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Biomedical subjects

K Lakhani

Publications and source records attributed to K Lakhani.

11 recordsLinked to original sources

Microvascular dysfunction in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors and an increased prevalence of arterial dysfunction. However, microvascular dysfunction in PCOS has not been assessed. METHODS: Subjects comprised 12 women with PCOS and 12 age-matched controls with normal ovaries. Microvascular function was assessed by observing forearm skin microvascular erythrocyte flux responses, to cumulative iontophoretic doses of 1% (w/v) acetylcholine (ACh) and 1% (w/v) sodium nitroprusside (SNP), using laser Doppler imaging. RESULTS: Basal microvascular perfusion was comparable in PCOS and controls. The increase in skin microvascular perfusion in response to ACh was however generally blunted in PCOS women (P = 0.018). Peak ACh-induced erythrocyte flux was also less (p < 0.04) in PCOS women (125.1 +/- 21.7, i.e. 5.3-fold basal flux) than in controls (200.8 +/- 28.5, i.e. 8.3-fold basal flux). Analysis of covariance indicated this effect was unrelated to differences in body mass index or serum testosterone but serum insulin may be a weak confounder. No differences were noted between the PCOS and control groups in their response to SNP. CONCLUSION: Despite its limited sample size studied, this is the first demonstration that women with PCOS exhibit microvascular endothelial dysfunction, indicated by an inhibited vasodilatory response to ACh.

Acetylcholine↗

Polycystic ovary syndrome, diabetes and cardiovascular disease: risks and risk factors.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.

Adult↗

Polycystic ovaries.

Transvaginal ultrasound is currently the gold standard for diagnosing polycystic ovaries. The results of studies using ultrasound suggest a prevalence in young women of at least 20%. Between 5% and 10% of these women with polycystic ovaries shown on ultrasound will have the classical symptoms of polycystic ovary syndrome such as infertility, amenorrhoea or signs of hirsutism and obesity, as originally described by Stein and Leventhal in 1935. However, the significance of polycystic ovaries in asymptomatic women is still under investigation, as is the role of Doppler (pulsed and colour) and three-dimensional ultrasound. Ultrasound has also contributed to our understanding of the local and systemic haemodynamic changes associated with polycystic ovaries, although the relationship of these changes to morbidity and mortality is unknown.

Adult↗

Biochemical composition of equine carpal articular cartilage is influenced by short-term exercise in a site-specific manner.

UNLABELLED: It was hypothesized that cartilage macro-molecular characteristics are influenced by exercise intensity and by location within a joint. OBJECTIVE: To determine the macromolecular characteristics of carpal articular cartilage at common and uncommon sites of pathology in horses undergoing high or low intensity exercise, and to compare this composition between exercise groups. DESIGN: Twelve horses (19.3+/-0.9 years) were assigned to exercise groups. Each group underwent 19 weeks high-intensity treadmill training (N=6) or low-intensity exercise (N=6). Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Cartilage was collected from each site, freeze-dried and assessed for water content. Hydroxyproline, glycosaminoglycan and DNA analyses were performed on cartilage from each test site. Adjacent cartilage underwent histological preparation and assessment for chondrocyte numerical density at each site and proteoglycan distribution through the depth of cartilage. RESULTS: Dorsal cartilage had a higher collagen content, DNA content, and chondrocyte numerical density, but lower glycosaminoglycan content than palmar cartilage. Cartilage from horses undergoing high-intensity training had a significantly higher glycosaminoglycan content than cartilage from horses undergoing low-intensity exercise, with maximal difference being observed in cartilage from dorsal radial and dorsal intermediate carpal articular surfaces. Overall no effect of exercise on collagen was observed, but at sites predisposed to clinical lesions cartilage from horses undergoing high-intensity training contained significantly less collagen than from horses undergoing low-intensity exercise. Distribution of proteoglycan was non-uniform in 52% of the sections examined, with superficial loss of toluidine blue staining primarily at dorsal sites and in the high-intensity exercise group. CONCLUSIONS: These results indicate that topographical and exercise related differences exist in carpal cartilage composition, and that the effect of exercise on overall composition and distribution within the cartilage was maximal at sites predisposed to clinical lesions. These findings could indicate that the combined effect of exercise and local load variations within a joint may lead to a risk of exceeding the physiologic threshold at high load sites that are predisposed to clinical injury.

Animals↗

Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (G(L)): induction of virus-neutralizing antibody and assessment of protection in ponies.

An Escherichia coli-expressed recombinant protein (6hisG(L)ecto) comprising the entire ectodomain (aa 18-122) of equine arteritis virus (EAV) glycoprotein G(L), the immunodominant viral antigen, induced higher neutralizing antibody titres than other G(L)-derived polypeptides when compared in an immunization study in ponies. The potential of the recombinant G(L) ectodomain to act as a sub-unit vaccine against EAV was evaluated further in three groups of four ponies vaccinated with doses of 35, 70 or 140 microg of protein. All vaccinated animals developed a virus-neutralizing antibody (VNAb) response with peak titres 1-2 weeks after the administration of a booster on week 5 (VNAb titres of 1.8-3.1), 13 (VNAb titres of 1.4-2.9) or 53 (VNAb titres of 1.2-2.3). Vaccinated and unvaccinated control ponies were infected with EAV at different times post-vaccination to obtain information about the degree of protection relative to the levels of pre-challenge VNAb. Vaccination conferred varying levels of protection, as indicated by reduced or absent pyrexia, viraemia and virus excretion from the nasopharynx. The degree of protection correlated well with the levels of pre-challenge VNAb and, in particular, with levels of virus excretion. These results provide the first evidence that a sub-unit vaccine protects horses against EAV. The use of the sub-unit vaccine in combination with a differential diagnostic test based on other EAV antigens would enable serological discrimination between naturally infected and vaccinated equines.

Amino Acid Sequence↗

Factors influencing blood flow in the equine digit and their effect on uptake of 99m technetium methylene diphosphonate into bone.

It was hypothesised that exercise may promote perfusion of the distal part of the limbs and enhance uptake of radiopharmaceutical into bone, but bandaging and lameness would have no effect. Two hundred and two horses undergoing routine nuclear scintigraphic examination for assessment of lameness or poor performance between November 1998 and November 1999 were assigned randomly to one of 4 groups: no bandages and no exercise (NB/NE); bandages and no exercise (B/NE); no bandages and exercise (NB/E); bandages and exercise (B/E). In the bandage groups, the distal forelimbs were bandaged for at least 16 h prior to injection of radiopharmaceutical. In the exercise groups, horses were lunged for 15 min at trot and canter prior to injection. Quantitative values for perfusion of the front feet and uptake of the radiopharmaceutical into the bones of the distal limb were obtained from scintigraphic measurements during the vascular and bone phases of radiopharmaceutical distribution. Perfusion of the front feet was classified as good in 60% of limbs, reduced in 21% and poor in 19%. There was a strong positive relationship between exercise and both perfusion of the front feet and uptake of the radiopharmaceutical into bone. Bandaging had no effect. There was a relationship between environmental temperature and both perfusion and uptake of the radiopharmaceutical into bone. Estimation of foot surface temperature using thermography was helpful in predicting perfusion of the distal limbs. There was no relationship between lameness and uptake of the radiopharmaceutical into bone. It is therefore recommended that, whenever possible, horses are exercised for 15 min prior to injection of radiopharmaceutical if nuclear scintigraphy of the distal parts of the limb is to be performed.

Analysis of Variance↗

Internal carotid-artery response to 5% carbon dioxide in women with polycystic ovaries.

Although polycystic ovary syndrome is associated with hypertension, hyperlipidaemia, and insulin resistance, mortality from cerebrovascular disease is not increased. We previously reported lower downstream resistance in the internal carotid artery in women with polycystic ovary syndrome. This study was designed to assess vascular reactivity by measuring the response to inhalation of 5% carbon dioxide. We studied 34 young women with polycystic ovary syndrome, 15 with symptomless polycystic ovaries, and 18 controls.

Administration, Inhalation↗

Internal carotid artery haemodynamics in women with polycystic ovaries.

Although polycystic ovarian syndrome (PCOS) is associated with risk factors for cerebrovascular disease, the available evidence does not demonstrate increased stroke mortality, and it has been suggested that some protective mechanisms must be operating in these women. Haemodynamic changes have been demonstrated in the pelvic vessels and aorta in this syndrome, but there have been no studies of the cerebral circulation. Since insulin resistance is a central feature of PCOS, it is of interest that cerebral blood flow may be altered in diabetic subjects. The present study was designed to assess internal carotid artery haemodynamics in women with PCOS, asymptomatic women with polycystic ovaries (PCO women) and healthy controls. Mean internal carotid pulsatility index, measured using pulsed Doppler ultrasound under standardized conditions, was significantly lower in 35 PCOS and 15 PCO women than in the 18 controls. This was also shown on multiple regression analyses. Peak systolic velocity did not differ between groups. In view of the difficulty of interpreting pulsatility index in low-impedance vascular beds, the 'back' pressure was calculated and found to be lower in women with polycystic ovaries. This is the first demonstration of lower pulsatility index and back pressure (suggestive of reduced vascular tone) in the cerebral circulation of these women, independent of blood pressure, insulin resistance and other endocrine or metabolic factors. Changes in internal carotid haemodynamics may offset the risk of cerebrovascular disease commonly associated with polycystic ovaries.

Adolescent↗

A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus.

Four Welsh Mountain pony mares at 3 months of gestation and one mare at 5 months were inoculated intranasally with equid herpesvirus-1 (EHV-1: Ab4 isolate) at doses of 10(5) to 10(6.6) TCID50. All five mares became infected, but no cases of paresis or abortion occurred. On days 8, 9, 11, 12 (3-month-pregnant mares) and 13 (5-month-pregnant mare) after infection, a detailed examination of the pregnant uterus was made. Small numbers of vascular lesions with EHV-1 antigen expression in endothelial cells were present in the uteri of the early gestational mares; thrombi were rare and foci of thromboischaemic damage were not seen. Six pony mares previously inoculated with EHV-1 Ab4 at 9 months of gestation had a significantly greater degree of vascular abnormality than that found in the four mares infected at 3 months of gestation, but the degree of EHV-1 antigen expression and thrombosis in the uterus was similar to that found in the single mare infected when 5 months pregnant.

Abortion, Veterinary↗

Fetal breathing movements and maternal hyperoxia.

The effect of maternal inhalation of 50 per cent oxygen upon fetal breathing movements was investigated. No significant effect was noted in patients with normal pregnancies or in those complicated by insulin dependent diabetes or mild pre-eclampsia. A significant increase in fetal breathing movements was observed in those pregnancies complicated by either severe pre-eclampsia or fetal growth retardation.

Female↗