Diminished medial prefrontal cortex activation during the recollection of stressful events is an acquired characteristic of PTSD.

BACKGROUND: Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD. METHODS: In this case-control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement. RESULTS: Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups. CONCLUSIONS: Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

Accelerated coronary artery stenosis at a site proximal to coronary angioplasty.

Rapid progression of coronary stenosis has been described in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), typically resulting in symptomatic angina 3 to 30 months postprocedure. We report a case of accelerated coronary stenosis in the instrumented vessel resulting in angina 3 days post-PTCA.

Percutaneous transluminal coronary angioplasty of a coronary artery stenosis at the site of myocardial bridging.

The incidence of myocardial bridging observed at angiography (0.5-16%) is far less than at pathologic study (greater than 50%). Myocardial bridging is felt to have a 'protective effect' on the coronary artery at the site of bridging, and significant atherosclerosis within the bridge is almost never seen at pathologic examination. To date, there have been no reports of significant atherosclerosis at the site of angiographically documented myocardial bridging. We report a unique case of an angioplasty of a left anterior descending artery stenosis within a myocardial bridge. This report also discusses the possible difference in the protective effect of myocardial bridging that is seen at angiography and myocardial bridging that is only appreciated pathologically but not angiographically.

Characterization of the site dependency of normal canine arterial fluorescence.

The difference in fluorescence between normal and atherosclerotic artery has been proposed as a feedback mechanism to guide selective laser ablation of atherosclerotic plaque. This fluorescence difference is due to the relative difference in collagen:elastin content of normal artery and atherosclerotic plaque. However, normal arteries have site-dependent variation in collagen: elastin content which may affect their fluorescence spectra. To evaluate the site dependency of normal arterial fluorescence, helium-cadmium (325 nm) laser-induced fluorescence spectra were analyzed in vitro from the ascending aorta, abdominal aorta, and carotid, femoral, renal, and coronary arteries (N = 57) of 12 normal mongrel dogs. Elastin and collagen contents were determined for a subset of these arteries (N = 15). The spectral width of normal arterial Fluorescence varied by site and correlated with the measured collagen:elastin content at each site (r = -0.84, P less than 0.005). Fluorescence spectra were decomposed into collagen and elastin spectral components by using a linear model with a least-squared error criterion fit. The derived collagen and elastin spectral coefficients correlated with the measured collagen and elastin tissue content (r = 0.75 and 0.83 respectively, P less than 0.005). Thus, the fluorescence spectra of normal arteries is site dependent and correlates with the collagen:elastin content. Therefore, spectral feedback algorithms for laser angioplasty guidance must be site specific.

Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time.

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence.

The observation that laser-induced fluorescence (LIF) spectra of atherosclerotic and normal artery are different has been proposed as the basis for guiding a "smart" laser angioplasty system. The purpose of this study was to investigate the causes of this difference in LIF. Helium-cadmium laser-induced (325 nm) fluorescence was recorded from pure samples of known constituents of normal and atherosclerotic artery including collagen, elastin, calcium, cholesterol, and glycosaminoglycans. Similarities between the LIF spectra of atherosclerotic plaque and collagen and normal aorta and elastin were noted. LIF spectroscopy was then performed on specimens of atherosclerotic aortic plaque (n = 9) and normal aorta (n = 13) and on their extracted lipid, collagen, and elastin. Lipid extraction did not significantly alter atherosclerotic plaque or normal aortic LIF, suggesting a minor contribution of lipid to arterial LIF. The LIF spectra of normal aorta wall was similar to the spectra of the extracted elastin, whereas the LIF spectra of atherosclerotic aortic plaque was similar to the spectra of the extracted collagen. These observations are consistent with the reported relative collagen-to-elastin content ratio of 0.5 for normal arterial wall and 7.3 for atherosclerotic plaque. A classification algorithm was developed to discriminate normal and atherosclerotic aortic spectra based on an elastin and collagen spectral decomposition. A discriminant score was formed by the difference of elastin and collagen (E-C) coefficients and used to classify 182 aortic fluorescence spectra. The mean E-C value was +0.83 +/- 0.04 for normal and -0.48 +/- 0.07 for atherosclerotic aorta (p less than 0.001). Classification accuracy was 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and evaluation of spectral classification algorithms for fluorescence guided laser angioplasty.

Laser angioplasty, or the ablation of atherosclerotic plaque using laser energy, has tremendous potential to expand the scope of nonsurgical treatment of obstructive vascular disease. Clinical laser angioplasty, however, has been hindered by an unacceptable risk of vessel perforation. Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal artery and may therefore be capable of guiding selective plaque ablation. To assess the feasibility of utilizing spectral information to discriminate arterial tissue type, several classification algorithms were developed and evaluated. Arterial fluorescence spectra from 350 to 700 nm were obtained from 100 human aortic specimens. Seven spectral classification algorithms were developed with the following techniques: multivariate linear regression, stepwise multivariate linear regression, principal components analysis, decision plane analysis, Bayes decision theory, principal peak ratio, and spectral width. The classification ability of each algorithm was evaluated by its application to the training set and to a validation set containing 82 additional spectra. All seven spectral classification algorithms prospectively classified atherosclerotic and normal aorta with an accuracy greater than 80 percent (range: 82-96 percent). Laser angioplasty systems incorporating spectral classification algorithms may therefore be capable of detection and selective ablation of atherosclerotic plaque.

Change in laser-induced arterial fluorescence during ablation of atherosclerotic plague.

Analysis of the change in arterial fluorescence during plaque ablation may provide the basis for developing a fluorescence-guided ablation system capable of selective plaque ablation without risk of vessel perforation. Accordingly, fluorescence spectra were recorded from 91 normal and 91 atherosclerotic specimens of cadaveric human aorta. The ratio of the laser-induced fluorescence intensity at 382 nm to 430 nm (LIF ratio) was capable of classifying these specimens with an 89% accuracy with a threshold value of 1.8 (atherosclerotic greater than or equal to 1.8, normal less than 1.8). To characterize the change in fluorescence during plaque ablation, mechanical plaque ablation with a cold microtome was performed on 16 atherosclerotic aortic specimens. Fluorescence spectra were recorded serially after each 100 microns of plaque ablation; recordings revealed a change in fluorescence spectra from atherosclerotic to a normal pattern. With an LIF ratio of 1.8 to signal termination of plaque ablation, 15 of the atherosclerotic plaques had a residual plaque thickness less than 200 microns; one specimen had a residual plaque thickness of 300 microns. No specimen demonstrated ablation of the media. There was a statistically significant correlation between LIF ratio and plaque thickness (r = .73, P less than .001), but considerable variation in LIF ratio existed at each thickness. Therefore, laser-induced fluorescence spectroscopy is capable of discriminating atherosclerotic from normal aorta and of signaling completion of plaque ablation.

Fluorescence spectroscopy guidance of laser ablation of atherosclerotic plague.

Laser-induced fluorescence (LIF) spectroscopy can only be used for laser angioplasty guidance if high-power laser ablation does not significantly alter the pattern of tissue fluorescence. Although the spectra of normal and atherosclerotic arteries differ, the change in fluorescence spectra following laser angioplasty has not been well studied. Therefore, the purpose of this study was to assess whether laser-induced fluorescence spectroscopy could guide selective laser ablation of atherosclerotic plaque and, if so, to develop a quantitative LIF score that could be used to control a "smart" laser angioplasty system. Baseline LIF spectroscopy of 50 normal and 50 atherosclerotic human aortic specimens was performed using an optical fiber coupled to a He-Cd laser and optical multichannel analyzer. LIF was then serially recorded during erbium:YAG laser ablation of 27 atherosclerotic specimens. Laser ablation was terminated when the arterial LIF spectrum visually appeared normal. Histologic analysis revealed a mean initial plaque thickness of 1,228 +/- 54 microns and mean residual plaque thickness of 198 +/- 27 microns. Ablation of the media occurred in only three specimens. A discriminant function was derived to discriminate atherosclerotic from normal tissue for computer guidance of laser angioplasty. The LIF score, derived from stepwise multivariate linear regression analysis of the LIF spectra, correctly classified 93% of aortic specimens. The spectra obtained from the atherosclerotic specimens subjected to fluorescence-guided laser revealed a change in score from "atherosclerotic" to "normal" following plaque ablation. Seven atherosclerotic specimens were subjected to laser angioplasty with on-line computer control using the LIF score. Mean initial plaque thickness was 1,014 +/- 86 microns, and mean residual plaque thickness was 78 +/- 29 microns. There was no evidence of ablation of the media. Therefore, LIF guidance of laser ablation resulted in minimal residual plaque without arterial perforation. These findings support the feasibility of an LIF-guided laser angioplasty system for selective atherosclerotic plaque ablation.

Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol.

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.

Twice-daily nicardipine in the treatment of essential hypertension.

The antihypertensive effect of twice-daily nicardipine, an investigational calcium-channel blocker, was evaluated in a placebo-controlled, single-blind trial in 18 adult patients with essential hypertension (supine diastolic blood pressure [BP] of greater than or equal to 95 and less than or equal to 120 mmHg). Following a 4-week run-in period in which patients received placebo for the final 2 weeks, nicardipine was administered for 12 weeks with a treatment goal of a supine diastolic BP of less than 90 mmHg at 12 hours postdosing or to a maximum dose of 60 mg twice daily. Supine and standing BPs and heart rates were determined at 1 hour and 12 hours postdosing. At all dose levels, supine and standing BPs were reduced at 1 hour after dosing, with partial loss of efficacy seen at 12 hours. Increases in heart rate seen at 1 hour were not significant at 12 hours. Eight patients withdrew from the study for minor, although troublesome, side effects, such as palpitations and headaches. These data suggest that nicardipine monotherapy given in a twice-daily dosing regimen has only a limited role to play in the chronic treatment of patients with essential hypertension.