Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations.

BACKGROUND: It is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach. METHODS: Here we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. RESULTS: We found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings for resistance in malaria vector populations. CONCLUSION: Importantly, the prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin and permethrin was correlated across malaria vector populations, and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

Development of Aedes albopictus (Diptera: Culicidae) Larvae Under Different Laboratory Conditions.

Critical to successful application of the sterile insect technique against Aedes albopictus (Skuse) is the development of an efficient and standardized rearing protocol to be employed in the mass production system. In this study, several life history traits of Ae. albopictus were analyzed to identify upper and lower thresholds of larval density and diet concentration. Survival to pupation, time to pupation, and sex ratio were evaluated under a range of larval densities (0.5-5 larvae/ml) and food levels (0.05-1.6 mg/larva/d) using two larval diets (one locally developed; one developed by the FAO/IAEA). The larvae reared at 28 °C, at a density of 2 larvae/ml and receiving a food dose equal to 0.6 mg/larva/d of a diet consisting of 50% tuna meal, 50% bovine liver powder (the FAO/IAEA diet), and, as an additive, 0.2 g of Vitamin Mix per 100 ml of diet solution, developed in 5 d and had 90% survival to the pupal stage. With this rearing regime male pupae production 24 h after the onset of pupation was the highest; these pupae were ∼94% male.

Occurrence of natural Anopheles arabiensis swarms in an urban area of Bobo-Dioulasso City, Burkina Faso, West Africa.

The swarming behaviour of natural populations of Anopheles arabiensis was investigated by conducting transect surveys on 10 consecutive days, around dusk, from March to April and from September to October 2012 in Dioulassoba, a district of Bobo-Dioulasso city in Burkina Faso (West Africa). Swarms were observed outside, around identified larval breeding sites on the banks of the Houet River, as well as in the open-air courtyards found at the centre of many homes in the region. Swarms were found to occur in open sunlit spaces, mostly located above physical or visual cues somehow visually distinct from the surrounding area. Overall 67 and 78 swarms were observed, respectively, during the dry season (March-April) and the rainy season (September-October) of 2012, between 1.5m and 4.5m above the ground at their centre. 964 mosquitoes were collected and analysed from dry season swarms, of which most were male, and all were An. arabiensis, as were the few resting mosquitoes collected indoors. Larvae collected from breeding sites found on the banks of the Houet River mostly consisted of An. arabiensis and only a minority of Anopheles coluzzii (formerly identified as An. gambiae M form). Of 1694 mosquitoes analysed from 78 swarms in the rainy season collections, a few An. gambiae (formerly known as An. gambiae S form) males were identified, and the remainders were An. arabiensis. The majority of larvae collected during the wet season from the same breeding sites were identified as An. arabiensis followed by An. coluzzii and An. gambiae. The same pattern of species composition was observed in resting mosquitoes, though the proportion of An. arabiensis was less overwhelming. These data support the conclusion that An. arabiensis is the most prevalent species in this area, though the difference in species composition when using different population sampling techniques is noteworthy. Further studies are required for more detailed investigations of male dispersal, feeding behaviour and mating patterns in this urban setting.

Swarming behaviour in natural populations of Anopheles gambiae and An. coluzzii: review of 4 years survey in rural areas of sympatry, Burkina Faso (West Africa).

The swarming behaviour of natural populations of Anopheles gambiae and An. coluzzii (formerly known as An. gambiae S and M forms, respectively) were investigated through longitudinal surveys conducted between July 2006 and October 2009 in two rural areas of south-western Burkina Faso where these forms are sympatric. In both sites, the majority of swarms were recorded above visual markers localised among houses. In Soumousso, a wooded area of savannah, 108 pairs caught in copula from 205 swarms were sampled; in VK7, a rice growing area, 491 couples from 250 swarms were sampled. If segregated swarms were the norm in both sites, many visual markers were shared by the two forms of An. gambiae. Furthermore, mixed swarms were collected annually in frequencies varying from one site to another, though no mixed inseminations were recorded, corroborating the low hybrid rate previously reported in the field. The occurrence of inter-specific mate-recognition mechanisms, which allow individuals to avoid hybridisation, is discussed.

Efficiency of three diets for larval development in mass rearing Aedes albopictus (Diptera: Culicidae).

A fundamental step in establishing a mass production system is the development of a larval diet that promotes high adult performance at a reasonable cost. To identify a suitable larval diet for Aedes albopictus (Skuse), three diets were compared: a standard laboratory diet used at the Centro Agricoltura Ambiente, Italy (CAA) and two diets developed specifically for mosquito mass rearing at the FAO/IAEA Laboratory, Austria. The two IAEA diets, without affecting survival to the pupal stage, resulted in a shorter time to pupation and to emergence when compared with the CAA diet. At 24 h from pupation onset, 50 and 90% of the male pupae produced on the CAA and IAEA diets, respectively, had formed and could be collected. The diet received during the larval stage affected the longevity of adult males with access to water only, with best results observed when using the CAA larval diet. However, similar longevity among diet treatments was observed when males were supplied with sucrose solution. No differences were observed in the effects of larval diet on adult male size or female fecundity and fertility. Considering these results, along with the relative costs of the three diets, the IAEA 2 diet is found to be the preferred choice for mass rearing of Aedes albopictus, particularly if a sugar meal can be given to adult males before release, to ensure their teneral reserves are sufficient for survival, dispersal, and mating in the field.

Density-dependent effects in experimental larval populations of Anopheles arabiensis (Diptera: Culicidae) can be negative, neutral, or overcompensatory depending on density and diet levels.

Anopheles arabiensis Patton (Diptera: Culicidae) larvae were reared from hatching to the adult stage in the laboratory under a range of diet and larval concentrations using a factorial design. The range circumscribed most of the larval densities and diet concentrations that would allow larval growth and survival using the particular diet formulation and water volume we tested. We determined how these variables affected three outcomes, as follows: larval development rate, survival, and wing length. As has been reported previously, negative density dependence of survival as a function of increased larval density was the prevalent effect on all outcomes when diet was limiting. When diet was not limiting, density dependence was not observed, and three cases of overcompensatory survival were seen. We discuss these results in the context of diet and larval densities for mass rearing and the effect of larval competition on control strategies.

Reversible and irreversible non-internalized LDL and methyl LDL accumulation by human fibroblasts.

In previous in vivo animal studies, we showed that low density lipoprotein (LDL) accumulated irreversibly at the edges of healing arterial lesions rather than being internalized and degraded. To see if similar LDL accumulation occurs in vitro, fibroblasts from normal and homozygous familial hypercholesterolemic (FH) subjects were incubated at 37 degrees C with 125I-LDL and 125I-methyl LDL; the latter is not recognized by any known LDL receptor. Normal fibroblast accumulation of LDL and methyl LDL (5 microg/ml) plateaued within 1 h at 200 and 100 ng/mg, respectively. With FH cells, both LDL and methyl LDL accumulation plateaued at 100 ng/mg. Lipoprotein accumulation by both cell types rose steeply at concentrations up to 15-25 microg/ml, and less so at higher concentrations. Except for degradation of LDL by normal cells, degradation was minimal, which indicated that much of the lipoprotein accumulation was unaccompanied by internalization. The accumulation of both lipoproteins by both cell types was greater at 37 degrees C than at 4 degrees C, and was inhibited between 43 and 75% by homologous unlabeled lipoprotein. To see if any accumulation was irreversible, cells were incubated with radiolabeled lipoproteins for 3 h (pulse), then with homologous unlabeled lipoproteins for up to 20 h (chase). About 50% of intact radiolabeled lipoprotein rapidly dissociated from cells into the medium in the first 4 h of the chase period. In contrast, between 4 and 20 h, most of the remaining intact LDL and methyl LDL appeared to be irreversibly bound, because it was released at a rate of only 0-1%/h. Thus, we conclude that, under the conditions studied, both reversible and irreversible non-internalized LDL binding play a major role in LDL accumulation by cultured cells.

The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function.

Angiotensin-converting enzyme inhibitors improve endothelial function, inhibit experimental atherogenesis, and decrease ischemic events. The Quinapril Ischemic Event Trial was designed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events (the occurrence of cardiac death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary artery bypass grafting, coronary angioplasty, or hospitalization for angina pectoris) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction. A total of 1,750 patients were randomized to quinapril 20 mg/day or placebo and followed a mean of 27 +/- 0.3 months. The 38% incidence of ischemic events was similar for both groups (RR 1.04; 95% confidence interval 0.89 to 1.22; p = 0.6). There was also no significant difference in the incidence of patients having angiographic progression of coronary disease (p = 0.71). The rate of development of new coronary lesions was also similar in both groups (p = 0.35). However, there was a difference in the incidence of angioplasty for new (previously unintervened) vessels (p = 0.018). Quinapril was well tolerated in patients after angioplasty with normal left ventricular function. Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis. However, the absence of the demonstrable effect of quinapril may be due to several limitations in study design.

Low-density lipoprotein apheresis therapy during pregnancy.

Pregnancy in patients with severe hypercholesterolemia and coronary artery disease results in multiple problems both for mother and fetus; the most potent agents for low-density lipoprotein (LDL) cholesterol reduction, the HMG-CoA reductase inhibitors (statins) cannot be used during pregnancy. We present a case in which LDL apheresis via heparin-induced extracorporeal LDL precipitation was employed safely and efficaciously during pregnancy in a woman with heterozygous familial hypercholesterolemia and stable coronary artery disease.

A new model-based technique for enhanced small-vessel measurements in X-ray ciné-angiograms.

Arterial diameter estimation from X-ray ciné angiograms is important for quantifying coronary artery disease (CAD) and for evaluating therapy. However, diameter measurement in vessel cross sections < or =1.0 mm is associated with large measurement errors. We present a novel diameter estimator which reduces both magnitude and variability of measurement error. We use a parametric nonlinear imaging model for X-ray ciné angiography and estimate unknown model parameters directly from the image data. Our technique allows us to exploit additional diameter information contained within the intensity profile amplitude, a feature which is overlooked by existing methods. This method uses a two-step procedure: the first step estimates the imaging model parameters directly from the angiographic frame and the second step uses these measurements to estimate the diameter of vessels in the same image. In Monte-Carlo simulation over a range of imaging conditions, our approach consistently produced lower estimation error and variability than conventional methods. With actual X-ray images, our estimator is also better than existing methods for the diameters examined (0.4-4.0 mm). These improvements are most significant in the range of narrow vessel widths associated with severe coronary artery disease.

Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet. QUIET Investigators. QUinapril Ischemic Event Trial.

Angiotensin-converting enzyme inhibitors have proven to be of clinical benefit in congestive heart failure. Whether they also provide benefit to patients with coronary artery disease in the absence of congestive heart failure via an antiatherosclerotic mechanism is a question the QUinapril Ischemic Event Trial quantitative coronary angiography (QCA) study attempted to answer: 1,750 patients with normal left ventricular function who were undergoing coronary angiography and angioplasty were randomized to 20 mg/day of quinapril versus placebo and followed for 3 years for cardiac end points. A randomly selected subgroup of the total cohort underwent follow-up angiography. The primary QCA end point was the categorical designation of progression versus nonprogression, defined either by QCA or by a cardiac event in patients selected for the QCA trial who had no usable follow-up x-ray film. Secondary end points in patients with 2 angiograms were: new stenosis development, change in minimum lumen diameter index, and change in percent diameter stenosis index. There were 119 progressors among 243 placebo-treated patients (49%) and 111 progressors among 234 quinapril-treated patients (47%) (p = NS). There were 44 patients with new stenosis development in the placebo group (19%) and 50 (22%) in the quinapril group (p = NS). Change in minimum lumen diameter index was -0.21+/-0.03 mm in the placebo group and -0.18+/-0.03 mm in the quinapril group (p = NS). Finally, change in percent diameter stenosis index was +5.1+/-1.0 in the placebo group and +3.5+/-1.0 in the quinapril group (p = NS). Potential confounders of this trial are presented and discussed.

Non-pharmacological lowering of low-density lipoprotein by apheresis and surgical techniques.

In the past year, new data have appeared on the long-term benefits of low-density lipoprotein apheresis in severely hypercholesterolemic patients who are refractory to lipid-lowering drug therapy. Such data are critical for clinical decision-making, because they confirm the hypothesis that the dramatic reduction in low-density lipoprotein made possible by this technique produces clear-cut clinical benefits. Because of its efficacy and low incidence of side-effects, apheresis for severe drug-refractory hypercholesterolemia has superseded surgical approaches, such as liver transplantation or ileal bypass.

Measurement of the time course of peripheral vasoactivity: results in cigarette smokers.

The brachial artery response to flow was assessed non-invasively by ultrasonic measurement of arterial diameter before and 1 min after 5 min of cuff-induced ischemia. It was hypothesized that continuous measurement of arterial diameter and flow velocity would provide a more complete and accurate evaluation of the response to change in blood flow. Therefore, a system to provide this data was developed and its utility in exploring the acute and chronic effects of smoking on arterial function was demonstrated. Brachial artery diameter and flow velocity were measured before, during and for at least 3 min after 5-min of forearm cuff occlusion. Measurements were acquired from 12 habitual smokers (mean 18.3 pack years), after at least 2 h (mean 6.5 h) without smoking ('pre-cigarette') and immediately after smoking one cigarette ('post-cigarette'), as well as from 12 age- and sex-matched lifelong non-smokers. The slope of brachial artery diameter versus time during the occlusion period and the maximum dilation after cuff release relative to the pre-occlusion diameter were significantly decreased in pre-cigarette smokers compared with non-smokers (P < 0.0001 for both comparisons). Importantly, the absolute arterial dilation during the period of increased flow (i.e. reactive hyperemia) was equal for the pre-cigarette smokers and non-smokers (0.31 +/- 0.03 vs. 0.32 +/- 0.04 mm, respectively). Immediately after smoking, the flow response parameters in chronic smokers changed toward non-smoker values (P < 0.001 for post-cigarette vs. pre-cigarette comparisons of the diameter slope during occlusion and the maximum dilation after cuff release relative to pre-occlusion diameter). Thus, continuous diameter measurements in smokers who refrained from smoking demonstrated abnormal constriction of the brachial artery during the low flow period of cuff occlusion, but normal absolute dilation during the period of increased flow. Immediately after smoking, the artery no longer constricted during occlusion. These findings demonstrate the potential value of continuous monitoring of arterial diameter and flow velocity before, during and after application of a vasoactive stimulus.

Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy.

BACKGROUND: Lesion composition, rather than size or volume, determines whether an atherosclerotic plaque will progress, regress, or rupture, but current techniques cannot provide precise quantitative information about lesion composition. We have developed a technique to assess the pathological state of human coronary artery samples by quantifying their chemical composition with near-infrared Raman spectroscopy. METHODS AND RESULTS: Coronary artery samples (n=165) obtained from explanted recipient hearts were illuminated with 830-nm infrared light. Raman spectra were collected from the tissue and processed to quantify the relative weights of cholesterol, cholesterol esters, triglycerides and phospholipids, and calcium salts in the examined artery location. The artery locations were then classified by a pathologist and grouped as either nonatherosclerotic tissue, noncalcified plaque, or calcified plaque. Nonatherosclerotic tissue, which included normal artery and intimal fibroplasia, contained an average of approximately 4+/-3% cholesterol, whereas noncalcified plaques had approximately 26+/-10% and calcified plaques approximately 19+/-10% cholesterol in the noncalcified regions. The average relative weight of calcium salts was 1+/-2% in noncalcified plaques and 41+/-21% in calcified plaques. To make this quantitative chemical information clinically useful, we developed a diagnostic algorithm, based on a first set of 97 samples, that demonstrated a strong correlation of the relative weights of cholesterol and calcium salts with histological diagnoses of the same locations. This algorithm was then prospectively tested on a second set of 68 samples. The algorithm correctly classified 64 of these new samples, thus demonstrating the accuracy and robustness of the method. CONCLUSIONS: The pathological state of a given human coronary artery may be assessed by quantifying its chemical composition, which can be done rapidly with Raman spectroscopic techniques. When Raman spectra are obtained clinically via optical fibers, Raman spectroscopy may be useful in monitoring the progression and regression of atherosclerosis, predicting plaque rupture, and selecting proper therapeutic intervention.

Determination of human coronary artery composition by Raman spectroscopy.

BACKGROUND: We present a method for in situ chemical analysis of human coronary artery using near-infrared Raman spectroscopy. It is rapid and accurate and does not require tissue removal; small volumes, approximately 1 mm3, can be sampled. This methodology is likely to be useful as a tool for intravascular diagnosis of artery disease. METHODS AND RESULTS: Human coronary artery segments were obtained from nine explanted recipient hearts within 1 hour of heart transplantation. Minces from one or more segments were obtained through grinding in a mortar and pestle containing liquid nitrogen. Artery segments and minces were excited with 830 nm near-infrared light, and Raman spectra were collected with a specially designed spectrometer. A model was developed to analyze the spectra and quantify the amounts of cholesterol, cholesterol esters, triglycerides and phospholipids, and calcium salts present. The model provided excellent fits to spectra from the artery segments, indicating its applicability to intact tissue. In addition, the minces were assayed chemically for lipid and calcium salt content, and the results were compared. The relative weights obtained using the Raman technique agreed with those of the standard assays within a few percentage points. CONCLUSIONS: The chemical composition of coronary artery can be quantified accurately with Raman spectroscopy. This opens the possibility of using histochemical analysis to predict acute events such as plaque rupture, to follow the progression of disease, and to select appropriate therapeutic interventions.

Peripheral vasoactivity in familial hypercholesterolemic subjects treated with heparin-induced extracorporeal LDL precipitation (HELP).

Hypercholesterolemia is associated with abnormalities in arterial vasoactivity which can be reversed with cholesterol-reducing therapies. Heparin-induced extracorporeal LDL precipitation (HELP), an invasive method for treating refractory hypercholesterolemia, causes regression of both xanthomas and atherosclerosis, but its effect on vasoactivity has not been investigated. We tested the effects of HELP on vasoactivity with an ultrasound system for continuous measurement of arterial flow velocity and end-diastolic diameter. We measured brachial artery vasoactivity before, during, and after a 5 min forearm vascular occlusion. Vasoactivity measurements were acquired from 6 subjects with familial hypercholesterolemia (FH) who had been treated chronically with HELP, immediately before and after each of 4 treatments, and from 12 age- and sex-matched normocholesterolemic subjects (2 matched with each HELP subject). Peak arterial dilation after cuff release, relative to the pre-occlusion diameter, was similar for the pre-treatment, post-treatment, and normocholesterolemic groups (0.29 mm pre-treatment, 0.30 mm post-treatment and 0.33 mm normocholesterolemic, P = NS). The slope of arterial diameter during occlusion was also similar for the three groups (-0.10 microm/s pre-treatment, 0.02 microm/s post-treatment, and 0.06 microm/s normocholesterolemic, P = NS). These two parameters are known to be decreased in hypercholesterolemic subjects to an extent which could be readily detected by the power of this study. Interestingly, one homozygous FH subject consistently demonstrated significant improvement in these two parameters immediately after HELP, suggesting an individual difference in arterial physiology. On average, FH patients treated chronically with HELP have similar vasoactivity to age- and sex-matched subjects with low risk for atherosclerosis. This result, in light of the many studies that have associated hypercholesterolemia with abnormal vasoactivity, suggests that chronic HELP therapy improves vasoactivity in patients with severe hypercholesterolemia.

Comparison of B-mode, M-mode and echo-tracking methods for measurement of the arterial distension waveform.

Measurements of arterial diameter throughout the cardiac cycle (i.e., the arterial distension waveform) are conducted increasingly to study mechanical properties of the arterial wall and changes associated with disease. The distension waveform of peripheral arteries can be measured noninvasively via ultrasonic echo tracking. M-mode imaging, and B-mode imaging. Of these, echo tracking is the most popular method because of its single micrometer resolution during continuous measurements under ideal conditions. However, high resolution within continuous measurements does not imply high reproducibility between measurements. Therefore, we compared repeated measurements of the amplitude of common carotid artery distension in 26 subjects, obtained sequentially in random order by: 1. Off-line echo tracking of digitized radiofrequency ultrasound; 2. M-mode imaging with automated edge detection; and 3. 30-Hz B-mode imaging with automated edge detection and model-based diameter estimation. In each case, the transducer was hand-held and was removed from the neck between repeated measurements. The amplitude of arterial distension was estimated from the serial diameter measurements by maximum likelihood (ML) estimation, by least-squares fit of a Fourier series model, and by application of a cubic smoothing spline. Within continuous measurements, the standard deviation of the ML distension amplitude for neighboring cardiac cycles was significantly smaller (p > 0.05) with echo-tracking (0.023 mm) than with the B-mode (0.036 mm) or M-mode (0.074 mm) methods. However, between discontinuous measurements on the same subject, the standard deviation of the ML distension amplitude was similar for the echo-tracking (0.076 mm) and B-mode (0.073 mm) methods. The Fourier series model and the cubic smoothing spline slightly reduced the standard deviation of the B-mode and M-mode distension amplitudes, but also reduced the mean amplitude estimate. On the basis of this relative comparison of methods, we conclude that, although echo tracking offers high resolution for continuous measurements, the reproducibility of discontinuous measurements of carotid artery distension is no better with echo tracking than can be obtained from 30-Hz B-mode images.

Baseline clinical and angiographic data in the Quinapril Ischemic Event (QUIET) Trial.

The QUinapril Ischemic Event Trial (QUIET) is the first prospective, double-blind, placebo-controlled trial to investigate the long-term antiatherosclerotic effects of angiotensin-converting enzyme inhibition. Normotensive, nonhyperlipidemic subjects (1,750) with normal left ventricular systolic function were randomly assigned to treatment or placebo at percutaneous transluminal coronary angioplasty (PTCA). The primary end point is time to first cardiac ischemic event. Baseline clinical characteristics are (mean +/- SD): age 58 +/- 9 years; blood pressure 123 +/- 15/74 +/- 10 mm Hg; low density lipoprotein cholesterol 124 +/- 27 mg/dL; high density lipoprotein cholesterol 37 +/- 10 mg/dL; and triglycerides 167 +/- 91 mg/dL. In addition, 81% are men; 22% are current smokers; 49% give a history of myocardial infarction. Baseline angiographic characteristics are (mean +/- SD): left ventricular ejection fraction 59% +/- 11%; per patient diameter stenosis (excluding the PTCA segment) 49% +/- 31%; 8.9 +/- 3.5 analyzable segments per patient (excluding the PTCA segment), 3.8 +/- 2.3 of which have visible stenosis. Including the PTCA segment, 52% have single vessel disease and 48% have multivessel disease. Baseline angiographic data for non-PTCA segments will be correlated with cardiac ischemic events which occur after 6 months. Up to 500 subjects will undergo follow-up angiography with quantitative coronary angiographic analysis (QCA) of baseline and follow-up films. The primary QCA end point will be per-patient categorical designation as progressor or nonprogressor based on the presence or absence of > or = 400 microns narrowing in > or = 1 vessels that did not undergo PTCA.

Biodistribution and autoradiographic localization of I-125--labeled synthetic Peptide in aortic atherosclerosis in cholesterol-fed rabbits.

I-125 labeled SP4 is a synthetic oligopeptide derived from apolipoprotein B of low-density lipoprotein that has been shown to localized in atherosclerotic plaques in experimental animals. However, its biodistribution and mechanism of localization need to be further elucidated. Twenty-four cholesterol-fed (CF) and 20 normal (NL) New Zealand White rabbits were injected with I-125-SP4 and killed 15 to 30 min (6 NL; 6 CF) or 2 h (14 NL; 18 CF) later. We obtained aortic autoradiograms and activity concentrations (% injected dose/gm) in aortic segments and other tissues. The uptake of I-125-SP4 was higher in CF than in NL rabbits in all aortic segments (p < 0.05). I-125-SP4 was cleared rapidly in both CF and NL rabbits with 60 to 70% of the injected dose cleared from the blood by 1 h. No statistically significant differences in radiotracer biodistribution were observed between NL and CF rabbits although activity tended to be higher in the liver, gallbladder, and intestine in NL rabbits and in the kidney and spleen in CF rabbits. Silver grains were distributed mainly on foam cells of the fatty streaks in aortic microautoradiograms from two additional rabbits that had been injected with I-125-SP4. There were 23,518 plus minus 15,878 (SD) grains/mm(2) in fatty plaques but only 14,669 plus minus 11,035 grains/mm(2) in media muscle (p < 0.0001 [9 sections, 17 areas evaluated] in an atherosclerotic animal) in injected animals and 13,439 plus minus 5,565 grains/mm(2) in media muscle (two sections, four areas) in the normal control animals (NS versus media of atherosclerotic animal). I-125-SP4 specifically localizes in aortic atherosclerotic plaques in CF rabbits. There is no significant difference in tissue distribution between normal and CF rabbits except in the aorta. Preliminarily, it appears that the site of tracer uptake is on foam cells and this suggests the possibility of relative specificity for fatty plaque.

New methods for arterial diameter measurement from B-mode images.

Arterial diameter is an important parameter of vascular physiology in vivo. Noninvasive measurements of arterial diameter can be used in the assessment of endothelium-dependent vasoreactivity (EDV) and arterial compliance. Measurements of EDV may serve for assessment of early atherosclerosis. The potential value of EDV measurements with specificity for individual subjects is a strong motivation for improvements in the ultrasonic measurement of arterial diameter. This article presents and evaluates new methods for the measurement and tracking of arterial diameter from B-mode images. B-mode images acquired in planes longitudinal to the vessel and in planes rotated slightly off of the vessel axis ("skew") are considered. The cross-sections of arteries in these planes are modeled as parabola pairs or as ellipses. For the brachial artery, the variance of caliper-based diameter estimates (0.0139 mm2) is twice as large as that of elliptical-model-based diameter estimates (0.0072 mm2) and five times as large as parabolic-model-based diameter estimates (0.0027 mm2). Diameter estimates from the skew and longitudinal planes perform equivalently in limited-motion quantitative comparisons. However, diameter estimates from skew planes are less sensitive to translational motions of the artery. Also, translational motions are unambiguously represented in the skew image, thus facilitating compensatory motions of the transducer. The methods described here are relatively simple to implement and may provide adequate resolution for noninvasive assessment of EDV with individual specificity.