Phase-based vascular input function: Improved quantitative DCE-MRI of atherosclerotic plaques.

PURPOSE: Quantitative pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI can be used to assess atherosclerotic plaque microvasculature, which is an important marker of plaque vulnerability. Purpose of the present study was (1) to compare magnitude- versus phase-based vascular input functions (m-VIF vs ph-VIF) used in pharmacokinetic modeling and (2) to perform model calculations and flow phantom experiments to gain more insight into the differences between m-VIF and ph-VIF. METHODS: Population averaged m-VIF and ph-VIFs were acquired from 11 patients with carotid plaques and used for pharmacokinetic analysis in another 17 patients. Simulations, using the Bloch equations and the MRI scan geometry, and flow phantom experiments were performed to determine the effect of local blood velocity on the magnitude and phase signal enhancement. RESULTS: Simulations and flow phantom experiments revealed that flow within the lumen can lead to severe underestimation of m-VIF, while this is not the case for the ph-VIF. In line, the peak concentration of the m-VIF is significantly lower than ph-VIF (p < 0.001), in vivo. Quantitative model parameters for m- and ph-VIF differed in absolute values but were moderate to strongly correlated with each other [K(trans) Spearman's ρ > 0.93 (p < 0.001) and vp Spearman's ρ > 0.58 (p < 0.05)]. CONCLUSIONS: m-VIF is strongly influenced by local blood velocity, which leads to underestimation of the contrast medium concentration. Therefore, it is advised to use ph-VIF for DCE-MRI analysis of carotid plaques for accurate quantification.

A Multiplex Real-Time Polymerase Chain Reaction (TaqMan) Assay for the Simultaneous Detection of Meloidogyne chitwoodi and M. fallax.

ABSTRACT This study describes a multiplex real-time polymerase chain reaction (PCR) approach for the simultaneous detection of Meloidogyne chitwoodi and M. fallax in a single assay. The approach uses three fluorogenic minor groove binding (MGB) TaqMan probes: one FAM-labeled to detect M. chitwoodi, one VIC-labeled to detect M. fallax, and one NED-labeled to detect the internal amplification control (IAC) to monitor false negative results. One common primer set is used for the amplification of part of the internal transcribed spacer (ITS) region of M. chitwoodi and M. fallax and one primer set for the amplification of the IAC. The test enabled detection of M. chitwoodi and/or M. fallax in DNA samples extracted from batches of juveniles, from single juveniles, and from infected plant material. Compared with current assays to detect M. chitwoodi and M. fallax, the multiplex real-time PCR offers the following advantages: it is faster because the test can simultaneously detect both quarantine species without the need for post-PCR processing; and it is at least 10 times more sensitive than a comparable regular PCR also targeting the ITS sequence. Inclusion of the IAC facilitates the interpretation of the FAM and VIC cycle threshold (Ct) values and can prevent the scoring of false negative results when FAM, VIC, and NED Ct values are high. The test allows precise quantification when only one of the two species is present in the sample. However, experiments with mixtures of genomic DNA of M. chitwoodi and M. fallax revealed that the ability of the multiplex real-time PCR assay to detect small quantities of DNA of one species is reduced when large quantities of DNA of the other species are present.

Analysing and interpreting routinely collected data on sharps injuries in assessing preventative actions.

BACKGROUND: Sharps injuries (SI) occur frequently in hospitals and are a risk for exposure to bloodborne pathogens. During the 1990s, the safety service of a university general hospital introduced, in collaboration with the occupational health service, specific measures to reduce the number of SI. AIM: The aim of this study was to assess the occurrence and evolution of SI during this period and to evaluate the effectiveness of the preventative measures taken, making use of routinely collected data. METHOD: In a retrospective study, we analysed the number of SI recorded from 1990 to 1997. The study population was all employees at risk of SI. Because the introduction of intensive preventative measures dates from 1996, an effect on the incidence of SI can be expected from 1996. To assess this effect, mean incidence rates for 1990-1995 and for 1996-1997 were compared. RESULTS: In the study period, a total of 4230 SI were recorded. The global SI incidence rate decreased from 33.4 SI per 100 occupied beds per year in 1990-1995 to 30.1 in 1996-1997 (P < 0.01). In the same period, among nurses a decrease in incidence rate from 17.2 to 12.7 SI per 100 person-years was noted (P < 0.0001) and for the hotel service from 4.8 to 3.7 (not significant). CONCLUSION: Although this study has various restraints, these results suggest that intensive preventative actions, in combination with technological advances, may have contributed to a drop of 67 SI cases per year.

Preparing children for venepuncture. The effect of an integrated intervention on distress before and during venepuncture.

Venepuncture for routine blood sampling is a very distressing experience for a considerable number of children. Not only do they express high levels of distress during venepuncture but also in anticipation of the procedure. Therefore, prevention or reduction of distress should focus on both phases of the procedure. To this end, three preparation elements were combined: local anaesthesia of the skin, provision of sensory and procedural information, and involvement of the parent. In order to test the effect of this integrated procedure on the distress reactions of young children before as well as during venepuncture, 31 children were randomly assigned to one of two conditions: preparation or no preparation. Independent raters, who were blind to group assignments, scored segments of the videotaped behaviour of the children, according to the Groninger Distress Scale. Prepared children displayed significantly less distress before and during venepuncture than not-prepared children, regardless of their gender, ethnical origin, age, injection history, and the tension of their parent.

Effect of strength training on blood pressure measured in various conditions in sedentary men.

To examine the effect of long term strength training on heart rate and blood pressure, measured in different conditions, and on their variability, thirty healthy, previously sedentary men were randomized into a training and a control group. The strength training program consisted of 48 training sessions on a multigym apparatus at a frequency of 3 sessions each week, involving leg press, bench press, leg curl, shoulder press, leg extension and sit ups. The control group was asked not to change their sedentary lifestyle. In the subjects of the training group the load could be increased significantly for all exercises (p < 0.01). Heart rate and blood pressure were measured at rest in the supine and sitting position, during 24 hours with a non-invasive ambulatory device and during an exercise test on a cycloergometer. Repeated measures analysis of variance did not show an effect of strength training on heart rate or on blood pressure. In addition, power spectral analysis of the RR interval (ECG) and of the beat-to-beat blood pressure in the supine subject revealed similar total, low frequency and high frequency power before and after training, indicating that the neural control of both heart rate and blood pressure was not affected by a 16-week program of strength training.

The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Why is antihypertensive drug therapy needed in elderly patients with systolodiastolic hypertension?

OBJECTIVE: This paper presents a meta-analysis of eight outcome trials of antihypertensive drug treatment in elderly hypertensive patients, and uses the results of these trials to discuss day-to-day issues in the treatment of elderly hypertensive patients. META-ANALYSIS: In an intention-to-treat analysis, cardiovascular mortality was decreased on average by 22% (95% confidence interval -32% to -10%). This decrease was a result of reductions in both coronary and cerebrovascular mortality, by 26% (-40% to -9%) and 33% (-50% to -9%), respectively. So far, the effectiveness of antihypertensive therapy in reducing cardiovascular mortality has not been established with confidence in trials where the diastolic blood pressure at random allocation to treatment groups was below 95 mmHg or in patients above 75 years of age. IMPLICATIONS FOR DAY-TO-DAY PRACTICE: No blood pressure treatment goal has been definitively established but a reduction in systolic blood pressure to about 150 mmHg may be optimal. Extrapolation of trial results to the elderly population with systolodiastolic hypertension at large seems acceptable for a Western population, but may be premature for elderly Asians and Africans. beta-Blockers and especially diuretics are recommended as first-line drugs in elderly patients with symptomless, uncomplicated hypertension, since the effectiveness of other drugs in reducing morbidity and mortality has not yet been established. Recommendations for the treatment of symptomless patients with isolated systolic hypertension may be premature. Ongoing trials on systolic hypertension in Europe (Syst-Eur) and China (Syst-China) may provide further information.

Effects of celiprolol vs. nifedipine on serum lipoproteins in patients with mild to moderate hypertension.

During a double-blind, randomized study in hypertensive patients, changes in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily), each time using a double-dummy technique. After 6 weeks, dosages of each drug could be doubled. After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks of treatment were different (p < 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol, and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified. The present study showed that celiprolol was at least equivalent to nifedipine in terms of secondary effects on plasma lipids and lipoprotein.

Comparison of the effect of celiprolol and nifedipine on blood pressure and plasma lipids.

During a double-blind, randomized study in hypertensive patients, changes in blood pressure (BP) and in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily) each time using a double dummy technique. After 6 weeks, dosages of each drug could be doubled. Both drugs caused similar reductions in blood pressure but after 12 weeks treatment, the percentage of decrease in diastolic BP (DBP) was more pronounced (p less than 0.01) in the nifedipine group (-18%) than in the celiprolol group (-12%). After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks treatment were different (p less than 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified, suggesting that reverse cholesterol transport was not affected by the drugs. In both treatment groups, a significant positive relationship was observed between changes in LDL cholesterol and apoprotein B. As compared with nifedipine, celiprolol after 12-week therapy had a rather favorable plasma lipid profile. The clinical relevance of such findings, in terms of prevention of cardiovascular complications, has yet to be established.

Mean and range of the ambulatory pressure in normotensive subjects.

To perform a meta-analysis of published reports in an attempt to determine the mean and range of normal ambulatory blood pressure (BP), 23 studies including a total of 3,476 normal subjects were reviewed. Most studies were compatible with a mean 24-h BP in the range of 115-120/70-75 mmHg, a mean day time BP of 120-125/75-80 mmHg, and a mean night time BP of 105 to 110/60 to 65 mmHg. With weighting for the number of subjects included in the individual studies, the 24-h BP averaged 118/72 mmHg, the day time BP 123/76 mmHg, and the night time BP 106/64 mmHg. The night/day pressure ratio averaged 0.87 for systolic and 0.83 for diastolic BP, with ranges across the individual studies from 0.79 to 0.92 and from 0.75 to 0.90, respectively. If the mean +/- 2 standard deviation interval in the various studies was considered normal, the range of normality was on average 97 to 139/57 to 87 mmHg for the 24-h BP, 101 to 146/61 to 91 mmHg for the day time BP, and 86 to 127/48 to 79 mmHg for the night time BP. Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals, which summarize the experience of 23 investigators, could serve as a temporary reference for clinical practice.

Predictability of the individual outcome of a physical training program of an Army Special Forces Unit.

In a search for parameters that could predict the chances of success in a 3-month basic training program of a Special Forces unit, 293 conscripts were studied before the start of the training period. Physical activities, smoking habits, and dietary and drinking habits were evaluated by questionnaire. Anthropometric values were noted. A blood sample was taken for determination of serum cholesterol, high-density lipoprotein (HDL)-cholesterol and gamma-glutamyltranspeptidase (GGT). Physical capacity was assessed by bicycle ergometry. Sixty-five trainees were discontinued from the program for intercurrent diseases or trauma, 132 went successfully through the whole program (group S), and 96 trainees failed (group F). More candidates of group S stated that they participated in sports (p less than 0.01) and fewer smoked (p less than 0.01) than in group F. Trainees of group F had a higher consumption of spirits (p less than 0.05) than trainees of group S. There was no difference between the two groups in weight, percentage body fat, physical capacity, total serum cholesterol, and GGT values. HDL-cholesterol was higher in group S compared to group F (p less than 0.01). Stepwise discriminant analysis applied to anthropometric, biochemical, and cycloergometric data indicated HDL-cholesterol, height, resting heart rate, heart frequency at maximal exercise, and serum cholesterol as significant discriminating variables (p less than 0.001), giving only a 63% chance of correctly classifying the candidates.

Effect of physical training on systemic and brachial artery haemodynamics in normal men.

The effect of endurance training on resting systemic and brachial haemodynamics was studied in 27 normal sedentary volunteers using a randomized cross-over design. After four months of physical training, peak oxygen uptake and physical working capacity at a heart rate of 130 beats/min (PW130) were increased by 16% (p less than 0.01) and 29% (p less than 0.001), respectively. At end-diastole left ventricular wall thickness was increased (p less than 0.01), whereas internal diameter was not changed. However, the change in internal diameter was positively related (r = 0.44, p less than 0.036) to the change in PWC130, indicating that the internal diameter increased, particularly in those subjects with the greatest increase in exercise capacity. The systemic haemodynamic adaptation to training was characterized by an increased stroke volume and concomitant reduction in heart rate so that cardiac output was not changed. On the other hand, brachial blood flow decreased by 36% on average. The change in blood flow was negatively related (r = -0.43, p = 0.03) to the change in PWC130 after training. Half the number of subjects were restudied after a four-month detraining period. The echocardiographic and Doppler variables tended to return to the pretraining level.

Mean and range of the ambulatory pressure in normotensive subjects from a meta-analysis of 23 studies.

To perform a meta-analysis of published reports in an attempt to determine the mean and range of normal ambulatory blood pressure (BP), 23 studies including a total of 3,476 normal subjects were reviewed. Most studies were compatible with a mean 24-hour BP in the range of 115 to 120/70 to 75 mm Hg, a mean daytime BP of 120 to 125/75 to 80 mm Hg, and a mean nighttime BP of 105 to 110/60 to 65 mm Hg. With weighting for the number of subjects included in the individual studies, the 24-hour BP averaged 118/72 mm Hg, the daytime BP 123/76 mm Hg, and the nighttime BP 106/64 mm Hg. The night/day pressure ratio averaged 0.87 for systolic and 0.83 for diastolic BP, with ranges across the individual studies from 0.79 to 0.92 and from 0.75 to 0.90, respectively. If the mean +/- 2 standard deviation interval in the various studies was considered normal, the range of normality was on average 97 to 139/57 to 87 mm Hg for the 24-hour BP, 101 to 146/61 to 91 mm Hg for the daytime BP, and 86 to 127/48 to 79 mm Hg for the nighttime BP. Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals, which summarize the experience of 23 investigators, could serve as a temporary reference for clinical practice.

Left ventricular hypertrophy in elderly hypertensive patients: a report from the European Working Party on High Blood Pressure in the Elderly trial.

In a double-blind, placebo-controlled trial, 840 elderly hypertensive patients were randomly assigned to treatment with a combination of hydrochlorothiazide and triamterene or placebo; methyldopa or matching placebo was added to the treatment regimen if blood pressures remained high. After adjustment for age, gender, and body mass index, initial electrocardiographic (ECG) voltage measures of RaVL and SV1 + RV5 were significantly related to systolic blood pressure; RaVL was also related to diastolic blood pressure. After one year of treatment, the decrease in RaVL and SV1 + RV5 in the treated patients, adjusted for age and body mass index, were not correlated with the changes in systolic blood pressure, but the decreases in SV1 + RV5 were positively related to the decrease in diastolic blood pressure. After four years of treatment, the decreases in RaVL and SV1 + RV5 were significantly and positively related to the decrease in systolic blood pressure after adjustment for age and changes in body mass index. In a four-year cohort of 222 patients, most of the decreases in ECG voltages in the treated patients and the increases in the placebo patients were found to have occurred during the first year of treatment. The type of treatment (diuretics alone or diuretics plus methyldopa) did not affect ECG voltages during the first year of follow-up. Total and cardiovascular mortality were related to initial amplitude of RaVL, but the significant correlation disappeared after adjustment for age.

Pulse rate and sodium intake interact to determine blood pressure. A population study.

It has been suggested that certain factors need to be present for the pressor effect of sodium to become apparent. The present population study investigated whether pulse rate (PR) and salt intake interact to determine blood pressure (BP). Twenty-four hour urinary sodium (UNaV) was used as a measure of salt intake. A random population sample, including 2081 subjects with a minimum age of 18 years, was stratified on tertiles of PR. In subjects with a slow PR(less than 68 beats/min) and in those with a fast PR (greater than 78 beats/min), a significant curvilinear relationship between BP and UNaV was found, while in subjects with an intermediate PR the BP-UNaV correlation was not significant. There was also a significant interaction between PR and UNaV, indicating that when UNaV increased from 160 to 300 mmol/24 h, systolic/diastolic BP rose by 2/1 mm Hg in the fast PR third, but declined by 1/1 mm Hg in the slow PR third. These divergent trends could not be explained by smoking habits or alcohol consumption and were still present after cumulative adjustment for other important correlates of BP, ie, gender, age, body weight, urinary potassium, and contraceptive pill intake in women. In conclusion, the present data suggest that in subjects with a pulse rate greater than 78 beats/min a high salt intake may be associated with blood pressure elevation, whereas the opposite tendency is observed in individuals with a pulse rate less than 68 beats/min.

Ambulatory blood pressure monitoring in clinical trials.

Monitoring ambulatory blood pressure, instead of taking pressure readings in hospital, avoids the so-called white-coat effect and allows more readings to be obtained over a longer period of time. It improves the accuracy of the blood pressure estimate and increases the statistical power of therapeutic trials for hypertension. Subjects with white-coat or office hypertension can be detected by ambulatory blood pressure monitoring and excluded from clinical trials. In 23 studies, including a total of 3304 normotensive subjects, the 24-h ambulatory blood pressure averaged 118/72 mmHg; the daytime and night-time pressures were 123/76 mmHg and 106/64 mmHg, respectively. If the mean plus two standard deviation (s.d.) interval is considered the upper limit of normal, the meta-analysis suggested that hypertension may be suspected if the 24-h pressure exceeds 129/87 mmHg, or if the daytime or night-time pressures are higher than 146/91 mmHg or 127/79 mmHg, respectively. On balance, most studies suggest that placebo effects on blood pressure are not observed when blood pressure is measured with ambulatory recorders. If confirmed, this observation indicates that it is possible to simplify the design of trials in the field of hypertension. Ambulatory blood pressure readings should be obtained with properly validated monitors. If the recordings are of sufficient quality, editing does not increase the precision of the subsequent statistical analyses. The statistical analyses should account for diurnal rhythms, and subject and treatment effects.