Estrogen and urinary incontinence

Hormone therapy (HT) has been one of the most commonly used methods to treat postmenopausal disorders including lower urinary tract symptoms such as urinary incontinence (UI). Although it has been suggested that HT improves urinary tract symptoms, little evidence has so far been presented to support this. Recently however, large randomized clinical trials have shown the adverse effects of estrogen on UI and indicate that HT should not be used for prevention or relief of UI in postmenopausal women. Here we review the effects of HT on UI in the light of these clinical trials.     

Causal inference in medicine--decision making]

In the field of occupational medicine, either when we consider some preventive plans or when we make decisions to compensate for occupational diseases, it has been necessary to discuss causality between work and disease. Furthermore, epidemiologic causality has recently been used in risk assessment in occupational and environmental settings. We have shown that the law of causality in medicine is recognized as probability and continuous variables. Such a law of causality has been recognized in the same way as probability in physics, too, and has been regarded as a model of science. Physicists and mathematicians had claimed the importance of probability in causal inference as well as the principle of uncertainty before it was discovered. We, then, explained Etiologic Fraction (EF), Attributable Proportion for the Exposed Population (APE), Probability of Causation (PC), and so on. The PC has been used to ascertain the conditional probability in an individual case of a disease having been caused by a particular prior exposure, by using the experience of exposed populations to determine the appropriate relative risk, and this has been used for compensation for exposed cases. Next the applicability of information from a population to individuals was presented. Third, we provided a brief historical aspect of epidemiology. The evolutions in Epidemiology have been very rapid, so we pointed out that, in Japan, we could observe many incommensurable phenomena in epidemiologists and physicians depending on the era which was studied by them. Fourth, we discussed judgement and political application based on epidemiologic evidence, using Yanagimoto's classification is also taken or not should be estimated and compared. We presented several examples of reasoning in judgements. Lastly, we discussed several tasks and assignments for the future of epidemiology.     

Development of an irradiation method of intraoperative radiation therapy for curatively resected rectal cancer

Background. Intraoperative radiation therapy (IORT) has been performed to prevent local recurrence of rectal cancer only when positive margins are suspected. To further reduce local recurrence, we attempted to develop a new IORT irradiation method in which electron beam irradiation is administered as uniformly as possible to the intrapelvic dissection surfaces. Methods. Low anterior resection and abdominoperineal resection were performed in one male and one female cadaver. Electron beam irradiation was administered by four different methods, and absorbed doses were measured at 15 sites within the pelvis. We also attempted to measure absorbed doses at nine sites within the pelvis in 14 patients treated with IORT. Results. The cadaver study revealed low absorbed doses in the lateral walls of the pelvis when a single irradiation was delivered from the anterior. When the lateral walls of the pelvis were irradiated twice, once each time on the right and left, the absorbed doses were low in the central pelvis and presacrum. Relatively high absorbed doses were achieved in all of these areas by a technique that combined these two methods. Adequate absorbed doses were not achieved by a single irradiation administered from the perineum. Conclusion. This study suggests that electron beam irradiation administered three times to the dissected surfaces in the pelvis after resection of rectal cancer (i.e., to the central pelvis and presacrum from the anterior, and to the left and right lateral walls of the pelvis) is the most suitable method for achieving adequate absorbed doses. Received: May 6, 1998 / Accepted: December 15, 1998     

Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens

In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method.     

Side effects of boil and bite type oral appliance therapy in sleep apnea patients

Introduction  

Based on a mail-out questionnaire, this study analyzed compliance and side effects of one commonly used (TheraSnore) boil and bite oral appliance (OA) in patients with obstructive sleep apnea.     

Butyrate,a bacterial metabolite,induces apoptosis and autophagic cell death in gingival epithelial cells

Tsuda H, Ochiai K, Suzuki N, Otsuka K. Butyrate, a bacterial metabolite, induces apoptosis and autophagic cell death in gingival epithelial cells. J Periodont Res 2010; 45: 626–634.©2010 John Wiley & Sons A/S Background and Objective: Butyrate is produced by some types of anaerobic periodontal bacteria. Millimolar concentrations of butyrate are found in mature dental plaque from periodontitis patients. Although butyrate reportedly has a variety of effects in many mammalian cells, its effect on gingival epithelial cells is not well known. In this study, we investigated the effect of butyrate on gingival epithelial Ca9‐22 cell death. Material and Methods: Death of Ca9‐22 cells was assessed after treating the cells with or without butyrate. A SYTOX Green dye, which exhibits strong green fluorescence once it enters dead cells through ruptured cell membranes, was used for cell death detection. Phosphatidylserine redistribution was measured using fluorescein isothiocyanate‐labeled annexin V. The activity of caspase‐3 was measured as the amount of cleaved substrate peptide. Anti‐apoptotic bcl‐2 mRNA expression was measured using real‐time RT‐PCR. Western blotting and fluoromicroscopic analysis with anti‐microtubule‐associated protein 1 light chain 3 (LC3) antibodies were performed for detection of autophagy. Results: Stimulation with millimolar concentrations of butyrate for 48 h induced Ca9‐22 cell death. The stimulation also caused increased caspase‐3 activity, phosphatidylserine redistribution and bcl‐2 down‐regulation, suggesting butyrate‐induced apoptosis. However, the pan‐caspase inhibitor, Z‐VAD‐FMK, did not inhibit cell death completely. This implies the existence of other types of cell death. In addition, markers of autophagy, namely, the conversion of LC3‐I to LC3‐II and increased LC3 accumulation, were observed. Moreover, inhibition of autophagy by 3‐methyladenine suppressed the butyrate‐induced cell death, suggesting that butyrate could induce cell death through autophagy. Conclusion: These data suggest that butyrate induces apoptosis and autophagic cell death.