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Biomedical subjects

E L Hansen

Publications and source records attributed to E L Hansen.

At least 19 recordsLinked to original sources
PubMed2001

Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions.

A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different alpha-oxygen-substituted, racemic aldehydes were initially transformed by asymmetric HWE reactions into mixtures of two major alpha,beta-unsaturated esters, possessing opposite configurations at their allylic stereocenters as well as opposite alkene geometry. Subsequently, these isomeric mixtures of alkenes could be subjected to palladium-catalyzed allylic substitution reactions with carbon, nitrogen, and oxygen nucleophiles. In this latter step, the respective (E) and (Z) alkene substrate isomers were observed to react with opposite stereospecificity: the (E) alkene reacted with retention and the (Z) alkene with inversion of stereochemistry with respect to both the allylic stereocenter and the alkene geometry. Thus, a single gamma-substituted ester was obtained as the overall product, in high isomeric purity. The method was applied to a synthesis of a subunit of the iejimalides, a group of cytotoxic macrolides.

Journal Article↗
PubMed2001

Lamotrigine plasma levels reduced by oral contraceptives.

Although it is known that the use of oral contraceptives (OC's) can induce glucuronide conjugating enzymes, currently no data exists as to the potential that the elimination of the glucuronidated drug lamotrigine (LTG) is increased by OC's. We present seven cases in whom the plasma levels of LTG were significantly decreased by OC's (mean 49%, range 41-64%). The interaction was of clinical relevance in most of the patients who either experienced increased seizure frequency/recurrence of seizures after OC's had been added, or adverse effects following withdrawal of OC's.

Adolescent↗
PubMed1997

Prospectively measured red cell folate levels in methotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects.

OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.

Aged↗
PubMed1996

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants.

This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of 6 months duration, 109 patients with active RA were randomly assigned to either treatment with or without a specialized diet. The energy consumption was adjusted to normal standards of body weights and the intake of fish meals and antioxidants were increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, number of swollen joints, pain status, and reduced cost of medicine, while doctors global assessment, laboratory data, X-ray, and daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.

Arthritis, Rheumatoid↗
PubMed1995

Simultaneous determination of lofepramine and desipramine by a high-performance liquid chromatographic method used for therapeutic drug monitoring.

A simple reversed-phase HPLC method with ultraviolet detection for the simultaneous measurement of lofepramine and desipramine is described. Only a single alkaline extraction was used, with clomipramine as internal standard. The column used was a Supelco PCN column, and the mobile phase was acetonitrile-methanol-0.015 M phosphate buffer (120:35:100, v/v). The average recoveries were 78.8% for desipramine and 103.8% for lofepramine, and limits of quantitation were 25 and 5 nmol/l, respectively. The inter-assay C.V.s for lofepramine and desipramine were 6.0 and 7.6%, respectively. The method is specific and has excellent accuracy, and has been used for therapeutic drug monitoring of patients with depressions treated with lofepramine. Mean steady-state plasma concentrations found for lofepramine and desipramine were 8.5 +/- 6.1 and 123.6 +/- 120.6 nmol/l, respectively. It is concluded that lofepramine in itself has an antidepressive effect.

Chromatography, High Pressure Liquid↗
PubMed1980

Gas chromatographic determination with flash methylation of palmitic acid in amniotic fluid in prediction of fetal lung maturity.

A new method for determination of palmitic acid in amniotic fluid was developed. The dipalmitoyl lecithin was hydrolysed, and after extraction the palmitic acid was flash methylated in the injector of the gas chromatograph. The between batch coefficient of variation was 6.0% at 40 and 70 mumol/l of palmitic acid concentrations in 500 microliters amniotic fluid. The accuracy of the method was demonstrated by linearity, recovery and correlation studies. The correlation coefficient was 0.98 between the new and bortrifluoride methylating method. The concentrations of lecithin and palmitic acid in amniotic fluid showed a correlation coefficient of 0.97. If the concentration of palmitic acid falls below 80 mumol/l respiration distress syndrome is likely. The new method was simple and easy to carry out and could be adjusted for haemoglobin contamination of the amniotic fluid. It was concluded that the determination of palmitic acid in amniotic fluid was a reliable method for the assessment of fetal lung maturity that could replace the determination of lecithin concentration.

Amniotic Fluid↗
PubMed1975

Artificial hyperventilation during 21 years in three cases of complete respiratory paralysis.

Three patients with paralytic poliomyelitis have been ventilated via tracheostomy with uncuffed silver cannula for 21 years, with high tidal volumes of atmospheric air (8.3, 7.2, and 5.4 ml/kg b.wt.), at a frequency of 20, passive expiration, and without periodic hyperinflation. No pulmonary complications were seen during the whole of this period. The total compliance was significantly decreased. The pulmonary physiological shunt relative to the total pulmonary blood flow (Qs/Qt) was slightly increased. PaO2 was nevertheless normal, probably due to a high alveolar PO2 caused by the hyperventilation. The physiological dead space realtive to the tidal volume (VD/VT) was within the noraml range, but VD was high in one case. Two of the patients disclosed an extremely low CO2 production and a PaCO2 averaging 12 mmHg, with small fluctuations during a 24-hour study. This profound respiratory alkalosis was only partly compensated in the arterial blood (pH: 7.54 and 7.50), suggesting a new state of acid-base equilibrium. The cerebrospinal fluid lactate was significantly increased to about 4 mmol/l, but the patients revealed no signs of impaired cerebral function. A reduction of the degree of hypocapnia by the use of a mechanical dead space is recommended.

Adult↗