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.     

Genetic medicine in Japan

Present status of genetic medicine in Japan is reviewed. More than five hundred medical doctors have now been qualified as Japanese board of clinical genetics. Training courses for genetic counselors have started in several colleges. Thirty-six hospitals organized by University or National Centers have independent units of clinical genetics. Two major Japanese homepages concerning about clinical genetics are available. Ethical guidelines for gene testing and prenatal diagnosis are published by Japanese Society for Human Genetics and other Japanese medical societies. Infrastructure for clinical genetics are now rapidly organized in Japan, however lots of problems are still waiting to be solved.     

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts: technical note

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke’s cleft cyst (RCC). In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst. Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall. Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.     

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.     

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder

Background

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT₂ gallbladder carcinoma with simple in vitro experiments.

Methods

Ninety patients with pT₂ gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.

Results

Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.

Conclusions

GnT-V expression in the subserosal layer of pT₂ gallbladder carcinoma is correlated with the aggressiveness of the disease.     

Effects of exercise on C-reactive protein,inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

Objective

C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines.

Materials/Methods

We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966–2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis.

Results

Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP = − 0.66 mg/l (95% CI, − 1.09 to − 0.23 mg/l; − 14% from baseline) and interleukin-6 (IL-6) = − 0.88 pg/ml (95% CI, − 1.44 to − 0.32 pg/ml; − 18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin = − 3.72 ng/ml (95% CI, − 6.26 to − 1.18 ng/ml; − 24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p = 0.001).

Conclusions

Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.