Biomedical subjects
Publications and source records attributed to P Barnes.
A 58-year-old Chinese woman was admitted to hospital with a presumed hypersensitivity reaction to allopurinol. Her illness was characterised by high fever, eosinophilia, exfoliative dermatitis and jaundice. She developed fulminant hepatic failure and septicemia with a fatal outcome. Clinical details are presented and the possible relationship of allopurinol hypersensitivity to renal impairment is discussed.
To localize fetal rabbit lung beta-adrenoreceptors before and after glucocorticoid treatment, light microscopic autoradiography was performed with the reversible radiolabeled beta-adrenergic antagonist, [3H]dihydroalprenolol, on day 26 of gestation. Autoradiograms of adult lung and fetal myocardium were also prepared. Examination of these autoradiograms showed densely labeled airways, alveoli, and myocardium. Specific labeling, defined as that prevented by incubation with l-propranolol (1 microM), was 90%. Analysis of grain counts in the fetus showed that airways were more densely labeled than alveoli (p less than 0.001), labeling was increased by treatment (p less than 0.001) and treatment increased alveolar (p less than 0.002) but not airway labeling. Adult lungs were much more densely labeled than fetal, and fetal myocardial labeling was not altered by treatment. Adult untreated lung showed the same pattern as fetal untreated lung with airways being more densely labeled than alveoli (p less than 0.001). To validate estimates of relative beta-adrenoreceptor concentration derived from autoradiograms, comparisons to determinations of beta-receptor concentration from scintillation counting of lung section digests and from previously performed radioligand binding studies, using membranes prepared from whole lung homogenates, were made. There is excellent agreement between estimates of relative receptor concentration and specific binding derived from the counting of autographic grains and both scintillation counting of lung section digests and previously performed radioligand binding of lung particulate. In all preparations, specific binding was (90%), increased with glucocorticoid treatment in fetal lung (50-100%), was greater in concentration in adult compared to fetal lung (7-10-fold), and did not increase in fetal myocardium with treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
A 16-year-old boy developed a left occipital lobe infarction after falling asleep with his head extended and rotated to the left. He was found to have an anomalous cerebrovascular system, in which the entire blood supply to the left occipital cortex derived from the right vertebral artery. It has been shown that vertebral artery flow can be compromised by physiologic degrees of extension of the neck and rotation of the head to the opposite side. To our knowledge, this is the only reported case of cerebral cortical infarction due to temporary arterial obstruction of the vertebral artery during physiologic hyperextension of the neck and rotation of the head. All previous cases attributed to this mechanism have been brainstem, cerebellar, or cervical spinal cord involvement with thrombosis of the vessel in question. Anomalies of the cerebrobasilar vascular system may place these individuals in jeopardy during otherwise harmless physical activities.
The sensitivity of computer simulated solvent structures to changes in both non-bonded (Lennard-Jones) coefficients and partial atomic charges has been investigated with use of amino acid hydrate crystals in which the water structure is well defined experimentally. The polarizable electropole (p.e.) model of water has been extended to describe water-protein interactions; thus, the cooperative nature of the hydrogen bond (i.e. non-pair additive effects) is allowed for through a polarizable dipole. By means of Monte Carlo calculations, the predicted water positions were found to be very sensitive to the input parameters used to define both the non-bonded and electrostatic interactions. Root mean square deviations between simulated and X-ray structures were not always adequate to describe these differences and so more detailed comparisons were made. Non-pair additive effects were shown to lead to large changes in water dipoles, the values of which depended specifically on the system under consideration.
1. Almitrine at a dose of 0.5 mg h-1 kg-1 given intravenously over 2 h had no effect on resting ventilation in normal males. 2. There was a small, but insignificant, rise in the hypercapnic drive to breathe as compared with placebo. 3. A large rise in the hypoxic drive to breathe was seen in response to almitrine. 4. These findings support the claim that almitrine has its action on ventilation via the peripheral chemoreceptors. 5. No correlation between blood levels of almitrine and the rise in hypoxic response was seen.
In order to find out how much sucking human newborns evidence when a sucking object is readily available, pacifiers were given to 10 newborns in response to the spontaneous occurrence of empty sucking, rooting, and mouthing and were left in their mouths until the babies relinquished them. The spontaneous occurrence of these behaviors and of finger sucking was also observed in a control group of 10 babies. Both groups were observed continually during the 2 hours before a feeding and the first hour afterward, starting before the very first feeding and continuing at regular 24-hour intervals for 4 days. The amount of time spent sucking a pacifier or finger(s) was recorded for both groups. The results indicated that the newborns spent about half an hour per hour sucking a pacifier starting on the very first day of life, and that this did not vary with feeding experience. They also indicated that some newborns in the control group sucked their fingers, 1 for considerable periods of time. The results suggest that human newborns, like other newborn mammals, program considerable sucking time for themselves regardless of whether or not milk is forthcoming.
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In the absence of cirrhosis, most children with portal hypertension and bleeding esophageal varices have extrahepatic portal vein occlusion. In the past 2 yr this clinical picture has been mimicked by two children with hepatoportal sclerosis causing their variceal hemorrhage. Hepatoportal sclerosis has been well described in adults. It is manifested by splenomegaly, portal hypertension, and variable ascites and hepatomegaly. Liver histology is initially normal but subsequently shows periportal fibrosis without cirrhosis. Hepatic manometrics indicate a presinusoidal block, but angiography demonstrates a patient portal vein. Typically there is abrupt narrowing of the intrahepatic portal branches, giving a "withered tree" appearance. These findings are illustrated by two children who presented with esophageal variceal bleeding at 21 and 20 mo of age, respectively. They are the youngest reported cases of hepatoportal sclerosis. The etiology of hepatoportal sclerosis is uncertain, but the disease appears to be only slowly progressive. Control of variceal bleeding by central portosystemic shunts in this condition is associated with a 50% incidence of hepatic encephalopathy. Therefore alternate methods of therapy need be considered. Endoscopic injection sclerotherapy successfully controlled variceal bleeding in one child reported here. Hepatoportal sclerosis is a distinct entity and must be considered in the differential diagnosis of portal hypertension in infants and children.
To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on the right ventricular muscle strips from normal and cardiomyopathic hamsters with alpha 1- and beta-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 x 10 (-6) mol . litre (-1) noradrenaline raised isometric tension by 27 +/- 4, 39 +/- 5, 52 +/- 5 and 61 +/-6% in normal animals (n = 6). Corresponding increase of 65 +/- 8, 92 +/- 8, 109 +/- 9 and 115 +/- 10% occurred in cardiomyopathic hamsters (n=11, all P less than 0.02). The responses to isoprenaline (Emax =82%) and ouabain did not differ between the two groups of hamsters. [3H]-prazosin, a new radioligand, and [-3H]-dihydroalprenolol were used to assess alpha 1- and beta-adrenoceptors in cardiac membranes. By Scatchard analysis, the KD values for both ligands did not differ between normal and cardiomyopathic hamsters, but the maximum number of binding sites was higher in the myopathic group: 5.5 vs 3.9 fmol . mg [-1] protein for [3H]-prazosin and 27 vs 20 fmol . mg [-1] protein for [-3H]-dihydroalprenolol (both P less than 0.05). Histochemically, oxidative and glycolytic activity were normal but lysosomal acid phosphatase was high. Possible explanations for the raise response to noradrenaline in cardiomyopathic hamster include and increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of alpha 1-(postsynaptic) adrenoceptors.
Compared with sham-operated guinea pigs, chronic heart failure produced by aortic constriction resulted in a 79% increase in alpha 1-adrenoceptor density as measured by [3H]prazosin binding (73 +/- 15 vs. 131 +/- 20 fmol/mg protein, P < 0.05); beta-adrenoceptor number, measured by (-)-[3H]dihydroalprenolol binding, increased by 93% (28 +/- 3.4 vs. 54 +/- 5.2 fmol/mg protein, P < 0.01). For each radioligand KD values were unchanged. Thus, congestive heart failure due to chronic pressure overload results in compensatory augmentation of alpha 1- and beta-adrenoceptor numbers.
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Six normotensive volunteers were infused with L-adrenaline at 0.01, 0.03, 0.05, 0.075 and 0.10 microgram/kg-1 min-1, each increment lasted 10 min. Plasma adrenaline rose from 0.27 to 4.61 nmol/l, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0.083 +/- 0.006 microgram kg-1 min-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1.40 to 6.01 nmol/min with a mean (+/- SEM, 6) of 2.82 +/- 0.76 nmol/min. Mean clearance (+/- SEM, 6) was 9.41 +/- 1.37 l/min and ranged from 4.86 to 14.61 l/min. The decline of plasma adrenaline following the infusion was biexponential. Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.
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