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Biomedical subjects

W A Phillips

Publications and source records attributed to W A Phillips.

At least 127 records · Page 7Linked to original sources
PubMed1977

Effects of colestipol hydrochloride and neomycin sulfate on cholesterol turnover in the rat.

Three groups of male rats were fed diets containing the bile acid sequestrant colestipol hydrochloride (1%), neomycin sulfate (0.25%), or basic diet during the test. After 15 days, each rat was injected IV with 3.9 muCi cholesterol-1,2(-3)H complexed with serum lipoproteins; specific radioactivity of the total serum cholesterol was measured at several time intervals for a period of 7 weeks. Computer analysis of the data indicated that the turnover of cholesterol could best be fitted by a three-pool model. In pool 1, colestipol HC1 caused a significant increase in production rate (10.09 to 15.96 mg/day) and the excretion rate constant (0.53 to 0.79 day-1) of cholesterol without significantly altering the size of the pool or serum cholesterol concentrations. These results are compatible with an agent capable of binding bile acids in the rat but do not cause a decrease of the sterol pool because of an adequate compensatory increase in cholesterol biosynthesis. Neomycin SO4 caused a significant reduction in serum cholesterol (9%) without altering turnover parameters and apparently exerts its hypocholesterolemia by some mechanism other than bile acid sequestration.

Animals↗
PubMed1976

Effects of colestipol hydrochloride on drug absorption in the rat II.

The effects of colestipol hydrochloride, a hypocholesterolemic bile acid-binding anion-exchange polymer, on the GI absorption of drugs commonly used in humans were studied in the rat. Colestipol hydrochloride was given by gavage in single doses of 71.5 or 214.5 mg/kg, equivalent to 5 or 15 g, respectively, in a 70-kg human; controls received equivalent amounts of microcrystalline cellulose. Single oral doses of labeled drugs were given concurrently with colestipol hydrochloride or microcrystalline cellulose at the human therapeutic dose range on a milligrams per kilogram basis. Subsequent changes in serum drug levels were measured at several time periods, and absorption was evaluated as the total area under the time-concentration curve. Colestipol hydrochloride at either dose did not significantly alter the absorption of 6-14C-nicotinic acid, 7-3H-tetracycline, 35S-chlorpromazine, 12alpha-3H-digoxin, warfarin (alpha-14C-benzyl), or clofibrate (14C-carboxyl). In addition, the effects of 214.5 mg/kg of colestipol hydrochloride were compared with the same dose of cholestyramine with respect to the absorption of 3-14C-hydrochlorothiazide, 2-14C-phenobarbital, and 3H-digitoxin. Cholestyramine reduced absorption of hydrochlorothiazide by 42%, but colestipol hydrochloride had no significant effect. Neither resin altered phenobarbital or digitoxin absorption when compared with the the control, but a significant difference occurred between the two resins with digitoxin; areas under the time-concentration curve [in (dpm/0.1 ml serum) x hr] were: colestipol hydrochloride, 2001; cholestyramine, 16,300; and cellulose, 17, 067. These results indicate that colestipol hydrochloride and cholestyramine can differ in their effects on the absorption of certain drugs from the GI tract of the rat.

Animals↗
PubMed1976

Nonisotopic method for estimating cholesterogenesis in the rat.

Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) mald rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HC l had no significant effect, while clofibrate or the combination with colestipated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis.

Androstenes↗
PubMedDate not supplied

Activity of ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate, a new hypocholesterolemic compound, in male rats and SEA Japanese quail.

Ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate (HMP), a new hypocholesterolemic compound, was evaluated in male rats at dosage levels ranging from 25-800 mg/kg/day and in SEA Japanese quail at approximately 200 mg/kg/day. In the rat, the atherogenic lipoprotein cholesterol, that is, the combination of very low density plus low density lipoprotein cholesterol (VLDL-C + LDL-C), was reduced 20-27% at dosage levels over 100 mg/kg/day, while high density lipoprotein cholesterol (HDL-C) and total serum cholesterol (TSC) were significantly decreased 25-46%, respectively, at all dose levels of HMP. Liver weights with HMP treatment were significantly elevated (11-26%) in the rat. HMP was not active in the SEA Japanese quail, since an initial reduction in artery cholesterol could not be confirmed in subsequent tests.

Animals↗
PubMedDate not supplied

MR imaging of early fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva is a rare disorder characterized by progressive heterotopic bone formation in connective tissue and muscle in association with congenital skeletal anomalies. The disease usually leads to extensive immobility and eventual disability. We report the magnetic resonance findings in a boy prior to ossification of his soft tissue masses.

Child, Preschool↗
PubMedDate not supplied

Management of scoliosis due to syringomyelia in childhood and adolescence.

To determine the effect of syringomyelia treatment (drainage) on the efficacy of orthotic management and safety of operative management of an associated scoliosis, the records of four boys with scoliosis due to syringomyelia were reviewed. The average follow-up was 8 years. On presentation, all had an abnormal neurologic examination. Each syrinx was treated by laminectomy and insertion of a syringosubarachnoid shunt. After drainage, three of four improved neurologically. Two older patients underwent uneventful posterior spinal fusion with Harrington distraction instrumentation after their drainage procedures. One boy developed kyphosis at the site of his laminectomy. Two young patients, whose curves were initially well controlled with bracing, developed continued curve progression over time. Drainage of the syrinx delayed but did not prevent curve progression in immature patients, but did allow use of distraction instrumentation without complication for operative management of the associated scoliosis.

Adolescent↗
PubMedDate not supplied

Natural history of scoliosis in congenital heart disease.

We defined the natural history of scoliosis in congenital heart disease (CHD) with respect to the risk of progression and indications for treatment. We reviewed radiographs of 48 children with CHD and scoliosis. Thirty-seven had developmental scoliosis (77%), and 11 (23%) had congenital scoliosis. Children with congenital scoliosis can be managed in the same way as children without CHD. Developmental curves less than 30 degrees in children aged greater than 10 years showed no progression. Developmental curves greater than 30 degrees with onset in children aged less than 10 years and progression greater than 9 degrees per year require treatment.

Adolescent↗