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Biomedical subjects

S Monaghan

Publications and source records attributed to S Monaghan.

16 recordsLinked to original sources
PubMed2000

A longitudinal study of HPV detection and cervical pathology in HIV infected women.

OBJECTIVE: To monitor the presence and persistence of high risk (HR) human papillomavirus (HPV) in cervical brushings from HIV infected women. METHODS: Prospective observational cohort study of HIV infected women. Women were enrolled from the cohort of 164 HIV infected women who attend the colposcopy clinic at the Edinburgh Regional Infectious Diseases Unit. A single cervical brush scrape was obtained from 39 women and two or more samples from 63 women who attended regularly at approximately 6 monthly intervals. HPV typing was carried out using a commercial hybrid capture assay (HCA). Details of antiretroviral therapy, cytological assessment, and histological evaluation were made available and the interrelation with HR-HPV detection analysed. RESULTS: Abnormal cervical cytology, particularly of low grade, was common in these HIV infected women. HR-HPV types were detected in 25% of the women with normal cytology, while over 80% of those with abnormal cytology of any grade were HR-HPV positive. Persistent HR-HPV, as defined by two or more consecutive HPV positive results, was common and found in 27/63 women from whom multiple samples were obtained. HR-HPV was detected at high levels whether or not patients were receiving antiretroviral therapy. Profound immunosuppression was not necessarily associated with progression of cervical disease and no cases of invasive cervical disease were seen. CONCLUSION: While mild dyskaryosis (low grade squamous intraepithelial lesion (LSIL)) and persistence of HR-HPV are common in HIV infected women in Edinburgh, regular cytological and colposcopic evaluation with appropriate intervention and treatment appears to limit the progression of cervical disease.

Adult↗
PubMed1999

The effect of estradiol and a combined estradiol/progestagen preparation on insulin sensitivity in healthy postmenopausal women.

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17beta-estradiol (50 microg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17beta-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.

Administration, Cutaneous↗
PubMed1998

A randomized controlled trial and economic evaluation of counselling in primary care.

BACKGROUND: Counselling in primary care settings remains largely unevaluated. Such evaluation has been strongly recommended. AIM: To determine the relative effectiveness and cost-effectiveness of generic counselling and usual general practitioner (GP) care for patients with minor mental health problems. METHOD: A randomized controlled trial and health economic evaluation were carried out in nine general practices. Access to generic counselling (brief counselling, generally involving up to six 50-minute sessions) was compared with usual GP care. A total of 162 patients aged 16 years and over with diverse mental health problems (excluding phobic conditions and psychoses) were randomized. The Hospital Anxiety and Depression (HAD) scale, COOP/WONCA (World Organization of Family Doctors) functional health assessment charts, and the delighted-terrible faces scale were used to assess outcome four months after randomization. RESULTS: The two groups were similar at baseline. There were significant improvements in both groups between randomization and follow-up for most outcome measures, but no significant differences between the study arms. The 95% confidence limits were narrow and excluded clinically significant effects. Under various assumptions concerning the cost of secondary care referrals and of counselling time, no clear cost advantage was associated with either intervention. CONCLUSIONS: This pragmatic trial demonstrates no difference in functional or mental health outcome at four months between subjects offered access to counselling and those given usual care by their GP. There is no clear difference in the cost-effectiveness of the two interventions. Purchasers should take account of these findings in allocating resources within primary care.

Adult↗
PubMed1997

Health status and disability among elderly people in three UK districts.

AIM: To obtain population data on health status and disability of elderly people which may help in planning and maintaining services and be used as comparators for research. METHOD: Random samples of people aged 70 and over were interviewed in their own homes in West Glamorgan, Dudley and North Staffordshire. The interviews included standardized assessments of health status (SF-36), disability (Barthel index) and cognitive function (Abbreviated Mental Test). RESULTS: 1608 interviews were completed. Response rates varied between 66 and 84%. Age and sex adjusted scores for five of the eight parameters of the SF-36 and the Barthel score differed significantly between districts. CONCLUSIONS: Local studies are required to provide appropriate normative data for each area. In the absence of such studies, the data in this paper are the best currently available.

Activities of Daily Living↗
PubMed1997

The cleavage activities of aphthovirus and cardiovirus 2A proteins.

The primary 2A/2B polyprotein cleavage of aphtho-and cardioviruses is mediated by their 2A proteins cleaving C-terminally. Whilst the aphthovirus 2A region is only 16 aa (possibly 18 aa) long, the cardiovirus 2A protein is some 150 aa. We have previously shown that foot-and-mouth disease virus (FMDV) 2A is able to mediate cleavage in an artificial (chloramphenicol acetyltransferase/FMDV 2A/beta-glucuronidase [CAT-2A-GUS]) polyprotein system devoid of any other FMDV sequences with high (approximately 85%), although not complete, cleavage. In this paper we show that insertion of upstream FMDV capsid protein 1 D sequences increases the activity. In addition, we have demonstrated that the cardiovirus Theiler's murine encephalomyelitis virus(TME) 2A protein, when linked to GUS in a single ORF, is able to cleave at its own C terminus with high efficiency--if not completely. The C-terminal 19 aa of TME 2A, together with the N-terminal proline residue of protein 2B, were inserted into the CAT/GUS artificial polyprotein system (in a single ORF). This recombinant [CAT-deltaTME2A-GUS] polyprotein was able to mediate cleavage with high (approximately 85%) efficiency--directly comparable to the activity observed when FMDV 2A was inserted. A similar insertion into [CAT-GUS] of the C-terminal 19 aa of the cardiovirus encephalomyocarditis virus (EMC) 2A, together with the N-terminal proline residue of protein 2B, produced a [CAT-delta EMC2A-GUS] polyprotein which also mediated cleavage at approximately 85%. Analysis of the products of expression of these artificial polyproteins in a prokaryotic translation system did not, apparently, reveal any GUS cleavage product.

Amino Acid Sequence↗
PubMed1996

Functional specialization in the ruminant placenta: evidence for two populations of fetal binucleate cells of different selective synthetic capacity.

Trophoblast binucleate cells (BNC) in the ruminant placenta demonstrate a characteristic development, mature structure and migratory capacity whether situated in cotyledonary or intercotyledonary regions of the placenta. However, previous immunocytochemical studies demonstrated clear differences in gene expression in granule contents of BNC according to their anatomical location with some proteins being expressed in all BNC (e.g. ovine placental lactogen) whereas others were unique to a particular origin (e.g. SBU3 antigen in cotyledonary BNC only). We have used enriched preparations of binucleate cells and showed differences in steroid metabolic capacity in vitro which is more related to their species origin (sheep or goat) than to their anatomical location. The predominant product from [3H]pregnenolone is progesterone (sheep) and 5 beta-pregnane-3 alpha, 20 alpha-diol (goat) and the amount formed (corrected for the number of BNC) is similar irrespective of whether BNC were derived from the cotyledonary or intercotyledonary regions. These studies indicate specific forms of regional functional specialization of BNC and emphasize their multifunctional role in the ruminant placenta.

Animals↗
PubMed1990

Effects of basal and acetylcholine-induced release of endothelium-derived relaxing factor on contraction to alpha-adrenoceptor agonists in a rabbit artery and corresponding veins.

1. The effects of an endothelium-dependent (acetylcholine) and an endothelium-independent (sodium nitroprusside) relaxant against noradrenaline-induced contractions were compared in three isolated superficial blood vessels of the rabbit, the lateral saphenous vein, plantaris vein and distal saphenous artery. Both produced concentration-related relaxations of all three vessels and were more effective against submaximal than maximal contractions to noradrenaline. Transient contractions to high concentration of acetylcholine occurred only in endothelium-intact preparations of saphenous vein and were inhibited by flurbiprofen. 2. In endothelium-denuded preparations sodium nitroprusside was 3 times more effective than in endothelium-intact preparations, while acetylcholine (less than 3 microM) was inactive. Sensitivity was similar for each relaxant: lateral saphenous vein greater than or equal to plantaris vein greater than distal saphenous artery. The similar profile of sodium nitroprusside and acetylcholine suggests that differences in susceptibility to endothelium-derived relaxing factor (EDRF) are caused by inter-vessel variations in the excitation-coupling process for noradrenaline. 3. Haemoglobin inhibited acetylcholine-induced relaxations in the endothelium-intact preparation of the lateral saphenous vein and distal saphenous artery, which suggests a similar EDRF in each preparation and the likelihood that this is a single substance, presumably nitric oxide. 4. The influence of basal, spontaneously released EDRF on alpha-adrenoceptor function was tested either by mechanical disruption of the endothelium or by adding haemoglobin to endothelium-intact segments. Endothelial disruption slightly reduced contractions to noradrenaline (NA) in distal saphenous artery but increased response size of lateral saphenous and plantaris veins, in the latter also increasing sensitivity to NA: haemoglobin mimicked endothelial disruption. Thus, basal release of EDRF like acetylcholine and nitroprusside was more effective in the veins than in the corresponding artery. 5. In lateral saphenous vein responses to phenylephrine were enhanced by endothelial disruption, but without change in sensitivity: responses to UK-14304, B-HT 920 and cirazoline, which had a relatively slow speed of onset of contraction were not affected. There was no correlation between enhancement and alpha-adrenoceptor sub-type although the agonists which were enhanced all activate alpha 1-adrenoceptors. Competitive antagonists failed to reveal an alpha-adrenoceptor subtype enhanced by endothelial disruption. However, effects of phenoxybenzamine suggest that alpha 1-adrenoceptors are necessary for the influence of basal EDRF.

Acetylcholine↗
PubMedDate not supplied

Collaborative research and research training through the "Family and Children of Ukraine" research program.

Family and Children of Ukraine, the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood, is a prospective, geographically-based study to evaluate pregnancy outcomes in 8,000 women in five cities in Ukraine and follow the cohort of births through 7 years of age. Family and Children in Ukraine has been the major collaborative research project for the University of Illinois' Fogarty-funded program, International Training and Research in Environmental and Occupational Health. This Fogarty program includes graduate training, U.S.-based training of visiting scientists, in-country training, and collaborative in-country research. Factors that have contributed to the success of the collaboration include: 1) its focus on the environmental health of mothers and children, which is a priority goal for both countries; 2) the adoption of an internationally-endorsed research protocol with strict quality-control criteria, specifically designed for international collaboration; 3) the establishment of an in-country data management center; and 4) the investment in a long-term research program rather than a short-term study. The major obstacles have been the difficult economic situation in Ukraine, which limits in-country research investment, and the difficulty in obtaining U.S. funding for an international research program.

Adult↗