Georges Rorive

Quantitative assessment of erythropoiesis in haemodialysis patients demonstrates gradual expansion of erythroblasts during constant treatment with recombinant human erythropoietin.

Recombinant human erythropoietin (rHuEpo) has been shown to be effective in correcting the anaemia of chronic renal failure. It has been reported that reticulocytes as well as erythroid progenitors increase within 1-2 weeks, with no further elevation beyond this time interval. However, the erythroblast pool is quantitatively the most important compartment of erythropoiesis, and the rate, extent and duration of the expansion of erythropoietic activity in response to rHuEpo is not known. Treatment with rHuEpo was given to 64 patients i.v. thrice weekly after haemodialysis. The effect of rHuEpo was obvious from the early elevation of reticulocyte counts, but much of this increase was due to a rapid output of shift reticulocytes which levelled off after a few weeks. Serum transferrin receptor (TfR), a quantitative measure of erythropoiesis, increased progressively over 6 weeks to reach a plateau phase at about twice baseline values. The Hct increased progressively and continued to rise steadily after the TfR plateau was reached. The speed and extent of the expansion of erythropoietic activity correlated with the later haematological response to rHuEpo. When rHuEpo was discontinued, erythropoietic activity returned progressively to baseline values, to rise again gradually when treatment was resumed. Part of the Hct increase was also due to haemoconcentration. The results indicate that changes in the various erythroid compartments vary considerably in intensity and speed, and that the erythroblast compartment in particular is slow to respond to modifications in the erythropoietin stimulus.

Comparison of plasma cardiac troponins T and I in chronically hemodialyzed patients in relation to cardiac status and age

Abstract Cardiac troponins (cTnT and cTnI) are useful tools for risk stratification in patients with unstable angina. However, their value in patients with renal failure has been questioned. In this study, we determined cTnT and cTnI at 3-month intervals during 9 months in 97 chronic renal failure (CRF) patients treated with hemodialysis. cTnT was measured using a third generation immunoassay and cTnI by fluorimetric immunoassay with a detection limit similar to that of cTnT (0.01 μg/l). In the renal patients without coronary heart disease (CHD(−) group), cTnT was more frequently elevated above cut-off for acute myocardial infarction (AMI) (up to 21.6%) than cTnI (no patient). In the absence of CHD, cTnT levels were positively correlated to age, and more than half of the CHD(−) patients aged over 60 years had cTnT levels above the upper reference limit (URL) of 0.04 μg/l (0.059±0.042 μg/l). cTnI increased with age in parallel to cTnT but mean levels did not exceed the URL of 0.08 μg/l in the CHD(−) patients aged over 60 years (0.036±0.031 μg/l). In the patients with documented cardiac events (CHD(+)) we found higher troponin levels than in the CHD(−) patients of the corresponding age, but for cTnI the differences between CHD(+) and CHD(−) patients were significant in the patients aged ≤60 years only (0.049±0.054 vs.0.019±0.018 μg/l, p<0.05). For cTnT, the differences between patients with and without coronary events also tended to be less important in the eldest patients. There was a significant correlation between cTnI and cTnT levels in the CHD(−) and in the CHD(+) groups. Changes in the plasma levels of cardiac troponins are common in hemodialysis patients in the absence of CHD, and advanced age appears to amplify these changes. The reason could be that most hemodialysis patients with advanced age have subclinical lesions and demonstrate release characteristics of troponins that compare to those in patients with symptomatic coronary events. Therefore, it will be important to analyze troponin elevations above the URL or above the cut-off concentration for AMI in asymptomatic renal patients in relation to prognosis.

The Ionic Composition of Rat Aortic Smooth Muscle Fibres

(1965). The Ionic Composition of Rat Aortic Smooth Muscle Fibres. Archives Internationales de Physiologie et de Biochimie: Vol. 73, No. 3, pp. 453-475.

Intracellular cation concentrations in essential hypertension and chronic renal failure

The aim of this study was to test basal and after treatment erythrocyte sodium and calcium concentrations, and calcium-ATPase activity and platelet cytosolic free calcium and pH in 20 normotensive controls, 20 hemodialysis-dependent chronic renal failure patients and in 18 essential hypertensives. Prior to treatment, essential hypertensive and uremic patients presented similar higher platelet calcium concentrations and lower pH than the normotensive control group. The erythrocyte sodium, calcium, and magnesium concentrations were only significantly elevated in chronic renal failure, with a significant decrease in the calcium-ATPase activity in the latter population. Hemodialysis partially reversed these intracellular ionic abnormalities with normalization of platelet pH. Significant correlations have been noted between weight loss and decreases in platelet calcium concentration (r = 0.60, p < 0.01) or in erythrocyte sodium (r = 0.50, p < 0.05). The systolic blood pressure decrease was only correlated to the increase in calcium-ATPase activity (r = 0.57, p < 0.05). Antihypertensive treatment (captopril and nifedipine) only tended to normalize the intracellular calcium concentration with correlation between the decrease of the latter and blood pressure decrease (r = 0.64 for the systolic blood pressure and 0.68 for the diastolic blood pressure, p < 0.01). Thus, in essential hypertension and in uremia, some cellular ionic abnormalities exist in platelets in baseline condition. Moreover, in uremia, erythrocyte presents abnormal ionic pattern. Some, but not all of these abnormalities could be corrected by treatment affecting blood pressure (cellular calcium) in essential hypertension or by hemodialysis (cellular sodium, calcium, and pH). In the latter treatment, the changes are linked to extracellular fluid modification. In essential hypertension, the intracellular calcium reduction was linked to blood pressure decrease.

Isradipine in essential hpertension: The Belgian general practitioners' study

Over 200 hypertensive patients were recruited by 37 general practitioners into a single-blind 12-week study to assess the efficacy, tolerability, and safety of isradipine as an antihypertensive, alone and in combination with guanfacine. A total of 212 patients were given isradipine at doses of 1.25 and 2.5 mg twice daily. Twelve hours after the last dose, diastolic blood pressure was reduced to no more than 90 mm Hg in 52.6 percent of patients treated with isradipine alone. After eight weeks of treatment, 30 percent of patients were also given guanfacine 1 mg daily. By Week 12, 67.6 percent of the patients had attained normotension. Compared with placebo, side-effect frequency was higher for flushing and edema with isradipine, and dry mouth was more frequent with added guanfacine. Electrocardiographic examinations and routine laboratory determinations showed no clinically relevant changes. These data indicate that isradipine as monotherapy and in combination with guanfacine is an effective antihypertensive agent. Most patients will continue to participate in a two-year follow-up involving bimonthly clinical visits and half-yearly electrocardiographic examinations and laboratory determinations.

Biometrological Evaluation of the Stratum corneum Texture in Patients under Maintenance Hemodialysis

Xerosis and hydration of the stratum corneum were evaluated in 60 hemodialyzed patients. Xerosis and a low capacitance of the stratum corneum were evidenced in more than 80% of the patients. Pruritus was present in two third of the subjects. We failed to disclose any significant relationship between severity of these three parameters.

Pathogenesis and reversibility of the aortic changes in experimental hypertension.

In renal hypertensive female rats (Goldblatt one-kidney, one-clip model) (G 1K-1C), an increase in DNA and collagen synthesis, in the proliferation fraction of smooth muscle cells, and in wet weight were observed in the aorta as early as 4 days after the renal artery was clipped at a time when blood pressure increased rapidly. When blood pressure stabilized at high values, the metabolism of nucleic acid within the aortic media resumed its normal level. When the blood pressure level was corrected either by removal of the clip or by antihypertensive drugs, a modification of the course of the aortic proliferation changes could only be obtained when the treatment was started, at the earliest phase of hypertension. Once the proliferation changes were established, they could not be corrected even after normalization of blood pressure, at least in such short-term experiments. Moreover, some dissociation between the effect of antihypertensive drugs on blood pressure level and on arterial hypertensive disease were observed. These data illustrate the complexity of the mechanisms involved in the response of the vascular wall to high blood pressure and in its correction as well.

Tolerability of isradipine in the treatment of mild-to-moderate hypertension in general practice: a large-scale surveillance study.

The tolerability of isradipine was evaluated in an open trial of patients with mild-to-moderate essential hypertension as treated in general practice. The primary objective was to identify all adverse reactions, especially those that were newly occurring (≥ 6 reports), with a frequency > 1/1,000. Over 1,100 general practitioners and 5,526 patients participated in this trial. After a 2-week washout period, and a 3-week placebo run-in, patients with diastolic blood pressure (DBP) ≥ 95 mm Hg were initially given isradipine at 1.25 mg twice daily. After 4 weeks, doses were doubled if DBP was > 90 mm Hg. If, after a further 4 weeks with doubled dosages, the DBP was still >90 mm Hg, a second (nonspecified free-choice) antihypertensive agent was added to the treatment. Adverse events were recorded by open questioning. The incidence of adverse events was found to be similar to that with placebo; adverse events were generally mild or moderate in intensity and disappeared over time. No newly occurring adverse events were found. In conclusion, isradipine is safe and well tolerated at effective antihypertensive doses in patients with mild-to-moderate hypertension as treated in general practice.

Cardiovascular structural changes induced by isolation-stress hypertension in the rat.

The cardiovascular structural remodelling associated with psychogenic hypertension was investigated in genetically normotensive rats subjected to isolation stress. Male Wistar rats were stressed by intermittent social isolation and compared to control rats living in groups. The stressed rats had higher systolic blood pressures than the control rats throughout the study. After 1 week of isolation, ornithine decarboxylase activity, a marker for hypertrophy, was increased in the right ventricle of the stressed rats. After 6 weeks of intermittent isolation, the myocardium of the stressed rats was hypertrophied, involving both right and left ventricles. The aorta was also hypertrophied, whereas the tail artery remained unaffected. Later, after 12 weeks of isolation, the left ventricular hypertrophy persisted whereas the right ventricle and aorta returned to normal. It seems, therefore, that social stress hypertension is accompanied by very early structural changes, which affect at least the heart and the aorta, and cannot be directly linked to the severity or duration of hypertension.

Arguments For The Presence of A Na-K ATPase Pump Inhibitor in The Plasma of Uremic and Essential Hypertensive Patients

The effect of salt and/or volume depletion has been tested in 6 end-stage renal disease and 11 essential hypertensive patients (HTA) on red blood cell (RBC) ionic fluxes. Volume depletion promotes an increase in the RBC Na-K ATPase activity with, as a result, a significant decrease in intracellular sodium concentration [Na)ic). Moreover, a factor has been found in the plasma of uremic subjects which causes natriuresis when injected in rat renal arteries. The concentration of this factor decreases during dialysis in relation to the weight loss and the increase in the RBC Na-K pump activity. In essential hypertension, the effect of a low salt diet on the blood pressure is correlated with the improvement of RBC Na-K ATPase activity. These experiments illustrate the presence of a Na-K ATPase inhibitor in the plasma of these subjects, dependent on sodium and water balance.