Hyperandrogenism in a patient with previous colorectal cancer.
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Adenocarcinoma↗
Biomedical subjects
P J Manning
Publications and source records attributed to P J Manning.
Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).
BACKGROUND: Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. OBJECTIVE: To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. METHODS: Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. RESULTS: Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. CONCLUSIONS: Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.
Adolescent↗
An unusual cause of hyperinsulinaemic hypoglycaemia syndrome.
Endogenous hyperinsulinism as a cause for hypoglycaemia can be attributed to a number of different causes including insulinoma, sulphonylurea drugs and the newly described disorder non-insulinoma pancreatogenous hypoglycaemia (NIPH). The calcium stimulation test is increasingly used as a method for not only localizing insulinoma but also for distinguishing the above entities. We describe a case in which felonious sulphonylurea administration was used to mimic either an insulinoma or NIPH. Importantly, this case demonstrates that, contrary to previous reports, the insulin response to calcium stimulation in such cases may be uniformly positive and should alert the physician to possible surreptitious sulphonylurea ingestion.
Calcium↗
Spinal overload: a concern for obese children and adolescents?
Heavy children require stronger bones than leaner children. The present cross-sectional observational study was undertaken to examine the magnitude of compensatory increases in the spinal bone mineral content (BMC) and area shown by overweight and obese children and adolescents. Vertebral area and BMC of lumbar vertebrae L2-L4 were measured by dual-energy X-ray absorptiometry in 202 boys and 160 girls aged 3-19 years. Subjects were categorized as of normal weight, overweight or obese using international cutoffs for body mass index. Compared with children of healthy weight our overweight and obese children had lower vertebral BMC for their bone area, body height, body weight and pubertal development: ratios and 95% CI for overweight and obese groups were 0.92 (95% CI 0.87-0.97) and 0.88 (95% CI 0.80-0.96) for girls and 0.96 (95% CI 0.91-1.02, NS) and 0.87 (95% CI 0.78-0.96) for boys, respectively. Spinal area was low in overweight and obese girls compared with girls of healthy weight but overweight and obese boys had enlarged their vertebral area appropriately for their increased body size. We conclude that during growth overweight and obese children do not increase their spinal BMC to fully compensate for their excessive weight. Limiting excessive adiposity in childhood and adolescence should help to avoid excessive loading and stresses on the lumbar spine.
Adaptation, Physiological↗
Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.
AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.
Administration, Oral↗
The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial.
BACKGROUND: Postmenopausal women with diabetes are at high risk for cardiovascular disease, compared with their nondiabetic counterparts. Combined continuous hormone replacement therapy (HRT) is associated with improvements in serum lipoprotein levels in nondiabetic women; however, the effect in women with diabetes has not been determined. We evaluated the effect of combined continuous HRT on lipoprotein and coagulation factor concentrations and glycemic control in postmenopausal women with type 2 diabetes mellitus. METHODS: In a randomized controlled crossover study, 61 subjects received combined continuous HRT or placebo. Each treatment phase was of 6 months' duration, with an 8-week washout phase between treatment phases. RESULTS: Total cholesterol concentration decreased by 7% (95% confidence interval [CI], 4%-11%) during HRT. For low-density lipoprotein concentration, the mean decrease with HRT was 12% (95% CI, 6%-17%). Apolipoprotein B levels decreased in keeping with the reduction in low-density lipoprotein cholesterol concentrations. There were no significant changes in concentrations of high-density lipoprotein, its subfractions, or triglycerides. Lipoprotein(a) and fibrinogen concentrations were reduced by 21% (95% CI, 10%-31%) and 8% (95% CI, 2%-13%), respectively, with HRT. Fructosamine concentrations declined by 5% (95% CI, 2%-9%) during HRT. CONCLUSIONS: In postmenopausal women with type 2 diabetes mellitus, combined continuous HRT has beneficial effects on lipoprotein concentrations and improves some markers of coagulation and glycemic control.
Aged↗
Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women.
The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL) in the blood and is low in patients with type 2 diabetes. Hormone-replacement therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1 arylesterase activity is uncertain. The aim of the present study was to determine the effect of 6 months' HRT with conjugated equine estrogen and medroxyprogesterone acetate on serum PON1 arylesterase activity in postmenopausal women with type 2 diabetes. Serum PON1 activity was measured immediately before and at the end of the second arm of a randomized, placebo-controlled, crossover with washout study originally designed to test the effect of HRT on plasma lipids in diabetic postmenopausal women. Baseline serum PON1 arylesterase activity was significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38 micromol/mL/min; n = 47) than values in healthy postmenopausal women (173 +/- 32 micromol/mL/min; n = 51). Serum PON1 activity increased (10%) significantly (P =.009) in diabetic women treated with HRT compared with placebo. A significant (P =.02) interaction between baseline PON1 activity and treatment indicated a greater increase in PON1 activity during HRT in women with lower baseline activities. At baseline, serum PON1 arylesterase activity was correlated significantly with plasma HDL cholesterol levels in diabetic women (r = 0.333, P =.01, n = 47), and the increase in serum PON1 activity was correlated significantly with the change in plasma HDL cholesterol during HRT (r = 0.659, P =.0001, n = 28). These data suggest that serum PON1 activity is abnormally low in postmenopausal women with type 2 diabetes and increases during HRT, particularly in women with lower baseline levels and in those who show a concomitant increase in HDL cholesterol.
Aged↗
Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy x-ray absorptiometry study.
OBJECTIVE: To determine whether boys with distal forearm fractures differ from fracture-free control subjects in bone mineral density (BMD) or body composition. STUDY DESIGN: A case-control study of 100 patients with fractures (aged 3 to 19 years) and l00 age-matched fracture-free control subjects was conducted. Weight, height, and body mass index were measured anthropometrically. BMD values and body composition were determined by dual-energy x-ray absorptiometry. RESULTS: More patients than control subjects (36 vs l4) were overweight (body mass index >85th percentile for age, P <.001). Patients had lower areal (aBMD) and volumetric (BMAD) bone mineral density values and lower bone mineral content but more fat and less lean tissue than fracture-free control subjects. The ratios (95% CIs) for all case patients/control subjects in age and weight-adjusted data were ultradistal radius aBMD 0.94 (0.91-0.97); 33% radius aBMD 0.96 (0.93-0.98) and BMAD 0.95 (0.91-0.99); spinal L2-4 BMD 0.92 (0.89-0.95) and BMAD 0.92 (0.89-0.94); femoral neck aBMD 0.95 (0.92-0.98) and BMAD 0.95 (0.91-0.98); total body aBMD 0.97 (0.96-0.99), fat mass 1.14 (1.04-1.24), lean mass 0.96 (0.93-0.99), and total body bone mineral content 0.94 (0.91-0.97). CONCLUSIONS: Our results support the view that low BMC, aBMD, and BMAD values and high adiposity are associated with increased risk of distal forearm fracture in boys. This is a concern, given the increasing levels of obesity in children today.
Absorptiometry, Photon↗
Overweight and obese children have low bone mass and area for their weight.
OBJECTIVES: To determine whether girls and boys categorized from body mass index (BMI) values as overweight or obese for their age have lower bone mineral content (BMC) or lower bone area in relation to total body weight than children of normal adiposity. DESIGN: Cross-sectional study in a university bone research unit. SUBJECTS: Two hundred girls and 136 boys aged 3-19 y recruited from the general population by advertisement. MEASUREMENTS: Total body BMC (g) and bone area (cm2) measured by dual energy X-ray absorptiometry (DXA) in relation to body weight (kg), lean tissue mass (kg) and fat mass (kg) in boys and girls of three different BMI percentile groupings: normal weight (BMI<85th percentile); overweight (85 to 94th BMI percentile); obese (> or =95th BMI percentile). RESULTS: Obese children had higher BMC, bone area, and fat mass for chronological age than those of normal body weight (P<0.001). In spite of this the observed values for age-adjusted total body BMC and bone area relative to body weight were each lower than predicted values, in both overweight and obese children (2.5-10.1% less, P<0.05) than in children of lower adiposity. CONCLUSION: In overweight and obese boys and girls there is a mismatch between body weight and bone development during growth: their bone mass and bone area are low for their body weight.
Adipose Tissue↗
More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures.
Predictors of childhood fractures have not been investigated previously. This study was undertaken to determine whether a previous history of forearm fracture, low bone mineral density (BMD; both areal bone mineral density [aBMD, g/cm2] and volumetric bone mineral apparent density [BMAD, g/cm3]), or anthropometry, influence fracture risk in young girls. At baseline, two cohorts of girls, aged 3-15 years, were evaluated: 100 had recently broken a forearm (group 1) and 100 were fracture free (group 2). Four years later we restudied 170 of these girls (82 from group 1 and 88 from group 2). We now report the relationships of previous fracture history, baseline BMD (measured by dual-energy X-ray absorptiometry), baseline weight, and height to risk of new fracture. More new fractures occurred in group 1 (37 fractures in 24 girls) than in group 2 (8 fractures in 7 girls; p = 0.0007). The independent predictors for occurrence of a new fracture at any skeletal site in a multivariate model adjusting for age, weight, total body aBMD, and fracture history were previous fracture (hazard ratio [HR], 3.28; 95% CI, 1.41-7.64); age (HR per 1-year increase, 0.91; 95% CI, 0.84-0.99); total body aBMD (HR per 1 SD decrease, 1.92; 95% CI, 1.31-2.81); and body weight (HR per 1 SD increase, 1.49; 95% CI, 1.06-2.08). Girls with two risk factors together had substantially greater fracture risk: previous fracture and low spinal BMAD (HR, 9.4; 95% CI, 2.8-32.0), previous fracture and high body weight (HR, 10.2; 95% CI, 2.8-37.6), or previous fracture and low total body aBMD (HR, 13.0; 95% CI, 3.9-43.1). We conclude that previous forearm fracture, low total body aBMD, low spinal BMAD, and high body weight each increase risk of new fractures within 4 years in young girls. Interventions to reduce the risk of fractures, particularly forearm fractures, in girls warrant further study.
Absorptiometry, Photon↗
Hypoglycaemia in type 1 diabetes.
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Diabetes Mellitus, Type 1↗
The case for growth hormone replacement in adult hypopituitarism.
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Adult↗
Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients.
The criteria for the diagnosis of the polycystic ovary syndrome (PCOS) have still not been agreed universally. A population of 1741 women with PCOS were studied, all of whom had polycystic ovaries seen by ultrasound scan. The frequency distributions of the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin and the body mass index, ovarian volume, uterine cross-sectional area and endometrial thickness were determined and compared with the symptoms and signs of PCOS. Obesity was associated with hirsutism and an elevated serum testosterone concentration and was also correlated with increased rates of infertility and cycle disturbance. The rates of infertility and cycle disturbance also increased with serum LH concentrations > 10 IU/l. A rising serum concentration of testosterone [mean and 95th percentiles 2.6 (1.1-4.8) nmol/l] was associated with an increased risk of hirsutism, infertility and cycle disturbance. The ovarian volume was correlated with serum concentrations of testosterone, LH and the body mass index, which was also correlated with the uterine area. This descriptive data from the largest reported series of women with PCOS enables the development of a management-orientated approach to the syndrome. Women who are overweight can expect an improvement in their symptoms if they lose weight. An elevated concentration of LH (> 10 IU/l) is associated with infertility and treatment should be chosen accordingly. If the serum testosterone concentration is > 4.8 nmol/l, other causes of hyperandrogenism should be excluded.
Adolescent↗
A case of isolated TSH deficiency presenting as infertility.
We report a case of late-onset isolated thyroid stimulating hormone deficiency in a woman who presented with oligomenorrhoea and secondary hyperprolactinaemia. Hypothalamic and pituitary radiology and function was otherwise normal. The underlying aetiology of this condition is thought to be due to an inborn defect in the thyrotroph and treatment is with standard thyroid replacement therapy.
Adult↗
Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects.
Previous studies have suggested that the endogenous release of inhibitory prostanoids limits the bronchoconstrictor response to repeated exercise. The aim of our study was to determine whether inhaled prostaglandin (PG)E2 attenuates exercise-induced bronchoconstriction or methacholine airway responsiveness in asthmatic subjects. Eight subjects with mild stable asthma and exercise bronchoconstriction were studied on 4 separate days, 48 h apart. Subjects inhaled PGE2 or placebo in a randomized, crossover, double-blind fashion, 30 min prior to an exercise challenge or a methacholine challenge. PGE2 inhalation significantly attenuated exercise bronchoconstriction. The mean maximal %fall in FEV1 after exercise was 26% (SEM 3.7%) after placebo, and was 9.7% (SEM 2.7%) after PGE2 (p < 0.001). PGE2 also significantly reduced the duration of exercise bronchoconstriction (p = 0.034). However, PGE2 did not significantly attenuate methacholine airway responsiveness. The geometric mean methacholine provocative concentration causing a 20% fall in FEV1 (PC20) was 0.77 (%SEM 1.48) after placebo day, and 1.41 (%SEM 2.20) after PGE2 (p = 0.30). These results demonstrate that inhaled PGE2 markedly attenuates exercise bronchoconstriction in asthmatic subjects and suggest that this effect is not occurring through functional antagonism of airway smooth muscle.
Administration, Inhalation↗
Effect of magnitude of airway responsiveness and therapy with inhaled corticosteroid on histamine tachyphylaxis in asthma.
Histamine challenge testing is used to measure airway responsiveness in asthma. Histamine tachyphylaxis has been demonstrated after repeated challenges in mild asthmatics not using inhaled corticosteroid. Other studies, using subjects with variable severity of asthma, have not demonstrated histamine tachyphylaxis. Forty patients with stable asthma were studied and stratified according to severity of airway hyperresponsiveness and use of inhaled corticosteroid, to examine the effects of these factors on histamine tachyphylaxis. Airway responsiveness was measured as the histamine provocative concentration causing a 20 percent fall in FEV1 (PC20). Twenty subjects had mildly increased airway hyperresponsiveness (PC20 > 1 mg/ml), of whom 10 were using inhaled corticosteroid. Twenty subjects had moderate to severely increased airway hyperresponsiveness (PC20 < 1 mg/ml), of whom 10 were using inhaled corticosteroid. On each of two study days, 1 week apart, two histamine challenges were performed 1 h apart. Histamine tachyphylaxis was found for the entire group on both study days. The geometric mean PC20 increased from 1.0 mg/ml (percent SEM 1.2) to 1.3 mg/ml (percent SEM 1.2) 1 h later on day 1 (p < 0.0005), and 1.1 mg/ml (percent SEM 1.2) to 1.3 mg/ml (percent SEM 1.2) 1 h later on day 2 p < 0.05). Subgroup analysis demonstrated that tachyphylaxis only occurred consistently in subjects with mildly increased airway hyperresponsiveness not receiving inhaled corticosteroid. In this group, the PC20 increased from 2.2 mg/ml (percent SEM 1.2) to 3.2 mg/ml (percent SEM 1.2) on day 1 (p < 0.001), and from 2.5 mg/ml (percent SEM 1.3) to 3.4 mg/ml (percent SEM 1.2) on day 2 (p < 0.05). This study confirms that histamine tachyphylaxis occurs in asthmatics, but is consistently present only in mild, noncorticosteroid-dependent asthmatics.
Administration, Inhalation↗
Bronchial provocation with leukotrienes and other stimuli.
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Administration, Inhalation↗
Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms.
Exercise-induced bronchoconstriction is caused, in part, by leukotriene (LT)D4 release in asthmatic airways. Asthmatics become refractory to exercise bronchoconstriction with repeated challenges, due to inhibitory prostaglandin release. The purpose of this study was to test the hypothesis that exercise refractoriness is caused by LTD4-induced inhibitory prostaglandin release. Fourteen stable asthmatic subjects with exercise-induced bronchoconstriction were studied. On the first 2 days, subjects underwent two challenges, 1 h apart, with either exercise or inhaled LTD4. Eight subjects then took part in three double-blind, randomized, placebo-controlled, crossover studies with flurbiprofen, a prostaglandin synthetase inhibitor, to determine whether cross refractoriness occurs between exercise and LTD4, whether flurbiprofen attenuates this effect, and whether flurbiprofen attenuates LTD4 tachyphylaxis. There was a reduction in the intensity of bronchoconstriction to the second challenge both with exercise (refractoriness) and with LTD4 (tachyphylaxis). The degrees of refractoriness and tachyphylaxis were correlated (r = 0.72, p = 0.005). Flurbiprofen attenuated LTD4 tachyphylaxis. Cross refractoriness occurred between exercise and LTD4, and flurbiprofen treatment also attenuated this effect. One hour after LTD4 challenge, the mean fall in FEV1 after exercise was 12.3% (%SEM 2.3) on placebo and 17.1% (%SEM 3.8) on flurbiprofen (p = 0.027). Similarly, 1 h after exercise, the LTD4 PC20 increased to 0.73 (%SEM 1.4) microgram/ml on placebo and 0.30 (%SEM 1.8) microgram/ml on flurbiprofen (p = 0.026). These results suggest that LTD4 released in asthmatic airways as a result of exercise stimulates inhibitory prostaglandin release, resulting in exercise refractoriness.
Adult↗