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Biomedical subjects

C E Wright

Publications and source records attributed to C E Wright.

At least 127 records · Page 7Linked to original sources

The influence of age on the spatial and temporal contrast sensitivity function.

A clinical technique for sampling the spatial and temporal CSF at low, intermediate and high frequencies is described. Reductions in contrast sensitivity with age were shown with the highest spatial and temporal frequency stimuli. The reductions can be almost completely accounted for by the reduction of pupil area with age, causing a reduction in retinal illuminance. The results show a significant deterioration in vision with age that is not revealed by standard visual acuity testing.

Adolescent↗

Liquid chromatographic assay for fluoxymesterone in human serum with application to a preliminary bioavailability study.

Fluoxymesterone was extracted from serum with a liquid-liquid extraction procedure. Serum containing both drug and internal standard, 6 alpha-methylprednisolone, was extracted with methylene chloride. The extract was washed with 0.1 M NaOH and water, evaporated, and reconstituted with mobile phase. Chromatography was performed on a Zorbax Sil column, preceded by a guard column, with a mobile phase composed of 50% water-saturated butyl chloride:tetrahydrofuran:methanol:phosphoric acid (880:100:15:0.5). Fluoxymesterone and methylprednisolone were detected by UV absorption at 236 nm. Overall recovery was 80%. Calibration curves were linear for fluoxymesterone concentrations from 5 to 100 ng/mL. The assay is accurate and precise (RSD values less than or equal to 7%); endogenous steroids did not interfere with the assay. Assay suitability was assessed in a bioavailability study in which six subjects each received two treatments of 10-mg fluoxymesterone tablets in a Latin-square crossover study. The two treatments were a tablet administered either buccally or orally. Cmax values ranged from 40 to 150 ng/mL with tmax values of 1-2 h. The harmonic mean half-life of fluoxymesterone was 2.0 h. Less than 8% of the AUC was extrapolated. Mean Cmax and AUC values from the oral treatment were 80 and 76%, respectively, of the mean values from the buccal treatment.

Adult↗

Primary presenile dementia: the use of the visual evoked potential as a diagnostic indicator.

The use of the flash and pattern reversal visual evoked potential (VEP) in the diagnosis of primary presenile dementia was investigated. The results from 20 patients with primary presenile dementia were compared with those from a control group of normals of equivalent age and from a control group of 20 patients with cortical atrophy but no dementia. Presenile dementia caused a slowing of the major positive (P2) component of the VEP to flash stimulation. However, the VEP to pattern reversal stimulation (P100) was of normal latency. The difference between these two latencies characterises this unusual combination of results and is found to be a more specific diagnostic indicator of primary presenile dementia than the EEG or CT scan.

Aged↗

Significance of growth modulators in human milk.

Human milk contains growth modulators of potential clinical importance to the neonate. Evidence from animal and cell culture models as well as ancillary evidence about their stability and the way some of them are processed for secretion suggest they are probably physiologically significant. Their presence in human milk does not by itself establish their importance; however, it is useful to explore their potential functional roles. Growth modulators present in human milk include: EGF, NGF, certain enzymes, and taurine.

Animals↗

Presenile dementia--the use of the flash and pattern VEP in diagnosis.

Flash, pattern reversal and pattern onset-offset VEPs were recorded in 17 patients with a clinical diagnosis of presenile dementia. The results were compared with those from two control groups--17 normal volunteers of equivalent ages and 17 patients from the same psychiatric hospital with affective disorders but no clinical evidence of dementia. The flash P2 component was found to be significantly delayed in the group of patients with dementia, but the latency of the P1 component and pattern VEP components were all within normal limits. This unusual finding presents a useful index for the diagnosis of presenile dementia.

Aged↗

Protective effect of taurine, zinc and tocopherol on retinol-induced damage in human lymphoblastoid cells.

Cultured human lymphoblastoid cells exposed for short times to retinol and retinoic acid, undergo a time- and dose-dependent decrease in viability, accompanied by cell swelling. The presence of taurine (5-20 mM) and zinc (50-100 microM) protected cells from retinol-induced injury. Taurine 20 mM and zinc 100 microM added simultaneously abolished cell swelling and increased cell viability from 7 to 55%. Tocopherol (200 microM) was also effective in protecting these cells from retinol. The three compounds together afforded complete protection. The effects of retinol and of taurine, zinc or tocopherol seem to be unrelated to lipid peroxidation. A membrane stabilizer action is proposed as the mechanism underlying the protective effect of taurine and zinc or of tocopherol.

Amino Acids↗

Sulfhydryl oxidase in human milk: stability of milk enzymes in the gastrointestinal tract.

Sulfhydryl oxidase (SOX) is present in human milk and in milk from all species that have been studied. The pH optimum of human milk SOX is in the neutral range between 7.0 and 7.5. Human milk SOX is stable in an acid environment: 50% of its activity remains after 1 h at pH 2.5. Acid stability is also characteristic of gamma-glutamyltranspeptidase, another membrane-bound enzyme in skim milk. SOX is resistant to pepsin (4000 U/ml), trypsin (50 micrograms/ml), chymotrypsin (200 micrograms/ml), and to trypsin plus chymotrypsin (25 micrograms each/ml). Milk SOX activity has been detected in the stomach and proximal small intestine contents of suckling rats. Human and bovine SOX are relatively heat stable: 75% of the latter remains after treatment at 62.5 degrees C for 30 min and 65% of the former remains after treatment at 60 degrees C for 10 min. Neither remains after 62.5 degrees C for 30 min.

Animals↗

Taurine uptake by cultured human lymphoblastoid cells.

Cultured human lymphoblastoid cells take up taurine from the medium by two processes: 1) a temperature-dependent, Na+-dependent, saturable "active"-transport system and 2) diffusion. The active transport has properties similar to those reported for taurine transport by other tissues. Apparent Km is about 25 microM and Vmax about 7.2 pmol/min/10(6) cells; saturation occurs at 100 microM taurine. Uptake is competitively inhibited by the beta-amino acids hypotaurine (50% inhibition at 44 microM) and beta-alanine (50% at 152 microM), as measured at 50 microM taurine. Taurocyamine inhibits 50% at 260 microM. Chlorpromazine and imipramine are strong uncompetitive inhibitors, giving 50% inhibition at 26 microM and 115 microM, respectively; at these concentrations cellular viability per se is not affected. Ouabain inhibits 40-50% over a concentration range of 4-500 microM. Diffusion of taurine into the cells is proportional to concentration up to 20 mM. However, at the concentration of taurine in human plasma, 40-100 microM, active transport would provide 90% of the taurine taken up.

Binding, Competitive↗

Influence of route of administration on the pharmacokinetics of methylprednisolone.

This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus; (b) as a 1 ml i.m. injection; (c) administered as an oral solution; and (d) as 5 X 8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.

Absorption↗

Ibuprofen and acetaminophen kinetics when taken concurrently.

We evaluated kinetics of ibuprofen and acetaminophen taken concurrently by 20 healthy adults in a randomized crossover design. Steady-state blood levels of ibuprofen and acetaminophen were measured by gas-liquid chromatography and HPLC. There were no significant differences in any of the ibuprofen serum concentrations, but there were differences in acetaminophen serum concentrations in 5 of 19 sampling times. When bioavailability and kinetic parameters for both drugs were compared, there were no significant differences. Our data demonstrate that steady-state kinetics of ibuprofen and acetaminophen are not changed when taken concurrently.

Absorption↗

Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin.

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.

Animals↗

Atypical Down syndrome and partial trisomy 21.

A case of "atypical" Down Syndrome (DS), where the proposita did not exhibit all of the clinical features of DS and had de novo partial trisomy 21, was studied. Results from phenotypic, chromosome banding and superoxide dismutase (SOD) gene dosage studies suggest a karyotype of 46,XX,-12,+t(12pter to 12qter::21q21 to 21q22.?2). Additional studies of such atypical cases will provide more precise sublocalization for both gene and phenotypic mapping of the bands that are responsible for the DS phenotype.

Child↗

Genetic heterogeneity of I-cell disease is demonstrated by complementation of lysosomal enzyme processing mutants.

I-cell disease (mucolipidosis II) is a fatal childhood disorder affecting the expression of multiple lysosomal acid hydrolases. The disorder is characterized by clinical and biochemical heterogeneity which may reflect different mutants with a similar phenotype. Genetic complementation studies demonstrating genetic heterogeneity within this disorder are described utilizing cultured fibroblasts from 11 different patients. Fibroblasts from I-cell disease (ICD) and from five different lysosomal storage diseases with single structural gene enzyme deficiencies were fused in different combinations, and fractions enriched for multinucleated heterokaryons were isolated and tested for acid hydrolase activity and electrophoretic mobility. In fusions of ICD fibroblasts and various single lysosomal enzyme-deficient fibroblasts, the activity of the deficient enzyme and of the other ICD hydrolases were restored, demonstrating that ICD is not a lysosomal enzyme structural gene defect and that the ICD defect, and not just the single enzyme deficiency, is corrected. In fusions involving only I-cell fibroblasts, at least two complementation groups were identified by the recovery of activities of all lysosomal enzymes tested in heterokaryons. These results demonstrate the existence of genetic heterogeneity within the disorder and suggest that different mutations can result in the I-cell clinical and biochemical phenotype. The data support an altered post-translational processing of lysosomal enzymes as the cause of ICD and suggest that at least two genes participate in this pathway.

Cell Fusion↗