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Biomedical subjects

R C Smart

Publications and source records attributed to R C Smart.

70 records · Page 4Linked to original sources

DT-diaphorase and peroxidase influence the covalent binding of the metabolites of phenol, the major metabolite of benzene.

The role of various enzymes and biological molecules on the activation and deactivation of the metabolites of phenol was investigated in vitro. Phenol, the major metabolite of benzene, is metabolized to hydroquinone and catechol. Activation of these metabolites and deactivation of their oxidized forms was assessed by the amount of covalent binding to microsomal protein. [14C]Phenol and NADPH were incubated with hepatic microsomes isolated from phenobarbital-pretreated guinea pigs, and 2.33 nmoles of hydroquinone and 0.12 nmole of catechol were formed per minute per milligram of microsomal protein. Covalent binding of the metabolites to microsomal protein incubated with microsomes isolated from guinea pigs pretreated with phenobarbital was 252 pmoles bound/min/mg; with microsomes from untreated guinea pigs, covalent binding was 146 pmoles bound/min/mg. Covalent binding was inhibited greater than 90% with the addition of N-octylamine, ascorbate, or GSH. The addition of superoxide dismutase inhibited covalent binding with microsomes isolated from phenobarbital-pretreated guinea pigs 35% but did not inhibit it with microsomes isolated from untreated animals. Partially purified guinea pig hepatic DT-diaphorase [NAD(P)H (quinone acceptor) oxidoreductase, EC 1.6.99.2] inhibited covalent binding 70%. This effect was reversed in the presence of dicumarol, a specific inhibitor of DT-diaphorase. DT-diaphorase present in the 10(5) X g supernatant fraction was also active in inhibiting covalent binding but only after the removal of endogenous reduced glutathione. This effect could also be reversed by dicumarol. The addition of diaphorase (NADH:lipoamide oxidoreductase, EC 1.6.4.3) partially purified from Clostridium kluyveri inhibited covalent binding 86%. The addition of hydrogen peroxide and horseradish peroxidase (peroxidase, EC 1.11.17) or myeloperoxidase(s) increased covalent binding 30-fold and 6-fold, respectively. Ascorbate decreased this binding greater than 95%. These results indicate that hydroquinone, catechol, and phenol as well as their oxidized forms can be activated or deactivated by several of the above model systems. These systems may play a role in the myelotoxicity of benzene by modulating covalent binding.

Animals↗

A simple aid to the differential diagnosis of oliguria.

A study was conducted in oliguric and acutely azotemic patients, measuring: (i) the fractional excretion of sodium (FENa) using creatinine clearance as a measure of glomerular filtration rate, and (ii) sodium clearance relative to urea clearance, designated as the sodium/urea clearance ratio (Na:urea CR). It was found that FENa discriminated between "tubular" and "non-tubular" disorders in 96% of patients. Further, Na:urea CR was as discriminating as FENa. Patients with Na:urea CR above 2.5% can be reliably diagnosed as having acute tubular necrosis or acute urinary tract obstruction; those with a value less than 2.5% will have acute glomerulonephritis or pre-renal azotemia. As urea and sodium measurements are so readily available, this test can now be applied in the assessment of the oliguric or acutely azotemic patient in any hospital practice.

Acute Kidney Injury↗

Prognostic factors in myelofibrosis.

The prognostic significance of spleen size, hemoglobin level (Hb), platelet count and hemopoietic cellularity of the bone marrow was assessed in 33 patients with myelofibrosis. Of these 4 parameters, only the Hb (P less than 0.01) and bone marrow cellularity (P less than 0.001) were found to be useful indicators of prognosis. Patients with Hb greater than 10 g/dl had a median survival greater than 110 mth while those with Hb less than 10 g/dl had a median survival of 22.5 mth; patients with hemopoietic hypercellularity in the bone marrow had a median survival greater than 110 mth while those with a normo- or hypocellularity had a median survival of 20.5 mth. There was significant correlation (P less than 0.01) between the marrow cellularity and the Hb level; 71% of patients with a normo- or hypocellular marrow had Hb less than 10 g/dl, while 79% of those with a hypercellular marrow had Hb greater than 10 g/dl.

Adult↗

The measurement of calcium absorption and absorption rate with an external arm radioactivity counter.

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.

Absorption↗

Hyposplenism in inflammatory bowel disease.

Splenic function was assessed in 35 patients with ulcerative colitis and 20 patients with Crohn's disease. Hyposplenism was diagnosed if there were Howell-Jolly bodies in the peripheral blood film or if there was prolongation of clearance from the peripheral blood of injected 51-Cr-labelled heat-damaged red blood cells. Thirteen of the patients with ulcerative colitis had hyposplenism as compared with only one patient with Crohn's disease. Conversely, heat-damaged red cell clearance values faster than the normal range were found in six out of the 20 patients with Crohn's disease. Four patients with hyposplenism and ulcerative colitis developed life-threatening septicaemia in the early postcolectomy period, two of these being further complicated by disseminated intravascular coagulation.

Colectomy↗

Relationship between splenic size and splenic function.

The rate of clearance of 51Cr labelled heat-damaged red cells from the circulation has been compared with the dimensions of the posterior scan of the spleen in 79 cases including nine controls. A strong negative correlation was found between the clearance half-time and the parameters of the scan but, as there was a large variation about the regression line, in the assessment of hyposplenism determination of the rate of clearance of heat-damaged red cells cannot be replaced by the easier determination of spleen size by scanning.

Erythrocyte Aging↗

Clinical study of liver blood flow in man measured by 133Xe clearance after portal vein injection.

During the course of a clinical trial to assess the value of adjuvant liver perfusion of 5-fluorouracil after surgery for colorectal cancer, liver blood flow was measured in 14 patients. Access to the portal circulation was achieved by dilatation and cannulation of the obliterated umbilical vein. The clearance from the liver of a bolus of 133Xe was monitored using a gamma-ray camera so that blood flow from different areas of the liver could be calculated. The clearance curve of 133Xe was a double exponential of which the initial fast component accounted for a consistently high proportion of the total clearance. The perfusion studies have shown wide differences in blood flow to the various areas of the liver in the same patient, in addition to a wide variation in perfusion rate between the 14 patients. This technique of quantitative estimations of liver blood flow to different areas of the liver may have importance in planning operative procedures and understanding the haemodynamic mechanisms involved in liver disease.

Humans↗

The use of technetium-99m labelled heat-damaged red cells for the quantitative measurement of splenic function.

A comparison of the rates of clearance of 51Cr labelled and 99mTc labelled heat-damaged red cells in 25 patients and 4 control subjects is reported. Very little correlation was found between the clearance half-times of the two types of labelled cells when the cells were labelled with 99mTc prior to heat damaging. The correlation was improved when the labelling step occurred after the cells had been damaged. Urinary excretion measurements revealed that the rate of excretion of 99mTc could be as much as nine times that of the 51Cr label. 99mTc labelled heat-damaged red cells were found not to be sufficiently stable a preparation for use in quantitative clearance studies.

Chromium Isotopes↗

Cerebral blood flow changes in acute experimental haemorrhagic vasospasm.

Subarachnoid haemorrhage was produced in 26 dogs by injecting fresh homogenous blood into the cysterna chiasmatica. Two types of vasospasm were observed, firstly segmental arterial spasm closely related to the bleeding point and secondly generalized arterial vasospasm not directly related to the bleeding point and often occurring some way from the bleeding point. Reduction in CBF occurred in 61% of cases and was always accompanied by radiological vasospasm. However, in about one quarter of the cases with vasospasm there was no alteration in CBF.

Animals↗