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Biomedical subjects

F Dunne

Publications and source records attributed to F Dunne.

At least 19 recordsLinked to original sources

Effect of treatment with nebivolol on parameters of oxidative stress in type 2 diabetics with mild to moderate hypertension.

AIM: The aim of this study was to examine the effect of the cadioselective B(1)-adrenoceptor blocker nebivolol on glycaemic control, lipid profile and markers of oxidative stress in patients with type 2 diabetes over a 6-month period. METHODS: Twenty-six patients with mild to moderate hypertension (140-160 mmHg systolic, 90-105 mmHg diastolic) confirmed on 24-h blood pressure monitoring, were treated with nebivolol 5 mg daily for 6 months. Total serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) subfractions, lipid hydroperoxides (LHPs) and total antioxidant capacity (TAC) were measured before and after 6 months of treatment. RESULTS: Nebivolol, as expected, reduced mean daytime systolic and diastolic pressures on ambulatory monitoring (149 +/- 9 to 140 +/- 13 mmHg, P = 0.02 and 84 +/- 7 to 77 +/- 9 mmHg, P < 0.001). There were no significant changes in serum cholesterol or triglycerides following treatment but a significant increase in HDL cholesterol was noted (1.12 +/- 0.19 to 1.25 +/- 0.36 mmol/L, P = 0.008). Patients showed a highly significant reduction in TAC from 501 +/- 57 to 422 +/- 29 trolox equivalent (P < 0.001). Baseline LHPs were very high and showed no significant change over the 6-month period (18.7 +/- 7.4 and 18.7 +/- 10.9 micromol/L). The LDL score increased significantly from 1.7 +/- 0.7 to 2.3 +/- 0.7 (P = 0.0002) at 6 months suggesting a change to a more atherogenic lipid profile. Neither weight nor glycaemic control changed during treatment. CONCLUSION: Nebivolol appears to be lipid neutral and may even have a positive effect on HDL cholesterol. Despite this it may promote the formation of potentially atherogenic LDL subfractions possibly as a result of reduced antioxidant defences. Further studies are needed to clarify the changes observed in parameters of oxidative stress.

Antihypertensive Agents↗

Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes.

The purpose of the present study was to determine changes in plasma lipids and markers of oxidative stress longitudinally in pregnancy complicated by diabetes compared with non-diabetic pregnancy. This was carried out by following a group of normal pregnant women (n=17) and groups of pregnant women with Type I diabetes (n=19), Type II diabetes (n=12) and gestational diabetes mellitus (n=12) throughout pregnancy, with sampling carried out at the end of each trimester. Serum total cholesterol and triacylglycerols (triglycerides) were determined using standard colorimetric techniques and low-density lipoprotein (LDL) subfraction profile by disc PAGE. Total antioxidant capacity (TAC) was determined by enhanced chemiluminescence and lipid hydroperoxides by the ferrous oxidation of Xylenol Orange method. Total cholesterol and triacylglycerols increased significantly throughout pregnancy in all groups, but there were no significant differences between normal and diabetic women with respect to either. The LDL score was significantly higher (P<0.001) in diabetic women compared with normal women at each point throughout pregnancy, although there were no significant differences between the diabetic groups. There was evidence of greater oxidative stress in diabetic compared with normal women throughout. Corrected TAC was significantly lower (P<0.001) in all diabetic women throughout pregnancy. In addition, lipid hydroperoxides were higher in all diabetic compared with normal women, particularly so in those with Type II diabetes (P<0.05). These changes may have important implications for diabetic women during pregnancy, as an elevated risk of pre-eclampsia is thought to reflect an oxidative stress-related mechanism. In addition, these changes may have important implications for the development of atherosclerosis and the long-term cardiovascular health of women with diabetes.

Adult↗

Maternal ante-natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro-Caribbeans, Asians and Caucasians.

AIMS: To measure the prevalence of persistent glucose intolerance at 6-12 weeks postpartum in various ethnic groups to assess the value of targeted postpartum screening. METHODS: A retrospective study was performed using computerized databases from two large maternity units within one UK region. Both units used the same screening strategy for gestational diabetes mellitus (GDM) and the same postpartum follow-up at 6-12 weeks using a 75-g oral glucose tolerance test (OGTT). A total of 221 women with a diagnosis of GDM/impaired glucose tolerance (IGT) in the index pregnancy in addition to a completed postpartum 75-g OGTT were studied. Of these, 91 were Caucasian, 89 were of Indo-Asian (Asian) origin and 41 were of Afro-Caribbean origin. RESULTS: The study showed that 35% Indo-Asians had persistent postpartum glucose intolerance compared with 7% Caucasians and 5% Afro-Caribbeans (P < 0.003). Insulin requirement during pregnancy and a diagnosis of gestational diabetes prior to 20 weeks of pregnancy were predictive for persistent postpartum glucose intolerance amongst Indo-Asians. CONCLUSIONS: The frequency of postpartum glucose intolerance among Indo-Asian women is significantly greater than among age-matched Caucasian and Afro-Caribbean women. We suggest that all Indo-Asian women with gestational diabetes should undergo postpartum screening for persistent glucose intolerance. However, in non-Asian women selective screening may be more cost effective.

Adult↗

Pregnancy in women with Type 2 diabetes: 12 years outcome data 1990-2002.

AIM: Twelve years' outcome analysis of pregnancies in women with Type 2 diabetes in a multiethnic geographically defined area. METHODS: Information about 182 women delivered between 1990 and 2002 was ascertained from a regional computerized database. The main outcome measures were rates of miscarriage, stillbirth, neonatal/postnatal deaths, congenital malformations, birth weight, mode of delivery, and neonatal unit care as well as maternal morbidities of polyhydramnios, postpartum haemorrhage, pregnancy-induced hypertension/pre-eclampsia. RESULTS: Among 182 singleton pregnancies, 161 (88%) resulted in a live outcome. There were 16 (8.8%) spontaneous miscarriages, two (1.2%) stillbirths, and three (1.6%) terminations. Congenital malformations occurred in 18 pregnancies (99/1000). There were two early and one late neonatal deaths and two further deaths in the postnatal period. Twenty-eight percent of infants were large for gestational age, with 15 (9.3%) greater than 4 kg. Fifty-three percent were delivered by caesarean section and 68 (37%) required admission to neonatal unit (NNU) care. Hypertension/pre-eclampsia was two times, polyhydramnios three times, and postpartum haemorrhage six times more common than in non-diabetic women. CONCLUSIONS: Women with Type 2 diabetes have a less satisfactory pregnancy outcome compared with the general population. Infants have a two-fold greater risk of stillbirth, a 2.5-fold greater risk of a perinatal mortality, a 3.5-fold greater risk of death within the first month and a six-fold greater risk of death up to 1 year compared with regional/national figures. They have an 11 times greater risk of a congenital malformation. We need to develop better educational and screening strategies if we are to improve.

Abortion, Spontaneous↗

Oxidative stress and normal pregnancy.

OBJECTIVE: To determine whether, in normal pregnancies, there is evidence of oxidative stress that is related to the lipid changes observed in pregnancy. DESIGN: Longitudinal study of healthy women having a normal pregnancy. Samples were obtained towards the end of each trimester and after 8 weeks postpartum. PATIENTS: Seventeen healthy women during a normal singleton pregnancy were compared with 12 healthy, non-pregnant women. MEASUREMENTS: Oxidative stress was determined by measuring total antioxidant capacity (TAC), uric acid and lipid hydroperoxides (LHP). Lipid status was evaluated by measuring total and high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein (LDL) subfractions. RESULTS: Pregnancy was associated with decreased TAC and uric acid in the first trimester, which gradually increased during pregnancy, reaching normal values during the postpartum period. LHP significantly increased towards the end of pregnancy. The changes observed in LHP were significantly correlated with increases in LDL subfraction profile. CONCLUSIONS: Late pregnancy was associated with the formation of susceptible, oxidisable particles (high LDL score) and an increase in oxidative damage. These biochemical changes may be relevant for the long-term cardiovascular health of women, especially those of high parity or those who are at high risk for cardiovascular disease (e.g. women with diabetes).

Adult↗

Substance use and other psychiatric disorders in impaired practitioners.

This paper describes the nature and comorbidity of substance use and other psychiatric disorders in 157 impaired practitioners notified to the Medical Practitioners Board of Victoria from 1983 to 1997. Diagnoses were reduced to three diagnostic categories, viz, substance use disorder (n = 62), other psychiatric disorder (n = 62), and combined substance use and other psychiatric disorder (n = 33). Sixty nine percent of those with other psychiatric disorders suffered either bipolar disorder (n = 27), schizophrenia (n = 22), or depression (n = 17). Psychiatric comorbidity in drug-related diagnoses was 26% and in alcohol-related diagnoses 64%. Sixty five percent of substance use disorders were notified more than 12 months after onset of impairment, and 49% of all practitioners (71% with substance use disorder) did not receive treatment prior to notification. This combined with a high relapse rate (41%) makes some impaired practitioners a risk to their patients.

Adult↗

Beta-blockers in the management of hypertension in patients with type 2 diabetes mellitus: is there a role?

It has been conclusively established that treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes mellitus will significantly reduce the incidence of stroke, heart failure and progression of diabetic complications. Beta-blockers are effective antihypertensive agents which, in long term studies, have proven beneficial in reducing important clinical end-points. However nonselective beta-blockers may have a negative effect on lipid profiles and contribute to hypoglycaemic unawareness, thus preventing their use in some patients with diabetes mellitus. The development of newer and more selective beta-blockers has overcome many of these problems. In addition, some of the newer agents have novel properties such as release of nitric oxide, which theoretically would make them more attractive in patients with diabetes mellitus. Overall, the adverse metabolic effects of beta-blockers do not appear to be important in clinical practice and these agents should no longer be contraindicated in patients with type 2 diabetes mellitus. Their proven cardiovascular benefits would seem to easily tip the balance in favour of their use.

Adrenergic beta-Antagonists↗

Effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients symptomatically stable on lithium.

BACKGROUND: Previous studies suggest that brain serotonin neurotransmission may mediate the actions of lithium carbonate. Acute tryptophan depletion reduces brain serotonin and allows the study of this neurotransmitter in patient groups. AIMS: To examine the effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients who were symptomatically stable on lithium. METHOD: Nineteen subjects satisfying DSM-IV criteria for bipolar I disorder participated in a within-subject, double-blind, placebo-controlled random-order crossover study. Symptoms were evaluated following acute tryptophan depletion, which was induced by a 100 g amino acid drink following an overnight fast. RESULTS: Plasma tryptophan fell significantly after the depleting drink, but not after the control drink (P < 0.05, paired t-test, mean reduction 83%). No significant changes in mood or suicidality scores were recorded after acute tryptophan depletion. CONCLUSIONS: Acute tryptophan depletion does not reverse lithium's effects on mood and suicidality in bipolar disorder.

Adult↗

Pregnancy outcome in women with type 2 diabetes mellitus needs to be addressed.

Maternal diabetes mellitus (types 1 and 2) is the most chronic prevalent medical condition affecting the pregnant population and is associated with a less satisfactory pregnancy outcome for both mother and infant when compared with the non-diabetic population. Most reports have focused on women with type 1 disease, type 2 disease being perceived as a less serious condition. However, type 2 disease is far more common (and is increasing) in some areas of the UK, especially where there is a high proportion of women from the Indian subcontinent. This paper shows that pregnancy complicated by type 2 diabetes mellitus is a high-risk state, with miscarriage and congenital malformations almost twice that seen in type 1 disease. These adverse outcomes are contributed to by poor attendance for pre-pregnancy care, later booking for antenatal clinic and poor glycaemic control at booking. Offspring of pregnancies complicated by type 2 diabetes are more likely to be delivered before 37 weeks gestation and be large in size for gestational age. We must dispel the myth, in women of childbearing age and in their healthcare providers, that diabetes treated with diet and/or tablets (type 2) is a less serious problem than type 1 disease.

Abortion, Spontaneous↗

Diabetes knowledge--are patients getting the message?

Diabetes knowledge in a multi-ethnic population was assessed in 161 insulin treated diabetic patients using a 21-point multiple choice questionnaire translated into the appropriate languages. Our data showed a significant difference in diabetes knowledge related to ethnicity, being less in Asians and Afro-Caribbeans groups compared to Caucasians. In all groups there was a negative correlation with age, with older adults achieving lower scores. Gender and duration of disease did not appear to influence knowledge scores. This information has implications for the way in which we deliver our diabetes educational programme to ethnic minority groups and the elderly.

Adult↗

Impaired practitioners notified to the Medical Practitioners Board of Victoria from 1983 to 1997.

OBJECTIVE: To describe the characteristics of and outcome for impaired medical practitioners notified to the Medical Practitioners Board of Victoria. DESIGN: Retrospective review of records for all impaired practitioners notified to the Board for the first time from January 1983 to December 1997. OUTCOME MEASURES: Number of notifications per year; characteristics of impaired practitioners; source of notification; diagnosis and diagnostic categories; actions by the Board; and outcomes for impaired practitioners. RESULTS: In 15 years, 170 impaired practitioners were notified to the Board for the first time, 86 in the last four years. Significantly more men than women were notified to the Board (ratio, 4.2:1; P < 0.001). Reporting by patients was uncommon, but 46 impaired practitioners reported themselves. One hundred and five impaired practitioners had a psychiatric disorder, 73 had a drug use disorder, 35 had an alcohol use disorder, and 13 had a physical disorder (not exclusive categories). The Board suspended 73 practitioners and imposed conditional registration on 76. Subsequently, 88 practitioners were able to improve their registration status. Fifty-nine practitioners were renotified to the Board or tested positive to a urinary drug screen. Eleven practitioners died, four before the age of 55 years. CONCLUSIONS: Increasing numbers of notifications in recent years coincided with changes in the legislative framework, making notification compulsory but also giving the Board more flexibility in dealing with impaired practitioners. Nonetheless, comparison with population data suggests that impaired practitioners (particularly those with substance use disorders) may be under-reported.

Adult↗

Is normal pregnancy atherogenic?

Serum cholesterol, triacylglycerols and low-density lipoprotein (LDL) subfractions were determined in 120 primagravid women during normal gestation (40 in each trimester) and in 20 non-pregnant age-matched controls. LDL subfractions were determined by PAGE, and an LDL score was calculated. The higher the score, the smaller the subfractions. The objective of the study was to determine the effects of the hyperlipidaemia, high oestrogen concentrations and insulin resistance known to exist in normal pregnancy on LDL subfraction formation. Pregnant women had an increased mean serum cholesterol concentration [5.78 (S.D. 1.09) mmol/l] in the first trimester compared with the non-pregnant controls [5.11 (0.77) mmol/l; P<0.01]. The serum cholesterol concentration increased progressively throughout gestation to a mean of 8.14 (1.39) mmol/l in the third trimester (P<0.001 compared with the second trimester). Triacylglycerol concentrations in the first trimester were similar to those of controls, and there was a non-significant increase by the second trimester to 1.32 (0.44) mmol/l. However, by the third trimester the mean triacylglycerol concentration had doubled [2.58 (0.98) mmol/l; P<0.001 compared with the first and second trimester]. During gestation the LDL score increased dramatically, from 1.17 (0.39) during the first trimester to 2.01 (0.37) in the second trimester (P<0.001) to 2.73 (0.48) in the third trimester (P<0.001 compared with the second trimester). Thus an atherogenic lipid profile develops during normal gestation. The significance of these changes remains unclear, but thay may have important implications for mother and foetus.

Adult↗

Age-independent oxidative stress in elderly patients with non-insulin-dependent diabetes mellitus.

Impaired antioxidant defence is implicated in the development of cardiovascular complications in non-insulin-dependent diabetes (NIDDM). However, as many of these patients are elderly, observed changes in antioxidant status may be due to the patient's age rather than their disease. We sampled blood from 47 elderly NIDDM patients (21 male and 26 female; mean age +/- SD, 75.62 +/- 7.97 years), 66 young (30 male and 36 female; 24.52 +/- 4.72 years) and 58 healthy elderly volunteers (17 male and 41 female; 70.74 +/- 4.85 years), and measured the antioxidant glutathione, the marker for free-radical-damage lipid hydroperoxide products (LHP), vitamin E and total antioxidant capacity (TAC). There was a significant increase in LHP in the healthy elderly group compared with the young volunteers (3.14 +/- 1.5 vs. 2.14 +/- 1.38 mumol/l, p < 0.01). The values were much higher in NIDDM patients (7.02 +/- 2.29 mumol/l, p < 0.0001 vs. healthy elderly). There was a reduction in TAC in healthy elderly compared with the young (359.99 +/- 54.82 vs. 471.47 +/- 94.29 mumol/l trolox equivalents, p < 0.0001), but there was no further reduction in NIDDM patients. Similarly, glutathione was reduced to the same degree in healthy elderly and NIDDM patients (0.29 +/- 0.09, 0.30 +/- 0.11 vs. 0.54 +/- 0.19 mumol/l in young volunteers, p < 0.0001). Vitamin E concentrations were comparable in all groups (26.34 +/- 5.39 young volunteers, 31.50 +/- 8.23 healthy elderly and 30.98 +/- 9.03 mumol/l NIDDM patients), but after correction for serum cholesterol there was a significant reduction in the diabetic group compared with the young, but not with the elderly (5.54 +/- 1.55 vs. 6.67 +/- 1.86 vs. 6.31 +/- 1.85 (mumol/l)/(mmol/l), p < 0.01). We have demonstrated an age-dependent reduction in total antioxidant capacity and glutathione defence and an age-independent increase in LHP in elderly patients with NIDDM. Reduced concentrations of vitamin E were demonstrated in NIDDM patients compared with young, but not elderly, volunteers. Increased oxidative damage occurs independently of age in NIDDM patients despite comparable antioxidant defences in this age group.

Adult↗