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Biomedical subjects

B Lacour

Publications and source records attributed to B Lacour.

At least 55 records · Page 3Linked to original sources
PubMed1998

Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Société Française de Greffe de Moelle study.

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.

Adolescent↗
PubMed1998

Early glomerular dysfunction in patients with sickle cell anemia.

The purpose of this study was to analyze the determinants of glomerular filtration in nonnephrotic young adult patients with sickle cell anemia (SCA). We prospectively screened 14 patients with homozygous SCA who had normal plasma creatinine concentrations and normal or moderately elevated albuminuria (< 1 g/d). Inulin, paraaminohippuric acid, and dextran clearances were evaluated and compared with values obtained from a control group (age-matched healthy volunteers). SCA patients had a significantly higher glomerular filtration rate and effective renal plasma flow than controls (146 +/- 9 mL/min/1.73 m2 v 120 +/- 3 mL/min/1.73 m2 [P < 0.01] and 1,052 +/- 69 mL/min/1.73 m2 v 709 +/- 38 mL/min/1.73 m2 [P < 0.001], respectively). We found no correlation between glomerular filtration rate or effective renal plasma flow and hematocrit. Fractional clearance of neutral dextran was significantly elevated in SCA patients for all radii between 3.4 and 5.4 nm. Theoretical analysis of dextran transport through a heteroporous membrane model revealed a slight increase in the mean radius (ro) of restrictive pores (5.68 nm v5.50 nm; P < .001) and no significant difference in shunt pathway (omega o) values. Among the other hemodynamic parameters, the most significant change was a dramatic increase in ultrafiltration coefficient (41.3 +/- 3.6 mL/mm Hg/min/1.73 m2 v 25.1 +/- 2.6 mL/mm Hg/min/1.73 m2; P < 0.001). Our results suggest that hyperfiltration in SCA patients is associated not only with enhanced renal perfusion but also with an alteration in glomerular permeability and with an increase in Kf. This change in Kf is fully in agreement with the large increase in glomerular area previously described in SCA patients. Based on our results and those of previous morphologic studies, we propose that enhanced transglomerular trafficking of macromolecules associated with podocyte stretch lesions (defects) induced by glomerular hypertrophy may play a role in the genesis of this particular form of focal segmental glomerulosclerosis, which is associated with SCA.

Adult↗
PubMed1998

Identification of crystals in kidneys of AIDS patients treated with foscarnet.

Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

AIDS-Related Opportunistic Infections↗
PubMed1998

Carotid atherosclerosis in renal transplant recipients.

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.

Adult↗
PubMed1998

Acute renal effects of AT1-receptor blockade after exogenous angiotensin II infusion in healthy subjects.

In 10 healthy normotensive volunteers on a normal sodium diet, we evaluated the renal effects of a single oral dose of 50 mg of irbesartan (SR 47436, BMS 186295), an angiotensin II AT1-receptor antagonist, in baseline conditions and during an exogenous angiotensin II infusion (2.5 ng/kg/min). We used a double-blind, placebo-controlled, crossover design. Hormones, blood pressure, renal hemodynamics, and urinary electrolytes were measured during each phase. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was performed, and sieving curves were applied on a hydrodynamic model of ultrafiltration. Irbesartan administration was followed by an increase in active renin and plasma angiotensin II concentrations and renal plasma flow without change of systemic blood pressure, glomerular filtration rate, or plasma aldosterone concentration. Irbesartan did not affect either sieving curves or glomerular ultrafiltration determinants. Angiotensin II infusion at 2.5 ng/kg/min elicited a slight pressor response accompanied by a decrease in glomerular filtration rate and renal plasma flow and an enhancement of fractional dextran clearance over the radius range explored (3.4-5.4 nm). The transcapillary glomerular pressure gradient deltaP and the ultrafiltration coefficient kf were computed to increase by 9% and to decrease by 23%, respectively, without change in intrinsic membrane properties. Pretreatment with irbesartan prevented all these effects of angiotensin II.

Adult↗
PubMed1998

Arterial response to mild balloon injury in the normal rabbit: evidence for low proliferation rate in the adventitia.

BACKGROUND: The role of constrictive remodeling, spasm and proliferation (particularly in the adventitia) in the genesis of chronic lumen narrowing after balloon injury remains under debate. This study analyzed the time course of these components following mild injury in normal arteries. METHODS: Iliac injury was induced by balloon overstretch in 32 rabbits, sacrificed at timed intervals from day 3 to 28. Angiographic response to nitrates, morphometric, immunohistochemical and biochemical analysis were performed at each time point. RESULTS: Quantitative angiography showed a decrease in lumen diameter and no change in response to nitrates over time. On morphometric analysis, remodeling was usually constrictive, appeared as early as day 3 and was responsible for 69+/-14% of the histologic lumen area stenosis at day 28. Constrictive remodeling was correlated negatively to intimal hyperplasia (r= 0.51, P< 0.002) and positively to the lumen area stenosis (r= 0.92, P< 0.0001). Macrophages (labeled by anti-RAM 11 antibodies) were very rare at all time points. Immunohistochemistry identified a high rate of proliferating smooth muscle cells in the media (13+/-7%) and intima (49+/-8%) at day 7, which decreased rapidly. Proliferating cells in the adventitia were rare (3+/-2% at day 7). The number of proliferating cells was time-dependent (r= 0.82, P< 0.0001) and related to cyclin A mRNA measured by reverse transcription-polymerase chain reaction (r= 0.84, P< 0.0001). CONCLUSIONS: In this model, luminal loss was mainly caused by constrictive remodeling rather than intimal hyperplasia. Constrictive remodeling appeared early and was not time-dependent. Macrophages, spasm and adventitial proliferation did not contribute to this constrictive remodeling.

Angioplasty, Balloon↗
PubMed1998

Role of transcellular pathway in ileal Ca2+ absorption: stimulation by low-Ca2+ diet.

The present study was performed to determine the respective involvement of the cellular and paracellular routes in ileal Ca2+ transport. Two groups of rats were either fed a normal Ca2+ diet (1. 0%) or a Ca2+-deficient diet (0.02%) for 14 days. Ileal Ca2+ absorption was determined using both an in situ method of continuous luminal perfusion and an in vitro method (Ussing chamber model). The low-Ca2+ diet stimulated net Ca2+ flux in the ileum twofold, associated with a twofold increase of the mucosal-to-serosal Ca2+ flux in both models. This effect was observed in the absence of concomitant changes in Na+ or water flux in the in situ model or mannitol flux in the in vitro model, excluding the participation of the paracellular pathway in Ca2+ transport. Thus only cellular Ca2+ flux was stimulated. These data suggest that the ileum plays a major role in the adaptation to low dietary Ca2+. Whereas under physiological conditions with usual Ca2+ intakes the transcellular pathway of Ca2+ transport is negligible, it becomes of major importance in the case of Ca2+ deficiency, at least under the present conditions of severe Ca2+ deprivation.

Animals↗
PubMed1998

[Evaluation and interest in new molecular markers in colon cancer].

The presence of colonic tumor cells in the circulation may predict colorectal carcinoma recurrence and metastases. We have developed a highly sensitive nested RT-PCR assay, with primers derived from the cytokeratin 20 (CK20) and the carcinoembryonic gene CGM2, to detect occult microdisseminated enterocytes in blood of colorectal cancer patients. Among 82 healthy controls analyzed, 40.2% (33/82) have a positive expression of CK20 mRNA which is not statistically different from the 45.5% (15/33) of positive results found in colon cancer patients. This sensitive method may detect non-tissue specific constitutive low level (illegitimate) expression of CK20 mRNA in peripheral nucleated blood cells (PNBC) of a significant number of healthy control as well as in a number of normal bone marrow. The low specificity of this assay therefore hampers its value to detect blood colon cancer dissemination. In 47 patients with colorectal carcinoma, CGM2 primers detected circulating enterocytes in 25 of them (53%). In disseminated Dukes' stage C disease patients, 17 out of 29 (59%) were found positive whereas in localized adenocarcinoma (Dukes's stage A and B), CGM2 primers detected enterocytes in 44% suggesting that an hematogenous spillage of colonic cells may be a relatively early event in colon cancer. None of the patients suffering from benign colonic pathologies or from diverticulitis were found positive for this assay. The analysis of 56 healthy individuals without known colorectal cancer, of 20 non-colorectal cancer patients and of 6 normal bone marrows provide evidence that this assay is highly specific and may predict an hematogenous spread of colonic cells in patients with organ-confined disease. Nevertheless, the clinical significance of enterocyte detection and the potential applications of this molecular tool merit longer term follow-up.

Biomarkers↗
PubMed1997

Paracellular calcium transport across Caco-2 and HT29 cell monolayers.

Intestinal calcium absorption has been shown to include two processes, a saturable transcellular movement and a non-saturable paracellular pathway. The potential utility of cell monolayers for studying transepithelial intestinal calcium transport has already been demonstrated; however, simultaneous evaluation of the contribution of the saturable transcellular and of the non-saturable paracellular processes to the total transepithelial transport has not yet been attempted. The aim of this study was to investigate the contribution both of transcellular and paracellular transport processes to the total transepithelial calcium transport in two cell culture monolayers. Caco-2 cells and a clone derived from HT-29 cells (HT29-Cl.19A), two cell lines derived from colon adenocarcinomas which are known to be able to exhibit typical enterocytic differentiation, were used. Cell monolayers were grown on a permeable support and used after 15 days of culture when these cells express enterocytic differentiation and high transepithelial resistance. Isotopic transport rate measurements were performed in the absence of a chemical gradient. The paracellular route was evaluated using [3H]mannitol. Calcium and [3H]mannitol transport rates across cell monolayers were not significantly different. Augmentation of calcium uptake by 200 mM sorbitol did not significantly increase calcium or mannitol transepithelial transport; however, calcium accumulation in the cells was increased by about 200%. Modulation of the monolayer permeability by addition of 10 nM vasoactive intestinal polypeptide (VIP) or 0.5 mM carbachol treatment, which respectively increased and decreased the transepithelial resistance, consequently modified calcium and mannitol transport in a parallel manner. Our results show that Caco-2 and HT29-Cl.19A cell monolayers are good models for studying the calcium paracellular transport pathway.

Caco-2 Cells↗
PubMed1997

Effects of silicon, citrate and the fasting state on the intestinal absorption of aluminium in rats.

1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorption of aluminium (Al) remains a matter of debate. The present study was designed to readdress this issue in the experimental animal, and to examine concomitantly the effects of citrate and the fasting state, respectively. 2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (< 0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l) Si concentration. 3. Two other groups of eight non-fasted rats each received the same distilled water or high-Si gavage solution, respectively, together with a high citrate concentration (62 g/l). In each case the animals had free access to drinking water for 5 days before and 2 days after the gavage, containing the same Si concentration as in the gavage solution. A sixth group of eight rats was gavaged by low-Si, Al and distilled water in the fasted state. 4. The animals were killed 48 h after gavage, and blood, tissue and urine samples were collected for 26Al measurements by accelerator mass spectrometry. 5. We found that the fraction of absorbed 26Al retained in the skeleton (0.025-0.030%) was of the same order of magnitude as the fraction excreted in the 48 h urine (0.035-0.037%). High Si concentrations in the drinking water failed to depress the 26Al fraction absorbed, as estimated on the basis of skeletal accumulation and urinary excretion. 6. The administration of citrate-containing fluid enhanced 26Al absorption 5- to 10-fold (P < 0.005), but again the Si content of drinking water did not interfere. Finally, the intestinal absorption of 26Al was approximately 15 times higher in the fasted than in the non-fasted state. 7. In conclusion, the provision of large amounts of Si in the drinking water failed to modify physiological intestinal Al absorption under basal conditions or after its stimulation by citrate. However, a prolonged fast greatly enhanced Al absorption, compared with the non-fasted state.

Aluminum↗
PubMed1997

Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study.

BACKGROUND: Accelerated atherosclerosis resulting in an abnormally high incidence of coronary and cerebrovascular occlusive accidents has been repeatedly reported in dialysis patients, but incidence and risk factors of such complications in chronic renal failure (CRF) predialysis patients are debated. METHODS: We prospectively assessed the incidence of first myocardial and cerebral infarction episodes in a cohort of 147 CRF patients (99 male) followed from January 1985 to December 1994. Relevant clinical and laboratory risk factors for atherogenesis were determined at yearly intervals. They included blood pressure, smoking, blood lipids, fibrinogen, and homocysteine which were compared in patients with (CVA+) or without (CVA-) occurrence of cardiovascular (CV) atherosclerotic accidents. RESULTS: Incidence of CV accidents was nearly three times higher in CRF patients than in the French general population in both genders. In particular, incidence of myocardial infarction in male patients aged 45-55, 55-65 and > 65 years was 7.6, 18.2, and 27.8/1000 patient-years, respectively, compared to 3.4, 8.9, and 10.4/1000 subject-years in the general population. Although age and degree of renal failure at onset of CV events or at end of follow-up did not differ between CVA+ and CVA- groups, cigarette smoking (24.5 [SD 24.3] vs 8.2 [14.7] pack-years, P < 0.0001) and systolic blood pressure (159 [19] vs 148 [19] mmHg, P < 0.001) were markedly higher in CVA+ patients. Similarly, mean plasma HDL-cholesterol was lower, whereas LDL-cholesterol, triglycerides, apoB, Lp(a), fibrinogen, and homocysteine levels all were significantly higher in CVA+ than in CVA- patients. Multivariate Cox analysis identified cigarette smoking, systolic pressure, HDL cholesterol, and fibrinogen as independent risk factors for developing CV accidents. CONCLUSIONS: Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients, suggesting that the uraemic state per se is associated with atherogenesis. As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions, prophylactic measures should be initiated long before start of renal replacement therapy.

Aged↗
PubMed1997

New aspects of urolithiasis in France. GERBAP: Groupe d'Evaluation et de Recherche des Biologistes de l'Assistance Publique des Hôpitaux de Paris.

OBJECTIVE: To confirm epidemiological studies showing a continuous progression of calcium oxalate nephrolithiasis in western countries, we investigated some aspects of the evolution of stone disease in France. METHODS: Calculi collected from 1977 to 1993 in 10,438 adult French patients were analyzed by infrared spectroscopy. Only 8,631 well-documented cases were available. The anatomical location, the removal mode of calculi, and the time evolution of stone composition were studied. RESULTS: The stones were more often retained in the upper urinary tract in females than in males and needed urological removal. Uric acid stones were more frequently observed on the left side in both sexes (p < 0.0001). Extracorporeal shock wave lithotripsy seems to have been used for a time in calculi which would have been spontaneously discharged. Calcium oxalate stones were preponderant, but their proportion did not change in both sexes. A significant decrease of the proportion of calcium phosphate stones was observed in females (p < 0.0001), probably responsible for the increase of the male/female sex ratio from 1.7 to 2.4. CONCLUSIONS: From our observations and from the evolution of dietary habits in France, it can be deduced that urolithiasis trends to a plateau.

Adult↗
PubMed1997

Gastrointestinal absorption, tissue retention, and urinary excretion of dietary aluminum in rats determined by using 26Al.

We used accelerator mass spectrometry (AMS) and 26AI to study the plasma concentration, urinary excretion, and retention in bone, brain, and liver of a single dose of a dietary concentration of aluminum ingested either with or without citrate by 2-month-old Wistar rats. In the absence of citrate, cumulative urinary excretion and skeleton retention were each approximately 0.05% of the total 26AI dose ingested. 26AI retention in brain and liver were approximately 4 x 10(-8) and 2 x 10(-6), respectively. Concomitant citrate intake increased these median values by about two- to fivefold, although this factor was highly variable in individual rats. Independent of citrate administration, 90% of the 26AI excreted in urine (measured cumulatively over 30 days) was excreted within the first 48 h. Uptake by bone was rapid (approximately 1 h) and permanent over the 30-day duration of the experiment.

Albumins↗
PubMed1997

[Urolithiasis in children in West Algeria].

We analyzed a series of 61 stones from children aged 3 to 14 years old using Fourier transform infrared spectroscopy. The calculi were collected from urology departments of the University Hospitals of Oran, Sidi-Bel-Abbès and Mostaganem in West Algeria. This series is the first investigation concerning the composition of stones in children based on infrared analysis. Calculi were more frequent in males (75.4%) and mainly localized in the bladder (55.8%). Upper urinary tract calculi were more frequent in children over the age of 10 years, and the sex ratio was about 1. Calcium oxalate monohydrate was present in 70.5% of stones and was the main component in 50.8% of cases both in whole stones and nuclei. In contrast, calcium oxalate dihydrate was the main component in only 9.8% of calculi although it was present in 75.4% of stones. Ammonium urate was detected in 29.5% of stones and was always the main component of nuclei. Uric acid, observed in 31.1% of calculi, was the major constituent in 14.7% of stones and 19.7% of nuclei. Magnesium ammonium phosphate was observed in 24.6% of stones as a consequence of urinary tract infection by urea-splitting bacteria. Our observations emphasized that the anatomical location of stone and their composition were in accordance with those previously reported in other countries.

Adolescent↗
PubMed1997

Stimulation by citric acid of calcium and phosphorus bioavailability in rats fed a calcium-rich diet.

The effect of dietary citric acid supplementation on calcium (Ca) and phosphorus (P) bioavailability was studied in rats fed 3 different diets containing 0.1, 0.5 or 1.0 g/100g Ca during 7 weeks. Citric acid supplementation increased intestinal Ca and P absorption and the Ca and P retention/intake ratio only in rats fed the 1% Ca diet. It also increased the P concentration of bone ashes in rats fed the 0.5% Ca diet (18.9 +/- 0.2 vs 17.5 +/- 0.5%) and the 1% Ca diet (20 +/- 0.1 vs. 19 +/- 0.3%), and the Ca bone ash concentration in rats fed the 1% Ca diet (36.7 +/- 0.4 vs. 35.7 +/- 0.5%). In rats fed the 1% Ca diet, plasma P concentration was decreased by citric acid supplementation (2.09 +/- 0.10 vs. 2.45 +/- 0.08 mmol/l) while urinary P excretion was increased (18.2 +/- 2.3 vs. 2.0 +/- 0.3 mmol/4 days), together with a decrease in plasma calcitriol concentration (54.4 +/- 2.6 vs. 79.6 +/- 2.5 ng/l), but no change of the circulating parathyroid hormone level. This study indicates that citric acid supplementation together with a Ca-rich diet allows to obtain an increased retention of Ca and P in bone. The prolonged administration of Ca citrate supplements may therefore help to increase bone mineral concentration.

Animals↗