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L Beilin

Publications and source records attributed to L Beilin.

15 recordsLinked to original sources

Advanced glycation end-products: a review.

Advanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occurring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications.

Aging↗

Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.

Adolescent↗

Study of plasma factors associated with neutrophil activation and lipid peroxidation in preeclampsia.

Neutrophil activation occurs in women with preeclampsia and is resolved after delivery. The present study examined whether circulating factors in plasma of women with preeclampsia caused neutrophil activation and lipid peroxidation. Twenty-one women with proteinuric preeclampsia were matched for age and gestational age with 19 normal pregnant women. Plasma was collected from all subjects before delivery and at 6 weeks postpartum and incubated with autologous white-cell buffy coat collected at the postpartum visit. Neutrophil activation was assessed by level of CD11b and CD18 expression after incubation with autologous antepartum or postpartum plasma. Lipid peroxidation was assessed by measurement of F(2)-isoprostanes in plasma, plasma-white cell incubates, and urine. Neutrophil CD11b and CD18 expression was not differentially altered by incubation with plasma from either women with preeclampsia or normal pregnant women and was similar between groups when incubation was performed with plasma collected after delivery. In preeclampsia, plasma F(2)-isoprostanes were significantly increased before and after delivery compared with controls. Plasma F(2)-isoprostanes were increased 2-fold after incubation of plasma with buffy coat, but preeclamptic women had higher levels compared with those of controls when either pregnant or postpartum plasma was used. In pregnant preeclamptics, plasma F(2)-isoprostanes were positively correlated with lymphocyte count. Six weeks after delivery, plasma F(2)-isoprostanes in the preeclamptic women were significantly positively associated with lymphocyte count and cholesterol and negatively associated with albumin. In conclusion, the present study does not suggest that a stable circulating factor causes neutrophil activation in preeclampsia. However, lipid peroxidation is elevated before and after delivery in women with preeclampsia, which suggests that these women may have an underlying predisposition to increased oxidative stress that may be driven by or contribute to a persistent low-grade inflammatory response.

Adult↗

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring.

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

Antihypertensive Agents↗

Strategies for prevention of adult hypertension and cardiovascular risk behaviour in childhood. An Australian perspective.

This paper addresses approaches to evaluating the importance of different childhood behaviours on subsequent risk of high blood pressure and related cardiovascular risk factors and outlines results of a randomised controlled trial of nutrition and exercise interventions in schoolchildren. Clustering of cardiovascular risk factors was studied in relation to diet, blood pressure, fitness, fatness and blood cholesterol in a representative sample of 555 Perth schoolchildren aged 15 years. Twenty-one percent of males and females had high risk profiles associated with dietary excesses, particularly in fat, cholesterol and sodium intake, and deficiencies of minerals, vitamins and dietary fibre. Socio-economic status was inversely associated with cardiovascular risk and undernutrition in girls. Thus 21% of the school children shared unhealthy lifestyles putting them at substantial risk of subsequent cardiovascular disease. A randomised controlled trial designed to reduce cardiovascular risk was conducted in 1147 children 10-12 years old, assigned to one of six groups for a year. The groups were fitness, fitness and school nutrition, school nutrition, school and home nutrition, home nutrition or controls. On cluster analysis 30% of the children were at higher risk at baseline in terms of blood pressure, blood cholesterol levels, fitness and body fat. With the fitness programmes fitness increased in both high and low risk girls but only in high risk cluster boys. Systolic pressure fell more in the high risk boys in the fitness group than in low risk boys, while diastolic pressure fell in girls regardless of initial risk. Triceps skinfold thickness fell more in higher than lower risk girls in the school and home nutrition group, and more in high risk boys in the home nutrition group. Higher risk girls showed a greater reduction in fat intake and increase in dietary fibre with home nutrition programmes. We concluded that higher risk children do show greater responses to lifestyle intervention programmes in general, with the greatest effects seen with home nutrition or fitness programmes. The results indicate the need for different approaches to prevention of hypertension and cardiovascular risk in higher and lower risk children and for boys and girls.

Adolescent↗

Mangostin inhibits the oxidative modification of human low density lipoprotein.

The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50 microM as monitored by the formation of conjugated dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 100 microM mangostin. We observed an inhibition of TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50 microM mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin (100 microM) significantly inhibited the consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in this in vitro system.

Amidines↗

A controlled trial of labetalol (Trandate), propranolol and placebo in the management of mild to moderate hypertension.

1. Labetalol, a new drug combining alpha-and beta-adrenoceptor blocking properties, has been compared with placebo in a double-blind crossover study of a group of patients with mild to moderate essential hypertension (blood pressure 150/100 to 189/114 mmHg). 2. Labetalol and propranolol lowered blood pressure satisfactorily in the supine position, but labetalol reduced blood pressure more in the erect posture and following exercise and induced less bradycardia. Thus alpha- as well as beta-adrenoceptor blocking actions appear to contribute to blood pressure reduction. 3. Side effects attributable to labetalol were few. The effective dose ratio labetalol: propranolol was 2.5:1 (w/w). 4. Labetalol, a new form of hypotensive agent, merits further controlled assessment of its usefulness in relation to existing drugs.

Adult↗

Early platelet consumption in pre-eclampsia.

One hundred and thirty-one women with chronic hypertension were studied serially during pregnancy to determine the sequence of events in the development of superimposed pre-eclampsia and to discover the time of onset. Twenty-seven women developed a sustained rise in plasma urate concentrations, which began at about 28 weeks' gestation and which is characteristic of pre-eclampsia. The mean platelet count was already significantly reduced and continued to fall until delivery, which was on average at 36 weeks' gestation. A comparable but smaller decrease in platelet count was seen in 55 women who had borderline but consistent increases in plasma urate concentrations. In 49 women whose plasma urate concentrations remained steady the platelet count did not change significantly before delivery. The reduced platelet count in women who develop pre-eclampsia suggests that increased platelet consumption is an early feature of the disorder.

Adult↗

Renal prostaglandin synthesis in experimental renal clip hypertension in the rat.

1. The hypothesis that suppression of prostaglandin E (PGE) synthesis by indomethacin exacerbates renal clip hypertension in the rat was investigated. 2. Indomethacin exacerbated hypertension in renal clip rats. 3. In vitro PGE synthesis determined by gas liquid chromatography (GLC) was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment. 4. The findings support the concept that PGs participate in blood pressure regulation in experimental renal hypertension.

Animals↗

Pressor effect of moderate alcohol consumption in man: a proposed mechanism.

Ingestion of alcohol was associated with a highly significant increase in systolic blood pressure and heart rate which occurred before the blood alcohol reached its peak concentration of 16.9 (s.e.m. = 1.1) mol/1. Drinking non-alcoholic cold liquids caused a marked but transient fall in adrenaline and a rise in noradrenaline concentration. Alcohol prevented this fall in adrenaline and led to a sustained increase in noradrenaline concentration. These changes may be implicated in the elevation of blood pressure associated with alcohol consumption.

Adult↗

A controlled trial of nurse counselling on lifestyle change for hypertensives treated in general practice: preliminary results.

1. We assessed whether a lifestyle modification programme implemented by nurse counsellors in a general practice setting would improve blood pressure (BP) control in treated hypertensive patients. 2. Patients were randomized into a control group or one of two intervention groups who received either a high or low level of counselling. 3. Patients in the intervention groups had appointments every 4th week for 18 weeks. The low intervention group had one practice appointment and five telephone counselling appointments while the high intervention group had six appointments in their general practice. The patients were counselled using a stage of change behavioural model and motivational interviewing to: reduce alcohol consumption, dietary fat and salt intake and weight; cease smoking; and increase leisure time physical activity. 4. Compared with controls the low intervention group showed significant decreases in alcohol and salt intake while the high intervention resulted in significant decreases in both weight and BP. 5. We conclude that nurse counselling targeted to specific aspects of lifestyle can improve BP control and weight in treated hypertensive patients over 18 weeks. Its longer term effectiveness in the management of hypertension warrants further evaluation.

Behavior Therapy↗

1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization.

The present Guidelines were prepared by the Guidelines Sub-Committee of the World Health Organization-International Society of Hypertension (WHO-ISH) Mild Hypertension Liaison Committee, the members of which are listed at the end of the text. These guidelines represent the fourth revision of the WHO-ISH Guidelines and were finalised after presentation and discussion at the 7th WHO-ISH Meeting on Hypertension, Fukuoka, Japan, 29th Sept-1st Oct, 1998. Previous versions of the Guidelines were published in Bull WHO 1993, 71:503-517 and J Hypertens 1993, 11:905-918.

Adult↗