Widely Extended [OIII] 88 um Line Emission around the 30 Doradus Region Revealed with AKARI FIS-FTS

We present the distribution map of the far-infrared [OIII] 88um line emission around the 30 Doradus (30 Dor) region in the Large Magellanic Cloud obtained with the Fourier Transform Spectrometer of the Far-Infrared Surveyor onboard AKARI. The map reveals that the [OIII] emission is widely distributed by more than 10' around the super star cluster R136, implying that the 30 Dor region is affluent with interstellar radiation field hard enough to ionize O^{2+}. The observed [OIII] line intensities are as high as (1-2) x 10^{-6} W m^{-2} sr^{-1} on the peripheral regions 4'-5' away from the center of 30 Dor, which requires gas densities of 60-100 cm^{-3}. However the observed size of the distribution of the [OIII] emission is too large to be explained by massive stars in the 30 Dor region enshrouded by clouds with the constant gas density of 10^2 cm^{-3}. Therefore the surrounding structure is likely to be highly clumpy. We also find a global correlation between the [OIII] and the far-infrared continuum emission, suggesting that the gas and dust are well mixed in the highly-ionized region where the dust survives in clumpy dense clouds shielded from the energetic photons.Comment: 17 pages, 9 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

抗悪性腫瘍薬・ダカルバジンのラットを用いた薬物動態学的モデル解析の基礎的検討

Dacarbazine is a therapeutic agent for melanoma of alkylating anti-tumor agents. In this study, we examined its pharmacokinetic characteristics using experimental animals and investigated using various pharmacokinetic model analysis methods. The pharmacokinetic behavior of the drug can be simulated in the various treatment routes and/or schedules and provide basic information on medical treatment.The pharmacokinetics of dacarbazine followed a 2-compartment pharmacokinetic model, namely some organs being rapidly distributed and some organs taking a long time, resulting in a relatively large volume of distribution. No accumulation of dacarbazine was observed in the body after intravenous administration once daily for 5 days, which is the standard treatment schedule in clinical practice. It shows effective pharmacokinetics as drugs with a concentration-dependent effect.Dacarbazine is usually administered rapidly intravenous bolus or by iv infusion, though it is considered that dacarbazine shows similar pharmacokinetics and is effective even in the extravascular route where rapid absorption, with an absorption rate constant (ka) of about 0.5 min-1 or more, can be obtained.Using the pharmacokinetic modeling technique, it is possible to predict the pharmacokinetics when administered under various conditions, and further to predict the degree of effect onset and the time transition (duration) of the effect. In addition, by proceeding with the study, it is possible to estimate how the pharmacokinetics will change and how the effects of the drug will be affected when combination therapy is given as compared to monotherapy. Similarly, when physiological conditions change, such as age and pathological condition, the outcome of drug therapy is estimated by how the pharmacokinetics and drug effects are affected or hardly affected.論

A multi-sinusoidal compartment model as an alternative to the dispersion model for hepatic extraction kinetic analysis

The analysis of hepatic availability or hepatic extraction ratio as a function of hepatic blood flow and intrinsic clearance is important to estimate first-pass effects and oral bioavailability for pre-systemically-eliminating drugs. The dispersion model can afford more accurate analysis of hepatic availability than the other conventional models (well-stirred model, parallel-tube model). However, the model is rather complicate. In the present study, a simpler model was derived by assuming the sinusoidal space in the liver as a number of well-stirred compartments sequentially connected through the hepatic blood flow (multi-sinusoidal compartment model). In comparison with the other models, this model demonstrated hepatic outflow profiles very similar to those obtained by the dispersion model. It gave a simpler equation for hepatic availability, and improved the inaccuracy of the well-stirred model or the parallel tube model. The number of compartments, around 3, for this model corresponded to the dispersion number, 0.33, which has been reported to give the best fit to the rat hepatic outflow in the dispersion model. Similarly, the number of compartments, around 5 corresponded to the dispersion number, 0.17, which has been reported to give the best fit to the human hepatic elimination kinetics in the dispersion model.論文 (Article

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III) : a multicenter prospective interventional study

Background Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. Method A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. Results 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %–5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %–94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %–92.4 %). Conclusion IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed

Tokyo Guidelines 2018 management bundles for acute cholangitis and cholecystitis

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: . Related clinical questions and references are also include

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also include

Tokyo Guidelines 2018 diagnostic criteria and severity grading of acute cholecystitis (with videos)

The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30-day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also include