Perception of discomfort by relatives and nurses in unresponsive terminally ill patients with cancer: a prospective study

Perception of discomfort in dying patients is a risk factor for distress and bereavement among relatives. This study determined the perception of discomfort, the frequency of observed behaviors, and their association among relatives and among nurses who care for unresponsive dying patients. Sixty unresponsive dying patients' relatives and their nurses were asked to evaluate patient discomfort levels, the frequencies of six observed behaviors, and the suspected reasons for the patient discomfort. The mean levels of perceived discomfort were similar, but the association was poor between the relatives and the nurses. Relatives reported significantly more observed behaviors and associated more pain as a reason for patient discomfort than did nurses. The findings suggest that relatives are intensely attuned to their loved ones' conditions and reactions, and nurses' responses are fairly similar. Further research is warranted, however, to distinguish between the distress that the relatives perceive and the actual suffering of patients.     

Lactobacillus crispatus capsules: single-use safety study in the Macaca nemestrina model

BACKGROUND: Lactobacillus crispatus is a part of the normal vaginal microflora of humans. GOAL: The goal of this study was to assess whether a capsule containing an H2O2-producing strain of L crispatus (CTV-05) would alter the vaginal microflora and/or epithelial tissues when applied intravaginally in the pig-tailed macaque model. STUDY DESIGN: Ten sexually mature female Macaca nemestrina were assessed at baseline for quantitative vaginal microbiology and vaginal pH and with colposcopy. One capsule containing 108 colony forming units of desiccated L crispatus CTV-05 was inserted into the vaginal fornix of each animal. Vaginal assessments were repeated on days 1 and 2 after capsule insertion. The L crispatus CTV-05 strain was identified with use of a DNA fingerprinting method. RESULTS: Before product use, four of 10 animals had detectable levels of H2O2-producing lactobacilli. L crispatus CTV-05 was detected in 1 of 10 animals on day 1 and in 3 of 10 animals on day 2 following insertion of the capsule. There were no tissue changes observed by colposcopy. Vaginal pH decreased in two animals colonized by CTV-05, from 7.0 at baseline to 4.5+/-0.5 on days 1 and 2 after product use. CONCLUSIONS: A single intravaginal application of capsules containing 108 L crispatus CTV-05 resulted in vaginal colonization in three of 10 animals 2 days after use. The absence of colposcopic changes in the vagina/cervical tissues indicates that L crispatus capsules are well tolerated.     

The Snark is a Boojum: the continuing problem of drug resistance in the antiangiogenic era.

If your Snark be a Snark, that is right: Fetch it home by all means-you may serve it with greens, And it's handy for striking a light. "But oh, beamish nephew, beware of the day, If your Snark be a Boojum! For then You will softly and suddenly vanish away, And never be met with again!" Lewis Carroll The Hunting of the Snark     

Need for GLUT4 activation to reach maximum effect of insulin-mediated glucose uptake in brown adipocytes isolated from GLUT4myc-expressing mice

There is a need to understand whether the amount of GLUT4 at the cell surface determines the extent of glucose uptake in response to insulin. Thus, we created a heterozygous mouse expressing modest levels of myc-tagged GLUT4 (GLUT4myc) in insulin-sensitive tissues under the control of the human GLUT4 promoter. Insulin stimulated 2-deoxyglucose uptake 6.5-fold in isolated brown adipocytes. GLUT1 did not contribute to the insulin response. The stimulation by insulin was completely blocked by wortmannin and partly (55 +/- 2%) by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Insulin increased surface exposure of GLUT4myc twofold (determined by fluorescent or enzyme-linked myc immunodetection in intact adipocytes). Such increase was completely blocked by wortmannin but insensitive to SB203580. Insulin increased the kinase activity of the p38 MAPK beta-isoform 1.9-fold without affecting p38-alpha. In summary, the GLUT4myc mouse is a promising model for measuring GLUT4 translocation in intact primary cells. It affords direct comparison between GLUT4 translocation and glucose uptake in similar cell preparations, allowing one to study the regulation of GLUT4 activity. Using this animal model, we found that stimulation of glucose uptake into brown adipocytes involves both GLUT4 translocation and activation.     

Intestinal anastomoses detected with a photopolymerized hydrogel

BACKGROUND: This study examines the efficacy of a novel, absorbable photopolymerized hydrogel sealant, Focalseal (Focal Inc, Lexington, Mass), in protecting high-risk suture deficient intestinal anastomoses (HRA) compared with conventional sutured anastomoses (CSA). METHODS: Twenty-four New Zealand white rabbits were either randomized to small bowel HRA constructed with 4 interrupted 5/0 polyglyconate sutures and treated with Focalseal or small bowel CSA constructed with 8 to 10 interrupted 5/0 polyglyconate sutures. Four rabbits from each group were killed at postoperative days 3, 7, and 21. Anastomoses were assessed for evidence of dehiscence, adhesion formation, stenosis, and bursting pressure; they were also examined histologically for collagen content estimation and blood vessel formation. RESULTS: Mean operative time was 35 minutes (SD 5) for CSA and 35 minutes (SD 5) for HRA. There was 1 postoperative death in the HRA group. A postmortem examination revealed no evidence of anastomotic leak. The remaining 23 animals were assessed as planned. There was no evidence of anastomotic dehiscence in any animal. There was no significant difference in adhesion formation (P =.09), stenosis (P =.6), or bursting pressure (P =.2) between HRA and CSA groups. Collagen (P =.007) and blood vessel (P =.002) formation were significantly increased in HRA. CONCLUSIONS: HRA treated with Focalseal heal well and have similar strength to CSA. This technique may prove valuable in procedures such as laparoscopic bowel resection.     

Fas-Fas ligand signaling pathway mediates an interleukin-12-induced rejection of a murine prostate tumor system

BACKGROUND: Recent data suggest that anti-tumor activities of interleukin-12 (IL-12) involve the induction of apoptosis. Fas (APO-1/CD95) is a type I membrane protein that is capable of initiating an apoptosis signaling pathway when bound to its ligand (FasL). We undertook this study to test the hypothesis that Fas-FasL-mediated apoptosis plays a role in IL-12-induced tumor regression. METHODS: An mIL-12 expression vector driven by cytomegalovirus promoter was used to express murine IL-12 cDNA in the RM-9 murine prostate carcinoma cell line. Control RM-9 cells and RM-9 cells stably transfected with IL-12 gene (RM-9-IL12) were inoculated subcutaneously in 4- to 6-week-old male C57BL/J6 mice. Tumor size was measured every 3 days. Western blot and immunohistochemical assays were used to evaluate Fas and FasL protein expression. In situ fluorescent end labeling was used to label apoptotic cells. RESULTS: IL-12-expressing RM-9 prostate carcinoma cells transplanted into C57BL/J6 mice grew more slowly than control RM-9 cells and vector control RM-9-Luc cells. The average survival time of the RM-9-IL12 mice was longer than 53 days, whereas the mean survival for mice transplanted with control RM-9 cells was only 16 days. Apoptotic cells were more numerous in RM-9-IL12 tumors: 10.3% vs. 1.5% in control (P = 0.001). Fas and FasL proteins were increased approximately twofold in the RM-9-IL12 tumors compared with the RM-9 control tumors as determined by Western blot and immunohistochemical analyses (P < 0.05). CONCLUSION: The Fas-FasL-mediated apoptosis pathway may contribute to the IL-12-induced rejection of prostate carcinoma.     

Integrated care pathways for vascular surgery: an analysis of the first 18 months

Design: A retrospective analysis of information gathered prospectively over an initial 18 month period of use of vascular surgical ICPs. Subjects: Patients admitted to a single vascular unit for "open" repair of abdominal aortic aneurysm (AAA), carotid endarterectomy, or femoropopliteal bypass grafting. Methods: An analysis of variance data, length of stay, and costings after the use of ICPs, compared with previous clinical practice. Results: Variance data were gathered for each of the three procedures. Variances of medication prescribing and delays in discharge were common to all procedures. In particular: (i) gastrointestinal complications were more specific to AAA repair and (ii) wound drains were removed a day later than originally proposed after femoropopliteal bypass. Overall, improved efficiency due to use of ICPs reduced the length of stay for all procedures, which was reflected in a potential cost saving of some 25%. Conclusion: There are clear benefits to the use of ICPs, resulting in more structured, efficient, and cost effective patient care. Recommended changes to current practice based on variance analysis will require continued audit to sustain this "evidence based" approach.