Effects on employees of controlling working hours and working schedules.

BACKGROUND: High levels of control over working time and low variability in working hours have been associated with improved health-related outcomes. The potential mechanisms for this association remain unclear. AIMS: To examine how work-time control and variability of working times are associated with fatigue recovery, sleep quality, work-life balance, and 'near misses' at work. METHODS: Manufacturing sector employees completed a questionnaire that assessed work-time control, work-time variability, fatigue recovery, sleep quality, work-life balance and the frequency of near misses in the past 6 months. Mixed model analysis of covariance and multiple logistic regression analysis tested the main effects of work-time control and variability and their interaction, while adjusting for age, sex, work schedules, and overtime work in the past month. Subscales of work-time control were also investigated (control over daily working hours and over days off). RESULTS: One thousand three hundred and seventy-two completed questionnaires were returned, a response rate of 69%. A significantly higher quality of sleep and better work-life balance were found in the 'high control with low variability' reference group than in the other groups. Significantly better recovery of fatigue was also observed in the group having control over days off with low variability. While near misses were more frequent in the group with high control over daily working hours coupled with high variability compared with the reference group this was not significant. CONCLUSIONS: High work-time control and low variability were associated with favourable outcomes of health and work-life balance. This combined effect was not observed for the safety outcome addressed here.

A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds.

In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.

Intraoperative use of Doppler ultrasound and endoscopic monitoring in the stereotactic biopsy of malignant brain tumors. Technical note.

An intraoperative monitoring tool is described that prevents mechanical injury to intracerebral vessels during stereotactic surgery. The method, which combines pulse Doppler ultrasonography and fiberendoscopy, allowed stereotactic biopsy to be performed without serious intracerebral bleeding in 25 patients with hypervascular malignant brain tumors, 13 with glioblastoma multiforme, five with anaplastic astrocytoma, five with metastatic tumor, and two with malignant lymphoma. The ultrasound apparatus has a built-in fast-Fourier transformation system analyzer and an improved filtering system that provide real-time measurement of blood flow velocity. The source of flow (arterial or venous) could be identified by both real-time sonography and acoustic signal frequencies. It was possible to measure the size and distance of a vessel by adjusting the Doppler signal gain dial from initially waxing to waning sounds, because the acoustic signal was adjusted to the axial flow of each vessel in 0.1-mm steps. Each of three Doppler probes (1 mm, 2 mm, and 3 mm in diameter) fit through the outer cannula of the biopsy needle. Vessels located within 7 mm from the tip of these probes could be detected easily and rapidly, so the biopsy needle could be advanced safely to the desired target in 7-mm steps. If sonograms revealed blood flow, indicating the presence of larger vessels in the intended stereotactic trajectory, the angle of the needle was changed slightly to avoid vascular injury. Because the fiberendoscope was connected to a video processor, the vessel could be visualized at a higher magnification on the video display, unless there was active bleeding. This technically simple and reliable system enhances operative safety while maintaining accuracy.

Development of an analytical method for beryllium in airborne dust by micellar electrokinetic chromatography.

The separation of diacetylacetonato-beryllium [Be(acac)2] from acetylacetone was achieved with micellar electrokinetic chromatography (MEKC) followed by subsequent beryllium analysis carried out using capillary electrophoresis. Analysis using a separation and absorption detector, with a 50 microns capillary cell, could detect approximately 1000 ppb of beryllium in the final sample. Be(acac)2 is a promising reagent for absorption spectrophotometry, because its molar absorption coefficient, (32,000 l mol-1 cm-1) is very large. As the complex and acetylacetone have a similar absorption wavelength, the excess free ligand must removed from the sample to be measured. Acetylacetone is a weak acid with keto-enol tautomerism in aqueous solution. Acetylacetone and neutral Be(acac)2 should be separated with capillary zone electrophoresis (CZE) using a neutral or basic buffer solution as the mobile phase. Although the pH and temperature of the mobile phase were optimized, separation with CZE was interfered with by a portion of acetylacetone. This interfering portion seems to be a neutral keto-form with the same migration time as Be(acac)2. As a neutral species separation method, MEKC with sodium dodecyl sulfate was tried and the separation was completed. The optimum pH value and buffer temperature are pH 7.8 and 15 degrees C, respectively.

T cells bearing gamma/delta T cell receptor and their expression of activation antigen in peripheral blood from patients with Sjögren's syndrome.

T cells bearing gamma/delta T cell receptor (gamma/delta + T cells) and their expression of activation antigen (HLA-DR) or the marker of natural killer (NK) cells (CD56), were examined in the peripheral blood lymphocytes (PBL) from twenty-two patients with Sjögren's syndrome (SS) by three-color flowcytometry to elucidate possible pathological roles of the T cell subset in SS. The frequency of gamma/delta + T cells in PBL was not elevated in SS patients, while that of gamma/delta - T cells, which are T cells bearing the alpha/beta T cell receptor (alpha/beta + T cells), was significantly low in the patients, as compared with 22 healthy controls. We found that the proportions of activated cells (HLA-DR+) in both the gamma/delta + and alpha/beta+T cell subsets were significantly higher in the patients than in the controls. The proportions of HLA-DR+ cells in cells in both patients and controls. Furthermore, the frequency of activated cells in both T cell subsets correlated with the duration of disease in SS patients. However, no difference was found in the percentages of total CD56+ cells, CD56+CD3- cells (true NK cells), CD56+CD3+T cells, CD56+gamma/delta+T cells, or CD56-gamma/delta+T cells between the patients and controls. The above results indicate that immunologic activation in SS patients is progressive and involves both alpha/beta+ and gamma/delta+ T cell subsets.

Accessory molecules expressed on the peripheral blood or synovial fluid T lymphocytes from patients with Sjögren's syndrome or rheumatoid arthritis.

We previously demonstrated that the cells expressed by activation antigens were increased in several T cell subsets from the peripheral blood (PB) and joint fluid (JF) of patients with Sjögren's syndrome (SS) or rheumatoid arthritis (RA). In the present report, we further determined by three-color flow cytometry the homing receptors (Leu8) for peripheral lymph nodes expressed on naive (CD45RA+) or memory (CD45RA-) CD4+ cells and on the two subsets of CD8+ cells (CD11b+ and CD11b-) in the PB and JF from SS and RA patients. In addition, the activation antigens (HLA-DR) and two adhesion molecules, including the alpha-chain of the leukocyte function associated antigen-1 (LFA 1 alpha: CD11a) and its ligand (intercellular adhesion molecule-1: ICAM-1: CD54) expressed on T cells, were compared. We found that CD45RA-CD4+ cells were markedly increased in JF, while CD45RA+CD4+ cells were almost absent. Leu8+ cells were decreased in both CD45RA-CD4+ and CD8+CD11b-cells (cytotoxic T cells) in the JF, and were also decreased in the CD8+CD11b-subset in the patients' PB. Furthermore, activated (DR+) T cells were markedly increased in JF, and the cells expressed more adhesion molecules in both the PB and JF from patients, compared with the DR-T cells. The DR+ T cells therefore are considered to be memory T cells, which are more efficient for cell-to-cell interactions. These observations also suggest that the Leu8- and DR+ T cells with increased adhesion molecules might preferentially migrate into inflammatory tissues, and that naive T cells are being further converted to to memory T cells by in vivo stimulation within the tissues.

T lymphocyte subsets of the infiltrating cells in the salivary gland and kidney of a patient with Sjögren's syndrome associated with interstitial nephritis.

Lymphocyte subsets in the salivary gland and kidney were examined in a 38 years-old female patient with Sjögren's syndrome associated with interstitial nephritis by PAP immunoperoxidase method using monoclonal antibodies. Predominant cells of the infiltrating cells in both tissues were T lymphocytes and most of them were Ia+, OKT4+ cells (activated helper/inducer T lymphocytes). A small number of T lymphocytes were OKT8+ (suppressor/cytotoxic T lymphocytes). Moreover, we found the OKT8+ cells invading the salivary duct epithelial cells. There was no difference in the proportion of lymphocyte subsets of the infiltrating cells between the salivary gland and kidney. A similar pathologic mechanism of tissue damage, therefore, was suggested in both tissues.

Familial Sjögren's syndrome in the Japanese: immunogenetic and serological studies.

Serological abnormalities and HLA haplotypes were studied in a Japanese family of two patients with Sjögren's syndrome (SS) associated with other autoimmune diseases. In contrast to the reports in the U.S.A. and Europe, we found a significant excess of HLA-DRw53 antigen in the family members. Two family members, mother and niece of the probands, had suffered from other connective tissue diseases. Although none of the siblings of probands had manifestations of connective tissue diseases, two siblings had several autoantibodies. No consistent segregation, however, was found between the HLA haplotypes and the serological abnormalities in the relatives. Therefore, HLA alone can not explain the familial clustering of autoimmune diseases including SS and of autoantibodies.

Lymphocyte subsets of the peripheral blood in Sjögren's syndrome and rheumatoid arthritis.

Lymphocyte subsets were determined in the peripheral blood from twenty-three patients with primary Sjögren's syndrome (SS) and sixteen patients with clinically active rheumatoid arthritis (RA) by two-color flowcytometry using various monoclonal antibodies. In both diseases, T-cells (CD3+), suppressor/cytotoxic cells (CD8+) and their cytotoxic subset (CD8+CD11-) were decreased, as compared with thirty-one healthy controls. B-cells (CD 21+ and CD 3-DR+) and activated T-cells (CD 3+DR+) were increased in SS patients. Helper T-cells (CD 4+Leu8-), suppressor-inducer T-cells (CD4+Leu8+), suppressor T-cells (CD8+Leu 15+) and three natural killer (NK) cell subsets determined by both CD16 and Leu7 antibodies did not differ between controls and SS or RA, although Leu7+NK cells were significantly increased in SS patients. In addition, we found that the treatment with low-dose prednisolone decreased B-cells and suppressor-inducer T cells, and increased suppressor T-cells, cytotoxic T-cells and Leu7+NK cells. The results indicate similar changes in the proportion of lymphocyte subsets and suggest immunologically activated and deficient conditions in both diseases. Immunomodulating effects of the treatment with low-dose prednisolone on some of the lymphocyte subsets in patients with these diseases were also supported by the study.

Serum thrombomodulin and anticardiolipin antibodies in patients with systemic lupus erythematosus.

Since thrombomodulin (TM) is a specific cell surface glycoprotein for vascular endothelial cells, serum TM (s-TM) might be a useful marker of endothelial cell damage. Antiphospholipid antibodies (aPL) frequently detected in systemic lupus erythematosus (SLE) have been associated with vascular occlusive diseases. Therefore we measured the s-TM in 60 patients with SLE, in 23 patients with other diseases including aPL (disease control group) and in 26 healthy subjects, by means of an enzyme immunoassay using monoclonal antibodies to human TM. A significant positive correlation was found between s-TM and serum creatinine levels in SLE patients (r = 0.813, p less than 0.001). When the s-TM level was divided by the serum creatinine level (TM/Cr) to exclude the effect of renal clearance, the TM/Cr ratios were significantly increased in SLE patients with active lupus nephritis (LN) compared to those without LN (p less than 0.05). The ratios did not correlate with the presence of aPL or antiphospholipid antibody syndrome (APLS) in SLE patients or in the disease control group, although a weak correlation between the TM/Cr ratios and IgG-anticardiolipin antibody titers was found in the SLE patients without LN (r = 0.449, p less than 0.01). The present results suggest that elevated TM/Cr ratios reflect renal and possibly extra-renal endothelial cell damage in SLE patients with active LN, but that s-TM levels do not associate with the presence of aPL or a history of APLS.

Lupus cystitis and performation of the small bowel in a patient with systemic lupus erythematosus and overlapping syndrome.

We describe a patient with systemic lupus erythematosus (SLE) and overlapping syndrome who had repeated gastrointestinal (GI) symptoms such as nausea, vomiting and malabsorption. With a subacute process, she developed paralytic ileus and contracted bladder, and died of perforation of the ileum. When 13 reported cases with lupus cystitis were reviewed, an extremely strong correlation between GI and urinary tract symptoms was observed, indicating the presence of a unique subgroup of SLE.

Abnormal expression of apoptosis-related antigens, Fas and bcl-2, on circulating T-lymphocyte subsets in primary Sjögren's syndrome.

OBJECTIVE: To clarify the pathological role of the apoptosis-related molecules expressed on peripheral blood (PB) lymphocyte subsets in primary Sjögren's syndrome (SS). METHODS: The levels of apoptosis-regulating proteins, Fas and bcl-2, were determined in the PB lymphocyte subsets from 21 patients with SS and 14 healthy controls by 2-color flow cytometry. RESULTS: In the PB from SS patients, lymphocytopenia, especially CD4+ cell-lymphocytopenia, was prominent. As observed in previous studies, the percentages of CD4+ CD45RA+ cells were lower in the SS patients than in the controls, while activated (DR+) cells were increased in CD4+ cells from the patients. Fas+ cells were also increased in the patients' CD4+ cells and CD8+ cells, but not in their B cells or natural killer cells. Furthermore, we observed several positive correlations among the percentages of activated cells (DR+ cells or CD45RA-cells) and Fas+ cells recognized in the CD4+ and/or CD8+ cells from the patients. On the other hand, intra-cellular bcl-2 proteins measured as mean fluorescence intensity were significantly diminished in the CD4+ cells, CD8+ cells, CD19+ cells, CD45RO+ cells and Fas+ cells from 14 SS patients compared with 12 healthy controls. In addition, the numbers and/or percentages of CD4+ cells and Fas+ cells positively correlated with their expression of bcl-2 in SS patients. CONCLUSION: The abnormal balance between Fas and bcl-2 expression detected in the PB lymphocyte subsets from SS patients relates, at least partially, to the lymphocytopenia observed in the patients.

Abnormalities of pulmonary blood flow during cold exposure in systemic lupus erythematosus.

The aim is to determine whether pulmonary blood flow is altered during cold exposure of the hands in individuals with systemic lupus erythematosus (SLE). Cold exposure was induced by immersion of the hands, one at a time, in 10 degrees C water in nine SLE patients in whom pulmonary fibrosis had been ruled out by a routine examination. Lung perfusion was measured by continuous venous infusion of krypton 81 m. Cold exposure to at least one of the hands caused an 8 to 22% decrease of pulmonary blood flow in five of the nine patients. A 10 to 33% increase in flow developed in three of the nine patients during cold exposure of the hands. We conclude that these abnormalities in pulmonary blood flow during cold exposure were revealed in SLE patients with scarcely any clinical symptoms.

Circadian variations and prednisolone-induced alterations of circulating lymphocyte subsets in man.

We determined the circadian variations and prednisolone (PSL)-induced alterations of circulating lymphocyte subsets in 10 healthy adults by two-color flow cytometry using monoclonal antibodies to various lymphocyte subsets in order to collect fundamental data for monitoring of the subsets in clinical practice. This study first examined the changes of CD5+ B cells, gamma delta+ or gamma delta-T cells, activated (HLA-DR+) CD4+ or CD8+ cells, CD11b+ or CD11b-CD8+ cells, and natural killer (NK) cell subsets (CD16+CD57-, CD16+CD57+, CD16-CD57+), in addition to other subsets described before. Compared with the base line values obtained at 9:00 (AM) on day 1, lymphocytes, total B cells, CD5+ B cells, total T cells, gamma delta-T cells, CD4+ cells, activated CD4+ cells, CD45RA-CD4+ cells, and activated CD8+ cells were significantly increased at 20:00 (PM). However, the numbers of CD45RA+CD4+ cells, CD11b+ or CD11b-CD8+ cells and three NK cells subsets did not show significant circadian variations. After oral PSL (30 mg), which was given at 7:00 (AM) on day 2, lymphocytes and almost all lymphocyte subsets, except for CD16+CD57- cells, were significantly decreased; these changes recovered between 13 and 26 hours after PSL administration. The circadian variations and PSL-induced alterations of lymphocyte subsets were relatively comparable, but PSL administration cause a decrease in a wider range of lymphocyte subsets including relatively corticosteroid-resistant subsets such as CD45RA+CD4+ cells, CD8+ cell and NK cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective determination method for vanadium (V) and vanadium (IV) controlling the pH of media for a solid-liquid extraction column.

Solid-liquid extraction separation based on a speciation method was studied for selective determination of vanadium (IV) and vanadium (V). Both V (IV) and V (V) cations transform to oxo-acid anion along with pH changes in the solution. The pH values for the transition points are different from each other and the difference was utilized in the separation. In the first step, particulate samples are dissolved by strong acids such as 1 M H2SO4 or 85% H3PO4. The pH of the strong acidic sample solutions of V (IV) and V (IV) are adjusted to the range between 3 and 4. In this condition, V (IV) is in the form of cation but V (V) is anion. The pH adjusted solution is applied to an anion exchange column. The solution is expected to contain V (IV) only. The trapped V (V) anion is eluted as VO2+ cation by a pH 1 acid. The author and coworker have already developed an HPLC separation method utilizing this separation concept. However, the HPLC method has some limitations, mainly originated in physical and chemical weaknesses of the HPLC column. In the present study, a firm solid-liquid column is adopted to replace the feeble HPLC column as a separation device. And a simple and convenient pH adjustment technique for making the sample solution is investigated at the same time. With these improvements, the speciation method developed with strong acidic solutions could determine the amount of V (IV) and V (V) in various environmental and biological samples.

Speciation of vanadium(IV) and vanadium(V) using ion-exchange chromatography and ICP-AES.

A speciation method for vanadium(IV) and vanadium(V) is presented that uses a combination of HPLC and ICP-AES. In this method, 1 mM HNO3 solution and 100 mM HNO3 solution were applied in sequence as eluent. A vanadium(IV) and vanadium(V) mixture was injected into a HPLC anion-exchange column; and vanadium(IV) cation was then eluted by 1 mM HNO3, while vanadium(V) oxoacid anion was trapped on the column. After this separation, vanadium(V) was eluted as a cation from the column by 100 mM HNO3. Vanadium was detected by ICP-AES. In this separation, about 15% of vanadium(V) interfered with vanadium(IV), and trace vanadium(IV) interfered with vanadium(V). This interference could be estimated by simple calculation based on standard observations, and the speciation of vanadium(IV) and vanadium(V) was performed. The lower determination limit was 1 microgram/mL, which is insufficient to speciate vanadium sampled by conventional sampling methods in a working environment. However, impurity of the other valent vanadium species in a vanadium(V) reagent can be determined by the present method, which should be valuable in precisely assessing the toxicities of vanadium species.

Estimation of fibrous aerosol deposition in upper bronchi based on experimental data with model bifurcation.

Lung deposition of fibrous aerosol was studied by using a model of the lung bifurcation with dimensions based on the symmetric model A of Weibel. The fibrous aerosols were introduced to the model under steady inspiratory flow conditions. Glass fibers depositing in the daughter tubes and these escaping from them were observed under a scanning electron microscope (SEM). The deposited fractions were calculated for each length and diameter using a bivariate lognormal distribution. In this study the authors propose empirical equations to estimate total deposited fractions of fibrous aerosol at upper bronchi. The dimensionless relationship among deposited fractions Fd, Stokes number St for randomly-oriented fibers and interception parameter I were used to estimate the deposited fraction at arbitrary position in the upper bronchi. The calculation procedure for Fd(St,I) consists of two steps: the determination of the four deposited fractions, Fdn for each In (n=1-4) followed by interpolation or extrapolation from Fdn to find the deposited fraction Fd at a given I. With this procedure, it is possible to determine the deposited fraction Fd in the range of 2 x 10(-3)

Lung lesions induced by intratracheal instillation of vanadium pentoxide powder in rats.

To clarify acute toxicity and histopathological changes in the lung after exposure to V2O5 powder, rats (SD, male, n=66) were observed for 4 weeks after an intratracheal administration of V2O5 powder (geometric mean diameter 0.31 microm, geomertic standard deviation sigmag=2.19) at three doses (0.88, 3.0, 13.0 mg/kg body weight). The histopathological lung lesions were developed dose-dependently, and characterized by exudative inflammation, injury of alveolar macrophages, and swelling and mucous degeneration in the broncho-bronchiolar epithelia. Growth rate of the V2O5 powder-instilled rat was also retarded dose-dependently. The V2O5 powder used was composed of not coagulated but well dispersed particles consisting of vanadium pentoxide of more than 99.8% (w/w) with vanadium tetraoxide of less than 0.2%. The V2O5 powder was found to be 8 times more soluble in an artificial biological fluid "Gamble's solution" than in a pure water. From the present findings as well as those from the related literature, it was inferred that the histopathological lesions induced by the intratracheally instilled V2O5 powder are caused not only by the V2O5 particles per se but also by vanadium ions dissolved from the particles into the lung fluid.

A probable case of chronic occupational thallium poisoning in a glass factory.

A male worker who handled thallium-containing raw material for glass manufacturing over a period of four years complained of alopecia, abdominal pain, diarrhea and tingling in the four extremities. Neurological examination of this patient revealed signs of mild glove-stocking-type polyneuropathy. Lower sensory nerve conduction velocity of the median nerve in the right hand than in the left hand suggested that conduction function in the dominant hand was reduced. The thallium content of the hair, as determined by an ICP-MS method, was 20 ng/g for the patient and 576 ng/g for his successor in the time of 32 months and 13 months, respectively, after they had ceased their glass production work. Those levels of thallium exposure were considered high, compared with the control levels so far reported. The clinical course of signs and symptoms, neurophysiological findings and thallium content of hair suggested that the patient suffered from chronic poisoning due to occupational exposure to thallium-containing dust.

Laboratory measurement of hazardous fumes and gases at a point corresponding to breathing zone of welder during a CO2 arc welding.

Concentrations of fumes, ozone (O3), carbon monoxide (CO), nitric oxide (NO), manganese (Mn) and total and hexavalent chromium (Cr) as well as size distribution of fumes were measured at a point corresponding to the welder's breathing zone during CO2-arc welding, using a welding robot and three kinds of wires. Concentrations of fumes, O3, CO, Mn and total-Cr were found to exceed their corresponding occupational exposure limit (OEL) values, while the concentrations of NO and Cr(VI) were below those OEL levels. Airborne concentration of Mn exceeded its OEL value, and the Mn content was 8 times higher in welding fumes than in the wire. Using an additive equation of OEL and exposure concentration of each hazardous component, health risk in welders with combined exposure to welding fumes and gases was assessed as 18.6 to 46.0 times of OEL, which exceeded the unity. This finding suggests that effective protection of welders from the exposure can be attained by use of the supplied-air respirator or combined use of a dust respirator and a local exhaust system.