Preparation of Short-life Berkelium Tracers by 241Am(α,xn) or 243Am(α,xn) Reactions

開始ページ、終了ページ: 冊子体のページ付

A new method to establish the rational extent of hepatic resection for advanced gallbladder cancer using dye injection through the cystic artery

BackgroundHepatic resection has been indicated to eliminate cancer at the surgical margin in cases of advanced gallbladder carcinoma, but there is considerable controversy about the reasonable extent of liver resection. A new on‐table dye injection technique has been introduced to determine the venous drainage of the gallbladder and ascertain the amount of liver to remove.MethodsIn four hepatic resections for pT2 gallbladder cancer, indocyanine green solution (25 mg/20 ml) was injected over a period of 30 seconds through the cystic artery. The stained area of the liver surface was completely resected, maintaining a margin of at least 2 cm from the gallbladder.ResultsThe entire serosal surface of the gallbladder takes on a light green stain immediately after dye injection, and then the liver surface around the gallbladder gradually becomes stained with a clear demarcation line. The distance between the demarcation line and the gallbladder ranged from 1.0 to 5.0 cm. The extent of the stained area differed from one individual to another. Histopathological examination of resected liver specimens revealed that one of the four resected livers had micrometastasis in the portal area 27 mm from the gallbladder wall and there were no cancer cells at the surgical margins. No recurrence has been seen in any of our 4 patients at 16–26 months after operation.DiscussionThe dye injection method is useful in determining the appropriate extent of hepatic resection for advanced gallbladder cancer, as it is possible to determine the necessary and sufficient amount of liver parenchyma that should be removed according to the perfusion area of the cystic veins in each individual patient

MIDCAB の Pitfall

金沢大学医薬保健研究域医学系Six thoroughly selected patients underwent minimally invasive direct coronary artery bypass grafting (MIDCAB). While monitoring left ventricular function with transesophageal echocardiography, MIDCAB was done by performing small left thoracotomy through the fourth intercostal space, dissection of the left internal thoracic artery without thoracoscopy, ischemic preconditioning, and grafting of the internal thoracic artery to the left anterior descending coronary artery with 8-0 polypropylene continuous suture. A home-made cardiac stabilizer and Visuflow enabled us to perform precise suturing of the internal thoracic artery. The patency of all grafts was confirmed by early transthoracic Doppler echocardiography and selective angiography. A new stenosis of the coronary artery distal to the anastomosis was detected probably due to coronary snaring in one patient. The anastomosis sites were confined to the distal segments of the left anterior descending coronary artery in MIDCAB patients. The optimal anastomosis site may be missed in the patients with proximal left anterior descending artery disease. An experimental study of myocardial tissue oxygen saturation using near infrared spectroscopy showed that two times of coronary occlusion and reperfusion provided satisfactory effects of ischemic preconditioning. Measurement of the myocardial tissue oxygen saturation may be helpful for confirming effective ischemic preconditioning and a safe coronary occlusion during MIDCAB. Although MIDCAB is an attractive procedure, we should consider the accuracy of anastomosis, the risk of possible incomplete revascularization, the indications, and long-term results

高齢者 (71歳) のFallot 四徴症の1根治例

金沢大学医薬保健研究域医学系A 71-year-old male is presented as ever the oldest patient of tetralogy of Fallot who underwent successful radical surgery. Heart murmur was pointed out at the age of 10 years. The patient consulted us because of dyspnea and cough, and was noted to have cyanosis and clubbing fingers. Polycythemia was also detected by hemoglobin of 20.8 g/dl and hematocrit of 58.4%, and a low PaO2 of 48.5 mmHg at room temperature was pointed out. Preoperative echocardiography and cardiac catheterization indicated a ventricular septal defect, overriding of the aorta, and right ventricular outflow tract stenosis with a pressure gradient of 115 mmHg between the right ventricle and the main pulmonary artery. Under cardiopulmonary bypass, the ventricular septal defect was closed with a dacron patch and the right ventricular outflow tract was enlarged by a patch of collagen-coated vascular graft with a commissurotomy of the pulmonary valve. Postoperatively, cyanosis disappeared and the pressure gradient was decreased to 26 mmHg

Stability Constants of Chloro and Bromo Complexes of Some Lanthanoids(III) and Actinoids(III)

開始ページ、終了ページ: 冊子体のページ付

Dolutegravir Interactions with HIV-1 Integrase-DNA: Structural Rationale for Drug Resistance and Dissociation Kinetics

<div><p>Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. In accord with clinical findings, in vitro drug resistance profiling studies with wild-type and site-directed integrase mutant viruses have shown significant fold increases in raltegravir and elvitegravir resistance for the specified viral mutants relative to wild-type HIV-1. Dolutegravir, in contrast, has demonstrated clinical efficacy in subjects failing raltegravir therapy due to integrase mutations at Y143, Q148 or N155, which is consistent with its distinct in vitro resistance profile as dolutegravir’s antiviral activity against these viral mutants is equivalent to its activity against wild-type HIV-1. Kinetic studies of inhibitor dissociation from wild-type and mutant integrase-viral DNA complexes have shown that dolutegravir also has a distinct off-rate profile with dissociative half-lives substantially longer than those of raltegravir and elvitegravir, suggesting that dolutegravir’s prolonged binding may be an important contributing factor to its distinct resistance profile. To provide a structural rationale for these observations, we constructed several molecular models of wild-type and clinically relevant mutant HIV-1 integrase enzymes in complex with viral DNA and dolutegravir, raltegravir or elvitegravir. Here, we discuss our structural models and the posited effects that the integrase mutations and the structural and electronic properties of the integrase inhibitors may have on the catalytic pocket and inhibitor binding and, consequently, on antiviral potency in vitro and in the clinic.</p> </div

Structural models of HIV-1 integrase with U5 LTR DNA and (A, B) raltegravir, (C) elvitegravir or (D) dolutegravir.

<p>For raltegravir, the terminal 3′ adenylate is depicted in 2 distinct conformations: panel 2A shows the published conformer and panel 2B shows an alternative conformer that is also consistent with the observed electron density. Raltegravir, elvitegravir and dolutegravir are in stick representation with carbon, nitrogen, oxygen, fluorine and chlorine atoms colored gray, blue, red, cyan and green, respectively. A select subset of amino acids and nucleotides is depicted and labeled with residue type and number (numbering schemes as listed in Figure S1); all residues are in stick representation with carbon atoms colored by secondary structure/chain and nitrogen and oxygen atoms colored blue and red, respectively. The Mg²⁺ ions are represented as small yellow spheres with coordinate bonds to the inhibitors depicted as dashed yellow lines.</p