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Biomedical subjects

M R Johnson

Publications and source records attributed to M R Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1988

Sensitivity and specificity of assessing coronary bypass graft patency with ultrafast computed tomography: results of a multicenter study.

Because a significant number of all patients seen by cardiologists have had coronary bypass surgery, a relatively noninvasive method of assessing coronary bypass graft patency would be very helpful. Ultrafast computed tomography, by virtue of its rapid data acquisition time and reasonable spatial resolution, may be useful in this regard. To determine the sensitivity, specificity and predictive accuracy of this imaging modality as compared with cardiac catheterization, a multicenter study was undertaken. There were two parts to the study. Part I involved the evaluation of 179 grafts in 74 patients studied in the five participating centers between March 1985 and August 1986. Twenty-nine percent of these graft studies were found to be technically inadequate and were excluded before patency determinations began. The remaining group of 127 bypass grafts in 62 patients had studies adequate for interpretation. Fifty-one grafts were to the left anterior descending coronary artery or a diagonal branch, 37 to branches of the left circumflex artery and 28 to the right coronary artery or a posterior descending vessel; in addition, there were 11 internal mammary artery bypass grafts primarily into the left anterior descending or diagonal artery distribution. The sensitivity of detecting angiographically open grafts was 93.4%, the specificity of detecting angiographically closed grafts 88.9% and the predictive accuracy was 92.1%. A subsequent study (Part 2) was performed 9 months later to assess the ability to carry out technically adequate examinations. Of the 138 consecutive graft examinations (50 patients) included in this part of the study, 94.2% of the examinations were found to be technically adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Videodensitometric analysis of coronary stenoses. In vivo geometric and physiologic validation in humans.

Assessment of the severity of coronary stenoses on arteriograms conventionally is based on subjective estimates of percent luminal diameter narrowing. However, in studies in patients with multivessel coronary artery disease, we have found a poor correlation between percent stenosis and the physiologic significance of an individual coronary obstruction. The purpose of this study was to determine whether computerized videodensitometry would allow estimation of coronary luminal area and therefore prediction of the physiologic significance of individual coronary stenoses in humans. Videodensitometry was used to define the minimal luminal area of 15 left anterior descending, 15 circumflex, and 15 right coronary artery segments in 43 patients. Computer-assisted quantitative coronary arteriography (method of Brown et al) was used to determine the minimal luminal cross-sectional area of these same segments. In each arterial segment, coronary vasodilator reserve was assessed using intraoperative (n = 18 segments) or intracoronary (n = 27 segments) Doppler measurements of coronary vasodilator reserve. Videodensitometric estimates of coronary luminal area correlated well with minimal luminal area defined using the independent geometric technique of quantitative coronary arteriography (r = 0.82, y = 0.97 X + 0.71, SEE = 1.83 mm2, n = 45) and with lesion physiologic significance as defined by studies of the peak-to-resting velocity ratio (r = 0.71, 0.92, and 0.74 for the left anterior descending, circumflex, and right coronary arteries, respectively). Thus, videodensitometry is a promising method that may supplement geometric approaches to quantitative analysis of coronary arteriograms in humans.

Absorptiometry, Photon↗
PubMed1988

Videodensitometric analysis of human coronary stenoses: validation in vivo by intraoperative high-frequency epicardial echocardiography.

Videodensitometry is a nongeometric method of coronary angiographic analysis that can be used to provide an index of coronary luminal area. However, there are few direct studies in vivo of the relationship of videodensitometric data to independent measures of luminal area in humans. Although videodensitometry is theoretically independent of angiographic projection and luminal shape, validation of these assumptions in vivo is also limited. We therefore used intraoperative high-frequency epicardial echocardiography, a technique that can directly determine human coronary luminal area and shape in vivo, to further validate videodensitometry. A total of 36 arterial segments in the left anterior descending and right coronary arteries were studied by videodensitometry and high-frequency echocardiography. Videodensitometry was performed on angiograms in which the arterial segment of interest was not markedly foreshortened and was uniformly filled with contrast. In 22 discrete lesions (13 with circular lumens and nine with oval or complex lumens), videodensitometric and echocardiographic measures of luminal area correlated well (r = .86). In 33 coronary arterial segments, the effect of angiographic projection on videodensitometry was determined by comparison of the results of videodensitometry performed on left anterior oblique vs right anterior oblique angiograms of the segments. Here too, the correlation was good (r = .94, y = 1.04x + 0.002). The good correlation of left anterior oblique with right anterior oblique videodensitometric results held true for lesions with circular and oval or complex lumens. This study further validates the ability of videodensitometry to provide an index of coronary luminal area and confirms in vivo previous assumptions that the results of videodensitometric analysis are independent of angiographic projection and luminal shape.

Adult↗
PubMed1988

The effect of coronary angioplasty on coronary flow reserve.

To determine the effects of coronary angioplasty on coronary flow reserve (CFR), we studied 32 patients before and immediately after single-vessel coronary angioplasty and 31 patients evaluated late after angioplasty (7.5 +/- 1.2 months, mean +/- SEM). The geometry (percent area stenosis and minimal cross-sectional area) of each lesion was determined by quantitative coronary angiography (Brown/Dodge method) and the integrated optical density was measured by videodensitometry. CFR was measured with a No. 3F coronary Doppler catheter placed immediately proximal to the lesion and a maximally vasodilating dose of intracoronary papaverine. The translesional pressure gradient was obtained in all lesions before and immediately after angioplasty and in 18 of 31 vessels late after angioplasty. CFR immediately after angioplasty returned to normal levels (greater than 3.5 peak/resting velocity ratio) in 14 of 31 patients and was improved, although not normalized, in the remaining 17 patients. CFR immediately after dilation was not significantly correlated with any of the angiographic variables of arterial stenosis nor the resting pressure gradient. Moreover, the pressure gradient and absolute distal coronary pressure at peak hyperemia were not significantly different in vessels with normal and those with abnormal flow reserve immediately after dilation, suggesting that the residual stenosis did not significantly limit hyperemia. Late after angioplasty, however, a significant relationship emerged between CFR and all four indexes of residual arterial stenosis (percent area stenosis r = .70, p less than .01; minimum arterial cross-sectional area r = .70, p less than .01; integrated optical density r = .60, p less than .01; and translesional pressure gradient r = .77, p less than .01). Furthermore, in the absence of restenosis, CFR eventually normalized in all patients. These findings demonstrate that in one-half of patients there is a transient reduction in coronary flow reserve immediately after angioplasty. In the absence of restenosis, coronary flow reserve later normalizes. Consequently, measurements of coronary flow reserve immediately after angioplasty may not reflect the eventual success of the procedure in removing physiologic obstruction to coronary blood flow.

Angiography↗
PubMed1988

Determination and characterization of a cannabinoid receptor in rat brain.

The determination and characterization of a cannabinoid receptor from brain are reported. A biologically active bicyclic cannabinoid analgetic CP-55,940 was tritium-labeled to high specific activity. Conditions for binding to rat brain P2 membranes and synaptosomes were established. The pH optimum was between 7 and 8, and specific binding could be eliminated by heating the membranes to 60 degrees. Binding to the P2 membranes was linear within the range of 10 to 50 micrograms of protein/ml. Specific binding (defined as total binding displaced by 1 microM delta 9-tetrahydrocannabinol (delta 9-THC) or 100 nM desacetyllevonantradol) was saturable. The Kd determined from Scatchard analysis was 133 pM, and the Bmax for rat cortical P2 membranes was 1.85 pmol/mg of protein. The Hill coefficient for [3H]CP-55,940 approximated 1, indicating that, under the conditions of assay, a single class of binding sites was determined that did not exhibit cooperativity. The binding was rapid (kon approximately 2.6 x 10(-4) pM-1 min-1) and reversible (Koff approximately 0.016 min-1) and (koff' greater than 0.06 min-1). The two Kd values estimated from the kinetic constants approximately 55 pM and exceeded 200 pM, respectively. The binding of the agonist ligand [3H]CP-55,940 was decreased by the nonhydrolyzable GTP analog guanylylimidodiphosphate. The guanine nucleotide induced a more rapid dissociation of the ligand from the binding site, consistent with an allosteric regulation of the putative receptor by a G protein. The binding was also sensitive to MgCl2 and CaCl2. Binding of [3H]CP-55,940 was displaced by cannabinoid drugs in the following order of potency: CP-55,940 greater than or equal to desacetyllevonantradol greater than 11-OH-delta 9-THC = delta 9-THC greater than cannabinol. Cannabidiol and cannabigerol displaced [3H]CP-55,940 by less than 50% at 1 microM concentrations. The (-)-isomer of CP-55,940 displaced with 50-fold greater potency than the (+)-isomer. This pharmacology is comparable to both the inhibition of adenylate cyclase in vitro and the analgetic activity of these compounds in vivo. The criteria for a high affinity, stereoselective, pharmacologically distinct cannabinoid receptor in brain tissue have been fulfilled.

Allosteric Regulation↗
PubMed1988

Pharmacology and stereoselectivity of structurally novel cannabinoids in mice.

The pharmacological effects of three stereoisomeric pairs of structurally novel cannabinoids were tested after i.v. administration in mice for depression of spontaneous activity and the production of hypothermia, antinociception and catalepsy. The (-)-enantiomers were as much as 770 times more potent than delta 9-6a,10a-trans-tetrahydrocannabinol and were 7 to 2000 times more potent than their respective (+)-enantiomers. The order of potency for cannabinoid-induced effects was spontaneous activity greater than antinociception greater than hypothermia greater than or equal to catalepsy. Levonantradol was active between 0.123 to 1.5 mg/kg, whereas dextronantradol, its (+)-enantiomer was inactive. (-)-CP 55,244 and (-)-CP55,940 analogs which lack the dihydropyran ring were 5 to 775 times more potent than delta 9-6a,10a-trans-tetrahydrocannabinol and 30 to 2000 times more potent than their respective (+)-enantiomers. Some separation of effects was demonstrated with (+)-CP 55,243 and (-)-CP 56,667 which were inactive in producing hypothermia and catalepsy but were active in the spontaneous activity and tail-flick procedures. The high degree of enantioselectivity and potency of these nonclassical cannabinoids are indicative of a highly specific mechanism of action such as a receptor.

Adenylyl Cyclases↗
PubMed1988

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia. A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as "nonclassical" cannabinoid analgetics that conform to this agonist-receptor three-point interaction model. At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor. A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro. Enantio- and stereoselectivity were exhibited by the nonclassical cannabinoid compounds for both the analgetic response and the ability to inhibit adenylate cyclase. The magnitude of the enantioselective response was equal for both the biochemical and physiological endpoints. Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo. A conceptualization of the cannabinoid analgetic receptor is presented.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Further observations on cerebral or retinal ischemia in patients with right-left intracardiac shunts.

Between October 1983 and November 1986, 20 patients suspected of having a paradoxical cerebral or retinal embolism were identified. Cerebral infarction was the most common presentation. Six patients had a patent foramen ovale demonstrated by cardiac catheterization or surgery. Three patients had a newly discovered atrial septal defect, and one had an atrial septal defect that had previously been treated surgically. Results of the cardiac physical examination, chest roentgenography, and electrocardiography were unremarkable in 12 patients. Eighteen patients had a right-to-left shunt demonstrated by contrast echocardiography. Nine of these patients underwent cardiac catheterization; seven had abnormal catheterization study results: four had a patent foramen ovale and three had an atrial septal defect. Sixteen patients received medical therapy only while four underwent surgery. All patients survived the initial insult. There were no deaths or ischemic recurrences on follow-up ranging from one month to three years. We believe that contrast echocardiography can provide important diagnostic information, even in situations in which cardiac involvement is not suspected. Additional studies are needed before the optimal treatment of presumptive paradoxical cerebral embolism can be determined.

Adult↗
PubMed1987

The importance of the determination of the myocardial area at risk in the evaluation of the outcome of acute myocardial infarction in patients.

On the basis of animal studies, we postulated that the size of the perfusion field (risk area) of an occluded coronary artery would be an important determinant of outcome in patients with acute myocardial infarction. To test this hypothesis, we measured size of the risk area in 27 patients with acute myocardial infarction by the intracoronary injection of 99mTc-macroaggregated albumin and gated nuclear imaging. After injection of the albumin spheres (5.3 +/- 1.4 hr after the onset of chest pain) streptokinase was administered and in 16 of 27 patients (59%) effective thrombolysis was achieved. Since none of the patients had evidence of a prior acute myocardial infarction, the 3 day nuclear left ventricular ejection fraction (LVEF) was considered an index of infarct size. Response to thrombolysis was analyzed according to success or failure of reperfusion and the size of the risk area (small risk area less than 25%, large risk area greater than 25% of left ventricular surface area). Standard clinical indexes correlated poorly with size of the risk area: electrocardiographic variables (r = .37), left ventricular end-diastolic pressure (r = .23), cardiac index (r = .55), and the LVEF obtained from a right anterior oblique contrast ventriculogram (r = .31). The coronary vessel responsible for the acute myocardial infarction significantly influenced size of the risk area (left anterior descending, 38 +/- 5% [mean +/- SD] vs circumflex or right coronary artery, 17 +/- 4%). However, knowledge of the site of coronary occlusion within a vessel was not helpful in predicting the size of the area at risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗