Moving beyond superficial communication to collaborative communication: learning processes and outcomes of interprofessional education in actual medical settings.

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.

Relationship between peer evaluation and interprofessional self-evaluation in a joint healthcare team-based learning class involving three universities.

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.

Cilostazol inhibits cytokine-induced tetrahydrobiopterin biosynthesis in human umbilical vein endothelial cells.

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.

Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure.

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.

2,4-Diamino-6-hydroxypyrimidine (DAHP) suppresses cytokine-induced VCAM-1 expression on the cell surface of human umbilical vein endothelial cells in a BH(4)-independent manner.

2,4-Diamino-6-hydroxypyrimidine (DAHP) is considered a specific inhibitor of BH(4) biosynthesis and is widely used in order to elucidate the possible biological function of BH(4) in various cells. In the present study, we found that both the synthesis of tetrahydrobiopterin (BH(4)) and expression of vascular cell adhesion molecule 1 (VCAM-1) were increased in human umbilical vein endothelial cells (HUVEC) treated with proinflammatory cytokines. Thus we examined the effects of DAHP to clarify whether BH(4) might be involved in the expression of VCAM-1 in HUVEC. DAHP reduced the levels of both BH(4) and VCAM-1 induced by TNF-alpha and IFN-gamma. However, the dose-response curves of DAHP for the suppression of the VCAM-1 level and that of BH(4) level were markedly different. Supplementation with sepiapterin failed to restore the depressed VCAM-1 level, although it completely restored the BH(4) level. Furthermore, DAHP significantly reduced the VCAM-1 level under the experimental conditions using TNF-alpha alone, which failed to induce BH(4) production. Taken together, these results indicate that DAHP inhibited the expression of VCAM-1 in a BH(4)-independent manner in HUVEC. In the present study, we also found that DAHP significantly suppressed the accumulation of cytokine-induced NF-kappaB (p65) in the nucleus as well as the mRNA levels of VCAM-1 and GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH(4) synthesis. The data obtained in this study suggest that DAHP reduced VCAM-1 and GTPCH protein synthesis at least partially via suppressing the NF-kappaB level in the nucleus of HUVEC.

Significance of transient left ventricular wall thickening in acute lymphocytic myocarditis.

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.

Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis.

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.

Role of myocardial interstitial edema in conduction disturbances in acute myocarditis.

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.

Clinical course of myocarditis through the acute, fulminant and fatal chronic stages: an autopsy case.

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.

Relief of left ventricular outflow obstruction by cibenzoline in a patient with Fabry's disease--a case report.

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 1 known to have had Fabry's disease. The patient was also diagnosed with Fabry's disease, based on reduced leukocyte alpha-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.

National survey on status of steroid therapy for cardiac sarcoidosis in Japan.

AIM: This investigation was undertaken to clarify the current status of steroid therapy for cardiac sarcoidosis in Japan. METHODS: A questionnaire survey was conducted throughout Japan concerning cases in which steroid therapy had been administered. Replies describing 52 cases (15 men, 37 women; mean age +/- SD, 59.8 +/- 14.5 years) were analyzed. RESULTS: Of the 49 patients whose New York Heart Association (NYHA) functional classification was reported, 29 (55.8%) were in class I; 13 (25.0%) class II; 4 (7.7%) class III and 3 (5.8%) class IV. The most common initial steroid dose (used in 35 cases, or 67.3%) was 30 mg/day or 60 mg on alternate days. In most cases (85.4%), this dose was continued for 1 month followed by tapering by 5 mg every 2 to 4 weeks until reaching the maintenance dose of 5 to 10 mg/day. Steroid therapy was reported to result in improvement in 54%, no change in 40%, and deterioration in 6%. CONCLUSION: This nationwide questionnaire survey indicated fairly uniform patterns of steroid therapy for cardiac sarcoidosis in Japan, with clinical improvement in over one-half of cases and possible stabilization in most others.

Relationship between basal thinning of the interventricular septum and atrioventricular block in patients with cardiac sarcoidosis.

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.

Suppressed expression of GTP cyclohydrolase I mRNA and accelerated expression of inducible nitric oxide synthase mRNA in endomyocardial biopsy specimens from patients with dilated cardiomyopathy.

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.

Diagnostic utility of tenascin-C for evaluation of the activity of human acute myocarditis.

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.

Risk factors for patients developing a fulminant course with acute myocarditis.

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.

Right ventricular endomyocardial biopsy findings in 25 patients with sick sinus syndrome.

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.

cGMP inhibits GTP cyclohydrolase I activity and biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells.

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.

Changes in the peripheral eosinophil count in patients with acute eosinophilic myocarditis.

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.