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1.
Marie Warrer Petersen Tine Sylvest Meyhoff Marie Helleberg Maj-Brit Nørregaard Kjær Anders Granholm Carl Johan Steensen Hjortsø Thomas Steen Jensen Morten Hylander Møller Peter Buhl Hjortrup Mik Wetterslev Gitte Kingo Vesterlund Lene Russell Vibeke Lind Jørgensen Klaus Tjelle Thomas Benfield Charlotte Suppli Ulrik Anne Sofie Andreasen Thomas Mohr Morten H. Bestle Lone Musaeus Poulsen Mette Friberg Hitz Thomas Hildebrandt Lene Surland Knudsen Anders Møller Christoffer Grant Sølling Anne Craveiro Brøchner Bodil Steen Rasmussen Henrik Nielsen Steffen Christensen Thomas Strøm Maria Cronhjort Rebecka Rubenson Wahlin Stephan Jakob Luca Cioccari Balasubramanian Venkatesh Naomi Hammond Vivekanand Jha Sheila Nainan Myatra Christian Gluud Theis Lange Anders Perner 《Acta anaesthesiologica Scandinavica》2020,64(9):1365-1375
Introduction
Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.Methods
The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.Discussion
The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.2.
3.
J Hildebrandt B D?ker 《Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete》1989,44(13):391-394
The interventional endoscopy and new knowledge about the spontaneous course of the cholelithiasis have obtained a far-reaching influence on the indication for operation and the surgical approach. Now as ever the adequate therapy of the symptomatic cholecystolithiasis consists in the early cholecystectomy. Since in the natural course the risk of lethality is small the operation for indication depending on the age and the risk factors given must be made cautiously. This in a still higher degree concerns the asymptomatic cholelithiasis in which at present no general indication for operation is regarded necessary. Due to the low lethality of circa 1% the endoscopic papillotomy has become the therapeutic method of choice in residual and recurrent calculi after cholecystectomy, but also in risk patients with cholecystocholedocholithiasis. The endoscopic papillotomy with stone extraction before the operation suggests a decrease of the operation lethality of 3 to 5% after cholecystectomy with revision of the choledochus. 相似文献
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6.
A. Z. M. Abosehmah-Albidy P. York V. Wong M. S. Losowsky & H. Chrystyn 《British journal of clinical pharmacology》1997,44(1):35-39
Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease.
Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study.
Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.
Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease. 相似文献
Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study.
Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.
Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease. 相似文献
7.
Cholinergically induced bronchoconstriction is thought to be a major cause of bronchospasm during anesthesia. We used tracheally intubated rabbits (4-mm endotracheal tube) stimulated with methacholine to assess the efficacy of beta-adrenergic agonist and anticholinergic treatment in reversing the increases in respiratory system resistance. Four groups were compared: (a) inhaled metaproterenol, 20 puffs via metered dose inhaler (0.65 mg/puff); (b) inhaled ipratropium bromide, 20 puffs from a metered dose inhaler (18 micrograms/puff); (c) 2 mg of intravenous atropine; and (d) no treatment after methacholine challenge as a control group. Methacholine increased respiratory system resistance from 0.041 +/- 0.001 (mean +/- SEM) to 0.098 +/- 0.006 cm H2O.mL-1.s-1 (P < 0.001). Whereas beta-adrenergic agonist treatment was ineffective in ameliorating bronchoconstriction, inhaled ipratropium bromide and atropine were highly effective, causing an 86%-88% reversal in the methacholine-induced increase in respiratory system resistance. Both these agents were also effective in improving dynamic compliance. We conclude that inhaled ipratropium bromide is effective in treating cholinergic bronchospasm even when administered via a small endotracheal tube and that the beta-adrenergic agonist metaproterenol is ineffective in rabbits in the face of maximal cholinergic stimulation. 相似文献
8.
These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation. 相似文献
9.
Nancy L York 《Dimensions of critical care nursing》2004,23(2):84-88
Families' needs of patients being resuscitated in critical care areas are frequently not a high priority for the healthcare team. However, recent research suggests family member presence during life-saving efforts may help families cope with the devastating outcomes of unsuccessful resuscitation. This article provides the rationale and process for implementing a family presence option during resuscitation. 相似文献
10.
The effects of glucocorticoids on the insulin secretory response to an intravenous glucose load have been studied in lean (Fa/?) and obese fa/fa Zucker rats. The role of parasympathetic drive to the pancreatic B-cells was assessed as that component of the insulin secretory response that was blocked by pretreatment of the rats with intravenous atropine. The insulin secretory response to the glucose load was greater in obese than in lean rats. Atropine significantly reduced basal and stimulated levels of insulin in obese but not in lean rats. Adrenalectomy reduced basal insulin levels and the secretory response in obese but not lean rats and also abolished the atropine-blockable component of the response. Peripheral corticosterone replacement of adrenalectomized fa/fa rats restored the hyperinsulinemia. Chronic infusion of dexamethasone intracerebroventricularly to adrenalectomized fa/fa rats increased basal insulin and the secretory response to glucose and this effect was blocked by atropine. In contrast, intracerebroventricular infusion of obese rats with corticotropin releasing factor reduced basal and stimulated insulin levels. It is concluded that the hypersecretion of insulin in obese fa/fa rats results, at least in part, from a central glucocorticoid-mediated stimulation of vagal drive to the pancreatic B-cells. 相似文献