Association of low back pain and sleep quality with presenteeism.

BACKGROUND: Low back pain (LBP) and poor subjective sleep quality (SSQ) are major risk factors for presenteeism. However, no studies have investigated whether combined LBP and poor SSQ are associated with presenteeism. AIMS: We aimed to examine whether a combination of LBP and poor SSQ is associated with presenteeism. METHODS: This cross-sectional study included 936 workers (median age, 38 years; men, 89%), with evaluated presenteeism using the work limitations questionnaire. We divided them into 'no presenteeism' and 'presenteeism' categories. The presence of LBP was defined as a numerical rating scale (NRS) score of ≥1 in current pain intensity. SSQ was assessed using a single question regarding whether the participants typically got enough sleep. We categorized the participants into four groups: (i) LBP + poor SSQ, (ii) non-LBP + poor SSQ, (iii) LBP + good SSQ and (iv) non-LBP + good SSQ. Logistic regression analysis was used to investigate the association between presenteeism and the presence of LBP and poor SSQ, adjusting for age, sex, work type, education, marital status, smoking status, body mass index and weekly working hours. RESULTS: The data from 533 participants were used for analysis (median age, 38 years; men, 90%, response rate, 66%). Combined LBP and poor SSQ were significantly associated with presenteeism (non-LBP + poor SSQ: adjusted odds ratio = 0.56, 95% CI 0.32-0.96; LBP + good SSQ: 0.33, 0.20-0.56; non-LBP + good SSQ: 0.29, 0.18-0.48). CONCLUSIONS: Evaluating both LBP and SSQ may be beneficial in considering presenteeism.

An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin.

Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of-care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG-IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG-IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non-fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non-fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non-fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin-combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.

Gender differences in maximum voluntary lip-closing force during lip pursing in healthy young adults.

The objectives of this study were to quantitatively evaluate the gender differences in the lip-closing force (LCF) generated during pursing-like lip-closing movement using a multidirectional LCF measurement system in healthy young adults. In 40 healthy subjects (20 women, 20 men; median age = 26·5 years, range = 22-41 years), LCF was recorded in eight directions during the performance of a voluntary pursing-like lip-closing task in four measurement sessions. The correlations between the total sum of the forces generated in all eight directions [total LCF (TLCF)] and each directional LCF (DLCF) and those between opposing DLCF were statistically analysed. The TLCF obtained from the highly reproducible measurements acquired in the four different sessions was normally distributed in both genders. The TLCF in men was significantly greater than that in women. Among the eight pairs of opposing DLCF, seven pairs of opposing DLCF showed significant correlations in men, while five pairs were significantly correlated in women. In men, no significant difference was observed between opposing DLCF; however, three pairs of opposing DLCF were significantly different in women. The present results quantitatively indicate that there are gender differences in the magnitude and directional specificity of the LCF produced during pursing-like lip-closing movement in healthy young adults.

Asymmetric lip-closing forces in children with repaired unilateral cleft lip and/or palate.

The objectives of this study were to estimate the effects of cleft lip and/or palate (CLP) repair on the multidirectional lip-closing forces (LCF) produced during maximum voluntary pursing-like lip-closing movement in children. Thirty Japanese children were divided into the control group and repaired unilateral CLP (RUCL) group, which was subdivided into the unilateral cleft lip and/or alveolus (UCLA) and the unilateral cleft lip and cleft palate (UCLP) groups. The maximum voluntary LCF were recorded in eight directions. No significant differences in any of the directional LCF (DLCF) or total LCF were observed between RUCL and control groups. Symmetrical DLCF were seen in the oblique directions on both sides of the upper lip in the control group, while the oblique DLCF on the non-cleft side was significantly greater than that on the cleft side in RUCL group. Furthermore, symmetrical vertical DLCF were observed in the upper and lower directions in control and UCLA groups, while the vertical DLCF obtained from the lower direction was significantly greater than that obtained from the upper direction in UCLP group. These results indicate that children with repaired CLP display impaired directional specificity, which may cause secondary deformities. These findings aid our understanding of the pathology of secondary deformities in CLP patients after primary surgery for cleft lip or palate. We propose that quantitative assessments of lip-closing function based on the directional specificity of the multidirectional LCF produced during maximum voluntary pursing-like lip-closing movement are useful for assessing the nature of lip-closing dysfunctions.

Regulatory relationship between tactile sensation at the vermilion of the lips and lip-closing force.

The objectives of this study were to identify the regulatory relationship between tactile sensation at the vermilion of the lips and the output of pursing-like lip-closing force (LCF), as measured by a multidirectional LCF measurement system. Thirty-six healthy subjects were divided into Anaesthesia and Vaseline groups. The tactile detection threshold (TDT) at six sites on the vermilion and the maximum voluntary LCFs in eight directions were recorded before and during partial or whole application of the agent and 6 h after whole application (Recovery). Five per cent lidocaine gel and Vaseline was applied to the vermilion in the Anaesthesia and Vaseline groups, respectively. These agents were applied to either the right part of the vermilion of the lower lip (Partial) or the whole vermilion (Whole). Partial application of 5% lidocaine gel significantly decreased the magnitudes of six of eight directional LCFs, while it only increased the TDT at one site. The subsequent whole application of 5% lidocaine gel did not affect the magnitude of the LCFs in five of these six directions although its application increased the TDTs at all sites. These reductions in LCF were reversed after recovery from surface anaesthesia. Vaseline application did not affect either TDT or LCF in any conditions. We concluded that tactile sensation at the vermilion of the lips is related to the output of LCF, without any particular directional specificity. The present results suggest the presence of a common synaptic drive ordering the pursing of the relevant muscles.

Reliability of novel multidirectional lip-closing force measurement system.

This study aimed to quantify the directional specificity of multidirectional lip-closing force (LCF) and evaluate the reliability of multidirectional LCF measurements made using a novel system. In fourteen healthy subjects (seven females, seven males, median age = 28 years), LCFs in eight directions and electromyograms (EMGs) from four parts of the orbicularis oris muscles (OOM) were recorded during voluntary pursing-like lip closure tasks. The quantitative reliability was assessed from repeated measurements of the LCFs in the eight directions and from summed values for all eight directions [total lip-closing force (TLCF)]. The intra- and inter-investigator reliabilities for TLCF were assessed by the interclass correlation of the measurements by the same investigator and two investigators, respectively. Lip-closing forces showed directional specificity in vertical, horizontal and oblique directions but those in oblique and horizontal directions were symmetrical bilaterally. The quantitative reliability of measurements was between 0·735 and 0·948 in the eight directions and that of TLCF was 0·934. Interclass correlations of intra- and inter-investigator reliabilities were 0·96 [lower limit of 95% confidence interval (95% LL), 0·87] and 0·96 (95% LL, 0·91), respectively. The intra- and inter-investigator differences of measurements were randomly distributed in the whole range of measurements. The 95% confidence intervals of these differences were significantly narrower than those of the limits of agreement (mean ± 1·96 s.d.). In 13 subjects, Pearson's correlation coefficients between LCF and EMGs from OOM were above 0·95. We conclude that this system has a reasonable quality and reliability for quantitative measurements of multidirectional LCF for evaluating lip functions.

Histomorphometric Evaluation of Cartilage Degradation using Rabbit Articular Chondrocytes Cultured in Alginate Beads - Effects of Hyaluronan.

OBJECTIVE: A 3-dimensional alginate bead culturing method using rabbit articular chondrocytes was studied for the screening of the effectiveness of drugs for articular diseases. DESIGN: The beads cultured with IL-1ß, TGF-ß, and Hyaluronan (HA) were evaluated histochemically with Alecian blue and immunohistochemically with CS-56 antibody. Chondrocytes in alginate beads were arbitrarily classified into four groups: 1) chodrocyte surrounded with cell-associated matrix (CAM) in which proteoglycan (PG) was positively stained (PG-possitive chondrocyte); 2) chondrocyte with PG-negative CAM; 3) PG-positive CAM alone, and 4) PG-negative CAM alone. Total sulfated GAG concentrations in the culture media were quantitated by dimethylmethylene blue (DMMB) assay. ProMMP-3, TIMP-1 and -2 concentrations in the culture media were determined by sandwich enzyme immunoassays. RESULTS: Significant increase of PG-nagative cells were immunohistochemically found by IL-1ß stimulation. The pretreatment with TGF-ß almost fully suppressed those increase of PG-negative cells by IL-1ß. Both GAG and proMMP-3 concentrations in the culture media were significantly increased after IL-1ß stimulation. There were no significant differences in both TIMP-1 and TIMP-2 concentrations in the culture media with or without IL-1ß stimulation. 800-kDa HA reduced significantly the number of PG-negative cells and proMMP-3 concentration in the culture media, but showed no effects on the concentrations of both TIMPs. CONCLUSIONS: Because this 3-dimensional chondrocyte culture in alginate beads is close to in vivo conditions, this method can be used for evaluation of the effectiveness of novel drugs for articular diseases.

Heel bone ultrasound predicts non-spine fracture in Japanese men and women.

A number of prospective studies in the USA and Europe have demonstrated that quantitative ultrasound (QUS) measurements predict fracture risk. To our knowledge, there has been no such study in a Japanese population, and very few studies have measured the prognostic value of QUS measurements among men, even in the USA and Europe. We performed a three-center prospective study to investigate the relationship between baseline heel QUS measurements and non-spine fracture risk. There were 4,028 subjects (1,004 men and 3,024 women), 67.5+/-8.9 years [mean +/- standard deviation (SD)] of age), who underwent heel QUS (Achilles device) at three centers between 1993 and 2000. In 2002, the subjects were mailed a standardized questionnaire that asked about their history of fracture. The mean follow-up period was approximately 5 years. The Achilles measured speed of sound (SOS) and broadband ultrasound attenuation (BUA). We used Cox regression analysis to determine the hazard ratio (HR), using weighted coefficients. SOS, BUA, and stiffness index (SI) predicted self-reported hip, wrist, and total non-spine fractures. After we had adjusted for age, gender, and weight, the HRs of total non-spine fracture were 1.54 [95% confidence interval (CI) 1.39-1.69], 1.53 (1.37-1.70), and 1.80 (1.62-1.98) for 1 SD decrease in SOS, BUA, and SI, respectively. In men, SOS and SI also predicted total non-spine fractures with HRs similar to those in women. The HR of prediction for hip fracture by SOS and SI was better in the short term than in the long term, and the prediction for hip, wrist, and non-spine fracture remained significant between 5 to 10 years of follow-up. Measurements obtained from heel QUS predicted non-spine fracture in Japanese men and women, and the HRs of Japanese of both genders was similar to the risk ratio (RR) of Caucasian men and women. QUS parameters can predict hip, wrist, and non-spine fracture up to 10 years.

Detection of Pneumocystis carinii by DNA amplification in patients with connective tissue diseases: re-evaluation of clinical features of P. carinii pneumonia in rheumatic diseases.

OBJECTIVES: We evaluated the polymerase chain reaction (PCR) detection of Pneumocystis carinii DNA in induced sputum of patients with connective tissue diseases and assessed the clinical features of patients positive for P. carinii. METHODS: Sputum was induced by nebulization in 29 in-patients with various connective tissue diseases who presented with symptoms suggestive of P. carinii pneumonia (PCP), and was examined by PCR. RESULTS: Detection of P. carinii DNA by PCR was significantly more sensitive than cytology; 54.5% patients were positive by PCR and only 4.5% by cytology. The prevalence of PCP was higher than previously considered and was especially high in patients receiving > 30 mg/day prednisolone with or without other immunosuppressants. P. carinii-positive patients had significant lymphocytopenia and a low serum IgG level compared with P. carinii-negative patients. P. carinii disappeared within 7-10 days after therapy with trimethoprim/sulfamethoxazole. CONCLUSION: We propose that the use of PCR for detection of P. carinii using induced sputum is a useful and non-invasive method that has high sensitivity and specificity for the early diagnosis of PCP.

Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for degradation products of type I collagen C-tlopeptides.

BACKGROUND: The Elecsys beta-CrossLaps serum assay measures type I collagen degradation fragments (beta-CTx) that contain the beta-isomerized octapeptide EKAHD-beta-GGR. We investigated the analytical performance of the assay and changes in beta-CrossLaps in patients with metabolic bone diseases. METHODS: The electrochemiluminescent sandwich immunoassay uses two monoclonal antibodies directed against different regions of the linear EKAHD-beta-GGR. RESULTS: beta-CrossLaps (beta-CTx) immunoreactivity was stable in serum and plasma stored at 4 degrees C for 24 h or at room temperature for 4 h, and it did not decrease appreciably in samples stored at -30 degrees C for 12 weeks. Nine cycles of repeated freezing-thawing did not affect serum beta-CTx. The intra- and interassay imprecision (CVs) for four samples was < or = 2.6% (n = 10) and < or = 4.1% (n = 10), respectively. The mean day-to-day biological variation (CV) was 20% in 10 postmenopausal women (n = 10 days). Serum beta-CTx and osteocalcin were correlated in patients with hyperparathyroidism (r = 0.796; P <0.0001; n = 28), chronic renal failure on hemodialysis (r = 0.784; P = 0.0003; n = 16), hypoparathyroidism (r = 0.950; P = 0.0001; n = 11), and pseudohypoparathyroidism (r = 0.987; P = 0.130; n = 4). Serum beta-CTx decreased by 47.4% +/- 8.8% (mean +/- SD) and 60.7% +/- 6.5% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy in 34 women. These decreases were greater than the decreases in urinary excretion of deoxypyridinoline (31.8% +/- 3.9% and 38.1% +/- 4.4%, respectively) or pyridinoline cross-linked C-terminal telopeptide of type I collagen (15.9% +/- 3.9% and 16.9% +/- 4.6%, respectively). CONCLUSIONS: The Elecsys beta-CrossLaps serum assay provides a potentially useful tool for assessing bone resorption state, including its response to estrogen replacement therapy.

The three-dimensional architecture of retinal blood vessels in KK mice, with special reference to the smooth muscle cells and pericytes.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branches were surrounded by atypical smooth muscle cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes.

[Biochemical markers for bone metabolism in severe osteoporosis].

Degrees of changes in biochemical bone markers following osteoporosis-related fractures depend on types and severity of fractures and markers selected. Although immobilization is known to raise values of bone resorption markers, it is likely that incomplete immobilization commonly induced by fracture has little impact on systemic bone metabolism. Since marked increase in bone markers in patients with osteoporosis implies presence of underlying diseases and/or "occult" fracture other than "high turnover" osteoporosis, clinician should make efforts to explore secondary cause of increased systemic bone metabolism and fractures occurred locally.

[Efficacy and safety assessments of pharmaceutical agents].

There have been several clinical end-points available for efficacy assessments of pharmaceutical agents for osteoporosis in clinical trials. In such trials with alendronate and risedronate, new generation of bisphosphonates, either bone mass measurements or incidental fractures assessments are primary end-points. Markers for bone turnover are frequently measured in trials with protocols for dose finding and action mechanisms of agents. Bone biopsy and bone histomorphometry are needed for assessments of long-term safety. Therefore, multiple clinical trials should be completed to establish efficacy and safety of bisphosphonates.

[Bisphosphonate and markers for bone metabolism].

Bisphosphonates (BPs) are widely applied to clinical use as first lines of therapeutic agents for metabolic bone diseases such as osteoporosis and Paget's disease of bone. Data on changes in markers for bone metabolism and their abilities to predict treatment efficacy have been accumulated in these bone disease and recently a guideline for adequate use of markers for metabolism in osteoporosis has been proposed. In the use of BPs, particularly ones containing amino residuals in their structures of side chains, attention should be paid to the choice of markers for bone metabolism since their degrees of changes depends on markers selected.

[Intravenous pamidronate delivery to a case with multiple bone metastasis of breast cancer].

MRI and bone scintigraphy of a 64-year-old woman admitted with severe lumbago showed multiple metastatic bone cancer mainly on vertebrae, and breast cancer was found by mammography. After enucleation was performed, treatment with tegafur, tamoxifen and oral bisphosphonate/etidronate was started. Because symptoms associated with bone metastasis worsened, we began to administer 30 mg of pamidronate intravenously every 4 weeks. Since that time the extent of metastasis has been inhibited, resulting in ameliorated lumbodynia and improved quality of life.

Electroretinographic assessment of early changes in ocular siderosis.

We examined a patient with an iron intraocular foreign body and recorded electroretinograms (ERGs) before and after the removal of the foreign body by vitrectomy. The amplitudes of the rod and cone ERGs and the oscillatory potentials (OPs) in the injured eye were reduced before the operation. In addition, the photopic on-responses (b wave) were more reduced than off-responses (d wave). One year after surgery, the amplitudes of the rod, cone and photopic on- and off-responses were markedly improved to within the low normal limit. However, the OP amplitudes remained unchanged with lower values. These findings suggest that iron retinotoxicity leads to a dysfunction of all layers but the changes may be reversible in the early period of the disease. The late period iron toxicity produces more severe damage to the inner retina than the outer retina.

Pathophysiology and diagnosis of primary hyperparathyroidism--strategy for asymptomatic primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia due to excessive secretion of PTH, is usually associated with hypophosphatemia and elevated serum chloride. Although PHPT was often complicated by renal stone disease and osteitis fibrosa in the past, routine screening of serum calcium (Ca) and development of sophisticated assay of parathyroid hormone have contributed to earlier detection of asymptomatic PHPT (APHPT). The proportion of APHPT patients, who have a mild elevation of serum Ca levels, usually within 1.0 mg/dL above the upper limit of normal, rose from 10-20% to approximately 45% of all PHPT patients in 1990-1995 in our clinic. Although it has been reported that the prevalence of PHPT is about 0.1% of the American population, the prevalence of PHPT appears to be far less in the Japanese population. Determination of a strategy for the increasing number of APHPT patients, is a pressing need but has yet to be accomplished. Treatment with bone antiresorptive drugs has met with some success, although the long-term efficacy of this treatment is not clear. The therapeutic effects of Ca-sensing receptor agonists appear promising.