Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958-2009.

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

Lifetime risk of suicide among survivors of the atomic bombings of Japan.

AIMS: The long-term physical health effects of the atomic bombings of Hiroshima and Nagasaki are well characterised, but the psychological effects remain unclear. Therefore, we sought to determine whether measures of exposure severity, as indirect measures of psychological trauma arising from exposure to the atomic bombings, are associated with suicide mortality among atomic bomb survivors. METHODS: The Life Span Study is a prospective cohort study of 93 741 Japanese atomic bomb survivors who were located within 10 km of the hypocentre in Hiroshima or Nagasaki at the time of the bombings in 1945, and 26 579 residents of Hiroshima and Nagasaki who were not in either city at the time of the bombings, matched to survivors on city, sex and age. Measures of exposure severity included: proximity to the hypocentre, type of shielding between the survivor and the blast and self-reported occurrence of acute radiation and thermal injuries. Date of death was obtained from the Japanese National Family Registry system. Cause of death was obtained from death certificates. Adjusted hazard ratios (HRs) were estimated from Cox regression models overall and stratified by sex and age. RESULTS: During the 60-year follow-up period (1950-2009), 1150 suicide deaths were recorded among 120 231 participants (23.6 per 100 000 person-years): 510 among 70 092 women (17.2 per 100 000 person-years) and 640 among 50 139 men (33.6 per 100 000 person-years). Overall, there was no association of proximity, type of shielding or the occurrence of acute injuries with suicide mortality. Among those <25 years of age at the time of the bombings, increased suicide risk was observed for survivors outside v. shielded inside any structure (HR: 1.24; 95% confidence interval (CI): 1.03, 1.48; interaction p = 0.054) and for those who reported flash burns (HR: 1.32; 95% CI: 1.00, 1.73; interaction p = 0.025). Sex-stratified analyses indicated that these associations were limited to men. Among women, closer proximity to the hypocentre was associated with a non-significant increase in suicide risk, with a positive association between proximity and suicide risk observed among women <15 years of age (HR: 1.09 per km; 95% CI: 1.00, 1.18; interaction p = 0.067). CONCLUSIONS: Proximity to the hypocentre, shielding and acute injury presence do not generally appear to influence suicide mortality among atomic bomb survivors. However, heterogeneity may exist by age and sex, with younger survivors potentially more sensitive to psychological trauma. Coupled with other studies, our results suggest the importance of long-term monitoring of mental health among young populations exposed to catastrophic events or mass trauma.

Individual response of humans to ionising radiation: governing factors and importance for radiological protection.

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo.

OBJECTIVES: The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. METHODS: Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. RESULTS: In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. CONCLUSION: This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes.Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362-372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. METHODS: From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. RESULTS: The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care.

DS02R1: Improvements to Atomic Bomb Survivors' Input Data and Implementation of Dosimetry System 2002 (DS02) and Resulting Changes in Estimated Doses.

Individual dose estimates calculated by Dosimetry System 2002 (DS02) for the Life Span Study (LSS) of atomic bomb survivors are based on input data that specify location and shielding at the time of the bombing (ATB). A multi-year effort to improve information on survivors' locations ATB has recently been completed, along with comprehensive improvements in their terrain shielding input data and several improvements to computational algorithms used in combination with DS02 at RERF. Improvements began with a thorough review and prioritization of original questionnaire data on location and shielding that were taken from survivors or their proxies in the period 1949-1963. Related source documents varied in level of detail, from relatively simple lists to carefully-constructed technical drawings of structural and other shielding and surrounding neighborhoods. Systematic errors were reduced in this work by restoring the original precision of map coordinates that had been truncated due to limitations in early data processing equipment and by correcting distortions in the old (WWII-era) maps originally used to specify survivors' positions, among other improvements. Distortion errors were corrected by aligning the old maps and neighborhood drawings to orthophotographic mosaics of the cities that were newly constructed from pre-bombing aerial photographs. Random errors that were reduced included simple transcription errors and mistakes in identifying survivors' locations on the old maps. Terrain shielding input data that had been originally estimated for limited groups of survivors using older methods and data sources were completely re-estimated for all survivors using new digital terrain elevation data. Improvements to algorithms included a fix to an error in the DS02 code for coupling house and terrain shielding, a correction for elevation at the survivor's location in calculating angles to the horizon used for terrain shielding input, an improved method for truncating high dose estimates to 4 Gy to reduce the effect of dose error, and improved methods for calculating averaged shielding transmission factors that are used to calculate doses for survivors without detailed shielding input data. Input data changes are summarized and described here in some detail, along with the resulting changes in dose estimates and a simple description of changes in risk estimates for solid cancer mortality. This and future RERF publications will refer to the new dose estimates described herein as "DS02R1 doses."

Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells.

OBJECTIVES: Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. METHODS: Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. RESULTS: Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. CONCLUSIONS: The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury.Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602-609. DOI: 10.1302/2046-3758.512.2000582.

Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

Initial Report for the Radiation Effects Research Foundation F1 Mail Survey.

To study the full health effects of parental radiation exposure on the children of the atomic bomb survivors, the Radiation Effects Research Foundation developed a cohort of 76,814 children born to atomic bomb survivors (F1 generation) to assess cancer incidence and mortality from common adult diseases. In analyzing radiationassociated health information, it is important to be able to adjust for sociodemographic and lifestyle variations that may affect health. In order to gain this and other background information on the F1 cohort and to determine willingness to participate in a related clinical study, the F1 Mail Survey Questionnaire was designed with questions corresponding to relevant health, sociodemographic, and lifestyle indicators. Between the years 2000 and 2006, the survey was sent to a subset of the F1 Mortality Cohort. A total of 16,183 surveys were completed and returned: 10,980 surveys from Hiroshima residents and 5,203 from Nagasaki residents. The response rate was 65.6%, varying somewhat across parental exposure category, city, gender, and year of birth. Differences in health and lifestyle were noted in several variables on comparison across city and gender. No major differences in health, lifestyle, sociodemographics, or disease were seen across parental exposure categories, though statistically significant tests for heterogeneity and linear trend revealed some possible changes with dose. The data described herein provide a foundation for studies in the future.

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

Dose- and time-dependent effects of triamcinolone acetonide on human rotator cuff-derived cells.

OBJECTIVES: To investigate the appropriate dose and interval for the administration of triamcinolone acetonide (TA) in treating tendinopathy to avoid adverse effects such as tendon degeneration and rupture. METHODS: Human rotator cuff-derived cells were cultured using three media: regular medium (control), regular medium with 0.1 mg/mL of TA (low TA group), and with 1.0 mg/mL of TA (high TA group). The cell morphology, apoptosis, and viability were assessed at designated time points. RESULTS: In the low TA group, the cells became flattened and polygonal at seven days then returned to normal at 21 days. The cell apoptosis ratio and messenger ribonucleic acid expression of caspase-3, 7, 8, and 9 increased, and viability was reduced in the low and high groups at seven days. In the low TA group, apoptosis and viability returned to normal at 21 days, however, in the high TA group, the cell morphology, apoptosis ratio, caspase-3, 7, 8, and 9 and viability did not return by day 21. Re-administration was performed in the low TA group at 7-, 14-, and 21-day intervals, and cell viability did not return to the control level at the 7- and 14-day intervals. CONCLUSION: A 0.1 mg/mL dose of TA temporarily decreased cell viability and increased cell apoptosis, which was recovered at 21 days, however, 1 mg/mL of TA caused irreversible damage to cell morphology and viability. An interval > three weeks was needed to safely re-administer TA. These findings may help determine the appropriate dose and interval for TA injection therapy. Cite this article: Bone Joint Res 2014;3:328-34.

Incidence of deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy with a latanoprost ophthalmic solution.

PURPOSE: Among some local side effects of prostaglandin-associated periorbitopathy (PAP), deepening of the upper eyelid sulcus (DUES) is the most prominent clinical feature, and is one of the most significant adverse cosmetic events. Here, we prospectively investigated the incidence of DUES in Japanese open-angle glaucoma patients initially treated with latanoprost (Xalatan 0.005%) ophthalmic solution. METHODS: This was an open-label prospective study. Facial photographs and subjective reports of the recognition of DUES were obtained at the beginning of latanoprost treatment and at 2, 4, and 6 months thereafter. Intraocular pressure (IOP) was measured at three consecutive visits before and after treatment with latanoprost. The incidence of DUES was evaluated objectively by three blinded investigators who compared the series of photographs. RESULTS: A total of 52 eyes of 52 newly diagnosed open-angle glaucoma Japanese patients (28 males, 24 females) were evaluated. The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. During this period, no patient self-reported an occurrence of DUES. Mean IOPs before and after treatment were 16.5±2.9 and 13.8±3.0 mm Hg, respectively. Latanoprost reduced the IOP significantly (P<0.0001, paired t-test). CONCLUSIONS: Latanoprost caused DUES rarely and had a robust IOP-lowering effect in Japanese glaucoma patients.

Impact of smoking on mortality and life expectancy in Japanese smokers: a prospective cohort study.

OBJECTIVE: To investigate the impact of smoking on overall mortality and life expectancy in a large Japanese population, including some who smoked throughout adult life. DESIGN: The Life Span Study, a population-based prospective study, initiated in 1950. SETTING: Hiroshima and Nagasaki, Japan. PARTICIPANTS: Smoking status for 27,311 men and 40,662 women was obtained during 1963-92. Mortality from one year after first ascertainment of smoking status until 1 January 2008 has been analysed. MAIN OUTCOME MEASURES: Mortality from all causes in current, former, and never smokers. RESULTS: Smokers born in later decades tended to smoke more cigarettes per day than those born earlier, and to have started smoking at a younger age. Among those born during 1920-45 (median 1933) and who started smoking before age 20 years, men smoked on average 23 cigarettes/day, while women smoked 17 cigarettes/day, and, for those who continued smoking, overall mortality was more than doubled in both sexes (rate ratios versus never smokers: men 2.21 (95% confidence interval 1.97 to 2.48), women 2.61 (1.98 to 3.44)) and life expectancy was reduced by almost a decade (8 years for men, 10 years for women). Those who stopped smoking before age 35 avoided almost all of the excess risk among continuing smokers, while those who stopped smoking before age 45 avoided most of it. CONCLUSIONS: The lower smoking related hazards reported previously in Japan may have been due to earlier birth cohorts starting to smoke when older and smoking fewer cigarettes per day. In Japan, as elsewhere, those who start smoking in early adult life and continue smoking lose on average about a decade of life. Much of the risk can, however, be avoided by giving up smoking before age 35, and preferably well before age 35.

[Cardiovascular surgery for patient with pulmonary dysfunction].

Pulmonary dysfunction is one of the major factors for postoperative pulmonary complication. Preoperative pulmonary function test reveals possible operative risk. Particularly, in the patient with stage Ⅲ and Ⅳ chronic obstructive pulmonary disease (COPD), open heart surgery with cardiopulmonary bypass is at higher risk of complication. In these patients, safe and reliable surgical procedures are required. Preoperatively, quitting smoking and incentive spirometry can reduce the risk of pulmonary complications. Furthermore, noninvasive positive pressure ventilation (NPPV) on the appropriate indication can help to improve the outcome in the patients with pulmonary dysfunction.

Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the Life Span Study of atomic bomb survivors.

Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed that unspecified bladder cancer had high radiation sensitivity with a notably high female-to-male excess relative risk (ERR) per radiation dose ratio and were the only sites for which the ERR did not decrease with attained age. These findings, however, did not consider lifestyle factors, which could potentially confound or modify the risk estimates. This study estimated the radiation risks of the most prevalent subtype of urinary tract cancer, urothelial carcinoma, while accounting for smoking, consumption of fruit, vegetables, alcohol and level of education (a surrogate for socioeconomic status). Eligible study subjects included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and had estimated radiation doses. Members were censored due to loss of follow-up, incident cancer of another type, death, or the end of calendar year 2001. Surveys (by mail or clinical interview) gathered lifestyle data periodically for 1963-1991. There were 63,827 participants in one or more survey. Five hundred seventy-three incident urothelial carcinoma cases occurred, of which 364 occurred after lifestyle information was available. Analyses were performed using Poisson regression methods. The excess relative risk per weighted gray unit (the gamma component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43-1.78) but the risks were not dependent upon age at exposure or attained age. Lifestyle factors other than smoking were not associated with urothelial carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00 compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to 3.4) were greatly changed after accounting for all lifestyle factors. A multiplicative model of gender-specific radiation and smoking effects was the most revealing though there was no evidence of significant departures from either the additive or multiplicative joint effect models. Among the LSS cohort members with doses greater than 0.005 Gy(w) (average dose 0.21 Gy(w)), the attributable fraction of urothelial carcinoma due to radiation was 7.1% in males and 19.7% in females. Among current smokers, the attributable fraction of urothelial carcinoma due to smoking was 61% in males and 52% in females. Relative risk estimates of smoking risk were approximately two for smokers compared to nonsmokers. After adjustment for lifestyle factors, gender-specific radiation risks and the F:M ERR/Gy(w), the ratios of excess urothelial carcinoma risk were similar to the estimates without adjusting for lifestyle factors. Smoking was the primary factor responsible for excess urothelial carcinoma in this cohort. These findings led us to conclude that the radiation risk estimates of urothelial carcinoma do not appear to be strongly confounded or modified by smoking, consumption of alcohol, fruits, or vegetables, or level of education.

Remote postconditioning may attenuate ischaemia-reperfusion injury in the murine hindlimb through adenosine receptor activation.

OBJECTIVE: This study aimed to determine the effect and mechanisms of remote postconditioning (RPC) upon ischaemia-reperfusion injury (IRI) in the ischaemic mouse hindlimb. DESIGN: RPC is the brief application of ischaemia to remote organs immediately before reperfusion of an ischaemic target organ, and it is a novel approach to IRI attenuation. MATERIALS AND METHODS: Right hindlimb ischaemia was induced in mice using a rubber tourniquet, the release of which initiated reperfusion. We established RPC by 5 min of ischaemia followed by 5 min of reperfusion in the left hindlimb immediately before right hindlimb reperfusion. The wet/dry ratio of skeletal muscle (degree of tissue oedema), myeloperoxidase (MPO) activity (accumulation of neutrophils), and nitroblue tetrazolium reduction (tissue necrosis) were evaluated. We also intra-peritoneally injected 8-sulphophenyltheophylline (SPT), an adenosine receptor inhibitor, in RPC mice. RESULTS: Wet/dry ratio, MPO activity and tissue necrosis were significantly lower in the RPC group than in the control group, and injection of SPT impaired the protective effect of RPC. CONCLUSIONS: Our results show that RPC attenuated IRI in murine hindlimb ischaemia, possibly through endogenous adenosine receptor activation, and that RPC might serve as a promising therapeutic option for treating serious limb ischaemia.

Acquired left ventricular-right atrial communication and severe aortic valve regurgitation caused by infective endocarditis.

We report here on a surgical case of acquired left ventricular right atrial communication (LV-RA communication) and aortic regurgitation (AR) caused by infective endocarditis (IE). We successfully treated the patient with composite patches made from polytetrafluoroethylene (PTFE) and autologous pericardium. In general, LV-RA communication is a rare congenital cardiac anomaly (Gerbode-type shunt). However, acquired LV-RA communications secondary to IE are occasionally reported.When repairing an acquired condition due to IE, particular care should be taken to avoid recurrence, persistent infection and iatrogenic atrioventricular block.

[New technology of intraaortic balloon pumping device].

Intraaortic balloon pumping (IABP) is the most popular circulatory assist device in cardiac surgery. In the development of IABP several modifications have been made. First, reduction in the caliber to 6 Fr is the most important modification of the IABP catheter to relatively small Japanese patients. Second, direct pressure measurement through the tip of the catheter enabled more accurate and real-time assist. Third, a novel balloon pump automatically selects the trigger source, arranges the timing of the IABP inflation/deflation, and detects the arrhythmias. Further development of IABP will bring safer and more reliable hemodynamic management in cardiac surgery.

[The use of 19 Fr silicone drains in chest surgery].

We evaluated a single 19 Fr Blake drain after chest surgery retrospectively. 50 patients underwent drainage of their pleural cavity using Blake drains. Blake drain was found to be effective in drainage of both air and fluid. In addition, this soft silicone drain seemed to improve the comfort of the patients. One single Blake drain is considered to be an option for chest drainage in most of general thoracic surgery.

Expression of immature and mature retinal cell markers in retinoblastoma.

AIM: To clarify the expression of immature and mature retinal cell makers in retinoblastoma cells and to give insights into the cell origin of the retinoblastoma. MATERIALS AND METHODS: Five samples from five eyes diagnosed with retinoblastomas were analysed by a standard immunohistochemistry using antibodies against Nestin and the hairy and enhancer of split mammalian homologue-1 (HES-1), both as markers for undifferentiated cells, and against Chx10, as a marker for both undifferentiated retinal cells and mature bipolar cells. Photoreceptor-specific nuclear receptor (PNR) was used as a postmitotic rod photoreceptor cell-specific marker, glial fibrillary acidic protein (GFAP) as a mature glia cell marker, and microtubule-associated protein (MAP) 2 as a mature neuronal cell marker. RESULTS: Nestin was detected in what were possibly Müller cells, but not in the tumour stroma. HES-1 was not detected in the retinoblastoma tissue. Chx10 was detected in one of the five samples. In this one sample, Chx10 expression was confined in a minor portion of the retinoblastoma cells. PNR was not detected in the retinoblastoma tissue. Expression of GFAP was detected only in the stromal cells of the tumour, which presumably represents reactive stromal astrocytes. In contrast, in all the samples, MAP2 was expressed in most of the retinoblastoma cells. CONCLUSIONS: The results of the current study support that retinoblastomas are derived from mature neural cells but do not originate from tumour stem cell(s).