Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study.

In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.

Prostaglandin E2, renin and angiotensin II in renovascular hypertension.

We studied a group of 12 hypertensive patients (seven men, five women) with unilateral renal arterial stenosis, and evaluated the morphological criteria on renal angiography for the significance of the stenosis and compared them with the prostaglandin-E2 (PGE2), plasma renin activity (PRA), and angiotensin II (ANG II) concentrations in both renal veins. PGE2 and PRA concentrations were significantly higher in renal veins of kidneys with arterial stenosis with patients supine and after sitting up for 15 min, but the ANG II concentration was raised only with the patient sitting. Assuming that a PRA ratio greater than 2 signifies stenosis of haemodynamic importance, correlation to the angiographic classification was seen in 11 of the 12 patients. The PGE2 ratios were better correlated to PRA ratios than to the angiographic findings. ANG II ratios showed an inconstant and variable pattern in relation to the morphological picture. Our results confirm that PGE2 concentrations in renal venous blood increase in parallel to PRA, and may be interpreted as a means of preserving the blood flow in a kidney with arterial stenosis. However, it is unclear whether this increase is the result of dilution factors or of increased net production of PGE2. Determination of PGE2 in renal vein blood apparently gives no additional information about the functional significance of renal arterial stenosis, and PRA determinations remain the best guide in the management of renovascular hypertension.

Acidification in developing countries: ecosystem sensitivity and the critical load approach on a global scale.

Acidification represents a growing threat to certain developing country ecosystems in tropical and subtropical climates. A methodology investigating the extent of acidification risks from sulfur emissions on a global scale is presented. Atmospheric transfer models have been used to calculate transfer and deposition of sulfur (using emissions for 1990 and a projection for 2050) and alkaline soil dust. A method to derive the relative sensitivity of terrestrial ecosystems is explained and preliminary critical load values are assigned. A range of values for critical loads and base cation deposition have been used to investigate uncertainty in maps depicting the excess of deposition above critical loads. These show an increasing risk of acidification in 2050 in extended regions of southern and eastern Asia, as well as parts of southern Africa, in comparison to 1990. Certain areas, especially in Asia, are shown at risk even when high values of critical load and base cation deposition are used.

Controlling persistent organic pollutants-what next?

Within the context of current international initiatives on the control of persistent organic pollutants (POPs), an overview is given of the scientific knowledge relating to POP sources, emissions, transport, fate and effects. At the regional scale, improvements in mass balance models for well-characterised POPs are resulting in an ability to estimate their environmental concentrations with sufficient accuracy to be of help for some regulatory purposes. The relevance of the parameters used to define POPs within these international initiatives is considered with an emphasis on mechanisms for adding new substances to the initial lists. A tiered approach is proposed for screening the large number of untested chemical substances according to their long-range transport potential, persistence and bioaccumulative potential prior to more detailed risk assessments. The importance of testing candidate POPs for chronic toxicity (i.e. for immunotoxicity, endocrine disruption and carcinogenicity) is emphasised as is a need for the further development of relevant SAR (structure activity relationship) models and in vitro and in vivo tests for these effects. Where there is a high level of uncertainty at the risk assessment stage, decision-makers may have to rely on expert judgement and weight-of-evidence, taking into account the precautionary principle and the views of relevant stake-holders. Close co-operation between the various international initiatives on POPs will be required to ensure that assessment criteria and procedures are as compatible as possible.

Report on a panel debate on agricultural subsidies from a water perspective.

The relationships between subsidies, trade and water issues and poverty are complex. If trade barriers and subsidies were removed by the developed countries, it is likely that opportunities for the developing countries would improve--not just for increased trade but also for improved livelihood opportunities.

Workshop 1 (synthesis): water as a catalyst for development.

The problem of allocating water resources is a political one, and water management teams now need to include political lobbyists and advisors. Education, at all levels, is a crucial element in any development strategy involving water.

Workshop 3 (synthesis): climate variability, water systems and management options.

Addressing climate variability now will better prepare us for future impacts of climate change. Sustained, multi-stakeholder dialogue at local through national levels is an approach that will reach the widest audience, helped by tools that illustrate vulnerability such as the Climate Vulnerability Index. Integrated water resources management deals with managing for variability and change and is therefore highly appropriate for dealing with climate impacts.

Hydrosolidarity intergenerational challenges: long-term commitment for long-term issues.

The year 2000 Young Professionals Seminar focused on long-term intergenerational challenges. Water related problems are symptoms of complex and ultimately societal problems linked to human behaviour, political support and managerial and institutional structures. Although integrated water resources management is presented as a solution, it is not always well understood, and can create a sense of hopelessness among professionals. To make it operational requires long-term commitments among various professionals and the involvement of new actors. A number of key topics crystallised as needing further attention, including ethical dimensions in policy making, the development of a framework for a "Future Generation Impact Assessment" (FGIA), and efforts to achieve true dialogue among stakeholders. Young water professionals must become more involved in political processes and take active part in institutional changes. Such engagement will require changes in the working environment facing many young professionals that causes frustration due to inefficient and conservative hierarchical structures and the lack of transparency.

Workshop 2 (synthesis): driving forces and incentives for change towards sustainable water development.

Water is a key resource in attaining sustainability--in social and economic development as well as in the long-term carrying capacity of the planet's life support systems, but consensus on the meaning and priority of these terms is still needed. Amongst the key points identified for water professionals: it is necessary to challenge compartmentalisation in water policy and management; water management strategies must focus clearly on the interdependence of the environment and socio-economic development; water professionals have a key role but must package the information and insight they can provide in a way that is attractive to intended recipients such as policy makers.

Sustainable water future with global implications: everyone's responsibility.

The current use and management of freshwater is not sustainable in many countries and regions of the world. If current trends are maintained, about two-thirds of the world's population will face moderate to severe water stress by 2025 compared to one-third at present. This water stress will hamper economic and social development unless action is taken to deal with the emerging problems. The Comprehensive Assessment of the Freshwater Resources of the World, prepared by the UN and the Stockholm Environment Institute, calls for immediate action to prevent further deterioration of freshwater resources. Although most problems related to water quantity and quality require national and regional solutions, only a global commitment can achieve the necessary agreement on principles, as well as financial means to attain sustainability. Due to the central and integrated role played by water in human activities, any measures taken need to incorporate a wide range of social, ecological and economic factors and needs. The Assessment thus addresses the many issues related to freshwater use, such as integrated land and water management at the watershed level, global food security, water supply and sanitation, ecosystem requirements, pollution, strengthening of major groups, and national water resource assessment capabilities and monitoring networks. Governments are urged to work towards a consensus regarding global principles and guidelines for integrated water management, and towards their implementation in local and regional water management situations. The alternative development options available to countries facing water stress, or the risk thereof, needs to be considered in all aspects of development planning.

Medical status and complications in relation to periodontal disease experience in insulin-dependent diabetics.

The aim of this study was to define a population of diabetics exhibiting an increased risk of developing severe periodontitis by comparing the medical status of 2 groups of diabetics, 1 with no/minor periodontal disease and 1 with severe periodontal disease. The case-control study consisted of 2 parts, a baseline study and a follow-up study. 39 case-control pairs were selected. They were adult, long-duration, insulin-dependent diabetics matched according to sex, age and diabetes duration. One individual in each pair (the CASE) exhibited severe periodontal disease while the other (the CONTROL) exhibited gingivitis or only minor alveolar bone loss. The median age of the cases was 58 years (range 36 to 70 years) and of the controls 59 years (range 37 to 69 years). The median disease duration in cases and controls was 24 years and 25 years, respectively. The median follow-up time was 6 years. The medical variables analysed were weight, insulin dose, systolic and diastolic blood pressure, vibratory threshold, triglycerides, total-cholesterol, HDL-cholesterol, creatinine, HbA1, proteinuria, ECG, retinopathy, stroke, transient ischemic attacks (TIA), angina, myocardial infarct, heart failure, hypertension, intermittent claudication, foot ulcer, death, cause of death, and smoking habit. Biochemical analyses and clinical variables used as a routine in the monitoring of diabetics failed to differentiate between diabetics with severe and minor periodontal disease. In the follow-up study, significantly higher prevalences of proteinuria and cardiovascular complications such as stroke, TIA, angina, myocardial infarct and intermittent claudication were found in the case group. An association between renal disease, cardiovascular complications and severe periodontitis seems to exist. This indicates that a closer cooperation between the diabetologist and the dentist is necessary in monitoring the diabetic patient.

Prostaglandin E2 and the renin-angiotensin system in primary aldosteronism and Cushing's syndrome.

8 patients with primary aldosteronism (PA) and 4 women with Cushing's syndrome (CS) were investigated with estimations of prostaglandin E2 (PGE2), plasma renin activity (PRA), and angiotensin-II (A-II) concentrations in renal venous blood, under resting and strictly standardized conditions and without pharmacological influence. In the PA group all hormone values were extremely low, but with a tendency to higher PRA and A-II concentrations in patients with idiopathic adrenal hyperplasia. Such low PGE2 concentrations have not previously been reported, and may be the consequence of decreased concentration of circulating A-II. However, a yet unidentified mechanism for the parallel suppression of the renin-angiotensin system (RAS) and of products of arachidonic acid metabolism cannot be excluded in hypertensive states where blood pressure is mainly dependent on volume factors. The number of patients in the CS group was too small to permit definitive conclusions, but a specific pattern of the PGE2 production is probably not seen in conjunction with hypercorticism. There seemed to exist only a covariation between PGE2 concentration and the degree of activation of the RAS.

Renal prostaglandin E2 and the renin-angiotensin system in hypertensive disorders in man.

We studied renal vein concentrations of prostaglandin E2 (PGE2) and activity of the renin-angiotensin system in 9 normotensive young men (NT), 17 hypertensive patients with unilateral renal artery stenosis (URS), and 26 patients with essential hypertension (EH) of whom 12 had low renin essential hypertension (LRH). The PGE2 concentration, plasma renin activity (PRA), and angiotensin II (A II) were measured in the inferior vena cava and were compared with the mean concentration for both renal veins under basal conditions and without pharmacological interference. The renal vein PGE2 concentrations were higher in NT (p less than 0.01) and URS (p less than 0.05) than in LRH. However, there were no significant differences in A II concentrations between the groups, nor were there any correlations to PGE2 concentrations. The positive correlation between PRA and PGE2 (r = 0.29, p less than 0.02) indicates that PGE2 may contribute to the activation of the renin-angiotensin system or that there may be a common mechanism for stimulation of both hormonal systems. Our results are not compatible with the hypothesis that a reduction of PGE2 production is a specific feature of patients with EH.

Hormonal responses to change in posture in hypertensive man. Evaluation by measurements of prostaglandin E2, renin activity, angiotensin II, and norepinephrine in renal venous blood.

The hormonal responses to the stimulus of changing from resting supine to sitting upright for 15 minutes were assessed in 20 patients with hypertension, divided into 2 groups. 8 patients had essential hypertension (EH) and 12 unilateral renal artery stenosis (URS). The prostaglandin E2 (PGE2) concentration, plasma renin activity (PRA), angiotensin II (A-II) concentration, and norepinephrine (NE) concentration were measured in renal vein blood using specific methods. The PGE2 concentration increased after sitting for 15 minutes in all patients (p less than 0.001), but the increment was significant only in those with URS. The PRA was lower both at rest and after sitting up in the EH group than in the URS group. After sitting up the A-II concentration increased more in patients with URS than in those with EH (p less than 0.05). NE levels rose significantly when all patients were included (p less than 0.01), mainly owing to changes in the EH group. Supine and sitting PRA and A-II were correlated (r=0.47 and r=0.52; both p less than 0.05), and also sitting PGE2 and A-II (r=0.46, p less than 0.05). The inverse relation between PGE2 and NE for the difference in hormone concentrations between supine and sitting (r=-0.44, p less than 0.05) may be explained by an inhibitory effect of PGE2 on renal NE release, earlier observed in experiments in vitro. Similar changes in PGE2 and the measured components of the renin-angiotensin system in response to change in posture may indicate these factors are interrelated.

Periodontal conditions in insulin-dependent diabetics.

The aim of this study was to compare the prevalence and severity of periodontal disease in age- and sex-matched adult long- and short-duration insulin-dependent diabetics and non-diabetics. The study involved 82 subjects with long- and 72 with short-duration diabetes and 77 non-diabetics, all aged 20-70 years. The clinical and radiographic examination comprised recordings of the number of existing teeth, absence or presence of plaque and supra- and subgingival calculus, gingival conditions, probing pocket depth and alveolar bone level. There were no significant differences in the number of existing teeth or presence of plaque and supra- and subgingival calculus between long- and short-duration diabetics and non-diabetics. Diabetics, irrespective of the duration of the disease, had a higher prevalence of sites with gingivitis than non-diabetics. Overall, there were no significant differences between the groups regarding the prevalence of tooth surfaces with probing pocket depths of 4 and 5 mm. However, on comparison between age subgroups, long-duration diabetics younger than 45 years had significantly more 4 and 5 mm pockets than non-diabetics. Long-duration diabetics altogether had significantly more tooth surfaces with probing depth greater than or equal to 6 mm than non-diabetics. The radiographs of alveolar bone height exhibited significantly more extensive alveolar bone loss in long-duration diabetics aged 40-49 years than in short-duration diabetics and non-diabetics. This, together with the increased number of subjects belonging to classification groups with severe periodontal disease experience among long-duration diabetics, indicates more periodontal disease in these diabetics.

Dental care habits and knowledge of oral health in insulin-dependent diabetics.

The aim of this study was to investigate dental care habits and knowledge of oral health in age- and sex-matched adult long and short duration insulin-dependent diabetics and non-diabetics. Ninety-four long and 86 short duration diabetics and 86 non-diabetics, aged 20-70 years, participated in the study. All subjects answered a questionnaire with 38 questions about dental visits, attitudes to and knowledge of dental diseases, toothcleaning, dietary and smoking habits, and oral sensations. Among the diabetics there was a rather large group that did not visit a dentist annually. The diabetics also required more emergency dental care and were not as willing as the non-diabetics to spend time and money on their teeth. The compliance with dietary advice was poor among the diabetics. Oral discomfort such as prickling and burning sensations, metallic and bad taste was rare in both diabetics and non-diabetics. In the diabetics, however, a feeling of mouth dryness was common.