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Biomedical subjects

W E Lambert

Publications and source records attributed to W E Lambert.

15 recordsLinked to original sources
PubMed1992

Pharmacokinetics and drug interactions of etretinate and acitretin.

Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years.

Acitretin↗
PubMed1992

Pharmacokinetics and safety of a new solution of vitamin K1(20) in children with cholestasis.

In cholestatic diseases, the absorption of fat-soluble compounds, including vitamin K1(20), is low and periodic administration of vitamin K1(20) is often necessary. Due to the low absorption of vitamin K1(20) from the Konakion formulation, late hemorrhagic disease of the newborn also occurs especially after oral vitamin K1(20) prophylaxis with Konakion. We investigated the pharmacokinetics and the safety of a new formulation of vitamin K1(20) in a mixed micelles (MM) solution. Compared to the old formulation (Konakion) using Cremophor EL as a solubilizer, the higher vitamin K1(20) levels (as measured by HPLC) in serum obtained after oral administration of the MM formulation clearly demonstrate a superiority of this new formulation. Additionally, the elimination of Cremophor EL as well as of propylene glycol from the formulation avoids possible adverse effects associated with intravenous or intramuscular administration. Furthermore, in most cases, the discomfort of parenteral injections can be overcome by simple oral administration even in children with severe cholestasis.

Administration, Oral↗
PubMed1992

Enzymatic sample hydrolysis and HPLC in a study of phylloquinone concentration in human milk.

Phylloquinone (vitamin K) is essential to prevent hemorrhagic diseases in newborns. We were interested in determining the concentration of phylloquinone in human milk and in elucidating the factors that influence that concentration. Human milk contains lipid constituents encapsulated with phylloquinone in the fat globules. To eliminate the lipids, we combined sonication and an enzymatic treatment with lipase to prevent degradation by drastic hydrolysis. Despite the low phylloquinone concentrations and the procedure's complexity (lipase treatment, two HPLC steps, and an on-line thermoinduced postcolumn reduction followed by fluorescence detection), within-day and day-to-day CVs of 5.2% and 5.8% were obtained (n = 8, mean = 1.86 micrograms/L, and n = 7, mean = 1.74 micrograms/L, respectively). The mean concentration of phylloquinone in 126 samples was 1.15 +/- 0.82 micrograms/L (mean +/- SD); no correlation was observed between the vitamin concentration and the postpartum date of collection. There was a positive correlation between phylloquinone concentration and phospholipid and cholesterol content (r = 0.5578 and 0.6020, respectively).

Animals↗
PubMed1991

Improved quantitation of 13-cis- and all-trans-acitretin in human plasma by normal-phase high-performance liquid chromatography.

A reliable analytical method has been developed for measurement of 13-cis- and all-trans-acitretin (Neotigason) in human plasma by normal-phase high-performance liquid chromatography, with ultraviolet detection. Human plasma was obtained after centrifugation of whole blood samples and deproteinized by ethanolic denaturation. After liquid-liquid extraction with water-n-hexane, and aliquot ws chromatographed on a silica column using isocratic elution with n-hexane-methylsalicylate-acetic acid (200:18:0.6, v/v). The wavelength was set at 360 nm, and for plasma samples a limit of quantification of 3-4 ng/ml was obtained. All manipulations were carried out under dim light conditions to prevent photoisomerization.

Acitretin↗
PubMed1991

Epidemiologic approaches for assessing health risks from complex mixtures in indoor air.

Indoor air may be contaminated by diverse gaseous and particulate pollutants that may adversely affect health. As a basis for controlling adverse health effects of indoor air pollution, the presence of a hazard needs to be confirmed, and the quantitative relationship between exposure and response needs to be described. Toxicological, clinical, and epidemiological studies represent complementary approaches for obtaining the requisite evidence. The assessment of the effects of complex mixtures poses a difficult challenge for epidemiologists. Understanding the effects of exposure may require accurate assessment of concentrations and personal exposures to multiple agents and analytical approaches that can identify independent effects of single agents and the synergistic or antagonistic effects that may occur in mixtures. The array of epidemiological study designs for this task includes descriptive studies, cohort studies, and case-control studies, each having potential advantages and disadvantages for studying complex mixtures. This presentation considers issues related to exposure assessment and study design for addressing the effects of complex mixtures in indoor air.

Air Pollution, Indoor↗
PubMed1990

High-performance liquid chromatographic determination of etretinate and all-trans- and 13-cis-acitretin in human plasma.

A high-performance liquid chromatographic procedure is described for the simultaneous determination of etretinate (Tigason), all-trans-acitretin (Neotigason) and 13-cis-acitretin in human plasma. The compounds are extracted from the plasma with n-hexane under acidic conditions. Quantification is performed on a normal-phase column (CP-Spher Si, 5 microns), followed by UV detection at 350 nm. The limit of quantification is 3 ng/ml. The day-to-day precision was 6.7, 13.6 and 9.1% for etretinate (means = 53 ng/ml), all-trans-acitretin (means = 95 ng/ml) and 13-cis-acitretin (means = 149 ng/ml), respectively (n = 13 for each compound). The within-day precision of nine determinations was 3.2, 11.7 and 6.5%, respectively, with mean concentrations of 128.53 and 261 ng/ml, respectively. The method was also applied to the study of the long-term pharmacokinetic behaviour of etretinate in psoriatic patients previously treated with etretinate but now on therapy with all-trans-acitretin.

Acitretin↗
PubMed1990

Comparison of cyclosporin A measurement in whole blood by six different methods.

In a multicentre trial, we analyzed and compared the cyclosporin concentrations in whole blood specimens (trough values) from renal and bone marrow transplant patients using six different methods: high-performance liquid chromatography (n-butyl reversed-phase column) as reference, and 5 immunoassay procedures using monoclonal specific or non-specific antibodies, or polyclonal antibodies, for measuring cyclosporin with and without its cross-reacting metabolites. Results obtained by the 2 specific RIAs show good correlations (r-values of 0.945 and 0.921) versus the HPLC method, with average assay ratios of: 1.52 for 3H-RIA/HPLC and 1.26 for 125I-RIA/HPLC. In contrast, ratios for non-specific immunoassay/HPLC show multiple-fold overestimations of cyclosporin with very wide variations: 4.58 for 3H-RIA/HPLC, 3.97 for 125I-RIA/HPLC and 3.87 for fluorescence polarization immunoassay (FPIA)/HPLC. These findings indicate 1) that the 'specific' 3H- and 125I-RIAs can be used for cyclosporin measurements in whole blood using normal therapeutic ranges established by HPLC, 2) that the important disparity and variable overestimations by 'non-specific' RIA or fluorescence polarization immunoassay, compared with HPLC, require adjustments in therapeutic ranges, and 3) that the available 'specific' and 'non-specific' immunoassays should enable establishment of within-house reference 'therapeutic/toxic' ranges for cyclosporin in individual centres, based on these 'specific' versus 'non-specific' assays.

Antibodies, Monoclonal↗
PubMed1977

Lateral eye movements during verbal and nonverbal dichotic listening.

A dichotic listening paradigm was used to study the relation of eye movement to cerebral lateralization. The eye movements of right-handed subjects were recorded during verbal and nonverbal dichotic-listening tasks. Subjects given a verbal dichotic-listening task made significantly more rightward than leftward eye movements and showed more accuracy and speed in processing information presented to the right than to the left ear. Subjects given a nonverbal dichotic-listening task made significantly more leftward eye movements and processed better information presented to the left ear. These findings suggest a potentially strong link between the direction of lateral eye movement during dichotic listening tasks and left- and right-ear advantages in performance on such tasks. They also suggest that both eye movement and ear performance may be related to cerebral laterality and when examined in combination both could provide valuable information for the further study of hemispheric specialization.

Acoustic Stimulation↗
PubMedDate not supplied

A study of respiratory illnesses in infants and nitrogen dioxide exposure.

Toxicologic and epidemiologic studies have elevated concern that exposure to nitrogen dioxide (NO2) in outdoor and indoor air may increase the frequency and severity of respiratory infections. We have developed and implemented a prospective cohort study to test the hypothesis that exposure to NO2 increases the incidence and severity of respiratory infections during the first 18 mo of life. This study, which was based on extensive pilot research, was designed to address the potential limitations of misclassification, confounding, and inadequate power. Enrollment of 1,315 subjects has been completed. This paper reviews the methods used in the study, characteristics of the enrolled subjects, NO2 concentrations in the homes of study participants, and rates of illness occurrence.

Air Pollution, Indoor↗