INDEX pathophysiology

While the use of preclinical disease models offers many advantages, such as the potential for identification of biomarkers for clinical trials and a direct estimation of the therapeutic index, there are also disadvantages to this approach. The disadvantages can include a paucity of historical/baseline data and inherent variability of the model, the technical feasibility of using a particular disease model, the onset/severity of the injury in the animals as this may be different from humans, and the fact that the model may only emulate select aspects of the human pathophysiology of the disease [43], It is important to use behavioral models that have adequate sensitivity and specificity to allow for correlation with morphological and biochemical findings, as in the area of spinal cord injury. 

Acute reduction in renal perfusion is considered important in the pathophysiology of contrast agent-induced nephrotoxicity. Color-coded duplex sonography has been used in assessing intrarenal vascular resistance in 10 patients (mean age 51 years) after intravenous injection of 100 ml of the low-osmolar contrast medium iopamidol (iodine 300 mg/ml) (182). The resistive index was measured at 1-minute intervals over 10 minutes after injection in each patient. There was a statistically significant rise in resistive index at 2, 3, 4, and 5 minutes after injection, mean values 0.74, 0.75, 0.72, and 0.75... 

Theophylline is not only characterized by a narrow therapeutic index and distinct relationships between serum concentration and therapeutic and toxic effects, but also by a high interindividual pharmacokinetic variabihty. This variability is predominantly based on a high patient-to-patient variability in the metabolic clearance of theophylline that is confounded by numerous additional physiological, pathophysiological, and enviromnental factors. Intravenous theophylhne (given as aminophyl-line), for example, has been shown to result in considerable variations in serum concentrations among patients despite the same dose, and theophylline dose requirements to maintain serum concentration in the range of 10 to 20 lig/ml varied from 400 to 3200 mg/day. ... 

Since blood serves as the primary metabolic transport system between the body organs, its composition is the preferred indicator with regard to the pathophysiological condition of the patient. This is the reason why most determinations are concerned with whole blood or biofluids derived from it. Glucose in urine is also an index component of metabolic disorders in patients. Other biological fluids have been considered as an alternative assay for blood glucose. 

Vassilakopoulos T, Zakynthinos S, Roussos C. The tension-time index and the liequency/tidal volume ratio are the major pathophysiologic determinants of weaning failure and success. Am J Respir Crit Care Med 1998 158 378-385. 

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