Biomedical subjects
Publications and source records attributed to R Miller.
Two pyrimido-pyrimidine derivatives (RA 233 and VK 744) were found effective aggregation inhibitors in vitro of human and monkey platelets and in vivo in stumptailed monkeys and chimpanzees. They also inhibited thrombotic occlusion of metal screens inserted into arteriovenous shunts.
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Forty-three patients with decompensated alcoholic liver disease and ascites of recent onset were randomized to salt and water restriction alone (control group) or to salt and water restriction plus diuretics (diuresis group). The two treatment groups were comparable in clinical findings and laboratory results. Seven patients in the control group and 5 patients in the diuresis group died during the acute illness. Weight loss was more marked and the disappearance of ascites more common in those given diuretics. A modest decrease in serum sodium and increase in serum potassium, and readily reversible elevations of blood urea nitrogen were noted in the diuresis group. Eight patients in each treatment group developed either the hepatorenal syndrome, marked electrolyte abnormalities, or encephalopathy. Diuresis can be accomplished in these critically ill patients without serious complications that can be attributed to the diuretic treatment.
The efficacy of corticosteroid therapy in severe viral hepatitis has never been demonstrated in a controlled clinical trial. For this reason, patients with severe viral hepatitis were randomly assigned to methyl-prednisolone or placebo treatment groups. The two groups were comparable in clinical findings, laboratory results and the presence of bridging necrosis on liver biopsy. Seven of the 14 patients assigned to methyl-prednisolone and two of the 15 assigned to placebo died during the 16-week study period. Although the apparent excess mortality in the steroid-treated patients is not quite statistically significant (P = 0.08), the trend persists when only patients positive for hepatitis B surface antigen (P = 0.04) are analyzed separately. Methyl-prednisolone does not enhance survival in patients with severe viral hepatitis, and it may be detrimental.
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The ventilatory responses to intravenous infusion of hypercapnic blood (equilibrated with 80% CO2: 20% O2) and inhaled CO2 (1.5-2.0% CO2) have been compared in anaesthetized rabbits. A control infusion of blood equilibrated with 4% CO2: 21% O2 produced no change in V, PaCO2 or PaO2. The ventilatory response to a given rise in PaCO2, deltaV - (delta PaCO2)-1, was greater during infusion of hypercapnic blood (69 +/- 33 ml-min-1-mm Hg-1, mean +/- SD) than during CO2 inhalation (28 +/- 16 ml-min-1-min Hg-1, P less than 0.01). There was no difference between the rates at which the final levels of ventilation were reached during inhalation of CO2 or infusion of hypercapnic blood. It is suggested that the difference between the responses may be accounted for by differences in the pattern of PaCO2 oscillations in the two situations.
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A case is reported of a patient with a cerebral aneurysm in whom it was difficult to induce hypotension. The hyperadrenergic state mimicked, in some respects, that seen in patients with neural crest lesions. Possible mechanisms are discussed and the anaesthetic management described.
Adenosine inhibits the aggregation of human but not of rat platelets whereas both are inhibited by prostaglandin E1 or by the pyrimido-pyrimidine compound RA233. In human platelets all three agents increase adenosine-3'-5'-cyclic monophosphate (cAMP). If the inhibition of aggregation depended on this increase, adenosine might be expected not to increase cAMP in rat platelets. Under conditions in which adenosine inhibited aggregation and increased cAMP in human platelets, adenosine caused a similar increase in cAMP in rat platelets without inhibiting their aggregation. The aggregation of rat platelets was inhibited as effectively as that of human platelets by PGE1 or RA233 at concentrations which caused greater increases in cAMP than did the highest concentrations (2.8 X 10(-4) M) of adenosine it was possible to use. When the increase of cAMP in rat platelets by PGE1 was limited to that produced by adenosine, PGE1 like adenosine failed to inhibit aggregation. Therefore, the difference in the inhibitory effectiveness of adenosine on rat and human platelets was quantitative rather than qualitative and apparently depended on the inability of adenosine to increase cAMP sufficiently in rat platelets. When cAMP had been increased by adenosine, PGE1 or RA233, the addition of ADP caused cAMP to decrease rapidly in both human and rat platelets to between +22 and -18% of control values, except that the decrease in rat platelets was to +40% after RA233 had been present for 0.5 min before ADP. The increase in cAMP produced in rat platelets by adenosine at 5 X 10(-6) to 2.8 X 10(-4) M for 3 min was associated with a small increase in aggregation velocity. It is suggested that the comparative ineffectiveness of adenosine as an inhibitor of platelet aggregation, particularly with rat but less so also with human platelets, is because, unlike PGE1 or RA233, adenosine has two opposing actions on aggregation; one being inhibition by activating adenylate cyclase and increasing cAMP, and the other being potentiation by uptake. This hypothesis accounts for the present results as well as for the earlier observation that dipyridamole which prevents the uptake of adenosine potentiates its inhibitory effect on the aggregation of human platelets.
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A 56-year-old woman developed a vesicular and bullous eruption followed by an efflorescence of lichenoid papules. The clinical and histologic features of this case were consistent with a diagnosis of lichen planus pemphigoides. Direct and indirect immunofluorescence studies demonstrated both in vivo-bound and circulating IgG with specificity for the epidermal basement membrane zone. A common pathogenic immunologic mechanism may exist for both lichen planus and lichen planus pemphigoides, which we believe are clinical variants of a similar disease process.
Commissural, cortico-cortical and cortico-caudate neurons have been investigated in the primary sensorimotor cortex of the cat, using antidromic stimulation techniques, and histological identification of recording sites. These neurons are to be found in all cortical laminae except the first; commissural and cortico-cortical neurons were found to be commonest in laminae III and VI, whilst cortico-caudate neurons were most abundant on the border between laminae III and V, in motor areas. In sensory areas topographically identified as representing distal parts of limbs, commissural neurons are very rare, confirming neuroanatomical studies on the origin and termination of callosal fibres. The intracerebral neuronal projections investigated in this study had slow conduction velocities (less than 1 m/sec, up to about 10 m/sec). It was found that projections from area 6, whether commissural, cortico-caudate, or cortico-peduncular have slower conduction velocities than their counterparts from area 4. It is suggested that this is related to the type of motor control in which these two areas are involved (slowly-responding postural movements, as opposed to more rapid distal limb movements). No neurons were found which had both commissural (or cortico-cortical), and cortico-fugal projections.