De novo synthesis of alkyne substituted tryptophans as chemical probes for protein profiling studies.

De novo synthesis of alkynalted tryptophan moieties as chemical probes for protein profilling studies, via an unexpected synthesis of Michael acceptor 12 is reported. Friedel Craft's alkylation of 12 and alkyne substituted indoles gave alkynalated tryptophan moieties, which perform as chemical probe by incorporating into actively translating Escherichia coli cells, whereby the alkyne moiety enables multimodal analyses through click chemistry mediated attachment of reporting groups.

Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis.

OBJECTIVES: The purpose of this study was to test the hypothesis that endothelial dysfunction occurs in humans before the development of structural coronary atherosclerosis when risk factors for this disease are present. BACKGROUND: Animal studies have demonstrated that known risk factors for coronary atherosclerosis (hyperlipidemia, hypertension, diabetes) result in impaired endothelium-dependent vascular reactivity before the development of structural atherosclerosis. Previous studies in patients have been unable to distinguish early structural atherosclerotic disease from dysfunctional endothelium. METHODS: Twenty-six patients with angiographically normal coronary arteries were studied at cardiac catheterization. The epicardial arteries were imaged using high resolution intravascular ultrasound to detect early structural changes and to determine changes in lumen size during pharmacologic provocation. A selective intracoronary Doppler velocity catheter was subsequently used to determine coronary blood flow velocity changes in response to the same pharmacologic provocation. Group I (9 patients) had no risk factors for atherosclerosis. Group II (17 patients) had one or more risk factors present. RESULTS: Although both Groups I and II had a normal microvascular vasodilator response to adenosine or papaverine infusion (estimated coronary flow increase 396 +/- 200% vs. 326 +/- 161% [mean +/- SD], respectively, p = 0.103), only Group I patients had an intact response to acetylcholine infusion (378 +/- 203% vs. 75 +/- 93% in Group II, p = 0.001). Group II patients had an abnormal epicardial artery cross-sectional area vasoconstriction response to acetylcholine infusion (-16.6 +/- 12.4% [13 patients] vs. 1.3 +/- 11.5% in Group I, p = 0.0007). An additional four Group II patients had severe spasm during acetylcholine infusion. Epicardial vasodilator response to nitroglycerin infusion, however, was preserved in Group II (14.6 +/- 4.3% vs. 9.6 +/- 3.5% in Group I, p = 0.212). All Group I patients had normal vessels by intravascular ultrasound. Of the 17 patients in Group II, 7 had minimal disease on ultrasound (intimal thickening or small eccentric plaque) in the study vessel. These patients did not respond differently from the 10 Group II patients without demonstrable disease on ultrasound. CONCLUSIONS: Patients with risk factors for coronary artery disease, normal coronary angiograms and no measurable disease by intracoronary ultrasound exhibit selective endothelial dysfunction at both the epicardial and microvascular levels. These findings may have implications for the treatment of "preclinical" coronary atherosclerosis.

Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty.

OBJECTIVES: This study was designed to establish the relation between ultrasound-derived atheroma morphology and the clinical, procedural and angiographic features of patients presenting for coronary angioplasty. BACKGROUND: Intracoronary ultrasound imaging provides accurate dimensional information regarding arterial lumen and wall structures. Atheroma composition may also be assessed by ultrasound; however, only limited studies have been performed in patients. METHODS: In 65 patients a diagnostic ultrasound imaging catheter or a combination imaging-angioplasty balloon catheter was used during coronary angioplasty to image both the lesion and the vessel segment just proximal to it (reference segment). Ultrasound images were analyzed for lumen, total vessel and plaque areas and were classified into five morphologic subtypes (soft, fibrous, calcific, mixed plaque and concentric subintimal thickening). These data were compared with angiographic morphologic features, procedural results and clinical angina pattern (stable vs. unstable). RESULTS: Morphologic analysis of the ultrasound images obtained from the lesion correlated well with the clinical angina syndrome. Compared with patients with stable angina, patients with unstable angina had more soft lesions (74% vs. 41%), fewer calcified and mixed plaques (fibrotic, soft or calcific components in one or more combinations [25% vs. 59%]) and fewer intralesional calcium deposits (16% vs. 45%) (all p < 0.01). There was no correlation between ultrasound and angiographic lesion morphologic characteristics for either the reference segment or the lesion. Ultrasound demonstrated greater sensitivity than angiography for identifying unstable lesions (74% vs. 40%). Dimensional analysis demonstrated a large plaque burden in the reference segments (45 +/- 15% of total vessel area). Postangioplasty plaque burden was also high (62 +/- 9%). There was a significant, but only fair correlation between lumen area determined by angiography and ultrasound for both the reference segment (r = 0.70, p < 0.001) and the postangioplasty lesion (r = 0.63, p < 0.05). CONCLUSIONS: Morphologic plaque classification by ultrasound is closely correlated to clinical angina but has little relation to established angiographic morphologic characteristics. Intracoronary ultrasound imaging during angioplasty identifies a large residual plaque burden in both the reference segment and the lesion. In the future, determination of plaque composition by intracoronary ultrasound may be important in selecting or modifying interventional therapeutic options.

Measurement by intracoronary ultrasound of in vivo arterial distensibility within atherosclerotic lesions.

Arterial distensibility is diminished by atherosclerosis. This process has not been well studied in the coronary arteries. The purpose of this study was to assess changes in coronary arterial distensibility in 4 groups of patients. Group I (n = 20) consisted of patients with normal vessels, group II (n = 40) with diseased undilated vessels, group III (n = 15) after successful percutaneous transluminal coronary angioplasty (PTCA), and Group IV (n = 20) after successful directional coronary atherectomy (DCA). Intracoronary ultrasound imaging was used to assess distensibility, plaque morphology and atherosclerotic burden (expressed as the percentage of total vessel cross-sectional area occupied by plaque: percent plaque area). Distensibility was defined as percent change in lumen area in a cardiac cycle. Group I (normal vessels) had a distensibility = 14 +/- 5%, which was significantly greater than that seen in group II (distensibility = 4 +/- 2%, p < 0.001). In undilated vessels, distensibility was related to the degree of atherosclerotic burden (r = 0.75). This relation was curvilinear with a marked decrease in distensibility when percent plaque area exceeded 30%. Distensibility in group III (after PTCA) was higher than in group II (10 +/- 3 vs 4 +/- 2%, p < 0.001) despite a larger plaque burden (percent plaque area of 56 +/- 12 vs 46 +/- 11%, p < 0.005). The distensibility in group IV (after DCA) was also higher than in group II (8 +/- 4 vs 4 +/- 2%, p < 0.001) despite a similar residual percent plaque area (49 +/- 13 vs 46 +/- 11%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial oxygen saturation in chronic congestive heart failure.

Continuous, 24-hour, ambulatory pulse oximetry was used in 10 subjects with New York Heart Association functional class II to III heart failure and in 5 age-matched controls to test the prevailing view that arterial oxygen saturation is preserved during wakefulness in chronic mild to moderate heart failure. Subjects with heart failure were stabilized on digitalis and diuretics at the time of the study. All subjects maintained time-activity logs, with an emphasis on self-reported sleep and wakefulness. A desaturation event was defined as a decrease in arterial oxygen saturation > or = 4% from baseline lasting > 5 seconds. Variables assessed included total desaturation events, decrease in arterial oxygen saturation duration/event, nadir of arterial oxygen saturation/event, and desaturation index ([cumulative desaturation time/total monitoring time] x 100). The ratio of self-reported wakefulness:sleep desaturation time was 47:53% for subjects with heart failure versus 64:36% for controls (p = NS). Mean (+/- SEM) time of arterial oxygen saturation < 90% was 123 +/- 67 minutes for subjects with heart failure versus 22 +/- 25 minutes for controls (p < 0.01). Total desaturations were 220 +/- 63 and 76 +/- 35 (p = NS) for the heart failure and control groups, respectively. The heart failure group had a statistically, significantly greater decrease in arterial oxygen saturation, and a longer duration and deeper nadir of the desaturation event than did the age-matched control group. The desaturation index was 21 +/- 3% and 4 +/- 1% for the heart failure and control groups, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term angiotensin-converting enzyme inhibitor therapy on arterial oxygen saturation in patients with mild to moderate heart failure.

STUDY OBJECTIVE: To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on continuous pulse oximetry recordings of arterial oxygen saturation (SpO2). DESIGN: Open-label study. SETTING: Cardiology clinics at two large teaching hospitals. PATIENTS: Eight patients with New York Heart Association Functional Class (NYHA FC) II-III heart failure. INTERVENTIONS: Patients were studied after an ACE inhibitor washout (baseline, B), and after 3 months following resumption of therapy (ACE). MEASUREMENTS AND MAIN RESULTS: Monitoring times for B and ACEI were approximately 22 hours. Reduction trends were observed for number (190 +/- 170 vs 125 +/- 67 B vs ACEI), magnitude (8.2 +/- 1.4% vs 7.5 +/- 1.8%), and duration (2.45 +/- 2.8 vs 1.35 +/- 0.8 min) of desaturations/monitoring period, and for nadir SpO2/desaturation (88.1 +/- 1.5% vs 89.9 +/- 3.3%). The B desaturation index [(cumulative desaturation time/monitoring period time) x 100, a measure of hypoxic stress or burden] decreased from 19.4 +/- 8.1% to 11.9 +/- 8.1% at ACEI (p = 0.024). CONCLUSION: Long-term ACE inhibitor therapy improves the profile of SpO2 values over time in patients with NYHA FC II-III heart failure.

Estimation of thoron concentration using scintillation cell.

Two counting techniques are proposed in this paper to estimate thoron ((220)Rn) concentration using a Lucas scintillation cell. The alpha activity build-up inside the cell is calculated theoretically by using Bateman equations. The first method is having a minimum detection limit of 325 Bq m(-3) and can be used for thoron measurement in thorium-processing plants. In the second method, thoron concentration is calculated using the alpha counts from thoron progenies and is a reference to the first method. The results obtained by these techniques compare well with the double filter method.

Coronary artery plaque morphology in stable angina and subsets of unstable angina: an in vivo intracoronary ultrasound study.

Little information is available regarding the in vivo composition of angina producing culprit atherosclerotic lesions in various anginal syndromes. In this study we used intracoronary ultrasound to determine the composition of culprit lesions in various subsets of anginal syndromes and correlated this composition with the patient's clinical presentation. One hundred and forty six patients referred for angioplasty or atherectomy were classified as having either chronic stable angina (angina which was clinically unchanged for > 2 months), crescendo angina (an accelerating pattern of frequent or prolonged anginal episodes), severe rest angina (abrupt onset of prolonged angina) or post-infarction angina (angina within 2 weeks of acute myocardial infarction). Intracoronary ultrasound imaging of the culprit lesion was performed before intervention. Lesions were classified as soft, mixed fibrous without calcium, mixed fibrous with calcium or calcified. Analysis of the ultrasound images revealed that the majority of culprit lesions were soft in severe rest (71%) and post-infarction angina (73%) whereas, the majority of culprit lesions were mixed fibrous or calcified in chronic stable (69%) and crescendo (53%) angina (X2 = 22.73, p = 0.007). In addition, the frequency of intralesional calcium in chronic stable or crescendo angina was significantly higher than that in severe rest or stable angina. We conclude that the composition of culprit lesions in various anginal subsets are different. The lesion morphology in crescendo angina frequently resembles that in chronic stable angina; while those in severe rest and post-infarction angina are frequently similar. These findings may have implications for medical or interventional treatment of patients with angina.

Mechanisms of angiographically successful directional coronary atherectomy: evaluation by intracoronary ultrasound and comparison with transluminal coronary angioplasty.

To assess the mechanisms of luminal improvement, 40 patients undergoing directional coronary atherectomy and a matched control group of 25 patients undergoing angioplasty were evaluated with intracoronary ultrasound imaging before and after intervention. Despite similar sized vessels, a similar angiographic severity of diameter stenosis (75 +/- 12% for the angioplasty group vs 69 +/- 15% for the atherectomy group, p = NS), and a similar plaque burden (percent plaque area) before intervention (84 +/- 5% in the angioplasty group vs 85 +/- 13% in the atherectomy group, p = NS), the residual plaque area after intervention was significantly smaller in the atherectomy group (54 +/- 14%) compared with the angioplasty group (65 +/- 13%, p = 0.002). Despite excellent angiographic results, significant residual plaque was noted after either successful intervention. Based on the absolute changes in lumen area, plaque area, and vessel area, improvement in the lumen area in the atherectomy group occurred as a result of plaque "compression" (48%), plaque removal (37%), and vessel expansion (15%). In the angioplasty group, plaque "compression" accounted for 94% of the improvement in lumen area, whereas vessel expansion contributed 6%. Thus "compression" of plaque remains the major mechanism of luminal improvement during atherectomy.