was 7.33. When both the cases were taken out from the O2-tent and were deeply respired in room air by their voluntary movement, their consciousness, blood gas content and pH improved rapidly. These results suggest a large influence of respiratory air content as a condition of environmental factors on homeostasis.

Incubation at 37°C for 30 min or the addition of CaCl2 (5 mM) generated platelet-clumping activity in citrated plasma and EDTA plasma previously acidified to pH 5.5 and in which heparin was added to give a concentration of 0.5 mg/ml. Similar treatment could not produce platelet-clumping activity in saline or denatured plasma that had been heated to 56°C. Heparin, chondroitin sulfate B, or heparan sulfate produced platelet-clumping activity in BaSO4-adsorbed serum over a given pH range. The effective pH range for each compound was; heparin 0.5 mg/ml, pH 5.16 ± 0.09 to 6.31 ± 0.14; chondroitin sulfate B 0.5 mg/ml, pH 5.62 ± 0.09 to 6.88 ± 0.06; 2 mg/ml, pH 5.17 ± 0.16 to 7.18 ± 0.16. The effect of heparan sulfate in generating platelet-clumping activity was estimated only qualitatively at pH 6.0 and proved to be positive. Chondroitin sulfate A, chondroitin sulfate C, and hyaluronic acid failed to yield platelet-clumping activity in BaSO4-adsorbed plasma. The minimal concentrations of heparin and chondroitin sulfate B necessary to induce platelet-clumping activity in the BaSO4-adsorbed serum were 0.5 mg/ml and 0.1 mg/ml, respectively.

SUMMARY A model is described for the study of factors affecting hemostasis. It consists of a Teflon extension of the carotid artery of rats. Holes of precise diameter are then produced in the extension with a micromanipulator and the aid of a microscope. The bleeding time of these holes is then recorded. The principal advantage of this method is that it makes possible the production in the “blood vessel” of holes the diameters of which are known with a high degree of accuracy, under known conditions of intravascular pressure. With holes below 75 μ in diameter, prolongation of the coagulation time with heparin did not affect the bleeding time. With increasing hole diameters, or with increasing intravascular pressure, coagulation time did affect the bleeding time. Bleeding time could be predictably modified by increasing or decreasing blood pressure. There is a striking interrelationship of these factors in influencing the bleeding time. Intravenous pyridinolcarbamate (12 mg/kg) significantly prolonged the bleeding time for a 20-minute period. At a lower dose (8 mg/kg), which was ineffective in prolonging the bleeding time, pyridinolcarbamate partially inhibited the shortening of the bleeding time that follows the administration of epinephrine. Intravenous polyvinylpyrrolidone (PVP), 750 mg/kg, caused a sustained prolongation of the bleeding time, lasting more than three hours.

Bovine tendon collagen suspension (4.5 mg/kg) was injected rapidly into the femoral vein of 14 normal (untreated) and 8 busulfan treated rats. Trasient effects included decreased platelet counts and arterial PO2, increased central venous pressure, apnea, bradycardia and variable A-V block. These findings were most prominent within 1 minute after injection and subsided or disappeared by 10 minutes. During this period, ADP and ATP in platelet-free plasma from carotid arterial blood were measured in a liquid scientillation counter using the firefly luciferase assay. In normal (untreated) rats, collagen injection was followed by increases in plasma ADP and ATP, a rise in plasma hemoglobin and minimal changes of fibrinogen and hematcrit. Pathological observations indicated the platelet emboli in pulmonary vessels. In contrast, rats made thrombocytopenic by intraperitoneally infected busulfan prior to collagen injection had minimal or no change in platelet count, plasma ADP, ATP, hemoglobin, fibrinogen, or cardiopulmonary functions following collagen injection. These findings suggest that collagen injection causes release of ADP and ATP from platelets; released ADP induces platelets to form aggregates which lodge in the coronary and pulmonary microcirculations and elsewhere, resulting in thrombocytopenia and the cardiopulmonary dysfunction, in the presence of shear, of red cells with vessel surfaces altered by platelet aggregates.

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.

MRIによって診断し得た成人Arnold-Chiari奇形(以下ACM)について報告する.従来, ACMの診断においてメトリザマイドCTや椎骨動脈撮影等比較的侵襲的な検査が行なわれてきたが,今回我々は,軽度の歩行障害を主訴とする39才,女性例を経験し, MRIによって成人ACMと診断し得た. MRIはその安全性と提供しうる情報量の多いことから, ACMの診断上有用な検査と考えられた.

Platelet aggregability was measured using the screen filtration pressure (SFP) method in 50 elderly healthy people, 93 persons with essential hypertension, 166 patients with cerebral thrombosis at the recovery stage (more than two months after onset), and 74 patients with cerebral hemorrhage at the recovery stage. SFP by 3 muM ADP in the healthy persons, the hypertensive patients, and the patients in the recovery stages of hemorrhage and thrombosis were 148.7 +/- 53.5, 176.2 +/- 74.4, 189.8 +/- 58.3 and 206.3 +/- 58.9 mm Hg, respectively. The differences of the SFP between the Healthy and each of the diseased groups were statistically significant (P less than 0.01 to 0.05). Meanwhile, SFP of nine patients with cerebral thrombosis and 18 patients with hemorrhage was measured during their time course of disease from the onset to 180 days. SFP in the acute stage of thrombosis showed an increase and a gradual decrease during the time course, while SFP in the acute stage of hemorrhage showed the opposite -a decrease and a gradual increase. A statistically significant difference was observed between both groups within 30 days from onset (P less than 0.001). Screen filtration pressure in the acute stage of hemorrhage showed 95.2 +/- 17.7 mm Hg in nine survival cases and 194.0 +/- 96.2 mm Hg in nine deaths with ten days from the onset. The difference was statistically significant (P less than 0.001). Such results suggest a role of platelets in cerebral thrombosis and hemorrhage and a usefulness in differential diagnosis of both diseases.

慢性進行性小脳症状を呈したクリプトコッカス髄膜脳炎の1例を報告した.症例は61才女性で,めまい,悪心,難聴で発症し,さらに歩行障害,構音障害,頭痛,微熱,尿失禁が順次出現した.入院時,四肢・躯幹失調を認め,髄液にてリンパ球増加と糖減少,培養にて莢膜陰性のCryptococcus neoformansが証明された. Amphotericin B, 5FC併用療法にて髄液所見,小脳症状は改善した.

症例は56才,女性.昭和59年3月,失語症が出現し,左前頭側頭葉に梗塞所見があり入院した.その後外来で血小板凝集抑制薬を投与し経過観察中, 6月に再び失語症が出現し, CTで新たに左側頭葉に梗塞所見があり再入院した.脳血管造影を施行後, 3日自と12日目に2回の脳梗塞再発作が出現した.この間血液凝固学的には慢性DICの所見を呈し,原因を検索した結果,卵巣癌が発見された.急性DICに脳血管障害が合併する事は良く知られているが,慢性DICによる脳血管障害の報告は少なく,本例を含め6例の報告しかない.一方本症例では,特に脳血管造影後に慢性DICの急性増悪を示し脳梗塞再発の誘因になったと考えられた.

A case of Noonan's syndrome with cervical syringomyelia is presented here representing the second reported instance of such association. A CT of metrizamide myelography revealed a high density in the middle subintradural space in the cervical region below C2. Sensory dissociation was minimal and localized in the left C4. It could not be determined whether this association between syringomyelia and Noonan's syndrome is related or represents a chance.

症例は22才,男性で, 20才時ヘルペス脳炎に罹患し軽快したが, 15カ月後再び発熱,意識障害が出現.単純ヘルペスウイルス(HSV)抗体価上昇より再発性HSV脳炎と診断した.免疫不全はなく再発の原因として弱毒HSVの再感染,またはHSVの潜伏感染が考えられた.頭部CTでは両側前頭葉の低吸収域のみ認めたが, MRIではさらに両側頭頂葉,右側頭葉にも異常信号域を認め, HSV脳炎の病巣検出にMRIは有用と考えられた.

症例は25才,男性で腎移植後メチルプレドニゾロンの投与を開始. 16mgから12mgに減量された後に光視症,後頭部痛が出現し,眼科で乳頭浮腫を指摘されたため,精査目的で当科に入院した.髄液圧は250mmH2Oと高かったが,他の髄液所見に著明な異常を認めず,また頭部CT, MRIでは頭蓋内に占拠性病変を認めないことから, pseudotumor cerebriと診断した.原因としてメチルプレドニゾロンの減量が最も疑われた.メチルプレドニゾロンを増量せずに経過観察をしたところ,光視症,後頭部痛は軽快し,髄液圧は正常化した.

Diphenyl-hydantoin長期服用中に発症したSLEを報告する. 24才,男子. 38°Cに及ぶ発熱,蛋白尿を主訴として入院.生後5カ月後に後頭部を強打,以後てんかん様発作が出現し,昭和36年より10年間diphenyl-hydantoin O.15～0.3g/日服用.入院時発熱,浮腫,多彩な尿沈渣所見のみで, SLEのいわゆる多種多彩な臨床像はみられなかつた.しかし血清挙的所見(LE細胞,抗核抗体,補体価),病理学的所見(腎生検像はlupus腎炎)からSLEが強く推測された.なお調査可能な限りの血縁家族の抗核抗体は陰性であつた.当初dipheny1-hydantoinにより誘発されたSLEと考えhydantoinを中止しsteroid薬投与を開始したが, hydantoin中止9週後にsteroid薬減量中病状の再燃を認めた.腎生検像所見ともあわせ,かかる経過はhydantoinによつて誘発されたSLEと考えるよりも, hydantoin服用中にたまたまSLEが発症したものと考えられた.またlupus diathesisの存在は否定的であつた.

SummaryADP, AMP, or ATP was injected rapidly intravenously in rats. ADP injection resulted in the f olio wing transient changes: a drop in platelet count, a rise in central venous pressure, a fall in carotid arterial PO2, bradycardia, arrhythmia, flutter-fibrillation, and arterial hypotension. AMP and ATP produced some of these same effects; but except for hypotension, their frequency and severity Avere much less than those following ADP.Prior intravenous administration of acetylsalicylic acid or pyridinolcarbamate, two inhibitors of the second wave of ADP-induced platelet aggregation in vitro, significantly reduced the frequency and severity of all the above ADP-induced changes except hypotension. These observations suggest that many of the changes (except hypotension) observed to follow ADP injection are produced by platelet aggregates which lodge transiently in various microcirculatory beds then rapidly disaggregate and recirculate.

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P