Sensitive and Comprehensive LC-MS/MS Analyses of Chiral Pharmaceuticals and Their Hepatic Metabolites Using Ovomucoid Column.

A sensitive analytical method was developed for the simultaneous detection of 11 chiral pharmaceuticals and their hepatic metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using an ovomucoid chiral column. After optimization of the LC conditions, all pharmaceuticals examined were enantio-separated with Rs of >0.82 in LC-MS/MS analysis. The limit of detections of all pharmaceuticals by MS/MS detection ranged from 1.2 to 92.3 nM, which is approximately 1000 - 25000 times lower than those obtained by UV detection. From hepatic metabolite analyses in P450-expressing cells, metabolites of three pharmaceuticals were detected and enantio-separated. By using the proposed method, changes in the optical isomer ratio of the hepatic metabolites chlorpheniramine and verapamil caused by differential cytochrome P450 enzyme expression for each isomer, could be successfully traced.

Postoperative quality of life and dysfunction in patients after combined total gastrectomy and esophagectomy.

BACKGROUND: Patients with esophageal cancer and a history of gastrectomy or concurrent gastric cancer undergo not only esophagectomy but also total gastrectomy. The goal of this study is to evaluate the postoperative quality of life (QOL) and dysfunction of these patients using two postoperative questionnaires. MATERIALS AND METHODS: From 1999 to 2015, 41 patients underwent concurrent esophagectomy and total gastrectomy. A jejunal pedicle with the subcutaneous supercharge technique was used for reconstruction. Patients were divided into two groups, including those undergoing concurrent esophagostomy and gastrectomy (Group 1), and those undergoing esophagectomy alone (Group 2, history of previous gastrectomy). Patients were analyzed by time interval, including patients within three years of surgery (Group A) and those more than three years after surgery (Group B). RESULTS: Eighteen patients completed the questionnaires. The mean DAUGS20 score was 26.4 ± 13.2. The DAUGS20 scores of groups 1 (N = 7) and 2 (N = 11) were 25.4 ± 12.5 and 27 ± 15.4 (p = 0.58), respectively. Global health status scored by the EORTC QLQC-30 were 71.4 ± 18.5 in group 1 and 67.4 ± 22.8 in group 2 (p = 0.85). DAUGS20 scores of group A (N = 10) and B (N = 8) were 28.1 ± 12.4 and 23.3 ± 14.4 (p = 0.35). No significant differences were found between groups A and B regarding the QLQ-C30 scores. CONCLUSION: DAUGS20 and QLQ-C30 scores showed no significant differences between groups 1 and 2 or groups A and B. These results suggest that postoperative QOL and dysfunction may be influenced more by current status than by surgical history and postoperative interval. Previous reports describe a DAUGS 20 score after gastrectomy of 27.8 and after esophagectomy of 36.1. The DAUGS20 score of these 18 patients is lower than DAUGS20 scores for patients undergoing either operation alone. Reconstruction using a subcutaneously placed jejunal segment seems to be reasonable.

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors.

During liver injury, hepatic stellate cells (HSCs) are activated by various cytokines and transdifferentiated into myofibroblast-like activated HSCs, which produce collagen, a major source of liver fibrosis. Therefore, the suppression of HSC activation is regarded as a therapeutic target for liver fibrosis. Several epidemiological reports have revealed that caffeine intake decreases the risk of liver disease. In this study, therefore, we investigated the effect of caffeine on the activation of primary HSCs isolated from mice. Caffeine suppressed the activation of HSC in a concentration-dependent manner. BAPTA-AM, an intracellular Ca2+ chelator, had no effect on the caffeine-induced suppression of HSC activation. None of the isoform-selective inhibitors of phosphodiesterase1 to 5 affected changes in the morphology of HSC during activation, whereas CGS-15943, an adenosine receptor antagonist, inhibited them. Caffeine had no effect on intracellular cAMP level or on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2. In contrast, caffeine significantly decreased the phosphorylation of Akt1. These results suggest that caffeine inhibits HSC activation by antagonizing adenosine receptors, leading to Akt1 signaling activation.

Implications for better nursing practice: psychological aspects of patients undergoing post-operative wound care.

AIMS AND OBJECTIVES: To understand the psychological aspects in patients undergoing post-operative wound care and to gain insights for improving nursing practice. BACKGROUND: Very few studies have examined education on or practice of wound care with a view towards the patient's psychology. DESIGN: Descriptive exploratory qualitative study. METHODS: Four patients who had undergone open surgery of the upper gastrointestinal tract were interviewed using a semi-structured format to gain an understanding of their feelings and opinions with regard to wound care. Interview transcripts were analysed using an inductive coding approach. RESULTS: Fifteen categories of responses were finally identified from the data. Patients wanted nursing staff to observe their wound more often so that patients could recognise improvement, to have better knowledge of the patient's disease and condition, to explain the patient's situation more completely and to appropriately answer questions. Patients also said that they felt more comfortable in posing questions or concerns regarding their condition to nursing staff than to their surgeons and did so while the wounds were being taken care of by nurses. CONCLUSIONS: These findings suggested the importance of nursing staff to fully understand and to be ready to share feelings regarding a patient's postoperative condition and to have skills in properly explaining the importance of each procedure or steps in treatments that a patient must undergo. The present study also indicates that it is imperative for nursing staff to learn methods to build relationships with patients so that they can express their feelings of fear or anxiety freely to nurses. RELEVANCE TO CLINICAL PRACTICE: It is not possible to develop nursing practice without understanding psychological aspects of patients undergoing postoperative wound care.

Postoperative quality of life: development and validation of the "Dysfunction After Upper Gastrointestinal Surgery" scoring system.

BACKGROUND: Although postoperative quality of life is an important outcomes measure, few tools exist to evaluate patients specifically after upper gastrointestinal surgery. The previously developed Dysfunction After Upper Gastrointestinal Surgery (DAUGS)32 scoring system has been further refined to include just 20 items. This study was undertaken to validate the refined evaluation tool. STUDY DESIGN: The study was performed as a survey, administered to patients after upper gastrointestinal resection at 3 separate institutions. RESULTS: The DAUGS20 score after gastrectomy (n = 662) was 27.8 and that after esophagectomy (n = 221) was 36.1, showing a significant difference (p < 0.05). The score after distal gastrectomy (n = 282) was 25.4 and that after total gastrectomy (n = 149) was 32.0, showing a significant (p < 0.05) difference. The α coefficient of all items on the DAUGS20 system was 0.904 and Cronbach's α coefficients of the subscales were 0.612 to 0.856, demonstrating high reliability of this evaluation tool. In addition, 7 factors were extracted from the 20 items using definitive factor analysis, to verify validity. CONCLUSIONS: Patient quality of life should be evaluated as an outcomes measure after surgical resection for cancer, just as overall survival is analyzed. The DAUGS20 score is reliable, has validity in the evaluation of postoperative patients, and is a valuable tool to assess patient quality of life after upper gastrointestinal surgery for cancer.

Extent of gastric resection impacts patient quality of life: the Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS32) scoring system.

BACKGROUND: Quality of life is an important outcome measure in the care of patients with cancer. We developed a new scoring system specifically for the evaluation of patients with upper gastrointestinal cancer and postoperative gastrointestinal dysfunction. This study was undertaken to evaluate the scoring system's validity in comparing outcomes after gastric resection. MATERIALS AND METHODS: Patients with gastric cancer, 3 months to 3 years postoperatively, were surveyed using the survey instrument. Postoperative dysfunction scores and the status of resuming activities of daily living were compared with the surgical procedure performed by analysis of variance and multiple-comparison techniques. RESULTS: Of 211 patients surveyed, 165 (119 men, 46 women; mean age, 65.1 ± 10.5 years) responded. Procedures included distal gastrectomy in 100, total gastrectomy in 57, and pylorus-preserving gastrectomy in 8. The overall dysfunction score was 61.8 ± 15.5. The dysfunction score was 58.9 ± 15.0 after distal gastrectomy, 66.8 ± 14.1 after total gastrectomy, and 62.4 ± 21.6 after pylorus-preserving gastrectomy. These values differed significantly among the groups (P = .007). Dysfunction scores according to postoperative activity status were 49.1 ± 15.6 in 71 patients who resumed their activities, 56.9 ± 15.7 in 39 patients with reduced activities, 57.3 ± 8.8 in 15 patients with minimal activities, and 63.3 ± 11.8 (P < .05) in 16 patients who did not resume activities because of poor physical condition. CONCLUSIONS: This scoring system for postoperative gastrointestinal dysfunction provides an objective measure of dysfunction related to specific surgical procedures and correlates with activities of daily living in the postoperative period.

Development of a 32-item scale to assess postoperative dysfunction after upper gastrointestinal cancer resection.

AIM: The purpose of this study was to develop a 32-item scale to assess postoperative dysfunction in patients who underwent surgery for gastric and oesophageal cancer and to evaluate its reliability and validity. BACKGROUND: For the objective assessment of postoperative dysfunction in patients with upper gastointestinal cancer, we performed a preliminary survey by mail using a 34-item questionnaire as a initial version. The results of the survey were assessed by item analysis of the scale. The scale items were further refined by researchers and specialists, and a 32-item scale for the assessment of postoperative dysfunction (initial scale) was developed. METHODS: Using this 32-item scale (initial scale), a mail survey was performed of 379 subjects selected by random sampling. RESULTS: The questionnaire was returned by 292 patients (77.1%) and 283 responses (74.7%) were valid. Of these, 221 respondents had gastric cancer and 62 oesophageal cancer. The mean age of respondents was 64.9 SD 9.8 (range 35-89) years. The mean total score of the 32-items on the initial version for the assessment of postoperative dysfunction was 60.8 SD 16.7. The mean total score for gastric cancer patients and oesophageal cancer patients was 58.1 SD 15.8 and 70.1 SD 16.7 respectively. After the elimination of scale items regarded as irrelevant based on statistical considerations and the judgement of experts, factor analysis was performed. Seven factors were valid: 'regurgitation reflux', 'limited activity because of decreased food consumption', 'passage dysfunction immediately after eating', 'dumping-like symptoms', 'transfer dysfunction', 'hypoglycaemic symptoms' and 'diarrhoea-like symptoms'. The cumulative proportion of variance by scale reliability was confirmed by a Cronbach's alpha-coefficient of 0.926. The Cronbach's alpha-coefficient for all 32 items on the initial version was 0.926, the Cronbach's alpha-coefficient for sub-items was 0.705-0.856, and Pearson's correlation coefficient of re-test for the total score of the 32 items was 0.865, which confirmed a high degree of internal consistency. The construct validity of the scale was confirmed using the known-group technique by operative procedures, and from the result of factorial validity. This scale was named 'Postoperative Dysfunction for Upper Gastrointestinal Cancer 32; PODUGC-32'. CONCLUSION: This scale is sufficiently reliable and valid and will be useful clinically. Relevance to clinical practice. We can use the new scale to assess postoperative dysfunction in patients with upper gastointestinal cancer for nursing practice.

Postoperative gastrointestinal dysfunction after 2-field versus 3-field lymph node dissection in patients with esophageal cancer.

PURPOSE: Using an instrument we developed to assess postoperative dysfunction objectively (Surg Today 2005;35:535-42), we compared postoperative dysfunction after 2 - field versus 3 - field lymph node dissection retrospectively, in patents undergoing esophageal cancer surgery. METHODS: Subjects were selected randomly from among patients who had undergone radical surgery for squamous cell carcinoma of the thoracic esophagus followed by reconstruction with a gastric tube and a cervical anastomosis. Patients rated 32 items related to postoperative dysfunction according to a 5-grade scale. Postoperative gastrointestinal dysfunction was evaluated on the basis of the total score and the scores for seven symptom categories: decreased physical activity, symptoms of reflux, dumping-like syndrome, nausea and vomiting, passage dysfunction, pain, and diarrhea or soft feces. RESULTS: We studied 42 patients, 22 of whom underwent 2-field lymph node dissection and 20 of whom underwent 3-field dissection. The total gastrointestinal dysfunction score was significantly higher in the 3-field group than in the 2-field group (78.4 +/- 14.1 points vs 67.9 +/- 16.9 points, P = 0.038). When we analyzed the data according to the symptom categories, the 3-field group had higher scores for decreased physical activity, symptoms of reflux, dumping-like syndrome, nausea and vomiting, and passage dysfunction. CONCLUSION: Three-field lymph node dissection was associated with greater postoperative gastrointestinal dysfunction than 2-field lymph node dissection. Thus, the preoperative identification of those patients with esophageal cancer who are most likely to benefit from concurrent cervical lymph node dissection is essential.

Reliability and validity of a new scale to assess postoperative dysfunction after resection of upper gastrointestinal carcinoma.

PURPOSE: We evaluated the purpose reliability and validity of a preliminary scale, which we developed to assess postoperative dysfunction after surgery for gastric and esophageal carcinoma. METHODS: After interviews with 12 patients, reviews of previous studies, and discussions with experts, we identified the physical symptoms that develop after resection of upper gastrointestinal (GIT) carcinoma, and devised a preliminary scale comprised of 34 items. A questionnaire survey based on this scale was then sent to 283 patients. RESULTS: The questionnaire was returned by 223 patients (78.8%), and 219 responses (98.2%) were valid. Among the 219 respondents, 168 had gastric carcinoma and 51 had esophageal carcinoma. After the elimination of scale items regarded as irrelevant based on statistical considerations and the judgment of experts, factor analysis was done. Seven factors were valid, namely, limited activity due to decreased food consumption, reflux, gastric dumping, nausea and vomiting, deglutition difficulty, pain, and difficulty with passing stools, which were often poorly formed. Scale reliability was confirmed by a Cronbach alpha-coefficient of 0.924. The validity of the construction of this scale was confirmed using the known-group technique based on the operative procedures performed, and the results of factorial validity. CONCLUSION: Our preliminary scale is sufficiently reliable and valid, and will prove to be clinically useful.