Test bolus

Fig. 5.27a,b. Cystic medial necrosis. Due to the high grade proximal stenoses, test bolus measurement prior to CE-MRA failed in this case, leading to superimposition of venous contrast (a). Evaluation is nevertheless possible on original source slices (b), showing stenoses and aneurysms along the proximal supraaortic vessels (arrows)... 

Test bolus Accounts for different patient physiology More complex requires 10-15 ml of additional contrast, not required for imaging... 

Multiphasic injection (Fleischmann) Uniform plateau of enhancement Accounts for varying patient physiology Requires test bolus Requires dual phase CT power injector... 

As an alternative to bolus tracking, a smartscan type function can be used, in which a test bolus is administered to determine the scan delay [64]. A region of interest is selected, typically in the proximal ICA, and 10 mL of contrast is injected. This region is scanned continuously using a low mAs/kVp technique, and the prep delay is chosen as the time corresponding to... 

Figure 4.10 demonstrates the limited utility of a scan when the delay is not chosen correctly. Both mathematical and animal models have demonstrated that, when there is reduced cardiac output, intravenous injection will result in a delayed intra-arterial arrival time and a greater peak arterial enhancement [65]. In patients with reduced cardiac output, therefore, once again, a 35- to 40-s prep delay is typically employed. Increasing the degree of arterial opacification can be accomplished simply by utilizing either a larger injection volume or a faster injection rate. With a test bolus, the time density curve generally has a slightly different geometry from that of the main bolus, as shown in Fig. 4.11. This is likely due to injection of a smaller...

Alternatively, Fleischmann and Hittmair [71] modeled aortic enhancement by treating the entire body as a black box, where the input function was defined by the administration of a small contrast test bolus, and the output function was simply the resulting measured time-attenuation curve. The patient function was the black box, which substitutes for the multiple compartment... 

Fig. 4.11 Time density curve of a test bolus (a) as compared with the standard bolus (b). The rectangle demonstrates the ideal enhancement...

The technical considerations and interpretation of the second portion of the acute stroke protocol, CTA, is discussed in detail in Chap. 4. Importantly, however, the source images from the CTA vascular acquisition (CTA-SI) also supply clinically relevant data concerning tissue level perfusion. It has been theoretically modeled that the CTA-SI are predominantly blood volume, rather than blood flow weighted [20, 27,70], The potential utihty of the CTA-SI series in the assessment of brain perfusion is discussed in detail below. This perfused blood volume technique requires the assumption of an approximately steady state level of contrast during the period of image acquisition [27], It is for this reason - in order to approach a steady state - that protocols call for a biphasic contrast injection to achieve a better approximation of the steady state [71, 72]. More complex methods of achieving uniform contrast concentration with smaller doses have been proposed that may eventually become standard, such as exponentially decelerated injection rates [73] and biphasic boluses constructed after analysis of test bolus kinetics [72, 74]. 

In addition to injection duration, variable cardiac output parameters of individual patients will have to be addressed. In principle, the two methods to assess the contrast arrival are test bolus techniques and so-called bolus tracking. Both approaches measure Carr and therefore adapt for varying cardiac output. The... 

Bae KT (2005) Test-bolus versus bolus-tracking techniques for CT angiographic timing. Radiology 236 369-370 author reply 370... 

Cademartiri F, Nieman K, van der Lugt A, Raaijmakers RH, Mollet N, Pattynama PM, de Feyter PJ, Krestin GP (2004b) Intravenous contrast material administration at 16-detec-tor row helical CT coronary angiography test bolus versus bolus-tracking technique. Radiology 233 817-823... 

Different circulatory phases can only be separated by precisely timing the scanning delay to the patient s individual circulation time timing can be determined by using fixed delay, a test bolus, or a computer automated scanner technology (CAST) (bolus tracking) (Fleischmann 2003b). 

One compound from this series, (10), has been tested in vitro in human myometrium tissue obtained at term following caesarean section and shown to inhibit contractions induced by oxytocin [44] with a pA2 of 7.6. This is one of the first direct indications that the use of an oxytocin antagonist may be of benefit in the treatment of preterm labour in humans. This compound has been extensively studied in the near-term baboon and has been shown to inhibit nocturnal and near-term contractions following an intravenous bolus injection [45]. Further studies on the effect of oxytocin antagonism in the weeks leading up to delivery in the baboon have also been published [46]. 

Similar to 5-FU, there is a polymorphism associated with irinotecan toxicity. UDP-glucuronosyltransferase (UGT1A1) is an enzyme responsible for the glucuronidation of SN-38 to inactive metabolites, and reduced or deficient levels of this enzyme correlate with irinotecan-induced diarrhea and neutropenia.39 Recently the FDA approved a blood test that detects variations in this gene. This test will assist health care providers in predicting which patients may develop severe toxicities from normal doses of irinotecan and can be ordered prior to patients receiving irinotecan. binotecan is administered as an IV bolus over 60 to 90 minutes in a variety dosing schedules. 

No animal or human data were available for inhalation exposure. There are no data regarding effects in humans after oral exposure. Information is available in animals regarding health effects following acute, intermediate, and chronic oral ingestion of diisopropyl methylphosphonate. The animal data obtained after oral exposure indicate that diisopropyl methylphosphonate is moderately toxic after acute bolus exposure but has a lower order of toxicity after intermediate and chronic exposures in food. No data were found on the toxicity of diisopropyl methylphosphonate after exposure in drinking water. Further, diisopropyl methylphosphonate is rapidly metabolized and excreted and does not accumulate. It does not appear to have reproductive or developmental effects. At the doses tested, it does not appear to be an acetylcholinesterase inhibitor, although this issue has not been resolved yet. Limited data are available for dermal exposure in humans and animals. Diisopropyl methylphosphonate does not appear to be a... 

Male CD-I mice were allowed 3 days to stabilize after arrival at the test facility. Groups of 10 mice each received 0.2 mL of the various concentrations of PGG in sterile saline by bolus intravenous (iv) injection (transthoracic cardiac puncture). A control group received 0.3 mL of sterile saline. Mice were returned to their cages, maintained on food and water ad libitum and were challenged 3-4 hours... 

Initial safety tests were carried out in beagle dogs and subsequently in cynomolgus monkeys. Single bolus i.v. doses of up to 100 mg kg-1 were used and were found to exert no negative effect upon general condition, blood pressure, heart or cardiovascular parameters, respiration rate or body temperature. No safety tests evaluating potential product effects upon the central nervous system were undertaken, as the protein is considered unlikely to cross the blood-brain barrier. 

The typical test (illustrated in Figure 15.7) is performed using mice, normally female CBA mice 6-10 weeks of age. Female BALB/c and ICR mice have also been used. After animal receipt, they are typically acclimated to standard laboratory husbandry conditions for 7-10 days. The usual protocol will consist of at least two groups (vehicle control and test article treated) of five mice each. They are treated on the dorsal surface of both ears with 25 pi (on each ear) of test article solution for three consecutive days. Twenty-four to forty-eight hours after the last test article exposure, the animals are given a bolus (0.25 ml) dose of [3H]thymidine (20 pCi with a specific activity of 5.0-7.0 Ci/mmol) in phosphate buffered saline via a tail vein. Five hours after the injection, the animals are euthanized by C02 asphyxiation and the auricular lymph nodes removed. 

Quantitative measurement of diffusional uptake and carrier-mediated transport of nutrients and drugs in experimental animals was greatly facilitated with the introduction of Olden dorfs brain uptake index (BUI) [42].Test and reference tracers are injected as an intraarterial bolus into the carotid artery of the anaesthetized animal. After 5 s the animal is killed and the brain is removed for radioactivity counting. This method measures the ratio of the unidirectional brain extraction, E, of the test substance and of the reference ([ H]-water, [ " C]-butanol), which are labelled with different isotopes, during a single passage through the brain capillary bed ... 

Figure 2.4. In vivo measurement of blood-brain barrier (BBB) permeability, (a) Internal carotid artery perfusion technique (i) in the rat. Other branches of the carotid artery are ligated or electrically coagulated (o, occipital artery p, pterygopalatine artery). The external carotid artery (e) is cannulated and the common carotid artery (c) ligated. Perfusion time may range from 15 s to 10 min, depending on the test substance. It is necessary to subtract the intravascular volume, Vo, from (apparent volume of distribution), to obtain true uptake values and this may be achieved by inclusion of a vascular marker in the perfusate, for example labelled albumin. Time-dependent analysis of results in estimates of the unidirectional brain influx constant Ki (pi min which is equivalent within certain constraints to the PS product. BBB permeability surface area product PS can be calculated from the increase in the apparent volume of distribution Vd over time. Capillary depletion, i.e. separation of the vascular elements from the homogenate by density centrifugation, can discriminate capillary uptake from transcytosis. (b) i.v. bolus kinetics. The PS product is calculated from the brain concentration at the sampling time, T, and the area under the plasma concentration-time curve, AUC.

The most sensitive technique for measuring brain uptake is the intravenous bolus administration or infusion and subsequent measurement of brain concentrations (Figure 2.4). Depending on the pharmacokinetics of the test compound in plasma, brain sampling may be performed after suitable circulation times ranging from minutes to hours or days. 

Intrathecal Management of severe spasticity of spinal cord origin in patients who are unresponsive to oral baclofen therapy or experience intolerable CNS side effects at effective doses. Intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the FDA specifically for the administration of baclofen into the intrathecal space. 

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