Physical activity thresholds for predicting longitudinal gait decline in adults with knee osteoarthritis.

OBJECTIVE: To investigate the longitudinal relationship between physical performance (via real-life accelerometry) and physical capacity (laboratory measurement of gait speed) in patients with knee osteoarthritis (KOA), and to derive accelerometry measured thresholds associated with gait speed decline in KOA that may provide targets for disease-specific physical activity guidelines. DESIGN: Longitudinal data from the Osteoarthritis Initiative (OAI) accelerometer sub-study was extracted from 1,229 participants assessed 2 years apart. Extracted data include functional capacity, demographic and anthropometric characteristics, patient-reported outcome measures, and accelerometry-based physical activity measures. A "poor capacity" group was defined based on the gait speed quintile decline between baseline and the 2-yr follow-up. A Random Forest classifier was trained to classify individuals' capacity status, and the impact of each extracted factor on the prediction outcome was analyzed using a novel machine learning interpretation algorithm. RESULTS: The most impactful predicting feature for gait decline is low minutes in the performance of moderate-vigorous activity (count per min 2,500+). Slower sit-to-stand performance, higher age and self-reported knee pain, and lower minutes in performance light activities (count per min 350-2499) also contributed to the model prediction. The overall classification accuracy is 76.3% (75.4% sensitivity, 76.5% specificity). CONCLUSIONS: We investigated the impact magnitude and direction of each predicting feature on the longitudinal capacity status among KOA patients. Using novel data interpretation method, we established feature thresholds that may increase the probability of gait decline. These identified thresholds may provide meaningful information for establishing specific physical activity guidelines for KOA.

Impact of lithium-ion ordering on surface electronic states of Li(x)CoO2.

Li(x)CoO(2) exhibits intriguing electronic properties due to a strong electron correlation and complex interplay between Co and Li ions. However, fundamental understanding of the nanoscale distribution of Li ions and its effect on the electronic properties remains unclear. We use scanning tunneling microscopy and density functional theory to elucidate the degree of Li(x)CoO(2) surface electronic state modification that can be achieved by Li ordering. The surface Li ions are highly mobile and preferentially form a (1 × 1) hexagonal lattice, whereas the surface CoO(2) layer shows metallic and insulating phases, indicating the coexistence of ordered and disordered Li ions in the subsurface layer. These results provide evidence of novel electronic properties produced by spatially inhomogeneous Li-ordering patterns.

Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats.

AIMS/HYPOTHESIS: The glomerular endothelial layer is coated by the endothelial surface layer (ESL), which is suggested to play a role in regulation of the permselectivity of macromolecules. Production of heparanase, a degrading enzyme of the ESL, is induced by reactive oxygen species (ROS). We hypothesised that oxidative stress could cause deterioration of the glomerular ESL by induction of heparanase, resulting in increased glomerular permeability. METHODS: Male Zucker fatty (ZF) rats with albuminuria and Zucker lean (ZL) rats were used in this study. Some of the ZF rats were treated with the angiotensin II receptor blocker, irbesartan. We determined the amount of ESL by wheat germ agglutinin staining and heparan sulphate proteoglycan production by western blot analysis. Glomerular hyperfiltration of macromolecules was visualised using in vivo microscopy. We used 2',7'-dichlorofluorescein diacetate-derived chemiluminescence staining to assess ROS production, and heparanase production and expression were determined by western blot analysis and quantitative real-time polymerase chain reaction respectively. RESULTS: By 18 weeks of age, ZF rats had developed albuminuria. The glomerular endothelial cell glycocalyx was significantly decreased in ZF compared with ZL rats. Glomerular filtration and the permeability of macromolecules were increased in ZF, but not in ZL rats. Glomerular ROS and heparanase production were significantly increased in ZF compared with ZL rats. These changes in ZF rats were reversed by irbesartan treatment. CONCLUSIONS/INTERPRETATION: Increased oxidative stress induces glomerular ESL deterioration in part through increased heparanase levels, resulting in exacerbation of glomerular permselectivity and development of albuminuria.

High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease.

SUMMARY: Vitamin K and D deficiency and decreased bone mineral density (BMD) were highly prevalent in patients with inflammatory bowel disease (IBD), especially Crohn's disease (CD). Dietary intakes of these vitamins, however, were above the Japanese adequate intakes in IBD patients, suggesting that malabsorption is the basis for hypovitaminosis K and D and decreased BMD. INTRODUCTION: We have studied the possible involvement of vitamin K and D deficiency in the pathogenesis of decreased BMD in IBD. METHODS: Seventy patients with IBD were evaluated for their BMD; plasma levels of vitamin K; phylloquinone (PK), menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein induced by vitamin K absence (PIVKA-II), and undercarboxylated osteocalcin (ucOC) levels; and their food intake. RESULTS: Compared with ulcerative colitis (UC) patients, CD patients had significantly lower plasma vitamin K and 25OH-D concentrations; significantly higher serum levels of PTH, PIVKA-II, and ucOC; and significantly lower BMD scores at almost all measurement sites. More IBD patients were vitamin K deficient in bone than in liver. Multiple regression analyses revealed that low plasma concentrations of vitamin K and 25OH-D were independent risk factors for low BMD and that they were associated with the patients' fat intake, but not with their intake of these vitamins. CONCLUSION: IBD patients have high prevalence of decreased BMD and vitamin K and D deficiency probably caused by malabsorption of these vitamins.

Anti-inflammatory sesquiterpenes from Curcuma zedoaria.

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent.

[Early results of new style aortosaphenous vein graft connector in coronary artery bypass grafting].

We retrospectively studied early clinical results of PAS-Port (PP) system. Fifty patients who underwent coronary artery bypass surgery with saphenous vein graft (SVG) from April 2004 to May 2005 were enrolled in this study. PP was tried for 36 SVGs in 32 patients. In 2 patients, SVG 4.0 mm in diameter could not be loaded into the device. In other 2 patients, anastomosis with PP was failed and followed by hand-sewing under aortic clamp or with Heartstring. Anastomosis with PP was successfully completed for 34 SVGs in 30 patients (group P) and conventional hand-sewing was performed for 23 SVGs in 20 patients (group C). The target vessels for SVG were similar between the 2 groups. No complication occurred in the use of PP. Postoperative angiography before discharge was performed for 31 SVGs in 27 patients (90.0%) in group P and 20 SVGs in 17 patients (85.0%) in group C. The patency rate of SVG was 96.8% in group P and 100% in group C. In conclusion, early results of PP were satisfactory compared with those of conventional hand-sewing. Severely sclerotic aorta and oversized SVG should be excluded because of possibility for incomplete deployment of the inner flange in PP.

High prevalence of vitamin D deficiency in patients with xeroderma pigmetosum-A under strict sun protection.

BACKGROUND/OBJECTIVES: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by defective repair of ultraviolet (UV) irradiation-induced DNA damage and high risk of skin cancer. Thus, these patients require strict photoprotection. Considering the importance of UV-mediated cutaneous vitamin D production, such rigorous photoprotection would cause vitamin D deficiency. Then, we have studied the vitamin D status in patients with XP-A, a group requiring the most strict photoprotection. SUBJECTS/METHODS: Twenty-one patients with XP-A (aged 6-25) were evaluated for their vitamin D intake, serum levels of 25-hydroxy-vitamin D (25OHD) and parathyroid hormone (PTH). Vitamin D intake was assessed by a 2-day food weighing method. RESULTS: Median dietary intake of vitamin D was 4.1 µg/day, and the median concentrations of serum 25OHD and PTH were 7.7 and 49.9 pg/ml, respectively. In 76% of the patients, serum 25OHD level was lower than 10 ng/ml, indicating vitamin D deficiency. Vitamin D intake and serum 25OHD level were significantly lower in patients under enteral nutrition (EN) than those with oral intake (OI). Multivariate analyses revealed that EN was a significant predictor of decreased serum 25OHD level (ß coefficient=-0.59, P=0.03). CONCLUSIONS: Vitamin D deficiency is highly prevalent in XP-A patients, and supplementation should be considered to avoid unfavorable skeletal consequences in these patients. In addition, determination of dietary vitamin D requirement has been a difficult work issue in the decision of dietary reference intakes (DRIs) because of its cutaneous production. Data from XP patients would yield useful information for the determination of DRIs for vitamin D.

Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells transfected with Edg-3, a putative lipid receptor.

Sphingosine 1-phosphate (S1P) induces phospholipase C (PLC) activation and Ca2+ mobilization in many types of cells. We examined the possible involvement of Edg-3, one of the putative S1P receptors, in the phospholipase C (PLC)-Ca2+ system. S1P increased the cytoplasmic free Ca2+ concentration without detectable inositol phosphate production in vector-transfected CHO cells. In the Edg-3-transfected cells, however, the S1P-induced Ca2+ response was clearly enhanced, which was associated with a significant production of inositol phosphate. These S1P-induced responses in the Edg-3-transfected cells were inhibited by U73122, a potent PLC inhibitor. We conclude that Edg-3 may be one of the S1P receptors participating in the activation of the PLC-Ca2+ system.

Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction.

OBJECTIVE: In patients with acute myocardial infarction (AMI), low triiodothyronine (T(3)) levels with normal or subnormal levels of thyrotropin (TSH), the euthyroid sick syndrome (ESS), have been reported, however, the mechanism of altered thyroid hormone metabolism is unknown. Recent reports have shown that interleukin-6 (IL-6) plays a key role in the pathogenesis of AMI and ESS. This preliminary study investigates the relationship between thyroid states and plasma levels of IL-6, the soluble IL-6 receptor (sIL-6R), and the soluble transducing 130kDa glycoprotein (sgp130) in AMI. DESIGN AND METHODS: We measured the concentration of TSH, free T(3) (FT(3)), free thyroxine (FT(4)), IL-6, sIL-6R and sgp130 in plasma from 24 patients with AMI and 20 normal controls. RESULTS: All 24 AMI patients showed significantly lower concentrations of FT(3) with normal or subnormal levels of TSH, and higher concentrations of IL-6 and sIL-6R than controls. IL-6 level was correlated with creatine phosphokinase (CPK) and FT(3) levels but not with FT(4 )or TSH levels in patients with AMI. The time course of IL-6 and FT(3 )concentration seemed to be closely linked. sIL-6R level was correlated with CPK and sgp130 levels, but not with FT(3), FT(4) or TSH levels. FT(4 )level was correlated with sgp130 level. CONCLUSION: Patients with AMI develop ESS through activation of IL-6 and its receptor system.

Enhanced sensitivity to anorexia and consumption of drinking water induced by interleukin-1 beta in obese yellow mice.

Exogenously administered interleukin-1 beta (IL-1) was reported to suppress food intake and endogenous CRF in the brain was reported to be involved in mediating the IL-1-induced anorexia. The present study was undertaken to investigate the effect of IL-1 (i.p.) on food and water intake in obese yellow mice and in lean mice. Enhanced sensitivity to IL-1-induced suppression of food and water intake were observed in obese yellow mice compared to lean mice (food intake suppression: lean 29.92%, obese 88.48%; water intake suppression: lean 25.18%, obese 71.56% of respective controls). After treatment of the mice with ibuprofen (10 mg/kg i.p.), the suppression of food and water intake was prevented in lean mice but unaffected in obese mice. The results suggest that there may be differential sensitivity to activation of CRF neurons induced by the peripheral injection of IL-1 in obese yellow and in lean mice.

Ulcerative colitis with overexpression of p53 preceding overt histological abnormalities of the epithelium.

A 53-year-old man with a 22-year history of ulcerative colitis(UC) (pancolitis), had an ulcerating rectal tumor. Resection of the rectum and sigmoid colon was performed. Pathology showed an expansive ulcerating adenocarcinoma tumor (type 2) invading the adventitia against a background of UC in a resolving phase. Dysplasia was also found in granular and flat mucosa adjacent to the invading carcinoma. Immunostaining for p53 showed diffuse positivity in both the carcinoma and dysplasia, and also in the mucosa with indefinite dysplasia or no dysplasia neighboring the dysplasia and carcinoma. Mapping of neoplasms and the area with p53 protein overexpression showed that the grade of dysplasia increased as the lesion approached the invasive carcinoma and that the mucosa with dysplasia was surrounded by mucosa without dysplasia or indefinite for dysplasia, but with p53 protein overexpression. In some areas without dysplasia showing p53 overexpression, there was significant morphometric enlargement of the area and diameter of the nucleus p53 Immunostaining is a good marker for assessing the genetic alterations that precede histological abnormalities and for diagnosing carcinoma in UC. Objective findings such as p53-protein overexpression and morphometric values should be used to evaluate cytological abnormalities in UC, as well as in common colorectal cancer.

Type IV collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus.

We measured urinary albumin (U-Alb) and type IV collagen (uIV.C) in spot urine collected from 82 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 205 controls. Eighty-two NIDDM patients that had no increased excretion of either U-Alb or uIV.C were observed for 6 months. Prevalence of increased excretion of U-Alb and uIV.C at 6 months in these patients were 32.9%, and 62.2%, respectively. Increased excretion of uIV.C was detected in 27 patients without microalbuminuria. chi(2) analysis suggested that uIV.C was more sensitive than U-Alb, and that hypertension enhanced increased excretion of both U-Alb and uIV.C. uIV.C was significantly correlated (P<0.01) with U-Alb but not glycosylated hemoglobin A1C (HbA1C) in NIDDM patients. Taken together, uIV.C may be a useful marker for early diabetic nephropathy.

Success rates of formocresol pulpotomy and indirect pulp therapy in the treatment of deep dentinal caries in primary teeth.

PURPOSE: This study was performed to retrospectively evaluate treatment of deep caries in primary molars with formocresol pulpotomy (FP) and indirect pulp therapy (IPT). METHODS: 133 primary molars with deep caries approaching the pulp were treated with FP (N = 78) or IPT (N = 55) and followed 2-7 years. All IPTs received immediate stainless steel crowns (SSCs); 61 FPs got an immediate SSC, 13 an intermediate restorative material (IRM), and 4 amalgam. Thirteen IPTs and 25 FPs had pre-operative pain compatible with a diagnosis of reversible pulpitis. Treatment notes and radiographs were independently assessed. RESULTS: Overall IPT success was 93% (51/55) versus 74% (58/78) for FP. Molars with pain compatible with a diagnosis of reversible pulpitis were successfully treated by IPT 85% (11/13) versus 76% (19/25) for FP. FP-treated molars exhibited earlier exfoliation 38% (30/78), while all IPT molars exhibited normal exfoliation. FPs receiving immediate SSCs had 50/61 (82%) succeed; FPs restored with an IRM temporary succeeded 5/13 (39%), amalgam 3/4 (75%). CONCLUSIONS: IPT success was significantly higher than FP (P = 0.01) in the treatment of deep caries. Both IPT and FP were successful in treating teeth with pain compatible with the diagnosis of reversible pulpitis. FP significantly hastened the exfoliation of pulpotomized primary molars (P = 0.001). IPT in primary teeth can be successfully used in a one step procedure. SSCs placed immediately after FP significantly increased FP success vs. FP followed by IRM temporary (P = 0.01).

[Pituitary system with special reference to pituitary antibodies].

Amino et al. postulated a postpartum autoimmune thyroid syndrome and Sugiura et al. established an assay for detecting antibodies to anterior pituitary cell surface membrane (PCSA) by immunofluorescent methods. Using this technique, we attempted to determine the prevalence of PCSA before and after delivery. Studies were conducted with 16 pregnant women without any apparent diseases. Serial measurements of PCSA from the sera of each woman before and after delivery were performed by immunofluorescent methods using AtT-20 cells (mouse ACTH secreting cells) and GH3 cells (rat prolactin and GH secreting cells). Antibodies to AtT-20 cells were detected in 5 of 16 pregnant women at 36 weeks (31.3%), while those to GH3 cells were detected in 3 cases (18.8%). Following delivery, positive antibodies were observed in 12 women (75.0%) at 1 month, 15(93.7%) at 3 months and 13 (81.3%) at 6 months. A similar result also was obtained with GH3 cells. It is possible that some of the patients with positive antibodies have functional abnormalities of the anterior pituitary. The results obtained suggest the presence of postpartum autoimmune endocrine syndrome at the anterior pituitary level.

[Assay of circulating thyroid stimulator determined by I- efflux].

The thyroid stimulating antibodies (TSAb) have been widely used as a clinical marker for diagnosis of hyperthyroidism due to Graves' disease. Immunoglobulins (IgG) of Graves' patients as well as TSH is known to stimulate cAMP production in FRTL-5 cells, a cell-line derived from normal rat thyroid. On the other hand, it has been shown that TSH-induced I- efflux in these cells is associated with production of inositolphosphate as well as intracellular Ca2+ increase. An attempt was made to determine whether Graves' IgG also can mimic such TSH action as a cause of Graves' disease. Polyethyleneglycol precipitated serum fraction of Graves' patients were prepared. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% calf serum, insulin and hydrocortisone for TSH depletion. After preincubation with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions stimulated I- efflux dose-dependently. The mean potency of 12 patient's sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%, which was significantly higher (p < 0.001) than that for 8 normal subjects (110 +/- 16.1%). The results obtained herein indicate that IgG of Graves' patients activate both adenylate aclase-cAMP system and a phospholipid-Ca2 system. I- efflux stimulating immunoglobulins (IESI) activity is a useful marker in making a diagnosis or determining a remission of hyperthyroidism due to Graves' disease.

[Right atrial lipoma with calcification in ascending aorta; report of a case].

A 67-year-old male was diagnosed to have a right atrial tumor by echocardiography incidentally. Computed tomography (CT) indicated a mass which showed very low radiodensity and magnetic resonance imaging (MRI) [T1-weighted] showed the high signal intensity of tumor. We could predict the mass as lipoma. Tumor removal was performed under cardio-pulmonary bypass and under ventricular fibrillation because of the calcification in ascending aorta. Microscopically the tumor was consisted of mature adipose tissue. The postoperative course was uneventful. Cardiac lipomas are rare tumors. CT and MRI are better investigations for preoperative diagnosis. After surgical excision the prognosis is excellent.

[Radiation treatment of metastatic breast cancer].

Breast cancer is rather radiosensitive. A total dose of 40-50 Gy (TDF about 80) is usually sufficient to control most metastatic breast cancer tumors. Radiation treatment should be applied to control tumors which are less responsive to chemo-endocrine therapy, i.e., large tumors or brain metastasis. Five-year survival rates after the start of radiation therapy to the first development of recurrence were 2/16 for local recurrence, 2/5 for supraclavicular node recurrence, 5/16 for bone recurrence and 1/4 for pulmonary recurrence, respectively. The quality of the remaining life of the patient should be the most important factor in deciding radiation treatment.

[Microsomal antibody].

Microsomal antibody is an antibody for the section of a microsome in thyroid cells. There are two methods of measurements of microsomal antibodies, the semiquantitative microtiter particle agglutination test(MCHA) and the high sensitive assay(RIA, ELISA) for the anti thyroid peroxidase(TPO-Ab). MCHA is broadly useful for the diagnosis of autoimmune thyroid diseases and TPO-Ab is mainly measured in the occult autoimmune thyroiditis. TPO-Ab is expensive to compare with MCHA, in Japan. We recommend that MCHA is used in the routine test and TPO-Ab should be measured in the cases of patients with thyroid goiter and MCHA negative.

Multi-Component Structure of Roland-Morris Disability Questionnaire (RDQ), a Lumbago-Specific QOL (Quality of Life) Measure.

Lumbago is one of the most prevalent symptoms in patients with osteoporotic vertebral fracture. Roland-Morris Disability Questionnaire (RDQ) is a quality of life (QOL) questionnaire targeted for evaluating lumbago. Although total score is the usual way of analysis, we have tried to make more use of it by subscale analysis. Forty-four osteoporotic patients were evaluated for their QOL using RDQ and SF-8; a widely accepted generic (non disease-specific) QOL questionnaire. Subscales and summary scores of SF-8 were significantly lower than Japanese norm. Patients with fracture had significantly lower scores including RDQ. Multiple regression analysis has shown that total score of RDQ was significantly contributed by bodily pain as well as other subscales of SF-8. Principal component analysis has revealed that RDQ consists of two components representing general, and mental or social aspect of lumbago. Defining the component structure and determining the procedure to obtain the subscales would make the most use of RDQ, and contribute to the better evaluation of patients with lumbago.