| 1. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 2. |
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| 3. |
- Reiz, S., et al.
(författare)
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Effects of halothane on coronary haemodynamics and myocardial metabolism in patients with ischaemic heart disease and heart failure
- 1982
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Ingår i: Acta Anaesthesiol Scand. ; 26:2, s. 133-8
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Tidskriftsartikel (refereegranskat)abstract
- Halothane was administered at an end-tidal concentration of 1% to 10 patients with stable ischaemic heart disease and clinical and haemodymanic signs of moderate heart failure. Measurements of central haemodynamic variables, coronary sinus blood flow and oxygen, lactate and hypoxanthine balances over the myocardium were done before and at steady state during halothane anaesthesia. Halothane induced marked haemodynamic changes with decreases in mean arterial pressure (-43%), mean pulmonary arteriolar occlusion pressure (-42%), systemic vascular resistance (-31%), cardiac index (-20%) stoke volume index (-31%) and left and right stroke work indices (-62% and -55%, respectively). Heart rate and pulmonary vascular resistance did not change. Coronary sinus blood flow decreased in parallel with perfusion pressure, and myocardial oxygen consumption decreased (-40%), as did myocardial oxygen extraction. Rate pressure product and triple product correlated better with changes in myocardial oxygen consumption in the present subset of patients than in healthy volunteers during halothane anaesthesia. The findings suggest that halothane, through its systemic vasodilatory effect, unloads the failing left ventricle and that this peripheral action predominates over the direct cardiodepressant action of the agent. The combined findings of unchanged coronary vascular resistance, decreased myocardial oxygen extraction and absence of increasing or pathological levels of lactate and hypoxanthine in coronary sinus blood imply a direct dilatory effect of halothane on the coronary vasculature.
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| 4. |
- Reiz, S., et al.
(författare)
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Myocardial oxygen consumption and coronary haemodynamics during fentanyl-droperidol-nitrous oxide anaesthesia in patients with ischaemic heart disease
- 1981
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Ingår i: Acta Anaesthesiol Scand. ; 25:3, s. 286-92
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Tidskriftsartikel (refereegranskat)abstract
- Eight patients with stable ischaemic heart disease were investigated to determine the effects of fentanyl (15 micrograms/kg) - droperidol (150 micrograms/kg) - nitrous oxide (75%) anaesthesia, without concomitant fluid challenge, on myocardial oxygen consumption and lactate uptake, and central and coronary haemodynamics. Anaesthesia induced reductions in mean arterial pressure (--35%, P less than 0.01), systemic vascular resistance (--30%, P less than 0.01), left ventricular stroke work index (--50%, P less than 0.01) and total body oxygen consumption (--23%, P less than 0.01), with no changes in heart rate, cardiac output or mean pulmonary arteriolar occlusion pressure. Mixed venous oxygen content increased (P less than 0.05). Systemic vasodilatation, circulatory adaptation to an overall lower metabolic rate, and clinically negligible cardiodepression are the likely mechanisms behind the central haemodynamic response to this form of anaesthesia. Coronary sinus blood flow (measured by the continuous thermodilution technique) decreased (P less than 0.01) in parallel with the decrease in coronary perfusion pressure. Thus coronary vascular resistance remained unchanged. As expected from the haemodynamic findings, myocardial oxygen consumption decreased (--37%, P less than 0.01). Coronary sinus oxygen content and myocardial oxygen extraction did not change, nor was myocardial lactate uptake affected. No ST-T-segment depressions or dysrhythmias were recorded. These observations indicate that myocardial oxygenation was adequate in spite of the reduction in coronary perfusion pressure. There was poor correlation between changes in myocardial oxygen consumption and rate pressure product (R = 0.455) or triple produce (R - 0.375).
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| 5. |
- Bålfors, E., et al.
(författare)
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Droperidol inhibits the effects of intravenous ketamine on central hemodynamics and myocardial oxygen consumption in patients with generalized atherosclerotic disease
- 1983
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Ingår i: Anesth Analg. ; 62:2, s. 193-7
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Tidskriftsartikel (refereegranskat)abstract
- A 2-mg/kg dose of ketamine was administered intravenously to 16 patients with generalized atherosclerotic disease. Eight patients were given 200 mu/kg of droperidol intravenously 10 min before ketamine administration; eight patients not given droperidol served as controls. Central hemodynamics, coronary flow (thermodilution technique) and myocardial oxygen, lactate, hypoxanthine, and catecholamine balances were studied. In control patients, ketamine increased mean blood pressure by 42%, pulmonary capillary wedge pressure by 144%, mean right atrial pressure by 60%, heart rate by 15%, and systemic vascular resistance by 40% without changes in cardiac index, stroke volume index, or left ventricular stroke work index. These data indicate that cardiac performance did not increase in parallel with the rise in afterload. However, the 50% increase in myocardial oxygen demand was associated with a 48% increase in coronary blood flow without changes in coronary vascular resistance or myocardial oxygen extraction. Augmented sympathetic activity was manifested by 397% and 164% increases in plasma levels of epinephrine and norepinephrine, respectively. The hemodynamic and cardiometabolic effects of ketamine were abolished when patients were pretreated with droperidol. The increase in plasma epinephrine levels was likewise inhibited by droperidol; significantly lower plasma norepinephrine levels also were observed. These findings suggest that droperidol inhibits the cardiovascular effects of ketamine by a centrally mediated reduction in sympathetic activity and by peripheral alpha receptor blockade.
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| 6. |
- Hohner, P., et al.
(författare)
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Anaesthesia for abdominal aortic surgery in patients with coronary artery disease, Part II : Effects of nitrous oxide on systemic and coronary haemodynamics, regional ventricular function and incidence of myocardial ischaemia
- 1994
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Ingår i: Acta Anaesthesiol Scand. ; 38:8, s. 793-804
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide-oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity.
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| 7. |
- Leymarie, N., et al.
(författare)
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Interlaboratory Study on Differential Analysis of Protein Glycosylation by Mass Spectrometry: The ABRF Glycoprotein Research Multi-Institutional Study 2012
- 2013
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 12:10, s. 2935-2951
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Tidskriftsartikel (refereegranskat)abstract
- One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods. T6G 2G2, Canada. [Cipollo, John F.; An, Yanming] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20993 USA. [Desaire, Heather; Go, Eden P.] Univ Kansas, Lawrence, KS 66045 USA. [Goldman, Radoslav; Pompach, Petr; Sanda, Miloslav] Georgetown Univ, Dept Oncol, Washington, DC [Halim, Adnan; Larson, Goran; Nilsson, Jonas] Univ Gothenburg, Sahlgrenska Acad, Dept Clin Chem & [Hensbergen, Paul J.; Wuhrer, Manfred] Leiden Univ, Med Ctr, Biomol Mass Spectrometry Unit, NL- [Jabs, Wolfgang; Marx, Kristina; Resemann, Anja; Schweiger-Hufnagel, Ulrike; Suckau, Detlev] Bruker [Ly, Mellisa; Staples, Gregory O.] Agilent Technol, Agilent Labs, Santa Clara, CA 95051 USA. [Mechref, Yehia; Song, Ehwang] Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA. [Nyalwidhe, Julius O.; Watson, Megan] Eastern Virginia Med Sch, Leroy T Canoles Jr Canc Res Ctr, Dept [Packer, Nicolle H.; Thaysen-Andersen, Morten] Macquarie Univ, Dept Chem & Biomol Sci, Biomol [Sihlbom, Carina] Gothenburg Univ, Prote Core Facil, Gothenburg, Sweden. [Tang, Haixu] Indiana Univ, Sch Informat, Bloomington, IN 47405 USA. [Valmuv, Leena] Finnish Red Cross Blood Serv, Helsinki 00310, Finland. [Wada, Yoshinao] Osaka Med Ctr Maternal & Child Hlth, Res Inst, Izumi Ku, Osaka 5941101, Japan.
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| 8. |
- Reiz, S., et al.
(författare)
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Beta-blockers and thoracic epidural analgesia. Cardioprotective and synergistic effects
- 1982
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Ingår i: Acta Anaesthesiol Scand Suppl. ; 76, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Seven groups of patients with and without hypertension or with ischaemic heart disease, treated with different beta blockers were investigated to study the circulatory effects of neurolept anaesthesia alone or combined with thoracic epidural analgesia from T4 to T12/L2 during abdominal surgery. The combination of thoracic epidural analgesia and neurolept anaesthesia in hypertensive subjects treated with non-cardioselective beta blockers induced slightly lower blood pressure than measured in similar patients on cardioselective beta blockers with neurolept anaesthesia only. Patients on non-selective beta blockers with intrinsic stimulatory activity (ISA) had higher blood pressure and heart rate after neurolept anaesthesia induction than patients on cardioselective blockers. During surgery, heart rate remained at a higher level in the patients treated with ISA blockers, whereas blood pressure increased to the same level as in patients with cardioselective blockers. Cardiovascular stability was, however, best maintained in the epidural group, where myocardial energy expenditure during maximal surgical stress was comparable to that in a group of healthy subjects with the same format of anaesthesia and significantly lower than in healthy subjects with neurolept anaesthesia alone. No circulatory side effects of the combination of thoracic epidural analgesia and beta blockade were seen. In patients with ischaemic heart disease, with or without non-selective beta blockade, similar haemodynamic changes were recorded following neurolept anaesthesia. During maximal surgical stress, unmasking of alpha adrenergic activity with marked rise in blood pressure was seen in the beta-blocked patients. Despite the more accelerated haemodynamic changes in the blocked patients, a lower increase in myocardial oxygen consumption was recorded compared with the non-blocked patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 9. |
- Reiz, S., et al.
(författare)
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Coronary haemodynamic effects of surgery during enflurane-nitrous oxide anaesthesia in patients with ischaemic heart disease
- 1985
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Ingår i: Acta Anaesthesiol Scand. ; 29:1, s. 106-12
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Tidskriftsartikel (refereegranskat)abstract
- The systemic and coronary haemodynamic effects of 1.5 MAC enflurane-nitrous oxide anaesthesia and abdominal surgery were investigated in nine patients with ischaemic heart disease. Anaesthesia decreased systemic blood pressure (-56%) by a combination of cardiodepression and peripheral vasodilation. A marked fall in myocardial oxygen extraction suggested a moderate coronary vasodilation. Surgery markedly increased the circulating levels of adrenaline and noradrenaline, manifested by increases in blood pressure (+76%) and systemic vascular resistance (+83%). Pulmonary capillary wedge pressure increased by 70% without any change in cardiac or stroke volume index, suggesting that the patients were performing at the horizontal part of their left ventricular function curve. Despite the marked rise in coronary perfusion pressure and a 62% increase in myocardial oxygen demand, coronary blood flow remained unaltered. This could be due either to coronary vasoconstriction overriding the normal coronary autoregulation or to an increase in coronary back pressure opposing the diastolic aortic pressure. When coronary blood flow could not increase to meet the demand for oxygen, the myocardium had to extract more oxygen to ensure appropriate oxygenation, demonstrating interference with coronary autoregulation. Surgery markedly increased myocardial extraction of adrenaline and noradrenaline. We could not find any relationship between myocardial adrenaline extraction and heart rate response to surgery or between myocardial noradrenaline extraction and changes in coronary blood flow, calculated coronary vascular resistance, incidence of myocardial ischaemia or cardiac dysrhythmias.
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| 10. |
- Rydvall, A., et al.
(författare)
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Effects of enflurane on coronary haemodynamics in patients with ischaemic heart disease
- 1984
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Ingår i: Acta Anaesthesiol Scand. ; 28:6, s. 690-5
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Tidskriftsartikel (refereegranskat)abstract
- The effects of enflurane with and without nitrous oxide on coronary haemodynamics and myocardial oxygenation were investigated in 11 patients with generalised atherosclerotic disease. Enflurane decreased systemic blood pressure (-50%) mainly by systemic vasodilation (SVR -41%) and to a lesser degree by impairment of cardiac performance (CO -27%). A change from 1MAC enflurane-nitrogen-oxygen (70/30) to 1MAC enflurane-nitrous oxide-oxygen (70/30) decreased blood pressure and cardiac output further (-16% and -14%). Enflurane-nitrogen-oxygen decreased coronary blood flow (-29%) and perfusion pressure (-47%). Coronary vascular resistance fell (-20%) along with decreases in myocardial oxygen consumption and extraction (-40% and -16%). Regional coronary blood flow measurements in four of the patients revealed maldistribution of blood flow. During enflurane-nitrous oxide-oxygen, myocardial oxygen consumption and extraction decreased further (-29% and -12%) without change in coronary blood flow or resistance. Myocardial ischaemia was observed in four patients during enflurane-nitrogen. During enflurane-nitrous oxide, ischaemia disappeared in two of the previously ischaemic patients and appeared in two not previously ischaemic. The regional blood flow maldistribution was abolished with nitrous oxide. It is concluded that enflurane is a powerful coronary vasodilator and in this respect slightly less potent than isoflurane. Enflurane may induce myocardial ischaemia by redistributing coronary blood flow and/or by producing hypotension. Nitrous oxide added to enflurane depresses cardiac function and augments the coronary vasodilatory effect of enflurane to a level at which coronary blood flow becomes totally pressure dependent.
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