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Biomedical subjects

A R Hansen

Publications and source records attributed to A R Hansen.

At least 37 records · Page 2Linked to original sources

Determination of flumequine and a hydroxy metabolite in biological fluids by high-pressure liquid chromatographic, fluorometric, and microbiological methods.

A sensitive and specific high-pressure liquid chromatographic method is described for the determination of the antibacterial drug flumequine and a major metabolite, 7-hydroxyflumequine, in human plasma and urine. The assay was linear over a concentration range of 1 to 120 micrograms/ml for both compounds. This method is compared with fluorometric and microbiological assays for flumequine. These latter methods did not differentiate between flumequine and any fluorescent or antimicrobiologically active metabolites. However, because essentially all drug in the plasma was found to be flumequine in radiolabeled studies, levels of unchanged drug in the plasma could be quantitated by either high-pressure liquid chromatography or fluorometry. Although only high-pressure liquid chromatography was able to specifically measure flumequine in the urine, the antimicrobial activity of the urine, which is more therapeutically relevant due to antimicrobially active metabolites, could be quantitated by either the fluorometric or the microbiological assay.

Biological Assay↗

Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties.

Two synthetic pathways are described for the preparation of 4-hydroxy-2-ethyl-2-phenylglutarimide (2), an active hydroxylated metabolite of glutethimide (1). Fourteen other glutethimide analogs were also synthesized and tested for biological activity. Most of the analogs exhibited sedative-hypnotic properties and compound 2 possessed the greatest activity compared to the parent drug. 4-Amino-2-ethyl-2-phenylglutarimide and 4-hydroxy-2-ethyl-2-phenylglutaconimide (13) exhibited the greatest potential as anticonvulsant agents. The structure-activity relationships of the series are discussed.

Animals↗

The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit.

1. Rabbit liver microsomes were subfractionated into rough- and smooth-surfaced types, and glucuronyltransferase activity in each microsomal subfraction was determined with p-nitrophenol, o-aminophenol and phenolphthalein as substrates. The glucuronyltransferase activity measured with p-nitrophenol and o-aminophenol as substrates was localized predominantly in rough-surfaced microsomes. Glucuronyltransferase measured with phenolphthalein as substrate was equally present in rough- and smooth-surfaced microsomes. 2. Phenobarbital pretreatment of rabbits did not stimulate any of the glucuronyltransferase activities measured in either rough- or smooth-surfaced microsomes. 3. Preincubation of rabbit liver microsomes for 30-60min. at 37 degrees under oxygen did not cause any loss of glucuronyltransferase activity. Such preincubation caused either no change or increased enzyme activity in both submicrosomal fractions. The relative distribution of transferase activity in rough- and smooth-surfaced microsomes was not affected by preincubation.

Animals↗

Transcranial Doppler findings of cerebral vasospasm in preeclampsia.

The objective of this study was to evaluate the effect of preeclampsia and its severity on maternal mean middle cerebral artery blood flow velocity (mean MCA-CBFV) using transcranial doppler sonography (TCD), as well as the effect of magnesium on mean MCA-CBFV in preeclampsia. This study used a prospective, comparative design. TCD was used to examine maternal mean MCA-CBFV in both healthy subjects (controls) and preeclamptic subjects (cases). The two groups were similar in age, gestational age, and parity. Healthy subjects were categorized into three groups: Group I, 6-14 weeks, n = 10; Group II, 24-40 weeks, n = 27; Group III, postpartum n = 15, 12-36 h. Serial TCD examinations of the middle cerebral artery were completed in 21 preeclamptic subjects at four different points in time: Time I is an initial measurement before delivery; Time 2 is also before delivery but after magnesium had been administered. Time 3 is postpartum while on magnesium (12-24 h), Time 4 is postpartum off magnesium, (24-48 h). Preeclamptic subjects had significantly increased mean MCA-CBFV when compared to healthy subjects: antepartum (mean 78.2 vs. 55.1 cm/sec, P < 0.0005); postpartum (mean 101.3 vs. 69.8 cm/sec, P < 0.0001). Severe preeclamptics had significantly higher mean MCA-CBFV than mild preeclamptics at each point in time: Time 1: P < 0.016; Time 2: P < 0.040; Time 3: P < 0.002; and Time 4: P < 0.028. These data support the theory that cerebral vasospasm of the smaller diameter vessels is a major component of preeclampsia.

Adult↗

Very low birthweight Infant's placenta and its relation to pregnancy and fetal characteristics.

Our objective was to relate pathology of the very low birthweight (VLBW) infant's placenta to pregnancy and fetal characteristics. We correlated the pathologic features of 1146 placentas from infants with birth weights of 500-1500 g who were born between 1/1/91 and 12/31/93 to the number of gestations per pregnancy, initiator of preterm delivery, gestational age, birth weight Z score, and duration of rupture of membrane (ROM). Placental correlates of acute inflammation and villous edema were associated with preterm labor (PTL), prelabor premature rupture of membranes (PROM), lower gestational age, and higher birth weight Z score. In PTL pregnancies delivered within 1 h of membrane rupture, 61% of placentas already had membrane inflammation. Placental correlates of pregnancy-induced hypertension (PIH) were seen more commonly with PIH pregnancies, older gestational age, and lower birth weight Z score. We found a more prominent histopathologic signature for singleton than for multiple gestation placentas. The placental pathologic findings associated with the clinical diagnoses of infection, PIH, and low-birth weight Z scores in our VLBW/preterm population are similar to those in the literature regarding term pregnancies. The presence of multiple histologic findings consistent with inflammation in placentas of PTL pregnancies with duration of ROM lasting <1 h suggests that some cases of PTL are precipitated by a more long-standing infection than that previously suspected. Morphologic placental features appear to be correlates of the phenomena leading to premature delivery. Examination of the VLBW infant's placenta provides insight into the etiology and management of VLBW/preterm deliveries.

Adult↗

Very low birthweight placenta: clustering of morphologic characteristics.

Our objective was to use factor analysis as a data reduction tool to organize a large number of placental pathologic features into useful aggregates. We examined 1146 placentas of live-born infants with a birth weight of 500-1500 g. We then conducted analyses of pairs of characteristics and multiple characteristics to identify "associated groups" and "factors," respectively. We found an associated group and factor that had placental features associated with acute inflammation and another associated group and factor that had features associated with vasculopathy. Acute umbilical vasculitis had the strongest correlation with other features of the acute inflammation associated group and factor. Gross evidence of acute inflammation (opacification and green appearance of membrane) was eliminated in the reduction from associated group to factor. Infarcts and syncytial knots were strongly dissociated with features of acute inflammation. The multiple pathologic features of the very low birthweight placenta can be aggregated into two associated groups or two factors. Lack of membrane opacification cannot be used as a criterion for declining microscopic examination. The absence of infarcts and syncytial knots should prompt a search for features of acute inflammation. If a placenta has two or more findings from the acute inflammation factor or the vasculopathy factor, it is unlikely to demonstrate features from the other factor.

Acute Disease↗