Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

缺血性中风(中经络)证候分类与血脂、血压、血液流变学关系的研究

目的探讨缺血性中风证侯分类的客观量度。方法本研究对118例缺血性中风患者按中医证类进行分组,观察各证类组病例的血脂、血压及血液流变学改变。结果研究表明,风痰阻络证、痰热腑实证及气虚血瘀证组脂质变化较正常组明显升高(P<0.05～0.01),其中风痰阻络证、痰热腑实证与气虚血瘀证组存在显著差异(P<0.05);气虚血瘀证、风痰阻络证及痰热腑实证组血液流变学指标较正常组有显著差异(P<0.05～0.01);肝阳暴亢证、痰热腑实证组血压明显高于气虚血瘀证、风痰阻络证及阴虚风动证组(P<0.05～0.01)。结论血脂、血压及血液流变学指标可为缺血性中风证候分类提供客观量度。     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

Thrombin activates the p21-activated kinase in pulmonary artery smooth muscle cells. Role in tissue factor expression

The p21-activated serine/threonine kinases (PAK) play an important role in a variety of cellular functions. However, their role in the smooth muscle response to thrombin, which is activated upon vascular injury and promotes vascular remodelling processes, is not resolved. Here we investigated the role of PAK in thrombin signalling and regulation of tissue factor (TF), the activator of the extrinsic coagulation cascade, in pulmonary artery smooth muscle cells (PASMC), the main cell type responsible for vascular remodelling in pulmonary hypertension. PAK was rapidly phosphorylated in response to thrombin. Thrombin and active PAKT423E phosphorylated p38 MAP kinase (p38MAPK), ERK1/2, phosphatidylinositol-dependent kinase-1 (PDK1) and protein kinase B/Akt (PKB) whereas kinase-deficient PAK1 prevented activation of these kinases by thrombin. In addition, kinase- deficient MKK3 inhibited activation of PDK1 and PKB by thrombin. Further, thrombin and active PAK1 induced TF expression and promoter activity while kinase-deficient PAK1 diminished thrombin-induced TF upregulation. Moreover, kinase-deficient MKK3, PDK1 and PKB inhibited thrombin- and PAK-dependent TF expression and promoter activity. Together these findings show that PAK is a critical element of thrombin signalling in PASMC which is involved in the regulation of TF expression by sequentially activating MKK3/p38MAPK, PDK1 and PKB. Thus, PAK may play an important role in promoting vascular remodelling processes in pulmonary hypertension.     

Mood change after anaesthesia with remifentanil or alfentanil

BACKGROUND AND OBJECTIVE: There are anecdotal reports of dysphoria occurring in patients on the first day after anaesthesia with remifentanil. This study was performed to investigate this allegation and to find a possible relationship to postoperative shivering or to nausea and vomiting. METHODS: Patients undergoing otorhinolaryngeal surgery took part in a prospective, randomized, double-blind study comparing total intravenous anaesthesia with propofol (2 mg kg(-1) bolus injection then 100 microg kg(-1) min(-1)) and remifentanil (1 microg kg(-1) bolus then 0.1-0.5 microg kg(-1) min-1) or alfentanil (30 microg kg(-1) bolus then 0.16-0.83 microg kg((-1) min(-1)). The patients were carefully insulated and actively warmed by convective heating and rectal temperature was monitored continuously. Postoperative shivering was graded on a three-point scale, and the cumulative incidence of nausea and vomiting were registered at 24 h after surgery. Pre- and postoperative mood was measured with the von Zerssen mood scale (Befindlichkeits-Skala) and changes tested for significance. High scores reflect discontent and dysphoria. RESULTS: The data of 98 patients (49 in each group, ASA I-II, age 42 +/- 13 yr, anaesthesia time 141 +/- 60 min; mean +/- SD; intergroup P values > 0.1) were evaluated. Core temperature did not change perioperatively (before 36.6 +/- 0.2 degrees C; after 36.8 +/- 0.3 degrees C, inter- and intragroup P > 0.1). The incidence of nausea was the same in each group; vomiting occurred with equal frequency (6/49 vs. 7/49). Shivering was significantly more frequent after remifentanil (41% vs. 10%, P < 0.001). The patients' mood remained stable after remifentanil but worsened after alfentanil (von Zerssen score from 9.3 +/- 2.5 to 13.9 +/- 3.6; mean +/- 95% confidence intervals; P < 0.01). DISCUSSION: Postoperative shivering was more frequent after remifentanil but was unrelated to intraoperative heat loss. Contrary to preliminary informal observations, there was no evidence that remifentanil caused postanaesthetic dysphoria on the day one after surgery.     

Effects of the phosphodiesterase 4 inhibitor RPR 73401 in a model of immunological inflammation

The study was performed to investigate effects of the phosphodiesterase 4 inhibitor RPR 73401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyl-oxy-4-methoxybenzamid] on an allergic skin reaction. To simulate an immunological inflammation, BALB/c mice were sensitized to dinitrochlorobenzene or toluenediisocyanate. At first, the abdominal skin was shaved and 50 microliter Freund's adjuvant were injected intracutaneously once. Then, the horny layer was removed by adhesive tape stripping and 100 microliter 0.5% dinitrochlorobenzene or 5% toluenediisocyanate were administered on the epidermis for 4 days. After repeated local treatment of the ear skin with 20 microliter 3% RPR 73401 or intraperitoneal administration of 1 and 5 mg/kg RPR 73401, 20 microliter 1% dinitrochlorobenzene or 0.5% toluenediisocyanate were given topically as a challenge. The vehicle controls showed a high increase in ear thickness over 48 h after challenge, whereas RPR 73401 administered on either route reduced this increase significantly. Nevertheless after topical administration, RPR 73401 had a longer lasting effect. These and other results may point to an indication for RPR 73401 in immunological dermatitis.