PCA-induced respiratory depression simulating stroke following endoluminal repair of abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Aim</p> <p>To report a case of severe respiratory depression with PCA fentanyl use simulating stroke in a patient who underwent routine elective endoluminal graft repair for abdominal aortic aneurysm (AAA)</p> <p>Case presentation</p> <p>A 78-year-old obese lady underwent routine endoluminal graft repair for AAA that was progressively increasing in size. Following an uneventful operation postoperative analgesia was managed with a patient-controlled analgesia (PCA) device with fentanyl. On the morning following operation the patient was found to be unusually drowsy and unresponsive to stimuli. Her GCS level was 11 with plantars upgoing bilaterally. A provisional diagnosis of stroke was made. Urgent transfer to a high-dependency unit (HDU) was arranged and she was given ventilatory support with a BiPap device. CT was performed and found to be normal. Arterial blood gas (ABG) analysis showed respiratory acidosis with PaCO₂81 mmHg, PaO₂140 mmHg, pH 7.17 and base excess -2 mmol/l. A total dose of 600 mcg of fentanyl was self-administered in the 16 hours following emergence from general anaesthesia. Naloxone was given with good effect. There was an increase in the creatinine level from 90 μmol/L preoperatively to 167 μmol/L on the first postoperative day. The patient remained on BiPap for two days that resulted in marked improvement in gas exchange. Recovery was complete.</p

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results

Cellular Cytoskeleton Dynamics Modulates Non-Viral Gene Delivery through RhoGTPases

Although it is well accepted that the constituents of the cellular microenvironment modulate a myriad of cellular processes, including cell morphology, cytoskeletal dynamics and uptake pathways, the underlying mechanism of how these pathways influence non-viral gene transfer have not been studied. Transgene expression is increased on fibronectin (Fn) coated surfaces as a consequence of increased proliferation, cell spreading and active engagement of clathrin endocytosis pathway. RhoGTPases mediate the crosstalk between the cell and Fn, and regulate cellular processes involving filamentous actin, in-response to cellular interaction with Fn. Here the role of RhoGTPases specifically Rho, Rac and Cdc42 in modulation of non-viral gene transfer in mouse mesenchymal stem (mMSCs) plated in a fibronectin microenvironment was studied. More than 90% decrease in transgene expression was observed after inactivation of RhoGTPases using difficile toxin B (TcdB) and C3 transferase. Expression of dominant negative RhoA (RhoAT19N), Rac1(Rac1T17N) and Cdc42 (Cdc42T17N) also significantly reduced polyplex uptake and transgene expression. Interactions of cells with Fn lead to activation of RhoGTPases. However, further activation of RhoA, Rac1 and Cdc42 by expression of constitutively active genes (RhoAQ63L, Rac1Q61L and Cdc42Q61L) did not further enhance transgene expression in mMSCs, when plated on Fn. In contrast, activation of RhoA, Rac1 and Cdc42 by expression of constitutively active genes for cells plated on collagen I, which by itself did not increase RhoGTPase activation, resulted in enhanced transgene expression. Our study shows that RhoGTPases regulate internalization and effective intracellular processing of polyplexes that results in efficient gene transfer

Origin and fate of methane in the Eastern Tropical North Pacific oxygen minimum zone

This work was funded by the Natural Environment Research Council (grant NE/E01559X/1)

Methane oxidation in the eastern tropical North Pacific Ocean water column

We report methane (CH4) concentration and methane oxidation (MO x) rate measurements from the eastern tropical north Pacific (ETNP) water column. This region comprises low-CH4 waters and a depth interval (~200-760 m) of CH4 supersaturation that is located within a regional oxygen minimum zone (OMZ). MO x rate measurements were made in parallel using tracer-based methods with low-level 14C-CH4 (LL 14C) and 3H-CH4 (3H). The two tracers showed similar trends in MO x rate with water depth, but consistent with previous work, the LL 14C rates (range: 0.034-15 × 10-3 nmol CH4 L-1 d-1) were systematically slower than the parallel 3H rates (range: 0.098-4000 × 10-3 nmol CH4 L-1 d-1). Priming and background effects associated with the 3H-CH4 tracer and LL 14C filtering effects are implicated as the cause of the systematic difference. The MO x rates reported here include some of the slowest rates measured in the ocean to date, are the first rates for the ETNP region, and show zones of slow CH4 turnover within the OMZ that may permit CH4 derived from coastal sediments to travel great lateral distances. The MO x rate constants correlate with both CH4 and oxygen concentrations, suggesting that their combined availability regulates MO x rates in the region. Depth-integrated MO x rates provide an upper limit on the magnitude of regional CH4 sources and demonstrate the importance of water column MO x, even at slow rates, as a sink for CH4 that limits the ocean-atmosphere CH4 flux in the ETNP region

Methane oxidation in the eastern tropical North Pacific Ocean water column

©2015. American Geophysical Union. We report methane (CH4) concentration and methane oxidation (MOx) rate measurements from the eastern tropical north Pacific (ETNP) water column. This region comprises low-CH4 waters and a depth interval (~200-760m) of CH4 supersaturation that is located within a regional oxygen minimum zone (OMZ). MOx rate measurements were made in parallel using tracer-based methods with low-level 14C-CH4 (LL 14C) and 3H-CH4 (3H). The two tracers showed similar trends in MOx rate with water depth, but consistent with previous work, the LL 14C rates (range: 0.034-15×10-3nmol CH4 L-1d-1) were systematically slower than the parallel 3H rates (range: 0.098-4000×10-3nmol CH4 L-1d-1). Priming and background effects associated with the 3H-CH4 tracer and LL 14C filtering effects are implicated as the cause of the systematic difference. The MOx rates reported here include some of the slowest rates measured in the ocean to date, are the first rates for the ETNP region, and show zones of slow CH4 turnover within the OMZ that may permit CH4 derived from coastal sediments to travel great lateral distances. The MOx rate constants correlate with both CH4 and oxygen concentrations, suggesting that their combined availability regulates MOx rates in the region. Depth-integrated MOx rates provide an upper limit on the magnitude of regional CH4 sources and demonstrate the importance of water column MOx, even at slow rates, as a sink for CH4 that limits the ocean-atmosphere CH4 flux in the ETNP region