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Biomedical subjects

G Rorive

Publications and source records attributed to G Rorive.

At least 55 records · Page 3Linked to original sources

Effect of recombinant human erythropoietin on platelets in patients with anemia of renal failure: correlation of platelet count with erythropoietic activity and iron parameters.

We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1) increased from 220 +/- 80 to 245 +/- 102 after 14 days and stabilized at that level up to day 90 (p < 0.0001). The increment was similar in complete or partial responders but was not observed in failures. Serum transferrin receptor (sTfR, a measure of total erythropoiesis) and Het rose much more progressively, but relative platelet increments correlated with relative increases in sTfR and Hct. Relative platelet increments correlated inversely with relative changes of SeFe or transferrin saturation, but not with their absolute values, nor with baseline ferritin or its progressive decrease. Although baseline platelet count was 12% higher in patients with inflammation and correlated with serum haptoglobin, relative increases were similar in patients with or without inflammation. In conclusion, rHuEpo produced a clinically minor but consistent elevation of platelet counts. These modifications were not related primarily to modifications in iron stores, functional iron deficiency, or inflammation, but paralleled the expansion of erythropoietic activity. The results suggest that rHuEpo has a small positive effect on platelet production, but it cannot be ruled out that this could be partially mediated through functional iron deficiency.

Anemia↗

[Concentration of free intracellular magnesium in the myocardium of spontaneously hypertensive rats treated chronically with calcium antagonist or angiotensin converting enzyme inhibitor].

In this study, we determined a) whether chronic antihypertensive treatment could alter myocardial free intracellular magnesium concentrations, b) whether changes in magnesium concentration would correlate with resistance to anoxia of hypertensive rat hearts. Six-month old male spontaneously hypertensive (HT) rats (n = 11) were compared to rats from the same strain treated with a calcium channel antagonist, nitrendipine (60 mg/kg/j; n = 11) or with a converting-enzyme inhibitor, perindopril (2 mg/kg/j; n = 9) during three months. The hearts were perfused in retrograde isovolumic mode and submitted to a standardized anoxia-recovery protocol. Aortic perfusion pressure and left ventricular pressure were constantly monitored. P-31 NMR spectra were simultaneously recorded and allowed to quantify the changes in myocardial inorganic phosphate, phosphocreatine and ATP. The pH was derived from the chemical shifts of inorganic phosphate and phosphocreatine, and the free intracellular magnesium concentration from the alpha-beta chemical shifts of ATP. Both treatments lowered systolic blood pressure and reversed left ventricular hypertrophy, perindopril being slightly more efficient at the dose administered. Intracellular magnesium concentration, calculated from the P-31 NMR spectra, was 277 +/- 17 microM in the untreated hypertensive group, 311 +/- 15 microM in the nitrendipine group and 401 +/- 17 microM in the perindopril group (p < 0.001 versus untreated and nitrendipine). There was a significant correlation between intracellular magnesium concentration and left ventricular developed pressure at the early stage of post-anoxic recovery (r = 0.61; p < 0.01). P-31 NMR spectroscopy demonstrates an increase in myocardial free intracellular magnesium concentration following chronic administration of an angiotensin-converting enzyme inhibitor, perindopril, spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Early prediction of response to recombinant human erythropoietin in patients with the anemia of renal failure by serum transferrin receptor and fibrinogen.

Recombinant human erythropoietin (rHuEpo) has been shown to be effective in correcting the anemia of chronic renal failure, but the dose needed may be variable. The reason for this variation is not known, but several factors could be involved, such as iron deficiency, inflammation, aluminum intoxication, hyperparathyroidism, blood losses, or marrow dysfunction. Treatment with rHuEpo was given intravenously thrice weekly after hemodialysis to 64 consecutive unselected patients with the anemia of chronic renal failure. The starting dose was 50 U/kg/dose, which was increased to 75 and 100 U/kg/dose if no response was observed after 1 and 2 months of treatment. After a minimum follow-up of 6 months, response was evaluated as early (hematocrit [Hct] > or = 30% before 3 months) or late (Hct > or = 30% after 3 months) response, or failure (target Hct not attained). We examined the value of various laboratory parameters (baseline values and early changes) as predictors of response to rHuEpo. The best prediction by pretreatment parameters only was obtained with baseline serum transferrin receptor (TfR) (< or > or = 3,500 ng/mL) and fibrinogen (< or > or = 4 g/L): 100% response rate when both parameters were low, versus only 29% when they were both high, and versus 67% when one was low and the other high. When the 2-week TfR increment was greater than 20%, the response rate was 96%. When TfR increment was less than 20%, the response rate was 100% when baseline TfR and fibrinogen were low, 12% when fibrinogen was elevated, and 62% when fibrinogen was low but baseline TfR high. The predictive value of baseline TfR and fibrinogen and of the 2-week increment of TfR was confirmed by life table analysis and stepwise discriminant analysis. Major reasons for failure or late response were identified and included subclinical inflammation, iron deficiency, functional iron deficiency, marrow disorders, hemolysis, bleeding, and low Epo dose. We conclude that response to rHuEpo can be predicted early by pretreatment fibrinogen and TfR, together with early changes of TfR levels. These prognostic factors illustrate the importance of the early erythropoietic response, subclinical inflammation, and functional iron deficiency. Early recognition of a low probability of response in a given patient could help identify and correct specific causes of treatment failure to hasten clinical improvement and avoid prolonged ineffective use of an expensive medication.

Anemia↗

Importance of weight loss and sodium restriction in the treatment of mild and moderate essential hypertension.

The effectiveness of non pharmacological treatment of chronic arterial hypertension has been evaluated in 116 treated or not primary hypertensive out-patients. Those receiving diuretics were however excluded. This population was requested to follow for 3 months a modification of their usual diet characterized by salt restriction combined with energy intake restriction when the patients were above their ideal body weight. Only 62 patients (53%) completed the study. However, this approach was effective by decreasing blood pressure and total cholesterol. The weight loss appears the most effective way to decrease blood pressure in untreated patients, but needs 3 months to be significant. In drug-treated patients, the sodium restriction significantly influences the blood pressure level, already after 1 month. However, salt sensitivity has been noted, especially in the most severe forms of the hypertensive disease. The combination of both modifications (weight loss and sodium restriction) does not appear to be more effective than each separate dietary measure.

Adult↗

Red blood cell Na-Li countertransport, hypertensive heredity, and cardiovascular risk in young adults.

The erythrocyte Na-Li countertransport (CT) has been considered as a marker of genetic propension to essential hypertension, but also to be linked to atherosclerosis risk factors. We have evaluated these relationships by measuring the Na-Li CT, blood pressure levels, the family predisposition to hypertension, body mass index, subscapular skin-fold thickness, waist/hip ratio, and plasma lipids in 43 young adults (22 to 23 years; 13 with a positive family history of hypertension), followed since adolescence (+/- 10 years) to analyze the natural history of blood pressure in this period of life. The Na-Li CT was negatively correlated with the HDL cholesterol (r = -0.37) and the HDL cholesterol/total cholesterol ratio (r = -0.44). This transport system was positively correlated to family history of hypertension (r = 0.38), waist/hip ratio, and the diastolic blood pressure. When the family history of hypertension was present, Na-Li CT and diastolic blood pressure were higher (P < .05), but the HDL cholesterol was lower (P < .01). After separating people according to the blood pressure level during adolescence in two groups, one lower than the 75th percentile (P75), and one higher, we notice that the latter remains characterized by a higher systolic blood pressure. But neither the Na-Li CT nor family history of hypertension and plasma lipids could explain the difference in the blood pressure behavior during this period. Thus, an increase of RBC Na-Li CT activity in young adults would suggest a higher cardiovascular risk rather than to be a simple marker of a hypertensive risk.

Adult↗

A sulphonylthiourea (BM 20) related to torasemide: a new loop diuretic with relative potassium-sparing properties.

A series of sulphonylthioureas related to torasemide, a high ceiling loop diuretic, were synthesized and found to inhibit the Na+ 2Cl- K+ co-transporter of the thick ascending limb of the loop of Henlé. Their diuretic properties were studied (30 mg kg-1) after oral administration to rats. Lipophilic derivatives, very active in-vitro, were found inactive orally and intraperitoneally in rats. The four most active compounds were examined for their dose-dependent diuresis. Three of them showed a potency, water and electrolyte excretion similar to torasemide. The fourth molecule, a sulphonylthiourea (BM 20), exhibited relative potassium-sparing properties and a minimal diuretic dose of 0.001 mg kg-1, 200 times lower than torasemide.

Administration, Oral↗

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.

Adult↗

Quantification of skin color in patients undergoing maintenance hemodialysis.

BACKGROUND: In patients undergoing long-term hemodialysis, a peculiar hyperpigmentation develops, the intensity of which may or may not be related to the duration of treatment and use of erythropoietin. OBJECTIVE: Our purpose was to conduct a comparative cross-sectional study of white patients with distinct diseases that modify their skin color. METHODS: A reflected-light colorimeter was used to compare the color of the forehead and forearms of 61 white patients receiving hemodialysis with that of matched controls and of patients with anemia or icterus. RESULTS: Significant differences were found in both reflectance and chromaticity between these groups of patients. Duration of hemodialysis and use of erythropoietin did not significantly influence the colorimetric measurements. CONCLUSION: The use of a color-reflectance meter allows precise evaluation of subtle changes in skin color and may be used to monitor several diseases.

Adult↗

Intrathoracic infections with bacteraemia due to Eikenella corrodens as a complication of peritonsillar abscesses: report of a case and review of the literature.

A 52-year-old man, without previous disease, presented with dysphagia, dyspnoea, high fever and sore throat after peritonsillar abscesses drainage. Physical and complementary examinations were consistent with pericarditis, mediastinitis, pneumonia and pleuritis. Blood cultures grew Eikenella corrodens resistant to clindamycin and amikacin. We emphasize the pathogenic potential of Eikenella corrodens. To the best of our knowledge, this is the first reported case of this organism as a pathogen in intrathoracic infections after peritonsillar abscesses drainage.

Bacteremia↗

Low sodium diet in essential hypertension. Effect on blood cell ions and hemodynamic parameters.

The influence of salt restriction for 3 months on blood pressure, peripheral vascular resistance (observed by occlusive plethysmography), erythrocyte sodium, platelet calcium, and pH, was studied in eight untreated essential hypertensive patients. A low salt diet decreases blood pressure, vascular resistances, erythrocyte sodium, and platelet calcium, but not platelet pH. A strong positive correlation was noted between baseline platelet calcium and vascular resistances (r = 0.95, P less than .01). But during the salt restriction period, a negative correlation has been observed between the changes in these parameters, which casts doubt on the use of the platelet as a model of the smooth muscle cell.

Adult↗

[Effect of dietary sodium in hypertension not treated with drugs].

The usefulness of salt restriction in essential hypertension is still now disputed. This study was designed to test the influence of a diet with and without salt restriction in 19 untreated essential hypertensives (12 with and 7 without family history of hypertension) and free of cardiovascular and renal complications. Each patient was examined after a placebo period, after 1 month of salt restriction, and after 1 month of salt supplementation. Weight, blood pressure, 24 hours urinary sodium excretion and red blood cell ionic fluxes were measured. In patients with hypertensive heredity, the blood pressure did not change. The intracellular sodium concentration, the cotransport and the countertransport remained stable. The ouabain sensitive sodium pump slightly increased during salt restriction and remained stable after salt supplementation. In patients without such hypertensive heredity (who were older and heavier), sodium restriction period was characterized by significant decrease in blood pressure, weight, intracellular sodium concentration and increase in sodium pump activity. When salt was increased, all the parameters remained stable. A more balanced diet with sodium restriction decreases the blood pressure in relation to age, weight and the blood pressure level. Hypertensive heredity does not seem to be a parameter of salt sensitivity. The blood pressure decrease is also related to the quantitative importance of sodium restriction. The ouabain sensitive pump activity changes during diet especially in relation to weight loss and decreasing salt intake.

Adult↗

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 (greater than or equal to 6 reports), with a frequency greater than 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) greater than or equal to 95 mm Hg were initially given isradipine at 1.25 mg twice daily. After 4 weeks, doses were doubled if DBP was greater than 90 mm Hg. If, after a further 4 weeks with doubled dosages, the DBP was still greater than 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.

Calcium Channel Blockers↗

Long-term (2-year) isradipine data in the treatment of mild-to-moderate hypertension.

At the end of a short-term (3-month) study of antihypertensive treatment of mild-to-moderate hypertension, 141 of the 200 study patients continued into a 2-year follow-up of isradipine as monotherapy or in combination with other antihypertensive agents. Although all 141 patients completed the first year, only 102 completed the study. Twenty-four patients dropped out: 2 with flushing; 1 each with arrhythmia, edema, angina, and headache; 12 who were noncompliant; 2 with disease unrelated to the study drug; and 4 for reasons unknown. Before the follow-up, 70% of the 141 patients were taking isradipine; after 2 years, 63% were still taking isradipine as monotherapy. During the follow-up study, the blood pressure remained stable (142.9/86.8 mm Hg after 3 months, and 142.9/86.2 mm Hg after 2 years), whereas the normalization rate was only slightly changed (73 vs. 75.2%). The incidence of reported adverse events decreased with time. At the end of the short-term study, 44.7% of patients had reported one or more adverse events; after 2 years of treatment, only 14.4% reported adverse events. Two patients had ECG signs of left ventricular hypertrophy: one showed no relevant changes while the other presented clear signs of regression. No clinically relevant laboratory abnormalities were noted during the study. In conclusion, isradipine is effective, well tolerated and safe in the long-term treatment of mild-to-moderate hypertension.

Calcium Channel Blockers↗

Sympatholytic drugs and cardiac remodelling in human and experimental arterial hypertension.

Perfusion of isoprenaline in the dog may induce left ventricular hypertrophy (LVH), and this effect is suppressed by propranolol. Cultured foetal cardiomyocytes exposed to catecholamines show an increase in protein synthesis and RNA turnover. In spontaneously hypertensive rats (SHR), and perhaps in man, sympatholytic agents appear to be more effective in preventing or reversing LVH than some other antihypertensive drugs. These data suggest that, if increased load remains the main trigger mechanism for cardiac remodelling in arterial hypertension, the sympathetic nerve activity may modulate the response of the cardiac cells.

Animals↗