Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, causes severe hepatotoxicity, a severe adverse event associated with the loss of treatment opportunities. We report a case of liver injury (grade 4) during treatment with abemaciclib, in which the patient was switched to palbociclib and successfully treated with this CDK4/6 inhibitor. A 73-year-old woman with bone metastatic breast cancer (hormone-positive, HER2-negative) was treated with abemaciclib, fulvestrant, denosumab, and precipitated calcium carbonate with cholecalciferol and magnesium carbonate (pCCCM). On day 17, the patient developed skin rashes on her trunk and arms. On day 22, abemaciclib and pCCCM were discontinued due to drug eruption. Grade 3 aspartate aminotransferase (AST) and grade 4 alanine aminotransferase (ALT) levels increased on day 29. Therefore, fulvestrant and denosumab were suspended as the causes of severe hepatotoxicity, in addition to the two drugs suspected of causing the skin eruption. On day 43, AST and ALT levels did not improve, and the patient was referred to a hepatologist. The hepatologist diagnosed hepatotoxicity as a drug-induced liver injury through additional tests and interviews. Fulvestrant treatment was resumed on day 78, and palbociclib on day 92, and denosumab and pCCCM on day 134. On day 287, treatment with the CDK4/6 inhibitor was continued without evidence of liver dysfunction. This case suggests that rechallenge with palbociclib after severe liver injury with abemaciclib may allow for continued treatment with CDK4/6 inhibitors.
The morphology of the thyroid C-cells in golden hamsters after short- and long-term treatment with ethanol was studied. Immunohistochemistry was applied to examine the distribution of the C-cells in the thyroid gland. In the short-term experimental animals, the Golgi complexes and the granular endoplasmic reticulum were well developed and the number of the secretory granules was decreased as compared with those of the control animals. These findings suggest that the cellular activity of the thyroid C-cell is stimulated after short-term treatment with ethanol. The morphology of the thyroid C-cells of the long-term experimental animals was similar to that of the controls. It is conceivable that long-term treatment with ethanol does not affect the function of the C-cell.
After a disaster, it is needed to provide large amount of temporary houses promptly for people who lose their own houses. In this paper, a housing construction technique that is suitable for Japanese historical surroundings is proposed. It is making use of the Japanese traditional plaster technique inherited for hundreds years. And the frame of this system is the shell structure that is one of the most efficient structural system, therefore, it can be build with very little amount of material.
This paper proposes two low-cost jitter generators for high-speed I/O interface jitter tolerance testing. (i) The first one uses inter-symbol interference positively with digital control. The proposed circuit consists of mostly digital circuits with small amount of analog circuits (simple RC low-pass filter), and the digital part can be realized using FPGA or high-speed digital unit of an automated test equipment (ATE). (ii) The second one uses a digital AS modulator with some amount of analog circuits, and the digital part can be realized using high-speed digital unit of the ATE; the digital AS modulator can be realized by software on the ATE, and its output controls switches in the analog circuits. Their principles, theoretical analyses and simulation results are presented.
Kasho Dam is a 46 meter high concrete gravity dam located in Tottori Prefecture in western Japan. On October 6, 2000, an earthquake of JMA—Japan Meteorological Agency—magnitude 7.3 (moment magnitude 6.6) occurred in the western part of Tottori Prefecture. According to the JMA, the source fault was thrust type in the EW direction of compression which is typical of this region. Kasho dam was built in 1988 for flood control and municipal water supply purposes. The dam has nine ungated crest spillways and one gated outlet in its middle elevation. Measured PGA was 0.5g and 2.0g at the foundation gallery and dam crest respectively. The dam sustained no damage except minor cracking of a concrete cantilever beam for the service gate hoist on the crest. 3-D reproduction analyses were performed of the crest structure and transverse joints, and the effects of modeling of crest structures, foundations and transverse joints on the numerical analysis results were examined.
