Masatsugu Ohtsuki

OBJECTIVE: This study aimed to clarify the relationship between interprofessional self-evaluation and peer evaluation during interprofessional education (IPE) using team-based learning (TBL). We also aimed to clarify differences in interprofessional cooperation between students with high and low peer evaluation scores. METHODS: In total, 483 students (grades 3-5) from nine faculties at three universities participated in a TBL-based IPE program. The students completed five interprofessional self-evaluation domains (the modified Tsukuba IPE model) before and after IPE. Students also completed peer evaluation after IPE. Students were divided into three groups by peer evaluation scores (low, middle, high), and the post-class self-evaluation scores of these groups were compared using a Kruskal-Wallis test. Multiple regression analysis was also performed. Peer evaluation comments were analyzed using a qualitative inductive method. RESULTS: Students in the low peer evaluation group had significantly lower scores in the "Regarding participation in group work" domain than students in the high group (P<0.05). Students in the high group received positive comments, such as [good communication] and [working cooperatively], whereas students in the low group were required to improve in two areas: [speaking up more] and [need more communication]. CONCLUSIONS: There was a significant relationship between peer evaluation by team members and self-evaluation for "Regarding participation in group work." Students with high peer evaluation scores participated with active attitudes, whereas students with low scores were considered passive. This study suggested that using peer evaluation may enhance students' professional cooperation by improving their communication and attitudes toward active participation.

Objectives: The current study sought to understand the learning outcomes experienced by students and to explain their learning process in detail using interpretive data analysis. Methods: A qualitative study examined students who participated in a multidisciplinary course in a ward. This study investigated latent meanings rather than factual information, using an interpretive paradigm. Data were collected via focus groups and analyzed using Steps for Coding and Theorization (SCAT). Results: Students in the Assembly IV trial (interprofessional education in actual medical settings) experienced a process of transition from a competing (exclusive) mode to a mutual-understanding mode when communicating with people in other professions, and they acquired the perspective of an interactive (dialectic) link between involved communication (communication that attempts to connect directly with patients) and uninvolved communication (communication with patients indirectly through data and other methods) for patient communication. This enabled students to move beyond superficial communication while deepening their connections with people in other professions, complementing each other's strengths, and learning about the possibilities inherent in the provision of collaborative medical practice. Conclusions: Students participating in interprofessional education within medical settings learned about the potential to achieve a circular realization of collaborative medical practice. A circular realization of collaborative medical practice involves incorporating diverse approaches into one's own professional work via exposure to the viewpoints of other occupations and avoiding decision-making based on assumptions that are only valid within one's own profession. This process enables the discovery of better methods and perspectives and the achievement of effective medical practice by moving beyond superficial communication.

<p>Objectives: The aim of this study was to investigate changes in health university students' attitudes toward community service before and after a community-oriented education program using team-based learning (TBL). </p><p>Methods: A community-oriented educational program using TBL was carried out with a total of 529 3rd- and 4th-year students in seven faculties of two departments at Fujita Health University, and a questionnaire survey was conducted before and after the program. There were eight questions on students' attitude toward community service.</p><p>Results: Responses with no missing information from 431 students were used in the analysis. There were significant increases in the number of positive responses to three questions after TBL. The item "I think there are things that university students can do as members of the community" increased from 81.9% before TBL to 86.5% after, "I can form specific images of activities that benefit the community" increased from 46.0% before to 70.3% after, and "In the future I want to participate in activities that benefit the community" increased from 74.7% before to 80.3% after.</p><p>Conclusion: The results suggest that this community-oriented educational program using TBL raised the motivation of university students in medical and health science programs to practice community health care.</p>

<p>Objective: This study aimed to examine the effects of interprofessional education (IPE) using team-based learning (TBL).</p><p>Methods: We analyzed the results of a scale to measure IPE among 449 fourth-year students from seven faculties of a health university in Japan. The students took the Assembly Special Lesson as part of IPE using TBL. Before and after the lesson, the participants completed a questionnaire, which consisted of the IPE Tsukuba Model, to which we added two items. The scale was divided into five domains. We compared the scores using the Wilcoxon signed-rank test.</p><p>Results: The overall scores of four of the five domains of the IPE evaluation were significantly higher after the lesson than before (P<0.05): "Understanding the role of each profession's specialization" ; "Regarding participation in group work" ; "Thoughts regarding the team in healthcare and welfare" ; and "Feelings about cooperation among different professions." </p><p>Conclusions: It was evident that the lesson enhanced the students' understanding of the role of other professionals, enabled them to participate in group work, and allowed them to understand the responsibilities of each profession within a team, thereby leading to greater cooperation and better health care. This TBL for IPE was found to be effective by producing valuable changes in perceptions and attitudes toward professional cooperation among students.</p>

<p>Introduction: Compared with faculties in clinical and medical research departments, those in medical departments are not appropriately evaluated in terms of their contributions to or achievements in medical education. Therefore, the aims of this study were to investigate the contributions of medical department faculties to medical education, and to examine differences in contributions according to duty positions and specialties.</p><p>Methods: Five-grade self-assessments in relation to 20 items on a rating form for performance in medical education, which was developed by the Japan Society for Medical Education's Committee for Performance Evaluation, were carried out by medical department faculties in Japanese universities. The data were then totalized and analyzed.</p><p>Results and Discussion: Although faculties belonging to departments other than medical education units did not actively participate in examinations or the education system, they still made contributions to lectures and practice. In addition, faculties with positions with more duties tended to show greater participation in the education system.</p><p></p><p>Conclusion: Based on these findings, we recommend the use of a rating form as a standard scale to evaluate performance in medical education.</p>

&lt;p&gt;Introduction: Compared with faculties in clinical and medical research departments, those in medical departments are not appropriately evaluated in terms of their contributions to or achievements in medical education. Therefore, the aims of this study were to investigate the contributions of medical department faculties to medical education, and to examine differences in contributions according to duty positions and specialties.&lt;/p&gt;&lt;p&gt;Methods: Five-grade self-assessments in relation to 20 items on a rating form for performance in medical education, which was developed by the Japan Society for Medical Education&#039;s Committee for Performance Evaluation, were carried out by medical department faculties in Japanese universities. The data were then totalized and analyzed.&lt;/p&gt;&lt;p&gt;Results and Discussion: Although faculties belonging to departments other than medical education units did not actively participate in examinations or the education system, they still made contributions to lectures and practice. In addition, faculties with positions with more duties tended to show greater participation in the education system.&lt;/p&gt;&lt;p&gt;&lt;/p&gt;&lt;p&gt;Conclusion: Based on these findings, we recommend the use of a rating form as a standard scale to evaluate performance in medical education.&lt;/p&gt;

<p>Abstract:</p><p></p><p> This study examined the ability of medical students to self-assess basic clinical competence and learning strategies including simulation-based medical education for sixth-year medical students (n=903) at nine universities in Japan. About 40% of 27 procedures to achieve clinical skills in a model curriculum were taught using simulators with or without clinical training in hospitals. We noted that significant numbers of procedures were not practiced through any learning strategies. Higher self-assessment scores were observed among students in 4 schools who had more frequent learning opportunities through simulation-based education than among those with less frequent opportunities in 5 schools.</p>

1）To learn the techniques required immediately after the start of clinical practice, new residents were introduced to the skills laboratory during their orientation period.<br>2）We attempted to establish the Yanegawara style, which is an overlapping teaching style in which the second–year residents plan the entire training schedule and simultaneously teach the first–year residents while being supported in their teaching by more senior physicians.<br>3）Training with the new system resulted in greater rapport among all residents as well as a greater feeling of security among first–year residents.

Since 2003, Clinical training center of Fujita Health University hospital has been cooperated with the Office for medical education of Fujita Health University, school of medicine, in reorganizing the previous training system based mainly on individual departments. After 9 years since then, we established Yanegawara style training system and the trainee–centered curriculums. Outcomes from new system are as follows:<br>1. Self–establishment by problem based learning became common understandings between trainers and trainees.<br>2. Teaching by trainers to trainees and between trainees （R2 to R1） became common in the hospital.<br>3. Trainees can learn the standardized approach in diagnosis and treatment of the patients in ER.<br>4. Unified understanding of the training system was established in the hospital.Although new system brought several good aspects, we found a large heterogeneity in fulfillment of our curriculums not only by the capability of individual residents but also by the effort induced by each department.

AIMS: Cilostazol, a type III phosphodiesterase inhibitor, is utilized for the treatment of intermittent claudication and is considered to have the beneficial effects against the atherogenic process. In the present study, we examined the effects of cilostazol on BH(4) biosynthesis in HUVEC treated with a mixture of the pro-inflammatory cytokines IFN-γ and TNF-α. METHODS: Isolated HUVECs were grown to confluence and treated with IFN-γ (300 units/mL) and TNF-α (300 units/mL) for 16 h in order to stimulate BH(4) biosynthesis. The BH(4) levels were measured by HPLC. The mRNA expression of GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH(4) biosynthesis, and GTPCH feedback regulatory protein (GFRP) were quantified by real-time PCR. The GTPCH protein expression was assessed by western blot analysis. RESULTS: Cilostazol significantly reduced the BH(4) levels in cytokine-stimulated HUVEC. Cilostazol produced a concomitant increase in the cAMP levels in HUVEC. Cilostazol decreased the GTPCH activity as well as the expression of GTPCH mRNA and protein. 8-bromo-cAMP (8Br-cAMP), a cell-permeable cAMP analogue, did not reproduce the effects of cilostazol. Cilostazol did not affect the cytokine-induced inhibition of GFRP mRNA expression. CONCLUSIONS: We conclude that cilostazol inhibited cytokine-stimulated BH(4) biosynthesis via a cAMP-independent mechanism in HUVEC. Our data indicate that cilostazol reduced GTPCH activity and did so by suppressing the GTPCH protein levels.

It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.

At the Fujita Health University School of Medicine, about 30% of medical students are admitted on the basis of recommendations.To evaluate the performance of these students after admission, a placement test was given to all new students just after the entrance ceremony to examine basic academic abilities.The scores were compared with the number of absences from lectures and with examination results for the first and second years.&lt;BR&gt;1) The 398 students admitted from 2002 through 2005 were classified into three populations: 126 recommended students, 137 students who scored in the top half on the entrance examination, and 135 students who scored in the bottom half.&lt;BR&gt;2) Scores on the placement test were highest for the top-half students, intermediate for the bottom-half students, and lowest for the recommended students.Scores on examinations in the first and second years were highest for the top-half students, intermediate for the recommended students, and lowest for the bottom-half students.&lt;BR&gt;3) The average number of absences from lectures in the first and second years tended to be lower for recommended students than for the top-half or bottom-half students.&lt;BR&gt;4) The examination scores in the second year were correlated with scores in the first year, and the average number of absences in the second year correlated with those in the first year.&lt;BR&gt;5) These results indicate that the motivation of students in each classification to study in the 1st year is, in addition to their basic academic abilities obtained in high school, an important factor affecting their performance in the second year and beyond.

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels &gt; 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 ± 148.6 to 286.9 ± 88.5 nmol/l, and adiponectin increased from 9.7 ± 7.4 to 13.9 ± 9.98 μg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.

A 45-year-old man developed fulminant myocarditis for which ventricular assist devices (intra-aortic balloon pumping and percutaneous cardiopulmonary support) were required for hemodynamic support. Echocardiography showed left ventricular akinesis and, since no improvement was noted on the following day, immunoglobulin (70 g/day for 2 days) was added to the therapy. The left ventricular ejection fraction increased to 25% and 40% at 12 and 36 h, respectively, representing a marked improvement in wall motion within a very short period. An endomyocardial biopsy specimen revealed focal lymphomononuclear infiltrate with adjacent myocytolysis, and acute lymphocytic myocarditis was diagnosed. Two days after administration of immunoglobulin, the serum level of interleukin-6 decreased rapidly from 180 to 5.9 pg/ml. In this patient, cardiac function improved immediately after immunoglobulin administration, suggesting the usefulness of this therapy. Three years after the diagnosis the patient is in good health, with steady normal left ventricular ejection fraction. We conclude that there are cases of acute myocarditis in which high-dose intravenous immunoglobulin therapy is effective.

Transient left ventricular (LV) wall thickening is observed in patients with acute lymphocytic myocarditis. The present study was undertaken to clarify the significance of transient LV wall thickening in patients with this disease. The subjects comprised 25 patients with acute lymphocytic myocarditis. Echocardiography was used to measure the thickness of the interventricular septum (IVS) and the LV posterior wall (PW) at four time points after myocarditis onset--namely, on days 1-3, 6-8, 13-15, and 28-30--to clarify the timing and frequency of wall thickening. The 25 patients were divided into a fulminant myocarditis group (n = 14) and a nonfulminant myocarditis group (n = 11), and the relationship between LV wall thickening and myocarditis severity was investigated. Left ventricular wall thickening was greatest on days 1-3 after myocarditis onset (IVS: 13.3 +/- 3.2 mm; PW: 12.1 +/- 2.6 mm), with this finding being noted in 14 of the 25 cases (56%). By days 6-8, the thickness of IVS had virtually normalized to 10.6 +/- 1.6 mm (P < 0.0001) and that of PW to 10.2 +/- 1.4 mm (P = 0.0006). The thickness of the IVS and PW on days 1-3 after myocarditis onset were 14.6 +/- 3.7 and 13.0 +/- 2.9 mm, respectively, in the fulminant group (P = 0.014), and 11.5 +/- 0.9 and 10.9 +/- 1.4 mm, respectively, in the nonfulminant group (P = 0.039). In lymphocytic myocarditis, LV wall thickening is greatest on days 1-3 after myocarditis onset and improves to near normal by days 6-8. Such transient LV wall thickening occurs in approximately 50% of cases. Left ventricular wall thickening was more marked in the fulminant compared with the nonfulminant group.

The presence of myocardial interstitial edema in acute myocarditis (AM) leads to thickening of the ventricular wall, and conduction disturbances, such as complete atrioventricular block (CAV), also frequently develop. This study was undertaken in order to clarify the relationship between conduction disturbances and myocardial interstitial edema in AM. The subjects comprised 50 patients with acute lymphocytic myocarditis. Based on the results of echocardiographic examinations during the acute stage, the patients were divided into a hypertrophy group (n = 29) in which the sum of the thickness of the interventricular septum and left ventricular (LV) posterior wall was >or=24 mm, and a non-hypertrophy group (n = 21) in which the sum of these parameters was <24 mm. Right ventricular endomyocardial biopsies were performed in the acute stage and the degree of interstitial edema was scored histologically. Left ventricular wall thickness and QRS duration in the acute stage were 27.7 +/- 3.6 mm and 124.1 +/- 29.6 ms, respectively, in the hypertrophy group, and 19.9 +/- 2.4 mm (P < 0.001) and 98.6 +/- 21.7 ms (P < 0.01) in the non-hypertrophy group. Complete atrioventricular block was found in 13 of 29 cases (45%) in the hypertrophy group and two of 21 cases (10%) in the non-hypertrophy group (P < 0.01). Myocardial interstitial edema was scored at 1.3 +/- 0.8 points in the hypertrophy group and 0.8 +/- 0.6 points in the non-hypertrophy group (P < 0.05). Left ventricular wall thickness and QRS duration in the convalescent stage decreased to 21.1 +/- 2.6 mm (P < 0.0001) and 97.1 +/- 17.4 ms (P < 0.01) in the hypertrophy group, respectively. Only one case (4%) in the hypertrophy group continued to show CAV during the convalescent stage (P < 0.05). The results of this study suggest that myocardial interstitial edema is implicated in the conduction disturbances that occur in AM.

Most patients with acute myocarditis manifest particular clinical signs and symptoms, including marked cardiac failure and/or a high degree of atrioventricular block on admission. However, a 78-year-old man did not have symptoms and was hospitalized as a result of abnormalities observed on an incidentally obtained electrocardiogram (ECG). Several days later, he developed cardiogenic shock and fulminant myocarditis, which required percutaneous cardiopulmonary support; however, the cardiac failure persisted and he died approximately 4 months later. The ECG showed findings similar to those of acute inferior myocardial infarction, and on left ventriculography, diffuse hypokinesis was observed most prominently in the inferoposterior wall. During autopsy, interstitial fibrosis was marked in the inferoposterior wall, with small, round, cell infiltration prominent at the same site. Clustering of these cells is a characteristic feature of chronic myocarditis.

A 46-year-old man was admitted for further evaluation of exertional chest discomfort. One family member had experienced sudden death, and 2 others had died of heart failure, including I known to have had Fabry's disease. The patient was also diagnosed with Fabry's disease, based on reduced leukocyte (X-galactosidase A activity, 2.0 nmol/mg protein/hour, as well as endomyocardial biopsy findings of marked sarcoplasmic vacuolization of cardiac muscle cells by light microscopy and lamellated "zebra bodies" in the cytoplasm shown by electron microscopy. Echocardiography disclosed marked left ventricular hypertrophy and systolic anterior motion of the mitral leaflets. On cardiac catheterization, a left ventricular peak systolic outflow gradient of 50 mm Hg was noted; this decreased to 10 mm Hg following intravenous administration of 100 mg of cibenzoline. It is imperative to recognize the existence of cases with Fabry's disease associated with left ventricular outflow obstruction.

Tenascin-C (TN-C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN-C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN-C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN-C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN-C. The immunostaining was semi-quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN-C levels were analysed. Expression of TN-C was specifically detected in endomyocardial biopsy specimens from patients with active-stage inflammation, and disappeared in healed stages. The degree of expression of TN-C correlated with the severity of histological lesions. These data suggest that TN-C reflects disease activity in cases of human myocarditis. Immunostaining for TN-C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens.

BACKGROUND: Basal thinning of the interventricular septum (IVS) and atrioventricular block (AVB) are characteristic features of cardiac sarcoidosis. Since the conduction system passes along IVS, it has been considered that a close connection exists between basal thinning of IVS and AVB. However, neither the incidence of cases showing basal thinning of IVS nor the relation between it and AVB has been clarified. We thus investigated to elucidate these two issues. METHODS: Thirty-five patients with cardiac sarcoidosis were selected for this study and underwent echocardiographic examination. The wall thickness of IVS was measured at a site 1 cm below the aortic valve inserted point of IVS. Thickness of this site < or = 5 mm was defined as thinning. Twelve-lead and Holter electrocardiograms were obtained to determine the presence/absence and degree of AVB. RESULTS: Basal thinning of IVS was noted in 7 of the 35 patients (20%). AVB was present in 4 of these 7 (57%), and was first degree in 3 (43%) and third degree in one (14%). AVB was not present in 3 patients. Basal thinning of IVS was not apparent in 28 of the 35 patients (80%). AVB was observed in 14 of the 28 patients, 3 had first degree block, 2 had second degree block, and 9 had third degree block. AVB was not observed in 14 of the 28 patients. CONCLUSIONS: These results clarified that basal thinning of IVS is not as common as previously thought in cardiac sarcoidosis, basal thinning of IVS and the presence/absence and degree of AVB are not necessarily correlated.

BACKGROUND: Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase, and GTP cyclohydrolase I (GCHI) is a rate-limiting enzyme in the biosynthesis of BH4. The expression of inducible nitric oxide synthase (iNOS) was earlier demonstrated in the ventricles of patients with dilated cardiomyopathy (DCM) although that of GCHI was not clarified. The present study was designed to determine the GCHI mRNA expression as well as to confirm iNOS mRNA expression in endomyocardial biopsy specimens from patients with DCM. METHODS: Clinical details were assessed in 19 patients with DCM and in 9 control subjects. The real-time reverse transcription polymerase chain reaction (PCR) was performed on total RNA extracted from endomyocardial biopsy specimens. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA was quantified for use as an internal control. RESULTS: iNOS/GAPDH for the DCM samples was 4.8-fold greater than that for the control ones (P<0.01), whereas the GCHI/GAPDH for the DCM samples was reduced to 31.1% of the control (P<0.05). CONCLUSIONS: The increased expression of iNOS mRNA was confirmed in endomyocardial biopsy specimens from patients with DCM. The GCHI mRNA level was suppressed in these specimens.

BACKGROUND: A fulminant course can be difficult to predict at the onset of acute myocarditis, so the aim of the present study was to identify the predictive clinical symptoms/signs or laboratory findings. METHODS AND RESULTS: Thirty-nine patients with acute lymphocytic myocarditis, excluding 8 who manifested shock at admission, were studied. The fulminant group was defined as 12 patients who developed shock after admission, requiring intraaortic balloon pumping or percutaneous cardiopulmonary support, and the non-fulminant group comprised the 27 patients without shock. Various parameters at admission were compared between the 2 groups, together with multiple logistic regression analysis, excluding 6 patients with partially missing values. In the fulminant group, C-reactive protein (7.0 +/- 7.0 vs 2.3 +/- 2.2 mg/dl, p<0.01) and creatine kinase (1,147 +/- 876 vs 594 +/- 568 IU/L, p<0.05) concentrations were higher, intraventricular conduction disturbances were more frequent (9/12 vs 7/27 patients, p<0.01) and the left ventricular ejection fraction was lower (40.7 +/- 13.9 vs 50.1 +/- 10.6%, p<0.05) than in the non-fulminant group. In the multiple logistic regression analysis model with the presence/absence of a fulminant course considered as the independent variable, and C-reactive protein, creatine kinase, intraventricular conduction disturbances, and left ventricular ejection fraction as dependent variables, a high-risk group (expected proportion of fulminant course > or = 0.5) and a low-risk group (<0.5) could be differentiated. A fulminant course occurred in 9/13 (69%) patients in the high-risk group, but in only 2/20 (10%) patients in the low risk group (p<0.001). CONCLUSIONS: The risk of a fulminant course of acute myocarditis was high in patients with elevated C-reactive protein, and creatine kinase concentrations, decreased left ventricular ejection fraction, and intraventricular conduction disturbances at the time of admission.

A variety of myocardial lesions have been demonstrated in atrial muscle in patients with sick sinus syndrome (SSS), but the right ventricular myocardium has not been studied in detail in a large series. Therefore, we performed right ventricular endomyocardial biopsies in 25 patients with SSS (SSS group), and the presence or absence of ventricular myocardial lesions was determined histologically. As a control, biopsies of corresponding sites in 12 normal autopsied hearts were obtained (N group). The mean cardiac myocyte transverse diameter was 14.2 +/- 3.6 microm in the SSS group and 11.7 +/- 3.1 microm in the N group (P < 0.01). In the SSS group, cardiac myocyte hypertrophy was observed in 20 of 25 subjects (80%), and myocyte size variation was more frequent. Although the difference was not significant, myocyte disorganization, myocytolysis, nuclear deformity, interstitial large mononuclear cell proliferation, and endocardial lesions, which were not seen in the N group, were observed in the SSS group. A variety of myocardial lesions, including cardiac myocyte hypertrophy, are present not only in atrial, but also in ventricular muscle in SSS.

Tetrahydrobiopterin (BH4) acts as an essential cofactor for the enzymatic activity of nitric oxide (NO) synthases. Biosynthesis of the cofactor BH4 starts from GTP and requires 3 enzymatic steps, which include GTP cyclohydrolase I (GCH I) catalysis of the first and rate-limiting step. In this study we examined the effects of cGMP on GCH I activity in human umbilical vein endothelial cells under inflammatory conditions. Exogenous application of the cGMP analogue 8-bromo-cGMP markedly inhibited GCH I activity in the short term, whereas an cAMP analogue had no effect on GCH I activity under the same condition. NO donors, NOR3 and sodium nitroprusside, elevated the intracellular cGMP level and reduced GCH I activity in the short term. This inhibition of GCH I activity was obliterated in the presence of an NO trapper carboxy-PTIO. NO donors had no effect on GCH I mRNA expression in the short term. Moreover, cycloheximide did not alter the inhibition by NO donors of GCH I activity. These findings suggest that stimulation of the cGMP signaling cascade down-regulates GCH I activity through post translational modification of the GCH I enzyme.

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was <500/mm(3) in four patients, >500/mm(3) but <1,000/mm(3) in three patients, and > or =1,000/mm(3) in one patient. In three of the four patients with an initial eosinophil count of <500/mm(3), an increase to > or =500/mm(3) occurred 7-12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

It has been reported that some patients with acute myocarditis have transient ventricular thickening associated with narrowing of the left ventricular cavity caused by interstitial edema. The present study investigated this phenomenon in 20 patients with acute myocarditis. Based on the sum of the interventricular septal wall thickness and left ventricular posterior wall thickness (IVST + PWT), measured by M-mode echocardiography, patients were divided into group A (IVST + PWT >/=25 mm, n=12) and group B (IVST + PWT <25 mm, n=8). The IVST + PWT was 31.8 +/-3.5 mm in group A and 21.9+/-2.7 mm in group B (p<0.0001). The left ventricular end-diastolic dimension (LVDd) was 42.3+/-6.0 mm in group A and 49.4+/-6.7 mm in group B (p<0.05). The stroke volume (SV) was 41.1+/-20.5 ml and 73.0+/-32.3 ml in groups A and B, respectively (p<0.05). The left ventricular ejection fraction (LVEF) was similar in group A (47.9+/-13.0%) and group B (56.9+/-9.0%). The SV correlated inversely with IVST + PWT (r=-0.62, p<0.01), and directly with both the LVDd (r=0.95, p<0.0001) and LVEF (r=0.64, p<0.01). The LVDd correlated inversely with IVST + PWT (r=-0.62, p<0.01). In conclusion, the reduction in SV that occurs during the acute phase of myocarditis is not only the result of systolic dysfunction, but also of the concentric left ventricular wall thickening associated with myocardial interstitial edema, which results in narrowing of the left ventricular cavity at end diastole.

Because of the marked side effects associated with conticosteroid use, a switch was made to methotrexate therapy in 4 patients with cardiac sarcoidosis and the utility of this agent was investigated. As side effects induced by methotrexate, anaplastic anemia developed in one case and liver dysfunction in two. In the former case, when this agent was discontinued and G-CSF (granulocyte-colony stimulating factor) filgrastim was administered, swift improvement was attained. In the two cases with liver dysfunction, dosage reduction was required. In the remaining case, despite the absence of obvious side effects, the switch to this agent was associated with a resurgence of sarcoidosis activity, necessitating a switch back to cordicosteroid administration. Accumulation of further experience with methotrexate therapy for cardiac sarcoidosis is awaited. Our present experience was not promising in that methotrexate therapy could not be considered effective in 3 of the 4 cases.

We studied the effects of cAMP on cytokine (interferon-gamma plus tumor necrosis factor-alpha)-induced stimulation of tetrahydrobiopterin (BH4) synthesis in human umbilical vein endothelial cells (HUVEC). The cytokine mixture caused a marked increase in the biosynthesis and release of BH4 by HUVEC. Dibutyryl-cAMP produced a dose-dependent inhibition of this cytokine-induced stimulation of synthesis and release of BH4 by these cells. 8-Bromo-cAMP also caused a significant inhibition, although the effects were less marked than those of dibutyryl-cAMP. Both forskolin and the stable analog of prostacyclin, iloprost, caused cAMP accumulation and a concomitant diminution of the cytokine-induced BH4 synthesis in HUVEC. Dibutyryl-cAMP and iloprost also significantly inhibited the cytokine-induced stimulation of GTP cyclohydrolase I (GCHI) activity and mRNA production. We concluded that the suppression by the cAMP messenger system of cytokine-induced stimulation of synthesis and release of BH4 by HUVEC can be attributed to the inhibition of the activity of GCHI, the rate-limiting enzyme in BH4 biosynthetic pathway, in HUVEC. The data also suggest that the caMP-mediated reduction in the GCHI mRNA level may at least partially explain the decline in GCHI activity. It is reasoned that under inflammatory conditions, cAMP-elevating agents such as prostacyclin exert regulatory effects on circulation by inhibiting cytokine-induced synthesis and release of BH4 by HUVEC. (C) 2002 Elsevier Science Inc. All rights reserved.

We first identified GTP cyclohydrolase I activity (EC 3.5.4.16) in the ciliated protozoa, Tetrahymena pyriformis. The V-max value of the enzyme in the cellular extract of T. pyriformis was 255 pmol mg(-1) protein h(-1). Michaelis-Menten kinetics indicated a positive cooperative binding of GTP to the enzyme. The GTP concentration producing half-maximal velocity was 0.8 mM. By high-performance liquid chromatography (HPLC) with fluorescence detection, a major peak corresponding to D-monapterin (2-amino-4-hydroxy-6-[(1'R,2'R)-1',2',3'-trihydroxypropyl]pteridine, D-threo-neopterin) and minor peaks of D-erythro-neopterin and L-erythro-biopterin were found to be present in the cellular extract of Tetrahymena. Thus, it is strongly suggested that Tetrahymena converts GTP into unconjugated pteridine derivatives. In this study, dopamine was detected as the major catecholamine, while neither epinephrine nor norepinephrine was identified. Indeed, this protozoa was shown to possess the activity of a dopamine synthesizing enzyme, aromatic L-amino acid decarboxylase. On the other hand, activities of tyrosine hydroxylase or tyrosinase which converts tyrosine into dope, the substrate of aromatic L-amino acid decarboxylase, could not be detected in this protozoa. Furthermore, neither dopamine B-hydroxylase activity nor phenylethanolamine N-methyltransferase activity could be identified by the HPLC methods. (C) 1998 Elsevier Science Inc. All rights reserved.