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Biomedical subjects

H Lyall

Publications and source records attributed to H Lyall.

At least 19 recordsLinked to original sources
PubMed2004

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction.

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.

Adult↗
PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗
PubMed2001

Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities?

OBJECTIVES: To assess use of antiretroviral therapy (ART) by HIV positive pregnant women in London since 1994 and the risk of congenital abnormalities associated with multidrug exposure during the first trimester of pregnancy. METHODS: Retrospective multicentre study of medical, obstetric, and paediatric notes of all mother-infant pairs, where the mother was known to be HIV infected before delivery, using a standardised proforma. RESULTS: In this study of 195 mother-infant pairs, use of ART during any stage of pregnancy increased from 33.3% in 1994 to 92.5% in 1999 (p=0.01, trend). First trimester exposure increased from 0% in 1994 to 27.5% in 1999 (p=0.00045, trend). Congenital malformations were observed in nine infants (4.6%). Compared with infants not exposed to ART or folate antagonists during the first trimester (n=148), exposure to both ART and folate antagonists during the first trimester (n=13) was associated with an increased risk of congenital abnormalities (4% v 23.1%; OR 7.10, 95% CI 1.5, 34.2). No malformations were observed in the 34 children exposed to either ART or folate antagonists alone during the first trimester. CONCLUSION: An increasing number of HIV infected women conceived while on ART. Although there is no evidence of teratogenicity caused by ART if given alone during the first trimester, exposure to the combination of ART and folate antagonists was associated with a significantly higher risk of congenital abnormalities in this cohort.

Abnormalities, Drug-Induced↗
PubMed2001

Low grade chronic inflammation in women with polycystic ovarian syndrome.

Low grade chronic inflammation as reflected by increased C-reactive protein (CRP) concentrations independently predicts those at risk for coronary heart disease (CHD) and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are insulin resistant and have increased risk for CHD and type 2 diabetes, but currently there are no data on markers of inflammation in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index were recruited. Measurement of CRP concentrations was made using a highly sensitive assay. Insulin resistance was assessed using the hyperinsulinemic euglycemic clamp technique. The women with PCOS had significantly elevated CRP concentrations relative to controls (geometric means, 2.12 and 0.67 mg/L, respectively; P = 0.016). Log CRP correlated with body mass index in both PCOS and controls (r = 0.58; P < 0.05 and r = 0.78; P < 0.01, respectively) and inversely with insulin sensitivity (r = -0.57; P < 0.05 and r = -0.69; P < 0.01). Total testosterone did not correlate with log CRP in either group. On adjustment for body mass index and age, there remained a significant difference in log CRP between PCOS and controls (t = 2.13; P < 0.05). On further adjustment for insulin sensitivity, log CRP was no longer significantly different between groups (t = 1.51; P = 0.14). We conclude that women with PCOS have significantly increased CRP concentrations relative to women with normal menstrual rhythm and normal androgen levels. We propose low grade chronic inflammation as a novel mechanism contributing to increased risk of CHD and type 2 diabetes in these women.

Adult↗
PubMed2000

Sex hormones induce insulin resistance in 3T3-L1 adipocytes by reducing cellular content of IRS proteins.

AIM/HYPOTHESIS: Numerous studies have suggested a relation between sex hormones and insulin sensitivity but the ability of sex hormones to directly influence insulin action in peripheral tissues has not been investigated. METHODS: We have examined the effects of estriol, estradiol and estrone on insulin action in cultured 3T3-L1 adipocytes, a useful model of adipocytes. RESULTS: Treatment of these cells with each of these sex hormones resulted in a statistically significant reduction in the ability of insulin to stimulate glucose transport independently of a reduction in total cellular GLUT-4 content. This diminished ability of insulin to stimulate glucose transport was accompanied by a reduction in the total cellular content of insulin receptor substrates -1 and -2 and the p85alpha subunit of phosphatidylinositol 3'-kinase. By contrast, cellular content of protein kinase B was unchanged by hormone treatment but the magnitude of insulin-stimulated kinase activity was statistically significantly reduced after incubation with each of the sex hormones tested. We have further shown that treatment of 3T3-L1 adipocytes with these hormones alters the subcellular distribution of insulin receptor substrate proteins such that the particulate and soluble pools of these proteins were differentially affected by hormone treatment. CONCLUSION/INTERPRETATION: These data show that sex hormones can directly induce a state of insulin resistance in 3T3-L1 adipocytes in culture. The mechanism of this defect seems to be at least in part due to decreased cellular content and altered subcellular distribution of insulin receptor substrate proteins which in turn results in a reduction in proximal insulin-stimulated signalling cascades.

3-O-Methylglucose↗
PubMed2000

Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH.

There has been much debate about the role of luteinizing hormone (LH) during follicle stimulating hormone (FSH)-treated ovarian stimulation for assisted reproduction, where the endogenous LH is suppressed using a gonadotrophin-releasing hormone analogue. The requirement for LH in oestradiol biosynthesis is established, but other effects of 'insufficiency' are less clear, and little attention has been paid to the specific origin of the FSH used. The aim of this study was to examine the roles of profoundly suppressed circulating LH concentrations in cycles of ovarian stimulation for IVF, which were affected in two large separate cohorts of patients undergoing assisted reproduction. They were stimulated by either purified urinary FSH (MHP) or recombinant human FSH (rFSH). Within each dataset, outcomes were examined with respect to the circulating concentrations of LH in the mid-follicular phase, as plasma samples were stored prospectively, and assayed retrospectively. Patients with profoundly suppressed LH showed much reduced oestradiol concentrations at mid-follicular phase and at human chorionic gonadotrophin administration in cycles treated with either MHP or rFSH. However, gross ovarian response, as became evident by FSH dose demands, duration of stimulation, and also oocyte and embryo yields and embryo cryopreservation were influenced only in cycles treated with MHP. Furthermore, no effect upon pregnancy survival was observed. Thus, it is concluded that there is a demand for additional exogenous LH treatment only in cycles treated with purified urinary FSH where the LH is profoundly suppressed.

Abortion, Spontaneous↗
PubMed2000

The long term health consequences of polycystic ovary syndrome.

Women with polycystic ovary syndrome have both insulin resistance and beta cell dysfunction. Consequently, they are at increased risk of developing diabetes and cardiovascular disease. Women with polycystic ovary syndrome present to clinicians at a young age and as such offer a unique opportunity to identify insulin resistant patients at an early stage. This enables the modification of risk factors and diagnosis of diabetes before the onset of macro- and micro-vascular symptoms. Increased emphasis should thus be placed on long term risk management and diabetic screening with advice on smoking, exercise and, if appropriate, weight loss. Where possible drugs that exacerbate insulin resistance should be avoided and consideration should be given to the use of insulin sensitising agents, particularly in the obese.

Diabetes Mellitus, Type 2↗
PubMed2000

Simultaneous presentation of ectopic pregnancy and hyperthyroidism.

Hyperthyroidism is known to occur uncommonly in pregnancy (about 0.5 per 1000). The incidence of ectopic pregnancy is approximately 9.6 per 1000 pregnancies. Both conditions, if unrecognised and untreated can have potentially fatal consequences. We describe a case of hyperthyroidism and ectopic pregnancy presenting concurrently, and highlight the difficulties encountered in diagnosis when two clinical conditions present with indistinguishable clinical signs.

Adult↗
PubMed1999

Rapid development of genotypic resistance to lamivudine when combined with zidovudine in pregnancy.

The prevention of mother to child transmission of HIV-1 by zidovudine monotherapy is well known, but increasingly combination anti-retroviral therapy is prescribed during pregnancy. In this prospective study, 19 pregnant women with human immunodeficiency virus-1 (HIV-1) infection who elected to take anti-retroviral therapy during the second and third trimesters were treated with zidovudine or zidovudine plus lamivudine. Fourteen women treated with zidovudine monotherapy had a mean 0.3 log(10) reduction in viral load and a mean 52 x 10(6)/L (17%) increase in CD4+ lymphocytes at delivery compared with pre-treatment samples. Genotypic mutations associated with decreased susceptibility to zidovudine were detected in 2 of 10 women at delivery. Five women with more advanced HIV-1 infection were treated with zidovudine plus lamivudine and a mean 1.5 log(10) reduction in viral load together with a mean 30 x 10(6)/L (33%) increase in CD4+ lymphocytes was observed in this group. However, four of five women in the dual therapy arm had the M184V mutation in the reverse transcriptase gene associated with decreased susceptibility to lamivudine at delivery. We conclude that zidovudine plus lamivudine reduced HIV-1 plasma viraemia to low levels in pregnant women with advanced HIV-1 disease but the rapid development of genotypic resistance to lamivudine indicates that additional therapy is required both for the long-term benefit of the mothers and to prevent the development of resistant virus that may be transmitted to the infant.

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↗
PubMed1999

GnRH analogue in everyday gynecology: is it possible to rationalize its use?

BACKGROUND: The study was an audit of patients who attended the Menstrual Disorders Clinic at Glasgow Royal Infirmary over a five year period, and received gonadotrophin-releasing hormone analog (GnRHa). We aimed to identify the clinical indications for the use of GnRHa, and the effect of the latter in terms of symptom resolution and ultimate outcome. We aim to use this information to formulate a strategy for the use of GnRHa by targeting this expensive therapy to those situations where maximum benefit will be achieved. METHODS: A retrospective case review analysis of 201 patients. RESULTS: Thirty-eight percent of women presented with pelvic pain, 33% with disordered menstruation and 26% with premenstrual symptomatology. Overall, 74% of patients reported a beneficial effect of GnRHa. In the non-cyclical pelvic pain group, those patients with adhesions constituted a much greater proportion of those who did not derive benefit from GnRHa than those who did (43% vs. 16%; p<0.05; data not shown). In those patients with disordered menses, there was no difference between the diagnosis in those who did or did not derive benefit from GnRHa. Also with the exception of endometrial preparation prior to ablation and in the correction of anemia, the ultimate outcome was no different in the two groups. Of the patients with premenstrual symptomatology, the greatest proportion of those deriving benefit from GnRHa (41%) ultimately had an operative resolution. CONCLUSIONS: Our results enable us to use GnRHa as a first line in those clinical situations where maximum benefit will be achieved, either in terms of symptom resolution or as a tool to identify the most appropriate therapeutic option. We can therefore rationalize our prescribing both to the benefit of the patient and to our budget.

Adult↗
PubMed1998

Should sperm donors be paid? A survey of the attitudes of the general public.

Gamete donation in assisted reproduction is an accepted treatment option for certain infertile couples. Traditionally, men donating spermatozoa have been paid a nominal fee, whilst women donating oocytes have not. The issue of payment for sperm donors has recently attracted attention following the Human Fertilisation and Embryology Authority's (HFEA) suggestion that such payment may be withdrawn. Prior to the final meeting of the HFEA working party which is examining this issue, here we report the results of a survey designed to solicit opinion on whether sperm donors should be paid, to identify social or other factors which influence this opinion, and to examine the influence of financial incentive on potential donors. We surveyed 717 individuals in three distinct groups: the general public, students (potential donors), and infertility patients (potential recipients). The majority of the potential donor group (students) was in favour of paying sperm donors, as were infertility patients. In contrast the general public was not. The opinion of the general public on this issue was influenced by their prior knowledge of whether donors were paid: those of the general public favouring the payment of sperm donors had a prior awareness that such payments were made. Although not in favour of paying sperm donors, the general public overwhelmingly approved of the use of donated spermatozoa for the treatment of infertile couples, and thought that ways should be sought to increase the availability of donor spermatozoa for the treatment of infertility and for research purposes. Within the potential donor group (students), the majority indicated that financial reward was an important factor which would influence their decision to donate spermatozoa. As the majority of both the potential recipients and potential donors feels that sperm donors should be paid, perhaps the views of these groups should carry significant weight when the decision whether or not to withdraw payment is taken. This is especially the case in view of the fact that the majority of the general public is in favour of the use of donated spermatozoa for the treatment of infertile couples.

Biomedical Research↗
PubMed1997

Hepatic glucose-6-phosphatase development in preterm and full-term guinea-pigs: comparison with rat and human development.

In term infants, hepatic glucose-6-phosphatase activity rises several-fold in the first few days after birth. In contrast, in many preterm infants, the postnatal rise in activity does not occur and the abnormally low levels can persist. In an attempt to determine if prematurity causes long-term changes in levels of glucose-6-phosphatase in liver of all mammals, we have studied the ontogeny of glucose-6-phosphatase in term guinea-pigs, and also in guinea-pigs delivered prematurely by Caesarean section. The activity of hepatic glucose-6-phosphatase in preterm guinea-pigs is about 5-fold lower than in term guinea-pigs at birth but the activity rises rapidly to very similar values to those found in term guinea-pigs. This indicates that prematurity alone does not result in abnormal development of hepatic glucose-6-phosphatase activity in guinea pigs. The changes in liver glucose-6-phosphatase activity in the postnatal period in term guinea-pigs were much smaller than those occurring in term postnatal rats or term infants.

Age Factors↗