Clinically relevant observations

One clinically relevant observation that arises from this relationship is that the apparent volume of distribution for a drug is dependent upon the extent of plasma protein binding. Hence, drugs with more extensive plasma protein binding, like tolbutamide (95% bound), will have a lower volume of distribution than expected based on its lipophilicity (log P= 2.34). This influence of plasma protein binding has been shown to contribute to the intersubject variability in the volume of distribution for a number of drugs (e.g., propranolol in liver disease Branch et al., 1976). 

Acquired resistance has been observed by constitutive upregulation of mdr efflux pump expression due to a mutation inactivating a respective repressor or inducibly, caused by molecules transiently inactivating repressor molecules upon binding. Depending upon the substrate spectra of the respective subset of efflux pumps upregulated, a multiple drug resistance (mdr) phenotype is expressed, which in combination with a specific resistance mechanism can contribute to a clinically relevant level of resistance. 

The clinical relevance of this finding was suggested by the observation that mice were more susceptible to sepsis following infection with Streptococcus pneumoniae when basophils were depleted before the second vaccination with pneumoccocal antigen [22]. Antigen-specific IgG antibodies produced after the second vaccination were significantly lower in the basophil-depleted mice than in control mice. Thus, basophils are important contributors to humoral memory immune responses. 

HHMC can also be activated by a variety of non-immunological stimuli. Some have clinical relevance because they might explain certain adverse effects observed in vivo when these compoimds are used for diagnostic (contrast media, etc.) or therapeutic... 

After oral administration of 400 mg of rifaximin to fasted healthy volunteers blood drug concentration was found to be lower than the detection limit of the analytical method (i.e. 2.5 ng/ml) in half of them [102]. In the remaining subjects very low amounts were detected at some of the time intervals during the first 4 h after intake. Along the same lines, the urinary concentrations of the drug were very low and often undetectable. The effect of food on the absorption of the antibiotic was also evaluated [34] and a significant, albeit not clinically relevant, increase of bioavailabity was observed after a high-fat breakfast (table 5). 

When an analyte is fluorescent, direct fluorometric detection is possible by means of a spectrofluorometer operating at appropriate excitation and observation wavelengths. This is the case for aromatic hydrocarbons (e.g. in crude oils), proteins (e.g. in blood serum, in cow milk), some drugs (e.g. morphine), chlorophylls, etc. Numerous fields of applications have been reported analysis of air and water pollutants, oils, foods, drugs monitoring of industrial processes monitoring of species of clinical relevance criminology etc. 

Pharmacokinetics The absolute bioavailability after a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In subjects with RA, maximum plasma concentrations occurred 3 to 7 hours after subcutaneous administration of anakinra at clinically relevant doses (1 to 2 mg/kg n = 18) the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation was observed after daily subcutaneous doses for up to 24 weeks. The estimated clearance increased with increasing Ccr and body weight. 

Fourth, due to ethical obligations that arise when patients are enrolled in trials, outcomes detected in trials may be treated more aggressively than they would be in usual care. In trials, it is likely that physicians will treat all detected treatable clinical outcomes. In usual care, physicians may treat only those outcomes that in their judgment are clinically relevant. This potential bias would tend to increase the costs of care observed in the trial compared to usual care. 

Classification is traditionally by examination of a well prepared and Romanowsky stained blood film although, increasingly, red cell indices are routinely provided by automated counters. These observations are given clinical relevance by their association with the most common causes in what is called the etio-logic approach. In addition it is also possible to relate cytomorphology to disturbances in the functional capacity of the erythron so that anaemia is seen to result from impaired production of red cells or their shortened survival (Table 1). 

Membrane conformational changes are observed on exposure to anesthetics, further supporting the importance of physical interactions that lead to perturbation of membrane macromolecules. For example, exposure of membranes to clinically relevant concentrations of anesthetics causes membranes to expand beyond a critical volume (critical volume hypothesis) associated with normal cellular function. Additionally, membrane structure becomes disorganized, so that the insertion of anesthetic molecules into the lipid membrane causes an increase in the mobility of the fatty acid chains in the phospholipid bilayer (membrane fluidization theory) or prevent the interconversion of membrane lipids from a gel to a liquid form, a process that is assumed necessary for normal neuronal function (lateral phase separation hypothesis). 

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