Widespread Frequent Methane Emissions From the Oil and Gas Industry in the Permian Basin.

Emissions of methane (CH4) in the Permian basin (USA) have been derived for 2019 and 2020 from satellite observations of the Tropospheric Monitoring Instrument (TROPOMI) using the divergence method, in combination with a data driven method to estimate the background column densities. The resulting CH4 emission data, which have been verified using model data with known emissions, have a spatial resolution of approximately 10 km. The CH4 emissions show moderate spatial correlation with the locations of oil and gas production and drilling activities in the Permian basin, as well as with emissions of nitrogen oxides (NOx). Analysis of the emission maps and time series indicates that a significant fraction of methane emissions in the Permian basin is from frequent widespread emissions sources, rather than from a few infrequent very large unplanned releases, which is important considering possible CH4 emission mitigation strategies. In addition to providing spatially resolved emissions, the divergence method also provides the total emissions of the Permian basin and its main sub-basins. The total CH4 emission of the Permian is estimated as 3.0 ± 0.7 Tg yr-1 for 2019, which agrees with other independent estimates based on TROPOMI data. For the Delaware sub-basin, it is estimated as 1.4 ± 0.3 Tg yr-1 for 2019, and for the Midland sub-basin 1.2 ± 0.3 Tg yr-1. In 2020 the emissions are 9% lower compared to 2019 in the entire Permian basin, and respectively 19% and 27% for the Delaware and Midland sub-basins.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists?

BACKGROUND: After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. OBJECTIVE: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery. METHODS: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day -5 before surgery (group H) or to VKA treatment until day -2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). RESULTS: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. CONCLUSIONS: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants.

Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study.

BACKGROUND: In view of recent substantial changes in the management of orthopedic surgery patients, a study was performed in order to update data on the epidemiology of venous thromboembolism (VTE) in patients undergoing lower limb arthroplasty according to contemporary practise. METHODS: We performed a prospective observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003. The primary study outcome was the incidence of symptomatic VTE at 3 months. All events were adjudicated by an independent critical event committee. RESULTS: Data from 1080 patients (mean age 68.0 years) were available; 63.2% were undergoing total hip replacement and 36.8% total knee replacement. Pharmacological thromboprophylaxis was administered for a mean time of 36 days. Injectable antithrombotics were used in more than 99% of patients, irrespective of the type of surgery. The incidence of the primary study outcome was 1.8% (20 events; 95% CI: 1.0-2.6%). The incidences were 1.3% and 2.8% in hip and knee surgery patients, respectively. There were two pulmonary embolisms, both in knee surgery patients; neither was fatal. Thirty-five per cent of VTEs occurred after hospital discharge. An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant (P < 0.05) predictors of VTE. The rate of clinically significant bleeding was 1.0% and the rate of death was 0.9%. CONCLUSIONS: The incidence of symptomatic VTE after lower limb arthroplasty is low, even if there is still a need to improve thromboprophylaxis, notably in patients undergoing knee arthroplasty.

Expression of the genetic variants of human alpha-1-acid glycoprotein in cancer.

OBJECTIVES: We have investigated the AAG and its genetic variants concentrations in plasma samples of 61 patients suffering from different types of cancers. DESIGN AND METHODS: The patients were shared out in three groups, breast, lung, and ovary cancers groups. AAG concentration was measured by an immunonephelometric method and the phenotype was determined, after desialylation of plasma by analytical isoelectric focusing. Detection of AAG variants was made by immunoblotting and their proportions were determined by laser densitometry analysis. A population of 74 healthy individuals served as controls. RESULTS: The plasma concentrations of AAG in the breast and lung cancer groups were 2.5 times increased, while in the ovary cancer group, the concentrations were 1.6 times increased. AAG concentrations in the cancer population ranged between 0.45 and 2.85 g/L (mean value 1.12 +/- 0.51 g/L). The proportions of the ORM1 and ORM2 variants were similar to those in the healthy population. In breast and lung cancer groups, the relative concentrations of genetic variants were increased more than 2.5 fold, whereas a 1. 6-fold increase was observed in the ovary cancer group. CONCLUSIONS: These results show that AAG plasma concentrations are increased in these types of cancers and that changes in the expression of the genetic variants of AAG could also occur according to the type of cancer.

In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood.

The binding of CPT-11 and SN-38 to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. In plasma, CPT-11 was 66-60% bound in the range 100-4000 ng/ml and SN-38 was 94-96% bound in the range 50-200 ng/ml. At these concentrations the plasma binding of CPT-11 was slightly saturable, but the plasma binding of SN-38 was concentration-independent. Albumin was the main carrier of CPT-11 and SN-38 in plasma. In blood, the binding of CPT-11 was moderate (80%), mainly to plasma proteins (47%) and erythrocytes (33%). The binding of SN-38 was high (99%) and most of SN-38 in blood was located in blood cells (approximately 66%) The simulation of a grade 3 hematotoxicity (according to National Cancer Institute's Common Toxicity Criteria grading) on the SN-38 blood distribution yielded an increase in fu (free fraction of drug in plasma) from 1.05 to 2.08 and a decrease in C(Bl)/C(P) from 1.66 to 1.14 (both resulting from a decreased cell binding).

Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences.

BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. METHODS: In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.

Low molecular weight heparin associated with spinal anaesthesia and gradual compression stockings in total hip replacement surgery. Arar Study Group.

The benefit/risk ratio of administering heparin during spinal anaesthesia in patients undergoing total hip replacement (THR) has not been studied widely. We conducted a prospective, randomized, double-blind study to compare low molecular weight heparin (LMWH) for 10 days and placebo in patients undergoing THR performed under spinal anaesthesia associated with gradual compression stockings. Efficacy was assessed by systematic bilateral ascending venography on day 10 +/- 2 in a sequential analysis. Among the 170 patients enrolled, data were available in 153 patients. In the LMWH group (n = 78) the total incidence of deep vein thrombosis (DVT) was 14.1% compared with 37.3% in the placebo group (n = 75) (P = 0.0016). No gross neurological sequelae were observed during the study. This study showed that the addition of LMWH in patients undergoing THR under spinal anaesthesia and wearing gradual compression stockings significantly decreased the incidence of venogram-proved DVT.

[Embolism and intramedullary femoral surgery]. / Embolies et chirurgie fémorale intra-médullaire.

All intramedullary femoral surgery entails embolic phenomena which explain peroperative collapses formally known as bone cement implantation syndrome, as well as perioperative fat embolism syndromes. Locally, the bigger the cavity is, the higher the number of accidents: 2.5-5 per cent for GUEPAR hinged-knee prosthesis, 1.75 per cent for total hip arthroplasty with long stem, and 0.1 per cent during classic THA with cement limited to the metaphysis. Anomalies in bone vascularization also increase risk: 10.5-13 per cent during prophylactic nailing for shaft metastases, 1-11.5 per cent during hemiarthroplasty cemented in osteoporotic bone of femoral neck fractures, and only 0.1 per cent during THA implanted because of arthrosis. Not only cement, but also rods, reamers, nails, implants, ultrasonic tool for cement extraction, increase the pressure inside the cavity. Methylmethacrylate is no longer the only incriminated factor, even if it is responsible for a major part of the compressive load. The intensity and duration of the pressure are correlated with the number of embolic phenomena and with measured cardiopulmonary parameters. The intracavity fat content is expelled (an empty cavity, as in THA revision, does not lead to embolic phenomena). Then filters through the intraosseous veins whose diameter limit the size of the extruded embolic phenomena. The ultrasonography of the inferior vena cava shows innumerable fine particles and thrombi which are already organized under the influence of procoagulant factors released from the operative shield and which remain crumbly. These emboli cross the cardiac cavities. Transesophageal echocardiography (TEE), of recent use, does quantify the amount of right atrial filling, duration of echogenesis and size of particles: the result is higher in patients who underwent cemented versus noncemented THA: however the embolism score is no an indicator of seriousness because it is not correlated with cardiorespiratory manifestations; TEE shows only one fourth of the patent foramen ovale, whereas the atrial septal defect is surely one of the most efficient systemic invasion mechanisms to produce perioperative fat embolism. Lung response is most often asymptomatic, even if all patients undergoing intramedullary surgery display an increase in pulmonary vascular resistance which is managed by the right heart only, as well as pulmonary (and sometimes systemic) microvascular fat obstruction. Common operating room monitoring procedures do not detect successive embolic phenomena before they cause pulmonary arterial hypertension which then has repercussions on the left heart and in turn causes peroperative hemodynamic accidents. Only pulmonary arterial pressure measurement with a Swan-Ganz catheter gives early and durable signs of an intolerance to embolic load. Preventive treatment is surgical as there is an inverse relation between embolic marrow and marrow eliminated by large volume washes (which is often more effective than draining). Cement indications in older patients as well as the choice of fixation techniques in femoral fractures must take into account the cardio-pulmonary condition of the patient. Resuscitation procedures dealing with these complications end in the patient's death in half of the cases.

Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein.

Human alpha 1-acid glycoprotein (AAG), a plasma drug transport protein, has three main genetic variants, the A variant and the F1 and S variants, which are encoded by two different genes. The binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main gene products of AAG-the A variant and a mixture of the F1 and S variants (60% F1 and 40% S)-separated by chromatography from native commercial AAG, a mixture of almost equal proportions of the F1, S and A variants, was studied by equilibrium dialysis. A selective binding of disopyramide and methadone to the A variant and a preferential binding of dipyridamole to the F1S variant mixture were found. Lignocaine and chlorpromazine had a slight preference for binding to the A variant and to the F1S mixture, respectively, but progesterone showed no selectivity with regard to any of the variants of AAG. The differences in drug-binding demonstrated between the A variant and the F1S mixture confirmed those of a previous study, in which a selective binding of imipramine to the A variant and of warfarin and mifepristone to the F1S mixture have been found. These results indicate specific drug transport roles for each AAG variant, according to its separate genetic origin. The results of control binding experiments performed with (unfractionated) commercial AAG and the series of tested ligands concurred with that for the separate AAG variants, with respect to the proportion of the A variant (27%) and that of the F1 and S variants (73%) in the commercial protein. In addition, disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone were used in equilibrium dialysis displacement experiments to study interactions on binding sites labelled with imipramine for the A variant and with warfarin for the F1S variant mixture. The four latter ligands were found to competitively inhibit the binding of warfarin to the F1S variant mixture and all of them that of imipramine to the A variant. The ligands association constants to each AAG variant obtained from such inhibitory experiments were comparable to those determined in the direct binding studies. As the stochlometry of the interactions of the A variant and the F1S variants, respectively, with their specific ligands was approximately one (1), it was concluded that these ligands bind to each of these variants via a single common binding site. These results indicate that the AAG molecule would have for its ligands at least two separate binding sites, showing different specificity and localization, and not one site, as it is generally assumed. The possible pharmacological and clinical consequences of the binding results with the separate AAG variants are discussed.

Docetaxel serum protein binding with high affinity to alpha 1-acid glycoprotein.

The binding of docetaxel to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. Docetaxel was extensively (> 98%) plasma protein bound. At clinically relevant concentrations (1-5 micrograms/ml), the plasma binding was concentration-independent. Lipoproteins, alpha1-acid glycoprotein and albumin were the main carriers of docetaxel in plasma, and owing to the high interindividual variability of alpha1-acid glycoprotein plasma concentration, particularly in cancer, it was concluded that alpha1-acid glycoprotein should be the main determinant of docetaxel plasma binding variability. Drugs potentially coadministered with docetaxel (cisplatin, dexamethasone, doxorubicin, etoposide, vinblastine) did not modify the plasma binding of docetaxel. In blood, docetaxel was found to be mainly located in the plasma compartment (less than 15% associated to erythrocytes).

[Intraoperative posture in the surgery of lumbar disk hernia]. / Etude des positions opératoires pour la chirurgie de la hernie discale lombaire.

For surgery of the lumbar disc, with a posterior route, the patient is placed either in a prone, or a knee-chest, or a lateral position. They aim at facilitating the surgical access in decreasing local bleeding and collapsing the dural sheath. This benefit, as a result of the maintenance of the pressure in the epidural venous system at a low level, is obtained through the absence of any abdominal compression as well as the posture. In the prone position, the abdominal compression and the increase of the physiologic lordosis impair the systemic venous return and carry the risk of cardiac arrest. In addition to these adverse effects, the conventional knee-chest position increases the haemodynamic repercussions in modifying the distribution of blood volume and increasing the potential risk of mediastinal compression and air embolism. The lateral position generates only minor haemodynamic modifications, except in the obese. However it is difficult to stabilize the patients' position and to maintain the alignment of the spine. Therefore it is used the less one. The postural risks of all three positions are numerous and include mainly the compression of nerves, vessels and skin. Finally the selection of the position depends basically on morphological criteria and the adaptative capacities of the patient. The optimal position is the one offering a low pressure level in the spinal venous system, while maintaining the venous return.

Diphytanyl glycerol ether distributions in sediments of the Orca Basin.

Archaebacterially produced diphytanyl glycerol ether (DPGE) was examined in core sediments from the Orca Basin, an anoxic hypersaline basin in the northwestern Gulf of Mexico, to observe its spatial variability and potential origin. A differential extraction protocol was employed to quantify the isopranyl glycerol ethers associated with unbound, intermediate-bound, and kerogen-bound lipid fractions. Archaebacterial lipids were evident at all depths for the unbound and intermediate-bound fractions. Concentrations of DPGE ranged from 0.51 to 2.91 micrograms/g dry sediment at the surface and showed secondary maxima deeper in basin sediments. Intermediate-bound DPGE concentrations exhibited an inverse relationship to unbound DPGE concentrations. Kerogen-bound DPGE concentrations were normally below detection limits. Earlier studies describing the general homogeneity of lipid components within the overlying brine and at the brine/seawater interface suggest that the large-scale sedimentary DPGE variations observed in this study result from spatial and temporal variations in in situ production by methanogenic or extremely halophilic archaebacteria.

Lack of a relationship between the polymorphism of debrisoquine oxidation and lung cancer.

1. Determination of debrisoquine oxidation phenotype was carried out in 119 healthy subjects, 135 patients with chronic bronchitis and 153 patients with lung cancer, all of Caucasian origin. 2. A non-Gaussian distribution of the log D/HD ratio was observed in the three groups. 3. Assuming an antimode of 1.12, the proportion of PMs was found to be 6.7% in healthy subjects, 8.9% in chronic bronchitics and 6.5% in patients with lung cancer. These differences were not significant. 4. The presence of a lung tumour itself had no influence on phenotype in a group of 14 patients who were phenotyped before and after surgery. 5. We conclude that a link between debrisoquine phenotype and lung cancer is unlikely.

Disease-induced variations in plasma protein levels. Implications for drug dosage regimens (Part II).

Part I of this article, which appeared in the previous issue of the Journal, discussed the implications of variations in plasma protein levels in a number of diseases: hepatic and renal disease, acute myocardial infarction, burns, cancer, diabetes mellitus, hyperlipidaemia and inflammatory diseases. In Part II the authors continue their review with a further range of disease states, and consider their import for drug dosages.

[Interference of anaesthesia and transfusion on rheological parameters (author's transl)]. / Interférence de l'anesthésie et de la transfusion sur les paramètres rhéologiques.

This study was designed to investigate the rheological and plasmatic parameters from multiple transfused patients and patients undergoing surgery non transfused. Blood filtrability compared with the erythrocyte electrophoretic mobility shows the perturbance resulting from the delay of conservation and the importance of the transfused blood. The 2-3 DPG, ATP and oxygen-hemoglobin affinity suggest the excellent recuperation of the erythrocyte metabolic function in vitro. The rheological parameters seems to be a good mean in the supervision of red massive transfusion blood cell.

[Radiological study of arthrogryphosis. 20 cases (author transl)]. / Etude radiologique de l'arthrogrypose. A propose de 20 cas.

Arthrogryphosis, a disease of unknown nature, is accompanied by radiological manifestations which involve essentially the limbs and spine. A distribution involving all four limbs is the most common. The commonest radiological abnormalities are equinovarus clubfoot, clubhand in ulnar deviation, scoliosis and dislocation of the hip. The radiologist examines such children in order to assess the extent of their disease and follow such orthopaedic problems as they may develop.