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Biomedical subjects

S Fraser

Publications and source records attributed to S Fraser.

At least 91 records · Page 5Linked to original sources

Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 2. Effect of pharmacological agents, retrograde perfusions, and enzyme inhibition on evans blue, sucrose, water, and taurocholate.

The effect of altered physiological conditions on the residence time distributions of sucrose, water, and taurocholate in the rat liver were studied using a bolus injection and quantifying fraction of total outflow per ml-time profiles. Retrograde perfusions increased the residence times of sucrose and water markedly and were associated with very low hepatic availabilities for taurocholate. Resistance by the inlet sinusoids sphincters, which become outlet sphincters during retrograde perfusions, is suggested as the explanation for the observation. Infusions of noradrenaline, propranolol, and lidocaine resulted in relatively small changes in the mean residence times for sucrose and water with no apparent relationship existing between the efficiency number of taurocholate and volumes of either water or sucrose. Taurochenodeoxycholate resulted in an increase in the availability and mean residence time for taurocholate relative to no infusion.

Animals↗

Selective antagonism of calcium channel activators by fluspirilene.

1. Fluspirilene has been claimed to bind to a high affinity site in the calcium channel in skeletal muscle. We have investigated its calcium-antagonistic effects in smooth muscle and affinity for the channel in radioligand binding assays. 2. Fluspirilene was weakly active as an antagonist of Ca2(+)-induced contractions in K(+)-depolarized taenia preparations from the guinea-pig caecum, with threshold antagonism starting from concentrations of 30 nM. Nitrendipine, nicardipine and nimodipine were very potent antagonists in this model (threshold antagonism, greater than 1 nM). 3. In contrast, fluspirilene (10-1000 nM) was a potent non-competitive antagonist of the effects of Bay K 8644 (1-3000 nM) on Ca2(+)-induced contractions and, at 10 nM, selectively antagonised the effects of Bay K 8644, abolished the Ca2(+)-channel activator effects of CGP 28392, without changing the calcium antagonist effects of nitrendipine, or modifying the sensitivity of the tissues to Ca2+. In contrast, the dihydropyridines were more effective as antagonists of Ca2+ than of Bay K 8644. Fluspirilene therefore selectively antagonised the effects of dihydropyridine Ca2+ channel activators without affecting the antagonist potency. 4. In radioligand binding experiments, fluspirilene was a potent displacer of [3H]-PN-200-110 binding to rat cerebral cortical membranes (EC50 30 nM), albeit with a low Hill slope (0.66), and was more potent than other lipophilic diphenylalkylamines such as flunarizine and lidoflazine. Fluspirilene interacted non-competitively with [3H]-PN-200-110 and increased dissociation of the radioligand.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Developmental potential of avian trunk neural crest cells in situ.

To analyze the developmental potential of individual neural crest cells or their precursors, we have microinjected a vital dye, lysinated rhodamine dextran (LRD), into single cells in the dorsal neural tube. The phenotypes of the descendants that inherited the LRD from the injected cells were evaluated based upon their position, morphology, and neurofilament expression. Individual neural crest cells labeled before or as they emigrated from the neural tube gave rise to both sensory and sympathetic neurons as well as nonneuronal cells, some of which had the morphological characteristics of Schwann cells or pigment cells. In numerous cases, the descendants of a single cell included both neural crest- and neural tube-derived neurons, suggesting that some cells of the peripheral and central nervous systems share a common lineage. Our data demonstrate definitively that both emigrating and premigratory trunk neural crest cells can be multipotent, giving rise not only to cells in multiple neural crest derivatives, but also to both neuronal and nonneuronal elements within a given derivative.

Animals↗

Reperfusion arrhythmia: myth or reality?

Early reports of "reperfusion arrhythmia" after experimental temporary coronary occlusion raised concern that these arrhythmias, particularly ventricular fibrillation and ventricular tachycardia, might occur in association with reperfusion of an occluded coronary vessel during thrombolysis. Such an occurrence could increase the risk of transfer of such patients. To provide a more definitive answer to this question, we reviewed hospital and transfer records for all patients with acute myocardial infarction transferred by our critical care transfer service between January 1, 1985, and November 30, 1987, noting the occurrence of five types of arrhythmia: ventricular fibrillation, ventricular tachycardia, premature ventricular contractions, bradycardia, and atrioventricular block, both before and during transfer. Five hundred patients with acute myocardial infarction less than 48 hours old were transferred during this period. Two hundred twenty-five patients received thrombolytic therapy; 270 did not (five unknown). The type of acute myocardial infarction was known for 471 patients: 192 were anterior, 203 were inferior, and 76 were lateral. There were no deaths during transfer. Overall survival through hospitalization was 91%. The incidence of arrhythmia was 36% before transport and 12% during transport. There was no difference in arrhythmias overall, or with respect to any of the five arrhythmias specified, between patients who received thrombolytic therapy before and during transport and those who did not. Reperfusion arrhythmia does not appear to be a clinically significant entity during the transport of patients who are receiving IV thrombolytic therapy.

Arrhythmias, Cardiac↗

Microwave thermography--an index of inflammatory joint disease.

Microwave thermography is a technique measuring microwave emission from sites of inflammation. Microwaves have a wavelength of around 10 cm and are therefore able to penetrate clinically useful depths of up to 4 cm directly measuring tissue thermal radiation. A microwave detector was applied to the study of joint inflammation in rheumatoid arthritis and in a normal control group. Fifty-two knees were scanned using the detector and a microwave thermographic index was calculated for each knee. A strong correlation was found between the microwave thermographic index, and the clinical and laboratory parameters measured. This technique was found to be reproducible, quick, simple to use at the bedside without a controlled environment and, since it measures internally emitted radiation, is inherently safe.

Arthritis, Rheumatoid↗

The effect of diazepam on indices of 5-HT function in man.

The effects of acute and chronic diazepam administration on L-tryptophan induced prolactin release was studied in seven male volunteers. Acute diazepam diminished the prolactin neuroendocrine response to L-tryptophan. On chronic administration this effect was lost, suggesting tolerance had developed. The sedative effects of L-tryptophan were unaltered by either acute or chronic diazepam administration. A possible explanation for the tolerance development to the neuroendocrine effects may be the observed reduction in platelet 3H-imipramine binding that was observed.

Adult↗

Binding of yohimbine and imipramine to platelets in depressive illness.

Radioligand binding to intact platelets was carried out in antidepressant-free patients and the 1 mg dexamethasone suppression test (DST) was performed. There were no differences in binding characteristics between patients and controls for either [3H]yohimbine or [3H]imipramine. There were no differences in binding between patients classified as endogenous using the Newcastle Scale, compared with non-endogenous patients, and no difference between DST suppressors and non-suppressors. The severity of depression did not affect binding values. After 4-6 weeks antidepressant treatment [3H]yohimbine binding was significantly reduced but [3H]imipramine binding was unaffected.

Adult↗

Measurement of the lineal density of red blood cells in capillaries in vivo, using a computerized frame-by-frame analysis of video images.

In order to study the oxygen supply system within a capillary bed it is desirable to know the lineal density of red blood cells (RBCs) in individual capillaries; viz number of cells per millimeter. We have developed a video computer method for "continuous" measurements of lineal density, based on frame-by-frame analysis of the spatial-average of blood opacity over a selected length of capillary. Each capillary is calibrated separately, in order to determine the relationship between mean opacity and lineal density for that vessel. Since the method does not attempt to detect individual RBCs, it can be applied to capillaries with RBCs which overlap each other to some extent. Also, since the opacity data is normalized with respect to "background" light intensity and "contrast," this technique can be applied to thick tissues such as skeletal muscle. The method has been tested on capillaries in frog sartorius muscle and is able to predict, on average, the number of frog RBCs in an 80-micron length of capillary to +/- one-quarter cell. At present, computation times limit "real time" measurement of lineal density to a sampling rate of 10 sec-1. The data may also be used (1) to compute red cell flux (cells X sec-1), if corresponding velocity measurements are available, and (2) to estimate capillary hematocrit.

Animals↗