RESUMEN
Vitamin D (VD) exerts a wide variety of biological actions in addition to its well-known roles in calcium homeostasis. Nutritional VD deficiency induces rachitic abnormalities in growing children and osteomalacia in adults, and it has been proposed to underlie the onset and development of multiple non-communicable chronic diseases. Therefore, the administration of VD or synthetic VD analogues represents a promising therapeutic strategy; indeed, VD and a VD agonist have shown clinical promise in mitigating osteoporosis and symptoms of insufficient calcium intake. However, even though high doses of VD analogues have shown pre-clinical efficacy against several diseases, including cancers, they have not yet had wide-spread clinical success. This difference may be due to limitation of clinical doses in light of the inherent calcemic action of VD. An approach to overcome this problem involves the development of VD analogues with lower calcemic activity, which could be administered in high doses to attenuate the onset and progress of disease. In a similar strategy, selective estrogen receptor modulators have had success as anti-osteoporosis drugs, and they have shown benefit for other estrogen target organs by serving as partial antagonists or agonists of estrogen receptor α. It is thus conceivable to generate synthetic partial antagonists or agonists for the VD receptor (VDR) that would exert beneficial effects on bone and other VD target organs. In this review, we discuss the molecular basis of the development of such synthetic VDR ligands from the viewpoint of roles of VDR in gene regulation.
RESUMEN
A 24-year-old woman underwent successful repair of a traumatic pseudoaneurysm of the aortic isthmus concomitant with right diaphragmatic hernia which developed after a traffic accident, and the steering wheel of the crashed car was considered responsible for both lesions. Due to the right diaphragmatic hernia, she could breathe mainly with the left lung only. The aortic isthmus aneurysm was considered to be a pseudoaneurysm, and because of the potential risk of rupture, we performed urgent aortic surgery. Prior to a left thoracotomy, we anastomosed an 8-mm prosthetic graft to the right axillary artery. When the left lung was collapsed in order to perform a femoro-femoral bypass, the SpO<sub>2</sub> level of her right index finger and her cerebral rSO<sub>2</sub> markedly decreased. Therefore, we administered additional perfusion via the right axillary artery, which provided sufficient oxygen to the upper body and brain. The patient underwent Marlex mesh reinforcement of the right diaphragmatic hernia 30 days after grafting, and is doing well 1 year postoperatively.
RESUMEN
Dermal ulcers related to infiltration of advanced cancer often release destruction-associated effluvia (cancerous malodor). We encountered a patient in whom metronidazole (MTZ) was effective for cancerous malodor at the dermal ulcer site related to pleural metastasis, involving the thoracic wall, from gastric cancer. The patient was a male in his 60's. As left subphrenic abscess associated with suture failure at the anastomotic site after surgery for gastric cancer led to pyothorax via the transdiaphragmatic route, a thoracic drain was inserted. Furthermore, bilateral pulmonary metastases and pleural dissemination were detected. Subsequently, the metastatic pleural focus infiltrated the thoracic wall via the space between the thoracic drain and chest wall. Its destruction resulted in fetid ulcer formation. The application of MTZ ointment relieved cancerous malodor. In addition to assessment using an odorimeter, the patient's subjective evaluation-based score confirmed the efficacy of this agent. Palliat Care Res 2009; 4(2): 339-345
RESUMEN
A 22-year-old woman had been treated with a Ross operation for aortic root aneurysm and aortic regurgitation 10 years previously. In the initial Ross operation, a handmade tri-leaflet conduit was used for the right ventricle outflow tract (RVOT) reconstruction. The conduit was prepared preoperatively, by sewing a folded 0.1 mm expanded polytetrafluoroethylene (ePTFE) membrane onto the luminal cavity of the 24 mm woven double velour vascular graft, thereby creating a tri-leaflet valve. During ambulatory follow up after discharge, dilation of the pulmonary autograft had been observed, and its maximal diameter reached 60 mm. Furthermore, preoperative a pressure study revealed a 25 mmHg pressure gradient between the right ventricle and the pulmonary artery. At the time of reoperation, we performed an aortic root replacement combined with RVOT conduit replacement. A 24-mm woven double velour vascular graft integrating a 21-mm On-X mechanical prosthesis was used for aortic root replacement. A handmade ePTFE tri-leaflet conduit, 26 mm in size, was used to replace the previous RVOT conduit. The operation was successful, and the postoperative course was uneventful. The explanted conduit was sent for microscopic examination, which revealed that the graft was covered by a fibrocollagenous membrane. On the contrary, no surface membrane was found on the ePTFE valve. Moreover the microscopic examination showed cystic medionecrosis of the pulmonary autograft. Both dilatation of the pulmonary autograft and RVOT conduit failure were successfully treated at the second operation. However this young patient will require follow-up of the mechanical prosthesis and RVOT conduit for the rest of her life.