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Biomedical subjects

A Akkad

Publications and source records attributed to A Akkad.

13 recordsLinked to original sources

Telomere length in small-for-gestational-age babies.

OBJECTIVE: Short telomeres are associated with adult cardiovascular disease. Our aim was to determine whether small-for-gestational-age (SGA) newborns have shortened telomeres compared with appropriately grown controls. DESIGN: Prospective cohort study. SETTING: Large tertiary referral unit in Trent, UK. POPULATION: Seventy-two women who delivered at 35-42 weeks of gestation were recruited; 34 delivered SGA babies (less than or equal to the third birthweight centile) and 38 had appropriately grown babies (greater than the tenth centile). METHODS: Maternal and cord blood samples were collected at delivery. A Southern blot of DNA from these samples was hybridised with a 32P-labelled telomeric probe and telomere length was measured. MAIN OUTCOME MEASURES: Mean maternal and newborn telomere length. RESULTS: Maternal and newborn telomere lengths were significantly correlated in both the SGA and the control groups (r2 = 0.25, P < 0.0001). Telomere lengths were similar in both maternal (control 8.41 +/- 0.9 kb versus SGA 8.29 +/- 1.0 kb, P = 0.57) and newborn (control 10.36 +/- 1.5 kb versus SGA 10.33 +/- 1.3 kb, P = 0.93) cohorts in the two groups. CONCLUSIONS: Intrauterine events associated with impaired fetal growth do not appear to be associated with increased telomere shortening.

Adult↗

Women's accounts of consenting to surgery: is consent a quality problem?

BACKGROUND: Consent has been placed at the centre of doctor-patient relationships. Attempts to improve the consent process in medicine have drawn on bioethical and legal traditions. Current approaches to consent emphasise the provision of information and have, in the UK, resulted in a single standardised format and process for both elective and emergency situations. Investigation of patients' perceptions and priorities are important in understanding the quality of the consent process. METHODS: In this qualitative study, semi-structured interviews were conducted with 25 women. Eleven had elective and 14 had emergency operations in obstetrics and gynaecology. All interviews were recorded and transcribed verbatim. Data analysis was based on the constant comparative method. RESULTS: Participants' perceptions of surgery strongly influenced the meanings they gave to consent. Some, particularly those undergoing elective operations, wanted surgery. Others were uncertain of their desire for surgery or felt that it was imposed on them. Consenting was interpreted as a ritualistic legal procedure. There was an overwhelming tendency to view consent as not primarily serving patients' needs, although some advantages of the consent process were identified. Accounts made no reference to ethics. CONCLUSION: Countering paternalism will remain difficult to achieve if issues surrounding consent continue to be debated between professionals without due effort to reflect patients' own views and values and to appreciate the circumstances under which consent is sought.

Adult↗

Intrapartum care for women on full anticoagulation.

Women requiring full anticoagulation in pregnancy and labour present their care providers with complex management problems, particularly during the peripartum period. Available guidelines often fail to address the practical issues of balancing the risks of recurrent thrombotic events and haemorrhage during labour. This is especially the case in women at high risk of recurrent thromboembolism, in whom the usually recommended temporary peripartum reduction in the level of anticoagulation may be considered unsafe. In order to achieve a satisfactory outcome without undue intervention, multidisciplinary management involving obstetricians, haematologists and anaesthetists is essential. Intrapartum care plans should be made during pregnancy to address the conduct of labour and delivery, anticoagulation, analgesia in labour and the management of any arising obstetric, anaesthetic or haematological complications. In the following we address the practical issues requiring particular attention, as well as management options, in fully anticoagulated patients using a clinical case for illustration.

Journal Article↗

Changes in serum vascular endothelial growth factor following initiation of estrogen replacement after hysterectomy and oophorectomy.

BACKGROUND: Vascular endothelial growth factor has been shown to play an important role in preservation and restoration of endothelial integrity. Similar effects on endothelial function have been described with estrogen replacement. This poses the question whether some of the mechanisms ascribed to estrogen are in fact vascular endothelial growth factor mediated. The objective of this study was to examine the effect of continuous transdermal estrogen replacement on serum levels of secreted vascular endothelial growth factor in women following hysterectomy and oophorectomy. METHODS: In a nonrandomized, prospective study, 40 hysterectomized and oophorectomized women were treated with transdermal estrogen. Their serum vascular endothelial growth factor levels were measured before and six months following estrogen treatment, using a commercially available ELISA kit. RESULTS: The mean serum vascular endothelial growth factor level fell from 328 ng/ml (s.d. 164) before treatment to 285 ng/ml (s.d. 124) following six months of estrogen replacement. This decrease was statistically significant (p<0.03). CONCLUSION: Transdermal estrogen replacement in hysterectomized and oophorectomized women appears to be associated with a significant reduction in secreted serum vascular endothelial growth factor. However, the effect of hysterectomy and oophorectomy per se needs to be explained in appropriately designed trials.

Administration, Cutaneous↗

Continuous combined hormone replacement therapy compared with tibolone.

OBJECTIVE: To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day. METHODS: In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test. RESULTS: One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group. CONCLUSION: Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.

Climacteric↗

The effect of oestrogen on intimal hyperplasia in cultured human ovarian veins.

The beneficial effect of oestrogen on blood vessels may include modulation of vascular response to injury. In this experiment we set out to develop an in-vitro model, using all human materials, for the study of vascular changes in culture, and their response to oestrogen treatment. Human ovarian vein segments were obtained from 15 hysterectomy specimens, and cultured with and without the addition of 17beta-oestradiol. Paired control veins were cultured with the inert 17alpha-oestradiol. The veins were stained with anti-alpha-smooth muscle actin and Miller's elastin, and intimal thickness measured. Cultured veins developed a significant degree of intimal thickening [15.7 versus 8.25 microm in fresh veins, 95% confidence intervals (CI) 13.6, 17.8 and 6.3, 10.2 respectively; P = 0.0001]. The addition of 17beta-oestradiol, but not 17alpha-oestradiol, led to a significant reduction in intimal hyperplasia (intimal thickness 8.85 microm; 95% CI 6.9, 10.8; P = 0.008). The mean number of nuclei per high-power field was also significantly lower in the intima of oestrogen-treated compared to untreated veins (11.6; 95% CI 9.9, 13.26 versus 14.05; 95% CI 12.5, 15.6; P = 0.001). Our data suggest that intimal hyperplasia in cultured ovarian veins is effectively reduced by oestrogen.

Cell Division↗

Immunohistochemical and hysteroscopic assessment of postmenopausal women with uterine bleeding whilst taking Tibolone.

The gonadomimetic steroid Tibolone, is currently widely used for the treatment of menopausal symptoms. Up to 20% of women have been reported to have episodes of bleeding whilst on therapy. We investigated 37 cases who experienced bleeding episodes whilst on Tibolone and compared these to six cases who experienced no bleeding whilst on therapy and who underwent similar investigations in the course of a clinical study. All women underwent a diagnostic hysteroscopy and an endometrial biopsy, under a local anaesthetic. The endometrium was assessed by histology and with immunohistochemical markers for cellular proliferation (Ki67, PCNA), Heat Shock Protein 27 (HSP27) and bcl-2. There were 17 women with intracavitary lesions on hysteroscopy (including one in the control group), 10 with polyps, five with fibroids, two with congenital uterine anomalies. Histological diagnosis was not obtained in 16 cases. The high incidence of uterine polyps in the group who bled on Tibolone suggests an etiologic relation. The staining pattern with HSP27 demonstrated an oestrogenic effect. There were no differences in the bcl-2 immunoreactivity between those who bled and those who did not bleed on treatment which suggests absence of a link. Similarly, there were no differences in the expression of the proliferation markers. We conclude that episodes of bleeding in patients receiving Tibolone for hormone replacement therapy, whilst warranting investigation, should not cause undue concern.

Adult↗

Carotid plaque regression on oestrogen replacement: a pilot study.

OBJECTIVE: To investigate the effect of unopposed oestrogen on atheromatous carotid plaques. SUBJECTS: Seventeen postmenopausal women with known carotid disease. METHODS: Carotid intimal thickness and plaque length and thickness were measured prior to and following 3 and 6 months of treatment, using Duplex ultrasound. A total of 22 plaques were followed up. RESULTS: There was a reduction in plaque length after 3 (-8.14%, p = 0.001) and 6 months (-28%, p = 0.001) of treatment. The reduction in plaque thickness (-18%, p = 0.004) was significant after 6 months of treatment. Reductions in intimal thickness were not statistically significant. CONCLUSION: Our results suggest that oestrogen replacement is associated with significant plaque regression.

Aged↗

Effect of a new cyclical sequential postmenopausal HRT on lipoprotein, apoprotein and thrombophilia profile.

We examined the changes in lipoprotein, apoprotein, and thrombophilia profile in postmenopausal women using a new cyclical sequential combined HRT regimen. The study medication consisted of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg and oestradiol 0.6 mg), daily and norethisterone (1 mg) BP (Shire Developments) for the last 12 days of every 28 day cycle. Serial fasting blood samples were collected at the beginning of the study and, thereafter, at 3-monthly intervals for 1 year, each patient acting as her own control. Thirty-five healthy postmenopausal women completed 1 year of follow-up and had a complete set of fasting blood samples. The lipid profile; total cholesterol, triglycerides, HDL, LDL, Apo AI, Apo AII, Apo B and Lp(a), as well as the coagulation parameters; antithrombin III, factor VII, fibrinogen, protein C and protein S, were measured at each occasion. There was a statistically significant drop in total cholesterol and LDL levels. Lp(a) level dropped after commencing treatment and remained below baseline for the rest of the study. The initial increase in Apo AII was not maintained for the duration of the treatment. The changes in Lp(a) and Apo AII were not statistically significant. The level of protein S dropped significantly throughout the study. The changes in other coagulation factors were not statistically significant. The effect of this hormonal combination on the lipid parameters is favourable, and although the change in protein S is striking, its clinical significance remains unclear.

Adult↗