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Objectives: Elevated risks of skin cancer following high doses of ionizing radiation have long been known. Recent reports on atomic-bomb survivors indicate that nonmelanoma skin cancer can be induced at low to medium doses. We studied atomic-bomb survivors to determine the effects of radiation on specific histologic types of skin cancer and to describe the dose-response relationship.Methods: Cases of melanoma, nonmelanoma skin cancers, and Bowen's disease were ascertained between 1958 and 1987 for the 80,000 cohort members through the population-based Hiroshima and Nagasaki (Japan) tumor registries augmented by searches of other records.Results: An excess of basal cell carcinoma (n = 80), with some suggestion of a non-linear dose-response, was observed. The excess risk decreased markedly as age at exposure increased, and there was no evidence for an interaction between ionizing and ultraviolet radiation. No dose-response was found for squamous cell carcinoma (n = 69). The excess relative risk point-estimates were large, but statistically nonsignificant for both melanoma (n = 10) and Bowen's disease (n = 26).Conclusions: The basal layer of the epidermis appears to be quite sensitive to radiation carcinogenesis, particularly at a young age. The suprabasal layer seems to be more resistant, as shown by the lack of an association for squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

Background: During tube exchange for percutaneous endoscopic gastrostomy (PEG), a misplaced tube can cause peritonitis and death. Thus, endoscopic or radiologic observation is required at tube exchange to make sure the tube is placed correctly. However, these procedures cost extensive time and money to perform in all patients at the time of tube exchange. Therefore, we developed the "sky blue method" as a screening test to detect misplacement of the PEG tube during tube exchange., Methods: First, sky blue solution consisting of indigocarmine diluted with saline was injected into the gastric space via the old PEG tube just before the tube exchange. Next, the tube was exchanged using a standard method. Then, we checked whether the sky blue solution could be collected through the new tube or not. Finally, we confirmed correct placement of the tube by endoscopic or radiologic observation for all patients., Results: A total of 961 patients were enrolled. Each tube exchange took 1 to 3 minutes, and there were no adverse effects. Four patients experienced a misplaced tube, all of which were detectable with the sky blue method. Diagnostic parameters of the sky blue method were as follows: sensitivity, 94% (95%CI: 92-95%); specificity, 100% (95%CI: 40-100%); positive predictive value, 100% (95%CI: 100-100%); negative predictive value, 6% (95%CI: 2-16%)., Conclusion: These results suggest that the number of endoscopic or radiologic observations to confirm correct replacement of the PEG tube may be reduced to one fifteenth using the sky blue method.

Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic-bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population-based study of spontaneous as well as radiation-related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic-bomb radiation exposure did not differ between UV-exposed and shielded parts of the body, suggesting the additivity of the radiation-related and background BCC risks., ((c) 2005 Wiley-Liss, Inc.)

Fibrates are commonly used lipid-lowering agents that act via PPARalpha, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARalpha, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.

Background: Absorption of water, as well as emptying of bile, are important functions of the gallbladder. We studied the changes of gallbladder function with age in gallstone patients and their influence on the outcome of extracorporeal shockwave lithotripsy (ESWL)., Methods: (i) A total of 123 consecutive patients with complete stone clearance by ESWL were examined. Gallbladder emptying was assessed before treatment using intravenous cholecystography. After stone clearance, the recurrence of gallstones was monitored by using ultrasonography. Cox regression analysis was used to determine the risk factors associated with stone recurrence. (ii) Gallbladder bile was sampled from 59 gallstone patients during surgery. Biliary cholesterol, phospholipids, and total bile acids were simultaneously quantified by using gas-liquid chromatography., Results: Impaired gallbladder function, but not gallstone recurrence, was more frequently observed in older patients (>/=65 years old) than in younger patients (<65 years old). Cox regression analysis revealed that poor gallbladder emptying was an independent predictor of stone recurrence after ESWL in the total study population, but not in the older patients (>/=65 years old). Analysis of bile from surgically treated patients with cholesterol stones showed a significantly higher total lipid concentration and a shorter nucleation time in the younger group (<65 years old), but the cholesterol saturation index did not differ between the younger and older groups., Conclusions: Our data suggest that the reduced concentrating function of the gallbladder in elderly gallstone patients helps to counteract stone recurrence despite their abnormal gallbladder motility. Therefore, aged gallstone patients may be preferentially treated by a non-surgical strategy.

Background: The risk of developing nervous system tumors following exposure to ionizing radiation is not well quantified. We characterized the incidence of nervous system tumors among atomic bomb survivors as a function of radiation dose., Methods: Tumors of the nervous system and pituitary gland diagnosed between 1958 and 1995 among 80 160 atomic bomb survivors were ascertained using the Hiroshima and Nagasaki tumor registries, medical records, and death certificates. Pathologists reviewed slides and medical records to provide histologic diagnoses. Poisson regression analyses were used to characterize radiation effects on tumor incidence, which are expressed as excess relative risk per sievert (ERR(Sv)). All statistical tests were two-sided., Results: A statistically significant dose-related excess of nervous system tumors was observed in the cohort (ERR(Sv) = 1.2, 95% confidence interval [CI] = 0.6 to 2.1). The highest ERR(Sv) was seen for schwannoma (4.5, 95% CI = 1.9 to 9.2). The risk for all other nervous system tumors as a group is also statistically significantly elevated (ERR(Sv) = 0.6, 95% CI = 0.1 to 1.3). Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5). The dose-response relationships were linear. For nervous system tumors other than schwannoma, excess risks were higher for men than for women and for those exposed during childhood than for those exposed during adulthood., Conclusions: A statistically significant dose response was observed for all nervous system tumors combined and for schwannoma considered separately, indicating that exposure to even moderate doses (i.e., <1 Sv) of radiation is associated with an elevated incidence of nervous system tumors.

To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1 mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study.

A 44-year-old diabetic female became unconscious one month prior to death due to acute suppurative meningitis. Although cerebrospinal fluid findings normalized with the administration of antibiotics, the status of unconsciousness did not improve and she expired. Examination of the brain revealed a small, relatively ill-defined, demyelinated lesion in the central part of the anterior pons, with which hypertrophied astrocytes, lymphocytes, macrophages phagocytizing disintegrated myelin were present. Neuronal perikarya and axons were well preserved. The findings are pathognomonic of central pontine myelinolysis. Moreover, multifocal, granular and rosary-shaped or nodular pseudocalcifications were noted within the lesion as an unusual additional finding. Only a few comparable cases of central pontine myelinolysis accompanied by pseudocalcification have been reported.

Butylated hydroxytoluene (BHT), a preservative widely found in food as a food additive, was orally administered at concentrations of 1% and 2% of the diet to B6C3F1 mice for 104 consecutive weeks. Treated animals underwent a 16-week recovery period prior to pathological examination. In male mice administered BHT, the incidence of mice with either a hepatocellular adenoma or a focus of cellular alteration in the liver was increased in a clear dose-response relationship. The incidences of male mice with other tumors and the incidences of female mice with any tumor were not significantly increased as a consequence of BHT administration. The results of this study indicate BHT to be tumorigenic to the liver of the B6C3F1 male mouse.

Sodium erythorbate (SE) was administered at concentrations of 0, 1.25, or 2.5% (maximum tolerated dose, MTD) in the drinking-water to groups of 50 male B6C3F1 mice respectively. Female groups, each consisting of 50 mice, received SE in the drinking-water at concentrations of 0, 2.5 or 5% (MTD). Treatment continued for 96 wks and the experiment was terminated during wk 110. Tumors were observed at various sites including the liver, hematopoietic system, lung and soft tissue. However, at any of the sites, the tumor incidence, the time to death with tumors or the histological distribution of tumors did not differ significantly from those in the untreated control group. Thus, the present study did not demonstrate a tumorigenic effect of SE on B6C3F1 mice by means of oral administration.

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.