Search

There is a significant unmet need for safe and effective anti-inflammatory treatment for cystic fibrosis. The aim of this study was to evaluate the safety of acebilustat, a leukotriene A4 hydrolase inhibitor, and its effect on inflammation biomarkers in patients with cystic fibrosis. Seventeen patients with mild to moderate cystic fibrosis were enrolled and randomized into groups receiving placebo or doses of 50 mg or 100 mg acebilustat administered orally, once daily for 15 days. Sputum neutrophil counts were reduced by 65% over baseline values in patients treated with 100 mg acebilustat. A modestly significant 58% reduction vs. placebo in sputum elastase was observed with acebilustat treatment. Favorable trends were observed for reduction of serum C-reactive protein and sputum neutrophil DNA in acebilustat-treated patients. No changes in pulmonary function were observed. Acebilustat was safe and well tolerated. The results of this study support further clinical development of acebilustat for treatment of cystic fibrosis. [ABSTRACT FROM AUTHOR]

The United Kingdom has successfully implemented a salt reduction programme. We carried out a comprehensive analysis of the programme with an aim of providing a step-by-step guide of developing and implementing a national salt reduction strategy, which other countries could follow. The key components include (1) setting up an action group with strong leadership and scientific credibility; (2) determining salt intake by measuring 24-h urinary sodium, identifying the sources of salt by dietary record; (3) setting a target for population salt intake and developing a salt reduction strategy; (4) setting progressively lower salt targets for different categories of food, with a clear time frame for the industry to achieve; (5) working with the industry to reformulate food with less salt; (6) engaging and recruiting of ministerial support and potential threat of regulation by the Department of Health (DH); (7) clear nutritional labelling; (8) consumer awareness campaign; and (9) monitoring progress by (a) frequent surveys and media publicity of salt content in food, including naming and shaming, (b) repeated 24-h urinary sodium at 3-5 year intervals. Since the salt reduction programme started in 2003/2004, significant progress has been made as demonstrated by the reductions in salt content in many processed food and a 15% reduction in 24-h urinary sodium over 7 years (from 9.5 to 8.1 g per day, P<0.05). The UK salt reduction programme reduced the population's salt intake by gradual reformulation on a voluntary basis. Several countries are following the United Kingdom's lead. The challenge now is to engage other countries with appropriate local modifications. A reduction in salt intake worldwide will result in major public health improvements and cost savings. [ABSTRACT FROM AUTHOR]

To study the relationship between pre-dialysis plasma sodium and blood pressure (BP), we performed an audit of patients who were on stable haemodialysis at St Bartholomew's and The Royal London Hospital from 1 June 2009 to 15 June 2010. There were 651 patients with 7445 dialysis sessions where both plasma biochemistry and BP were measured before haemodialysis. We found a significant association between plasma sodium and both systolic and diastolic BP. A 1 mmol l−1 increase in plasma sodium was related to 0.65/0.36 mm Hg increase in BP (P<0.001 for both systolic and diastolic BP) after adjusting for potential confounding factors, including weight gain between dialyses and plasma albumin, both of which are crude indices of extracellular fluid volume. A separate analysis excluding individuals who were on BP treatment showed a similar relationship, with a 1-mmol l−1 increase in plasma sodium associated with 0.82/0.56 mm Hg increase in BP (P<0.001 for both, N=177). These results provide further support for the accumulating evidence that plasma sodium has an important role in regulating BP, which may be independent of extracellular volume. Our findings in conjunction with other evidence suggest that small changes in plasma sodium could be an important mechanism for the beneficial effects of lower dialysate sodium and lower salt intake on BP in haemodialysis patients. [ABSTRACT FROM AUTHOR]

High dietary salt is a major contributor to increased blood pressure, the leading risk for death worldwide. In several countries, national programmes to reduce dietary salt have been implemented with leadership and involvement of hypertension experts. Other hypertension experts may be interested in assisting or leading a national programme to reduce dietary salt, however, may not have the experience or training to do so. The article is based on the experiences of three hypertension experts who have led the development of national dietary salt reduction programmes in the United Kingdom, Australia and Canada. The article advises developing leadership and a coalition, conducting a nation-specific environmental scan of facilitators and barriers, estimating the national health and financial costs of high dietary salt and the benefits of reducing salt intake, obtaining core documents to provide the scientific rational for the programme, developing a policy statement to outline the required actions to be undertaken, engaging government and industry, using media to gain public support, overcoming industry supported opposition and sustaining the effort long term. Resources and potential sources for international collaboration are provided as well as caveats for developing the programme within the specific nations' context and overall effort to improve health. Developing and leading a national salt reduction programme is a major commitment, however, reducing dietary salt is estimated to be one of the most effective strategies to improve a nation's health. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Raised blood pressure (BP), cholesterol and smoking, are the major risk factors. Among these, raised BP is the most important cause, accounting for 62% of strokes and 49% of coronary heart disease. Importantly, the risk is throughout the range of BP, starting at systolic 115 mm Hg. There is strong evidence that our current consumption of salt is the major factor increasing BP and thereby CVD. Furthermore, a high salt diet may have direct harmful effects independent of its effect on BP, for example, increasing the risk of stroke, left ventricular hypertrophy and renal disease. Increasing evidence also suggests that salt intake is related to obesity through soft drink consumption, associated with renal stones and osteoporosis and is probably a major cause of stomach cancer. In most developed countries, a reduction in salt intake can be achieved by a gradual and sustained reduction in the amount of salt added to food by the food industry. In other countries where most of the salt consumed comes from salt added during cooking or from sauces, a public health campaign is needed to encourage consumers to use less salt. Several countries have already reduced salt intake, for example, Japan (1960–1970), Finland (1975 onwards) and now the United Kingdom. The challenge is to spread this out to all other countries. A modest reduction in population salt intake worldwide will result in a major improvement in public health.Journal of Human Hypertension (2009) 23, 363–384; doi:10.1038/jhh.2008.144; published online 25 December 2008 [ABSTRACT FROM AUTHOR]

Objectives – Hypertension has been associated with impaired cognition. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy were applied to assess white matter abnormalities in treated vs untreated hypertension and if these correlated with neuropsychological performance. Methods – Subjects were 40 patients with medically treated hypertension (mean age 69.3 years), 10 patients with untreated hypertension (mean age 57.6 years) and 30 normotensive controls (mean age 68.2 years). Hypertension was defined as a previous diagnosis and taking hypertensive medication, or a resting blood pressure of >140/90 mmHg on the day of assessment. Results – Patients with treated hypertension performed worse on immediate ( P = 0.037) as well as delayed memory tasks ( P = 0.024) compared with normotensive controls. Cognitive performance was worse in untreated compared with treated hypertension on executive functions ( P = 0.041) and psychomotor speed ( P = 0.003). There was no significant correlation between cognition and any of the imaging parameters in treated hypertension. However, in untreated hypertension the results revealed a positive correlation between an executive functioning and attention composite score and DTI mean diffusivity values ( P = 0.016) and between psychomotor speed and spectroscopy NAA/tCr levels ( P = 0.015). Conclusions – These results suggest there is cognitive impairment in hypertension. Treated hypertension was associated with deficits in memory while untreated hypertension revealed a more ‘subcortical’ pattern of cognitive impairment. [ABSTRACT FROM AUTHOR]

In the presence of aldosterone, plasma sodium in the high physiological range stiffens endothelial cells and reduces the release of nitric oxide. We now demonstrate effects of extracellular potassium on stiffness of individual cultured bovine aortic endothelial cells by using the tip of an atomic force microscope as a mechanical nanosensor. An acute increase of potassium in the physiological range swells and softens the endothelial cell and increases the release of nitric oxide. A high physiological sodium concentration, in the presence of aldosterone, prevents these changes. We propose that the potassium effects are caused by submembranous cortical fluidization because cortical actin depolymerizatiori induced by cytochalasin D mimics the effect of high potassium. In contrast, a low dose of trypsin, known to activate sodium influx through epithelial sodium channels, stiffens the submembranous cell cortex. Obviously, the cortical actin cytoskeleton switches from gelation to solation depending on the ambient sodium and potassium concentrations, whereas the center of the cell is not involved. Such a mechanism would control endothelial deformability and nitric oxide release, and thus influence systemic blood pressure. [ABSTRACT FROM AUTHOR]

Rationale: Markers of inflammatory activity are important for assessment and management of many respiratory diseases. Markers that are currently unrecognized may be more valuable than those presently believed to be useful.Objectives: To identify potential biomarkers of suppurative and inflammatory lung disease in induced sputum samples.Methods: Induced sputum was collected from 20 healthy control subjects, 24 patients with asthma, 24 with chronic obstructive pulmonary disease, 28 with cystic fibrosis (CF), and 19 with bronchiectasis. Twelve patients with CF had sputum sampled before and after antibiotic therapy for an infective exacerbation. The fluid phase of induced sputum was analyzed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy on three protein array surfaces. Some protein markers were selected for identification, and relevant ELISA assays sought. For 12 patients with CF, both SELDI-TOF and ELISA monitored changes in inflammatory responses during infective exacerbations.Measurements and Main Results: SELDI-TOF identified potential biomarkers that differentiated each of the disease groups from healthy control subjects: at a significance of P < 0.01, there were 105 for asthma, 113 for chronic obstructive pulmonary disease, 381 for CF, and 377 for bronchiectasis. Peaks selected for protein identification yielded calgranulin A, calgranulin B, calgranulin C, Clara cell secretory protein, lysosyme c, proline rich salivary peptide, cystatin s, and hemoglobin alpha. On treatment of an infective CF exacerbation, SELDI-TOF determined falls in levels of calgranulin A and calgranulin B that were mirrored by ELISA-measured falls in calprotectin (heterodimer of calgranulins A and B).Conclusions: Proteomic screening of sputum yields potential biomarkers of inflammation. The early development of a clinically relevant assay from such data is demonstrated. [ABSTRACT FROM AUTHOR]

To study the relationship between salt intake and blood pressure in children and adolescents, we analysed the data of a large cross-sectional study (the National Diet and Nutrition Survey for young people), which was carried out in Great Britain in 1997 in a nationally representative sample of children aged between 4 and 18 years. A total of 1658 participants had both salt intake and blood pressure recorded. Salt intake was assessed by a 7-day dietary record. The average salt intake, which did not include salt added in cooking or at the table, was 4.7±0.2 g/day at the age of 4 years. With increasing age, there was an increase in salt intake, and by the age of 18 years, salt intake was 6.8±0.2 g/day. There was a significant association of salt intake with systolic blood pressure as well as with pulse pressure after adjusting for age, sex, body mass index and dietary potassium intake. An increase of 1 g/day in salt intake was related to an increase of 0.4 mm Hg in systolic and 0.6 mm Hg in pulse pressure. The magnitude of the association with systolic blood pressure is very similar to that observed in a recent meta-analysis of controlled trials where salt intake was reduced. The consistent finding of our present analysis of a random sample of free-living individuals with that from controlled salt reduction trials provides further support for a reduction in salt intake in children and adolescents.Journal of Human Hypertension (2008) 22, 4–11; doi:10.1038/sj.jhh.1002268; published online 6 September 2007 [ABSTRACT FROM AUTHOR]

Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of coronary heart disease (CHD) in many epidemiological studies, however, the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of CHD by carrying out a meta-analysis of cohort studies. Studies were included if they reported relative risks (RRs) and corresponding 95% confidence interval (CI) of CHD with respect to frequency of fruit and vegetable intake. Twelve studies, consisting of 13 independent cohorts, met the inclusion criteria. There were 278 459 individuals (9143 CHD events) with a median follow-up of 11 years. Compared with individuals who had less than 3 servings/day of fruit and vegetables, the pooled RR of CHD was 0.93 (95% CI: 0.86–1.00, P=0.06) for those with 3–5 servings/day and 0.83 (0.77–0.89, P<0.0001) for those with more than 5 servings/day. Subgroup analyses showed that both fruits and vegetables had a significant protective effect on CHD. Our meta-analysis of prospective cohort studies demonstrates that increased consumption of fruit and vegetables from less than 3 to more than 5 servings/day is related to a 17% reduction in CHD risk, whereas increased intake to 3–5 servings/day is associated with a smaller and borderline significant reduction in CHD risk. These results provide strong support for the recommendations to consume more than 5 servings/day of fruit and vegetables.Journal of Human Hypertension (2007) 21, 717–728; doi:10.1038/sj.jhh.1002212; published online 19 April 2007 [ABSTRACT FROM AUTHOR]

Purpose-To report on the work of the SPEIR project and indicate its relevance beyond the Scottish information environment. SPEIR was funded by the Scottish Library and Information Council to identify, research, and develop the elements of an internationally interoperable Scottish Common Information Environment (SCIE) for Library, Museum and Archive domain information services, and to determine the best path for future progress. A key focus was to determine the distributed information infrastructure requirements of a pilot Scottish Cultural Portal being developed in parallel with the SPEIR work, building on existing pilot initiatives such as the CAIRNS distributed catalogue and landscaper, the SCONE collections database, the SCAMP staff portal and an embryonic organisational infrastructure based on the Confederation of Scottish Mini-cooperatives (CoSMiC).Design/methodology/approach-A series of practical pilots was undertaken. These were underpinned by relevant desk and field research and conducted within an overarching holistic approach to developing the distributed environment.Practical implications-Key outcomes included the creation of a single upgraded integrated service incorporating an extended distributed catalogue, collections database, and landscaper, the creation of a pilot distributed digital library, the development of open-URL-based facilities to permit portals to incorporate 'canned searches' of the catalogue, the collections database, the SDDL, and other compatible services, an illustrative pilot Scottish terminology mapping service, and various organisational infrastructure and professional support improvements.Originality/value-The embryonic technical and organisational infrastructure reported may provide a model for other small countries (or regions within larger countries) seeking a coherent approach to the development of an interoperable information environment. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death and disability world-wide. Blood pressure, throughout the range seen in developed countries, is the most important risk factor for cardiovascular disease. Lowering blood pressure within the whole population by lifestyle interventions, such as reducing dietary salt intake and increasing the consumption of fruit and vegetables, will be of great benefit. Blood pressure-lowering trials also demonstrate immense benefits in preventing strokes, heart failure and coronary heart disease. There are no differences in outcome between the different methods used to lower blood pressure and the benefit is proportional to the degree of blood pressure-lowering. Thiazide diuretics are effective in lowering blood pressure and have been the most widely prescribed blood pressure-lowering drugs. They work by causing both sodium and water loss, but also cause potassium loss and a fall in plasma potassium levels. The latter may mitigate the beneficial effects from blood pressure-lowering. Some diuretics, such as spironolactone, affect the distal tubule and do not cause a fall in plasma potassium levels. However, spironolactone has endocrine side-effects associated with the fact that it is not specific for the mineralocorticoid receptor. The development of a more selective aldosterone antagonist without endocrine side-effects could be a major advance as it would be able to oppose the effects of aldosterone, both on sodium retention and potassium loss and the other vascular effects. [ABSTRACT FROM AUTHOR]

Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the overriding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of < 140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or β blockade (B). Most other patients have Iow-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the 'AB' and 'CD' categories of drugs. However, the diabetogenic potential of the older 'B' and 'D' classes leads us to advise against combining 'B' and 'D' in older patients, and to recommend 'A' + 'C' + 'D' as standard triple therapy for resistant hypertension. [ABSTRACT FROM AUTHOR]

Two recent meta-analyses of randomised salt reduction trials have concluded that there is little purpose in reducing salt intake in the general population. However, the authors, as with other previous meta-analyses, included trials of very short duration (eg 1 week or less) and trials of acute salt loading followed by abrupt reductions to very Iow salt intake (eg from 20 to less than 1g of salt/day). These acute salt loading and salt depletion experiments are known to increase sympathetic tone, and with salt depletion cause a rise in renin release and, thereby, plasma angiotensin II. These trials are not appropriate, therefore, for helping to inform public health policy, which is for a more modest reduction in salt intake, ie, from a usual intake of &ap;10 to &ap;5g of salt per day over a more prolonged period of time. We carried out a meta-analysis to assess the effect of a modest salt reduction on blood pressure. Our data sources were MEDLINE, EMBASE, Cochrane library, CINAHL, and the reference lists of original and review articles. We included randomised trials with a modest reduction in salt intake and a duration of 4 or more weeks. Meta-analysis, meta-regression, and funnel plots were performed. A total of 17 trials in hypertensives (n=734) and 11 trials in normotensives (n=2220) were included in our study. The median reduction in 24-h urinary sodium excretion was 78 mmol (equivalent to 4.6g of salt/day) in hypertensives and 74 mmol in normotensives. The pooled estimates of blood pressure fall were 4.96/2.73 ± 0.40/0.24 mmHg in hypertensives (P<0.001 for both systolic and diastolic) and 2.03/ 0.97 ± 0.27/0.21 mmHg in normotensives (P<0.001 for both systolic and diastolic). Weighted linear regression analyses showed a dose response between the change in urinary sodium and blood pressure. A reduction of 100 mmol/day (6g of salt) in salt intake predicted a fall in blood pressure of 7.11/3.88 mmHg (P<0.001 for both systolic and diastolic) in... [ABSTRACT FROM AUTHOR]

Background: The loss of cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride conductance does not fully explain the diverse pathologies evident in patients with cystic fibrosis (CF). Bicarbonate (HCO(3)(-)) secretion is also impaired in CFTR expressing tissues and CFTR is thought to regulate HCO(3)(-) secretion at the apical membrane of epithelial cells. We hypothesised that the epithelial lining fluid (ELF) of patients with CF would be acidified and that this may be worsened during an infective exacerbation due to the increased inflammatory burden.Methods: pH and nitrite levels in exhaled breath condensate (EBC) from 12 healthy non-smoking controls and 30 patients with CF (11 of whom were in an infective exacerbation) were measured. A further nine patients were studied before and after intravenous antibiotic treatment for an exacerbation of CF.Results: The pH of EBC was significantly lower in patients with stable CF than in controls (5.88 (0.32) v 6.15 (0.16), p=0.017), and was further reduced in CF patients with an exacerbation (5.32 (0.38), p=0.001) compared with stable CF patients. EBC pH increased significantly following antibiotic treatment from 5.27 (0.42) to 5.71 (0.42), p=0.049). Nitrite levels in EBC were increased in CF patients with an exacerbation compared with control subjects (4.4 (4.0) micro m v 1.6 (1.6) micro m p=0.047). No correlation was found between EBC pH and nitrite levels.Conclusions: These findings support the hypothesis that airway acidification occurs in CF. This acidity is in part a function of inflammation as the pH of the EBC of patients increased significantly with treatment of an exacerbation, although not to control levels. Acidic pH of the ELF may play a role in the pathophysiology of CF lung disease and requires further investigation. [ABSTRACT FROM AUTHOR]

Introduction: The sodium-hydrogen exchanger (NHE) is integral to the processes that facilitate cell growth and may contribute to the development of left ventricular hypertrophy. The aim of this study was to examine the relationship between platelet sodium-hydrogen exchanger activity and left ventricular mass index (LVMI). Methods: Twenty male untreated Caucasians (mean age ± s.d.: 48 ± 13; body mass index: 29 ± 4 kg/m[SUP2]) with a wide range of blood pressures were studied (mean BP: 152 ± 22/93 ± 15 mm Hg; range: 115-190/61-117 mm Hg). Sodium-hydrogen exchanger activity was determined as the rate of sodium-dependent recovery of intracellular pH in isolated platelets loaded with BCECF and acidified to pH 6.25 using nigericin. LVMI was calculated from measurements made by M-mode echocardiography. Associations between continuous variables were examined using parametric tests. Results: The mean rate of pHi recovery was 0.15 ± 0.03 dpHi/s (range: 0.09-0.21). Mean LVMI was 120 ± 32 g/m[SUP2] (range: 56-178) and was not significantly correlated with either systolic (r = 0.39, P = 0.09) or diastolic blood pressure (r = 0.27, P = 0.3). Platelet NHE activity was not significantly correlated with LVMI (r = 0.06; P = 0.8). Platelet NHE activity was not significantly different between subjects with (n = 7 with LVMI > 131 g/m[SUP2]) and without left ventricular hypertrophy (n = 13). Conclusions: The results of this study show that platelet NHE activity is not significantly correlated with LVMI. These data contrast with previously described correlations of LVMI with exchanger activity measured in leucocytes and erythrocytes; and indicate that the relationship between LVMI and exchanger activity may be specific to the cell type in which exchanger activity is measured. [ABSTRACT FROM AUTHOR]

Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reabsorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the β subunit of the epithelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40-59 years, of black African origin from general practices' lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP &ges;160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) according to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P = 0.05) and was more common in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P = 0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may contribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population. [ABSTRACT FROM AUTHOR]

Background: We have previously reported the use of a hospital based respiratory nurse service (Acute Respiratory Assessment Service, ARAS) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD.Methods: Patients with COPD admitted as emergencies were identified the next working day. They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD, but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management. Of 360 patients reviewed, 209 were being assessed for other active medical problems and were excluded, 33 potential participants were already involved in research studies and so were ineligible, and 37 did not wish to participate in the study. Eighty one patients were randomised to receive conventional inpatient care (n=40) or to planned early discharge the next working day (n=41). Those discharged early continued treatment at home under the supervision of specialist respiratory nurses. Outcome measures were readmission, additional hospital days, and deaths within 60 days of initial admission. Process measures included number of visits, duration of follow up by the respiratory nurse, and additional treatment provided to support early discharge.Results: On an intention to treat basis, a policy of early discharge reduced inpatient stay from a mean of 6.1 (range 1-13) days with conventional management to 3.2 (1-16) days with an early discharge policy. Twelve patients (30% conventional management, 29.3% early discharge) were readmitted in each group giving a mean difference in readmission of 0.7% (95% CI of the difference -19.2 to 20.6). In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group, giving a mean difference of 0.92 days (95% CI of the difference -6.5 to 8.3). There were two deaths (5%) in the conventional management group and one (2.4%) in the early discharge group, a mean difference of 2.6% (95% CI of the difference -5.7 to 10.8).Conclusions: Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses. No difference was found in the subsequent need for readmission. [ABSTRACT FROM AUTHOR]

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means ± s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 ± 0.54 and 5.84 ± 0.53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 ± 13.7 vs 16.7 ± 10.7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production. [ABSTRACT FROM AUTHOR]

• Use non-pharmacological measures in all hypertensive and borderline hypertensive people. • Initiate antihypertensive drug therapy in people with sustained systolic blood pressures (BP) &ges;160 mm Hg or sustained diastolic BP &ges;100 mm Hg. • Decide on treatment in people with sustained systolic BP between 140 and 159 mm Hg or sustained diastolic BP between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease or a 10-year coronary heart disease (CHD) risk of &ges;15% according to the Joint British Societies CHD risk assessment programme/risk chart. • In people with diabetes mellitus, initiate antihypertensive drug therapy if systolic BP is sustained &ges;140 mm Hg or diastolic BP is sustained &ges;90 mm Hg. • In non-diabetic hypertensive people, optimal BP treatment targets are: systolic BP <140 mm Hg and diastolic BP <85 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some hypertensive people. • In diabetic hypertensive people, optimal BP targets are; systolic BP <140 mm Hg and diastolic BP <80 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <140/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some people with diabetes and hypertension. • In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or beta-blockers are preferred as first-line therapy for the majority of hypertensive people. In the absence of compelling indications for beta-blockade, diuretics or long acting dihydropyridine calcium antagonists are preferred to beta-blockers in older subjects. Compelling indications and contra-indications for all antihypertensive drug classes are specified. • For most hypertensives, a combination of antihypertensive drugs will be... [ABSTRACT FROM AUTHOR]

The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects. In view of evidence that with long-term treatment both cicletanine 50 and 100 mg have anti-hypertensive effects, these findings suggest that cicletanine may act by a different mechanism in lowering blood pressure at low and high dose. [ABSTRACT FROM AUTHOR]

The effect of digoxin (0.25 mg t.d.s.) given orally for 5 days, on sodium excretion, plasma renin activity, plasma aldosterone and blood pressure has been studied in 6 normotensive subjects, on a constant sodium intake. Average serum digoxin level measured in 5 subjects on the 5th day of treatment was in the upper range of the therapeutic level (1.92 +/- 0.3 nmol/l). Red cell sodium content increased from 9.75 +/- 1.2 mmol/l of cells in the control period to 15.3 +/- 1.7 mmol/l of cells on the 5th day of digoxin treatment when measured in 4 of the 6 subjects. In spite of this evidence of inhibition of the red cell sodium pump, there was no detectable change in sodium excretion, blood pressure, plasma renin activity and aldosterone. [ABSTRACT FROM PUBLISHER]