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S Evans

Publications and source records attributed to S Evans.

At least 271 records · Page 15Linked to original sources
PubMed1989

Characterization of the major metabolites of flavone acetic acid and comparison of their disposition in humans and mice.

Flavone acetic acid represents a novel chemical structure currently undergoing clinical investigation. Broad spectrum activity has been observed in preclinical animal screens, but at doses close to toxic in mice. Phase I clinical trials have established that equivalent plasma drug levels can be achieved in humans, but to date Phase II trials have not demonstrated significant activity in a range of tumor types. Little is known about the drug's biotransformation, although metabolites have been implicated in proposed mechanisms of action. In this paper, we have purified the two major human metabolites present in urine (also the only two metabolites detected in plasma) and characterized their structure, chemical properties, activity, and pharmacokinetics. Metabolite 1 (M1) was a glucuronide conjugated to the 8-acetic acid grouping (Mr 456), was chemically labile, and showed a strong tendency to undergo chemical rearrangement at mildly alkaline pH. Metabolite 2 (M2) was also a glucuronide (Mr 456) but appeared to be an unusual isomer of M1. Both were noncytotoxic. In patients, biotransformation represented the predominant mechanism of drug clearance with as much as 80% of a low dose (0.5 g/m2) recovered in urine as M1 and M2 after only 6 h. At high dose (4.8 to 8.6 g/m2, 1- to 6-h infusion) the appearance of peak concentrations of metabolites in plasma and urine was delayed, apparently due to saturation of glucuronidation pathways. This resulted in an overall reduction in drug clearance by 3- to 4-fold. Mice cleared flavone acetic acid much more slowly than patients (289 ml/h/m2 after 600 mg/m2 i.p. versus 2.3 liters/h/m2 after 4.8 g/m2-1-h i.v. infusion) without producing M1 or M2. A different metabolite, exhibiting characteristics of a conjugate, was detected at low concentrations in plasma, tissues, and tumor. Extensive metabolism to inactive products followed by their rapid clearance may contribute to the lack of activity so far seen in humans.

Animals↗
PubMed1989

In vitro photodynamic therapy of human lung cancer: investigation of dose-rate effects.

The influence of light dose-rate delivery was studied in human lung adenocarcinoma A549 cells treated with hematoporphyrin derivative (Photofrin II)-based photodynamic therapy. Clonogenic cell survival curves were generated for cells treated for 2 h with 25 micrograms/ml of Photofrin II followed by exposure to light delivered at 0.3, 0.15, 0.075, or 0.0375 milliwatts/cm2. Cellular sensitizer levels, as determined by fluorescence measurements, remained constant over the entire time course of all light exposures. As the dose rate of light delivery was decreased, a significant increase in cell survival was observed at equal light energies (225 mJ/cm2). The enhancement in survival from the highest to the lowest dose rate used was 1.6-fold (at the 50% survival level). These findings may have important clinical implications relating to photodynamic therapy of tumors and may provide a partial explanation for treatment failure.

Adenocarcinoma↗
PubMed1989

Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients.

4-Hydroxyandrostenedione (CGP32349; 4-OHA) is a clinically effective treatment for advanced postmenopausal breast cancer by both the parenteral and p.o. routes, as a result of its inhibition of aromatase and consequent suppression of plasma estrogen levels. Thirty patients were randomized to treatment with 250 mg 4-OHA orally once, twice, and 4 times daily for 2 weeks and 29 of these plus a further 11 patients were then randomized to treatment with 250 or 500 mg i.m. every 2 weeks to determine the optimal dose for each route according to the suppression of serum estradiol levels. There was no significant difference between the 3 oral doses in their suppression of estradiol levels indicating that the maximum required p.o. dose of 4-OHA is probably 250 mg daily. Suppression by the parenteral dose of 250 mg every 2 weeks was marginally suboptimal but clinical considerations of response and tolerability indicate this as the optimal dose for i.m. injection. 4-OHA had no effect on serum levels of androstenedione, testosterone, or 5 alpha-dihydrotestosterone when given by either route but p.o. treatment with 4 doses of 250 mg daily reduced sex hormone-binding globulin levels by a mean of 34%. Serum levels of estrone as measured by gas chromatography-mass spectrometry were suppressed to approximately 40% of baseline by parenteral treatment. The half-life of 4-OHA p.o. was approximately 3 h, whereas the apparent half-life of injected drug was between 5 and 10 days after a more rapid clearance during the first 4 days after injection.

Administration, Oral↗
PubMed1989

The Saccharomyces cerevisiae RAD2 gene complements a Schizosaccharomyces pombe repair mutation.

Two Saccharomyces cerevisiae genes necessary for excision repair of UV damage in DNA, RAD1 and RAD2, were introduced individually, on a yeast shuttle vector, into seven Schizosaccharomyces pombe mutants - rads 1, 2, 5, 13, 15, 16 and 17. The presence of the cloned RAD1 gene did not affect survival of any of the S. pombe mutants. The RAD2 gene increased survival of S. pombe rad13 to near the wild-type level after UV irradiation and had no effect on any of the other mutants tested. S. pombe rad13 mutants are somewhat defective in removal of pyrimidine dimers so complementation by the S. cerevisiae RAD2 gene suggests that the genes may code for equivalent proteins in the two yeasts.

DNA Damage↗
PubMed1989

Potentiation of phototherapy cytotoxicity with light scattering media.

Lung cancer cells are susceptible to photodynamic therapy (PDT) using 630 nm light and dihematoporphyrin ether (DHE). A light scattering media, intralipid (IL), was compared to balanced salt solution (PBS) for PDT of A549 human lung cancer cells. Differences in cellular DHE content after IL or PBS exposure were determined. Cells were incubated in 25 micrograms/ml DHE for 2 hr and then incubated in various concentrations of IL or PBS at room temperature for 2.5 to 10.0 min. Significant amounts of DHE were lost from IL-incubated cells compared to cells incubated in PBS. After 5 min in 1% IL, cellular DHE content was 0.32 +/- 0.04 microgram DHE/10(6) cells compared to 0.56 +/- 0.11 microgram DHE/10(6) cells in PBS-incubated cells (P less than 0.05). Despite this, superior PDT cytotoxicity was noted when cells were treated in IL with energy densities greater than or equal to 105 mJ/cm2. At an energy density of 210 mJ/cm2, the survival fraction (SF) of cells treated in 1% IL was 0.004 +/- 0.001 compared to 0.071 +/- 0.022 in PBS-treated cells (P less than 0.05). SF was dependent upon the IL concentration with the greatest cell killing noted with 1% IL. An apparent loss of cellular DHE ("DHE washout") was confirmed by demonstration of a higher SF of cells incubated in IL, rinsed, and subsequently PDT-treated in PBS with 157.5 mJ/cm2 (SF = 0.85 +/- 0.11) compared to cells incubated and treated in PBS (SF = 0.50 +/- 0.03, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗
PubMed1989

Pulmonary vasculitis associated with cholangiocarcinoma of liver.

A 62 year old woman presented with an acute pulmonary vasculitis which responded to treatment with oral steroids. Investigations over one year revealed a cholangiocarcinoma of the liver. The association of vasculitis with neoplastic diseases remains a diagnostic challenge.

Acute Disease↗
PubMed1989

International Collaborative Effort (ICE) on birthweight; plurality; and perinatal and infant mortality. I: Methods of data collection and analysis.

This paper describes the collection and analysis of data by a group of international collaborators (International Collaborative Effort on Perinatal and Infant Mortality) interested in comparative studies on birthweight distributions and reproductive outcome. This is the first of a series of reports on the results of these studies. It gives an account of the countries or states involved, and the collection and characteristics of the data. The countries and states included sixteen of the United States, plus England and Wales, Denmark, Bavaria and North Rhine-Westphalia from the Federal Republic of Germany, Israel, Japan, Norway, Scotland, and Sweden. The data comprised birthweight distributions in 500-gram groups for all births and for singletons separately, for livebirths, stillbirths, first week deaths and, where available, late neonatal and infant deaths, from 1970 up to 1985.

Birth Weight↗
PubMed1989

International Collaborative Effort (ICE) on birthweight; plurality; and perinatal and infant mortality. II: Comparisons between birthweight distributions of births in member countries from 1970 to 1984.

Member states of the International and Collaborative Effort (ICE) are the United States of America, England and Wales, Denmark, Bavaria and North Rhine-Westphalia of the Federal Republic of Germany, Israel, Japan, Norway, Scotland and Sweden. The group has collected, analysed and compared distributions of birthweight for member countries, where available from 1970 onwards, for singleton and all livebirths, stillbirths, early and late neonatal and postneonatal deaths. The present paper is an account of the differences in birthweight distributions, and trends over time seen between and within countries, for livebirths and stillbirths. The major findings are the relative robustness over time of the parameters which characterize the distribution of birthweight within countries, and the marked and consistent differences between these distributions in different countries.

Birth Weight↗
PubMed1989

Herbal teas.

Explore the source record for details and available documents.

Beverages↗
PubMed1989

Reconstruction of a functional hemidiaphragm with use of omentum and latissimus dorsi flaps.

After ablative surgery that involves the diaphragm, autologous tissue is the material of choice for reconstruction--particularly if adjuvant radiotherapy is planned. Latissimus dorsi muscle and omentum are reliable sources of such tissue. A case is reported describing a method of diaphragm reconstruction after resection by mobilization of the upper latissimus dorsi and passing the free muscle portion over the residual costal margin to form a neodiaphragmatic leaflet. Suture of the transposed latissimus free end to the residual diaphragm tendon and the use of omentum to fill defects residual after muscle transposition were used to complete the reconstruction.

Adult↗
PubMed1988

Factors affecting the uptake of screening for neural tube defect.

A questionnaire concerning pregnant women's knowledge of, and attitudes to, serum alpha fetoprotein (AFP) screening for spina bifida was sent to all pregnant women receiving a health education leaflet on AFP screening who booked at the Birmingham Maternity Hospital in the first quarter of 1984. The majority said that they would accept the test, and subsequently did so. This suggests that low uptake of the test is not a result of patients' resistance, and the results indicated that the provision of early information about the test is likely to improve uptake and decrease anxiety. With the increasing clinical usefulness of the AFP test, routine screening of pregnant women with an 'opt-out' system is becoming clinically desirable, and the survey suggests that it would be acceptable to the patients.

Attitude to Health↗
PubMed1988

A clinical tool for nursing.

The background of this software tool stretches back nearly 20 years to original systems techniques developed within an area of computer science called artificial intelligence. Research reflects efforts to capture the reasoning processes of healthcare experts.

Clinical Protocols↗