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Biomedical subjects

F Stewart

Publications and source records attributed to F Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1999

Lessons to be learned: a case study approach: severe hyponatraemia induced by primary hypothyroidism and associated with possible increased hepatic sensitivity to thyroxine replacement.

The case is presented of a 74 year-old woman who was admitted with severe hypo-osmolar hyponatraemia associated with inappropriately raised urinary osmolality, and who was subsequently discovered to have primary hypothyroidism. A normal serum sodium concentration was restored by means of judicious fluid restriction and thyroid hormone replacement. Low dose thyroxine therapy led to rapid but modest increases in the serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP); both returned to normal over a period of three weeks. These sub-clinical enzyme changes may indicate tissue 'hyperthyroidism'; and in this case, the fact that they occurred acutely at only low doses of thyroxine possibly suggests an increased hepatic sensitivity to the hormone.

Aged↗
PubMed1999

Cloning, sequencing and functional expression of zebra (Equus burchelli) LH.

Although donkey luteinizing hormone exhibits a very high degree of amino acid sequence identity with horse LH, its FSH activity in non-equine species is tenfold lower. The coding regions of the common zebra (Equus burchelli) glycoprotein hormone alpha-subunit and LH beta-subunit transcripts were cloned by reverse transcription-PCR from pituitary gland RNA to investigate more precisely the structure-function relationships of this gonadotrophin family. Zebra LH was then expressed in COS-7 cells and its LH and FSH activities were assessed in a rat Leydig cell bioassay (for LH) and in a cell line stably expressing the human FSH receptor bioassay (for FSH). The recombinant zebra LH, although displaying LH activity similar to that of recombinant donkey and horse LH, had no detectable FSH activity. The LH amino acid sequences of these three species are very similar, leaving only very few amino acids as potential candidates to explain the difference in their FSH activities. Moreover, according to the difference in FSH bioactivity and to the percentage identity between the sequences, the common zebra is phylogenetically closer to the donkey than it is to the horse.

Amino Acid Sequence↗
PubMed1999

Cell proliferation patterns in the equine endometrium throughout the non-pregnant reproductive cycle.

Immunohistochemical detection of the proliferation marker Ki-67 antigen was used to monitor mitotic activity in the endometrium of mares. The monoclonal antibody MIB1 was validated for use on equine tissues by demonstrating its reaction with activated peripheral blood lymphocytes, and endometrial biopsies were recovered from 26 non-pregnant mares at selected stages during the reproductive cycle. The proportion of positively stained nuclei was counted in five random areas on each histological section to determine the percentage and type of proliferating cells. Multiplication rates in the types of cell found in the superficial strata, comprising the luminal epithelium, the epithelium of the gland necks and the stromal cells of the stratum compactum, were greatest during oestrus, presumably under the influence of oestrogens secreted by the growing ovarian follicles. In contrast, the mitotic activity in the cells of the deeper secretory portions of the endometrial glands was restricted to a brief phase between day 3 and day 7 of dioestrus, most likely as a delayed response to the decreasing oestrogen concentrations after ovulation. Some of the degenerate glands in subfertile mares did not follow this pattern of increased epithelial proliferation at that stage. After day 7 of dioestrus, the proliferation rates of cells in the endometrium decreased to basal values and remained low for as long as progesterone concentrations remained evaluated, even during prolonged dioestrus. The technique enabled characterization of normal cell proliferation patterns in the endometrium of mares and it will be a useful tool in the future for monitoring the endometrial responses of reproductively healthy and subfertile mares.

Analysis of Variance↗
PubMed1999

Cell proliferation patterns during development of the equine placenta.

Placentation involves considerable growth and reorganization of both maternal and fetal tissues. In this investigation, immunohistochemical localization of the proliferation marker Ki-67 antigen was used to monitor cell division during placentation in mares. Endometrial biopsies were obtained from eight mares between day 14 and day 26 of pregnancy and from eight anoestrous mares that had been treated with various combinations of progesterone and oestrogen. Samples of endometrium and fetal membranes were obtained from 19 mares carrying normal horse conceptuses between day 30 and day 250 of gestation and from three failing extraspecific donkey-in-horse pregnancies. Proliferation in the superficial strata of the endometrium was increased by day 18 of gestation and this effect could be mimicked by supplementing with oestradiol benzoate during the last 6 days of a prolonged period (18-36 days) of progesterone administration. Fetal chorionic girdle cells were proliferating vigorously at days 30-32 of gestation, but stopped dividing after they invaded the endometrium, while the trophoblast cells of the allantochorion showed an increase in mitotic activity after day 38. The luminal epithelium of the endometrium started to proliferate only after the primary villi of the true epitheliochorial placenta had been formed, and during days 58-70 this effect was seen only in the pregnant horn in which placentation was further advanced. During the second half of gestation, most of the mitotic activity was confined to the periphery of the microcotyledons which were still growing. In the donkey-in-horse pregnancies, proliferation rates of the maternal and fetal epithelial at day 70 of gestation were markedly reduced in areas of heavy endometrial lymphocyte infiltration and poor placentation. These results provide a basis for further studies on factors that influence invasive and non-invasive placentation.

Animals↗
PubMed1998

Promoting emergency contraception.

The use of available oral contraceptive agents for emergency contraception has been judged safe and effective by the U. S. Food and Drug Administration and other agencies. Yet implementation by physicians has been limited, and only a small percentage of women take advantage of this option each year. Lack of a specially packaged--and marketed--product for this indication has been a major barrier.

Contraceptives, Postcoital↗
PubMed1998

The genetics of epigenetics.

Cis-acting binding sites for transcription activators cannot explain the patterned expression of genes during development, nor a large range of phenomena that result from gene transplacement. Heritable states of transcriptional regression or activation sequences are influenced not only by the chromosomal context of the promoter but also by modifications of histones and DNA, and long-range interactions between distant chromosomal elements. The molecular dissection of these epigenetic phenomena has become an exciting topic of research, revealing highly conserved mechanisms at work in chromatin-mediated gene control.

Animals↗
PubMed1998

What does photodynamic therapy have to offer radiation oncologists (or their cancer patients)?

Major advances have recently been made in photodynamic therapy (PDT) for clinical application, including the development of more powerful photosensitizers and light sources and suitable light applicators. PDT is emerging as an attractive new form of cancer therapy, suitable for treating superficial lesions (less than 1 cm in depth) and carcinoma in situ, or as an adjuvant to surgery for more bulky disease. PDT is therefore complementary to radiotherapy which is better suited to treating larger tumours. There are some qualitative similarities between light distribution in tissue during superficial illumination and ionizing radiation dose distributions during external beam irradiation, or between interstitial PDT and brachytherapy, although the geometric scale is very different (visible light penetrates a maximum of 5-10 mm in tissue). The contribution of scattered light to tissue irradiance is much greater than for ionizing radiation and in situ light dosimetry is very important (although rather complicated) to ensure adequate illumination without over-treating. Dosimetry and treatment planning are highly advanced for ionizing radiation and are routine in all radiotherapy departments. Proper in situ light dosimetry and dose distribution calculation for PDT is in its infancy. Physicists have an important role to play in the further optimization of clinical PDT and much of the infrastructure and expertise present in the radiotherapy department is ideally suited to accommodate PDT. In this review, parallels and contrasts are made between PDT and ionizing radiation for both mechanistic and dosimetric aspects of the therapies. A summary of the most interesting clinical applications is also given.

Humans↗
PubMed1998

Transfer of a uterine lipocalin from the endometrium of the mare to the developing equine conceptus.

One of the major, progesterone-dependent proteins secreted into the uterine lumen of the mare is a 19-kDa lipocalin (P19). It associates strongly with the embryonic capsule that envelops the young horse conceptus in early gestation, suggesting that it may be involved in sustaining early development. However, it was not known whether the protein was transported through the capsule and/or trophoblast layer and into the yolk sac cavity. To address this question, polyclonal antisera were raised against a C-terminal peptide (based on the deduced amino acid sequence of P19) and a recombinant-derived P19 fusion protein. The antiserum raised against the C-terminal peptide recognized P19 on Western blots of denatured uterine secretions (subjected to SDS-PAGE), but it did not bind to the protein in tissue sections. However, the antiserum raised against the recombinant-derived fusion protein recognized P19 both on Western blots and in histological sections. Western blot analysis of tissues and fluids collected from early-pregnant mares demonstrated significant quantities of P19 in the endometrium and uterine secretions and in the embryonic capsule, the chorion, and the yolk sac fluid, showing that the protein is transferred through to the developing embryo. Concentrations of immunoreactive P19 declined during gestation so that, by Day 30, it had virtually disappeared from both maternal and fetal tissues and fluids. Immunohistochemical staining of endometrial biopsies collected during early pregnancy localized P19 to the glandular and luminal epithelia and to the lumina of the endometrial glands. The capsule and the trophoblast layer of the chorion from early (Days 16-17) horse conceptuses also stained positively with localization of P19 to the apical surface of the trophoblast cells. There was no detectable staining either in or on the embryonic disc. The presence of P19 in both the trophoblast layer and the yolk sac fluid suggests that P19 passes into the yolk sac fluid via trophoblast cells.

Animals↗
PubMed1998

Vaginal epithelioid angiosarcoma.

A case of epithelioid angiosarcoma of the vagina is described. Only five cases of angiosarcoma at this site have been reported, three of which followed radiotherapy for other gynaecological malignancies. None is described as an epithelioid angiosarcoma, an unusual and recently described variant which is readily confused with carcinoma. This is thought to be the first reported epithelioid angiosarcoma at this site and highlights the difficulties in diagnosis.

Aged↗
PubMed1998

Expression of epidermal growth factor and its receptor in equine placental tissues.

Northern blot and in situ hybridization techniques have demonstrated a marked increase in mRNA encoding epidermal growth factor (EGF) in the endometrium of mares, coincident with the start of interdigitation between the allantochorion and endometrium during placentation. In the present study, the unusually high EGF expression in the epithelium of the endometrial glands was shown to be maintained until at least day 250 of gestation (term = 320-340 days) in mares carrying normal horse conceptuses. However, in mares carrying failing donkey-in-horse pregnancies created by embryo transfer, EGF expression was severely retarded in those areas of the endometrium that were heavily infiltrated with lymphocytes and which showed a failure of placental development. Specific receptors for EGF were also detected in tissue homogenates from pregnant mares using 125I-labelled human EGF. Binding was high in the fetal membranes (allantochorion), both before implantation (days 30-34) and in the fully developed placenta (days 150-250), and was equivalent to the level of binding to homogenates of adult liver and kidney. Binding was much reduced in endometrial homogenates before implantation and from non-pregnant mares but increased after implantation to reach values equivalent to those exhibited by the fetal membranes. Scatchard analysis of displacement curves indicated a single class of high-affinity binding sites in the fetal membranes and pregnant endometrium sampled at day 150 of pregnancy and chemical cross-linking of the receptor-125I-labelled EGF complexes in fetal membranes revealed two radiolabelled bands of 170 kDa and 150 kDa. A large excess of insulin-like growth factor I (IGF-I) failed to displace any labelled EGF from the tissue homogenates. The marked and sustained upregulation of endometrial EGF expression during pregnancy in mares, and the presence of EGF receptors in the fetal allantochorion and maternal endometrium, suggest a possible role for EGF in the marked growth of these two tissues during placentation in equids.

Allantois↗
PubMed1998

Pre-school assessment project comparing assessment in the clinic or home.

From clinical experience it has been found that it is often difficult to assess young children in a clinical environment. Therefore, the aim of this project was to assess the communication of children in either the home or the clinic environment and to determine whether a more realistic impression of the child's language was obtained from home initial assessment. The results of this study suggest that for children who are 39 months old or less on the date of referral to speech and language therapy, a more representative sample of communication skills does emerge from initial assessment in the home environment. The conclusions drawn also indicate that the attendance rates for home assessments were significantly better than those for clinic appointments and this in turn meant that there was a subsequent cost saving to the department.

Child, Preschool↗
PubMed1997

Does tumour uptake of Foscan determine PDT efficacy?

Preferential retention of photosensitizers in tumours has always been one of the major goals in the search for new photosensitizers and has determined the design of clinical trials with respect to the interval between drug administration and illumination. The purpose of this study was to investigate the importance of tumour and plasma concentrations of Foscan (mTHPC, meta-tetrahydroxyphenylchlorin) in relation to PDT effect. Both pharmacokinetic and tumour response studies were carried out in mice bearing s.c. RIF1 tumours. mTHPC was injected in 1 or 2 doses of 0.3 mg x kg-1. For distribution studies, 14C-labelled mTHPC was given 5 min to 48 hr before determination of plasma and tumour drug levels. Non-labelled sensitizer was used to determine the PDT efficacy for illumination at 5 min to 48 hr after drug administration. PDT efficacy was greatest for illumination at 1 to 3 hr, and for an interval of 48 hr there was no significant tumour-growth delay. In contrast, mTHPC tumour drug levels reached a maximum 6 hr after injection and remained high for 48 hr. A comparison of pharmacokinetics and response studies revealed no significant correlation between tumour mTHPC levels and tumour response. There was, however, a significant correlation between plasma drug levels and tumour response for time intervals of 1 to 48 hr. This association may imply that PDT protocols should use shorter drug-light intervals in combination with lower drug doses. This would increase safety and decrease the extent and duration of normal tissue photosensitization.

Animals↗
PubMed1997

Elejalde syndrome: a case report.

Elejalde syndrome is a rare condition comprising a high birth weight, swollen globular body, a short neck with redundant skin folds, postaxial polydactyly, omphalocele, enlarged liver and kidneys, and renal dysplasia. The syndrome, also known as acrocephalopolydactylous dysplasia, is thought to be an autosomal recessive trait. We report on a liveborn infant with this condition.

Abnormalities, Multiple↗
PubMed1997

The multisite field trial of the consultation-liaison psychiatry assessment instrument.

A multisite field trial was conducted at 11 institutions to test the clinical reliability of a 29-item consultation-liaison (C-L) psychiatry assessment instrument. Twenty-five raters viewed videotapes of two "trainees" conducting clinical interviews with a simulated patient. One trainee was a medical student, the other was a fellow in psychiatry. Raters completed the 29-item assessment instrument for each trainee. The mean value scores reflected the skill of each trainee. The medical student had a mean score of 1.93, whereas the C-L fellow had a mean score of 3.13 which parallels the expected level of skill for the two interviewers. Eighty-six percent of the items (25/29) had a standard deviation (SD) of less than 1.0. Each of the remaining four items (14%) had a SD minimally greater than 1.0. These results reflect clear wording of items with measurable parameters defined for assessing trainees' skills. The authors present different uses for the assessment instrument, including giving feedback to trainees regarding interviewing techniques and skills; setting "gold" and "lead" standards for clinical C-L interviewing skills; and training supervisors in evaluation using a standardized assessment instrument.

Curriculum↗
PubMed1997

Expression of horse and donkey LH in COS-7 cells: evidence for low FSH activity in donkey LH compared with horse LH.

Horse (Equus caballus) luteinizing hormone (eLH) and chorionic gonadotrophin (eCG), which have the same amino acid sequence, are unusual in that, although they express only LH activity in equids, they express dual LH and FSH activities in all other species tested. Donkey (Equus asinus) LH (dkLH) and CG (dkCG), which also share an identical peptide backbone, have been less well characterized and conflicting results concerning their FSH activity in heterologous species have appeared in the literature. In order to assess and compare the intrinsic LH and FSH activities of the horse and donkey LHs in heterologous species, recombinant eLH (r.eLH/CG) and recombinant dkLH (r.dkLH/CG) were expressed, for the first time, in COS-7 cells. Their LH activities were assessed in a rat Leydig cell bioassay, and their FSH activities were estimated in a bioassay using Y1 cells stably expressing the human FSH receptor. Human CG (hCG) was expressed (r.hCG) and analysed in the same system. The results showed that, whereas r.dkLH/CG was about twice as active as r.eLH/CG in the LH bioassay, it was five times less active than r.eLH/CG in the FSH bioassay; r.hCG was about three times less active than r.eLH/CG in the LH bioassay but was completely inactive in the FSH bioassay. These results confirm that dkLH/CG possesses significant FSH activity in heterologous species that is not attributable to contamination with FSH.

Animals↗
PubMed1997

Evidence that the alpha-subunit influences the specificity of receptor binding of the equine gonadotrophins.

Horse LH/chorionic gonadotrophin (eLH/CG) exhibits, in addition to its normal LH activity, a high FSH activity in all other species tested. Donkey LH/CG (dkLH/CG) also exhibits FSH activity in other species, but about ten times less than the horse hormone. In order to understand the molecular basis of these dual gonadotrophic activities of eLH/CG and dkLH/CG better, we expressed, in COS-7 cells, hybrids between horse and donkey subunits, between horse or donkey alpha-subunit and human CG beta (hCG beta), and also between the porcine alpha-subunit and horse or donkey LH/CG beta. The resultant recombinant hybrid hormones were measured using specific FSH and LH in vitro bioassays which give an accurate measure of receptor binding specificity and activation. Results showed that it is the beta-subunit that determines the level of FSH activity, in agreement with the belief that it is the beta-subunit which determines the specificity of action of the gonadotrophins. However, donkey LH/CG beta combined with a porcine alpha-subunit exhibited no FSH activity although it showed full LH activity. Moreover, the hybrid between horse or donkey alpha-subunit and hCG beta also exhibited only LH activity. Thus, the low FSH activity of dkLH/CG requires an equine (donkey or horse) alpha-subunit combined with dkLH/CG beta. These results provide the first evidence that an alpha-subunit can influence the specificity of action of a gonadotrophic hormone.

Animals↗
PubMed1997

Preventing unintended pregnancy: the cost-effectiveness of three methods of emergency contraception.

OBJECTIVES: This study examined the cost-effectiveness of emergency contraceptive pills, minipills, and the copper-T intrauterine device (IUD) as emergency contraception. METHODS: Cost savings were modeled for both (1) a single contraceptive treatment following unprotected intercourse and (2) emergency contraceptive pills provided in advance. RESULTS: In a managed care (public payer) setting, a single treatment of emergency contraception after unprotected intercourse saves $142 ($54) with emergency contraceptive pills and $119 ($29) with minipills. The copper-T IUD is not cost-effective as an emergency contraceptive alone, but savings quickly accrue as use continues. Advance provision of emergency contraceptive pills to women using barrier contraceptives, spermicides, withdrawal, or periodic abstinence saves from $263 to $498 ($99 to $205) annually. CONCLUSIONS: Emergency contraception is cost-effective whether provided when the emergency arises or in advance to be used as needed. Greater use of emergency contraception could reduce the considerable medical and social costs of unintended pregnancies.

Contraceptives, Oral, Hormonal↗