International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change... 相似文献
The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.
Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.
Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.
Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low Km value was relatively comparable to that for marmoset livers.
These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.
We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness. 相似文献
There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).
Methods
Patients with AEG and UGC who were judged as non-sarcopenic before surgery were reassessed the presence of postoperative development of sarcopenia 6 months after surgery. Patients were divided into the development group or non-development group, and clinicopathological factors and prognosis between these two groups were analyzed.
Results
The 5-year overall survival rates were significantly poorer in the development group than non-development group (68.0% vs. 92.6%, P?=?0.0118). Multivariate analyses showed that postoperative development of sarcopenia was an independent prognostic factor for poor overall survival (P?=?0.0237).
Conclusions
Postoperative development of sarcopenia was associated with a poor prognosis in patients with AEG and UGC. 相似文献
Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid. 相似文献
The insular cortex plays essential roles in nicotine addiction. However, much is still unknown about its cellular and synaptic mechanisms responsible for nicotine addiction. We have previously shown that in layer 5 pyramidal neurons of the mouse insular cortex, activation of the nicotinic acetylcholine receptors (nAChRs) suppresses synaptic potentiation through enhancing GABAergic synaptic transmission, although it enhances both glutamatergic and GABAergic synaptic transmission. In the present study, we examined whether dopamine receptors might contribute to the nicotine‐induced inhibition of synaptic potentiation. The nicotine‐induced inhibition of synaptic potentiation was decreased in the presence of a D1 dopamine receptor antagonist SCH23390 irrespective of the presence of a D2 dopamine receptor antagonist sulpiride, suggesting that D1 dopamine receptors are involved in nicotine‐induced inhibition. We also investigated how dopamine receptors might contribute to the nAChR‐induced enhancement of glutamatergic and GABAergic synaptic transmission. The nAChR‐induced enhancement of GABAergic synaptic transmission was decreased in the presence of SCH23390 irrespective of the presence of sulpiride, whereas that of glutamatergic synaptic transmission was not altered in the presence of SCH23390 and sulpiride. These results suggest that D1 dopamine receptors are involved in the nAChR‐induced enhancement of GABAergic synaptic transmission while dopamine receptors are not involved in that of glutamatergic synaptic transmission. These observations indicate that the interaction between nAChRs and D1 dopamine receptors plays critical roles in synaptic activities in layer 5 pyramidal neurons of the mouse insular cortex. These insular synaptic changes might be associated with nicotine addiction. 相似文献
Even for patients with multiple pancreaticoduodenal aneurysms, successful treatment with noninvasive operative procedures can be employed, if intraoperative devices are considered. A 73‐year‐old man, without any symptoms, was admitted to our hospital and had computed tomography (CT) scanning to examine his liver for hepatitis C virus (HCV). Selective superior mesenteric artery (SMA) angiography confirmed multiple aneurysms in the anterior inferior pancreaticoduodenal artery (AIPDA), one aneurysm in the posterior inferior mesenteric artery (PIPDA), and another in the occluded celiac trunk, all with severe calcification. All of the aneurysms were thought to communicate with each other. With the celiac artery occlusion, the right hepatic artery (RHA) was revealed to be supplied by collateral arteries from the aneurysms in the AIPDA, and the left hepatic artery was shown to be supplied by collaterals from the left gastric artery. Intraoperative Doppler echography, at the time of the clamping of both IPDAs, demonstrated a marked decrease of blood velocity in all aneurysms (before clamping, >50 cm/s; after, <10 cm/s), although loss of pulsation and a marked decrease of flow in the RHA were inevitable. Therefore, each of these two IPDAs were ligated on the proximal side to the aneurysm, thus preserving the blood flow of the pancreas head fed by the PIPDA; bypass grafting from the AIPDA to the RHA, using the great saphenous vein, was done at the same time. After the creation of an anastomosis, the hepatic venous oxygen saturation (ShvO2) increased from 38% (at the time of ligation of the IPDAs) to 57% under ventilation. The patient's postoperative clinical course was uneventful. We describe and discuss our successful noninvasive operative management of multiple pancreaticoduodenal aneurysms, done while monitoring the blood flow and ShvO2, with some consideration of the literature. 相似文献