Evaluation of a new rapid immunometric method for the measurement of the MB isoenzyme of creatine kinase in serum.
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Biomedical subjects
Publications and source records attributed to C M Francis.
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In order to determine whether the cholinergic fibres that innervate the substantia nigra make synaptic contact with dopaminergic neurons of the substantia nigra pars compacta, a double immunocytochemical study was carried out in the rat and ferret. Sections of perfusion-fixed mesencephalon were incubated first to reveal choline acetyltransferase immunoreactivity to label the cholinergic terminals and then tyrosine hydroxylase immunoreactivity to label the dopaminergic neurons. Each antigen was localized using peroxidase reactions but with different chromogens. At the light microscopic level, in confirmation of previous observations, choline acetyltransferase-immunoreactive axons and axonal boutons were found throughout the substantia nigra. The highest density of these axons was found in the pars compacta where they were often seen in close apposition to tyrosine hydroxylase-immunoreactive cell bodies and dendrites. In the ferret where the choline acetyltransferase immunostaining was particularly strong, bundles of immunoreactive fibres were seen to run through the reticulata perpendicular to the pars compacta. These bundles were associated with tyrosine hydroxylase-immunoreactive dendrites that descended into the reticulata. The choline acetyltransferase-immunoreactive fibres made "climbing fibre"-type multiple contacts with the tyrosine hydroxylase positive dendrites. At the electron microscopic level the choline acetyltransferase-immunoreactive axons were seen to give rise to vesicle-filled boutons that formed asymmetrical synaptic specializations with nigral dendrites and perikarya. The synapses were often associated with sub-junctional dense bodies. On many occasions the postsynaptic structures contained the tyrosine hydroxylase immunoreaction product, thus identifying them as dopaminergic. It is concluded that at least one of the synaptic targets of cholinergic terminals in the substantia nigra are the dendrites and perikarya of dopaminergic neurons and that in the ferret at least, the dendrites of dopaminergic neurons that descend into the pars reticulata receive multiple synaptic inputs from individual cholinergic axons.
In normal hearts, the critical value of the endocardial viability ratio (EVR) is thought to be less than 0.5. As myocardial regional dysfunction is a sensitive index of subendocardial ischaemia, the relationship between EVR and regional function has been studied in an experimental model of coronary artery constriction. In 13 dogs anaesthetized with halothane (0.5-2.0% inspired concentration), diastolic and systolic pressure time indices were obtained by planimetry, and their ratio (EVR) correlated with regional function. Halothane alone caused a significant reduction in EVR from 1.38 +/- 0.08 to 1.15 +/- 0.04 (mean +/- SEM). In the presence of coronary artery constriction a similar decrease in EVR was observed and was accompanied by post-systolic shortening (PSS), an indicator of regional dysfunction. At high concentrations of halothane, there was an inverse correlation between reduction in EVR and increase in PSS. Mean EVR of approximately 0.9 (mean = 0.92 +/- 0.02) was associated with significant worsening of regional function.
In the dog, stepped increases in isoflurane concentration (up to 1.5 MAC) caused peripheral and coronary vasodilatation. In the presence of significant decreases in arterial pressure (-35%), contractility (-46%), cardiac output (-17%) and coronary perfusion pressure (-40%), coronary blood flow remained unchanged, while the effective coronary vascular resistance was halved. The coronary reserve, estimated by the hyperaemic response to short periods (10 s) of coronary occlusion was reduced by the stepped increases in isoflurane concentration. Linear relationships were observed between peak hyperaemic flow, volume repayment, repayment: deficit ratio and coronary perfusion pressure. The vasodilation induced by isoflurane was of such magnitude that, at 1.5 MAC, the repayment: deficit ratio was close to unity, indicating that the vasodilatory reserve was almost exhausted.
To determine the protective effect of oxprenolol-induced beta-blockade on the compromised myocardium (critical constriction of the left anterior descending coronary artery) against the adverse effect of high concentrations of halothane, halothane dose-response curves were obtained in six dogs in each of three phases: preconstriction (control), critical constriction, and critical constriction with the addition of 0.3 mg/kg intravenous oxprenolol. The extent of depression of ventricular function was essentially the same in the three phases. However, at high halothane concentrations (2.0% inspired), the depression of systolic shortening in the compromised segment was significantly minimized after oxprenolol so that shortening was 10.2% +/- 1.8 instead of 6.5% +/- 1.4 (P less than 0.05); moreover the large increase in postsystolic shortening observed during critical constriction was abolished after oxprenolol. This suggests a protective effect of oxprenolol on regional myocardial function in the presence of critical constriction, possibly by an effect on myocardial metabolism or endocardial blood flow.
Regional myocardial function was studied using sonomicrometry in six mongrel dogs, anaesthetized with halothane (1% inspired), as increasing doses of verapamil were given i.v. In addition to a gradual increase in end-diastolic length and a reduction in systolic shortening, an abnormal (paradoxical) contraction pattern appeared in the apical region. This occurred in the absence of coronary artery damage and at coronary perfusion pressures unlikely to result in ischaemia. Administration of verapamil in the presence of halothane results in regional dysfunction similar to that caused by the intracoronary administration of nifedipine.
Of 160 patients with pernicious anaemia, none had current duodenal ulceration, whereas in a random population of similar age and sex distribution some 5% would be expected to have a duodenal ulcer. Parietal-cell antibody was detected in serum from 8 of 169 men (4-7%) and from 2 to 31 women (6-4%) with duodenal ulceration. None of the 200 duodenal ulcer patients had antibody to intrinsic factor. The prevalence of these antibodies in duodenal ulcer patients was not significantly different from that in control subjects of similar age and sex distribution. The decreased prevalance of duodenal ulcer in pernicious anaemia patients implies that pernicious anaemia must be less prevalent in duodenal ulcer patients than in a random population; but it appears that this cannot be attributed to an absence of gastric autoimmunity in patients with duodenal ulcer. To resolve this disrepancy, we suggest that pernicious anaemia is determined not only by autoimmune reactions, but also by independent genetic and environmental factors which influence the state of the gastric mucosa.
The prevalence of circulating antibodies to gastric intrinsic factor and parietal cells was examined in 60 patients with histologically proven gastric carcinoma and was found not to differ from the prevalence of these antibodies in control subjects of similar age and sex distribution.Amongst the 60 patients with gastric carcinoma seven were thought to have actual or potential pernicious anaemia. The absence of an increased prevalence of antigastric antibodies in gastric carcinoma indicates that gastritis itself, whether autoimmune or not, is the likely common denominator underlying the predisposition to gastric carcinoma in both pernicious anaemia and chronic atrophic gastritis.
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2,4-dichlorophenoxy acetic acid (2,4-D) produces myotonia in healthy animals. The action of this drug was studied on smooth muscles in vitro using isolated strips of rabbit's duodenum. The drug was found to have a stimulant action on the smooth muscle. The action seems to be a direct one.