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Biomedical subjects

R H Glew

Publications and source records attributed to R H Glew.

At least 235 records · Page 13Linked to original sources

Gentamicin dosage in children with extensive burns.

During the treatment of Gram-negative bacillary infections in severely burned children, it was noted that administration of standard dosages of gentamicin commonly produced inadequately low serum concentrations of the antibiotic. Pharmakokinetic studies demonstrated that mean peak serum gentamicin levels were significantly lower in 18 burned children as compared with peak serum levels in five unburned children. Furthermore, inadequately low peak serum levels (less than 3.0 mug/ml) were observed in 15 of 18 burned children and in only one unburned child. Clearance studies in two children suggested that the increased requirement for gentamicin can result from either loss of the antibiotic across burn wounds or increased urinary excretion. These studies indicate that the therapy of severe infections in children with major burns often requires administration of gentamicin at higher doses and more frequent intervals than usually employed.

Adolescent↗

Fine structural observations of the liver in alpha-1-antitrypsin deficiency.

Morphologic studies of liver tissue in individuals deficient in alpha-1-antitrypsin (alpha-1-AT) have established the presence of membrane-delimited deposits which are diastase resistant, perodic acid-Schiff positive, sialic acid deficient, and immunologically related to serum alpha-1-AT. The molecular basis for the accumulation alpha-1-AT-like substance in hepatocytes and the serum deficiency in alpha-1-AT patients is unknown. In an effort to gain insight into the membrane sites involved in the storage of the alpha-1-AT-like material, we examined liver biopsies by light and electron microscopy from 3 children with homozygous PiZZ deficiency and varying degrees of liver pathology. Contrary to the more widely held belief that accumulation occurs primarily in the rough endoplasmic reticulum, we find the earliest and greatest accumulation of alpha-1-AT-like material in smooth endoplasmic reticulum of hepatocytes. We have combined our ultrastructural observations with the current knowledge which is available concerning the structural properties of M-type and Z-type alpha-1-AT and have proposed a model which may explain the basis for the hepatic accumulation of alpha-1-AT-like material and the serum deficiency state in the PiZZ genotypes.

Child↗

A microassay for Gaucher's disease.

We report a new assay for the detection of individuals heterozygous and homozygous for Gaucher's disease which requires relatively small samples of whole blood (0.3 ml), and which determines 4-methylumbelliferyl-beta-D-glucopyranoside:beta-glucosidase activity under conditions optimal for the determination of leukocyte glucocerebroside:beta-glucocereborsidase activity. The procedure involves the preparation of a leukocyte pellet from 50 mul of whole blood by hypotonic lysis of erythrocytes, followed by assay of beta-glucosidase activity at pH 5.5 in the presence of sodium taurocholate (0.6 g/100 ml). The methods described may also prove to be useful for the diagnosis of other diseases of enzyme deficiency which use fluorogenic substrates and leukocytes as a source of enzyme, such as Fabry's disease, Tay-Sachs disease, and generalized gangliosidosis.

Diagnosis, Differential↗

Serum complement and immunity in experimental simian malaria. I. Cyclical alterations in C4 related to schizont rupture.

Previous studies indicated that the level of whole serum complement (C') falls during malaria, and that the fall in C' is linked to schizont rupture and the appearance of humoral antibody. For a more detailed study of the role of C' in malaria, levels of C4 were monitored in rhesus monkeys infected with Plasmodium coatneyi. After one to two weeks of infection, significant and abrupt declines in C4 levels occurred, and these were temporally related to the process of schizont rupture. The level of C4 began to fall within a few hours after the onset of schizont rupture and fell to values as low as 2% of prerupture levels. Over the next 24-36 hr, C4 returned to normal levels, and fell again during the next cycle of schizont rupture. In general, the decline in C4 levels was positively correlated with the onset of immune response (functional and serologic) and degree of parasitemia. This marked cyclincal depletion of C4 indicates tremendous turnover of C' in primates with malaria.

Animals↗

Serum complement and immunity in experimental simian malaria. II. Preferential activation of early components and failure of depletion of late components to inhibit protective immunity.

The role of complement in the control of parasitemia was examined. Depletion of late components (3-9) by cobra venom factor did not alter either the degree or course of parasitemia during the pre-immune or immune stages of infection. The pattern of consumption of complement components was therefore examined. Concomitant with schizont rupture there was depletion of early-acting components (C1, C4, and C2) of the clasical complement pathway. The magnitude and remporal relationships of the fall were similar for these three components. Serum levels returned to prerupture values over 36-48 hr, and then the cycle was repeated. There was no simultaneous change in the levels of C3, C3 proactivator, or C6. These results delineate a new pattern of cyclical consumption of early components of the classical complement pathway associated temporally with schizont rupture and suggest that the late-acting components are not required for protective host immunity in malaria.

Acute Disease↗

Comparative synergistic activity of nafcillin, oxacillin, and methicillin in combination with gentamicin against.

The effectiveness of three semisynthetic, penicillinase-resistant penicillins alone and in combination with gentamicin was tested against 29 clinical isolates of enterococci. The minimal inhibitory concentrations of nafcillin were considerably lower than those of oxacillin and methicillin but were slightly higher than those of penicillin. At clinically achievable concentrations, the combination of nafcillin plus gentamicin produced enhanced killing against 13 of 14 strains of enterococci and was synergistic (by very rigid criteria) against 10 of 14 strains. In contrast, combinations of oxacillin plus gentamicin were synergistic against only 3 of 14 strains, and methicillin plus gentamicin produced synergistic killing against only 1 of 14 strains.

Adolescent↗

Enzymatic degradation of uric acid by uricase-loaded human erythrocytes.

Erythrocytes containing pig liver uricase have been prepared by hypotonic hemolysis in the presence of the enzyme. Uricase is shown to be active within the erythrocytes and to degrade uric acid as rapidly as it enters the cells when high intracellular enzyme concentrations are employed. The kinetics and characteristics of uric acid entry are shown to be the same for hemolysed and normal erythrocytes. At physiological concentrations of uric acid, loaded erythrocytes can degrade a maximum of about 21 mumol uric acid/liter erythrocytes per min. The possible application of enzyme-loaded erythrocytes to medicine is discussed.

Biological Transport↗

Failure to demonstrate circulating endotoxin in malaria (38572).

The possibility that endotoxin or an endotoxin-like substance plays a role in malaria has been suggested by the clinical similarity between human malaria and the febrile reaction to endotoxins, as well as the occurrence of endotoxin tolerance in humans infected with malaria. However, endotoxin or endotoxin-like activity was not demonstrable, using the Limulus test, in the plasma of humans or monkeys infected with plasmodia. The data indicate that the febrile paroxysm of malarial infection is not associated with detectable levels of endotoxin in the blood.

Animals↗

Relationship of serum complement levels to events of the malarial paroxysm.

Malarial paroxysms due to Plasmodium vivax were studied for alterations in whole serum complement (C') and certain C' components. The objective was to relate C' values with events of the parasite cycle during schizogony and with the febrile pattern. Substantial decreases in C' were found in 9 of 18 paroxysms studied during relapse. In contrast, only one of 22 paroxysms occuring during the primary attack was associated with a striking depression in C', and this case exhibited certain characteristics of a relapse paroxysm. The mean change in C' levels during paroxysms in relapse (-23%) was significantly different from paroxysms of the primary attack (-2%). Depletion of C' was associated directly with degree of parasitemia and presence of complement-fixing (CF) antibody. Lowest levels of C' were found within a few hours after completion of schizont repture and peak fever. C4 levels reflected changes in whole serum C' and appeared to be a more sensitive indicator of C' alterations during malaria. While the alterations in C4 as well as C1 and C2 indicated that the classical C' pathway was involved, some preliminary results showed little or no depletion of late components, C3 and C6. Overall results are compatible with C' activation and depletion during or soon after schizont repture if parasite density is sufficiently high and if CF antibody is present.

Adult↗