Water Pollution and Environmental Concerns in Anesthesiology

Medications administered by anesthesia health care providers and subsequently excreted into the water supply system have the potential to affect ecological systems. Presently, there is a lack of literature examining which medications or metabolites enter the waste stream. Further, assessments of their potential environmental impact are often unknown or simply not considered as an externality of medical practice. Recent work examining the practice of anesthesiology has explored the solid waste stream, and the global warming potential of anesthetic gases, however the potential aquatic impacts remain unexplored. To address the potential for waterborne pollution and environmental toxicity, we extracted the total intravenous medications (by mass) administered by anesthesiologists in 2017 at The University of Vermont Medical Center (UVMMC), a mid-size regional Level 1 trauma center in Burlington, VT. The most commonly administered medications were: cefazolin, propofol, acetaminophen, sugammadex and lidocaine. To estimate the amount of each medication that entered the wastewater stream, we used published metabolism profiles to adjust from the total amount administered to the amount excreted unchanged or as prominent metabolites. For each medication we reviewed existing literature concerning their environmental fate and impacts in water. Due to the constraints of current knowledge, it is not possible to determine the exact fate and impacts of these drugs. Some medications, like propofol, have the potential for significant bioaccumulation and persistence. Others, such as lidocaine and acetaminophen, have short half-lives in the environment but their constant delivery and excretion result in pseudo-persistence. The current literature mostly assesses acute exposure at doses higher than could be expected in the environment on select species. While significant toxicities across a variety of species have been found repeatedly, chronic low dose exposures require further study for all the medications discussed. Finally, multi-drug impacts are likely to be more impactful than single-drug toxicities. While we cannot state definitive impacts, the pharmaceuticals most used in anesthesiology have a clear toxic potential and future studies should more closely examine the relative contribution of anesthesia to pharmaceutical pollution, as well as points of intervention for minimizing these unintended consequences of healthcare delivery

David Hume on Banking and Hoarding

David Hume opposes banks and favors hoarding. The only bank he reluctantly approves of is a public, 100% reserve bank. Other banks increase money supply and prices, hindering exports and economic growth. For Hume, a 100% reserve public bank would lead to ‘‘the destruction of paper-credit’’ ([1752] 1985, p. 285), fostering economic growth instead by preventing inflation. Additionally, a 100% reserve bank hoards a large quantity of gold and silver, which is available in case of national emergency

An observational study of end-tidal carbon dioxide trends in general anesthesia

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO RESULTS: Both TWA-AUC and median ETCO CONCLUSIONS: Between 2008 and 2016, intraoperative ETC

Heavy-mineral associations as tracers of limited compositional mixing during turbiditic sedimentation of the Marnoso-arenacea Formation (Miocene, Northern Apennines, Italy)

Petrographic and mineralogical analyses of 567 sandstone samples indicate that the turbidite beds of the Marnoso-arenacea Formation (Miocene, Northern Apennines foredeep basin) are the product of distinct yet contemporaneous detrital inputs derived from different source areas. These inputs were deflected along the main axis of the basin and flowed side by side with only minor mixing, as shown by the detrital modes of discrete stratigraphic intervals and of multi-sourced marker beds traceable in the basin over long distances. The bulk of the basin fill is made of sandstone turbidite beds with southeastward paleocurrents, and can be subdivided into three petrofacies (A, B and C), based on heavy-mineral and framework compositions. A is characterised by zircon, tourmaline and rutile (ZTR), garnet, staurolite, and abundant plutonic rock fragments; B features ZTR, garnet, epidote-group minerals, sphene, staurolite, kyanite, glaucophane and abundant metamorphic rock fragments; C contains ZTR, garnet, very abundant epidote-group minerals, hornblende, sphene, staurolite, kyanite, glaucophane and abundant metamorphic rock fragments. Petrofacies A and B are time-equivalent (Langhian-Serravallian), while petrofacies C ranges from the late Serravallian to the late Tortonian. Petrofacies A occurs mainly in the thrust sheets closest to the Apenninic (SW) side of the basin, petrofacies B in the thrust sheets toward the Adriatic (NE) side, and petrofacies C comprises the late-stage deposits in the evolution of the basin, when the depocenter shifted further to the northeast. Petrofacies A is made of detritus derived from the Western Alps and/or from the Corsica-Sardinia massif, while petrofacies B and C was derived from the terrains of the Central Alps. The southern portion of the basin is still volumetrically dominated by turbidite beds derived from the northwest but is also characterised by detrital inputs derived from south and south-west (petrofacies D, E and F). These produced turbidite beds which are interbedded with the predominant NW-derived beds and have a distinctive composition characterised by abundant bioclasts (D; including the Contessa megaturbidite marker bed) plus mudrock lithics and staurolite (E), or plus mudrock lithics, very abundant staurolite and chrome spinel (F)

SSTR5 P335L monoclonal antibody differentiates pancreatic neuroendocrine neuroplasms with different SSTR5 genotypes

Background: Somatostatin receptor type 5 (SSTR5) P335L is a hypofunctional, single nucleotide polymorphism of SSTR5 with implications in the diagnostics and therapy of pancreatic neuroendocrine neoplasms. The purpose of this study is to determine whether a SSTR5 P335L-specific monoclonal antibody could sufficiently differentiate pancreatic neuroendocrine neoplasms (PNENs) with different SSTR5 genotypes. Methods: Cellular proliferation rate, SSTR5 mRNA level, and SSTR5 protein level were measured by performing MTS assay, a quantitative reverse transcription polymerase chain reaction study, Western blot analysis, and immunohistochemistry, respectively. SSTR5 genotype was determined with the TaqMan SNP Genotyping assay (Applied Biosystems, Foster City, CA). Results: We found that the SSTR5 analogue RPL-1980 inhibited cellular proliferation of CAPAN-1 cells more than that of PANC-1 cells. Only PANC-1 (TT) cells, but not CAPAN-1 (CC) cells expressed SSTR5 P335L. In 29 white patients with PNENs, 38% had a TT genotype for SSTR5 P335L, 24% had a CC genotype for WT SSTR5, and 38% hada CT genotype for both SSTR5 P335L and WT SSTR5. Immunohistochemistry using SSTR5 P335L monoclonal antibody detected immunostaining signals only from the neuroendocrine specimens with TT and CT genotypes, but not those with CC genotypes. Conclusion: A SSTR5 P335L monoclonal antibody that specifically recognizes SSTR5 P335L but not WT SSTR5 could differentiate PNENs with different SSTR5 genotypes, thereby providing a potential tool for the clinical diagnosis of PNEN. © 2011 Published by Mosby, Inc

The hypofunctional effect of P335L single nucleotide polymorphism on SSTR5 function

Background: Somatostatin receptor subtype 5 (SSTR5) mediates the inhibitory effect of somatostatin on insulin expression/secretion and cell proliferation. A number of single nucleotide polymorphisms (SNPs) of SSTR5 have been identified, including P335L, a nonsynonymous SNP located in the protein C-terminal region and encrypted by the codon CCG (proline) or the codon CTG (leucine). In the present study we sought to determine the distribution of the SSTR5 P335L SNP in a cohort of pancreatic cancer patients and whether the P335L SNP affected cellular function of SSTR5 in human pancreatic cancer. Methods: The P335L germline genotype of 246 patients with pancreatic cancer (213 Caucasians, 16 Hispanics, and 17 African Americans) and 17 human pancreatic cell lines was determined with the TaqMan SNP Genotyping assay. Human SSTR5 leucine variant (L335) was generated by performing site-directed mutagenesis using SSTR5 proline variant (P335) as a template. Transient transfections were performed in HEK293, Mia PaCa-2, and β-TC-6 cells using Lipofectamine 2000. The expression of SSTR5 L335 was determined with a mouse monoclonal anti-SSTR5 L335 antibody generated in our laboratory. The cell proliferation rate was measured by performing MTS assays. Insulin concentration was measured by performing ELISA assays. Results: Genotyping of the patients' blood indicated that the frequency of the T allele (CT and TT genotypes) in codon 335 of SSTR5 in Caucasians, Hispanics, and African Americans was 52, 69, and 35%, respectively, which was race-dependent. Statistical analysis indicated that association between the frequency of the T allele and the existence of pancreatic cancer in each race missed significance perhaps due to limited sample size. In 17 tested human pancreatic cancer cell lines, 5 (Capan-2, HPAF-II, Panc03.27, Panc-1, and -3) were homozygous (TT genotype) and 9, including Mia PaCa-2, were heterozygous (CT genotype). Overexpression of SSTR5 L335 in Mia PaCa-2 cells enhanced cell proliferation compared to overexpression of SSTR5 P335. Overexpression of SSTR5 P335 enhanced the inhibitory effect of SSTR5 agonist RPL-1980 on cell proliferation of Mia PaCa-2 cells and glucose-stimulated insulin secretion from mouse insulinoma cells, while overexpression of SSTR5 L335 blocked the inhibitory effect of RPL-1980. Overexpression of SSTR5 L335 enhanced PDX-1 expression in Mia PaCa-2 cells. A specific monoclonal antibody was generated to detect SSTR5 P335L. Conclusion: SSTR5 P335L SNP widely exists in the human population, in patients with pancreatic cancer, and is race-dependent. The SNP is also present in selected human pancreatic cancer cell lines. In contrast to SSTR5 P335, overexpression of the SSTR5 L335 variant resulted in cellular proliferation and PDX-1 overexpression in human pancreatic cancer cells. Its overexpression blocked the inhibitory effect of an SSTR5-specific analog on human pancreatic cancer cell proliferation and on glucose-stimulated insulin secretion from mouse insulinoma cells. These data suggest that SSTR5 P335L is a hypofunctional protein with a potentially harmful effect on function, as well as potential latent effect, and therefore it could affect the clinical response to somatostatin analog therapy for patients with pancreatic cancer. © 2011 Société Internationale de Chirurgie

Étude observationnelle sur les tendances des valeurs du dioxyde de carbone en fin d’expiration au cours de l’anesthésie générale

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO 2) levels in surgical patients, there is still insufficient data to formulate guidelines for ideal intraoperative ETCO 2 targets. As it is unclear which intraoperative ETCO 2 levels are currently used and whether these levels have changed over time, we investigated the practice pattern using the Multicenter Perioperative Outcomes Group database. METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO 2 thresholds ( 45 mmHg). Additionally, a median ETCO 2 was studied. A Kruskal-Wallis test was used to analyse differences between years. Random-effect multivariable logistic regression models were constructed to study variability. RESULTS: Both TWA-AUC and median ETCO 2 showed a minimal increase in ETCO 2 over time, with a median [interquartile range] ETCO 2 of 33 [31.0-35.0] mmHg in 2008 and 35 [33.0-38.0] mmHg in 2016 (P <0.001). A large inter-hospital and inter-provider variability in ETCO 2 were observed after adjustment for patient characteristics, ventilation parameters, and intraoperative blood pressure (intraclass correlation coefficient 0.36; 95% confidence interval, 0.18 to 0.58). CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO 2 values did not change in a clinically important manner. Interestingly, we found a large inter-hospital and inter-provider variability in ETCO 2 throughout the study period, possibly indicating a broad range of tolerance for ETCO 2, or a lack of evidence to support a specific targeted range. Clinical outcomes were not assessed in this study and they should be the focus of future research