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Biomedical subjects

H Lyall

Publications and source records attributed to H Lyall.

At least 19 recordsLinked to original sources

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

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

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

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

Total middle ray amputation.

Eight patients underwent middle ray amputation with excision of the whole of the middle metacarpal and careful soft tissue repair. Excision of the base of the middle metacarpal allowed easier approximation of the index and ring rays without the tendency of these fingers to either scissor on finger flexion or to remain slightly apart. Complete removal of the middle metacarpal appears to allow the bases of the index and ring metacarpals to migrate together. The removal of the metacarpal base caused no functional problems and the technique created a good three-finger hand from both a functional and cosmetic point of view.

Adult

Hypothalamic GLUT 4 expression: a glucose- and insulin-sensing mechanism?

The insulin-regulatable glucose transporter, GLUT 4, is expressed primarily in peripheral tissues (skeletal muscle and adipose tissue). In response to insulin this transporter moves rapidly from an intracellular storage site to the plasma membrane, thus accounting for the substantial increase in glucose uptake by these tissues following insulin stimulation. The recent finding that GLUT 4 is also expressed in the hypothalamus suggests that this brain region, which is outside the blood-brain barrier and therefore sensitive to circulating insulin, may experience stimulation of glucose uptake in response to insulin. We propose that this may allow regions of the hypothalamus to respond directly to elevated blood glucose, constituting a form of metabolic regulation by allowing circulating glucose (and therefore insulin) in concert with other mechanisms to maintain blood glucose homeostasis. We consider the possible physiological role of such a mechanism and speculate that disturbances of this mechanism may occur in endocrine disease associated with insulin resistance.

Animals

Donated ovarian tissue in embryo research and assisted conception--the view of women of reproductive age.

In response to widespread interest by the media, the Human Fertilisation and Embryology Authority (HFEA) recently produced a document entitled 'Donated Ovarian Tissue in Embryology Research and Assisted Conception'. Interested organizations and the public were asked for their views on the use of eggs or ovarian tissue obtained from live donors, cadavers or fetuses for both research and the treatment of infertility. For 6 weeks from mid-March 1994, we made the HFEA document available to women attending a Family Planning/Well Woman Clinic (n = 1142), an Infertility Clinic (n = 241) and 200 women about to have a termination of pregnancy, in an attempt to develop an understanding of the attitudes of the general public. We asked them to answer anonymously the questions posed by the HFEA. Over 89% of women thought that ways should be sought to increase the supply of eggs for research and treatment. There were no significant differences in attitudes between the three groups, except that women seeking an abortion were significantly less likely to support the use of cadavers as a source of eggs for either research (48 versus 67%) or treatment (48 versus 59%) (P < 0.05 in both cases). Although all three groups of women found live donors the most acceptable source (90% for research, 88% for treatment), the majority supported the use of fetal eggs/tissue for both research (60%) and treatment (54%) of infertility. This study represents the first systematic attempt to determine the opinion of women who may not otherwise make their views known to the HFEA.

Aborted Fetus

Early detection of metabolic abnormalities in preterm infants impaired by disorders of blood glucose concentrations.

We recently reported (Acta Paediatr Scand 1992;8: 580-4) three preterm infants with severe respiratory distress syndrome and abnormal glucose profiles for the first 5 days of life who subsequently died in infancy; only at autopsy were they shown to have abnormal glucose-6-phosphatase activity. We have therefore studied retrospectively in a matched cohort of 109 infants the blood glucose profiles correlated with the severity of respiratory distress syndrome (expressed as the fraction of inspired oxygen, FiO2): group A, mild, FiO2 < 0.25; group B, moderate, FiO2 0.26-0.50; group C, severe, FiO2 > 0.51. All groups had a similar frequency of low blood glucose values (15% < or = 2.2 mmol/L; 29% < or = 2.6 mmol/L), but high blood glucose values and greater variability in glucose values were more common in groups B and C despite lower caloric intakes (A, 4.3%; B, 9.3%; C, 9.6% > or = 7 mmol/L). We conclude that the early blood glucose patterns in those three previously described preterm infants with abnormal hepatic glucose-6-phosphatase activity at autopsy cannot be viewed as abnormal when considered against a matched cohort of infants. Preterm infants at risk of genetic or developmental delays in blood glucose homeostasis should be reassessed after recovery from their acute illnesses.

Blood Glucose

Impairment of the activity of the hepatic microsomal glucose-6-phosphatase system in three preterm infants.

Three preterm infants born at 26-30 weeks' gestation who died between 103 and 266 days after birth were found to have elevated hepatic glycogen levels. Kinetic analysis of the hepatic microsomal glucose-6-phosphatase system demonstrated that one infant had abnormally low levels of activity of the glucose-6-phosphatase enzyme (partial type 1a glycogen storage disease) and two had deficiencies of T2, a microsomal phosphate/pyrophosphate transport protein (type 1c glycogen storage disease). In all three cases glycogen storage disease was not suspected prior to death even though both hypo- and hyperglycaemic episodes were recorded in the first 15 days after birth indicating that they had somewhat disordered blood glucose regulation. In the infant with low glucose-6-phosphatase enzyme activity, abnormal development of the glucose-6-phosphatase enzyme cannot be ruled out. This is the first description of abnormalities in the glucose-6-phosphatase system in preterm infants.

Biopsy

Glucose metabolism and hypoglycaemia in SIDS.

Once a child is born its survival depends on the maturation of the blood glucose homeostatic control mechanisms. When this fails or where there is an inborn error of metabolism the infant is susceptible to potentially fatal hypoglycaemic episodes. A variety of environmental stresses, either singly or in combination, such as inappropriate or low caloric intake, acute infections of childhood, endotoxaemia, fever, xenobiotic exposure, oxidative stress or anaphylaxis, can greatly exacerbate the deficiency of the normal homeostatic compensatory mechanism and result in the onset of hypoglycaemia. Various inborn errors have been found in infants who died of SIDS. Our approach to this problem has been to use the six microsomal glucose-6-phosphatase proteins as a model system to study defects in carbohydrate metabolism in cases of SIDS. Initial studies determined the ontogeny of the glucose-6-phosphatase proteins and showed that intact microsomes isolated from unfrozen liver samples can be used to study glucose-6-phosphatase in cases of SIDS that were presumably due to the low concentrations of liver lipid peroxidation. More recently we have used a combination of techniques to demonstrate the abnormalities of glucose-6-phosphatase in cases of SIDS. Classic gross pathology and histology have now clearly defined the various subgroups of sudden and unexpected deaths of infancy. This now enables us to develop new molecular approaches to predict and prevent hypoglycaemia in infants who are at risk of SIDS.

Blood Glucose

Anterior fontanelle size in Scottish infants.

Very limited information is available on the normal size of the anterior fontanelle but this measurement may be of value in the early diagnosis for example of bone diseases, and of hypothyroidism. The purpose of this study was to provide a reference range applicable to the first two years of life, using a larger sample population than previous studies. Measurements were made of the anterior-posterior and transverse dimensions in 334 full term infants between birth and the age of 24 months. Despite the wide variation, both in size and age of closure, it proved possible to define a reference range and also, for the first time, to present a centile chart.

Bone Diseases