Comparative Study of the Effect of ACE-Inhibitors and Other Antihypertensive Agents on Proteinuria in Diabetic Patients

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure. However, some authors reported disparate renal protective effects of different antihypertensive drugs in diabetic animals and humans. In an attempt to resolve the controversy surrounding this possibility, previously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clinical proteinuria (UProt), treated during ≥ 4 weeks with ACE inhibitors, Ca2+ antagonists, or conventional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists other than nifedipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, P 5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, P < .05) was in an intermediate position between ACE inhibitors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r = -0.55, P < .0001). On conventional therapy or Ca2+.antagonists, variations in GFR were unrelated to changes in BP. As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbuminuria or overt proteinuria in initially normotensive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca2+ antagonists all have a distinct antiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal effects may antagonize a BP-dependent antiproteinuric action and even counteract the effect of lowering systemic pressure. It is of note that ACE inhibitors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR. Am J Hypertens 1994;7:84S-92

Albuminuria in Diabetes Mellitus: Relation to Ambulatory Versus Office Blood Pressure and Effects of Cilazapril

This study aimed to investigate the relationship between microalbuminuria and office blood pressure (BP) as compared with ambulatory BP in patients with diabetes mellitus under everyday practice conditions. It was also undertaken to assess the effect of the angiotensin converting enzyme inhibitor cilazapril on diabetes-associated albuminuria. Ambulatory BP was recorded during daytime in 54 patients with type II diabetes mellitus at the end of a 4-week period during which they received no vasoactive drug. The difference between office and ambulatory BP was unpredictable in the individual patient. There was no significant correlation between either ambulatory or office BP and urinary albumin/ creatinine ratio. Fifty-one patients underwent a 40-week treatment with 5 mg/day of cilazapril. There was, in the absence of satisfactory BP control, the possibility of adding the calcium antagonist amlodipine (5 mg/day) from the 10th week onward and 12.5 mg/day of hydrochlorothiazide from the 20th week onward. Office mean BP was significantly reduced after 30 to 40 weeks of therapy in patients with normoalbuminuria (n = 19, − 14%, P <.001), in those with microalbuminuria (n = 22, −6.6%, P < .01), as well as in those with clinical proteinuria (n = 9, − 11.4%, P < .01). During the same time, the urinary albumin/creatinine ratio was not modified in normoalbuminuric patients (n = 19, + 24.6%, P = .72) as well as in those with clinical proteinuria (n = 9, −29.4%, P = .09). On the other hand this value was significantly reduced for the group with microalbuminuria (n = 23, −24.3%, P <.05). In the overall population, as well as in hyperalbuminuric patients (patients with microalbuminuria + patients with clinical proteinuria), the reduction of the albumin/ creatinine ratio was also significant (n = 51, −7%, P < .01 and n = 32, −25,7%, P < .01, respectively). In conclusion, the findings of this study performed by practicing physicians show that ambulatory BP may differ greatly from office BP in diabetic patients. They also indicate that urinary albumin excretion is poorly correlated with office and ambulatory BP in type II diabetics. Finally, they demonstrate the antiproteinuric action of prolonged treatment with the angiotensin converting enzyme inhibitor cilazapril, whether given alone or combined with amlodipin

Testing peas for legume fatigue (OK-Net Arable Practice Abstract)

The method offers reference points regarding the soil's contamination with these pathogens, and thus indication for a possibly required cultivation break. Refraining from cultivating on contaminated soils helps avoid the situation of a high yield loss due to legume fatigue. Practical recommendation 1. Extract 10 litres of humid soil from the field plot you wish to examine and sieve it down to a grain size of 10 mm. 2. Moisten dry samples and mix them up evenly. 3. Fill four aluminium trays with the humid soil and store the remaining soil. 4. Cover the trays filled with soil with tinfoil and place them in the baking oven. Sterilise the samples for at least 12 hours at 70-100 °C in the oven. 5. Let the aluminium trays cool for 12 hours after sterilisation. 6. Mark four flowerpots with "R" (for untreated reference) and another four with "H" (for heat-treated soil). 7. Fill the four H-flowerpots with the heat-treated soil and fill the four R-flowerpots with the untreated soil. 8. Place 5 field-pea seeds in each pot and cover them with 0, 5 cm of soil. 9. Place the pots in a tray with some water and keep them in a sheltered place with at least 18 °C and daylight. 10. Keep the pots humid during about 6 weeks by pouring water into the trays

A meridional 14C and 39Ar section in northeast Atlantic deep water

14C, 39Ar, and complementary hydrographic and nutrient data are presented for deep water below 2500 m depth, from stations along a meridional section (8°S to 45°N) through the Romanche Trench and along the deep northeast Atlantic basins (F/S Meteor, cruise 56, leg 5). The large-scale 14C distribution along the section is resolved at the 14C data precision of ±2‰. Bottom water Δ14C decreases by 6‰ from the equator to 45°N, and farther up there is a weak Δ14C minimum (−123‰) over much of the section. The 14C data are interpreted as giving a turnover time of about 30 years for the waters below the depth of the 14C minimum (∼4250 m). It is found that water of 1.50±0.05°C potential temperature enters the East Atlantic from the west through the Romanche Trench (sill depth about 4000 m), and a preliminary value for the inflow rate of 3.6×106 m3/s is deduced. This rate greatly exceeds estimated deep inflow rates through the Vema fracture zone or across the northern boundary of the East Atlantic. 39Ar data that cover an entire deep-ocean circulation system are presented for the first time. The observed 14C and 39Ar distributions are mutually consistent. Transit times from the source regions to the equator for water from northern and southern deepwater sources are estimated to be about 170 and 105 years, respectively, and the 39Ar concentration of young Antarctic Bottom Water is deduced as 60±7% modern. The 39Ar-14C correlation in the ocean appears to be affected by mixing of waters of different age and by more efficient raising of 39Ar in the deepwater formation processes

Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease

Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease. The cardiovascular pressor responsiveness to infused norepinephrine (NE) or angiotensin II (AII) as related to endogenous plasma NE or renin levels was assessed in 20 patients with mild parenchymal kidney disease (plasma creatinine 2.20 ± 0.58 mg/dl, ± SEM) and in 20 normal subjects approximately matched for sex and age. The two groups did not differ significantly in mean body weight, heart rate, blood volume, plasma electrolytes, exchangeable or urinary sodium, plasma aldosterone, epinephrine and renin levels, or AII threshold or pressor doses. Basal (including pre-infusion) plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance of NE (5.0 ± 0.8 vs. 5.5 ± 0.5 liter/min) also did not differ significantly between the two groups. In contrast, the threshold or pressor doses of infused NE decreased significantly in the patients with kidney disease (94 ± 11 vs. 134 ± 14 ng/kg/min and 21 ± 3 vs. 40 ± 7 ng/ kg/min; P < 0.05). Moreover, based on analysis of covariance, the individual pressor doses as related to basal plasma NE levels were distributed differently (P < 0.01) between the patients and normal subjects. These findings suggest that the kinetics of plasma NE are unaltered largely in early stage kidney disease. However, such patients tend to develop an exaggerated pressor responsiveness to NE in the presence of normal plasma NE levels. This disturbance may favor the development of hypertension.Stimulation de la réactivité pressive cardiovasculaire à la noradrénaline dans les néphropathies modérées. La réponse pressive cardiovasculaire après perfusion de noradrénaline (NE) ou d'angiotensine II (AII) en fonction des concentrations endogènes de NE ou de rénine plasmatiques a été étudiée chez 20 malades ayant une maladie rénale parenchymateuse modérée (créatininémie 2,20 ± 0,58 (± SEM) mg/dl) et chez 20 sujets normaux d'âge et de sexe voisins. Les deux groupes ne différaient pas significativement par le poids corporel moyen, le rythme cardiaque, le volume sanguin, les électrolytes plasmatiques, le sodium échangeable ou urinaire, l'aldostérone plasmatique, les niveaux d'adrénaline et de rénine, ou les doses seuils ou pressives d'All. Les concentrations plasmatiques de NE basales (y compris les valeurs avant perfusion), la relation entre la NE plasmatique mesurée pendant la perfusion de NE et la vitesse de perfusion de NE correspondante, ainsi que la clearance plasmatique totale de NE (5,0 ± 0,8 contre 5,5 ± 0,5 1/ mn) ne différaient également pas entre les deux groupes. A l'inverse, les doses seuils ou pressives de NE perfusées étaient significativement diminuées chez les malades ayant une néphropathie (94 ± 11 contre 134 ± 14 ng/kg/mn et 21 ± 3 contre 40 ± 7 ng/kg/mn; P < 0,05). En outre, par analyse de covariance, les doses pressives individuelles en fonction des concentrations plasmatiques basales de NE étaient distribuées différemment (P < 0,01) entre les malades et les sujets normaux. Ces résultats suggèrent que la cinétique de la NE plasmatique est en grande partie inchangée au cours des néphropathies au stade initial. Cependant les malades tendent à développer une réponse pressive exagérée à la NE en présence de concentrations plasmatiques de NE normales. Cette anomalie pourrait favoriser le développement d'une hypertension

Dynamic studies of aldosterone in anephric man

Dynamic studies of aldosterone in anephric man. Aldosterone metabolism in the absence of a functioning renin-angiotensin system was evaluated in twelve anephric subjects. Plasma aldosterone concentrations determined while subjects were in a supine position were usually low, correlated with the plasma potassium concentration (r = 0.38; P < 0.01) and responded to acute alterations in plasma potassium concentration (r = 0.64; P < 0.001), thus indicating an important role for potassium in aldosterone regulation in anephric man. In contrast, plasma aldosterone concentration did not increase following volume and sodium depletion with ultrafiltration hemodialysis. Its response to angiotensin and corticotropin administration was usually diminished. We felt this was due in part to potassium depletion secondary to maintenance hemodialysis, since potassium repletion in two subjects improved aldosterone responsiveness. Another factor in the diminished aldosterone responsiveness in anephric subjects may be renin deficiency. Upright posture caused increases in plasma aldosterone concentration which could not be explained by concomitant alterations in the concentrations of adrenocorticotropic hormone (ACTH) or plasma electrolytes or metabolic clearance rate of aldosterone.Etudes dynamiques de l'aldostérone chez l'homme anéphrique. Le métabolisme de l'aldostérone en l'absence d'un système rénine angiotensine fonctionnel a été évalué chez douze sujets anéphriques. Les concentrations d'aldostérone en position debout étaient habituellement basses, corrélées avec la kaliémie (r = 0,38; P < 0,01) et répondaient aux modifications aiguës de la kaliémie (r = 0,64; P < 0,001), ce qui indique un rôle important du potassium dans la régulation de l'aldostérone chez l'homme anéphrique. Au contraire, la concentration d'aldostérone du plasma n'a pas augmenté après une déplétion d'eau et de sodium réalisée par ultrafiltration au cours de l'hémodialyse. La réponse à l'angiotensine et à l'ACTH était habituellement diminuée. Il est proposé que cela soit du en partie à la déplétion en potassium secondaire à l'hémodialyse chronique puisque la recharge en potassium chez deux sujets a amélioré la réponse aux stimuli. Un autre facteur dans la diminution de la réponse chez les sujets anéphriques peut être le déficit de rénine. La position debout a déterminé des augmentations de l'aldostérone du plasma qui ne peuvent pas être expliquées par des modifications concomitantes de l'ACTH, des électrolytes du plasma ou du débit de la clearance métabolique de l'aldostérone

Cardiovascular Pressor Reactivity After Chronic Converting Enzyme Inhibition

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with Cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, Cilazapril decreased arterial pressure in both study groups (from 124/83 ± 9/6 to 114/77 ± 9/5 mm Hg and from 143/102 ± 13/7 to 137/96 ± 10/10 mm Hg; Ρ < .025); exchangeable sodium (−158 mmol and, respectively, −104 mmol) and upright plasma aldosterone (−24% and −15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of Cilazapril. Plasma renin activity increased (+175% to + 650%) These findings indicate that the blood pressure lowering effect of Cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or ^-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged. Am J Hypertens 1991;4:348-35

Diastolic dysfunction precedes myocardial hypertrophy in the development of hypertension

Background: Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing. Methods: We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were determined at baseline and after 5 years. Pulmonary vein flow pattern assessment and septal myocardial Doppler imaging were additionally performed at follow-up. Results: At follow-up, BP was not significantly different between the two groups (128 ± 11 / 84 ± 10 v 123 ± 11 / 81 ± 5 mm Hg, OHyp v ONorm) but five OHyp had developed mild hypertension. LV mass index remained unchanged and was not different between the two groups at follow-up (92 ± 17 v 92 ± 14 g/m2). Diastolic echocardiographic properties were similar at baseline, but, at follow-up, the following differences were found: mitral E deceleration time (209 ± 32 v 185 ± 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 ± 15 v 107 ± 12 msec, P < .05) were prolonged in the OHyp as compared to the ONorm. Compared to the normotensive subjects, the five OHyp who developed hypertension had more pronounced alterations of LV diastolic function, that is, significantly higher mitral A (54 ± 7 v 44 ± 9 cm/sec, hypertensives v normotensives, P < .05), lower E/A ratio (1.31 ± 0.14 v 1.82 ± 0.48, P < .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 ± 0.3 v 0.81 ± 0.16, P < .005), longer myocardial isovolumic relaxation time (57 ± 7 v 46 ± 12 msec, P < .05) as well as smaller myocardial E (10 ± 1 v 13 ± 2 cm/sec, P < .05) and E/A ratio (1.29 ± 0.25 v 1.78 ± 0.43, P < .05), despite similar LV mass (91 ± 16 v 93 ± 18 g/m2). Conclusion: Over a 5-year follow-up, initially lean, normotensive, young men with a moderate genetic risk for hypertension, developed Doppler echocardiographic alterations of LV diastolic function compared to matched offspring of normotensive parents. These alterations were more pronounced in the OHyp who developed mild hypertension and occurred without a distinct rise in LV mass. Am J Hypertens 2001;14:106-113 © 2001 American Journal of Hypertension, Lt

The Metrology Enhanced Tooling for Aerospace (META) Framework

Railway traffic management is the process of executing production plans, supervising traffic, detecting conflicts, and applying dispatching measures to resolve them. The activity space of traffic managers is constrained by infrastructure, rolling stock, and operations related features and rules. These constraints result in functional requirements that mathematical models should satisfy to be useful to support realtime traffic management. First, this paper identifies and describes these requirements. Second, it presents an overview of the most prominent mathematical formulations for timetabling and rescheduling in the literature. Using sample scheduling problems, it highlights how individual train runs and interactions are represented. The similarities and the differences among the formulations are strengthened to distinguish two main categories of models. Finally, the models are analysed with respect to the functional requirements from real-time traffic management. As expected, off-line scheduling models do not satisfy the requirements related to real-time monitoring and intervention. In contrast, on-line models satisfy most requirements. In particular, there are two rescheduling models that satisfy all functional requirements: the Resource Con- flict Graph and an extension of the Alternative Graph