Thyroid-Stimulating Antibody/Thyroid-Stimulating Hormone Receptor Antibody Ratio as a Sensitive Screening Test for Active Graves' Orbitopathy.

OBJECTIVE: Graves' orbitopathy (GO), an extrathyroidal manifestation of Graves' disease, can seriously threaten a patient's quality of life. Given that immunosuppressive treatment during the early active phase of GO has been found to reduce both disease activity and severity, sensitive screening tests are needed. METHODS: The present study included 86 patients with GO, in whom serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine, thyroid-stimulating antibody, TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin, and thyroglobulin antibody were measured within 2 months before magnetic resonance imaging (MRI) for orbit assessment. RESULTS: The thyroid-stimulating antibody/TSH receptor antibody ratio was able to distinguish MRI results with a correct classification rate of 81%. When focusing on patients without T3 predominant Graves' diseases, the ratio distinguished MRI results at a rate of 92%. Receiver operating characteristic curve analysis revealed a cutoff antibody ratio of 87, which yielded a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 91%, 95%, 18.2, and 0.0957, respectively, for distinguished MRI results. CONCLUSIONS: The thyroid-stimulating antibody/TSH receptor antibody ratio is a highly sensitive and specific indicator for active GO, especially in patients without T3 predominance, and serves as a good screening test for active GO in primary care settings.

Adenosine inhibits TNFα-induced MMP-3 production in MH7A rheumatoid arthritis synoviocytes via A2A receptor signaling.

Adenosine causes the anti-inflammatory effect of MTX; however, the contributions of synoviocyte adenosine receptors (AdoRs) are unknown, and matrix metalloproteinase 3 (MMP-3) is released by fibroblast-like synoviocytes in response to inflammatory signaling. To understand the mechanism of the clinical observation that the matrix proteinase-3 concentration of patients with rheumatoid arthritis treated successfully with methotrexate does not usually normalize, we investigated the effects of A2A AdoR activation and inhibition on tumor necrosis factor-alpha (TNFα)-induced MMP-3 release by MH7A human rheumatoid synovial cells. MH7A cells constitutively expressed membrane-associated A2A AdoRs, and HENECA enhanced intracellular cAMP. Stimulation with TNFα markedly enhanced release of MMP-3 from MH7A cells, whereas HENECA partially and dose-dependently inhibited TNFα-evoked MMP-3 release. Similarly, dbcAMP partially inhibited TNFα-induced MMP-3 release. Pretreatment with ZM241385 reversed the inhibitory effects of HENECA. Further, TNFα induced p38 MAPK and ATF-2 phosphorylation, whereas HENECA suppressed p38 MAPK and ATF-2 phosphorylation. We concluded that adenosine signaling via A2A AdoRs, adenylyl cyclase, and cAMP reduces TNFα-induced MMP-3 production by interfering with p38 MAPK/ATF-2 activity. Activation of A2A AdoR signaling alone using HENECA did not reduce TNFα-induced MMP-3 production to the basal levels, which may explain why MTX usually decreases but does not eliminate serum MMP-3.

Clinical efficacy of teicoplanin in the treatment of bloodstream infection caused by methicillin-resistant coagulase-negative staphylococci.

Empirical combination therapy with ß-lactams and glycopeptides is recommended for patients with presumed staphylococcal bloodstream infection (BSI). While coagulase-negative staphylococci (CNS) remain susceptible to vancomycin, such isolates have become less susceptible to teicoplanin. The aim of this retrospective study was to evaluate the clinical efficacy of teicoplanin in the treatment of BSI caused by methicillin-resistant CNS according to teicoplanin susceptibility. Inclusion criteria were patients with intravascular-catheter related BSIs caused by methicillin-resistant CNS (positive for two or more specimens); teicoplanin therapy; and at least one of the signs or symptoms caused by BSI. Antimicrobial resistance was defined as minimum inhibitory concentration (MIC) ≥8 µg/mL. The primary efficacy endpoint was clinical success evaluated 2 weeks after the completion of teicoplanin therapy [test of cure (TOC)]. Resistant rate of CNS was 0% for vancomycin and 22.9% for teicoplanin, and geometric mean MICs were 1.31 µg/mL and 3.41 µg/mL, respectively (p < 0.001). The catheter was removed in all patients except one, and high early clinical response at 72 h after starting therapy was obtained irrespective of teicoplanin susceptibility. The clinical success rate at TOC was 60% in patients with BSIs caused by teicoplanin-resistant strains, while 90% in patients with BSIs caused by susceptible strains (p = 0.052). In multivariate analyses, teicoplanin resistance was significant factor for decreased clinical success at TOC (adjusted odds ratio 0.138, 95% confidence interval 0.020-0.961, p = 0.045). Because of the poor clinical efficacy of teicoplanin against teicoplanin-resistant CNS, combination therapy comprising vancomycin and ß-lactam antibiotics should be considered in presumed staphylococci BSI.

Effect of acute aerobic exercise on arterial stiffness and thyroid-stimulating hormone in subclinical hypothyroidism.

Acute exercise has been reported to increase thyroid hormone levels and decrease arterial stiffness in healthy young subjects. However, the effect of acute aerobic exercise on circulating thyroid hormone levels and arterial stiffness in patients with subclinical hypothyroidism remains unclear. The aim of this study was to investigate the effects of acute aerobic exercise on arterial stiffness and thyroid hormone levels, and any relationship between these endpoints, in patients with subclinical hypothyroidism. We studied patients with untreated subclinical hypothyroidism (n = 53, 65 ± 12 years old) compared with euthyroid subjects (n = 55, 64 ± 10 years old). Exercise analysis was performed with a ramp cycle ergometer test. Arterial stiffness (cardio-ankle vascular index, CAVI) was measured at baseline and 5 min after exercise. We collected participant blood samples for serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurements before and 5 min after exercise. The CAVI and serum TSH levels significantly decreased after exercise in the subclinical hypothyroidism group (CAVI; 8.1 ± 1.6 vs. 8.5 ± 1.5, p < 0.001, TSH; 6.7 ± 1.4 vs. 7.6 ± 1.2 µIU/ml, p < 0.001) and euthyroid group (CAVI; 7.6 ± 1.0 vs. 8.3 ± 0.9, p < 0.001, TSH; 2.2 ± 1.1 vs. 2.4 ± 1.2 µIU/ml, p = 0.005). The changes in CAVI from baseline compared with after exercise were lower, in absolute values, in the subclinical hypothyroidism group than in the euthyroid group (subclinical hypothyroidism group vs euthyroid group; ΔCAVI: - 0.4 ± 0.6 vs. - 0.7 ± 0.7, p = 0.012). The changes in serum TSH from baseline to after exercise were higher, in absolute values, in the subclinical hypothyroidism group than in the euthyroid group (subclinical hypothyroidism group vs euthyroid group; Δ serum TSH: - 1.3 ± 1.4 vs. - 0.3 ± 0.5, p < 0.001). The changes in CAVI from baseline to after exercise were negatively correlated with changes in TSH (r = - 0.32, p = 0.038) in the subclinical hypothyroidism group. In conclusion, acute aerobic exercise decreased both arterial stiffness and serum TSH levels in patients with subclinical hypothyroidism and euthyroid subjects. While the absolute change in arterial stiffness decreased, the absolute change in serum TSH levels increased in patients with subclinical hypothyroidism compared with euthyroid subjects. These data suggest that subclinical hypothyroidism reduces CAVI during acute aerobic exercise. Further changes in absolute levels of serum TSH in subclinical hypothyroidism may result in reduced CAVI improvement by acute aerobic exercise.

Serum Macro TSH Level is Associated with Sleep Quality in Patients with Cardiovascular Risks - HSCAA Study.

Macro thyroid-stimulating hormone (TSH) has been reported to be associated with seasonality and regulated by changes in day length in rodents, different from free TSH. In the present study, we investigated structural differences between macro TSH and free TSH levels in human serum, as well as the association of macro TSH with sleep quality. We enrolled 314 patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) study. Sleep quality shown by actigraphy, sleep physical activity, and percent sleep in all and TSH closely matched subjects were significantly associated with high macro TSH levels. Macro and free TSH were similarly increased following thyrotropin-releasing hormone (TRH) stimulation, while circadian changes associated with those were distinct. To further analyze the structure of macro TSH, serum samples were separated by gel filtration chromatography. Although treatment with glycosidase did not affect morbidity, the macro TSH fraction had a markedly low affinity to the Con A column as compared with free TSH, indicating a distinct glycosylation structure. In conclusion, an increase in serum macro TSH is associated with low sleep quality and regulated in a manner distinct from free TSH, potentially due to an altered glycosylation structure.

[Review of Safety Management from Infection Control Perspectives--Chairmen's Introductory Remarks].

The Japanese Society of Laboratory Medicine has been running its own Medical Safety Committee, and holding a symposium on medical safety during the annual meeting every year. Adopting a team approach to medicine plays a critical role in the development of medical safety culture and advancing medical safety in clinical practice. The infection control team plays a major role in team medical care. This time, the review of safety management from infection control perspective was discussed in the medical safety symposium, which is hoped will help advance medical and patient safety, leading to improvements in the quality of medical care.

Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.

Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.

[Molecular Targeted Therapy and Laboratory Tests].

Molecular targeted therapy is medical treatment targeting specific molecules, which are essential in the pathology of diseases. Most agents used are monoclonal antibodies ("biologics") and low-molecular-weight compounds. Molecular targeted therapy is widely utilized against malignancies, such as imatinib for chronic myelogenous leukemia blocking BCR-ABL tyrosine kinase, gefitinib for non-small cell lung cancer interrupt- ing signal transduction through EGFR, and trastuzumab for HER2-positive breast cancer. It is a companion diagnostic used as a companion to a molecular targeted drug to determine its applicability for a specific patient, showing the importance of laboratory tests for cancer treatment. While the pathogeneses of connective tissue diseases are still unknown, recent progress in understanding the pathophysiology enables us to use molecular targeted drugs for effective treatment. Rheumatoid arthri- tis (RA) is the most common connective tissue disease, and inflammatory cytokines such as TNFa and IL-6 play a pivotal role in the pathogenesis of RA. In Japan, successful treatment of RA with a chimeric antibody to TNFa(infliximab) is followed by a number of anti-cytokine drugs, such as humanized anti-TNFa, anti- TNF receptor, and anti-IL-6 receptor antibodies. A fusion protein (abatacept), an inhibitor of activated T- cells, composed of the extracellular domain of CTLA-4 and the Fc region of IgG1, and more recently Janus kinase inhibitor (tofacitinib), have also been demonstrated to be highly effective. Since molecular targeted therapy suppresses the immune function, patients receiving the therapy become susceptible to infection. Thus, clinical laboratory tests are of great importance, not only to classify potentially high-risk patients (especially in the case of the so-called post-infectious state of tuberculosis and hepatitis B to avoid reactivation) before treatment but also for the early detection of infections during treatment. [Review].

[Practice and Role of Team Approach to Medicine in Clinical Laboratory Medicine--Chairmen's Introductory Remarks].

The Japanese Society of Laboratory Medicine has been running its own Medical Safety Committee, and holding a symposium on medical safety during the annual meeting every year. The activities based on a team approach to medicine play a critical role in the development of medical safety culture and the driving forward of medical safety in clinical practice. The best medical practice involves cooperation among information-sharing medical staff from a variety of professions, providing medical care based on medical safety, which patients hope for. It is hoped that the present symposium on medical safety can help drive medical safety into the future.

[Verification of complete blood cell count (CBC) data from heparinized blood gas samples].

Complete blood cell count (CBC) data from heparinized blood gas (H-Gas) samples were verified with primary focus on the platelet count (PLT). When a part of H-Gas sample was taken to a separation tube from the blood collection syringe and CBC of the sample in the separation tube was repeatedly measured (Procedure 1), the PLT from 5 samples relative to that obtained immediately after the separation was gradually reduced to 72.6-94.2% during serial measurements (every 5 minutes, up to 30 minutes). The change in the scattergram pattern suggested that this PLT decrease was due to the formation of platelet clumps. The white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) values did not significantly change during the repeated measurements. On the other hand, PLT was significantly improved to 96.8-99.8% when the H-Gas sample was kept in the blood collection syringe so as to minimizing the exposure to the air, and the sample for the measurement from H-Gas was taken every time to separation tube from the syringe, followed by CBC measurement without delay (Procedure 2). In addition, while there were significant variations (CV: 11.8-18.2%) in PLT reproducibility among H-Gas samples by Procedure 1, measurements utilizing the Procedure 2 resulted in much smaller variations (CV: 2.2-3.7%). Thus the CBC data obtained from H-Gas samples were equivalent to those from EDTA samples when the Procedure 2 was applied. These data suggest that H-Gas samples can be used for the accurate CBC measurement, including PLT, by applying the Procedure 2.

Elevated arterial stiffness and diastolic dysfunction in subclinical hypothyroidism.

BACKGROUND: Thyroid hormone is associated with arterial stiffness and left ventricular diastolic function in hypothyroid disease. The relationship of thyroid hormone level to cardio-ankle vascular index (CAVI) and left ventricular diastolic function, however, remains unclear in subjects with subclinical hypothyroidism. METHODS AND RESULTS: We conducted a cross-sectional study of 83 patients with untreated subclinical hypothyroidism and compared them with 83 randomly selected controls from health check-ups. Log N-terminal prohormone of brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and arterial stiffness were measured. In addition, we measured early diastolic mitral annular velocity (E') in 43 participants with subclinical hypothyroidism and in 40 controls. When compared with the control group, patients with subclinical hypothyroidism had higher logNT-proBNP (1.9±0.5 vs. 1.7±0.3pg/ml, P<0.05), CRP (0.22±0.04 vs. 0.09±0.06mg/dl, P<0.05), and CAVI (8.8±1.7 vs. 7.8±1.4, P<0.001) and lower E' (5.8±1.7 vs. 7.5±2.1cm/s, P<0.001). CAVI was significantly associated with logNT-proBNP, CRP and E' in the subclinical hypothyroidism group. CONCLUSIONS: High logNT-proBNP was associated with a raised CAVI in patients with subclinical hypothyroidism. Subclinical hypothyroidism may be a risk factor for cardiovascular events related to arterial stiffening and left ventricular diastolic dysfunction.

Long-term effects of irbesartan on plasma aldosterone concentration and left atrial volume in hypertensive patients.

BACKGROUND: Plasma aldosterone concentration (PAC) is related to cardiac remodeling in patients with hypertension. However, we do not know the detailed relationship between changes in PAC and regression of left atrial (LA) volume following long-term treatment with angiotensin II receptor blocker (ARB) or calcium-channel blocker (CCB). OBJECTIVE: The aim of this study was to investigate the effects of anti-hypertensive monotherapy, an ARB irbesartan or a CCB amlodipine, on PAC and LA reverse remodeling in hypertensive patients. METHODS: A total of 48 patients with untreated hypertension were randomly assigned to irbesartan (ARB group, n=26) and amlodipine (CCB group, n=22). We examined the correlation between LA volume index (LAVI) and other echocardiographic parameters or PAC (n=40) at the baseline and after 12 months of treatment. RESULTS: After 12 months, blood pressure (BP) decreased similarly in both groups. LAVI and PAC significantly decreased in the ARB group, but not in the CCB group (-16±8% vs. 22±9%, p<0.01, -16±9% vs. 11±9%, p<0.05). Larger %-decrease in PAC was associated with larger %-reduction of LAVI in the ARB group (r=0.54, p<0.05), but not in the CCB group. CONCLUSIONS: While BP reduction was similar between the two groups, decrease in LA volume was larger in the ARB group than in the CCB group. Decrease in LA volume was larger in patients with a greater decrease in PAC than in those with smaller decrease in PAC. ARB may facilitate reverse remodeling of LA through decreases in PAC in hypertensive patients.

[Points of revision of the guideline JSLM 2012].

The revised version of the guideline JSLM 2012 was published in December 2012 by the Japanese Society of Laboratory Medicine. This version included new sections, such as blood gas analysis, sleep apnea syndrome, interstitial lung disease, liver and pancreas cancer, chronic kidney disease, acute kidney disease, gout and hyperuricemia, bone metabolism abnormality, malignant lymphoma, and rheumatoid arthritis. The guideline committee was composed of specialists in each field of internal medicine, who were responsible for selecting and requesting the authors and also in promoting and proofreading the manuscripts. In special program I at the 60th annual meeting, each specialist gave lectures concerning the points of the revision in their fields. The questionnaire surveys were performed using FAX or the Internet. Analysis of eighty-seven (2.5%) responses from 3,500 individuals/facilities, which were sent the guideline, revealed that this guideline was graded as excellent by 38 readers, fair by 42, and average by in 6. Significant opinions on the guideline were obtained from the readers, and they will be the bases for the next revision. The main subjects of this guideline were confirmed to be the residents and general physicians, by whom it is hoped the routine laboratory tests will be properly utilized. Therefore, based on the section of 'approach of the laboratory test results', which is a representative characteristic of this guideline, the sections of 'symptoms' will be fulfilled for the next version. This guideline needs to be periodically revised with advances in medicine.

[Laboratory management fee in national health insurance; what is required from clinical laboratory physicians? --message from Chairpersons].

The laboratory management fee (LMF) in national health insurance ("Kentai-Kensa-Kanri-Kasan" in Japanese) has had a major impact on Japanese clinical laboratories, especially in recent years. In 2012, the fee was raised to approximately 5,000 yen per admitted patient. In order to address this national support, clinical pathologists are required to increase their knowledge and skills. On the other hand, there are insufficient clinical pathologists in Japan. In order to solve this problem, the Japanese Society of Laboratory Medicine (JSLM) approved a new license for Qualified Clinical Laboratory Managing Physicians (CLMPs), in addition to Certified Clinical Laboratory Physicians (CCLPs). The requirements to become a CLMP are less strict than for CCLP. There are approximately 500 CLMPs and 600 CCLPs in this country. The aim of this symposium was to offer opportunities to increase attendees' clinical skills, especially CLMPs and young clinical pathologists. Four CCLPs were chosen as speakers from a university hospital, a major city hospital, a medium-sized acute care hospital, and a university hospital anatomical pathologist, together with a chief medical technologist from a university hospital. All the speakers presented their ideal role models of clinical pathologists matching LMF requirements. JSLM together with the Japanese Association of Clinical Laboratory Physicians (JACLaP) sponsored this symposium. It was a successful meeting with more than two hundred attendees.

Tacrolimus ameliorates dextran sulfate sodium-induced colitis in mice: implication of interferon-γ and interleukin-1ß suppression.

We investigated the effect of tacrolimus, a calcineurin inhibitor, on dextran sulfate sodium (DSS)-induced colitis. After inducing colitis in C57BL/6 mice by administering DSS solution as drinking water for 7 d, the animals were treated with tacrolimus. Severity of colonic inflammation was evaluated based on colon weight per unit length. Levels of cytokines (interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-12, and tumor necrosis factor (TNF)-α) released from isolated inflamed colons of mice treated with tacrolimus or vehicle were also measured. Treatment with tacrolimus for 14 d reduced the colon weight per unit length and suppressed the release of IFN-γ and IL-1ß, but not other cytokines, in inflamed colons of colitic mice compared with vehicle-treated mice. A positive correlation was noted between colon weight per unit length and released level of IFN-γ or IL-1ß. The release of IFN-γ and IL-1ß was also suppressed after single dosing with tacrolimus to colitic mice. Taken together, these results suggested that tacrolimus ameliorated DSS-induced colitis by suppressing release of IFN-γ and IL-1ß from inflamed colon.

Preventive and therapeutic effects of tacrolimus in an interleukin-10-deficient mouse model of colitis.

OBJECTIVE: To investigate the preventive and therapeutic effects of tacrolimus on colonic inflammation in interleukin-10-deficient (IL-10(-/-)) mice, which spontaneously develop T-cell-mediated colitis. METHODS: Tacrolimus or prednisolone, an anti-inflammatory glucocorticoid, was administered to IL-10(-/-) mice with pre- or post-symptomatic colitis. Effects on colonic inflammation were examined by measuring indices of colitis such as colonic weight/length ratio, cell infiltration, and goblet cell depletion. Effects on cytokine production in colonic lamina propria mononuclear cells (LPMCs) isolated from IL-10(-/-) mice were also examined. RESULTS: Tacrolimus prevented development of colitis and improved already-developed colitis. Prednisolone prevented the development of colitis, but had no effect on already-developed colitis. Tacrolimus completely inhibited IFN-γ and TNF-α production of activated T-cells in LPMCs, but only partially inhibited IFN-γ, TNF-α, and IL-12 production of activated monocytes/macrophages in LPMCs. Prednisolone inhibited cytokine production in both cell types but exhibited greater potency on monocytes/macrophages than on T-cells. CONCLUSION: These results suggest that the preventive and therapeutic effect of tacrolimus in IL-10(-/-) mice colitis might be attributed to the inhibition of colonic T-cell activation rather than monocyte/macrophage activation. T-cell immunosuppression may thus be a promising strategy for treating colonic inflammation.

[Reference range of the auditory brainstem response for the patients in the NICU].

Since the auditory brainstem response (ABR) test is a test for the brainstem capacity and hearing function, it is recorded at the discharge from the neonatal intensive care unit (NICU) in our hospital. Although the reference range for the normal full-term newborn infants is well documented, that for the pre-term newborn and/or low birth weight infants is yet to be determined. The latency between wave-I peak and wave-V peak (I-V inter peak latency) on the ABR test was measured on the 254 infants (124 males and 130 females) of 36 to 45 corrected weeks old which was defined as the sum of the gestational weeks and weeks after birth at the test. The reference range for each corrected age group is set as mean +/- standard deviation. The mean value tends to be short as the corrected age increases, while it is not affected by the gestational weeks, body weight on birth, blood bilirubin level, neonatal asphyxia (defined as Apgar score at 1 minute after birth is less than 5), or intrauterine growth retardation. Eight out of 254 patients showed the abnormal values; among the 8 patients, 3 had brain diseases (intraventricular hemorrhage, intracranial hemorrhage, and microcephaly) and 1 with Down's syndrome. Thus the brain stem function testing at a discharge from NICU is important for the neurophysiological prognosis of the patients and the ABR test with the reference range defined here can be a useful tool.

Characterization of cardiac size and function in SHRSP.Z-Lepr(fa)/IzmDmcr rats, a new animal model of metabolic syndrome.

Cardiac structural and functional abnormalities are observed in metabolic syndrome. However, such changes have not been investigated in the SHRSP.Z-Lepr(fa)/IzmDmcr rat (SHRSP-fatty) model of metabolic syndrome. Here we compare cardiac size and hemodynamic function in these rats with their lean littermates (SHRSP) and normotensive control Wistar-Kyoto rats (WKY). In male 16-week-old SHRSP-fatty, we determined heart rate and systolic blood pressure (SBP) by tail-cuff, cardiac output (CO), subcutaneous peripheral blood flow (BF) and stroke volume (SV) by plethysmography, and systolic and diastolic functions by echocardiography. We also assessed weight and collagen type I expression by Western blot in isolated atrium and ventricle, and beat rate in isolated atrial preparation by myography. Heart rate was lower in conscious SHRSP-fatty than SHRSP, and the beat rate of isolated atria was lower in SHRSP-fatty and SHRSP than that of WKY. Atrial weight was larger in SHRSP-fatty than others. Ventricular weight of SHRSP-fatty and SHRSP was larger than WKY. There were significant inverse correlations between atrial weight and heart rate or beat rate in SHRSP-fatty. SBP, CO, BF and SV were increased in SHRSP-fatty similarly to SHRSP. Increased deceleration time and decreased E/A ratio, and preserved fractional shortening were observed in SHRSP-fatty. Expressions of collagen type I were increased in atria and ventricle of SHRSP-fatty. SHRSP-fatty with metabolic syndrome exhibit cardiac changes, including slowed heart rate, ventricular diastolic dysfunction, and fibrosis, and atrial enlargement. SHRSP-fatty may be a useful rat model to study on cardiac abnormalities in metabolic syndrome.

[Electrophysiological tests in a case of Hashimoto's encephalopathy].

Hashimoto's encephalopathy is regarded as an autoimmune disorder that appears in patients with anti thyroid antibodies. The thyroid function tests of the patients are not necessarily abnormal, which sometimes makes the diagnosis difficult. Since most of the patients show consciousness disturbance, psychiatric symptoms, and cognitive function decline, Hashimoto's encephalopathy must be distinguished from other disorders showing dementia. We performed the electrophysiological tests on a 38 year old woman with Hashimoto's encephalopathy. Event-related potentials showed impaired cognitive function, and somatosensory evoked potentials and motor evoked potentials showed abnormalities of central nervous system. Although the steroid pulse therapy with the following oral prednisolone treatment resulted in the remission of symptoms, results of electrophysiological tests remained unimproved. Thus the disease course of the patient should carefully be monitored, and the clinical importance of these tests in Hashimoto's encephalopathy may be further considered.