New diagnostic and evaluative tests for rheumatoid arthritis

To prevent joint destruction, it is important to diagnose RA early and to consider the prognosis. For this purpose, several new laboratory tests, such as IgG-RF, anti-agalactosyl IgG antibodies (CARF), and matrix metalloproteinase-3 (MMP-3), have become available for diagnosing RA. RF has a tolerable sensitivity of 68.5% for RA, but low specificity of 77.1%, and also 76.0% for patients with other rheumatic diseases and chronic inflammatory disease, respectively. CARF showed slightly higher sensitivity but low specificity for other rheumatic diseases and chronic inflammatory patients. In contrast, anti-cyclic citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA, demonstrated significantly high specificity for other rheumatic diseases, and also for chronic inflammatory disease patients. Anti-CCP was superior to other laboratory tests by ROC analysis. Moreover, both CARF and anti-CCP had higher sensitivity of 66.7%, 61.5%, respectively, for the diagnosis of early RA than RF. On the other hand, MMP-3 is thought to be not only an evaluative test for the activity of RA because of its significant correlation with CRP, but also has potential as a prognostic test to identify joint damage from RA. Anti-CCP was also reported to associate with the progression of joint damage and may be also used as a prognostic test. We next examined the efficiency of RA diagnosis made by combining these laboratory tests. The specificity of RF was not as high as anti-CCP but reached 92% when combined with MMP-3. Thus, it is concluded that anti-CCP is superior to other laboratory tests in sensitivity and specificity, and that these combination assays are useful in the early diagnosis of RA.     

Urinary iodine kinetics after oral loading of potassium iodine

We studied the kinetics of iodine in various forms, in order to establish appropriate guidelines of iodine prophylaxis for thyroid blockade at nuclear emergency in "iodine rich areas", such as Japan. First, the effect of equivalent dose of potassium iodide (KI) (solution vs. tablet) was evaluated with excretions of urinary iodine (UI) at Nagasaki, Japan, and it was revealed that there was no difference of iodine kinetics between solution and tablet. We also performed the same study at Gomel, Belarus, which was known to be an iodine deficient area, and obtained the same results. Second, the kinetics of iodine included in "iodine rich" food was also evaluated with excretions of UI. Interestingly, the ratio of UI excretion with iodine rich food was significantly lower than that with KI tablets until 6 h after the intake (ANOVA, p = 0.02). These results proved that 1) KI solution as well as its tablet is useful for prophylaxis and 2) prophylaxis by iodine rich food is not effective for rapid blockade of thyroid gland at nuclear emergency. Finally, we emphasized that the approach from social medicine is definitely important to establish an effective iodine prophylaxis.     

Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase.

AIMS: Vascular endothelium is a major organ involved in hyperglycaemia and is affected by plasma asymmetric dimethylarginine (ADMA). ADMA is an endogenous, competitive inhibitor of nitric oxide synthase and is induced by inflammatory cytokines of tumour necrosis factor (TNF)-alpha in vitro. We hypothesized that a tight glycaemic control may restore endothelial function in patients with type-2 diabetes mellitus (DM), in association with modulation of TNF-alpha and/or reduction of ADMA level. METHODS AND RESULTS: In 24 patients with type-2 DM, the flow-mediated, endothelium-dependent dilation (FMD: %) of brachial arteries during reactive hyperaemia was determined by a high-resolution ultrasound method. Blood samples for glucose, cholesterol, TNF-alpha, and ADMA analyses were also collected from these patients after fasting. No significant glycaemic or FMD changes were observed in 10 patients receiving the conventional therapy. In 14 patients who were hospitalized and intensively treated, there was a significant decrease in glucose level after the treatment [from 190+/-55 to 117+/-21 (mean+/-SD) mg/dL, P<0.01]. After the intensive control of glucose level, FMD increased significantly (from 2.5+/-0.9 to 7.2+/-3.0%), accompanied by a significant (P<0.01) decrease in TNF-alpha (from 29+/-16 to 11+/-9 pg/dL) and ADMA (from 4.8+/-1.5 to 3.5+/-1.1 microM/L) levels. The changes in FMD after treatment correlated inversely with those in TNF-alpha (R=-0.711, P<0.01) and ADMA (R=-0.717, P<0.01) levels. CONCLUSION: The intensive correction of hyperglycaemia is associated with the improvement of endothelial function, which is coupled with the decrease in the levels of reduction of plasma TNF-alpha and ADMA in patients with type-2 DM. A strict glycaemic control may exert anti-cytokine and anti-atherogenic effects and may therefore be pathophysiologically important.     

Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: initial description of a new variable.

BACKGROUND: Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (< 5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P < .001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.     

Effect of the herbal medicine Dai-kenchu-to for serum ammonia in hepatectomized patients

BACKGROUND/AIMS: Prolonged paralytic ileus occurring in hepatectomized patients may induce hyperammonemia or bacterial translocation, which injures the remnant liver function and sometimes causes post-resection liver failure. We examined the effectiveness of the herbal medicine, Dai-kenchu-to (DKT), on postoperative serum ammonia levels in patients with liver resection and compared it with lactulose. METHODOLOGY: Patients with liver resection were divided into three groups. Lactulose group (n=31), 16g of lactulose was administered orally three times a day from the first postoperative day. DKT group (n=27), 5g of DKT was administered in the same fashion. Control group (n=26), neither lactulose nor DKT was administered. In all three groups, 16g of lactulose was administered three times a day for three days preoperatively. RESULTS: There was no significant difference among the groups in age, gender and preoperative hepatic functional values, such as ICG-R15 or galactose tolerance test. There was also no difference in parenchymal hepatic resection rate, operative time and amount of intraoperative bleeding volume. Postoperative serum ammonia levels were significantly lower in the DKT group than control and lactulose groups. Instances of delayed flatulence and occurrence of diarrhea were also fewer in the DKT group. CONCLUSIONS: DKT may become a more effective and safe agent than lactulose in postoperative management of liver resection.     

Carotid intima-media thickness is increased in subjects with ischemic heart disease having a familial incidence

OBJECTIVES: A family history of ischemic heart disease (IHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. The authors hypothesized that an important mediator of the familial incidence of IHD is subclinical atherosclerosis, which is detectable by noninvasive imaging. METHODS: One hundred forty-seven consecutive subjects (mean age 61.9 years, 57% men) were studied for one year using carotid ultra-sonogrophy for general medical screening, and familial IHD events were validated. Using a 7.5 MHz linear array transducer, carotid intima-media thickness (IMT) and carotid plaque were assessed. Subjects were subsequently divided into four groups based on the severity of IMT. RESULTS: The familial incidence of IHD and incidence of plaque were associated with the severity of IMT. No significant differences in risk factors were found between subjects with and without a family history of IHD. CONCLUSIONS: These findings suggest that subclinical atherosclerosis, as assessed in the carotid arteries, is more prevalent in individuals with a family history of IHD.