PubMed Health⌕ Search

Biomedical subjects

H Gregory

Publications and source records attributed to H Gregory.

At least 19 recordsLinked to original sources
PubMed2001

Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach.

We have developed a computer assisted learning package for teaching clinical medical students about familial breast cancer. It explains the principles of genetic predisposition to breast cancer, the association with other cancers, the principles of family history taking and confirmation, risk assessment and possible interventions. Clinical medical students were randomised to either conventional teaching or CAL, 48 students attended the evaluation session. Students randomised to conventional teaching received a 20 min mini-lecture, those randomised to CAL completed the package with technical, but not academic support available. At the end of the intervention both groups of students completed a short written assessment of acceptability and knowledge and understanding of breast cancer genetics. There was no significant difference between the CAL and mini-lecture groups in terms of marks or acceptability. Thus CAL appears to be an acceptable and effective method of teaching clinical medical students about familial breast cancer. Although time consuming to develop, CAL can be used in a variety of settings to increase curriculum flexibility. Methods of motivating students to complete the CAL, and of providing educational support are being explored.

Breast Neoplasms↗
PubMed1999

Routine antenatal Rhesus D immunoglobulin prophylaxis: the results of a prospective 10 year study.

OBJECTIVE: To assess the clinical and financial impact, and identify the problems, of providing routine antenatal RhD immunoglobulin prophylaxis for Rhesus D negative nulliparae. DESIGN: A retrospective (1980-1986) and prospective (1987-1996) comparison between two similar populations, one population with nulliparae offered routine RhD immunoglobulin 500 IU prophylaxis at 28 and 34 weeks of gestation part way through the study period, and the other population not offered prophylaxis at any time. SETTING: Obstetric units in two counties (three health districts) with similar annual numbers of maternities and the Regional Blood Transfusion Service antenatal serology laboratory. PARTICIPANTS: Non-sensitised Rhesus D negative pregnant nulliparae. INTERVENTIONS: Intramuscular RhD immunoglobulin 500 IU at 28 and 34 weeks of gestation to eligible women booked for confinement in one county; the intervention not offered in the other county. MAIN OUTCOME MEASURES: 1. Rhesus D sensitised second pregnancy rate; 2. success in providing prophylaxis to eligible women; 3. serology laboratory activity changes; 4. potential savings from the prophylaxis programme. RESULTS: Prophylaxis significantly reduced iso-immunisation in the next pregnancy when compared with historical (OR 0.28, CI 0.14-0.53; P < 0.0001) and contemporary controls (OR 0.43, CI 0.22-0.86; P = 0.02). However, success at achieving comprehensive prophylaxis was disappointing, with only 89% of eligible women receiving the first injection, 74% both injections, and for only 29% were both at the correct gestation. Fifty-two percent of women delivered after 40 weeks of gestation, beyond the period of adequate prophylaxis protection. The savings in antenatal interventions, neonatal care and possible long term ill-health that result from very preterm birth should be considerable. CONCLUSION: Routine prophylaxis for nulliparae significantly reduces the incidence of sensitised next pregnancies with consequent savings, and its adoption nationwide should be encouraged. A programme offering antenatal prophylaxis for all Rhesus D negative women is unlikely to be economic. Improvement in uptake of prophylaxis is needed; alternative administration strategies should be explored.

Female↗
PubMed1999

Efficacy of early diagnosis and treatment in women with a family history of breast cancer. European Familial Breast Cancer Collaborative Group.

BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan-Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first ("prevalence") round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of "breast awareness" as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.

Adult↗
PubMed1996

Ascertainment of familial ovarian cancer in the Aberdeen Genetic Clinic.

Ovarian cancer is the fifth most common malignancy in women in the UK. Patients with a family history including ovarian cancer make up nearly 15% of family cancer referrals to the Genetic Clinic in Aberdeen. To date, only one pedigree has been suitable for linkage studies, which has enabled us to target screening more accurately at those people at highest risk. Following discovery of a strong candidate for the BRCA1 gene, direct mutation testing may soon be possible. People who seek testing will require further counselling. Therefore we anticipate an increased demand on both clinical and laboratory resources, but more accurate ascertainment of high risk subjects should lead to more appropriate targeting of screening services.

Adult↗
PubMed1992

Neutrophil-activating proteins in psoriasis.

Neutrophil accumulation in the epidermis is a histologic characteristic of psoriasis. We addressed the question: What is the major protein-like chemotactic principle responsible for neutrophil accumulation? Purification of proteinaceous neutrophil chemoattractants from extracts obtained from psoriatic scales by multistep high-performance liquid chromatography (HPLC) yielded three biochemically distinct polypeptides with potent neutrophil chemotactic activity. Aminoterminal amino acid sequence analysis of the quantitatively major neutrophil attractant revealed the sequence ELRXQXIKTYSK, which is identical to that of a 69 residue form of neutrophil-activating peptide-1/interleukin 8 (NAP-1/IL-8). The second major attractant showed the sequence XXVATELRXQXL . . ., which is identical to that of the gene product of the oncogene "gro" as well as "melanoma growth stimulatory activity, MGSA," whereas the third and minor neutrophil chemotaxin has an NH2-terminal sequence identical with NAP-1/IL-8. Estimation of NAP-1/IL-8-related proteins and gro/MGSA by HPLC combined with bioassay revealed a mean of 3.3 +/- 1.7 ng NAP-1/IL-8-related proteins (n = 11) and 3.2 +/- 1.9 ng gro/MGSA (n = 11) per 1 mg psoriatic scales. In normal heel callus (n = 8), these neutrophil attractants were found at concentrations below 0.02 +/- 0.01 ng/mg. The finding of more than 150-times increased amounts of both NAP-1/IL-8 and gro/MGSA in lesional psoriasis material suggest that these mitogenic as well as neutrophil- and lymphocyte-chemotactic compounds may play an important role in the pathogenesis of psoriasis.

Amino Acid Sequence↗
PubMed1992

Evolution of bereavement counselling in sudden infant death syndrome, neonatal death and stillbirth.

There have been changing attitudes to death and grief in Western society in recent centuries. During the twentieth century complex medical and social changes have resulted in changing attitudes to and experiences with death. Specifically, the impact of death in childhood is reviewed. In recent decades sudden and unexpected death associated with stillbirth, the newborn and infants appears to have a more profound affect on the bereaved parents than in the past when the overall death rates in childhood were higher. The evolution of parent support groups developed since the 1960s to alleviate the psychological trauma of unexpected and sudden death in childhood has been traced. These groups were founded initially for support with sudden infant death syndrome and later extended to include families with stillbirth and neonatal death.

Attitude to Death↗
PubMed1990

Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence.

A potent inhibitor of human leukocyte elastase (EC 3.4.21.37) and porcine pancreatic elastase (EC 3.4.21.36) was purified to homogeneity from human horny layers. It inhibits human leukocyte elastase and porcine pancreatic elastase in a 1:1 molar ratio and shows equilibrium dissociation constants of 6 x 10(-10) M and 1 x 10(-9) M, respectively. Inhibition of plasmin, trypsin, alpha-chymotrypsin, and cathepsin G was not observed. This inhibitor proved to be an acid stable basic peptide with an isoelectric point of 9.7. The complete amino acid sequence appears to be unique with 38% homology to the C-terminal half of antileukoprotease. The sequence shows that the inhibitor is composed of 57 amino acids and predicts a Mr of 7017. The high affinity as well as the apparent specificity for elastases suggests a functional role in preventing elastase-mediated tissue proteolysis. It is suggested that the term "elafin" be used to designate this inhibitor.

Amino Acid Sequence↗
PubMed1989

Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.

Animals↗
PubMed1989

Effect of orally-administered epidermal growth factor on intestinal iron absorption and mucosal permeability.

A progressive increase in intestinal 59Fe3+ absorption was observed on oral feeding of mice with physiological doses of EGF/UGO. Maximal changes were apparent after 3d and appeared to be dose-dependent. In addition to a small increase in intestinal cell proliferation, as reflected by increased ornithine decarboxylase activity, EGF/UGO-feeding increased mucosal permeability (evaluated with [51Cr]-EDTA): the latter could account for the increase in iron absorption. Sialoadenectomy, to remove the major source of endogenous EGF/UGO, had no appreciable effect on the intestinal absorption of iron.

Administration, Oral↗
PubMed1989

The constitution and properties of phosphorylated and unphosphorylated C-terminal fragments of progastrin from dog and ferret antrum.

Antibodies to the extreme C-terminal tryptic (nona-) peptide fragment of porcine progastrin have been used in radioimmunoassay to identify progastrin fragments in dog, ferret and pig antral mucosa extracts and to monitor their purification. In addition to previously characterised phosphorylated and unphosphorylated C-terminal tryptic peptides of porcine progastrin a minor form corresponding to the C-terminal octapeptide (i.e. des-Ser C-terminal nonapeptide) was isolated and characterised. The latter form together with phosphorylated and unphosphorylated forms of the nonapeptides were also isolated and chemically characterised from dog antrum, and the unphosphorylated nonapeptide was characterised from ferret antrum. The primary amino acid sequences of the dog, ferret and pig nonapeptides were identical. In ferret the unphosphorylated nonapeptide predominated, and in dog the phosphorylated form predominated; in pig both forms of the nonapeptide were well represented. Intact progastrin was identified in gel filtration eluates of extracts of all 3 species, but occurred only in relatively low concentrations. The nonapeptides did not stimulate acid secretion in the conscious gastric fistula rat and they did not modify the acid response to G17. Phosphorylation of progastrin-derived peptides is evidently well conserved across a range of species even though there appear to be differences in the relative proportions of phosphorylated and unphosphorylated forms.

Animals↗
PubMed1989

Epidermal and transforming growth factor alpha in patients with breast tumours.

Measurements of transforming growth factor alpha (TGF-alpha) in cancer patients have produced variable results. We have now used a specific radioimmunoassay (RIA) and a mitogenic assay to evaluate TGF-alpha content of tumour and urine samples separated by an analytical HPLC system. Urine samples from patients with breast tumours and from age matched controls gave TGF-alpha amounts ranging from 0 to 61.5 ng 24 h-1 compared to urogastrone epidermal growth factor figures of 3.0-26.2 micrograms 24 h-1. The quantities of TGF-alpha in patient and control groups were not significantly different. The majority of breast tumour extracts contained mitogenic material eluting from the HPLC system at the TGF-alpha calibration point. Measurement by RIA of combined samples from each group showed that steroid receptor positive tumours had a mean figure of 14.8 ng g-1 tissue and steroid receptor negative 7.4 ng g-1. Receptor positive tumours from patients treated with an antioestrogen, tamoxifen citrate (Nolvadex), had 0.16 ng g-1. Thus TGF-alpha is found in tumours as a biologically active entity and in quantities sufficient to promote cell division. In addition the observation that tamoxifen causes a significant reduction in the content of TGF-alpha may be an additional beneficial action.

Breast Neoplasms↗
PubMed1989

Is polyamine synthesis involved in the proliferative response of the intestinal epithelium to urogastrone-epidermal growth factor?

1. Intestinal epithelial cell proliferation was measured in rats maintained on total parenteral nutrition (TPN), in TPN rats given 300 micrograms of recombinant human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) day-1 kg-1, and in further groups given URO-EGF and difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase (ODC). 2. URO-EGF significantly increased intestinal cell proliferation throughout the gastrointestinal tract. The proliferative response of the colon was particularly pronounced. 3. DFMO reduced the proliferative effect of urogastrone in the stomach and small intestine. DFMO also reduced URO-EGF-stimulated intestinal cell proliferation in the colon, but to a lesser extent. 4. It is concluded that ODC is essential for effecting the proliferative response of the stomach and small intestine to URO-EGF, but this role may be less important in the colon.

Animals↗
PubMed1989

Human amniotic fluid urogastrone (epidermal growth factor) and fetal lung phospholipids.

Urogastrone was measured by radioimmunoassay in amniotic fluid obtained from 186 complicated pregnancies at 22 to 40 weeks gestation. Amniocentesis was performed for a variety of indications to obtain information about fetal lung maturity or bilirubin levels before induction of labour or caesarean section in various obstetric conditions. In 114 specimens lung phospholipids extracted from amniotic fluid were also assayed using two-dimensional thin layer chromatography. Urogastrone concentrations became measurable at approximately 30 weeks gestation and thereafter there was a 10-fold rise in concentrations between 30 and 40 weeks gestation. This increase in urogastrone concentration was positively correlated with a rise in phosphatidylcholine and phosphatidylglycerol concentrations and the phosphatidylcholine (lecithin)/sphingomyelin ratio (L/S). These results are compatible with a role for urogastrone in human fetal lung maturation.

Amniotic Fluid↗
PubMed1988

The human gastrin precursor. Characterization of phosphorylated forms and fragments.

There is a potential phosphorylation site in the C-terminal region of the precursor for the acid-stimulating hormone gastrin, which is immediately adjacent to an important cleavage point. In the present study we have sought to identify, separate, quantify and characterize phosphorylated and unphosphorylated forms of human progastrin and its fragments. Identification was made by two radioimmunoassays: (a) a novel assay employing an antibody raised to intact human progastrin; and (b) an assay using antibody reacting with the C-terminal tryptic fragment of human progastrin, as well as progastrin itself. Two forms of human progastrin isolated from a gastrinoma were separated by ion-exchange h.p.l.c., and had similar elution positions on reverse-phase h.p.l.c. and on gel filtration. The more acidic peptide contained close to equimolar amounts of phosphate. On trypsinization, peptides were released that co-eluted on ion-exchange h.p.l.c. with, and had the immunochemical properties of, naturally occurring C-terminal fragments of progastrin. One of the latter was isolated and shown by Edman degradation after derivatization with ethanethiol to have the sequence Ser (P)-Ala-Glu-Asp-Glu-Asn. Similar peptides occur in antral mucosa resected from ulcer patients. The unphosphorylated forms of progastrin predominated, whereas the phosphorylated forms of the C-terminal fragments were predominant. This distribution could be explained by preferential cleavage of phosphorylated progastrin. We conclude that in human progastrin, Ser-96 can occur in the phosphorylated form; this residue immediately follows a pair of basic residues (Arg-Arg) that are cleaved during synthesis of the biologically active product.

Amino Acid Sequence↗