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"Guidelines for the use of red blood cell products, platelet transfusion concentrates and fresh frozen plasma based on scientific evidence" was published by the Japan Society of Transfusion Medicine and Cell Therapy. Each transfused blood product carries a certain risk of an acute or late adverse event. Hematologists must be familiar with transfusion-associated adverse events, such as transfusion-related acute lung injury, transfusion-associated circulatory overload, post-transfusion graft-versus-host disease, transfusion-transmitted viral infection, etc. Thus, these guidelines should be followed for the appropriate use of blood products according to trigger values and indications for transfusion.

Here we report a case of secondary graft failure that was effectively treated with donor lymphocyte infusion (DLI). A 64-year-old female patient with acute myeloid leukemia obtained partial remission with azacitidine therapy and subsequently underwent unrelated allogeneic bone marrow transplantation (BMT). After confirming successful engraftment and achieving complete remission with incomplete blood count recovery, she was subsequently followed up at an outpatient clinic. A routine test performed by day 110 after BMT revealed the presence of pancytopenia. A bone marrow aspirate did not reveal any evidence of disease relapse or hemophagocytic syndrome but demonstrated hematopoietic insufficiency. Donor chimerism also declined over time; thus, the patient was diagnosed with secondary graft failure. Supportive treatment, including granulocyte-colony stimulating factor and blood transfusion, failed to improve the blood parameters. Because the patient refused a second BMT, we performed DLI on day 147 after BMT (CD3 + cells: 1.0×10 7 /kg, single dose). Consequently, the blood cell count improved promptly and dramatically without adverse events. Following this, we discussed the case and analyzed the related literature.

Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD). The 2nd case was a 47-year-old woman who had received cadaveric renal transplantation. The initial immunosuppressive therapy was comprised of cyclosporine, azathioprine, and prednisolone. Twenty-seven years after transplantation, she developed MDS (RA). Both patients received 75 mg/m 2 AZA once daily for five consecutive days on a 28-day cycle. After 2 courses of therapy, both patients achieved hematological improvement (IWG 2006 criteria) without severe (grade 3/4) non-hematological adverse events. Moreover, AZA did not affect the status of organ transplantation in terms of engraftment and function of the graft. In conclusion, AZA would be a safe and effective agent for patients with MDS after solid organ transplantation. However, long-term follow-up is needed to confirm the safety and efficacy of AZA for patients undergoing solid organ transplantations.

In the present study, we compared the incidence and severity of oral mucositis among patients undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with busulfan 12.8 mg/kg (FB12.8), with busulfan less than or equal to 9.6 mg/kg (FB9.6), and with melphalan 140 mg/m 2 (FM). The incidence of oral mucositis after FB12.8 was the highest among these 3 groups. After FM, all of the patients had developed oral mucositis by day 7. The mean disease duration of oral mucositis after FB12.8 was 13.5 days, whereas the mean disease duration after FM was 24.9 days, and was significantly prolonged as compared to that after FB12.8 (p=0.0009). The incidence of severe oral mucositis (grade 3) after FM was significantly higher than that after FB12.8 (p=0.03). As stated above, although the incidence of oral mucositis after FB12.8 was higher than that after FM, oral mucositis after FB12.8 showed improvement relatively quickly without deterioration. In contrast, the higher incidence of severe oral mucositis and the delay in resolution of mucositis after FM were remarkable.

Acute esophageal mucosal lesion (AEML) is a comprehensive disease that includes necrotizing esophagitis and acute erosive esophagitis, which result in upper gastrointestinal bleeding. However, little is known about AEML. We examined the clinicopathological features of 57 AEML cases. AEML presented as acute diffuse esophagitis showing an endoscopically erosive mucosa. The disease did not include corrosive injury, radiation-induced damage, infectious esophagitis, or acute exacerbation of chronic gastroesophageal reflux disease. AEML predominantly affected elderly men, and upper gastrointestinal bleeding was the frequent presenting symptom. Severe underlying diseases such as cranial nerve disease or pneumonia were observed in 98% of the patients. Esophageal sliding hernia and gastroduodenal ulcers were endoscopically observed in 67% and 63% of the patients, respectively. Deaths due to exacerbation of the underlying diseases accounted for 16%. Most cases rapidly improved with conservative management using a proton pump inhibitor or an H2 blocker. Therefore, AEML should be considered a disease having characteristics different from those of common gastroesophageal reflux disease.

We retrospectively investigated the status of transfusional iron overload at Kinki University Hospital. One hundred and sixty three patients received more than 10 red blood cell (RBC) units per year in 2009 and 2010. Myelodysplastic syndrome (37.4%) and aplastic anemia (11.0%) accounted for about 50% of the underlying diseases. At the time of receiving a total of 20 RBC units, 90.8% and 66.2% of the 65 patients evaluated had more than 500 and 1,000 ng/ml of serum ferritin, respectively. The frequency of organ dysfunction associated with iron overload was 56.9% of all the patients assessed, 37.8% of patients with serum ferritin levels of 500∼999 ng/ml, and 67.4% of patients with serum ferritin levels >1,000 ng/ml. Although the Japanese guidelines propose 40 units of RBC transfusion and/or a serum ferritin level of 1,000 ng/ml as a good point to start iron chelation therapy, our results suggest that iron overload and consequent organ dysfunction may occur earlier than this. Therefore, it may be necessary to start iron chelation therapy earlier than that suggested by the Japanese guidelines.

Although macrocytic anemia can develop in patients with acute blood loss, such anemia in very old patients is uncommon. In this report, we describe the course of an 89-year-old woman who had a rapid recovery from macrocytic anemia by medication only after acute blood loss due to a gastric ulcer. She had been treated with antihypertensive drugs for the previous 28 years at our outpatient clinic, and was admitted because of acute anemia 6 days after she had experienced tarry stool. Her hemoglobin (Hb) count and mean corpuscular volume (MCV) were 8.4 g/dl, and 103 fl, respectively. A gastroscopic examination indicated that the tarry stool originated from a fresh gastric ulcer. She was treated with an iron preparation, a diuretic and a proton pump inhibitor. The anemia was rapidly improved to Hb 10.5 g/dl and MCV 106 fl in one week, and to Hb 14.5 g/dl and MCV 99 fl in 4 weeks. At admission, she had slight pleural effusion and slight edema associated with an increase in her plasma brain natriuretic peptide (BNP) level (323 pg/ml), and her left ventricular ejection fraction was 76% based on the echocardiography findings, which are signs of the high-output heart failure without remarkable left ventricular diastolic dysfunction (E/e': 11.2). However, these signs improved rapidly, and her BNP level thereafter decreased to 114 pg/ml within four weeks.

We herein reviewed the clinical applications of glucocorticoid (GC) hormones to inflammatory bowel disease (IBD). In the therapeutic strategy for active ulcerative colitis, topical/systemic GC administration is still central during these fifty years. However, non -responders to GC are present at 30-40% of the active UC patients. We analyzed the expression of GC receptor isoform, namely hGRbeta, in peripheral blood mononuclear cells, and suggest the possibility that expression of hGRbeta, induced by proinflammatory cytokine IL-18, is closely related GC resistance in UC.

A 76 year-old man had had hypertension, diabetes mellitus and hyperlipidemia since 1985, and bruit in his left neck since 1993. He had abrupt decrease in left visual acuity on November 24, 2005, and visited an ophthalmologist. On November 28, his corrected visual acuity was 1.0 in the right and 0.1 in the left. The examination of optic fundi showed ear-side edema of the left optic disk. Fluorescence examination of the left optic fundus showed delay in early filling and later hyperfluorescence. Goldman visual field examination showed horizontal lower semiblindness. Since he did not complain of eye pain, his blood examination showed no reaction of inflammation, and he had hypertension, diabetes mellitus and hyperlipidemia, anterior ischemic optic neuropathy was diagnosed. The treatment with aspirin, alprostadil and prednisolone transiently improved the optic fundi and visual acuity, but his left visual acuity returned to 0.1. Carotid ultrasonography showed 95 percent stenosis in the left internal carotid artery. As there is no established treatment for ischemic optic neuropathy, the management of risk factors is most important.

Background: In previous reports, all pregnant women with VKH were successfully treated in the second or third trimester with high-dose systemic corticosterioids without any severe complications. We present a case of fetal death during systemic steroid treatment of a VKH disease patient., Results: A 28-year-old woman in the 30th week of pregnancy was diagnosed with VKH disease. Because of the progression to high bullous retinal detachment in spite of topical corticosteroid therapy, systemic intravenous prednisolone (PSL, 200 mg/day) was begun. On day 18 (PSL, 55 mg/day), sudden intrauterine fetal death occurred. Maternal conditions were normal and there was no apparent abnormality in the umbilical cord, placenta, or fetus; no autopsy was allowed. With gradual tapering of the PSL, the patient's vision was preserved, without recurrence of the VKH disease., Conclusions: We present a case of fetal death in a 28-year-old pregnant woman being treated with intravenous prednisolone for VKH disease. The cause of the fetal death was not clear. It was reported as an adverse event.

Topical or systemic administration of glucocorticoid (GC) plays major role in UC therapeutic strategy. For severely-active cases, more than 60 mg/day intravenous regimen has been recommended. Oral prednisolone at 30-40 mg/day dose for moderate severity of UC, or GC enema for localized UC are also used in general practice. However, it is proved by controlled trial that low-dose GC has no effect on preventing the relapse of UC. To improve the QOL in UC patients, all administrated GC must be tapered off after achieving the remission. GC receptor expression is essential for pharmacophysiological effects of GC on target cells. It is reported that beta isoform of the GC receptor contributes the unresponsiveness to GC. Prediction of GC-sensitivity by measuring the expression of GC receptor isoforms in PBMC of UC patients is also discussed.

A Japanese man who died at age 86 had been followed since the age of 58, when he presented with hypertension of 150/95 mmHg. The patient remained socially active until he died suddenly of a ruptured thoracic aortic aneurysm, although he experienced angina pectoris in August 1974, and myocardial infarction was identified on electrocardiography in October 1974. He underwent operation for rectal cancer in 1987, and an abdominal aortic aneurysm 38mm in diameter was identified at that time. The patient underwent an operation for rupture of the abdominal aortic aneurysm in 1991. A thoracic aneurysm of 40 mm diameter was identified in 1995, and this expanded to 53 mm by 1997. Autopsy revealed a thoracic aortic aneurysm in the arch (8 x 5 x 5 cm) and descending aorta (7 x 7 x 8 cm). A large volume (2,080 ml) of bloody pleural fluid was present

The status of reduced-intensity stem cell transplantation (RIST) in the Kinki area was investigated by questionnaires. We sent out questionnaires to 72 institutions and received 51 replies (72.2%). RIST was performed in 16 institutions (31.4%). A total of 91 cases were included of whom approximately 70% were non-remission or advanced hematological malignancies. Various conditioning regimens were used for RIST, most often consisting of fludarabine, busulfan and antithymocte globulin. Acute GVHD developed in 57% of all patients. Relapse or disease progression developed in 42.7% of evaluable patients. The overall survival rate was 54.6%, and 80% of low risk patients were alive at the time of analysis.

A 75-year-old man had a 26-year history of hypertension and an 18-year history of effort angina pectoris. He suffered acute myocardial infarction at age 61. According to serial echocardiography, the initially hypokinetic segment of the left ventricular apex was transformed to an apical aneurysm over the course of 10 years (at age 71). Ten months later, a transient ischemic attack occurred, despite the administration of aspirin. At age 72, echocardiography revealed a hyperechoic lesion that was suspected to be a thrombus within the aneurysmal cavity. Cerebral infarction (right occipital lobe) occurred 13 years after myocardial infarction, at age 73. After warfarin therapy for 3 months, the thrombus-like echo in the left ventricular aneurysm disappeared.

Kanagawa Occupational Health Promotion Center conducted a survey on how the MSDS is utilized at workplaces with more than 50 employees handling chemical substances, and what measures are taken to help employees to thoroughly understand information in the Material Safety Data Sheet (MSDS). Questionnaires were sent out to 265 enterprises in Kanagawa prefecture, putting questions to industrial physicians and industrial hygiene supervisors. The objective of the survey was to find out how MSDS is adopted in the system to manage occupational health, what improvements the survey respondents want in MSDS and what expectations the respondents have of our center. 193 enterprises (72.8%) returned answers to the questionnaire. The major findings are as follows. (1) In many companies, information on hazardous/toxic materials is "controlled by a division using such materials", and roughly half of the companies have compiled a common list shared throughout the company. (2) For the most part suppliers submit to the MSDS. Larger companies have a higher rate of posting up or filing the MSDS at their workplaces. Only 25.8% of the companies "rewrite the MSDS so that workers can understand it." (3) Companies that carry out a hazard/toxicity assessment before introducing a new chemical substance account for 72.1%, which is higher than we expected. It indicates that even though the companies don't manage the MSDS adequately, they are highly concerned about hazard control of chemical substances. (4) The rate of answering that "the current MSDS is not easy to understand" is higher among large-sized enterprises and lower among enterprises with fewer than 300 employees. (5) Asked what improvement needs to be made on the MSDS, the industrial physicians and industrial hygiene supervisors gave same answers such as "Workers find the terminology difficult to understand." and "Levels of toxicity can't be clearly identified." (6) The respondents expect our center to provide information for the MSDS. In conclusion, it is considered that in order to prepare understandable MSDSs to workers in enterprises, the role of our center to provide information and education on the MSDS to respondents was important.

A Japanese man who died at age 85 had been followed since the age of 59, when he first presented. He had hypertension of 162/102 mmHg and a loud systolic murmur on his first visit. He had had an active daily life without any medication for the next 10 years. At the age of 72 he complained of mild chest discomfort on exercise. Although electrocardiography showed no abnormalities, echocardiogram showed calcified bicuspid aortic valve with mild stenosis. At the age of 81 the dyspnea and chest oppression were exacerbated, associated with marked ST depression on exercise electrocardiogram and restriction of aortic valve opening on echocardiograms. In the following years a gradual increase in QRS voltage and ST depression with T wave inversion were recorded on resting electrocardiograms and sharp increases in both left ventricular end-diastolic diameter and flow velocity at the aortic root were observed on echocardiograms. At the age of 85 he died of intractable heart failure with massive pleural effusion. Autopsy revealed marked hypertrophy and moderate dilatation of the heart (weight: 580 g). The bicuspid aortic valve had anterior-posterior cusps with a raphe on the anterior cusp. The mobility of the cusps was almost lost because of severe calcification and thickening. Severe stenosis was found near the orifice of the right coronary artery, but there were no significant ischemic myocardial lesions.

The patient was 47 years old on his first visit in 1969 and has been treated at our outpatient clinic until now, at the age of 79. The initial blood pressure was 164/98 mmHg without abnormalities on electrocardiogram or urinalysis. He was followed-up for 8 years with non-pharmacologic treatment, which was eventually changed to antihypertensive drug treatment. At the age of 71 he was admitted because blood pressure increased to 210/110 mmHg, with marked fluctuation. At admission bilateral ocular (right < left) and carotid bruits (right < left) were detected. At the age of 75 he had cerebellar infarction with reversible neuro-logic deficits. At the age of 76 he was again addmitted because the labile hypertension was difficult to control. Cerebral angiography which was performed to clarify the relationship between labile hypertension and cerebral ischemia revealed significant bilateral stenosis at the portion of the cavernous sinus in the internal carotid arteries. The stenosis was more remarkable on the left side than the right side. Based on the angiographic findings we considered the ocular bruits to be not a murmur of augmentation flow but a stenotic murmur.

Chronic myeloid leukemia(CML) is a generic term that includes five subtypes; i.e. chronic granulocytic leukemia(CGL) (95% of all CML, 90% are Ph+, 5% are Ph-, BCR/ABL+), atypical CML(survival is worse than that of CGL), chronic myelomonocytic leukemia(a subtype of myelodysplastic syndrome), chronic neutrophilic leukemia (Ph-, BCR/ABL-) and juvenile CML(Ph-, BCR/ABL-). It is not so easy to make a diagnosis of Ph-negative CML. Also, about 25% of adult acute lymphoid leukemia(ALL) patients and some essential thrombocythemia patients have Ph chromosome. In addition, about a half of cases with Ph-positive ALL have the same size of BCR/ABL fusion protein as that in Ph-positive CML. It is necessary to distinguish them by the distinctive morphological, cytogenetical and immunological characteristics of these diseases.

An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.

Lifestyle modifications are the first approach to the treatment of dyslipidemia and hypertension, that is, control of overweight; reduced intake of saturated fat, cholesterol, sodium chloride, and alcohol; and increased physical activity. In high doses, thiazide diuretics and loop diuretics can induce at least short-term increases in levels of total plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol. Low-dose thiazide diuretics do not produce these effects. beta-blockers may increase levels of plasma triglycerides transiently and reduce levels of high-density lipoprotein cholesterol. alpha-blockers may decrease serum cholesterol concentration to a modest degree and increase high-density lipoprotein cholesterol. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, and central adrenergic agonists have clinically neutral effects on levels of serum lipids and lipoproteins.

The purpose of this study was to assess whether regimen comprehension deteriorates in the elderly without obvious mental disability. Eligible patients were elderly who could visit hospitals by themselves. We recruited 138 patients (age: 43-89, 75 males and 63 females, underlying diseases: hypertension, hyperlipidemia, arrhythmia etc.) from our outpatient clinic. The participants were tested with a regimen comprehension scale (RCS: Jpn J Geriat 1997; 34:209-214). The differences in scores among individuals increased with age. Scores of 5 or less were recorded in 10 of 69 patients aged 65 or more, but in non of 69 patients aged less than 65 (p < 0.01). The 60 patients who could not get full marks were classified into 2 groups: the tutored group (T) who were tutored by pharmacists about taking drugs, and the non-tutored group (N). Both group were tested again with RCS to evaluate the effect of tutorial. In T-group (n = 28), the second scores increased significantly (from 7.2 +/- 0.9 to 8.6 +/- 2.0 (m +/- SD); p < 0.01). Although the second scores showed a tendency to increase in N-group (n = 29), there was no statistical significance. In 7 patients who obtained less than a score of 5 on the RCS and age- and gender-matched controls who received full marks on the RCS, the HDS-R test failed to show any differences between the two groups. Thus, we concluded that even in the self-attending elderly patients, the regimen comprehension deteriorated with age, and tutorials were considered to be effective.

An 88-year-old woman was admitted to our hospital because of palpitations, dyspnea, orthopnea and appetite loss. On admission, small crackles were heard on her lower back, and her liver was swollen. Chest rentogenogram showed cardiomegaly (cardio-thoracic ratio 65.5%) and bilateral pleural effusion. Electrocardiograms showed atrial fibrillation with an average heart rate of 95 per minute. Echocardiography revealed mitral stenosis. Because the patient was considered to be suffered from heart failure due to mitral stenosis with atrial fibrillation, furosemide (20 mg per day) and digoxin (0.25 mg per day) was started. After digoxin had been raised to a dose of 0.50 mg per day because of sustained rapid ventricular response on the fourth hospital day, she complained of nausea and vomiting. Serum digoxin concentration was 2.55 ng/ml on the next day, and 1.08 ng/ml 96 hours after discontinuing digoxin. There was no complaint after digoxin was restarted with a dose of 0.05 mg per day. She complained of nausea again on the third day when the digoxin was raised to a dose of 0.083 mg in a blinded study. This observation indicates that digoxin intoxication could occur even in the smaller dose of digoxin than usual in the elderly.

Previous echocardiographic studies have indicated that the basal portion of interventricular septum is locally thickened in many patients with essential hypertension. This retrospective study investigated whether this localized thickening is decreased by antihypertensive treatment. Twenty-four patients with mild essential hypertension (15 males, 9 females, mean [+/- SD] 55 +/- 9 years) were selected who had local thickening at the basal portion of interventricular septum (> or = 11 mm) on echocardiograms recorded within 3 months after the first visit and were followed up by echocardiography 6 months or more after the start of antihypertensive treatment. Interventricular septal wall thickness at the mid portion (IVST), posterior wall thickness (PWT), left ventricular mass index (LVMI), aorto-septal angle, blood flow velocity in left ventricular outflow tract, and the thickness of the basal portion of interventricular septum (septal wall maximum thickness within 1.5 cm apex side from the joint of interventricular septum and aorta in the long-axis view of B-mode echocardiograms) were measured. Blood pressure was significantly decreased from 152.7 +/- 8.7/93.1 +/- 8.0 mmHg to 140.0 +/- 8.2/86.6 +/- 8.2 mmHg by treatment (p < 0.0001). The thickness of the basal interventricular septum was significantly reduced by treatment from 12.3 +/- 1.7 mm to 10.3 +/- 1.4 mm (p < 0.0001). Mean IVST, PWT and LVMI were slightly reduced by treatment, but the differences were not statistically significant. These results suggest that the thickening of basal interventricular septum is induced by high blood pressure, and the measurement of the thickness of basal interventricular septum might be a useful tool to estimate and monitor the effect of antihypertensive treatment in patients with mild essential hypertension.

It has been already described that the average axis of QRS complex is deviated by aging as well as various diseases, such as ventricular overload or bundle branch block. In this study, we first tested the hypothesis that the extra-cardiac factor changes with aging, such as the body shape or diaphragm position, which are represented by body weight (WT) and/or cardiac-thoracic ratio (CTR), are the main cause of QRS axis deviation. In 28 cases including 1 right (RAD) and 27 left axis deviation (LAD) patients whose QRS axis have been deviated during observed periods, WT and X-ray CTR were compared to the degree of axis deviation. Unfortunately no clear relationship was found among these parameters. On the other hand, in 8 cases out of 27 LAD patients, confirmed or suspected left anterior hemiblock (LAH) was found by vector electrocardiogram. Pathological studies showed that the degeneration of the stimulation pathway occurred with aging and it caused the bundle branch block. Therefore, we conclude that the degenerative change in left anterior stimulation pathway by aging should be, at least, one of the cause of the QRS axis deviation.

Cervical vagal stimulation in rabbits frequently causes systolic murmur with bigeminy due to premature ventricular contractions. The bigeminy disappears in a few minutes, but the systolic murmur persists for a few days. The present study used Doppler echocardiography to examine whether or not this systolic murmur is due to mitral regurgitation. Electrocardiographic monitoring was performed on anesthetized rabbits forced into the supine position. Doppler echocardiography was performed in the animals which showed systolic murmur 6 hours, 3 days, and 1, 2, 3 and 4 weeks after vagal stimulation. Six hours after vagal stimulation, phonocardiography detected systolic click and late systolic murmur, and Doppler echocardiography detected marked mitral regurgitation. The systolic murmur and mitral regurgitation were attenuated and the papillary muscle was swollen 3 days after vagal stimulation. The mitral regurgitation disappeared within a week and swelling of the papillary muscle improved 3 weeks after vagal stimulation. Doppler echocardiography confirmed that the systolic murmur observed in rabbits after vagal stimulation is due to transient mitral regurgitation.

We compared trends in the prescription of antihypertensive drugs in elderly patients with those in middle-aged patients. We analyzed prescriptions given to 141 patients with hypertension who were 65 years old or older (mean age, 73 years) and to 511 patients with hypertension who were 64 years old or younger (mean age, 59 years). The numbers of drugs prescribed did not differ between the elderly and the non-elderly patients. In both groups, about 50% of patients were given prescriptions for one antihypertensive drug, about 40% were given prescriptions for two drugs, and about 10% were given prescriptions for three drugs. Calcium antagonists were the agents most commonly prescribed as monotherapy (51.4% and 56.4% in the non-elderly and elderly respectively; n.s.); followed by beta-blockers (32.2% and 25.6%; n.s.). Diuretics were prescribed less often to non-elderly patients than to elderly patients (5.1% and 10.0%; p < 0.01). When prescriptions for more than one antihypertensive agent were included in the analysis, calcium antagonists were still the most commonly prescribed agents (63.8% and 66.4%; n.s.), followed by the beta-blockers (53.3% and 66.4%; p < 0.05). Diuretics were less commonly prescribed to non-elderly patients (13.5% and 21.3%; p < 0.005), while ACE inhibitors (19.0% and 11.6%; p < 0.005) and beta-blockers (52.3% and 44.0; p < 0.05) were more commonly prescribed to non-elderly patients. When we classified the data according to the time of the first visit, we found that patients whose first visit was earlier were more likely to have been given a prescription for a diuretics, whether they were elderly or non-elderly. Calcium antagonists were the most commonly prescribed agents in all time periods studied, followed by beta-blockers. Comparison of our results with those of a similar study done at our clinic in 1990 showed that the use of calcium antagonist monotherapy doubled in both groups (non-elderly: 26.4% in 1990 to 51.4% in 1995, p < 0.001; elderly: 29.5% in 1990 to 56.4% in 1995, p < 0.001) and that the use of diuretics declined markedly (non-elderly; 20.3% to 5.1%, p < 0.001; elderly: 30.2% to 10.0%, p < 0.001). A similar trend was seen when prescriptions for more than one antihypertensive drug were included in the analysis.

We examined changes in mean QRS axis of electrocardiogram during the deep breathing test in outpatients with hypertension, ischemic heart disease, and/or diabetes mellitus. The mean age of all patients (n = 596; male 327, female 269) was 63.0 years (male 62.7 years, female 63.4 years). The average of the mean QRS axis in all patients was shifted to the right during deep inspiration. The changes in mean QRS axis during deep breathing test were more than 60 degrees in 27 patients (4%) (mean age: 70.0 years), 30-59 degrees in 118 patients (20%) (mean age: 65.5 years), and 0-29 degrees in 451 patients (76%) (mean age: 61.9 years). These results suggest that the changes in mean QRS axis during deep breathing are greater in the aged patients.

Cervical vagal stimulation in rabbits frequently causes peculiar mitral complex lesions which are detected by deposition of colloidal carbon. The present study examined the effects of vagal stimulation on the calcium (Ca) contents in the mitral complex lesions. Anesthetized rabbits were forced into the supine position with electrocardiographic monitoring. The animals were divided into those with vagal stimulation (n = 37), and those without manipulation as controls (n = 25). Colloidal carbon (1 ml) was intravenously injected into the animals on the next day. All animals were sacrificed after 1 week. After perfusion of the heart by heparinized saline, Ca content per g myocardium in the mitral annulus, papillary muscle, free wall or apex in the left ventricle was measured by the atomic absorption method. Immediately after vagal stimulation, bigeminy due to premature ventricular contractions was observed in 76%, and systolic murmur was heard in 30%. Mitral complex lesions detected by carbon deposits were found in 73% of the rabbits with vagal stimulation. Ca content in the mitral annulus or papillary muscle was significantly greater than that in the free wall or apex (p < 0.001). Ca content in the mitral annulus was significantly greater in the rabbits with vagal stimulation than in the control group (p < 0.001). In the former group, Ca content in the mitral annulus in animals with mitral complex lesions was significantly greater than that in those without mitral complex lesions (p < 0.01). These results suggest that these mitral complex lesions might provide an experimental model of mitral annular calcification, and that the autonomic nervous system and arrhythmia might be involved in the mechanism of this calcification.

The patterns of interventricular septal hypertrophy were analyzed on two-dimensional echocardiograms to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive cardiac hypertrophy. The control group comprised 110 patients without cardiovascular disease who were matched for age and gender with the hypertension group. The hypertension group comprised 110 patients with uncomplicated essential hypertension, and the HCM group comprised 32 patients in whom the wall thickness of the interventricular septum was 12 mm or more at the mid-portion and no underlying heart disease responsible for cardiac hypertrophy was detected. The interventricular septal thickness was measured both at the thickest portion within 15 mm distal to the aortoseptal junction (basal portion: B) and at the mid-portion (M) in the end-diastolic image on the left parasternal long-axis tomograms, and the B/M ratio was calculated in each patient. The B/M ratio was 1.07 +/- 0.16 in the control group, 1.19 +/- 0.18 in the hypertension group, and 0.83 +/- 0.12 in the HCM group. Compared with the control group, the B/M ratio was significantly high in the hypertension group (p < 0.05) and significantly low in the HCM group (p < 0.01). These results indicate that hypertrophy of the interventricular septum is dominant at the basal portion in hypertensive patients but at the mid-portion in patients with HCM.

Ventricular bigeminy or trigeminy can spontaneously occur in anesthetized rabbits forced into the supine position. Premature ventricular contractions (PVCs) of this type are characterized by a long coupling time and superimposition of the following P waves. Rabbits with PVCs of this type frequently develop peculiar mitral complex lesions which are detected by deposition of colloidal carbon. This study examined the effects on the tricuspid complex of artificial PVCs induced by left ventricular pacing in rabbits. Anesthetized rabbits were forced into the supine position under electrocardiographic monitoring. The animals were divided into those with spontaneous PVCs, those with artificial PVCs, and those without PVCs as controls. Colloidal carbon (1 ml) was intravenously injected into the animals the next day. All animals were sacrificed after 1 week. Tricuspid complex lesions were found in 2.0% of animals with spontaneous PVCs, in 17.6% of those with artificial PVCs, and in none of the controls. These results indicate that artificial PVCs induced by left ventricular pacing can cause peculiar tricuspid complex lesions.

Therapeutic efficacy of Elental and Enterued as home enteral nutrition (HEN) for the maintenance of remission in 32 patients with quiescent Crohn's disease was studied retrospectively. Their cumulative rates of continuous remission and non hospitalization were statistically compared in relation to following five factors; type of disease, history of bowel resection, duration of disease, oral bile acid tolerance test (OBATT) and radiological lesion score (RLS). As to the cumulative rates of continuous remission and non hospitalization, there was no significant difference between two groups treated with Elental and Enterued. In patient with ileocolitis type, > or = 5-year history, and a high score of RLS, few cases could continuously maintain remission following a long-term HEN. Especially, patients with low absorption in OBATT had a significantly lower cumulative rate of continuous remission than those with normal absorption in OBATT. The present results suggest that above factors may be useful in the application of HEN to patients with Crohn's disease.

To clarify the pathogenesis and endoscopic features of ischemic lesions of the colon, experimental ischemia was induced in dogs by arterial ligation, gelfoam injection, and clipping. In addition, clinical and endoscopic features of ischemic lesions in ischemic colitis cases in human were studied. In the experimental model, arterial ligation including marginal arteries frequently induced erosions in the large intestine, whereas ligation of the colic artery alone did not induce apparent mucosal lesions of the large intestine. Gelfoam injection to produce thrombi into caudal mesenteric artery or middle colic artery induced ulcers with a high rate of incidence and frequently accompanied by intestinal perforation. Temporal impairment of blood supply by arterial clipping produced erosion, but not ulcers. A high incidence of erosion was obtained in a group that underwent clipping for a prolonged period and a group of receiving Alosenn. Mucosal blood flow measured by the hydrogen gas clearance method was significantly decreased at 1 hr and 4 hr after gelfoam injection compared with those after arterial ligation. In human cases of ischemia following arterial surgery, endoscopic features were similar to those lesions of the experimental ischemia induced by gelfoam injection. These results suggest that thrombi in peripheral small arteries may play a major role in the pathogenesis of ischemic lesions of the large intestine.

Oral bile acid tolerance test has been used to detect a functional impairment of the small intestine in Crohn's disease. The damage should be strongly expressed in the terminal ileum because of preferential involvement, therefore, we devised the retrograde ileal bile acid tolerance test, where bile acid was administered into closed segment of the terminal ileum using a 4 lumen double balloon tube through a colonoscope. In basic experiment using dogs with or without experimentally induced ileitis by trinitrobenzene sulfonic acid, ursodeoxycholic acid (UDCA) solution of several concentrations was given into the duodenum (corresponding to oral test) or the terminal ileum. Plasma was collected for 60 min at given time points, and then plasma total bile acid level (TBA) and bile acid fraction were measured. In a clinical study, both oral test and retrograde ileal bile acid tolerance test were carried out in 5 cases of Crohn's disease with ileitis and 6 healthy control subjects. Plasma was collected for 30 min after ileal loading of 30 ml UDCA solution (10 mg/ml). In oral bile acid tolerance test, plasma was collected for 180 min after taking 600 mg of UDCA. Basic experiments in dogs showed: 1) TBA was increased in proportion to dose of UDCA loaded in the intact ileum. 2) Absorption of bile acid after ileal loading of UDCA was significantly suppressed in experimentally induced ileitis, whereas no difference was observed after duodenal loading of UDCA. Clinical study in human subjects showed; 1) Absorption of bile acid after ileal loading of UDCA was significantly suppressed in Crohn's disease, compared with controls. 2) Examination of bile acid fraction showed that more than 90% of bile acid increased in serum after ileal loading of UDCA was free type UDCA. These findings indicated that retrograde ileal bile acid tolerance test is useful for an accurate evaluation on absorptive function in the ileum.

We examined the rhythm of weight velocity in eight patients with Crohn's disease. In this paper we used the spline smoothing technique to study the cycle in the weight increment velocity curves derived from individual data during nutritional therapy. As a result of the weight measurement at four-day intervals, an infradian rhythm with the average cycle of 9.6 +/- 0.7 was recognized in all of the subjects in terms of the weight increment velocity. This rhythm was especially conspicuous in three adolescent patients with serious nutritional lesion. The cycle of the rhythm was unaffected by any of the following factors: energy intake, contents of nutritional therapy, medical examination during the period. Our findings of a common cycle in the process of convalescence from a low nutritious stage in patients with Crohn's disease suggest that, in others as well, the weight increment velocity might have an infradian rhythm with a kind of inherent periodicity.

The results of unrelated bone marrow transplantation (BMT) is poor because of the rejection of bone marrow graft and graft versus host disease (GVHD). However, the rate of rejection has been reported to be decreased by intensive immuno-suppressive preconditioning regimens combined with total body irradiation (TBI). We report a case of an 18-year-old male with severe aplastic anemia who received a matched BMT from an unrelated donor. The pre-conditioning regimen included cyclophosphamide (50mg/kg) for 4 days, total lymphoid irradiation (TLI: 6Gy) and TBI (5Gy). GVHD (grade 1), hemorrhage cystitis and varicella occurred after BMT but were cured. His performance status is now 100% on the Karnofsky score at 10 months after BMT.

A 65-year-old man was admitted because of bleeding from gastric ulcer. A massive deposition of AL lambda type amyloid proteins in the gastric lesion was found. There were a few Bence-Jones (BJ) proteins in the urine, but serum M proteins and bone lesions were not found. Bone marrow puncture showed no dysplastic change of plasma cells. Moreover, there were no amyloid proteins deposited anywhere in the digestive tract examined, except for the stomach, nor were they found in the bone marrow, prostata, liver or kidney. Gastric amyloidosis was diagnosed. Gastrectomy was performed because of uncontrollable bleeding. Sixteen months later, bone swelling occurred in the sternoclavicular joint and the 3rd rib. At that time, plasma cells with dysplasia and increasing levels of urine BJ protein were revealed. BJ type multiple myeloma was finally diagnosed. For remission induction, cyclo-VAMP chemotherapy was given in 3 courses. Decreased levels of urine BJ protein, diminished bone lesion, normalization of bone marrow and fewer amyloid deposits were seen, and partial response was obtained. The patient is well with no signs of recurrence evident 42 months after treatment. This is an interesting case of initial gastric amyloidosis that developed into BJ type multiple myeloma and was effectively treated with cyclo-VAMP chemotherapy.

A 67-year-old man was diagnosed as non-Hodgkin lymphoma (diffuse, mixed cell type, B cell) with clinical stage IV in March 1989. He had been treated many times with salvage chemotherapy on admission including CHOP-etoposide and ProMACE-Cyta BOM. Recurrence, however, occurred in two or three months after any therapy. He had a therapeutic history of chronic daily administration of etoposide. In November 1991, recurrence was found in the peripheral lymph node and the colon. A new regimen of oral administration of etoposide, 50 mg/day four times a week, was employed. Two months later, the peripheral lymph node swelling disappeared. Seven months later, the patient showed no signs of recurrence by Ga-scintigraphy. This therapy is being continued. It is suggested that anti-neoplastic activity of etoposide is dependent on the schedule of administration. This regimen is suggested to be effective in the treatment of patients with refractory malignant lymphoma.

A novel monoclonal anti-human coagulation factor XIII (F. XIII) antibody (2C3 antibody) raised in BALB/c mice was established by Kohler and Milstein methods. The monoclonal antibody recognized F. XIII of 85 KD demonstrated by western blotting analysis. Plasma F. XIII-IR levels measured by ELISA with 2C3 antibody were significantly lower in active disease than in quiescent disease in a total of 21 Crohn's disease (CD) patients. Plasma F. XIII levels were significantly lower on admission in CD with fistulas than in CD without fistulas. Relationships between activities of CD and plasma F. XIII levels were shown. No significant relationships, however, were observed between F. XIII-IR levels and nutritional states assessed by TP, ALB, TF, PA, RBP, %IBW. Low levels of F. XIII in active CD patients with fistulas may occur regardless of hyponutrition. By using 2C3 antibody, global functions of F. XIII will become clarified as well as pathologic and diagnostic roles of plasma F. XIII in CD.