Impact of menopausal symptoms on presenteeism in Japanese women.

BACKGROUND: Menopausal symptoms are common among middle-aged women. Working women with severe menopausal symptoms are more likely to experience presenteeism-a condition where employees continue to work despite feeling unwell. However, it remains unclear as to which specific symptoms women experience during the menopausal transition and postmenopausal periods that primarily contribute to presenteeism. AIMS: To evaluate the associations between types of menopausal symptoms and presenteeism among Japanese women. METHODS: A cross-sectional study of 4000 women aged 40-59 years who were currently working was conducted in Japan in September 2022. We used an online self-administered questionnaire that included items on demographic characteristics, the Menopause Rating Scale for measuring menopausal symptoms and the Work Functioning Impairment Scale for measuring presenteeism. Logistic regression analysis was performed. RESULTS: Women with severe overall menopausal symptoms had 12.18-fold (95% confidence interval [CI] 9.09-16.33, P < 0.001) increased odds of presenteeism compared with those without symptoms. Participants with psychological symptoms also had significantly higher presenteeism (severe: odds ratio: 9.18, 95% CI 6.60-12.78, P < 0.001). However, after controlling for psychological symptoms, there were no significant associations between somatic and urogenital symptoms and presenteeism. CONCLUSIONS: The results indicate that menopausal symptoms, especially psychological symptoms, have a significant impact on presenteeism among Japanese women. Organizations need to address menopausal symptoms in the workplace, with an emphasis on reducing work-related stress for women with menopausal symptoms.

Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan.

OBJECTIVE: The objective of this study was to investigate possible differences in treatment responses between two categories for the onset of lupus nephritis. METHODS: We performed a multicentre, retrospective cohort study of class III-V lupus nephritis patients diagnosed between 1997 and 2014. The renal responses to initial induction therapy were compared between patients who developed lupus nephritis within one year from diagnosis of systemic lupus erythematosus (early (E-) LN) and the remainder (delayed (D-) LN) using the Kaplan-Meier method. We determined the predictors of renal response as well as renal flares and long-term renal outcomes using multivariate Cox regression analyses. RESULTS: A total of 107 E-LN and 70 D-LN patients were followed up for a median of 10.2 years. Log-rank tests showed a lower cumulative incidence of complete response in D-LN compared with E-LN patients. Multivariate analysis identified D-LN (hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.33-0.70), nephrotic syndrome at baseline, and a chronicity index greater than 2 as negative predictors of complete response. D-LN patients were more likely to experience renal flares. D-LN (HR 2.54, 95% CI 1.10-5.83) and decreased renal function were significant predictors of chronic kidney disease at baseline. CONCLUSION: D-LN was a predictor of poorer treatment outcomes, in addition to renal histology and severity of nephritis at lupus nephritis onset.

Superparamagnetic iron oxide-enhanced MRI at 3 T for accurate axillary staging in breast cancer.

BACKGROUND: The aim of this study was to evaluate whether MRI at 3 T with superparamagnetic iron oxide (SPIO) enhancement is an accurate and useful method for detecting metastases in sentinel nodes identified by CT-lymphography (CT-LG) in patients with breast cancer. The results were compared with those obtained using CT-LG alone and diagnosing metastasis according to size criteria. METHODS: Patients with clinically node-negative breast cancer were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MRI at 3 T. Sentinel node size was measured on CT-LG, and a node larger than 5 mm in short-axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. RESULTS: Sentinel nodes were identified successfully by CT-LG in 69 (99 per cent) of 70 patients. All 19 patients with a finding of metastasis in sentinel nodes at pathology were also shown to have metastases on MRI. Forty-eight of 50 patients with non-metastatic sentinel nodes diagnosed at pathology were classified as having non-metastatic nodes on MRI. On a patient-by-patient basis, the sensitivity, specificity and accuracy of MRI for the diagnosis of sentinel node metastases were 100, 96 and 97 per cent; respective values for CT-LG were 79, 56 and 62 per cent. The specificity and accuracy of MRI were superior to those of CT-LG (P < 0·001 and P = 0·002 respectively). CONCLUSION: SPIO-enhanced MRI at 3 T is useful for accurate diagnosis of metastatic sentinel nodes, indicating that sentinel node biopsy may be avoided in patients with breast cancer who have non-metastatic sentinel nodes on imaging.

Circulating levels of maternal plasma cell-free pregnancy-associated placenta-specific microRNAs are associated with placental weight.

The aim of this study was to investigate the relationship between plasma concentration of cell-free pregnancy-associated placenta-specific microRNAs and clinical variables (placental weight, maternal body mass index, and neonatal birth weight). Circulating levels of cell-free pregnancy-associated placenta-specific microRNAs (miR-515-3p, miR-517a, miR-517c and miR-518b) in maternal plasma were measured by quantitative real-time RT-PCR in sixty-two pregnant women. The levels of cell-free pregnancy-associated placenta-specific microRNAs were significantly associated with placental weight, but not associated with body mass index or birth weight. Therefore, the measurement of cell-free pregnancy-associated placenta-specific miRNAs levels in maternal plasma may reflect the pregnancy status related to placenta volume.

Characterization of 5C11-positive activated interferon-producing cells in patients with systemic lupus erythematosus.

OBJECTIVE: 5C11 antibody is a novel monoclonal antibody against human BST2 and can be used to detect activation of interferon-producing cells (IPCs). Activated IPCs, which produce large amounts of interferon-α (IFNα), are considered to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characterization of 5C11-positive cells in patients with SLE. METHODS: The proportions of 5C11-positive cells among blood dendritic cell antigen 2 (BDCA-2)-, CD3-, CD19- and CD14-positive cells in peripheral blood from SLE patients (SLE-PBMCs) and healthy controls (control-PBMCs) were analyzed by flow cytometry. The effect of 5C11 antibody on IFNα production from SLE-PBMCs under stimulation with cytosine-phosphate-guanosine (CpG2216, bacterial oligonucleotide motif) was also examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The proportions of 5C11-positive cells among BDCA-2-, CD3- and CD19-, but not CD14-positive cells in SLE-PBMCs were significantly increased compared to those in control-PBMCs (p < 0.0001, all). Especially, the number of 5C11-positive cells among BDCA-2-positive cells was significantly increased in SLE-PBMCs by about six-fold compared to that in control-PBMCs (p < 0.0001). 5C11 antibody inhibited IFNα production by SLE-PBMCs induced by CpG and the inhibition rates was 27% (p < 0.001). CONCLUSION: SLE patients had a significantly higher proportion of 5C11-positive cells among CD3 and CD19 cells, and especially BDCA-2 positive cells. The ability of 5C11 antibody to inhibit IFNα production from SLE-PBMCs warrants further investigation for its possible clinical application for the treatment of SLE.

Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy.

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study was to evaluate whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in this trial were twelve patients with lupus nephritis who were diagnosed by renal biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive treatments. ARB, losartan or candesartan, was administered for six months. Various clinical parameters were compared before and after ARB administration. Proteinuria decreased after ARB treatment in 83% of the patients and the median amount of proteinuria significantly decreased from 2530 mg/g Cr to 459 mg/g Cr (P = 0.03). In addition, serum albumin and cholesterol levels were significantly improved. Systolic blood pressure significantly decreased, but none had symptoms of hypotension. The antiproteinuric effect of ARB did not correlate with the reduction of blood pressure. Interestingly, higher total complement activity levels before ARB treatment were associated with a greater reduction of proteinuria. The addition of ARB would be a safe and effective treatment for lupus nephritis with persistent proteinuria despite corticosteroids and/or immunosuppressive treatments.

Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens.

Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. The yeast Saccharomyces cerevisiae Rad18 protein plays a pivotal role in the process together with the Rad6 protein. Here, we have cloned a human homologue of RAD18, hRAD18. It maps on chromosome 3p24-25, where deletions are often found in lung, breast, ovary, and testis cancers. In vivo, hRad18 protein binds to hHR6 protein through a conserved ring-finger motif. Stable transformants with hRad18 mutated in this motif become sensitive to UV, methyl methanesulfonate, and mitomycin C, and are defective in the replication of UV-damaged DNA. Thus, hRAD18 is a functional homologue of RAD18.

[Usefulness of rapid bedside cardiac troponin T assay for the diagnosis of acute myocardial infarction].

Cardiac troponin T(cTnT) is one of the most myocardial-specific markers for the diagnosis of acute myocardial infarction(AMI). Recently, the rapid bedside cTnT assay(Trop T rapid assay sensitive version), which can provide qualitative determinations within 15 min, has been developed for the emergency clinical setting. To evaluate the usefulness of rapid bedside cTnT assay, we performed the Trop T test and measured serum levels of myoglobin(Mb), creatine kinase MB isoenzyme(CK-MB) and cTnT in 256 consecutive emergency patients with suspected AMI(65 found to have AMI and 191 without AMI). The diagnostic sensitivities for AMI of Trop T, Mb and CK-MB measurements were 66%, 92% and 52%, respectively, whereas the specificities were 80%, 18% and 74%, respectively. The diagnostic accuracy for AMI of Trop T(77%) was significantly higher than that of Mb(37%, p < 0.001) and CK-MB(69%, p < 0.05). The sensitivity for AMI of Mb(86%) was significantly(p < 0.001) higher than that of Trop T (31%) and CK-MB(31%) in patients admitted < or = 3 hr after the onset of AMI. In contrast, the sensitivities of Trop T(80% and 100%) in patients admitted at 3-6 hr and > 6 hr showed no significant differences from those of Mb(100% and 96%). Furthermore, Trop T in patients admitted > 6 hr had significantly(p < 0.01) higher sensitivity compared with CK-MB(69%). The mortality rate in the non-AMI group during hospitalization in patients with positive Trop T test(39%) was significantly(p < 0.001) higher than that in patients with negative test(9%). When the positive Trop T test was regarded as > or = 0.10 ng/ml of serum cTnT, Trop T test had the best concordance of 92% with a quantitative of cTnT assay.

Topostatin, a novel inhibitor of topoisomerases I and II produced by Thermomonospora alba strain No. 1520. III. Inhibitory properties.

A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. The inhibitory activity of topostatin was shown to be pH- and temperature-dependent with a maximum around at pH 6 and 28 degrees C. The stability of topostatin decreased with decreasing pH and rising temperature. Topostatin inhibited topoisomerases I and II in a competitive manner with respect to DNA. The inhibitor also inhibited some restriction endonucleases such as Sca I, Hind III and Pst I, but not Alu I, Bam HI, Eco RI, RNase A, DNase I, DNase II and DNA ligase. Topostatin did not induce the nuclear accumulation of p53 protein by DNA damage in the normal human cells.

Intussusception: the role of general anesthesia during hydrostatic barium reduction.

MATERIALS AND METHODS: A total of 74 patients with intussusception were divided into two groups: 43 cases in 39 patients between April 1974 and June 1988 were treated under general anesthesia, and 39 cases in 35 patients between July 1988 and January 1994 were treated without it. We compared the success rates of barium reduction of intussusception in the two groups and used Fisher's exact probability test to assess whether they differed significantly. RESULTS: The overall success rates with general anesthesia and without general anesthesia were 91% (39/43) and 95% (37/39), respectively. The use of general anesthesia did not significantly affect the success rate of barium reduction (p > 0.3). CONCLUSION: The use of general anesthesia for hydrostatic barium reduction of intussusception did not improve the success rate of this procedure. Therefore we recommend that, in view of its associated disadvantages, general anesthesia should not be used during this procedure.

Effects of iron and copper supplementation on the formation of thiobarbituric acid-reactive substances and phosphatidylcholine hydroperoxide in the livers of iron- and copper-deficient rats.

Free radicals and lipid peroxide formation are related to tissue damage. This damage is thought to be associated with various diseases. To accurately assess the degree of lipid hydroperoxidation in biological materials, three different thiobarbituric acid (TBA) assay methods and the measurement of phosphatidylcholine hydroperoxide (PCOOH) by the chemiluminescence-HPLC (CL-HPLC) method were compared. Iron and copper deficiencies in rats reduced the contents of these metals. The addition of iron and copper to liver homogenates produced dose-dependent increases and decreases in TBARS, respectively. TBARS measured by the Shinnhuber method slightly increased with the addition of copper. The measurement of PCOOH was less affected by the addition of these metals. TBARS did not reflect lipid peroxidation when different concentrations of metals were present in the samples. The TBARS level is thus not a suitable marker for the assess of lipid peroxidation. PCOOH, accumulated as a primary peroxidation product from membrane phospholipids in the liver, was found to be a more appropriate marker for the estimating hepatic lipid peroxidation in the iron- and/or copper-deficient condition.

Use of the QRS scoring system in the early estimation of myocardial infarct size following reperfusion.

While the QRS scoring system has been established as a convenient tool for estimating infarct size in nonreperfused patients during the chronic stage of myocardial infarction, its applicability to reperfused patients in the acute stage has not been established. To investigate whether infarct size could be estimated by the QRS scoring system soon after reperfusion, we evaluated QRS scores obtained serially 6 hours to 1 month after reperfusion, total creatine kinase release, and left ventricular ejection fraction in 126 patients with acute myocardial infarction who underwent successful reperfusion therapy. A significant correlation was observed between the QRS score obtained after 6 hours and that obtained after 1 month (r = .89). The QRS scores obtained after 6 hours and 1 month were significantly correlated with total creatine kinase release (r = -.65 and r = -.75, respectively) and left ventricular ejection fraction (r = .62 and r = .76, respectively). Thus, the QRS scoring system can be used as a simple and economical method for estimation of infarct size soon after reperfusion.

Assessment of blood flow in the small intestine by laser Doppler flowmetry: comparison of healthy small intestine and small intestine in Crohn's disease.

Blood flow and blood distribution were investigated in 40 patients with normal small intestine and the relation between blood flow and the morphological features of Crohn's disease was examined in 11 patients with Crohn's disease by laser Doppler flowmetry from the serosal side during surgery. In normal small intestine, blood flow was measured at six points: upper, middle, and lower small intestine, each of the mesenteric borders, and the antimesenteric surface. In Crohn's disease, macroscopically normal tissue and affected lesions were observed in detail by intraoperative endoscopy after blood flow measurement. The blood flow values in the normal small intestine gradually decreased from the upper to the lower small intestine. As the level of inflammation progressed in Crohn's disease the blood flow values gradually decreased; the exudative stage of Crohn's disease (aphthoid ulcer) showed blood flow values that were slightly below those in macroscopically normal tissue. These results are the first to demonstrate decreased blood flow in affected lesions in Crohn's disease and changes in blood flow according to the degree of inflammation in vivo.

Cell cycle control is aberrant in Chinese hamster ovary cell mutants exhibiting apoptosis after serum deprivation.

We isolated mutants of Chinese hamster ovary cells that exhibit excessive apoptosis after serum deprivation. In the medium containing 10% serum, the growth rates of the mutants were 1.4 to 1.5-fold faster than those of wild-type cells. Whereas the cell cycle of wild-type cells was arrested at the G1 phase after serum deprivation, the cell cycle of the mutant cells was not fully arrested at this phase, suggesting that cell cycle regulation was disorganized in the mutants. The mutants were highly sensitive to a nucleotide-analogue 5-fluorouracil in the absence of serum, whereas wild-type cells were resistant to the drug. Based on the sensitivity to the drug after serum deprivation, we could classify the mutants into dominant groups and at least two recessive complementation groups. Thus, these mutants presumably contain different lesions in gene(s) required for cell cycle regulation and apoptosis.

[Two cases of recurrent, massive hemoptysis with contralateral, concurrent hemoptysis].

Bilateral, concurrent massive hemoptysis with respiratory failure is rare and difficult to manage. We encountered two patients with this condition. One was a 51-year-old woman and one was a 63-year-old woman. Both had inactive pulmonary tuberculosis and episodes of hemoptysis. Home oxygen therapy was prescribed to the former patient and bronchial artery embolization was done in the latter. The sites of initial bleeding were in the left basal segment and in the lingular segment. Bleeding was well controlled by endobronchial tamponade with a Fogarty balloon catheter in the left main bronchus, contralateral intubation, and systemic artery embolization. Use of water instead of air in the balloon was more effective in over the long term. Concurrent bleeding from the contralateral upper lobe bronchus was controlled by compression with a tracheal tube cuff at the bronchial orifice. Afterward, an infiltrative shadow was seen on the chest X-ray film and hemoptysis occurred in case 2 occurred in case 2. Treatment with erythromycin and antituberculosis drugs brought about improvement of chest X-ray findings and disappearance of the hemoptysis.

Management of chronic fatigue syndrome: case study.

1. Chronic fatigue syndrome (CFS) is a complex disorder marked by incapacitating fatigue of uncertain etiology which has resulted in a least a 50% reduction in activity and is of at least 6 months' duration. 2. Definitive diagnosis can be very challenging. Because no markers objectively identify the presence of CFS, diagnosis depends heavily on the presence of subjective complaints. 3. The current philosophy of CFS management is to use a multidisciplinary approach incorporating these rehabilitation goals: restore a sense of self efficacy and control; gradually increase physical activity; and decrease the restrictions imposed by CFS.

Separation of protein factors that correct the defects in the seven complementation groups of xeroderma pigmentosum cells.

We fractionated HeLa cell extracts by gel filtration and then micro-injected them into cells derived from the seven complementation groups (A-G) of xeroderma pigmentosum (XP). Distinct fractions that corrected the unscheduled DNA synthesis (UDS) of the complementation group XP cells were identified. The apparent molecular weights corresponding to complementation groups A, B, C, D, E, F, and G were estimated to be 80, 600, 600, 240, 100, 240, and 280 kDa, respectively. These factors were stable in the respective cell lines, the shortest half life being 16 h for the XP-A and XP-G complementing factors. The fraction (80 kDa) that corrected the UDS in XP-A cells also complemented the defect of the XP-A cell extract in the incision of DNA containing a pyrimidine dimer in a cell-free system. The separated fractions will be useful for understanding the molecular nature of these factors and for assigning complementation groups of cells derived from suspected XP patients.

[A case of remarkable response of colon cancer with multiple liver and bone metastasis treated with tegafur and cisplatin].

A 47-year-old man with ascending colon cancer with multiple liver metastases and bone metastasis (VII thoracic vertebra) showed a remarkable response to the combination therapy of tegafur and cisplatin. Tegafur (1,200 mg/day) was administered through continuous intravenous infusion mixed with IVH, and cisplatin was given every two weeks at a dose of 100 mg. The total dose of tegafur was 39.6g and that of cisplatin was 300mg. After therapy, primary and metastatic lesions were remarkably reduced according to various imaging techniques, and the serum CEA level of 34ng/ml at diagnosis decreased 3.7 ng/ml. Various tumor-related symptoms were improved. Drug toxicity caused slight nausea and leucopenia. Right hemicolectomy with R2 lymph node dissection was performed after chemotherapy. Histologically, primary lesion and regional lymph nodes showed diffuse fibrosis and necrosis, and only a few cancer cells remained some vessels. These results suggested that the combination chemotherapy of tegafur and cisplatin is useful for the treatment of colon cancer.

[An autopsy case of adenosquamous cell carcinoma of the extrahepatic bile duct with endobronchial mass obstructing the left main bronchus and masquerading as asthma].

A 65-year-old male was admitted with diagnosis of bronchial asthma. On admission, he was orthopneic, cyanotic and distressed. Marked hypoxemia with PaO2 of 31.1 mmHg was noted, but no obvious localized airway obstruction on plain chest X-ray film could be detected. These was minimal response to intensive treatment with steroid in addition to various bronchodilators on the presumed diagnosis of bronchial asthma. Two weeks later, chest X-ray disclosed complete atelectasis of the left lung. Stenosis of the left main bronchus with enlarged mediastinal lymph nodes on chest CT was suggested. Endoscopic examination disclosed complete obstruction of the left main bronchus just beyond the carina and polypoid tumors in the right main bronchus and basal segment bronchus. The biopsy specimens revealed squamous cell carcinoma. Chemotherapy with CDDP and VDS resulted in disappearance of atelectasis after one week and marked relief of respiratory distress. Four months later, at the completion of irradiation therapy, an abdominal tumor associated with pain appeared and bone scintigram showed multiple bone metastases. After four times chemotherapy including CDDP, hypercalcemia and renal hypofunction developed, and the patient died. Autopsy disclosed a tumor in the extrahepatic bile duct, cystic lesions of the pancreas and swelling of subcarinal lymph nodes, but no tumorous lesion in the lung and endobronchial tissue. Histological examination of the extrahepatic bile duct tumor revealed adenosquamous cell carcinoma, with predominantly squamous cell carcinoma. Other metastatic lesions consisted of squamous cell carcinoma. These findings are compatible with pulmonary metastases of adenosquamous cell carcinoma of the extrahepatic bile duct.