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1.
The plasma protein binding of propranolol has been described as nonrestrictive for its hepatic extraction to explain the observation that propranolol is efficiently removed by the liver, in spite of extensive protein binding. The present study was designed to examine the relationship between propranolol protein binding, metabolism by isolated hepatocytes, and extraction by the isolated perfused rat liver. In isolated hepatocytes, the intrinsic clearance of free drug increased three- to fourfold as albumin and alpha 1-acid glycoprotein (AAG) concentrations increased, suggesting that albumin and AAG facilitate the elimination of propranolol by hepatocytes. In the isolated perfused liver, propranolol extraction was almost complete (E = 0.996) in the absence of albumin and AAG. With 40 g/L of albumin and 2 g/L of AAG in the perfusate, the free fraction of propranolol decreased to 0.031, but extraction remained high (E = 0.960). With 40 g/L of albumin and 10 g/L of AAG in the perfusate, the free fraction further decreased to 0.014 and extraction dropped sharply (E = 0.820). The observed relationship between propranolol extraction and the free fraction of propranolol was in good agreement with that predicted using estimates of intrinsic clearance measured in isolated hepatocytes suspensions. These data indicate that propranolol extraction is sensitive to changes in binding at very low free fraction values and suggest a facilitation of propranolol clearance by albumin and AAG. 相似文献
2.
The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration. 相似文献
3.
Abdulrahman Al-Dowaisan Nasser Fakim M Riaz Khan Nermina Arifhodzic Radakrishnan Panicker Abdulatif Hanoon Irfan Khan 《Annals of allergy, asthma & immunology》2004,92(2):262-267
BACKGROUND: Respiratory allergies are common in Kuwait, and the role of certain allergens has been previously documented. OBJECTIVE: To evaluate the results of skin prick tests to a range of allergens that were considered relevant to the vegetation surveys and aerobiological studies performed in Kuwait. METHOD: New patients attending our center during August 2002 to February 2003 with asthma or allergic rhinitis underwent skin prick tests to a battery of allergens. RESULTS: A total of 451 patients aged 5 to 60 years (mean age, 29.5 years) were tested. Of these patients, 403 (89.4%) had a positive test result to at least one allergen and were considered allergic. A total of 76.7% of the allergic patients had a positive reaction to Salsola pollen, with a mean wheal diameter of 8.25 mm (median, 8 mm). Chenopodium album was positive in 57.6% and Bermuda grass was positive in 38.2% of the allergic cases. Indoor allergens seemed to play a lesser role than pollens: Dermatophagoides pteronyssinus was positive in only 37.5%, and American and German cockroaches were positive in 33.2% and 22.3%, respectively. All the allergens other than Salsola elicited a mean wheal diameter of less than 6.25 mm (median, < or = 6 mm). CONCLUSIONS: Indoor allergens seem to play a lesser role in respiratory allergies in Kuwait. Most allergic patients become sensitized to pollens; the strongest and most frequent reaction is from Salsola pollen. Salsola imbricata is found growing extensively in most areas of the country, flowering mainly in autumn, when the most common pollen is of the Chenopod-Amaranth type and when most patients with seasonal allergic rhinitis become symptomatic. 相似文献
4.
M Lafortune G Gariépy A Dumont G Breton R Lapointe 《AJR. American journal of roentgenology》1986,147(3):505-508
Among 20,000 patients who had undergone abdominal or gallbladder sonographic examinations, 36 had a short V-shaped artifact originating from an hyperechoic focus in the gallbladder wall. Associated symptoms were varied and nonspecific. The 10 gallbladders excised because of associated cholelithiasis showed a thickened wall, and seven patients had diverticulosis of the wall with impacted stones. In vitro sonographic examination of five gallbladders reproduced the "V" artifact and showed that it originated from a small intramural cholesterol stone. The V artifact should be distinguished from the larger comet-tail and ring-down artifacts, which arise from metal or gas. 相似文献
5.
K Sheldon D Liu J Ferguson J Gariépy 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(6):2056-2060
Defined branched peptides (loligomers) incorporating cytoplasmic translocation signals, nuclear localization sequences, and fluorescent probes were designed and synthesized to demonstrate the feasibility and simplicity of creating novel classes of intracellular vehicles. Loligomers containing all the above signals were rapidly internalized by Chinese hamster ovary (CHO) cells and accumulated in their nucleus. At 4 degrees C, the interaction of peptide constructs with CHO cells was limited to membrane association. Loligomers entered cells at higher temperatures by adsorptive endocytosis. Inhibitors of ATP synthesis affected cytoplasmic import only weakly but abolished nuclear uptake. The peptide signals guided both cytoplasmic and nuclear localization events. The properties exhibited by loligomers suggest a strategy for the facile design of "guided" classes of intracellular agents. 相似文献
6.
This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade. 相似文献
7.
Shadi Lahham Brent A. Becker Abdulatif Gari Steven Bunch Maili Alvarado Craig L. Anderson Eric Viquez Sophia C. Spann John C. Fox 《The American journal of emergency medicine》2018,36(6):962-966
Background
Measurement of the common bile duct (CBD) is considered a fundamental component of biliary point-of-care ultrasound (POCUS), but can be technically challenging.Objective
The primary objective of this study was to determine whether CBD diameter contributes to the diagnosis of complicated biliary pathology in emergency department (ED) patients with normal laboratory values and no abnormal biliary POCUS findings aside from cholelithiasis.Methods
We performed a prospective, observational study of adult ED patients undergoing POCUS of the right upper quadrant (RUQ) and serum laboratory studies for suspected biliary pathology. The primary outcome was complicated biliary pathology occurring in the setting of normal laboratory values and a POCUS demonstrating the absence of gallbladder wall thickening (GWT), pericholecystic fluid (PCF) and sonographic Murphy's sign (SMS). The association between CBD dilation and complicated biliary pathology was assessed using logistic regression to control for other factors, including laboratory findings, cholelithiasis and other sonographic abnormalities.Results
A total of 158 patients were included in the study. 76 (48.1%) received non-biliary diagnoses and 82 (51.9%) were diagnosed with biliary pathology. Complicated biliary pathology was diagnosed in 39 patients. Sensitivity of CBD dilation for complicated biliary pathology was 23.7% and specificity was 77.9%.Conclusion
Of patients diagnosed with biliary pathology, none had isolated CBD dilatation. In the absence of abnormal laboratory values and GWT, PCF or SMS on POCUS, obtaining a CBD measurement is unlikely to contribute to the evaluation of this patient population. 相似文献8.
Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias 总被引:26,自引:0,他引:26
Care RS Valk PJ Goodeve AC Abu-Duhier FM Geertsma-Kleinekoort WM Wilson GA Gari MA Peake IR Löwenberg B Reilly JT 《British journal of haematology》2003,121(5):775-777
DNA from 110 adult de novo acute myeloid leukaemia (AML) patients exhibiting either inv(16) (n = 63) or t(8;21) (n = 47) was screened for mutations in the c-KIT (exon 8 and Asp816) and FLT3 (ITD and Asp835) genes. c-KIT exon 8 mutations were found in 15/63 (23.8%) inv(16) patients and 1/47 (2.1%) t(8;21) patients. c-KIT Asp816 mutations were present in 5/63 (7.9%) inv(16) AML and 5/47 (10.6%) t(8;21) AML. FLT3 mutations were identified in five patients (7.9%) with inv(16) and three patients (5.6%) with t(8;21) AML. All mutations were mutually exclusive; 40% of inv(16) AML patients possessed either a c-KIT or FLT3 mutation. c-KIT exon 8 mutations were shown to be a significant factor adversely affecting relapse rate. 相似文献
9.
Joachim Behar Alistair Johnson Gari D. Clifford Julien Oster 《Annals of biomedical engineering》2014,42(6):1340-1353
The abdominal electrocardiogram (ECG) provides a non-invasive method for monitoring the fetal cardiac activity in pregnant women. However, the temporal and frequency overlap between the fetal ECG (FECG), the maternal ECG (MECG) and noise results in a challenging source separation problem. This work seeks to compare temporal extraction methods for extracting the fetal signal and estimating fetal heart rate. A novel method for MECG cancelation using an echo state neural network (ESN) based filtering approach was compared with the least mean square (LMS), the recursive least square (RLS) adaptive filter and template subtraction (TS) techniques. Analysis was performed using real signals from two databases composing a total of 4 h 22 min of data from nine pregnant women with 37,452 reference fetal beats. The effects of preprocessing the signals was empirically evaluated. The results demonstrate that the ESN based algorithm performs best on the test data with an F1 measure of 90.2% as compared to the LMS (87.9%), RLS (88.2%) and the TS (89.3%) techniques. Results suggest that a higher baseline wander high pass cut-off frequency than traditionally used for FECG analysis significantly increases performance for all evaluated methods. Open source code for the benchmark methods are made available to allow comparison and reproducibility on the public domain data. 相似文献
10.
Norbert Schmitz Ph.D. Geneviève Gariépy M.Sc. Kimberley J. Smith Ph.D. Ashok Malla M.D. Richard Boyer Ph.D. Irene Strychar E.D.D. Alain Lesage M.D. JianLi Wang Ph.D. 《Annals of behavioral medicine》2014,47(2):172-179