Blood flow velocity alterations during coronary vasospasm.
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Acetylcholine↗
Biomedical subjects
J A Moore
Publications and source records attributed to J A Moore.
Patterns of phasic coronary collateral flow velocity in patients.
Antegrade or retrograde collateral flow velocity Doppler signals, acquired with the flowire, permit the quantitation of collateral blood flow and its phasic patterns. The velocity spectra are easily visualized, and reproducible alterations during balloon occlusion may be directly related to coronary collateral flow-dependent variables of ischemia and left ventricular wall motion. The effects of pharmacologic stimulation on collateral flow remain under study.
Aged↗
Translesional pressure and flow velocity after thrombolysis: assessment of suboptimal angioplasty for serial lesions.
Translesional pressure and flow velocity observations in the right coronary artery remain among the most difficult data to interpret because of variation in the location and relative size of branches, and unsuspected diffuse disease. Use of distal hyperemic response and translesional pressure gradients provides the most accurate assessment of serial lesions in such patients. In addition, the use of intracoronary thrombolysis can improve the angiographic appearance of lesions and facilitate later successful interventions. The post-infarction distal microvascular responsiveness may be impaired and, thus, abnormal coronary reserve values in this particular setting should be considered with lesion specific indicators of successful recanalization.
Blood Flow Velocity↗
Cultural and scientific literacy.
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Adolescent↗
Alterations of coronary flow velocity distal to coronary dissections before and after intracoronary stent placement.
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Aortic Dissection↗
Coronary flow velocity during coronary angioplasty in regions of myocardial infarction.
In patients undergoing angioplasty for angina after myocardial infarction, patterns of post-stenotic coronary blood flow velocity depend not only on satisfactory dilation of the flow-limiting lesion, but also on the vasoregulatory capacity of infarcted myocardium. The case examples demonstrate both normal and persistently abnormal flow velocity patterns following successful coronary angioplasty for post-infarction ischemia. Recognition of collateral flow patterns, easily available using the Doppler angioplasty guidewire, may provide valuable information predicting the viability of post-infarcted myocardium and the resolution of abnormal distal coronary flow patterns.
Adult↗
Ancrod infusion for anticoagulation during and after PTCA in a patient with heparin-induced thrombocytopenia.
Ancrod is a rapid-acting defibrinogenating agent derived from the venom of the Malayan pit viper which has been used successfully as an alternative to heparin sulfate for anticoagulation during peripheral vascular procedures and coronary artery bypass surgery. We describe the first use of ancrod for anticoagulation before and during percutaneous transluminal coronary angioplasty (PTCA) in a patient with heparin-associated thrombocytopenia.
Ancrod↗
Part XII: Assessment of serial lesions in the proximal right coronary artery following intracoronary thrombolysis.
Assessment of angiographically serial coronary lesions at the time of diagnostic catheterization remains a difficult clinical problem. Doppler flow velocity data is easily obtainable and allows physiologic interrogation of the distal coronary microcirculation, but has limitations in the detection of some flow-limiting stenoses. In cases of serial lesions or distal arterial disease, particularly after thrombolysis, flow velocity data may be insufficient to identify the hemodynamic significance of the coronary lesions. Translesional pressure measurements may be combined with flow velocity data to support an appropriate physiologically based therapeutic approach.
Adult↗
Cyclization reactions leading to beta-hydroxyketo esters.
The purpose of the research was to synthesize beta-diketo esters and to evaluate them for anticonvulsant activity. The reaction of methyl vinyl ketone with dimethyl malonate in the presence of potassium carbonate gave an uncyclized product that underwent a Claisen condensation to yield methyl 2-hydroxy-4-oxocyclohex-2-en-1-oate (5a). Similarly, other cyclized beta-hydroxyketo esters were prepared, and their spectrometric data confirmed that the enol tautomers were preferred to the beta-diketo tautomers. The synthetic work clarified the reaction pathway for the Michael addition of malonate esters to enones. Of the intermediates and products tested for anticonvulsant activity, dimethyl 2,2-bis-(3-oxobutyl)malonate (9a) was found to possess anticonvulsant property. However, it is emphasized that the beta-hydroxyketo esters could be useful intermediates in the synthesis of enaminone anticonvulsants.
Animals↗
Synthesis, reactions, and preliminary evaluations of enaminone esters.
The objective of this work was to design enaminone esters that would possess potential medicinal properties. The reaction between beta-hydroxyketo esters and primary or secondary amines yielded secondary or tertiary enaminone esters, respectively. The UV spectra of the enaminone esters were determined in acidic, alkaline, and neutral media; the spectra have a hypsochromic shift in acidic media in comparison with neutral media. The enaminone esters provided nucleophilic and electrophilic sites for a variety of reactions. Thus, the enaminone esters were converted into enaminone amides and O-alkylation products exclusively. Although the enaminone esters were generally resistant to reduction by metal hydrides, one unhindered enaminone ester was reduced to an alcohol with sodium borohydride. Another enaminone ester reacted with guanidine to give the corresponding quinazolinone. Due to the variety of nucleophilic and electrophilic sites in the enaminone system, enaminone esters possess a great potential as reaction intermediates and medicinal compounds. Preliminary evaluations of the enaminone esters revealed a histaminergic effect, uterine relaxant properties, and anticonvulsant activity.
Animals↗
Nuclear magnetic resonance studies of anticonvulsant enaminones.
1H nuclear magnetic resonance (NMR) spectra of enaminones were determined and compared to the anticonvulsant activity of the compounds. Although the precise employment of the NMR data to predict anticonvulsant activity of the enaminones could not be established, general inferences were made. The NMR data confirmed that the enaminones existed predominantly in the amino tautomer, and no evidence was found for the imino tautomer. The ketamine form of the enaminones was supported by the observed spin-spin splittings of the NH with the alpha-protons on certain enaminones. The NH of secondary enaminones was very important in conferring anticonvulsant activity to the enaminones. The peak for the NH proton which could be seen between delta (ppm) 4.50 and 9.70 was present in all of the active enaminones. The tertiary enaminones, which were devoid of the NH proton, were uniformly inactive. It appeared that a combination of steric and electronic effects, lipophilicity, and hydrogen bonding were necessary for the anticonvulsant activity of the enaminones. The cyclic enaminones existed in the trans-S-trans fixed conformation, and the NMR data supported our hypothesis that enantioselectivity is retained in synthesizing enaminones from cyclic, diasteriomeric 1,3-diketones. In addition, the AB system and many unique features were observed in some enaminones. The para, meta, and ortho substituted patterns were observed for monosubstituted phenyl protons, and the NMR patterns for di- and trisubstituted phenyl groups were elucidated.
Anticonvulsants↗
A comparison of liver tumor diagnoses from seven PCB studies in rats.
Through a policy assumption, all polychlorinated biphenyls (PCBs) are considered probable human carcinogens by most regulatory agencies based on experimental studies in rodents where an increased incidence of liver tumors has been observed. Recognizing that new consensus criteria for the diagnoses of liver tumors in rats had been promulgated, a reevaluation of liver tumor diagnoses from seven PCB studies in rats was undertaken. These seven studies, in which rats were fed PCB mixtures containing 42, 54, or 60% chlorine, were considered to be the best studies from which to evaluate the cancer potential of PCB mixtures. The reevaluation results, where consistent diagnoses now exist across all studies, clearly indicate major differences in carcinogenic potential based on degree of chlorination. Studies of mixtures with 60% chlorination consistently resulted in a high incidence of liver tumors, whereas studies in which rats were fed mixtures with 54 or 42% chlorination showed no statistically significant increases in liver tumors. These data indicate that continuation of a science policy of assuming that all PCBs are probable human carcinogens with a potency equivalent to the mixture that contains 60% chlorine has no scientific foundation and should be reconsidered.
Animals↗
Continuous coronary flow velocity monitoring during coronary interventions: velocity trend patterns associated with adverse events.
Continuous measurement of blood flow velocity during interventional procedures has the potential to provide an early warning of coronary flow instability, which can lead to abrupt closure or other adverse events before angiography. The magnitude and fluctuations of the average velocity over time (trend) was studied by using a 0.018-inch Doppler-tipped angioplasty guide wire in 32 patients after coronary angiography (n = 20), atherectomy (n = 2), urgent stent (n = 6), urgent vein graft thrombolysis (n = 4), or acute myocardial infarction (n = 2). The patients (mean age 60 +/- 11 years) had postprocedural in-laboratory flow monitoring for a mean of 19 +/- 11 (range 8 to 36) minutes. The coronary artery monitored was the left anterior descending in 13, circumflex in 6, right coronary artery in 9, and saphenous vein graft in 4. Seven patients had flow-related events during continuous flow velocity monitoring before serial angiographic study. These events included coronary vasospasm (abrupt flow acceleration), vasovagal flow cessation, cyclical flow variations resulting from accumulation of intraluminal thrombus, and rapid decline of flow velocity. The last two patterns were associated with abrupt vessel closure during angioplasty. Continuous flow velocity monitoring is easily incorporated into routine interventional procedures and provides an early indication of unstable flow and the potential for abrupt vessel closure and other adverse events.
Adult↗
Synthesis and evaluation of amino analogues of valproic acid.
Valproic acid, an antiepileptic drug, is extensively metabolized in humans. Two putative metabolites, 2-n-propyl-3-aminopentanoic acid (3-aminovalproic acid, 3-amino-VPA; 2a) and 2-n-propyl-4-aminopentanoic acid (4-amino-valproic acid, 4-amino-VPA; 4a), which may result from the transamination of the respective keto acids 1a and 3a may explain the unusual extended seizure protection elicited by valproic acid. The title compounds were synthesized as their diasteriomeric ethyl esters 2b and 4b and submitted for anticonvulsant evaluation by the Antiepileptic Drug Development Program of the National Institute of Neurological and Communicative Disorders and Stroke. The results verified our hypothesis, as 4b was active in the subcutaneous pentylenetetrazol (scMet) evaluation at 30 mg/kg. Both compounds were highly toxic at 300 mg/kg.
Animals↗
Synthesis and CLOGP correlation of imidooxy anticonvulsants.
Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss structure activity and the Craig plot analytical approaches as well as a semiempirical method. CLOG P analysis was also applied to this series after experimentally determining the NOR fragment. All compounds were minimized and these physicochemical parameters correlated to anticonvulsant activity. Several interesting substituted benzyloxy compounds emerged from this study: the 2',4'-dichloro (2b), 4'-(trifluoromethyl) (2c), 2'-bromo (2d), 3'-chloro (2o), 2'-chloro (2r), 2'-fluoro (2p), and 3'-fluoro (2w) analogs, all of which had comparable, or better activity than the parent unsubstituted analog (2a). X-ray crystal analysis of the active 2a versus inactive N-benzyl-2-azaspiro[4.4]nonane-1,3-dione (10) is discussed.
Animals↗
Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations.
This report continues the in-depth evaluation of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate , 1 (ADD 196022), and methyl 4-(benzylamino)-6-methyl-2-oxocyclohex-3-en-1-oate, 2, two potent anticonvulsant enaminones. These compounds were evaluated employing the amygdala kindling model. Neither 1 nor 2 was active against amygdala kindled seizures, further supporting the corneal kindled model as a definitive tool for antielectroshock seizure evaluation as previously reported. Additional intraperitoneal (ip) data on 1 revealed toxicity at 24 h at 100 mg/kg. Several active analogs have been prepared with the view to minimizing toxicity. In a special ip rat screen developed by the Antiepileptic Drug Development (ADD) Program, these newer analogs were evaluated for protection against maximal electroshock seizures (MES) at 10 mg/kg and neurotoxicity at 100 mg/kg. From this screen, several compounds were shown to be safer alternatives, the most notable was methyl 4-[(p-bromophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate, 13. Compound 13 had an ip ED50 of 4 mg/kg in the rat and a TD50 of 269 mg/kg, providing a protective index (TD50/ED50) of > 67. By variation in the ring size, additional aromatic substitutions and the synthesis of acyclic analogs, these newer compounds provide a more definitive insight into the structure-activity correlation. CLOGP evaluation and molecular modeling studies are also provided to further elaborate the molecular characteristics of potential anticonvulsant enaminones.
Animals↗
A kinematic technique for describing wrist joint motion: analysis of configuration space plots.
This paper describes an experimental method for determining the minimum number of degrees of freedom of a human joint. Application of this technique to the wrist suggests that the normal, intact wrist joint uses only two degrees of freedom to move in a plane that is not aligned with the anatomic planes. The technique may be useful in identifying emerging joint pathologies and in simplifying kinematic models of joint function.
Biomechanical Phenomena↗
Re-aiming the canon.
Although it is unlikely that the national goals for educational reform--such as that, by the year 2000, U.S. students will be first in the world in science and mathematics achievement--can be achieved, a vigorous effort must be made to reach those goals as rapidly as possible. Reform will come not from a massive expansion of what we now do but from a basic shift in the manner in which we educate students in grades K-16 in the sciences and mathematics. Important elements in that basic shift must include an increase in teaching of science, mathematics, and technology (SMT), to about 20%-25% of the curriculum; SMT must include rich hands-on experiences, with an emphasis on concepts and understanding, rather than on facts and memorization, and on how science as a way of knowing differs from other ways of knowing; SMT must consider human problems; and SMT must deal with the basic problem facing humanity--how we must adjust our behavior so as not to exceed, on a worldwide basis, the carrying capacity of the environment.
Curriculum↗