Effects of Smoking on Menopausal Age: Results From the Korea National Health and Nutrition Examination Survey, 2007 to 2012

Objectives:

Decreased fertility and impaired health owing to early menopause are significant health issues. Smoking is a modifiable health-related behavior that influences menopausal age. We investigated the effects of smoking-associated characteristics on menopausal age in Korean women.

Methods:

This study used data from the Korea National Health and Nutrition Examination Survey from 2007 to 2012. Menopausal age in relation to smoking was analyzed as a Kaplan-Meier survival curve for 11 510 women (aged 30 to 65 years). The risk of entering menopause and experiencing early menopause (before age 48) related to smoking were assessed using a Cox proportional hazards model.

Results:

The menopausal age among smokers was 0.75 years lower than that among non-smokers (p<0.001). The results of the Cox proportional hazards model showed pre-correction and post-correction risk ratios for entering menopause related to smoking of 1.26 (95% confidence interval [CI], 1.09 to 1.46) and 1.27 (95% CI, 1.10 to 1.47), respectively, and pre-correction and post-correction risk ratios for experiencing early menopause related to smoking of 1.36 (95% CI, 1.03 to 1.80) and 1.40 (95% CI, 1.05 to 1.85), respectively.

Conclusions:

Smokers reached menopause earlier than non-smokers, and their risk for experiencing early menopause was higher.     

The role of fibrinolysis in the therapy of peripheral vascular disease

In vivo thrombolytic studies in stumptailed monkeys indicated that pentoxifylline potentiates thrombolysis induced by urokinase activated human plasmin. Pentoxifylline as well as prostaglandin E1 released plasminogen activators and activated the fibrinolysin system. From this point of view pentoxifylline and prostaglandin E1 synergized with each other. Pentoxifylline potentiated the thrombolytic effect of prostaglandin E1 in vivo.     

Studies on human pregnancy-induced insulin-like growth factor (IGF)-binding protein-4 proteases in serum: determination of IGF-II dependency and localization of cleavage site

Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4), a consistent inhibitor of IGF action, is subject to proteolytic cleavage by the IGF-II-dependent IGFBP-4 protease. However, regulation of the IGF-II-dependent IGFBP-4 protease in vivo is not known. As IGFBP proteases are known to be triggered during pregnancy, we systematically evaluated the changes in IGFBP-4 proteolysis by serum collected throughout human pregnancy. Results from in vitro protease assays using recombinant IGFBP-4 revealed that IGFBP-4 proteolysis determined in both the presence and absence of exogenous IGF-II significantly increased during the first and second trimesters and reached a plateau by the third trimester. However, in the absence of IGF-II, IGFBP-4 proteolysis by pregnancy serum was only observed after prolonged incubation. IGF-II dose dependently increased IGFBP-4 proteolysis by pregnancy serum, with maximal stimulation observed at a concentration of 0.7 mol/L relative to IGFBP-4. In contrast, IGF-II at an equimolar dose had little effect on proteolysis of recombinant human IGFBP-3, whereas excess IGF-II reproducibly inhibited recombinant human IGFBP-3 proteolysis by pregnancy serum. Although IGF-II enhanced IGFBP-4 proteolysis, results from N-terminal sequence and mass spectrometric analyses of IGFBP-4 proteolytic fragments demonstrate that the cleavage site (Met135-Lys136) in human IGFBP-4 was not altered by IGF-II. Deletion of the residues 121-141 containing this cleavage site blocked IGFBP-4 proteolysis. These findings demonstrate that the increase in IGFBP-4 proteolysis during pregnancy was accounted for mainly by the IGF-II-dependent IGFBP-4 proteolysis. Because IGFBP-4 is a potent inhibitor of IGF actions, it can be speculated that the pregnancy-induced IGFBP-4 proteases may play an important role in regulating fetal growth.     

Low grade gastric mucosa associated lymphoid tissue lymphoma：Treatment strategies based on 10 year follow-up

AIM: To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS: A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS: Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (H pylori) regimen only. The duration to reach complete remission was 12 months (85 percentile, 2-33 months). Five patients showed complete remission with radiation therapy (26-86 months). Two of them were H pylori treatment failure cases. CONCLUSION: H pylori eradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of H pylori infection or who do not respond to H pylori eradication therapy 12 months after successful eradication.     

Comparison of microvessel density before and after peripheral blood stem cell transplantation in multiple myeloma patients and its clinical implications: multicenter trial

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.     

Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A major feature of CTCL is profound immunosuppression, such that patients with advanced mycosis fungoides or Sézary syndrome have been compared with patients with advanced HIV disease and are susceptible to opportunistic infection. The etiology of this immunosuppression is unclear. We analyzed peripheral blood T cells of patients with CTCL with stage I to IV disease, using a sensitive beta-variable complementarity-determining region 3 spectratyping approach. Our data revealed a profound disruption of the complexity of the T-cell repertoire, which was universally observed in patients with advanced disease (stages III and IV), and present in up to 50% of patients with early-stage disease (stages I and II). In most patients, multiple monoclonal and oligoclonal complementarity-determining region 3 (CDR3) spectratype patterns in many different beta-variable families were seen. Equally striking was a reduction of normal T cells (as judged by absolute CD4 counts) across multiple beta-variable families. In general, CTCL spectratypes were reminiscent of advanced HIV spectratypes published elsewhere. Taken together, these data are most consistent with a global assault on the T-cell repertoire in patients with CTCL, a process that can be observed even in early-stage disease.     

Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS).METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia,endotoxin TNF-~, 1L-6 and prothrombin activity (PTA),cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study.RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully.Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P&lt;0.01), while the serum TBIL,endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities.CONCLUSION: The proinflammatory cytokines (TNFα, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome.