A new method for quantitative regional cerebral blood volume measurements using computed tomography

BACKGROUND AND PURPOSE: Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements. METHODS: The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV = CBF x MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue. RESULTS: The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs. CONCLUSIONS: The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT x CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.     

Plasma fibrinogen levels in healthy postmenopausal women: physical activity and hormone replacement status

BACKGROUND: Fibrinogen is a major component of the coagulation system and a powerful independent risk factor for cardiovascular disease in postmenopausal women. Regular physical activity has been recommended as an effective clinical approach to lowering plasma fibrinogen levels; currently, however, there are little or no data to support a relationship between habitual exercise status and plasma fibrinogen levels in healthy postmenopausal women who either use or do not use hormone replacement therapy (HRT). METHODS: Plasma fibrinogen levels were measured in 20 physically active (56 +/- 1 yr) and 31 sedentary (58 +/- 1 yr) healthy postmenopausal women. Nine (45%) physically active and 15 (48%) sedentary women had been using HRT for > 1 year; the others were nonusers of HRT. RESULTS: Plasma fibrinogen levels were approximately 15% lower (p = .001) in the physically active women (2.48 +/- .08 g/L) than the sedentary controls (2.92 +/- .06 g/L) and approximately 7% lower (p = .04) in the users (2.65 +/- .08 g/L) versus nonusers (2.84 +/- .08 g/L) of HRT. Moreover, the lower (0.4 g/L) plasma fibrinogen levels associated with regular physical activity were evident in both the users (2.39 +/- .11 vs 2.80 +/- .08 g/L, p = .001) and nonusers (2.56 +/- .11 vs 3.03 +/- .08 g/L, p = .006) of HRT. Stepwise multiple regression analysis revealed that percent body fat was the primary determinant of plasma fibrinogen levels, accounting for 30% of the variability. CONCLUSIONS: Regular physical activity is associated with lower plasma fibrinogen levels in postmenopausal women; the lower plasma fibrinogen levels associated with regular physical activity are evident in both users and nonusers of HRT; and plasma fibrinogen levels are positively related to percent body fat in postmenopausal women differing in physical activity and HRT status. Lower plasma fibrinogen levels in physically active postmenopausal women may contribute to their lower risk of cardiovascular disease.     

Bismuth carbomer foam enemas for active chronic pouchitis: a randomized, double-blind, placebo-controlled trial

One biological effect of nitric oxide (NO) has been believed to be exerted through induction of the ADP-ribosyltransferase activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Though this notion is based on the finding that NO increases the auto-ADP-ribosylation of GAPDH, controversial data have also been reported. To determine whether or not NO really activates ADP-ribosylation, we re-examined the NO-induced modification of GAPDH with NAD+. GAPDH was modified equally with [adenosine-14C]NAD+ and [carbonyl-14C]NAD+, indicating that the glycoside bond of NAD+ between ADP-ribose and nicotinamide is intact. The release of nicotinamide from NAD+ was not evident during incubation of GAPDH with [carbonyl-14C]NAD+. Thus, the modification of GAPDH is apparently not ADP-ribosylation. In addition, we found that basal and glyceraldehyde-3-phosphate-induced modifications of GAPDH, both of which have also been explained as ADP-ribosylation, were not ADP-ribosylation, and that the modification of GAPDH in the absence and presence of NO or GA3P was distinct in the dithiothreitol effect or resistance to HgCl2.     

Incident reporting in acute pain management

Incident reporting is an effective tool for continuous quality improvement in clinical practice. A prospective study on voluntary incident reporting in pain management was conducted at a major teaching hospital in Hong Kong. Over a 12-month period, 53 incidents were reported in 1275 patients who received pain relief treatments which were supervised by the acute pain service. The majority of the incidents were first detected by the pain team. The most common incidents involved delivery circuits, delivery pump and drug administration. A large proportion (81.4%) of the incidents were thought to be preventable. Human factors were involved in 41.9% of the patients reported, most commonly associated with unfamiliar technique/inexperience, inattention and inadequate communication. Four patients developed major morbidity of which two were attributed to inadequate analgesia, while three others had major physiological changes without morbidity. Strategies have been formulated to prevent further occurrence of these incidents. We propose that incident reporting is a potentially useful tool in identifying and preventing adverse events in postoperative pain management.     

Quality adjusted survival analysis with repeated quality of life measures

One way of examining trade-offs between quantity and quality of life (QOL) is to combine them into a single measure such as quality-adjusted life year (QALY). If censoring occurs, then estimation presents some difficulties. One approach, known as Q-TWiST, is to define a series of health states, use a 'partitioned' survival analysis to calculate the average time in each state, and then weight each state according to its quality of life to calculate QALYs. Such health-state models, however, are unhelpful when the transitions between health states are unclear or if they do not adequately reflect variations in quality of life. We therefore examine an alternative analysis to be used when repeated measures of quality of life are available from individual patients in a clinical trial. The method proceeds by separating quality of life and survival, that is, dQALY/dt = S(t)Q(t), where S(t) is the survival curve, estimated from the standard Kaplan-Meier method, and Q(t) is the quality of life function, derived from individual repeated measures of quality of life. We derive single health-state (QALY) and multiple health-state (Q-TWiST) models and illustrate the approach by comparing different durations of adjuvant chemotherapy for breast cancer.