Characterization of 5-Fluorouracil Daily Oral Dosing versus Dietary Restriction on Femoral Growth Plates in Rats.

We evaluated the growth plates (GPs) of rats after a 14-day reduction in food consumption caused by either daily oral dosing with 5-fluorouracil (5-FU: a positive control reducing food consumption and affecting the GPs) or a direct reduction in food consumption to determine whether the observed changes were attributable to a direct effect of drug toxicity. Histomorphometric analyses of the femoral GP were performed for a nontreated (NT) control group, three groups treated with 5-FU (12, 15, and 18 mg/kg/day) and three groups with food intake restricted to levels corresponding to those consumed by the rats in the three 5-FU-treated groups. Compared with the NT group, the GP widths and the number of chondrocytes in the proliferative zone decreased significantly in all the 5-FU-treated groups and the dietary restriction groups. Importantly, no significant differences between the 5-FU-treated groups and the groups with matched dietary restrictions were seen for most parameters. Thus, the 14-day dietary restriction caused significant changes in the proliferative zone of the GP, and similar changes observed in the 5-FU-treated groups were presumed to result from the comparable reduction in food intake rather than being a direct toxic effect of the drug.

Prevention of Medication Errors in Hospitalized Patients: The Japan Adverse Drug Events Study.

INTRODUCTION: The nature of medication errors (MEs) and the frequency of identified or intercepted MEs are not being scrutinized in daily practice in Japan. OBJECTIVES: The aim of this study was to clarify the epidemiology of MEs and the risk factors for non-intercepted and unidentified MEs. METHODS: The Japan Adverse Drug Events (JADE) study was a prospective cohort study carried out at three tertiary-care teaching hospitals in Japan. Participants were consecutive patients (N = 3459) aged ≥15 years who were admitted to the study wards. MEs were identified by on-site reviews of all medical charts, self-reports, and prescription queries by pharmacists. Two independent physicians reviewed and classified all MEs and adverse drug events and determined the stages at which the MEs occurred and whether there was interception or identification of the MEs. RESULTS: A total of 514 MEs were observed among 433 patients. Sixty-four percent of MEs occurred at the ordering stage. Among these, 60 % were due to duplicate drug orders. Overall, 63 % and 45 % of MEs were not intercepted or identified during hospitalization, respectively. The independent risk factors for non-intercepted MEs were hospitalization in the surgical ward (odds ratio [OR] 2.94) and the intensive care unit (OR 3.57). MEs by resident physicians were more likely to be intercepted (OR 0.52 for non-intercepted MEs). CONCLUSIONS: MEs frequently occurred and most at the ordering stage. Almost half of MEs were not intercepted or identified. Many MEs at the later stages were less likely to be intercepted and resulted in actual patient harm. Systems to improve the identification and interception of MEs should be implemented.

Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case.

Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.

Evaluation of bone toxicity in various bones of aged rats.

The aim of the present study was to provide a method for evaluating bone toxicity induced by drugs in various bones in aged rats. Male Crl:CD (SD) rats at 46 weeks of age were administered 15 mg/m(2) body surface area of doxorubicin, which effects the growth plate in weanling rats, weekly for 9 weeks by intravenous injection, and the femur, sternum, humerus and tibia were examined histopathologically. In the doxorubicin-treated group, thinning of the growth plate was remarkably observed in the proximal tibia and humerus; however, these changes were not observed in other regions. In addition, the osteoclast number per bone perimeter in the proximal tibia was significantly higher than others in control aged rat. Thus, recognizing the various histological reactions related to the time of epiphyseal closure is important for evaluating bone toxicity in aged rats.