Restless legs syndrome is associated with headache-related disabilities in patients with migraine: a prospective 7-year follow-up study.

BACKGROUND AND PURPOSE: No prospective study has evaluated the impact of restless legs syndrome (RLS) on clinical factors in patients with migraine. We planned a prospective study to assess the impact of RLS comorbid status on clinical factors in patients with migraine. METHODS: A total of 101 patients with migraine who were evaluated for RLS twice at 7-year intervals in a university hospital setting were included in this study. The RLS group was defined as positive for RLS at either baseline or follow-up and the non-RLS group was defined as negative for RLS at both baseline and follow-up. The Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale were administered to all patients. RESULTS: The RLS prevalence was 16.8% at baseline and 20.8% at follow-up. Compared with the non-RLS group (n = 27), the RLS group (n = 74) showed a significantly higher rate of smoking and higher MIDAS and BDI-II scores at 7-year follow-up. A significant reduction in MIDAS and BDI-II scores at 7-year follow-up compared with those at baseline was observed in the non-RLS group, but not in the RLS group. The non-RLS group showed a significantly lower MIDAS score at 7-year follow-up than the RLS group after adjusting for confounding variables such as age, gender, smoking status, Epworth Sleepiness Scale and PSQI scores using analysis of covariance. The persistent RLS group (n = 11) (positive for RLS at both baseline and follow-up) showed a significantly higher rate of smoking and increased MIDAS, BDI-II and PSQI scores compared with the non-RLS group (n = 74) at 7-year follow-up. CONCLUSION: Our prospective study showed that RLS had a significant impact on headache-related disability in patients with migraine.

Risk factors of recurrent sickness absence due to depression: a two-year cohort study among Japanese employees.

PURPOSE: Depression has a high recurrence rate among employees. There have been few studies investigating risk factors for recurrent sickness absence due to depression after return to work (RTW). The objective of this study was to identify potential risk factors. METHODS: Subjects were 540 full-time employees at the biggest telecommunication company in Japan who returned to work from April 2002 to March 2008 after their first leave of absence due to depression. The Cox proportional hazard model was employed to find risk factors for recurrent sickness absence by analyzing variables including demographic, work-related and work environmental factors. RESULTS: Of 540 study subjects, 200 employees (37.0 %) experienced recurrent sickness absence due to depression after RTW within the follow-up period. Higher organizational job demand evaluated by the Brief Job Stress Questionnaire (BJSQ) was found to be a risk factor (OR 1.46, 95 % CI 1.01-2.10) for recurrent sickness absence due to depression adjusted for confounding factors. CONCLUSIONS: High organizational job demand (evaluated by BJSQ) is a risk factor for recurrent sickness absence due to depression after RTW.

Heavy overtime work and depressive disorder among male workers.

BACKGROUND: The association between overtime and depression is unclear and very few studies have examined the association between heavy overtime work, i.e. working more than 60 h per week, and depression. AIMS: To examine the association between heavy overtime work and the onset of depressive disorder among male workers. METHODS: A 1-year follow-up cohort study of male workers in a manufacturing company in Japan, between 2008 and 2009. Working hours, depressive disorder, assessed by the Center for Epidemiologic Studies Depression (CES-D) Scale (score ≥16 points), and covariates were measured at baseline and at follow-up. Participants who had depressive disorder at baseline were excluded. RESULTS: At follow-up, 1194 participants aged between 18 and 71 years were analysed. Multiple logistic regression analysis revealed that the odds ratio for the new onset of depressive disorder was 4.5 (95% CI 1.8-11.1) times higher for employees working >60 h per week than for those working ≤50 h per week, when adjusted for age, lifestyle factors, work-related characteristics and socio-demographic characteristics at baseline and working hours at follow-up. However, the correlation between working 50.1 to 60 h per week and depressive disorder was not significant. The trend test of depressive disorder among groups by working hours was significant (P < 0.01). CONCLUSIONS: Heavy overtime work is a risk factor for the new onset of depressive disorder in this population of male workers. Working >60 h per week may be the cut-off to screen for high-risk groups who need preventive action against depressive disorder.

Oral management with polaprezinc solution reduces adverse events in haematopoietic stem cell transplantation patients.

The aim of this study was to analyse the effects of gargling with and then swallowing PPAA (polaprezinc in polyacrylic acid solution), in addition to regular oral management, on patients with a haematopoietic neoplasm scheduled for haematopoietic stem cell transplantation (HSCT). A total of 120 patients scheduled for HSCT during the years 2006-2016 were recruited. Patient background, oral adverse events, the incidence and severity of systemic adverse events (sepsis/septic shock, acute graft-versus-host disease (GVHD) after transplantation), and outcomes (survival/death) were compared between groups treated with and without PPAA. The severities of oral adverse events (oral mucositis, oral pain, and dysgeusia) were significantly lower in patients treated with PPAA. There was no significant difference in the incidence of febrile neutropenia (P=0.622) or sepsis/septic shock (P=0.665) as systemic adverse events. The severity of allograft-induced acute graft-versus-host disease (GVHD) was significantly lower in the PPAA group (P=0.011). There was no significant difference in outcome between the two groups (P=0.285). Within the limitations of the study design, it may be concluded that oral management with PPAA reduces adverse events in HSCT. Oral management with concomitant use of PPAA decreased oral adverse events and reduced the systemic complication of GVHD.

Synergistic effect of progesterone on prostaglandin E modulation of the mitogenic response of human peripheral lymphocytes.

The combined effects of prostaglandins of the E series (PGE) and progesterone (P), both of which are found to increase locally in the secretory endometrium, were studied in mitogen-stimulated cultures of lymphocytes from human peripheral blood. When added separately to lymphocyte cultures, both PGE and P produced a concentration-dependent inhibition of T-cell, but not B-cell, mitogenesis. If added together, these agents caused a much greater inhibition of T-cell mitogenesis, with marked synergy, than that observed with either agent alone. The synergistic inhibition was achieved with endometrial concentrations of PGE and P. The kinetics of PGE- and P-mediated inhibition investigated at various times during lymphocyte activation indicated that both agents affected the early events of T-cell mitogenesis. PGE- and P-inhibition of T-cell mitogenesis were shown to be reversible phenomena by washing the cells treated with these agents. These results suggest that elevated levels of PGE and P in the secretory endometrium, acting synergistically in inhibiting the proliferative response of T cells, may participate in facilitating implantation of histoincompatible fetal tissue in the maternal uterus as non-specific local immunosuppressive factors.

Effects of endometrial IgG on PHA-induced T cell mitogenesis.

To clarify the characterization and immunologic mechanisms of endometrial extract as a suppressive factor in tissues of the implantation site, the effects of endometrial extract and IgG on mitogen-stimulated cultures of lymphocytes from human peripheral blood were investigated. The inhibitory activity of endometrial extracts was observed to be augmented markedly in the secretory phase of the menstrual cycle as compared to the proliferative phase. Secretory endometrial extract, at a concentration of 0.6 mg protein/ml, caused 50% suppression of PHA-induced lymphocyte blastogenesis (PHA-BL). Column fractionation of endometrial extract on a Sephadex G-200 column showed a profile with three peak fractions and demonstrated that the 2nd peak fraction was mainly responsible for the suppression of PHA-BL. The 2nd peak fraction was shown to contain IgG by the method of immunodiffusion with anti-human IgG. The 2nd peak fraction from which IgG was removed with affinity chromatography caused significant depression of PHA-BL. Furthermore, the Fc fraction of IgG showed marked suppression compared to the F(ab')2 fraction. From these results, we suggest the possibility of an endogenous substance containing IgG as a suppressive factor which is implicated in the suppression of T cell function. The Fc fragment seemed to be the major fraction possessing such suppressive activity.

Lecithins enhance leukotriene production from white cells.

36 x 10(7) WBC were isolated from 120 ml heparinized venous blood by 5% dextran T-500 sedimentation. 20 mg egg lecithin and 20 mg dipalmitoyl lecithin were respectively pretreated in 2 ml 0.15 M Tris buffer by vibration and sonication. WBC were incubated with the pretreated lecithins for 20 min. Leukotrienes (LTs) were identified by HPLC and bioassay, and quantified with an RIA Kit. Crude incubation medium of both lecithin groups caused guinea pig ileum contractions which were antagonized with FPL55712. Incubation media were partially purified with Bond elut C18. Purified samples of both lecithin groups showed LTC4 and LTD4 peaks on HPLC. LTC4 production (pg/10(7) WBC, M +/- SD) was 194.5 +/- 61.7 (n = 5) in control group, 348.9 +/- 95.4 (n = 6) in dipalmitoyl lecithin group, 543.8 +/- 105.6 (n = 6) in egg lecithin group and 105.62 +/- 63.2 (n = 6) in AA-861 + dipalmitoyl lecithin group. LTC4 production of both lecithin groups was significantly higher than that of control group (P less than 0.01 in dipalmitoyl lecithin group and P less than 0.001 in egg lecithin group). Both egg lecithin and dipalmitoyl lecithin enhanced LT production from WBC. LT production was suppressed in the presence of AA-861. The mechanism of the enhancement in LT production is unclear, but these lecithins are apparently not substrates because dipalmitoyl lecithin contains no arachidonic acid.

[Pharmacokinetics of cefuzonam in peripheral venous serum, uterine arterial serum and intrapelvic female organs].

Concentrations of cefuzonam (CZON) in peripheral venous serum, uterine arterial serum and intrapelvic female organs of 29 women undergone simple total hysterectomy were determined by bioassay, using the cylinder-plate diffusion method. With an intravenous injection of CZON 1 g, the concentration at time 0 (Cp0) of peripheral venous serum and uterine arterial serum were 148.1 micrograms/ml and 155.4 micrograms/ml, respectively. Biological half-lives (T 1/2) of CZON were 1.07 hours in peripheral venous serum and 1.02 hours in uterine arterial serum. Concentrations in peripheral arterial serum were higher than 1.0 micrograms/ml at 4 hours after injection and remained at higher levels than minimal inhibitory concentrations necessary for most Escherichia coli strain for at least 4 hours. Concentrations of CZON in female organs were kept as high as peripheral venous serum, and ratios of CZON concentrations in uterine tube and endometrium to that in peripheral venous serum were 0.74 +/- 0.34 and 0.44 +/- 0.25, respectively. Since CZON is characterized by potent antibacterial activity and broad spectrum, it should be effective for infectious diseases of the female uro-genital tract.

Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study.

Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a microdose of atorvastatin along with probe substrates for OATPs (pravastatin) and CYP3A4 (midazolam) was orally administered to eight healthy volunteers. The pharmacokinetics of this cocktail was observed at baseline, after an oral dose of 600 mg rifampicin (an inhibitor of OATPs), and after an intravenous dose of 200 mg itraconazole (a CYP3A4 inhibitor). Rifampicin increased the pravastatin dose-normalized area under the plasma concentration-time curve (AUC) (4.6-fold), and itraconazole significantly increased the midazolam dose-normalized AUC (1.7-fold). The atorvastatin dose-normalized AUC increased 12-fold when coadministered with rifampicin but did not change when coadministered with itraconazole. These results indicate that hepatic uptake via OATPs makes the dominant contribution to the hepatic elimination of atorvastatin at a subtherapeutic microdose.

Absolute detection efficiencies of a microchannel plate detector for 0.5-5 keV neutrals.

The absolute detection efficiencies of a microchannel plate detector for neutral atoms were measured using the coincidence method for neutralized incident ions and ionized target atoms in electron capture collisions. This method does not require knowledge of the absolute electron-capture rates for determination of the detection efficiencies. Results for Ne, Ar, and Kr atoms at energies of 0.5-5 keV are reported. The detection efficiencies for all atomic species increase concomitantly with increasing impact energy and plateau at the efficiency of about 50%. For low impact energies, the efficiency decreases with increasing mass of the impact atom at a given energy.

[Placental implantation as the cause of breech presentation].

The ultrasonographic study of 5294 singleton pregnancies between the 16 and 41 gestational weeks and 47 breech presentations at term revealed the following: The placenta was found in the mid-anterior or mid-posterior region of the uterus in 60.9 to 74.0%. In 12.8 to 18.7% of cases, the placenta was implanted in the fundal region before gestational week 28, but thereafter it was found in the cornual region in 13.8 to 19.1%. Of 47 cases with breech presentation at term, the placenta was implanted in the cornual region in 28, in the fundus in 7, in the lateral in 6, and in the mid-anterior or mid-posterior in another 6. In gestational weeks from 16 to 19, the breech presentation was found in 38% when the placenta was implanted in the cornual region, in 50% when it was implanted in the lateral region, 52.8% in the fundus, and 47.2% in the middle, with no significant difference in the incidence of occurrence. However in gestational weeks from 36 to 41, the incidence was 20.2, 6.4, 9.0 and 1.1% respectively and the spontaneous version rate was significantly higher when the placenta was implanted in the middle region than in others (p less than 0.01). The author has concluded that the breech presentation in single pregnancy is caused by the placental position; when it markedly indents and changes the inverted pear shape of the amniotic cavity, the spontaneous fetal cephalic version is inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)